Feline Internal Medicine Secrets (Veterinary) .

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Feline Internal Medicine Secrets/ edited by Michael R. Lappin.
p. ; em. - (SecretsSeries)
ISBN-13: 978-1-56053-461-7 ISBN-I0: 1-56053-461-3
I. Cats-Diseases-Examinations, questions, etc. I. Lappin, Michael R. 1956-
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FELINE INTERNAL MEDICINE SECRETS
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DEDICATION
To those cat owners, friends, veterinary students, graduate students, interns,
residents, technicians, and research associates who have accompanied me
through my adult life with cats. Dr. Craig Greene at the University of Georgia
first gave me the idea to study Toxoplasma gondii, which ultimately led to the
strengthening of my bond with cats. Inmy office at Colorado State University re-
sides a composite of photographs of my first 10 research cats that was presented
to me by Pat Shroeder. Pat and Amanda Marks helped me care for these fine ani-
mals during that first project and ultimately helped me adopt them to private
homes. Donald Dawe, Anne Prestwood, Cynthia Powell, Christie Cooper, Derek
Burney, Chris McReynolds, Cindy Stubbs, Julia Veir, Lisa McReynolds, Sherrill
O'Neil, Matthew Chavkin,Anthony Basher, Melissa Brewer, Kristy Dowers, Don
Westfall, David Maggs, and Jennifer Ansbaugh are just a few of those who have
directly or indirectly influenced me in the writing of this book.
To my parents, Barbara and Rex Lappin, and my partner in life, Catriona
MacPhail, for tolerating my excessive work habits and supporting this endeavor.
To the multitude of people who have adopted our cats and have given them
the lives they deserve-I cannot thank you enough.
MRL
CONTRIBUTORS
RobinW. Allison, D.V.M.
Research Associate, Department of Pathology, Colorado State University College of Veterinary
Medicine and Biomedical Sciences, Fort Collins, Colorado
Tammy E. Anderson, D.V.M.
Assistant Professor of Medicine, Department of Small Animal Clinical Sciences, University of
Tennessee College of Veterinary Medicine, Knoxville, Tennessee
DinaA. Andrews, D.V.M., Ph.D.,DACVP
Assistant Professor of Clinical Pathology, Department of Veterinary Pathobiology, Purdue University
School of Veterinary Medicine; Clinical Pathologist, Purdue University Veterinary Teaching Hospital,
West Lafayette, Indiana
Paul R. Avery,V.M.D.
Instructor, Department of Pathology, Colorado State University College of Veterinary Medicine and
Biomedical Sciences, Fort Collins, Colorado
JosephW. Bartges, B.S., D.V.M., Ph.D.,DACVIM, DACVN
Associate Professor of Medicine and Nutrition, Staff Internist and Nutritionist, Department of Small
Animal Clinical Sciences, University of Tennessee College of VeterinaryMedicine, Knoxville, Tennessee
JeffD. Bay, D.V.M.
Staff Veterinarian, Department of Internal Medicine, Rowley Memorial Animal Hospital, Springfield,
Massachusetts
EllenN. Behrend, V.M.D., M.S.,Ph.D.
Assistant Professor, Department of Clinical Sciences, Auburn University College of Veterinary
Medicine, Auburn, Alabama
Michelle L. Berry,D.V.M.
Department of Veterinary Clinical Sciences, Oklahoma State University College of Veterinary
Medicine, Stillwater, Oklahoma
Laurie J. Blanco, D.V.M.
Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary
Medicine, Knoxville, Tennessee
Cynthia L. Bowlin, D.V.M., DABVP (Feline)
Cats Only Veterinary Clinic, Columbus, Ohio
Hazel C. Carney, M.S., D.V.M., DABVP
Animal Emergency Clinic and Referral Center, Boise, Idaho; Four Rivers Feline Special Treatment
Center, Ontario, Oregon
JohnM. Cheney, D.V.M., M.S.
Associate Professor, Department of Pathology, Veterinary Diagnostic Laboratory, Colorado State
University College of Veterinary Medicine and Biomedical Sciences; Veterinary Teaching Hospital,
Fort Collins, Colorado
Elizabeth J. Colleran, D.V.M., M.S.
Owner, Chico Hospital for Cats, Chico, California
Heather E. Connally, D.V.M., M.S.
Wheat Ridge Animal Hospital, Wheat Ridge, Colorado
RickL. Cowell, D.V.M., M.S.,DACVP
Professor, Department of Veterinary Pathobiology; Director, Clinical Pathology Laboratory, Oklahoma
State University College of Veterinary Medicine, Stillwater, Oklahoma
xi
xii Contributors
Karen E. Dorsey, D.V.M.
Department of Veterinary Pathobiology, Oklahoma State University College of Veterinary Medicine,
Stillwater, Oklahoma
Kristy L. Dowers, D.V.M.
Department of Clinical Sciences, Colorado State University College of Veterinary Medicine and
Stephen J. Dullard, D.V.M., DABVP
Chief of Staff, Ancare Veterinary Clinic, Mendota, Illinois
Timothy M. Fan, D.V.M., DACVIM
Visiting Assistant Professor, Department of Small Animal Medicine, University of Illinois College of
Veterinary Medicine, Urbana, Illinois
Julie R. Fischer, D.V.M., DACVIM
Staff Internist, South Bay Veterinary Specialists, San Jose, California
Deb Greco, D.V.M.
Department of Pathology, Veterinary Diagnostic Laboratory, Colorado State University College of
Veterinary Medicine and Biomedical Sciences; Veterinary Teaching Hospital, Fort Collins, Colorado
Rebecka S. Hess, D.V.M., DACVIM
Senior Lecturer, Department of Clinical Studies, University of Pennsylvania School of Veterinary
Medicine; Veterinary Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
Armando R. Irizarry-Rovira, D.V.M., DACVP
Department of Veterinary Pathobiology, Purdue University School of Veterinary Medicine, West
Lafayette, Indiana
C. Bisque Jackson, V.M.D.
Department of Emergency and Critical Care, University of Pennsylvania School of Veterinary
Medicine; Veterinary Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
Jordan Q. Jaeger, D.V.M.
Clinical Instructor, Department of Veterinary Clinical Sciences, Ohio State University College of
Veterinary Medicine, Columbus, Ohio
Chad Johannes, D.V.M.
Department of Veterinary Medicine and Surgery, University of Missouri-Columbia College of
Veterinary Medicine, Columbia, Missouri
Alice J. Johns, D.V.M., DABVP (Feline)
The Cat Doctor, Indianapolis, Indiana
Lynelle Johnson, D.V.M., Ph.D.
Research Assistant Professor, Department of Veterinary Biomedical Sciences, University of Missouri-
Columbia College of Veterinary Medicine, Columbia, Missouri
Tina S. Kalkstein, D.V.M., M.A., DACVIM
Staff Internist, SouthPaws Veterinary Referral Center, Springfield, Virginia
Elyse M. Kent, D.V.M., DABVP
Hospital Director and Founder, Westside Hospital for Cats, Los Angeles, California
India F. Lane, D.V.M., M.S., DACVIM
Assistant Professor of Internal Medicine, Department of Small Animal Clinical Sciences, University of
Tennessee College of Veterinary Medicine; Internist, Veterinary Teaching Hospital, Knoxville,
Tennessee
Michael R. Lappin, D.V.M., Ph.D., DACVIM
Professor, Department of Clinical Sciences, Colorado State University College of Veterinary Medicine
and Biomedical Sciences, Fort Collins, Colorado
Contributors xiii
NicoleLeibman, D.V.M., M.S., DACVIM (Oncology)
Ultravet Diagnostics, Mineola, NewYork
Jill Lurye, D.V.M.
Department of Small Surgery and Medicine, Auburn University College of Veterinary Medicine,
Auburn, Alabama
Catriona M. MacPhail, D.V.M.
Surgical Fellow, Department of Clinical Sciences, Colorado State University College of Veterinary
DennisW. Macy,D.V.M.
ElisaM. Mazzaferro, M.S., D.V.M.
Department of Small Animal Clinical Sciences, Colorado State University College of Veterinary
Elizabeth A. McNiel, D.V.M.,Ph.D.,DACVIM (Oncology)
Research Associate, Department of Radiological Health Sciences, Colorado State University College
ofVeterinary Medicine and Biomedical Sciences, Fort Collins, Colorado
MargoL. Mehl, D.V.M.
University of California, Davis, School of Veterinary Medicine; University of California, Davis,
Veterinary Medical Teaching Hospital. Davis, California
JamesH. Meinkoth, D.V.M.,Ph.D.,DACVP
Associate Professor, Department of Veterinary Pathobiology, Oklahoma State University College of
Veterinary Medicine, Stillwater, Oklahoma
LyndaMelendez, D.V.M.,M.S., DACVIM
Assistant Professor, Department of Small Animal Medicine, Oklahoma State University College of
Veterinary Medicine, Stillwater, Oklahoma
TammyL. Miller,D.V.M.,M.S.
Department of Ophthalmology, North Carolina State University College of Veterinary Medicine,
Raleigh, North Carolina
James K. Olson,D.V.M.
Cat Specialist, Castle Rock, Colorado
Christine S. Olver, D.V.M., Ph.D.
Department of Pathology, Colorado State University College of Veterinary Medicine and Biomedical
Sciences, Fort Collins, Colorado
DavydPelsue,D.V.M.
Cynthia C. Powell,D.V.M., M.S.
Assistant Professor, Department of Clinical Sciences, Colorado State University College of Veterinary
Marcella D. Ridgway, V.M.D., M.S.
Assistant Professor, Department of Small Animal Medicine, University of Illinois College of
Veterinary Medicine, Urbana, Illinois
Tammy P. Sadek, D.V.M., DABVP(Feline)
Director, Kentwood Cat Clinic, Kentwood, Michigan
Margie Scherk,D.V.M., DABVP(Feline)
Cats Only Veterinary Clinic, Vancouver, British Columbia, Canada
xiv
Contributors
KimA. Selting, D.V.M.
Department of Oncology, Colorado State University College of Veterinary Medicine and Biomedical
Sciences, Fort Collins, Colorado
StacyB. Smith, D.V.M.
Department of Clinical Pathology, Oklahoma State University College of Veterinary Medicine,
Stillwater, Oklahoma
JohnE. Stein, D.V.M.
SaraStephens, D.V.M., DABVP (Feline)
Alpine Veterinary Service, Missoula, Montana
Cynthia J. Stubbs, D.V.M., M.S., DACVIM
Department of Internal Medicine, Cobb Veterinary Clinic, Marietta, Georgia
Severine Tasker, B.Sc.,B.V.Sc., DSAM, MRCVS
Feline Centre, Department of Clinical Veterinary Science, University of Bristol, Bristol, United
Kingdom
Glenda F. Taton-Allen, B.S.,M.S.
Microbiologist, Veterinary Diagnostic Laboratory, Department of Pathology, Colorado State University
College of Veterinary Medicine and Biomedical Sciences; Veterinary Teaching Hospital, Fort Collins,
Colorado
Helen Tuzio, D.V.M., M.S.
Associate Dean of Administration, Ross University School of Veterinary Medicine, New York, New
York; VeterinaryAssociate, Forest Hills Cat Hospital, Glendale, NewYork
JuliaK. Veir,D.V.M.
Craig B. Webb, D.V.M., Ph.D.
Drew D. Weigner, D.V.M., DABVP (Feline)
President, Academy of Feline Medicine; The Cat Doctor, Inc., Atlanta, Georgia
Donald S. Westfall, D.V.M., M.S.
PREFACE
My experiences with the feline species began with Mittens and Sport and the other barn cats
that resided near my childhood home in Tonganoxie. Kansas, and at Deer Creek Ranch in
Edmond, Oklahoma. These experiences influenced me through my formative years. As I pro-
gressed through veterinary college and my postgraduate training program, I realized that this
wonderful and unique species would direct my research studies for the remainder of my career.
Through interactions with cats in research projects, in the clinic, and with my personal "herd," I
have had many wonderful experiences. I am pleased to be able to interact with my colleagues and
present to you this compilation of chapters on feline internal medicine. I have tried to incorporate
the problem-based approach to internal medicine with the well-received and easy-to-use ques-
tion-and-answer format used in the Secrets Series". This book is unique among current feline
textbooks in that a significant percentage of our authors are board certified in feline medicine and
work in exclusively feline practices. These individuals spend the entirety of their professional
time working with cats and their diseases in the clinical setting. This has led to a very practical
and user-friendly textbook.
A special thanks is extended to William Larnsback and Cecelia Bayruns at Hanley & Belfus
for helping bring this book to the veterinary profession.
Michael R. Lappin. D.V.M.. Ph.D.
xv
Fungal
Cryptococcus neoformans
Aspergillus spp.
Viral
Feline herpesvirus I
Calicivirus
I. Cardiopulmonary Disorders
Section Editor: Lynelle Johnson, D.v.M.
1. SNEEZINGAND NASAL DISCHARGE:
INITIAL DIAGNOSTIC PLAN
Michael R. Lappin, D.V.M., ph.D.
1. What is sneezing?
A superficial reflex that originates in the mucous membranes lining the nasal cavity.
Sneezing is easily induced by chemical or mechanical stimuli. The sneeze results in forceful,
high velocity expulsion of air through the airways that clears the respiratory passageways. Most
diseases of the nasal passages can induce sneezing.
2. What are the major nasal discharges?
Serous Mucopurulent
Mucoid Hemorrhagic
Depending on the primary cause of disease, mixed types of discharges also can occur.
Respiratory epithelium has serous, mucous, and mixed tubuloalveolar glands. Goblet cells also
are distributed throughout the nasal cavity. Most diseases of the nasal cavity result in serous nasal
discharge that can become mucoid or mucopurulent depending on chronicity and secondary bac-
terial overgrowth.
Differential Diagnoses for Sneezing and Nasal Discharge in Cats
Local diseases
Congenital; palate defects
Nasopharyngeal or sinus masses (neoplasia, granulomas, or nasopharyngeal polyps)
Allergic
Dental disease with oronasal fistula
Trauma
Otitis media (if nasopharyngeal polyps are present)
Foreign body
Dysphagia, vomiting, regurgitation (resulting in food aspirated into the nasopharynx)
Infectious diseases
Bacterial
Primary pathogens
Bordetella bronchiseptica
Chlamydia psittaci
Mycoplasma spp.
Secondary floral overgrowth
Coagulation abnormalities
Systemicarterial hypertension
Vasculitis
2 Sneezing and Nasal Discharge: Initial Diagnostic Plan
3. What are the differential diagnoses for serous nasal discharge?
Serous nasal discharge is characteristic of most acute diseases of the nasal cavity. If the
serous nasal discharge is chronic, viral, parasitic, and allergic diseases are most common.
However, parasitic disease of the nasal cavity is extremely rare in cats of the United States.
4. What are the differential diagnoses for mucoid nasal discharge?
Mucoid nasal discharge occurs most commonly with allergic diseases, neoplasia, and fungal
diseases.
5. What are the differential diagnoses of mucopurulent nasal discharge?
Appearance of neutrophils in nasal discharges suggests bacterial involvement. The disease
may be associated with the primary bacterial pathogens or overgrowth of normal bacterial flora
secondary to any chronic nasal disease, including neoplasia, oronasal fistula, foreign body, in-
flammatory polyp, or viral disease. Mucopurulent discharge also occurs with fungal rhinitis.
6. What are the differential diagnoses for hemorrhagic nasal discharge?
Acute epistaxis that occurs without other detectable discharges is most common with
trauma, acute foreign body impaction, hypertension, vasculitis, and coagulopathy. However, vas-
culitis causing a nasal discharge is rare in cats. Epistaxis that develops after a mucoid to mucopu-
rulent discharge is most common with fungal disease, neoplasia, and oronasal fistula.
7. Howdo you organize the diagnostic work-up in cats with sneezing and nasal discharge?
The diagnostic work-up can be divided into three phases that progress from least invasive to
most invasive.
8. What physical examination techniques do you emphasize in phase 1 of a diagnostic
work-up for sneezing and nasal discharge?
A thorough physical examination is performed first. Otic examination should be performed
to evaluate for bulging or discoloration of the tympanum; these changes commonly occur with
nasopharyngeal polyps (see Chapter 5). Oral examination and palpation should be performed to
assess for oronasal fistula of the canine teeth, tooth root infections that may extend into the si-
nuses, and for defects in the soft palate. Ophthalmic examination may provide evidence of ante-
rior uveitis (herpesvirus I) and chorioretinitis (Cryptococcus neoformans).
9. What diagnostic tests should be considered during phase 1 of a diagnostic work-up for
sneezing and nasal discharge?
Cytology of nasal discharge should be performed on all cats with mucoid to mucopurulent
nasal discharge to evaluate for the presence of Cryptococcus neoformans. Neutrophils and bacte-
ria are commonly detected if mucopurulent disease is present but do not prove primary bacterial
disease. Secondary infections result in the same discharge as primary infections. Bacterial culture
and antimicrobial susceptibility testing on nasal discharge collected from the nasal planum are
usually not performed because results are difficult to interpret. It is better to collect tissue for cul-
ture from deep within the nasal cavity while under general anesthesia in phase 2 of the diagnostic
workup. Complete blood cell count, feline leukemia virus antigen test, and feline immunodefi-
ciency virus antibody test are usually performed in cats with nasal discharge. Results of the com-
plete blood cell count rarely give a definitive diagnosis, but the presence of eosinophilia may
support the diagnosis of allergic rhinitis. Feline leukemia virus and feline immunodeficiency
virus infections do not cause sneezing and nasal discharge primarily but may induce immunode-
ficiency that predisposes to other infections. If epistaxis without other nasal discharge is present,
a platelet count, activated clotting time, and systemic arterial blood pressure should be performed
to evaluate for coagulopathies or hypertension. Virus isolation, fluorescent antibody staining or
polymerase chain reaction (PCR) can be used to help detect infections by specific upper respira-
tory pathogens like herpesvirus I or calicivirus (see Chapter 3).
Sneezing and Nasal Discharge: Initial Diagnostic Plan 3
10. Do you perform therapeutic trials during phase 1 of the diagnostic work-up?
Therapeutic trials often are performed in cats with acute or chronic sneezing and nasal dis-
charge, particularly if the client cannot afford further diagnostic procedures to be performed in
phase 2. Antibiotics, antivirals, immunostimulants, anti-inflammatory agents, topical deconges-
tants, or topical glucocorticoids are used in certain situations (see subsequent chapters for spe-
cific recommendations).
11. What diagnostic procedures do you consider in phase 2 of a diagnostic work-up for
sneezing and nasal discharge?
If a definitive diagnosis is not made during phase I and routine therapeutic trials fail, more in-
vasive diagnostic testing is indicated. Phase 2 diagnostics usually consist of laryngeal function ex-
amination, pharyngeal examination, skull and dental radiographs, rhinoscopy, bacterial and fungal
cultures, and biopsy for histology. Since biopsies are generally made in phase 2, a platelet count,
activated clotting time, and systemic arterial blood pressure are performed prior to anesthesia.
General anesthesia is induced by administering approximately one-third of an induction dose of a
thiobarbiturate. The arytenoids are examined to make sure both are abducting normally.
Oropharyngeal examination is performed to evaluate thoroughly for masses, foreign bodies, or
palate defects. The nasopharynx is examined with a dental mirror or rhinoscope. If a definitive di-
agnosis is not apparent, nasal, sinus, and dental radiographs are made. Rhinoscopy of the anterior
nasal cavity is then performed. If indicated, bacterial and fungal cultures are made using tissue
biopsy collected from within the nasal cavity. The nasal cavity is flushed with sterile saline to eval-
uate for the presence of foreign material. Placing the nipple of a 60-ml syringe filled with sterile
saline into the anterior nares and flushing rapidly will usually drive foreign material into the mouth
where it can be removed. Biopsies are then made using a bone curette or small biopsy instrument.
Finally, teeth are probed for evidence of oronasal fistula or periodontal pockets> 3 mm in depth.
Dental mirror examination of the nasal pharynx.
12. What procedures are used in phase 3 of the work-up of sneezing and nasal discharge?
Rhinotomy is rarely indicated in cats but may be utilized in phase 3 evaluation of cats with
sneezing and nasal discharge. For most cats with nasal cryptococcosis, medical therapy is suc-
cessful, and debulking of a mass in the nasal cavity is usually not needed. There is also no added
benefit to debulking nasal tumors prior to radiation therapy. Although removing turbinate tissue
can increase airflow through the nasal cavities in cats with chronic rhinitis, bacterial os-
teomyelitis and some nasal discharge often remain.
BIBLIOGRAPHY
I. Hawkins EC: Chronic viral upper repiratory disease in cats: Differential diagnosis and management.
Comp Cont Educ Pract Vet 10:1010-1013, 1988.
2. Lappin MR: Sneezing and nasal discharge.ln, Lorenz MD, Cornelius LM (eds): Small Animal Medical
Diagnosis, 2nd ed. Philadelphia, 1.B. Lippincott, Philadelphia, 1993, pp 235-244.
2. BACTERIAL DISEASES
John E. Stein, D.v.M.
1. What clinical signs are most common in cats with bacterial upper respiratory disease?
Cats with sneezing and a mucopurulent nasal discharge most likely have a bacterial compo-
nent to their disease, although it may be a primary or secondary condition. Some cats may have
an ocular discharge as part of underlying disease or because the nasolacrimal duct has become
obstructed. Coughing and retching occur in some cats when the nasal discharge is aspirated or
swallowed or when pharyngitis is induced by the infectious agent. Epistaxis may be seen with in-
vasive or chronic disease that disrupts the nasal mucosa, although this finding is rare with pri-
mary bacterial diseases alone. Noisy breathing is commonly noted, and open mouth breathing
can be seen in cats with bilateral nasal obstruction due to discharge.
2. How common is primary vs, secondary bacterial rhinitis as a cause of clinical disease?
Bacterial rhinitis is rarely the primary cause of nasal disease in cats, but it is commonly
noted as a secondary complication to other diseases affecting the nasal passageways and in cats
with impaired immune systems. Secondary bacterial rhinitis can follow many diseases, including
viral upper respiratory disorders, oronasal fistula, nasal foreign body, bony sequestrum, or nasal
neoplasia.
3. What bacterial agents can be responsible for primary rhinitis in cats?
Bordetella bronchiseptica, Mycoplasmaspp., and Chlamydiapsittaci.
4. Describe the clinical manifestations of chlamydiosis.
C. psittaci is an intracellular bacterium that may account for 5-32% of feline respiratory
tract diseases, depending on the study. In North America, however, the agent is associated most
commonly with mild-to-severe conjunctivitis. In fact, primary infection with C. psittaci should
be considered unlikely in cats with sneezing but no evidence of conjunctivitis. The most common
clinical signs, therefore, are serous to mucopurulent ocular discharge, chemosis, blepharospasm,
and eyelid swelling. Other clinical signs that may be noted include fever, submandibular lym-
phadenopathy, sneezing, nasal discharge, anorexia, and weight loss. Chlamydiosis is seen pre-
dominately in young cats, generally between 5 weeks and 9 months of age, and is more
commonly diagnosed in the summer months.
5. What evidence suggests that Mycoplasma spp, are associated with rhinitis in cats?
Mycoplasma spp. have been cultured from the upper respiratory tract of both healthy and
diseased cats. In one study, the organism was isolated from the nasopharynx of 35% of healthy
cats. Because the organism is common in healthy cats, most species are probably opportunistic
pathogens. Mycoplasmafells may cause conjunctivitis, mucopurulent nasal discharge, and sneez-
ing in cats when it colonizes mucosal surfaces. Mycoplasma spp., however, are not found in the
lower airways of healthy cats; thus the resident flora of the nasopharynx may represent a possible
source of infection in cats that develop mycoplasmal pneumonia (see Chapter 12).
6. What evidence supports Bordetella bronchiseptica as a primary cause of rhinitis?
B. bronchisepticais a common organism in cats and has been isolated from the oropharynx
of both healthy and diseased cats. In one study, over 3% of cats without evidence of respiratory
disease were found to have B. bronchisepticaon bacterial culture of oropharyngeal swabs. In ad-
dition, 24% of healthy cats were seropositive for B. bronchiseptica, indicating previous exposure
to the organism. Its role as a potential primary pathogen has been confirmed by experimental in-
duction of disease in specific pathogen-free kittens. Life-threatening pneumonia can develop,
4
Bacterial Diseases 5
particularly if kittens are infected before 4- 6 weeks of age (see Chapter 12). Of importance,
however, B. bronchiseptica appears much more likely to cause clinical disease in young kittens
and group-housed cats, suggesting that concurrent disease, immune status, and stress factors such
as overcrowding, poor hygiene, and recent weaning are also important in the pathogenesis of dis-
ease. Its role as a primary pathogen of adult household cats remains controversial.
7. What are the most common causes of secondary bacterial rhinitis?
A diverse population of gram-positive, gram-negative, aerobic, and anaerobic bacteria is
found in the nasal passages of healthy cats, including Streptococcus spp., Staphylococcus spp.,
Corynebacterium spp., Pasteurella multocida, Escherichia coli, Pseudomonas spp., and
Enterobacter spp. Anaerobic bacteria are commonly found under the mucus layer in the nose
where oxygen tension is low. Any of these organisms or other normal inhabitants can overgrow
and cause clinical signs of bacterial rhinitis in cats with concurrent local disease or compromised
immune system. Overgrowth of normal nasal microflora can occur with viral, fungal, or (rarely)
parasitic infections; trauma; foreign bodies such as plant material; aspiration of food into the na-
sopharynx following dysphagia, vomiting, or regurgitation; neoplasia; nasopharyngeal polyps;
and extension of disease from the oral cavity, such as tooth root abscesses and oronasal fistulas
(see Chapter 1). Specifically, cats with chronic viral respiratory tract infections may develop
severe mucosal ulceration and turbinate destruction, resulting in chronic bacterial rhinitis/sinusitis.
Patients with feline leukemia virus (FeLV) or feline immunodeficiency virus (FlY) infections may
have impaired immune function and be particularly susceptible to secondary bacterial infections,
although positive serologic tests for these agents do not prove the existence of immunodeficiency.
8. What is the initial diagnostic plan for cats with suspected bacterial rhinitis?
Because bacterial rhinitis is most commonly a secondary complication, cats with mucopuru-
lent nasal discharge and sneezing should be evaluated carefully for an underlying primary dis-
ease (see Chapter I). A thorough history and physical examination, with particular attention to
otic, oral, and ophthalmic examinations to detect evidence of local or systemic disease, is para-
mount. Ideally, vaccine history and retroviral (FeLVIFIV) infection status should be known for
every feline patient with chronic mucopurulent rhinitis. Cytology of nasal discharge is usually
considered in the initial diagnostic plan to rule out infection with Cryptococcus neoformans.
Whether more expensive and invasive tests are performed depends on history, physical examina-
tion, and initial diagnostic findings.
9. Howdoes cytology potentially aid in the management of a cat with rhinitis?
Cytology of the nasal discharge confirms the presence of neutrophils and possibly bacteria,
although it cannot differentiate primary from secondary infection or distinguish normal flora
from pathogenic bacteria. C. neoformans may be detected in some cats (see Chapter 4).
10. Should I culture the nasal discharge?
Bacterial culture of the exudates from the nasal planum is not typically performed because
of difficulty in interpreting the results. Since the nasal cavity has a rich normal flora, a mixed
bacterial population is usually obtained from both healthy and diseased cats. If bacterial cultures
are performed, samples are best obtained from deep tissue biopsies with the patient under general
anesthesia and only after the presence of significant underlying disease has been ruled out (see
Chapter 1). Isolation of a pure bacterial culture may be significant. C. psittaci is difficult to cul-
ture. Polymerase chain reaction is superior to culture for detection of the organism from conjunc-
tival swabs but has not been evaluated for respiratory disease.
11. Are there radiographic abnormalities associated with bacterial rhinitis?
Few changes, if any, are seen on nasal radiographs, particularly if the disease course is
acute. Rarely, turbinate destruction or bone lysis is caused by chronic bacterial disease alone.
Either finding strongly suggests a more aggressive disease process, such as neoplasia or fungal
infection.
6 Bacterial Diseases
12. How should I use systemic antibiotic therapy for management of bacterial rhinitis?
Acute, non-life-threatening cases of rhinitis may resolve spontaneously and often are man-
aged with symptomatic care alone. Antibiotic therapy may prove unnecessary if an underlying
disease is identified and treated effectively. In mild, relatively acute cases, a short course (7-10
days) of relatively broad-spectrum antibiotic may prove sufficient to alleviate clinical signs.
Treatment for chronic bacterial rhinitis, Whether as a primary or secondary condition, gen-
erally involves long-term antibiotic therapy.
13. Which antibiotic agents are appropriate for bactrial rhinitis?
Drugs with anaerobic spectrum that penetrate bone and cartilage, such as amoxicillin or clin-
darnycin, are effective in many cases. Clindamycin is a popular choice because of excellent
gram-positive and anaerobic coverage, good tissue penetration, availability of a liquid prepara-
tion, and once-daily dosage. Although nausea, vomiting, and diarrhea occur in some cats, nausea
may be lessened by storing the liquid in the refrigerator between administrations. Metronidazole
is effective in some cats because of excellent anaerobic coverage as well as a potential anti-in-
flammatory effect due to T-lymphocytic modulation. However, an anti-inflammatory effect in
nasal tissues has not been substantiated. Because metronidazole tablets are difficult to administer
to cats, formulated suspensions may be indicated. IfB. bronchiseptica or Mycoplasma spp. infec-
tion is suspected, doxycycline, chloramphenicol, a quinolone, or azithromycin should be admin-
istered. Many B. bronchisepticaisolates are susceptible to amoxicillin-clavulanate, but it is not
an appropriate choice for Mycoplasma spp. Systemic doxycycline combined with topical tetracy-
cline or chloramphenicol is the preferred treatment for suspected C. psittaci infections, although
azithromycin is also effective. Administration of doxycycline tablets has been associated with
esophageal strictures in cats (see Chapter 26). Thus, formulated suspensions should be used, or a
small amount of water should be given orally after administration of tablets. Systemic tetracy-
clines may cause teeth enamel discoloration in kittens. Chronic bacterial rhinitis, usually associ-
ated with the feline viral rhinotracheitis, neoplasia, or fungal infections, may require long-term
therapy (minimum of 4---6 weeks) in addition to addressing the underlying disease. In some cats
with severe turbinate destruction, pulse therapy with antibiotics may be needed to control clinical
signs of disease.
Drugs Commonly Usedfor Treatment ofBacterialRhinitisin Cats
DRUG DOSE REGIMEN COMMENTS
Amoxicillin
Amoxicillin-
clavulanate
Azithromycin
Cephalexin
Chloramphenicol
Clindamycin
Doxycycline
Enrofloxacin
Metronidazole
PO=oraJly.
11-22 mglkgPOevery 12hr
11-22 mg POevery 12hr
5-10mg/kg POevery24 hr for
3 days, thenevery72 hr
22-50 mg/kgPOevery8-12 hr
25-50 mg/cat POevery 12hr
11-24 mg/kgPO every24 hr
5-10 rug/kg PO every 12-24 hr
5 rug/kg POevery 12-24 hr
7.5- I0 mg/kg POevery8-12 hr
Gram-positive, anaerobes
Gram-positive, anaerobes, select gram-
negative, B. bronchiseptica
B. bronchiseptica, Mycoplasmaspp.. C.
psittaci, gram-negative, anaerobes
Gram-positive, anaerobes
B. bronchiseptica, Mycoplasmaspp., C.
psittaci, anaerobes,gram-positive
Gram-positive, anaerobes;goodtissue
penetration
B. bronchiseptica, Mycoplasmaspp.. C.
psittaci; possiblyanti-inflammatory
Gram-negative, select gram-positive, B.
bronchiseptica, Mycoplasmaspp., but
poor anaerobiccoverage
Anaerobes;possiblyanti-inflammatory
Bacterial Diseases
7
14. What adjunct treatments are used in addition to systemic antibiotics?
The nares should be kept clean and free of significant discharge. Humidification therapy to
improve mucociliary apparatus function may be beneficial and can be achieved by humidifying
the area where the cat sleeps, by bringing the cat into the bathroom while running hot water
through the shower, or by nebulization. Some cats may tolerate nasal instillation of saline, which
is mucolytic. Topical treatment with antibiotic nose drops or with nebulization of antibiotics may
be beneficial for some cases, particularly with infection by B. bronchiseptica and Mycoplasma
spp., which are thought to dwell on the surface (see Chapter 12). Nasal decongestants are gener-
ally not indicated if mucopurulent discharge is present. If a poor appetite is identified, feeding
warm, soft food may increase the aroma and encourage cats to eat (see Chapter 62).
15. What is the prognosis for cats with bacterial rhinitis?
The overall prognosis for primary bacterial upper respiratory tract infections is excellent,
with the possible exception of C. psittaci infections, which can be difficult to eliminate and may
recur in times of stress. The prognosis for secondary bacterial infections of the upper respiratory
tract depends on the successful identification and management of the underlying cause.
Idiopathic chronic rhinitis generally is characterized by frequent recurrence of clinical signs with
variable responsiveness to therapy.
16. Can bacterial rhinitis be prevented in cats?
Bacterial rhinitis in cats is generally a secondary complication; therefore, prevention centers
on minimizing conditions that predispose the upper airways to invasion by bacteria. Careful hus-
bandry practices, including adequate hygiene, appropriate weaning, good nutrition, and avoiding
overcrowding, are critical to lessen exposure to infectious agents.
17. What is the role of vaccination?
Bolstering immunity through vaccinations against respiratory pathogens is also important. In
particular, immunization against feline viral rhinotracheitis (FHV-l) and calicivirus (FCV) is cru-
cial; these vaccines should be considered core vaccines, along with panleukopenia (FPV) and
rabies virus, as recommended in the 1998 vaccine guidelines from the American Association of
Feline Practitioners and the Academy of Feline Medicine (see Chapters 3 and 81).
Vaccines against the potential primary disease pathogens, C. psittaci and B. bronchiseptica,
are available. Neither vaccine prevents infection or eliminates shedding. Additionally in most pet
cats the diseases are relatively rare, non-life-threatening, and effectively treated with inexpensive
antibiotics. Thus, it appears unnecessary to vaccinate all cats against these organisms. Use of C.
psittaci and B. bronchiseptica vaccines probably are of most benefit in catteries and humane
shelters with persistent respiratory problems (see Chapter 81).
BIBLIOGRAPHY
1. American Association of Feline Practitioners, Academy of Feline Medicine: 1998 Report of the
American Association of Feline Practitioners and Academy of Feline Medicine Advisory Panel on
Feline Vaccines. J Am Vet Moo Assoc 212:227-241, 1998.
2. Boothe DM: Principles of drug selection for respiratory infections in cats. Comp Cont Educ Pract Vet
19:5-15,1997.
3. Gaskell R, Dawson S: Feline respiratory disease. In Greene CE (00): Infectious Diseases of the Dog and
Cat, 2nd ed. Philadelphia, wn. Saunders, 1998, pp 97-106.
4. Greene CE: Respiratory infections. In Greene CE (ed): Infectious Diseases of the Dog and Cat. 2nd ed.
Philadelphia, wa Saunders, 1998, pp 582-594.
5. Hawkins EC: Disorders of the nasal cavity. In Nelson RW, Couto CG (eds): Small Animal Internal
Medicine, 2nd ed. SI. Louis, Mosby, 1998, pp 225-237.
6. Hoskins JD, Williams J, Roy AF, Peters JC, McDonough P: Isolation and characterization of Bordetella
bronchiseptica from cats in southern Louisiana. Vet Immunol ImmunopathoI65:173-176, 1998.
7. Randolph JF, Moise NS, Scarlett JM, et al: Prevalence of mycoplasmal and ureaplasmal recovery from
tracheobronchial lavages and of mycoplasmal recovery from pharyngeal swab specimens in cats with
or without pulmonary disease. Am J Vet Res 54:897-900, 1993.
8 Viral Diseases
8. Speakman AJ, Dawson S, Binns SH, et al: Bordetella bronchiseptica infection in the cat. J Small Anim
Pract 40:252-256, 1999.
9. Sykes JE: Comparison of polymerase chain reaction and culture for the detection of feline Chlamydia
psittaci in untreated and doxycycline-treated experimentally infected cats. J Vet Intern Med
13:146-152.1999.
10. Sykes JE: Prevalence of feline Chlamydia psittaci and feline herpesvirus 1 in cats with upper respiratory
tract disease. J Vet Intern Med 13:153-162, 1999.
11. Welsh RD: Bordetella bronchiseptica infections in cats. J AmAnim Hosp Assoc 32:153-158, 2000.
3. VIRAL DISEASES
Michael R. Lappin, D.V.M., Ph.D.
1. What are the common viral causes of feline upper respiratory disease?
Feline herpesvirus I (FHV-1), a double-stranded DNA virus and calicivirus (FCV), a single-
stranded RNA virus, are thought to be most common. FHV-1 strains vary little and have similar
pathogenicity, whereas FCV strains are variable. Coinfection with different FCV strains can
occur with variation in clinical signs. Feline leukemia virus (FeLV) and feline immunodeficiency
virus (FIV) do not directly cause respiratory disease. However, immunodeficient cats may be
predisposed to chronic clinical disease due to FHV-I or FCV.
2. How prevalent isFHV-I infection?
Instudies in the United States and Australia, the prevalence of FHV-I infections in cats with
and without upper respiratory tract disease or conjunctivitis was 13.7% and 21.2%, respectively.
Prevalence varies by detection technique and study but was 31% by polymerase chain reaction
(PCR) in one study of healthy cats.
3. How are the respiratory viruses transmitted?
Susceptible cats contract both FHV-I and FCV infections after common exposure to infected
animals in a crowded environment. Transmission can be by direct contact, fomites, or aerosaliza-
tion. FCV survives outside the host for up to I week if it remains moist, whereas FHV-I survives
outside the host for up to 18 hours if it remains moist. Both viruses cause a carrier state in recov-
ered cats despite vaccination status.
4. How does FHV-I cause disease?
Epithelial infection causes local necrosis and neutrophilic inflammation. The upper respira-
tory tissues, conjunctiva, and cornea are affected most commonly. Local bacterial nora may
cause secondary infection. Viremia is rare, but replication occurs in lower airways of some cats,
particularly kittens, and may result in pneumonia.
After a 2-6-day incubation period, acute disease generally lasts for 1-3 weeks. Approx-
imately 80% of recovered cats are thought to develop a latent infection that is maintained in the
trigeminal ganglion. Repeat shedding is thought to occur in 50% and may be stress-induced (e.g.,
glucocorticoid administration, other infections). After a stressful event, shedding begins in ap-
proximately I week and lasts approximately 2 weeks. Clinical signs recur in some infected cats.
5. How does FCV cause disease?
The virus replicates primarily in oral and respiratory tissues. Ability to induce disease varies
by strain. A form fatal to some adult cats was recently described. As with FHV-1, inflammation
can result from viral replication or secondary bacterial overgrowth. Pneumonia in kittens is more
likely to result from FCV than FHV-I infection. Latent infection occurs. and the virus can be
Viral Diseases
9
shed continually even without clinical signs of disease. After a 2-5-day incubation period, acute
disease generally lasts for 2-3 weeks.
6. What are the clinical signs of viral upper respiratory tract disease?
Both FHV-I and FCV infections initially result in varying degrees of sneezing and serous
nasal discharge that can progress to mucopurulent nasal discharge.
Varying degrees of fever and inappetance occur with acute infection with both viruses.
Chronic recurrent rhinitis and sinusitis can occur in some cats and is probably most
common with FHV-I infection.
Conjuctivitis occurs with both viruses but is thought to be more prevalent with FHVI in-
fection.
If keratitis with dendritic ulcer or corneal sequestrum is present, FHV-l infection is most
likely.
Anterior uveitis may berelated to FHV-l infection with or without keratitis.
Cough or dyspnea may occur in some infected kittens but is most common with FCV in-
fection.
Vesicles or erosions on the lips and tongue are most common with acute FCV infection but
may occur with reactivated disease.
Chronic lymphocytic plasmacytic stomatitis is possibly related to chronic FCV infection.
Stiffness and lameness of short duration result from polyarthritis due to acute FCV infec-
tion or modified live vaccination in some kittens.
7, Howis infection with FeV or FHVl diagnosed?
1. Organism demonstration techniques
Both viruses can be grown in appropriate culture (virus isolation).
Direct fluorescent antibody staining of conjunctival smears has been used to document
the presence of FHV-l infected cells.
PCR can be used to amplify DNA of the organisms and is the most sensitive technique
for documenting presence of FHV-I.
Because both FHV-I and FCV can bedetected in healthy as well as sick cats, the value of
these tests for proving disease is low. For example, in one study of cats with conjunctivitis,
more healthy control cats were FHV-l-positive on PCR than cats with conjunctivitis.
2. Detection of serum antibodies
Serum neutralization and enzyme-linked immunosorbent assay (ELISA) have been used
to detect antibodies against FHV-I or FCY.
Most cats have been exposed to or vaccinated with FCV or FHV-l antigens and so are
seropositive.
Antibodies persist for years after exposure or vaccination.
Increasing FCV or FHV-l antibody titers can be demonstrated for a short time after
acute exposure, but titers usually do not rise on secondary exposure or with activation of
chronic infection.
Because so many healthy cats are antibody-positive, the diagnostic utility of serology
testing is minimal except for predicting whether vaccination is needed (see Chapter 81).
3. Testing of aqueous humor
In aqueous humor of cats suspected to have idiopathic anterior uveitis, local production
of FHV-l antibodies was documented frequently.
FHV-I DNA was detected frequently in aqueous humor of cats with uveitis but infre-
quently in normal FHV-I-infected cats. These results suggest that FRV-I infects the in-
traocular tissues of cats and may be associated with anterior uveitis in some cats.
8. Howare viral upper respiratory tract infections treated?
Manifestations of acute disease resolve in most adult cats without specific treatment. Fever
or mucopurulent nasal discharge suggests secondary bacterial infections, and antibiotic therapy
10 Viral Diseases
o Topical antibiotic administration
o Appetite stimulants
may be indicated. Antibiotics with an anaerobic and Pasteurella spp. spectrum often are used, in-
cluding amoxicillin, amoxicillin-ciavulanate, first-generation cephalosporins, and clindamycin
(see Chapter 2). Ocular FHV-I infections are managed systemically and topically. Symptomatic
and supportive care is also important. Examples include:
o Airway humidification
o Nebulization or topical instillation of saline
9. Describe theroleof interferon alpha.
Daily administration of interferon alpha (25 units orally) lessened clinical scores in acutely ill
cats experimentally inoculated with FHV-I. Although controlled studies are lacking. some author-
ities believe that administration of interferon alpha at 30 U/day orally lessens clinical signs of dis-
ease in some cats with chronic FHV-l infection. Information is not available for FCV infection.
Interferon alpha at 10,000-20,000 Ulkg/day subcutaneously is thought to have antiviral ef-
fects and is indicated for treatment of acute FHV-l or FCV infections, particularily if viral pneu-
monitis is suspected. Again, controlled studies are lacking.
10. Whatothertreatments havebeeninvestigated?
o Lysine administered orally at 250 mg every 12 hours lessened viral shedding rates in cats
experimentally inoculated with FHV-l. Although controlled studies are lacking, some be-
lieve that this dose of L-lysine helps to lessen chronic or recurrent clinical signs induced
by FHV-l.
o Intranasal vaccines may lessen clinical signs of chronic FHV-I infection in some cats.
Controlled studies are lacking.
o Administration of acyclovir may be beneficial for the treatment of FHV-1 infections, but
hematologic side effects may occur.
11. Withwhatotherdisorder is FeV associated? Howis it treated?
It is proposed that FCV is associated with chronic lymphocytic-plasmacytic stomatitis in
cats. No therapeutic protocol has been shown to be 100% effective. Controlled studies are lack-
ing, but the following approaches are recommended:
Diseased teeth should be removed or repaired, and a biopsy should be procured to rule out
neoplasia.
o Glucocorticoids help to control inflammation in some cats but are not curative.
o Antibiotics (metronidazole, clindamycin) with anaerobic bacterial spectrums aid in con-
trolling secondary infections.
o Oral administraton of bovine lactoferrin has lessened disease in some cats.
o Immunostimulants (e.g., immunoreglan) and cytokines (e.g., interferon alpha) have been
anecdoctally successful in some cats.
o Carbon dioxide laser ablation of diseased tissues has been beneficial in some cases.
12. Howare viral upperrespiratory tractinfections prevented?
o The best way to avoid FCV and FHV-l infections is to avoid infected cats. However, be-
cause of the presence of chronic, subclinical carriers, this strategy is almost impossible.
o Topical or parenteral vaccines lessen disease in exposed cats but do not provide sterilizing
immunity (see Chapter 81).
o Intranasal vaccines are indicated in kittens in crowded environments because of the rapid
development of secretory IgA but may cause mild clinical signs.
o Booster vaccines currently are recommended every 3 years after 1 year of age.
o Stress should be avoided in multiple-cat households.
o Hospital biosecurity should be maintained (see Chapter 80).
13. Dofelineupperrespiratory viruses infecthumans?
To date, neither FHV-1 or FCV is considered a risk to human health.
Fungal Infections
BIBLIOGRAPHY
II
I. Burgesser KM, HotalingS, SchiebelA, et a1: Comparison of PCR, virus isolation, and indirect fluores-
cent antibodystainingin thedetectionof naturallyoccurringfelineherpesvirusinfections. 1VetDiagn
Invest 11:122-126, 1999.
2. GaskellR, DawsonS: Felinerespiratory disease.In GreeneCE (ed): Infectious Diseasesof the Dog and
Cat, 2nded. Philadelphia, W.B.Saunders, 1998,pp 97-106.
3. Maggs 01, Lappin MR, Nasisse MP: Detection of feline herpesvirus-specificantibodies and DNA in
aqueoushumorfromcats withor withoutuveitis.Am1VetRes 60:8932-936, 1999.
4. Maggs01, LappinMR, Reif IS, et a1: Evaluation of serologicand viral detectionmethodsfor diagnosing
feline herpesvirus-I infectionin cats with acute respiratory tract or chronicocular disease. 1AmVet
MedAssoc214:4502-507, 1999.
5. Maggs 01, Nasisse MP: Effects of oral L-Iysinesupplementation on the ocular sheddingrate of feline
herpesvirus (FHV-l) in cats. Proceedings of the 28th Annual Meeting of the American College of
Veterinary Ophthalmology, Santa Fe, NM, November, 1997,p 101.
6. Nassisse MP, Halenda RM, LuoH: Efficacy of lowdose,oral, natural humaninterferon alpha(nHulRN") in
acutefelineherpesvirus-I infection. Apre1iminary dosedetermination trial.Proceedings of the 27thAn-
nualMeeting oftheAmerican College ofVeterinary Ophthalmology, Newport. RI, November 1996, p 79.
7. PedersenNC, ElliottIB, Glasgow A, et al: An isolatedepizooticof hemorrhagic-like feverin cats caused
by a noveland highlyvirulentstrainof felinecalicivirus. VetMicrobiol73:281-300, 2000.
8. Poulet H, Brunet S, Soulier M, et al: Comparisonbetween acute oral/respiratoryand chronic stomati-
tis/gingivitisisolates of feline calicivirus: Pathogenicity, antigenic profile and cross-neutralisation
studies.ArchVrroI145:243-261,2000.
9. SatoR, Inanarni 0, TanakaY, et a1: Oral administration of bovinelactoferrin for treatmentof intractable
stomatitisin feline immunodeficiency virus (FlV)-positive and FlV-negative cats. Am1Vet Res 57:
1443-1446,1996.
10. Sykes IE, Anderson GA, Studdert VP, et al: Prevalence of feline Chlamydia psittaci and feline her-
pesvirus I in cats withupperrespiratory tract disease.1VetInternMed 13:153-162, 1999.
II. White SO, RosychukRAW, lanik TA, et al: Plasmacell stomatitis-pharyngitis in cats: 40 cases (1973-
1991). J AmAnimHospAssoc200:1377-1380, 1992.
4. FUNGAL INFECTIONS
Stephen J. Dullard, D.v.M.
1. What are the primary upper respiratory fungal pathogens in cats?
Cryptococcus neoformans is the primary fungal pathogen that colonizes the nasal cavity of
cats; systemic dissemination occurs in some cats. Rarely, Aspergillus spp. or Penicillium spp.
infect the nasal passages of cats. Other fungal pathogens, such as Blastomyces dermatitidis,
Histoplasma capsulatum, and Coccidiomyces immitis, initially colonize the lungs and then dis-
seminate to various sites.
2. What causes cryptococcosis?
C. neoformans is a 3.5-7.0 micron, yeastlike organism with a thick polysaccharide capsule
that may approach 30 microns in diameter. The organism reproduces by narrow-base budding.
There are two varieties, C. neoformans var. neoformans and C. neoformans var. gatti. C. neofor-
mans var. gatti occurs in tropical and subtropical climates such as Australia and is associated with
eucalyptus trees. C. neoformans var. neoformans is found worldwide and has been associated prin-
cipally with bird excrement and decaying plant matter. In the United States, southern California
has the most cases. Cats of all ages may be affected, with no breed or sex predilection. The initial
route of transmission is most likely through inhalation, which most commonly leads to nasal dis-
ease. Infection of skin, subcutaneous tissues, eyes, lymph nodes, and central nervous system
(CNS) probably results from hematogenous or lymphatic dissemination from the nose. CNS infec-
tion also may result from direct invasion across the cribiform plate from the nasal cavity.
12 Fungal Infections
3. What factors predispose to cryptococcosis?
Approximately 50% of human cryptococcal infections occur in immunosuppressed patients.
In most feline cases, an underlying cause of immune suppression cannot be found, but dissemi-
nated disease is more common in FlV-infected cats. Cats should be evaluated serologically for
feline leukemia virus antigen and antibodies against feline immunodeficiency virus, although
studies have not confirmed an increased prevalence of these viral infections in cats with crypto-
coccosis. Other predisposing causes may include glucocorticoid administration, neoplasia, or
other diseases that compromise the immune system.
4. What are the presenting signs of feline cryptococcosis?
Clinical signs are variable and depend on lesion location. Infection of the nasal cavity result-
ing in sneezing, nasal obstruction, or nasal discharge occurs in 56-83% of cases. The nasal dis-
charge may be serous, mucopurulent, or hemorrhagic, unilateral or bilateral. Stertorous breathing
may result. Granulomatous lesions often arise within the nasal cavity, on the nasal planum, or
over the facial bones. In one study, 33% of cases had single or multiple cutaneous or subcuta-
neous nodules of variable fluctuance. Nodules may ulcerate and exude a serous discharge that
forms a crust. Regional lymphadenopathy often develops. Occasionally, ocular manifestations
such as granulomatous chorioretinitis, retinal detachment, optic neuritis, lens luxation, or ante-
rior uveitis occur. Ocular and CNS signs occur concurrently in some cats. In approximately 25%
of cases of feline cryptococcosis, CNS disease results from diffuse or focal meningoencephalitis.
Granulomatous masses may develop within the brain or spinal cord, resulting in signs of depres-
sion, ataxia, circling, seizures, blindness, and paresis. Signs of systemic disease, such as fever,
weight loss, anorexia, and malaise, are uncommon but possible. Variability in presenting signs
may relate to the thick polysaccharide capsule of the organism. The capsule inhibits plasma cell
function, phagocytosis, and leukocyte migration, which enhances local infection and may ac-
count for the lack of systemic signs.
Chorioretinitis from Cryptococcus
neoformans infection. (Courtesy of
Dr. Cynthia Powell, Colorado State
University.)
5. How do other nasal fungal diseases of cats manifest themselves?
Only a few cases of feline aspergillosis have been reported. The clinical findings are similar
to those associated with cryptococcosis. Most cats have a chronic, unilateral nasal discharge that
can be serous, purulent, or hemorrhagic. The disease may become bilateral and involve the si-
nuses or cribiform plate. Orbital cellulitis was reported in I case. Systemic mycoses such as blas-
tomycosis, histoplasmosis, and coccidioidomycosis rarely are associated with nasal disease.
Fungal Infections 13
6. Whatare differential diagnoses for nasal fungal infections?
Other diseases to consider for cats with unilateral nasal discharge include nasal tumors, dental
disease, oronasal fistula, nasopharyngeal polyps, and foreign bodies (see Chapter 1). Causes of bi-
lateral nasal discharge include viral respiratory disease, nasal tumors (advanced disease), allergic
rhinitis, cleft palate, and extranasal causes. Rarely, bacterial infections are the primary cause of
disease; Bordetellabronchiseptica, Mycoplasmaspp., and Chlamydiapsittaci are most likely (see
Chapter 2). Most bacterial infections result from damage caused by a primary disease process.
7, Whichdiagnostictests shouldbe performedinitiallyto establisha diagnosisof nasal
fungal disease?
Nonregenerative anemia and monocytosis are the most common hematologic abnormalities;
biochemical panels are usually normal. Definitive diagnosis of nasal cryptococcosis can be made
by demonstrating the organism cytologically. Microscopic examination of stained thin smears of
nasal exudates or fine-needle aspiration of granulomas, cutaneous lesions, and lymph nodes often
yields organisms. Cryptococcal organisms can be identified with routine hematologic stains, but
new methylene blue, Gram stain and periodic acid-Schiff (PAS) provide better contrast. The cap-
sule does not absorb staining and appears as a large, clear halo around the organism. The smaller
and narrow-base budding helps to differentiate C. neoformans cytologically from B. dermatitidis,
which tends to be larger (5-20 um) and reproduces by broad-base budding.
Branching, septate fungal hyphae seen on 10% KOH wet mounts or thin smears of nasal dis-
charge stained with new methylene blue or with routine hematologic stains suggest nasal as-
pergillosis. However, because the organism has been reported as a normal contaminant of the nasal
cavity in dogs, presence of only a few hyphae should not be used to make a definitive diagnosis.
Cryptococcus neoformans stained
with new methylene blue wet
mount. Note the thickcapsuleand
relatively uniform size.
8. Howcanserologyaid inthe diagnosis of fungal rhinitis?
Cryptococcal antigen can be detected in serum, aqueous humor, or cerebrospinal fluid in
most cats with cryptococcosis via the latex cryptococcal antigen test (LCAT) or enzyme-linked
immunosorbent assay (ELISA). Measurement of antibody is not useful. LCAT detects antigen
from the polysaccharide capsule produced by the organism. Positive titers appear within 3 weeks
of infection and strongly support the diagnosis. False-negative results can occur with acute dis-
ease, low-grade chronic infections, nondisseminated disease, and drug-induced remission with-
out complete clearance. The incidence of false-positive and false-negative titers in cats is
unknown. False-positive results have been reported in humans with Klebsiellainfection or posi-
tive rheumatoid factor. Because the organism usually is demonstrated, serum antigen testing for
C. neoformans is rarely needed to confirm the diagnosis. However, most authorities recommend
measurement of titers for monitoring treatment (see question 14). Measurement of antibodies
14 Fungal Infections
against Aspergillus spp. by agar gel immunodiffusion confirms exposure but not active disease.
The percentage of cats with nasal aspergillosis that are seropositive is unknown.
9. What is the further diagnostic plan for cases of suspected fungal rhinitis for which a di-
agnosis is not made cytologically?
Definitive diagnosis of the cause of chronic nasal disease is made with the combination of
radiology (computed tomography, if available), rhinoscopy, periodontal probing, histopathologic
evaluation of nasal tissue, and, potentially, bacterial and fungal culture (see Chapter I).
10. What radiographic abnormalities are seen with fungal rhinitis?
Radiographic abnormalities seen with cryptococcal infections are usually nondestructive
with increased soft tissuelfluid opacity in the nasal cavities or sinuses. Occasionally, bony lysis in
the nasal cavity and overlying tissues of the maxilla is seen. Thoracic radiographs are often
normal but may reveal diffuse to miliary interstitial lung patterns with hilar lymphadenopathy.
Radiographs in feline nasal aspergillosis may reveal turbinate bone loss, punctate bone lysis, and in-
creased fluid opacity in the nasal cavity and sinuses due to secretions or direct fungal involvement.
11. What endoscopic abnormalities are associated with fungal rhinitis?
Typically, cryptococcal infection results in space-occupying granulomas with variable amounts
of nasal discharge. These masses and the surrounding discharges should besampled and examined
cytologically because C. neoformans usually is found in high numbers in aspirates or biopsies.
Infection by Aspergillus spp. often results in white, black, or yellow-green fungal plaques located
within the turbinates. Granulation tissue or increased turbinate space resulting from destructive rhini-
tis may beseen. Necrotic debris and mucus may fill the turbinates and obscure visualization initially.
12. When is fungal culture useful in the diagnosis of fungal rhinitis?
In establishing a definitive diagnosis, fungal culture should be performed on any infected
material, such as swabs from nasal or cutaneous exudates, aspirates of lesions, cerebrospinal
fluid, or biopsy specimens. C. neoformans and Aspergillus spp. can be cultured from the nasal
cavity of healthy cats; thus, a disease association cannot be based on positive cultures alone.
Materials for culture should be placed in a media suitable for supporting the growth of fungi
during transport to the laboratory.
13. How is cryptococcosis treated?
Several drugs have been used in the treatment of cryptococcosis-most frequently, ketoco-
conazole, itraconazole, fluconazole, 5-flucytosine, and amphotericin B alone or in combination.
Because ketoconazole commonly causes anorexia, vomiting, diarrhea, weight loss, and increased
activity of liver enzymes, it is rarely used in cats. Oral fluconazole and itraconazole have been suc-
cessfully used with minimal toxicity. Cats receiving 100 mg/day of itraconazole occasionally de-
velop anorexia, depression, and increased alanine aminotransferase activity; these findings are rare
at doses of 50 mg/day. Because of expense, most clinicians choose itraconazole. Fluconazole
should be given to cats with CNS involvement because it is superior to itraconazole for penetrating
the blood-brain barrier. Treatment with either agent should continue at least 1-2 months after res-
olution of clinical signs. Cats with immunosuppressive diseases may require longer-term therapy.
Antifungal Drugs Used in the Management of Feline Fungal Rhinitis
DRUG DOSAGE
AmphotericinB
AmphotericinB (lipid or
liposomal)
Fluconazole
0.25 mg/kg, IV, 3 times/week*
0.5-0.8 mg/kg SQ 2 times/week!
0.5 mglkg IVas test dose, then 1.0 mg/kgIV3-5 times/week!
50 mg PO every 12-24 hr
Table continued on following page
Fungal Infections
AntifungalDrugs Usedin the Management of FelineFungal Rhinitis(Continued)
DWG O O S ~ E
15
Flucytosine
Ketoconazole
Itraconazole
50 mg/kgPOevery8 hr
10 mglkgPOSID
5 mglkgPOtwicedailyfor 4 days; then5 mglkgPOSID
IV=intravenously, SQ=subcuteneously, PO=orally, SID=onetimedaily.
* Incatswith normal renal function, dilute in50--100 ml5% dextrose andadminister IVover3-6 hours.
t Mixed in0.45% saline and2.5% dextrose. Total volume of400ml in catsand500 mlindogs. Subcutaneous
route rarely leads to sloughing of tissues andis lesstoxic than IVroute. Todate, this regimen hasbeenre-
ported primarily for C. neoformans.
+Dilute thecontents of a vialwith 5% dextrose to a final concentration of 1.0 mg/ml, andshake for 30 sec-
onds. Draw upneeded volume, andfilter through an IS-gauge monoject filter needle into100 mlof5% dex-
trose. Infuse IVover15 minutes. (Abelcet, Liposome Co., Princeton, NJ.)
14. How is antigen testing used to monitor treatment of cryptococcosis?
Antigen titers can be used to monitor effectiveness of therapy because titers parallel severity
of disease. Effective therapy and a good prognosis are indicated by a decline in antigen titer.
Serum cryptococcal antigen titers are monitored every 1-2 months to evaluate treatment.
Preferrably cats should be treated until serum antigen negative, however, many cats have had res-
olution of clinical disease but maintained serumtiters. This may be suggestiveof persistent infec-
tion, lack of susceptibility to a given antifungal agent, or a false positive titer. If this occurs,
switching to a different treatment drug is indicated. If low titers are seen for several months,
treatment can be discontinued. Titers can be monitored and treatment reinstituted if titers in-
crease or clinical signs reoccur.
15. What should I do if my feline patient fails to respond to itraconazole or fluconazole?
Failure to respond to triazole therapy may be due to a number of reasons. For example, cure
may be more difficult in immunosuppressed cats or cats with central nervous system (CNS) or
ocular infections. Resistance to one triazole (itraconazole or fluconazole) does not confer resis-
tance to the other, and a trial of an alternate drug in this class may be attempted.
In cats with poorly responsive CNS cryptococcosis, flucytosine can be administered concur-
rently with a triazole or amphotericin B. Flucytosine may cause vomiting, diarrhea, hepatotoxic-
ity, cutaneous eruptions, and bone marrowsuppression.
AmphotericinBalsocan be usedto treat resistantcases, includingthosewithCNSinvolvement.
Regular amphotericinB administeredintravenouslyis rarely used in cats because of renal toxicity.
Use of liposomal or lipid encapsulatedamphotericinB appears to be less toxic because of its renal
epithelial cell-sparing effect. For clients unable to afford Iiposomal or lipid encapsulated ampho-
tericinB, a subcutaneous protocol has provedto be safe and effective(seetable in question 13).
16. What is the prognosis for cryptococcosis?
Most cats with nasal cryptococcosis can be cured or controlled. The prognosis is more
guarded for those with ocular or CNS involvement.
17. Are cats with nasal cryptococcosis or aspergillosis a public health risk?
Infection by these organisms is acquired from the environment. There is minimal to no risk
of acquiring infection from contact with affected cats (see Chapter 89).
BIBLIOGRAPHY
l. Flatland B, et a1: Clinical andserologic evaluation of cats withcryptococcosis. J AmVet Med Assoc
209:1110--1113.1996.
2. Jacobs GJ,et al:Cryptococcal infection incats: Factors influencing treatment outcome. andresults of se-
quential serum antigen titers in35 cats. J Vet Intern Med 1J:1-4, J997.
16 Nasopharyngeal Polyps
3. Lappin M: Polysystemic mycotic diseases. In Nelson RW, Couto CG (eds): Small Animal Internal
Medicine, 2nd ed. St. Louis, Mosby, 1998, pp 1302-1312.
4. Legendre AM, Toal RL: Diagnosis and treatment of fungal diseases of the respiratory system. In Bonagura
JD (ed): Kirk's Current Veterinary Therapy XIII. Philadelphia, WB. Saunders, 2000, pp 815-819.
5. Malik R, et al: Asymptomatic carriage of Cryptococcus neotormans in the nasal cavity of dogs and cats.
J Med Vet MycoI35:27-31, 1997.
6. Malik R, et al: Combination chemotherapy of canine and feline cryptococcus using subcutaneously ad-
ministered amphotericin B. Aust Vet J 73:124-128, 1996.
7. Malik R, et a1: Cryptococcosis in cats: Clinical and mycological assessment of 29 cases and evaluation of
treatment using orally administered fluconazole. J Vet Med MycoI30:133-144, 1992.
8. Malik R, et a1: Nasopharyngeal cryptococcosis. Aust Vet J 75:483-488, 1997.
9. Medleau L, et al: Evaluation of ketoconazole and itraconazole for treatment of disseminated cryptococ-
cosis in cats. Am J Vet Res 51:1454-1458,1990.
10. Medleau L: Feline cryptococcus. In Kirk RW (ed): Current Veterinary Therapy X. Philadelphia. WB.
Saunders, 1989, pp 1109-1111.
II. Medleau L, et a1: Itraconazole for the treatment of cryptococcosis in cats. J Vet Intern Med 9:39-42, 1995.
12. Rogers KS: Cytology of nasopharyngeal diseases. In August JR (ed): Consultations In Feline Internal
Medicine, vol. 2. Philadelphia, W,B. Saunders, 1994, pp 279-286.
13. Wolf AM, Troy GC: Deep mycotic diseases. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary
Internal Medicine, 4th ed. Philadelphia, WB. Saunders, 1995, pp. 439-463.
5. NASOPHARYNGEAL POLYPS
Julia K. Veir, D.V.M.
1. What are nasopharyngeal polyps?
Benign, pedunculated masses typically arising from the middle ear. They are composed of a
core of loosely arranged fibrovascular tissue covered by an epithelial layer that varies from strat-
ified squamous to ciliated columnar epithelium. The core has scattered plasma cells, lympho-
cytes, and, occasionally, neutrophils. Sometimes there are small numbers of mucous secreting
cells just beneath the surface, which is commonly ulcerated.
2. Why do nasopharyngeal polyps form?
No one really knows. The most popular theory currently is that they are secondary to an inflam-
matory stimulus, possibly associated with upper respiratory tract infections. In early case series,
most cats were very young, leading to the hypothesis that they were remnants of the branchial arches.
3. What clinical signs are commonly associated with nasopharyngeal polyps?
Clinical signs depend on the physical location. The overwhelming number of cases are uni-
lateral, although bilateral disease has been reported in the literature. Most polyps arise from the
eustachian tube, protrude through the tympanic membrane into the middle ear, and extend into
the nasopharynx or grow in both directions. Polyps in the middle ear and external ear lead to
otitis interna, media, and externa. Signs range from mild otic discharge to constant head shaking
with or without signs of vestibular disease (circling, head tilt), as well as Horner's syndrome or
facial nerve paralysis. Polyps that grow into the nasa- and oropharynx are associated with respi-
ratory signs (stertorous breathing, wheezing, chronic nasal discharge, and sneezing) and oropha-
ryngeal signs (dysphagia, gagging, and retching).
4. What is the typical signalment of cats with a nasopharyngeal polyp?
Cats with nasopharyngeal polyps are typically young. The reported median age of onset
varies between 3 and 5 years. However, polyps have been reported in cats as old as 14 years.
Gender and breed predilections have not been reported.
Nasopharyngeal Polyps 17
5. How do I diagnose nasopharyngeal polyps?
Because polyps can grow into the middle ear, otic examination may reveal a bulge or discol-
oration of the tympanic membrane. Polyps protruding through the tympanic membrane can be vi-
sualized by otic examination. Nasopharyngeal polyps sometimes can be palpated through the soft
palate. Polyps in the nasopharyngeal or oropharyngeal regions sometimes can be seen on oral ex-
amination under anesthesia. Retraction of the soft palate rostrally with a spay hook helps to visu-
alize polyps confined to the nasopharynx, and direct visualization is usually possible with caudal
rhinoscopy using a flexible endoscope. Lateral skull radiographs can reveal a mass lesion in the
nasopharyngeal region. Radiographs of the bullae usually are obtained to detect middle ear in-
volvement and to assist in decisions about surgical treatment. Radiographs demonstrate a soft
tissue opacity in the middle ear canal or bulla, and the bulla is often thickened. Computed tomog-
raphy also can be used to delineate the tissues involved.
Plain radiographs of the bulla of a cal with a
nasopharyngeal polyp. Note the thickened
bulla wall.
Computed tomography scan showing a na-
sopharyngeal polyp in the middle ear and
external ear canal.
6. How are nasopharyngeal polyps treated?
Physical removal of the polyp is the only proven method of treatment. External ear canal and
nasopharyngeal polyps can be removed successfully by the traction-avulsion technique that re-
quires little expertise or special equipment. Removal is performed under general anesthesia. For
18 Nasopharyngeal Polyps
polyps in the nasopharynx, the mass is visualized via retraction of the soft palate with a spay hook.
Alternately, stay sutures can be placed in the soft palate to aid in manipulation. The soft palate usu-
ally does not need to be surgically incised unless the polyp is very large.
Polyps in the external ear canal can be visualized with an otoscope. The mass is grasped as
close to the base of the stalk as possible, using an endoscopic cup biopsy instrument, alligator
forceps, towel forcep, or hemostat, and pulled out with steady, firm traction. If bulla involvement
is detected radiographically, surgical removal is performed via a ventral bulla osteotomy (VBO).
The bulla is approached via the lateral aspect of the skull, the mass is removed, and the epithelial
lining is curetted.
7. What is the recurrence rate after treatment with the traction-avulsion technique?
Polyps removed by simple traction-avulsion recur in about 40% of affected cats. Because re-
currence with traction-avulsion is more common in cats with evidence of bulla involvement at the
time of diagnosis, the author currently recommends VBO as the initial treatment in such cats.
However, VBO requires an increased level of technical skill and a longer anesthetic period, has
an increased chance of postoperative complications, and can be much more expensive for the
owner. Risks and benefits of each option should be discussed with the owner.
8. What complications are associated with removal of nasopharyngeal polyps?
In some cats, polyps are quite large at diagnosis and occlude the oropharynx. If the polyp is
in the oropharynx, endotracheal intubation can be difficult. Difficulty in gaining control of the
airway during anesthetic induction can be life-threatening, and the need for an emergency tra-
cheostomy should be anticipated. Little blood loss should be associated with removal of a na-
sopharyngeal polyp. Postoperatively, ipsilateral Homer's syndrome is not uncommon. It is
usually transient, especially with the simple traction-avulsion technique, but may be permanent
with VBO. Facial nerve paralysis and head tilt are also common postoperative complications that
are usually transient but may be permanent.
9. What postoperative care is recommended after polyp removal?
If facial nerve paralysis is present after polyp removal, lubrication for the affected eye is
mandatory until the problem resolves. Peri- and postoperative antibiotics for otitis media should
be continued until results of culture and sensitivity testing of the removed tissue are available and
for at least 21 days if the culture is positive.
10. What is the overall prognosis for cats with nasopharyngeal polyps?
Overall, the prognosis for surgical removal of a polyp is excellent, and a dramatic improve-
ment in clinical signs is evident almost immediately after removal. Owners should be aware that
some cats develop a polyp on the other side.
BIBLIOGRAPHY
1. Allen HS, Broussard J, Noone KE: Nasopharyngeal diseases in cats: A retrospective study of 3 cases
(1991-1998). J AmAnim Hosp Assoc 35:457-461,1999.
2. Bedford PG: Origin of the nasopharyngeal polyp in the cat. Vet Record 110:541-542,1982.
3. Kapatkin AS, Matthiesen DT, Noone KE, et al: Results of surgery and long-term follow-up in 31 cats with
nasopharyngeal polyps. J Am Anim Hosp Assoc 26:387-392, 1990.
4. Little CJ: Nasopharyngeal polyps. In August JR(ed): Consultations in Feline Internal Medicine, vol, 3.
Philadelphia, W.B. Saunders, 1997, pp 310-316.
5. Parker NR, Binnington AG: Nasopharyngeal polyps in cats: Three case reports and a review of the litera-
ture. JAm Anim Hosp Assoc 21:473--478,1985.
6. Pope ER: Feline inflammatory polyps. Semin Vet Med Surg (Small Anim) 10:87-93. 1995.
6. CONFORMATIONAL DISEASES
Lynelle Johnson, D.V.M., Ph.D.
1. What types of conformational diseases of the respiratory tract are seen in cats?
Conformational disorders of the respiratory tract may be structural or functional, congenital
or acquired, and can be encountered at different levels of the respiratory tract.
2. Define the most common examples of conformational disease in the upper respiratory tract.
Stenotic nares is a congenital conformational abnormality of the upper respiratory tract.
Elongated, cleft, or deformed soft palate is usually a congenital lesion, but deformation
may result from trauma.
Nasopharyngeal stenosis can be congenital but more often is due to chronic rhinitis. It has
been proposed that chronic inflammation from rhinitis stimulates production of a web of scar
tissue across the caudal opening of the nasal cavity.
Pharyngeal mucocoele is a rare cause of upper respiratory obstruction and respiratory dis-
tress due to a structural lesion.
Laryngeal paralysis is a functional conformational disease, in which a normally mobile
structure has been rendered immobile and dysfunctional by peripheral or central damage to the
recurrent laryngeal nerve. Damage may occur with trauma to the neck, iatrogenic injury to the re-
current laryngeal nerve (during thyroidectomy or other neck surgeries), or compression, infiltra-
tion, or interruption of the caudal laryngeal nerve anywhere in its course from the vagus trunk. In
some cats, laryngeal paralysis may be a congenital condition.
3. Define the most common conformational lesions in the lower respiratory tract.
Bronchial dysgenesis is a rare conformational abnormality caused by malformation of the
bronchial tree. Progressive signs of respiratory difficulty may be apparent, or the cat may be rela-
tively asymptomatic, depending on the extent of involvement of lower airways.
Bronchiectasis, an irreversible dilatation of the airways, is more common in males than in fe-
males and results from long-standing inflammatory diseases of the lower airways. It does not appear
to be primarily responsible for clinical signs, but it may worsen the clinical course of disease.
Cats with a bronchoesophageal flstula may have a history of recurrent pneumonia or present
acutely with aspiration pneumonia. If the fistula is acquired secondary to a foreign body in the
esophagus, a long history of dysphagia, gagging, or excessive salivation may be present.
4. Describe the typical signalment of cats affected by conformational diseases.
Brachycephalic cats may be predisposed to conformational abnormalities in the upper respira-
tory tract because of the breed preference for shortening of facial features. A true brachycephalic
syndrome has not been reported, but it is wise to be aware that signs can occur in Persian and
Himalayan cats. Cats with congenital lesions usually are presented at a young age, but the possibility
of a congenital lesion should not be ruled out solely on the basis of age. Owners may fail to notice
that the cat has a respiratory problem until later in life because of inexperience with pet ownership.
Alternatively, owners may acquire an adult cat with a previously undiagnosed lesion, or a mild prob-
lem that was recognized at an early age may suddenly worsen because of concurrent disease.
5. Describe the typical history of cats with conformational diseases.
Cats with upper airway lesions such as stenotic nares or elongated, deformed, or cleft soft
palate usually are presented for signs of abnormal, difficult, or noisy breathing. In mildly affected
cats, signs may be apparent only with exercise. In contrast, bilateral laryngeal paralysis generally
causes marked signs of respiratory distress at rest, and owners often note a voice change, dysphagia,
coughing, or anorexia. The cause of laryngeal paralysis is inapparent in most cats, but questions
19
20 Conformational Diseases
should be raised about a recent history of neck surgery, difficult intubation, or trauma to the neck.
Acquired nasopharyngeal stenosis is more often found in older cats with a history of chronic
rhinitis. Historically, such cats have longstanding, recurrent upper respiratory signs, such as
sneezing and nasal discharge, that are gradually replaced by signs related to nasal obstruction.
6. What are common presenting complaints in cats with conformational diseases?
Presenting complaints depend on the site within the respiratory tract that is affected. Open-
mouth breathing is a nonlocalizing sign because it can occur with respiratory distress at any level
of the pulmonary system and can be seen in cats that are stressed. However, cats that are unable
to breathe with the mouth held closed generally have disease of both nasal passages or the na-
sopharynx.
7. What complaints suggest conformational disease of the upper respiratory tract?
Diseases of the upper respiratory tract usually lead to loud and abnormal breathing sounds
such as stertor and stridor. Stertor resembles a snoring noise and is heard when passage of air
through the nose or pharynx is obstructed, as may occur with stenotic nares or an elongated soft
palate. With an elongated soft palate, intermittent airway obstruction or stertor may be observed
by the owner. Stridor classically is associated with laryngeal paralysis. Cats with laryngeal dis-
ease often present with a history of a voice change and inspiratory dyspnea.
8. What complaints suggest conformational disease of the lower respiratory tract?
Bronchial dysgenesis may lead to progressive signs of tachypnea and respiratory distress as-
sociated with obstruction of the airways. Cats with bronchoesophageal fistula may present with
recurrent pneumonia associated with the presence of gastrointestinal organisms on airway cul-
ture. Clinical signs can include lethargy, depression, anorexia, and a respiratory pattern consis-
tent with pneumonia. Eating or drinking may exacerbate clinical signs.
9. What physical examination abnormalities are seen in cats with stenotic nares?
Stenotic nares can be difficult to identify because the opening to the rostral portion of the
nasal cavity is naturally small in cats. Significant breed variations in appearance also make it im-
possible to construct guidelines for the diagnosis. Young kittens should be examined carefully at
each veterinary visit to assess the alar opening, particularly in brachycephalic breeds such as
Himalayan and Persian. Normally, the opening to the nasal cavity increases slightly as the cat
grows, and the kitten should have no difficulty with nasal respiration. Stenotic, slit-like openings
to the nasal cavity cause difficulty in inspiration and may be associated with noisy respirations
and increased effort on inspiration.
10. What physical examination abnormalities suggest obstruction of both nasal passages or
obstruction of the caudal nasopharynx?
Cats with obstruction of both nasal passages (due to a mass lesion or bilateral nasopharyn-
geal polyps) or obstruction of the caudal nasopharynx (due to a mass or stenosis) can present
with open-mouth breathing (see Chapter 5). Open-mouth breathing may be associated with respi-
ratory distress, or the cat may simply hold its mouth slightly open at all times. In the latter case, it
can be difficult to tell that the cat fails to breathe through the nose until it is forced to do so by
closing the mouth. Nasal airflow should be assessed by holding a cooled microscope slide in
front of the nose and watching for condensation or by holding a wisp of cotton in front of each
naris and looking for subtle movement of the cotton. Airflow should be assessed as present or
absent bilaterally or as decreased or absent unilaterally.
11. Describe the physical examination rmdings associated with palatal abnormalities.
Cats with palatal abnormalities may present with nasal discharge from passage of oral con-
tents into the nasal cavity. After drinking, the cat can be observed for nasal discharge or sneezing.
A deformed or cleft soft palate can be visible on physical examination but often requires sedation
for complete evaluation. Stertor that varies in character as the soft palate obstructs respiration
Conformational Diseases
21
may be the most obvious physical examination finding in cats with an elongated soft palate.
Stertor can be difficult to distinguish from stridor. Stridor is usually a more continuous sound
and has less of a musical quality. Stridor and inspiratory dyspnea are suggestive of laryngeal
paralysis. The cat with stridor should be closely examined for signs of neck injury.
12. Describe the physical examination findings of conformational lesions in the lower res-
piratory tract.
Cats with bronchiectasis or bronchial dysgenesis usually present with expiratory effort be-
cause both diseases are associated with obstructed airways. Cats with pneumonia secondary to a
bronchoesophageal fistula typically have an increased respiratory rate, mild tracheal sensitivity.
and crackles on auscultation. Fever mayor may not be present.
13. What differential diagnoses should be considered in cats with conformational respira-
tory diseases?
Upper respiratory signs may be due to infectious or inflammatory diseases of the nasal
cavity or mass lesions (abscess, granuloma, parasites, neoplasia) in the nose, pharynx, larynx, or
trachea. Lower respiratory signs may indicate bacterial or aspiration pneumonia, asthma,
pleural effusion, or congestive heart failure; however, auscultation and percussion findings usu-
ally help to rule out causes other than pneumonia.
14. How are stenotic nares and cleft palate diagnosed?
Stenotic nares and cleft palate can be diagnosed on visual inspection. Because the finding of
an elongated soft palate is subjective and requires surgical correction, a full oral and laryngeal
examination should be performed under anesthesia for accurate diagnosis.
15. Describe the diagnosis of nasopharyngeal stenosis.
Diagnosis of nasopharyngeal stenosis is relatively easy if a flexible endoscope can be
retroflexed into the caudal nasopharynx to allow visualization of the caudal opening of the nares.
Generally, this opening should be 5-6 mm across, and the nasal turbinates are seen on each side
of the nasal cavity. In cats with nasopharyngeal stenosis, the opening to the nasal cavity is re-
duced by a fibrous web of tissue, and the caudal aspect of the turbinates cannot be visualized.
The narrowed region can be present at any location within the nasopharynx. If an endoscope is
not available, a spay hook should be used to retract the soft palate rostrally while a dental mirror
is used to examine the nasopharynx (see Chapter I). The patency of the ventral nasal meatus also
can be assessed by attempting to pass a tom-cat catheter through the nasal cavity into the phar-
ynx, similar to the way that a nasogastric tube is passed. Care should be taken to ensure that the
catheter goes ventrally rather than into the dorsal meatus, which terminates in the ethmoid
turbinates and brain. If an obstruction is met at the appropriate level within the ventral meatus,
nasopharyngeal stenosis should be considered.
16. How is laryngeal paralysis diagnosed?
Laryngeal examination is generally quite straightforward in cats because of their marked la-
ryngeal sensitivity. A light plane of anesthesia is induced (by giving '/4-
1/2
the calculated dose of
thiobarbiturate), and the arytenoid cartilages should be seen to abduct with inspiratory motions.
Paresis or paralysis may be unilateral or bilateral. Thoracic and cervical radiographs are often ab-
normal in cats with laryngeal paralysis and are indicative of obstructive airway disease.
Abnormalities included caudal displacement of the larynx, lung hyperinflation, and aerophagia.
17. How are conformational diseases of the lower respiratory tract diagnosed?
Evidence of bronchial dysgenesis and bronchiectasis may be visible radiographically, but
definitive diagnosis requires histologic studies. A high index of suspicion is required for clinical
diagnosis. It can be difficult to obtain a definitive diagnosis of pneumonia caused by a broncho-
esophageal fistula. Radiographicchanges may be similar to those expected in aspiration pneumonia,
22 Conformational Diseases
particularly if the fistula occurs in the dependent lung field or the middle lung lobes, which are
common sites of aspiration. An atypical location for aspiration pneumonia, along with suggestive
clinical findings, should encourage suspicion for a bronchoesophageal fistula. The presence of
megaesophagus or an esophageal diverticulum in the region of a pulmonary infiltrate also should
be considered suspect.
18. What other tests may be required in cats with conformational respiratory diseases?
To achieve a definitive diagnosis of bronchoesophageal fistula, an esophagram may be re-
quired. Fluoroscopy can reveal dynamic reflux of contrast material from the esophagus into the
airways, or static radiography may be used to define a connection between the gastrointestinal
and respiratory tracts.
19. Describe the management of stenotic nares and conformational diseases of the palate.
Stenotic nares can be opened by wedge resection of part of the alar fold. A deformed soft
palate may require reconstructive surgery or use of an implant to close the defect. An elongated
soft palate is trimmed to an appropriate length; complete apposition of mucosal edges should be
ensured to avoid dehiscence. Trimming the palate too short should be avoided because it can lead
to dysphagia.
20. How is nasopharyngeal stenosis managed?
Management of nasopharyngeal stenosis is problematic because the tough, fibrous band of
tissue is difficult to break down and often reforms after surgery. Methods used to remove the ob-
struction include balloon dilation of the stricture, laser removal of excessive scar tissue, use of a
stent to increase the diameter of the opening, conventional surgery to open the lesion, and surgi-
cal resection of the affected region with placement of a mucosal advancement flap to cover the
defect. Variable results are encountered, and a tracheostomy may be required to allow adequate
respiration.
21. Describe the management of laryngeal paralysis.
Treatment of laryngeal paralysis can involve lateralization of the arytenoid (as in dogs) or
occasionally tracheostomy. Thus far, reasonable quality of life has been reported in cats treated
with surgery.
22. How are bronchoesophageal fistulas and bronchiectasis managed?
A bronchoesophageal fistula requires surgical resection. Similarly, if bronchiectasis of a
single lung lobe is believed to be contributing to clinical signs, lung lobectomy should be consid-
ered.
23. What is the expected treatment response in cats with conformational respiratory dis-
eases?
In cats with stenotic nares and cleft or elongated soft palate, surgery is usually curative.
Generally, cats with laryngeal paralysis respond well to treatment, although occasionally tra-
cheostomy is required. Cats with nasopharyngeal stenosis are more problematic because exces-
sive fibrous tissue can reform after the stricture is opened. Little clinical information is available
about these cases, but control of inflammation and infection in the area is essential. Antibiotics
effective against primary and secondary pathogens should be used. Doxycycline or enrofloxacin
may be used to control Bordetella bronchiseptica and Mycoplasma spp. infections; these drugs
are also effective against some of the normal upper respiratory flora. Coverage against anaerobes
also should be considered, and long-term therapy is recommended in cats with chronic rhinitis
(see Chapter 2). Anti-inflammatory dosages of corticosteroids may help to control excessive de-
position of scar tissue, although the risk for poor wound healing at other surgical sites must be
considered. Cats with bronchiectasis or bronchial dysgenesis require management of obstructive
airway disease.
Nasal Tumors
BIBLIOGRAPHY
23
I. Basher AWP, Hogan PF, Hanna PE, et al: Surgical treatment of a congenital bronchoesophageal fistula in
a dog. J Am Vet MedAssoc 199:479-482, 1991.
2. Griffon DJ, Tasker S: Use of a mucosal advancement flap for the treatment of nasopharyngeal stenosis in
a cat. J Small Anim Pract 41:71-73,2000.
3. Larue MJ, Garlick DS, Lamb CR, et al: Bronchial dysgenesis and lobar emphysema in an adult cat. J Am
Vet MedAssoc 197:886-888, 1990.
4. Mitten RW: Acquired nasopharyngeal stenosis in cats. In Bonagura JD, Kirk RW (eds): Current Veterinary
Therapy XI. Philadelphia, W.B. Saunders, 1992, pp 801-803.
5. Norris CR, Samii VF: Clinical, radiographic, and pathologic features of bronchiectasis in cats: 12 cases
(1987-1999). J Am Vet MedAssoc 216:530-534, 2000.
6. Novo RE, Kramek B: Surgical repair nasopharyngeal stenosis of in a cat using a stent. JAm Anim Hosp
Assoc 35:152-156,1999.
7. Schachter S, Norris CR: Laryngeal paralysis in cats: 16 cases (1990-1999). J Am Vet Med Assoc
216:1100-1103,2000.
7. NASAL TUMORS
Stephen J. Dullard, D.v.M.
1. How common are nasal tumors in cats?
They represent approximately 1% of all tumors and 75% of all respiratory tumors in cats. Of
primary nasal tumors, 80% are malignant; local invasion of surrounding tissue is the main biologic
feature. Distal metastases are rarely found at the time of diagnosis 10%) but may occur late in
the disease. The most common sites of metastases are regional lymph nodes, lung, and brain.
Paraneoplastic syndromes are rarely associated with nasal neoplasia. Benign nasal tumors are
quite rare, but inflammatory polyps (which have the gross appearance of a tumor) are common in
cats (see Chapter 5). Males have twice the risk of females for developing a nasal tumor.
2. What are the most common types of feline nasal tumors?
Tumors of epithelial origin are more common than tumors of mesenchymal origin. Squamous
cell carcinoma (SCC) is the most common type, followed by adenocarcinoma and lymphoma.
Lymphoma of the nasal cavity can be solitary or part of a multicentric neoplastic disease. The most
common types of mesenchymal tumors are osteosarcoma, fibrosarcoma, and chondrosarcoma.
3. What are the clinical signs of a nasal tumor?
Nasal tumors usually occur in older patients, but younger cats can be affected. SCC usually de-
velops on the planum of the nose. Prolonged exposure to ultraviolet light results in preneoplastic
changes to the nonpigmented planum, such as ulceration, crusting, swelling, and erythema. Tumor
formation results in slow, progressive local invasion of the nasal cavity with destruction of underly-
ing soft tissues and bone. In one study of 90 cats with nasal planum SCC, 73% had some white skin
or hair. White-haired cats have a 13.4 times greater risk of developing SCC than cats of other colors.
Other tumors and advanced sec often elicit a nasal discharge (unilateral or bilateral), sneez-
ing, epistaxis, stertor, pain on examination of the nose or mouth, deformation of the facial bones
or hard palate, and regional lymphadenopathy. Weight loss and anorexia may be evident. Rarely,
the patient may present with neurologic disease (seizures, abnormal mentation) or ocular abnor-
malities (exophthalmos), which result from direct invasion of the cranial vault or orbit.
4. What nasal discharge is associated with tumors?
The nasal discharge can be serous, mucoid, mucopurulent, or hemorrhagic. One or both nos-
trils may be involved. Bilateral disease is suggestive of more extensive involvement. and often one
24 Nasal Tumors
side has more discharge than the other. History should note if the condition initially was unilateral
and progressed. This observation may help to direct further examination to one side vs. the other.
5. Howcan nasal airflow be assessed?
Assessment of nasal airflow is easily accomplished by placing a cold microscope slide in
front of the nasal planum and observing for symmetrical condensation on the slide.
6. What are the differential diagnoses for nasal tumors?
The main differential diagnoses for unilateral nasal discharge are nasal fungal infections, dental
disease, oronasal fistula, nasopharyngeal polyps, and foreign bodies (see Chapter I). Causes of bi-
lateral nasal discharge include viral respiratory disease, fungal infections, allergic rhinitis, cleft
palate, and extranasal diseases, Differentials for early SCC include pemphigus, mycoses, plastic
dish syndrome, solar dermatitis, eosinophilic granuloma complex, and other rare skin diseases.
7. What diagnostic tests should be performed?
All patients should have a complete blood count, serum chemistry profile, and urinalysis to
detect systemic disease. Definitive diagnosis is based on identifying abnormal tissue on the nasal
surface or within the nasal cavity on physical examination, radiographs, rhinoscopy, fine-needle
aspiration, or computed tomogram (CT). Once the abnormal tissue is identified, it must undergo
biopsy and histologic examination. If lymphadenopathy is present, needle aspiration with a cyto-
logic examination or biopsy of the lymph node is warranted. If lymphoma is suspected, the cat
should be tested for feline leukemia and feline immunodeficiency virus. Cytologic examination
of bone marrow and abdominal radiographs or ultrasound should be performed to determine the
stage of the disease (see Chapter 68).
8. What is the best radiographic viewfor evaluating nasal disease?
Open-mouth ventral dorsal radiographic views are essential in evaluating patients with nasal
disease. The open-mouth procedure requires anesthesia but allows radiographic evaluation of the
entire nasal cavity without interference of the mandible as well as separate visualization of both
nasal cavities. The use of ultraspeed nonscreen dental occlusal film sheets (2.25" x 3") works
well in cats and allows detailed evaluation of the turbinates. The patient is placed in dorsal re-
cumbency with the head parallel to the table. The x-ray tube is angled 10-15 from its normal po-
sition with the beam centered on the hard palate of the opened mouth. The head should be as
centered and as parallel to the table as possible.
A lateral open-mouth view may be helpful in identifying a nasopharyngeal mass lying dorsal
to the soft palate. Because such masses often originate in the middle ear, the bullae should be ex-
amined as well (see Chapter 5). Obtaining radiographs of the maxillary arcade ofteeth using a bi-
secting angle technique allows evaluation of tooth roots to rule out sinusitis as a cause for nasal
discharge. Thoracic radiographs should be taken to detect metastatic pulmonary disease.
9. What radiographic lesions are seen with nasal tumors?
Radiographs may show evidence of turbinate, vomer bone, or facial bone lysis. Deviation or
lysis of the nasal septum may occur. Soft tissue mass lesions may be present along with increased
fluid opacity of the nasal cavity resulting from increased nasal secretions. However, these find-
ings are not diagnostic for nasal neoplasia because chronic rhinitis can result in similar radi-
ographic changes.
10. What lesions are seen on rhinoscopy?
Rhinoscopy should be performed anteriorly through the naris and posteriorly over the soft
palate, using a flexible endoscope or a dental mirror and light source. It is important to rule out
masses in the nasopharyngeal region. On rostral rhinoscopy, the nasal cavity should be evaluated
for increased or decreased air space. Neoplastic masses grow between the turbinates and de-
crease nasal air space. Frequently, nasal neoplasms elicit marked inflammation of the nasal
mucosa with secondary bacterial or fungal infections. The nasal cavity may be filled with large
Nasal Tumors
25
amounts of nasal discharge that must be flushed and suctioned to provide adequate visualization.
Any mass lesions must be biopsied.
Chondrosarcoma occluding right
andleft posterior choanal openings.
11. Howshoulda suspected mass be biopsied?
Suspicious areas should be biopsied with either an alligator cup biopsy forcep, Tru-cut
biopsy needle (Travenol Laboratories, Inc., Deerfield, IL), or a sharpened plastic tube fashioned
from the protective sleeve of an intravenous catheter or spinal needle. The sharpened tip of the
plastic tube is forced into the suspected mass and rotated; a negative pressure is applied with a
l2-ml syringe; and then the plastic tube is withdrawn. The biopsy instrument should never pass
caudal to the medial canthus of the eye to avoid penetration of the cribiform plate and brain.
Different types of biopsy instru-
ments: Tru-cut biopsy device, en-
doscopicbiopsyforcep, and tissue
core biopsy device made from a
polypropylene catheteranda l2-ml
syringe.
12. What shouldyoudo if lesionsare not identified but neoplasia is still suspected?
Some cases of neoplasia are not diagnosed on initial examination. Diagnostic tests may need
to be repeated in 1-3 months when a definitive diagnosis is not made but signs of nasal disease
persist. Because viral respiratory disease is a cornmon differential diagnosis in cats, client educa-
tion about follow-up examinations and disease differentials is important. Observation of type, lo-
cation, and change in nasal discharge volume should be attempted. CT may be recommended
because it detects soft tissue changes that may not be evident on radiographs or endoscopy.
13. Cana diagnosis be madecytologically?
Care should be taken in diagnosing nasal neoplasia based on cytology. Chronic inflamma-
tion and metaplastic changes within the nasal cavity may cause alterations in cytology that mimic
neoplasia. Some tumors can have similar cytologic characteristics, leading to incorrect classifica-
tion and improper treatment. All nasal tumors should have histiologic confirmation.
26 Nasal Tumors
14. When should CT or magnetic resonance imaging be used?
Whenever possible, because they are more sensitive in detecting and determining the extent
of abnormal tissue within the nasal cavity and paranasal sinuses than conventional radiography.
In recent years, they have become increasingly available.
IS. Once diagnosed, how are intranasal tumors treated?
Because most nasal tumors are malignant, the recommended treatment is usually radiation
therapy with or without surgical debulking. Surgery alone does not prolong survival time; in fact,
it may shorten survival times.
Chemotherapy can be used for tumors that do not respond to radiation or when radiation
therapy is not a viable option. Carboplatin and various multi agent chemotherapy protocols for
carcinomas can be tried. Cisplatin (which is toxic to cats) has resulted in palliation of clinical
signs in some dogs for up to 12 months. Piroxicam, given orally at 0.3 mglkg every 48 hours. has
been used for treatment of epithelial tumors of the nasal cavity when the owner cannot afford
other modalities. Liver, clotting and renal functions should be evaluated periodically because
piroxicam is a potent nonsteroidal anti-inflammatory agent.
Lymphoma can be treated with various chemotherapy protocols or radiation (see Chapter
68). Local radiation avoids the systemic adverse effects of chemotherapy, but chemotherapy is
recommended to minimize the development of systemic lymphoma. Cats with localized in-
tranasallymphoma had disease-free intervals that lasted more than 500 days.
16. How does radiation therapy affect survival in cats with nasal tumors?
Few studies have been performed in cats with intranasal tumors. but in dogs receiving local-
ized radiation median survival times improved substantially from 8 to 36 months. Dogs receiving
no therapy usually live < 6 months. In one study of cats receiving 48 Gy of telecobalt or ortho-
voltage radiation, survival times ranged from 1-36 months. The l-year survival rate was 44.3%.
and the 2-year survival rate was 16.6%. In another study, cats receiving orthovoltage radiation
after rhinotomy had mean and median survival times of 27.9 and 20.8 months, respectively.
Survival rates were 66% at 1 year, 44% at 2 years, and 33% at 3 years.
17. How should SCC of the nasal planum be treated?
SCC of the planum, if detected early, can be treated by surgical removal of the planum, local-
ized radiation, photodynamic therapy, or carboplatinlcisplatin intralesional injection. If surgical re-
section is contemplated. advanced imaging techniques are recommended to assess extent of disease.
18. How is surgical resection done?
Surgical resection involves the removal of the planum, the underlying cartilage. and a por-
tion of the turbinates. Surgical margins should be submitted for histopathology to ensure tumor-
free borders. This procedure is well accepted by cats and owners as a treatment modality. In one
series of 9 feline cases treated with aggressive resection of the planum, the median postoperative
tumor-free period was 16 months with a range of 1-27 months.
19. How successful is localized radiation for treatment of SCC?
In cats with localized SCC of the nasal planum (1-2 em diameter), l-year control rates of
85% have been reported with localized radiation. Survival times for deeply invasive SCC tumors
have improved with higher dose and modified dose-fractionation schemes. After irradiation. l-
and 5-year progression-free survival rates were 60.1 and 10.3%, respectively.
20. What is photodynamic therapy?
Photodynamic therapy is a new modality for cutaneous tumors. It involves the use of laser
light to activate a dye that absorbs light and produces oxygen radicals that destroy surrounding
tissue. The dyes themselves are nontoxic and have the advantage of localizing in abnormally pro-
liferating tissues in preference to normal tissue. Cure rates in a group of 60 cats with SCC were
reported at 60--90%. This modality is used for superficial tumors.
Nasal Tumors
27
21. Howis chemotherapy used for See?
Carboplatin or cisplatin given intralesionally has caused remission of small tumors. Cisplatin
(10 mg in I m1 of saline) may be mixed with 2 m1 of sterilized sesame oil and injected intrale-
sionally. Of cats treated with this regimen, 83% had> 50% reduction in tumor volume; complete
resolution was reported in 64% of cats after 6 treatments with a similar protocol using cisplatin
and a collagen-matrix vehicle. Because of the depot nature of the treatments and slow release of
cisplatin, the systemic toxicity typically seen with cisplatin was not noted. Carboplatin has been
used in a similar manner, resulting in a complete remission rate of 73% and a l-year control rate
of 55%. Carboplatin is safer to use in cats and can also be given as a systemic treatment.
22. What is the overall prognosis for nasal tumors?
The prognosis for cats with untreated malignant nasal tumors is poor. Survival is usually a
few months. Persistent dyspnea, epistaxis, anorexia, weight loss, and neurologic signs are often
reasons for euthanasia.
Radiation treatment is well tolerated, improves survival, provides palliation of clinical signs,
and improves the quality of life in many cats. Reported adverse reactions to radiation therapy in-
clude radiation-induced dermatitis, cataract formation, and nasocutaneous fistula.
seeof the planum can be cured if aggressive treatment is instituted before deep invasion of
the nose. Early skin changes (crusting or hyperemic plaques) should be investigated immediately
to obtain a diagnosis. A "wait-and-see" approach is not appropriate.
Prognosis for lymphoma is difficult to provide for individual cats (see Chapter 68). Important
prognostic factors include stage of disease, anatomic site, response to therapy, and retroviral status.
BIBLIOGRAPHY
I. Beck ER: Shedding light on feline cancers: Photodynamic therapy on the brink of the 21st century.
Proceedings of the 1997 Fall meeting of the American Association of Feline Practitioners, Atlanta. pp
219-220.
2. Carothers M, Couto CG; Respiratory Neoplasia. In Kirk RW, (ed), Current Veterinary Therapy X.
3. Elmslie RE, Ogilvie GK, Gillette EL, et al: Radiotherapy with and without chemotherapy for the control
of localized lymphoma in cats: 10 cases (1983-1989). Vet Rad 32:277-280, 1991.
4. Evans SM, Hendrick M: Radiotherapy of feline nasal tumors: A retrospective study of nine cases. Vet
RadioI30:128-132,1989.
5. Hahn KA, Anderson TE: Tumors of the respiratory tract. In Bonagura JD (ed): Kirk's Current Veterinary
Therapy XIII. Philadelphia, WB. Saunders, 2000, pp 500-505.
6. Hawkins EC: Disorders of the nasal cavity. In Nelson RW, Couto CG (eds): Small Animal Internal
Medicine, 2nd ed. St. Louis, Mosby, 1998, pp 231-232.
7. Ogilvie, GK, Moore AG: Tumors of the respiratory tract. In Managing the Veterinary Cancer Patient.
Trenton, NJ, Veterinary Learning Systems, 1995, pp 314-326.
8. Ogilvie, GK, Moore AG: Tumors of the skin and surrounding structures. In Managing the Veterinary
Cancer Patient. Trenton, NJ, Veterinary Learning Systems, 1995, pp 479-482.
9. Orenburg EK, Luck EE, Brown DM, et al: Implant delivery system: Intralesional delivery of chemotherapeu-
tic agents for treatment of spontaneous skintumors in veterinary patients. Clin Derrnatol 9:561-568, 1992.
10. Peaston AE, Leach MW, Higgins RJ: Photodynamic therapy for nasal and aural squamous cell carci-
noma in cats. JAm Vet Assoc 202:1261-1265,1993.
II. Ruslander D, Kaser-Hotz B, Sardines JC: Cutaneous squamous cell carcinoma in cats. Comp Cont Educ
PractVet 19:1119-1129,1997.
12. Theon AP: Indications and applications of radiation therapy. In Bonagura JD (ed): Kirk's Current
Veterinary Therapy XII. Philadelphia, WB. Saunders, 1995, pp 467-474.
13. Theon AP, Madewell BR, Sheam VI: Prognostic factors associated with radiotherapy of squamous cell
carcinoma of the nasal plane in cats. J Am Vet MedAssoc 206:991-996,1995.
14. Theon AP, Peaston AE, Madewell BR, et al: Irradiation of nonlymphoproliferative neoplasms of the
nasal cavity and parasinuses in 16 cats. JAm Vet Assoc 204:78-83,1994.
15. Theon AP, VanVechten MK, Madewell BR: Intratumoral administration of carboplatin for treatment of
squamous cell carcinomas of the nasal plane in cats. Am J Vet Res 57:205-210, 1996.
16. Withrow SJ, Straw RC: Resection of the nasal planum in nine cats and five dogs. J Am Anim Hasp Assoc
26:219-222,1990.
8. COUGH AND DYSPNEA:
INITIAL DIAGNOSTIC PLAN
1. What is a cough?
The forceful expulsion of air from the lungs. Coughing is a normal physiologic response to
airway irritation. Irritant receptors from the oropharynx throughout the airway epithelium can
stimulate the afferent pathway, resulting in cough. Receptor density is greatest in the larynx and
major lobar airways. Foreign body contact with the airway epithelium stimulates mechanorecep-
tors. Exogenous chemicals (e.g. smoke) and endogenous chemicals (e.g., histamine) stimulate
chemoreceptors. It is possible that all causes of cough induce bronchospasm, which then acts as
the primary stimulus to the cough receptors.
2. What are the physiologic components of a cough?
The vagus and glossopharyngeal nerves carry afferent impulses to the cough center in the
dorsolateral region of the medulla. The efferent impulses resulting in cough are carried by the
vagal nerves, phrenic nerves, recurrent laryngeal nerves, and some spinal motor nerves. Cough
is divided into three phases: respiratory, compressive phase, and expiratory. Once a cough is in-
duced, the animal inspires deeply (respiratory phase). The compressive phase begins with clo-
sure of the glottis and contraction of the expiratory musculature. The expiratory phase occurs as
the glottis suddenly opens, leading to a sudden flow of air from the lungs through the airways.
3. What are the differential diagnoses for cough?
Differential diagnoses for cough in cats can be categorized into upper airway, lower airway,
and cardiovascular causes. Dirofilariasis is the exclusive cardiovascular cause of cough in cats.
Cardiac failure leads to dyspnea, not cough, in cats. Diseases resulting in coughing are relatively
rare in cats compared with dogs.
Differential Diagnoses for Cough in Cats
Upper respiratory tract disease
Congenital disorders
Masses
Allergic
Anatomic
Trauma
Lower respiratory tract disease
Congenital disorders
Masses (neoplastic or granulomatous)
Allergic
Anatomic
Irritants
Foreign body
Infectious diseases (see table in question 8)
Irritants
Foreign body
Gastrointestinal disease with nasal aspiration
Infectious diseases (see table in question 7)
Dysphagia, vomiting. or regurgitationresulting
in aspiration
Pulmonary thromboembolicdisease (dyspnea
more common than cough)
Noncardiogenicpulmonary edema (dyspnea
more common than cough)
4. Define dyspnea and orthopnea.
Dyspnea is a state of difficult, labored, or painful breathing. It can occur intermittently or
continuously or may be more pronounced after exertion. Orthopnea is a state of difficult breath-
ing in a recumbent position.
28
Cough and Dyspnea: Initial Diagnostic Plan 29
5. Definetachypnea, polypnea, andhyperpnea.
Tachypnea, polypnea, and hyperpnea describe conditions resulting in increased respiratory
rates. Tachypneagenerally refers to rapid shallow respirations; polypneaand hyperpnea refer
to rapid deep respirations. Tachypnea, hyperpnea, and polypnea do not denote difficult breathing
and may be due to physiologic changes.
6. What are the differential diagnosesfor dyspnea?
Dyspnea is a pathologic event; conditions resulting in dyspnea can be divided into nasal!
sinus diseases, pharyngeal diseases, airway diseases, pulmonary parenchymal diseases, pleural
diseases, diseases of the muscles of respiration, diseases affecting erythrocyte oxygen carrying
capability, central nervous system diseases, and pain. Several conditions including acidosis,
fever, glucocorticoid excess, and psychological anxiety, can cause tachypnea, polypnea, or hy-
perpnea and are commonly confused with dyspnea.
Differential Diagnoses for Dyspnea in Cats
Cardiac disease
Airway diseases
Pulmonary parenchymal diseases
Pleural diseases
Pneumothorax
Hemorrhage pleural effusions
Transudative pleural effusions
Modified transudate pleural effusions
Pyothorax
Chylothorax
Feline infectious peritonitis
Neoplasia
Peritoneopericardial hernia
Diaphragmatic diseases
Hernia
Muscular weakness
Neurologic (paralysis)
Impingement
Organomegaly (especially hepatomegaly)
Peritoneal effusions
Obesity
Masses
Erythrocyte diseases
Anemia
Methemoglobinemia
Central nervous system diseases
7. What infectious diseasesmay causecoughand dyspneain cats?
Infectious Causes of Cough and Dyspnea in Cats
INFECTIOUSAGENT SYNDROME
Bacterial
Mycoplasma spp.
Bordetella bronchiseptica
Yersinia pestis
Chlamydia psittaci
Aerobes and anaerobes
Viral
Feline calicivirus
Feline herpesvirus I
Feline leukemia virus
Feline immunodeficiency virus
Feline infectious peritonitis virus
Fungal (rare in cats)
Blastomyces dermatitidis
Cryptococcus neotormans
Histoplasma capsulatum
Coccidioides immitis
Aspergillus spp.
URI, pneumonia (17)
URI, pneumonia (17)
Pneumonia
URI
Pyothorax, secondary pneumonia
URI, pneumonia in kittens
URI, pneumonia in kittens
Mediastinal lymphoma, secondary URI or pneumonia
Mediastinal lymphoma, secondary URI or pneumonia
Pleural or peritoneal effusion; granulomatous pneumonia
Pneumonia
URI, rarely pneumonia
Pneumonia
Pneumonia
URI
Table continued onfollowing page
30 Cough and Dyspnea: Initial Diagnostic Plan
Infectious Causes of Cough and Dyspnea in Cats (Continued)
INFECTIOUSAGENT SYNDROME
Parasitic
Migratory
Toxocara cati
Strongyloides stercoralis
Primary
Aelurostrongylus abstrusus
Paragonimus kellicotti
Capillaria aerophila
Polysystemic
Dirofilaria immitis
Toxoplasma gondii
URI= upper respiratoryinfection.
Small airway disease, pneumonia
Small airway disease, pneumonia, pneumothorax
Small airway disease, pulmonary embolism
Pneumonia
8. Can the signalment help in ranking the differential diagnoses?
The age, breed, and gender of a cat with cough or dyspnea lends valuable information for
localization of lesions and identification of primary differentials. Kittens are more likely than
cats to present with congenital abnormalities resulting in cough or dyspnea. Young, nonvacci-
nated kittens commonly develop respiratory tract infections. Older cats commonly develop neo-
plasia, cardiac failure, and chronic bronchitis. Cough due to migratory parasitism is more likely
in kittens. Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infection can
lead to immunosuppression and predispose to infectious causes of respiratory disease. Clinical
FeLV and feline infectious peritonitis virus (FIPV) infections are common in young cats; clinical
FlV infection is common in older cats. Pulmonic toxoplasmosis is more common in neonatal cats
than in older cats. Older cats with cough are likely to have chronic bronchitis and are more re-
fractory to treatment than young cats. Male cats may be more likely to hunt and thus, in the
Southwestern states, may become infected with Yersinia pestis.
9. How can the history help to rank differentials for cough and dyspnea?
Severe, acute coughing occurs commonly with exposure to airway irritants, aspiration, for-
eign body inhalation, and acute infectious diseases.
Coughing in cats with serous oculonasal discharge and pruritic skin disease that occurs sea-
sonally may suggest allergic lung disease.
Mucopurulent oculonasal discharge with or without oral erosions suggests feline rhinotra-
cheitis, especially if the cat has been kenneled or a cattery problem is identified.
Mild cough in cats with low-grade conjunctivitis may beconsistent with chlarnydiosis.
Gagging and dysphagia are reported commonly in cats with pharyngeal or laryngeal causes
of cough, especially cats with nasopharyngeal polyps.
Fungal diseases, heartworm disease, and many parasitic diseases depend on travel to en-
demic areas for exposure.
Respiratory parasites are more common in outdoor cats than indoor cats.
Unvaccinated cats, particularly those in contact with other cats, are likely to have infectious
causes of cough.
Dirofilariasis commonly presents with a history of gagging or vomiting as well as cough.
Slowly progressive cough is common with neoplasia.
Hemoptysis is most common with dirofilariasis, pulmonary contusions, and neoplasia.
Cough after eating may indicate diseases inducing dysphagia.
10. What historical evidence suggests respiratory tract abnormalities associated with dis-
eases of other body systems?
Evidence of other clinical abnormalities, such as vomiting (aspiration pneumonia), polyuria!
polydipsia (uremic pneumonitis), or weakness (diaphragmatic abnormalities).
11. How should clinical problems be characterized?
Owners should be asked to identify the predominant clinical signs of respiratory disease, in-
cluding sneezing, nasal discharge, gagging, dysphagia, stridor (wheezing), stertor (snoring or
snorting), cough, terminal retch, dyspnea, and tachypnea. They should be questioned to deter-
mine whether a perceived cough is truly vomiting, regurgitation, or gagging. Each clinical prob-
lem should be characterized for duration, frequency, time of occurrence, and progression. Nasal
discharges should becharacterized as continuous or intermittent, unilateral or bilateral, whether
they occur with sneezing, and whether they are serous, mucoid, mucopurulent, or hemorrhagic.
12. What physical examination findings are most helpful?
A complete physical examination should be performed on all cats with respiratory tract dis-
ease, including the following:
Emaciation commonly occurs with chronic respiratory tract diseases, including dirofilaria-
sis, neoplasia, cardiac failure, and fungal pneumonia.
Mucous membrane color (cyanotic or pale) and capillary refill time.
Occasionally cats with gastrointestinal tract disease predisposing to aspiration have ab-
dominal palpation abnormalities or evidence of megaesophagus on evaluation of the cervi-
cal region.
Neurologic abnormalities occur with several causes of respiratory tract disease, including
FIPV infection, toxoplasmosis, and systemic mycoses.
Ocular abnormalities can be seen with infectious diseases (FIPV infection, toxoplasmosis,
respiratory viruses, and systemic mycoses) as well as with coagulopathies, hypertension.
and diseases inducing vasculitis.
Abnormalities associated with cardiac dysfunction, including cardiac murmur or gallop
rhythm, arrythmias, jugular pulse, jugular distention, tachycardia, weak arterial pulses.
muffled heart or lung sounds, pulmonary crackles or wheezes, abdominal fluid wave, and
hepatosplenomegaly.
Lymph nodes should bepalpated carefully; lymphadenopathy occurs commonly with lym-
phosarcoma and systemic mycoses.
Cats with dyspnea due to uremic pneumonitis commonly have either large kidneys (acute
nephrosis) or small kidneys (chronic renal failure) on abdominal palpation.
The cat should be carefully assessed for evidence of pain; discomfort can lead to dyspnea
or tachypnea.
The nares should be examined for discharge and size. Airflow through the nares can be es-
timated by holding a cool microscope slide over the nares and observing the area of vapor
condensation.
The oral cavity should be evaluated carefully for evidence of masses, dental disease.
phlegm, tonsillar changes, or foreign bodies.
The skull should bepalpated for evidence of trauma or asymmetry (tumor or fungal disease).
The trachea and larynx should begently palpated to assess for tracheal cough or masses.
13. How should respiratory patterns be assessed?
Respiratory rate should be assessed at rest and after minimal exercise. The respiratory rate
should be 10-30 breaths/minute and should be effortless with minimal abdominal component.
An abdominal press or increased expiratory time is characteristic of obstructive airway disease
or asthma. If the respiratory rate or character is abnormal, attempt to characterize whether the
primary abnormality is dyspnea, tachypnea, or orthopnea. An abnormal respiratory pattern
should be characterized as obstructive (slow and deep) or restrictive (rapid and shallow).
Respiration should be evaluated carefully for the presence of stertor or stridor. Stertor occurs
most commonly with diseases of the nasal cavity, sinuses, and pharynx. Stridor occurs with la-
ryngeal and tracheal diseases. Inspiratory stridor is most common with laryngeal paralysis and
extrathoracic tracheal collapse. Inspiratory and expiratory stridor occur most commonly with
fixed lesions of the larynx and trachea.
14. Discuss the proper technique for thoracic auscultation.
The thorax should be palpated gently for rib fractures, evidence of discomfort, compressibil-
ity (which can be decreased in cats with mediastinal disease), and evidence of cardiac thrill and
or a decreased apex beat. Thoracic auscultation is best performed in a quiet room on a cat that is
not panting or trembling. The respiratory tract should be ausculted prior to cardiac auscultation,
and the trachea should be auscultated to differentiate lower respiratory tract wheezes or crackles
from referred sounds from the trachea.
15. What are the relevant findings of respiratory tract auscultation?
Normal breath sounds vary based on the respiratory pattern, site of auscultation, and thickness
of the thoracic wall. Normal breath sounds are designated as bronchial, vesicular, and bron-
chovesicular. Bronchial sounds are heard predominantly in the perihilar area and trachea; they are
relatively loud and easy to detect. Bronchial sounds are slightly louder on expiration and the expi-
ratory phase is slightly longer than the inspiratory phase. Vesicular sounds develop in the lobar and
segmental bronchi and can be heard distal to the perihilar area. These sounds are described as sim-
ilar to the rustling sound made by wind blowing through trees and are more prominent on inspira-
tion than expiration. Bronchovesicular sounds are generated in the terminal airways and alveoli
and are very soft or difficult to hear. These sounds are heard at the periphery of the thoracic cavity.
Crackles, wheezes, or absence of breath sounds are abnormal. Crackles (rales) sound like crum-
pling cellophane and can be inspiratory, expiratory, or continuous. Crackles are most commonly
induced by fluid in the alveoli or inflammatory diseases of the small airways. End-inspiratory
crackles are consistent with fluid in the alveoli. Right-side and dependent lung lobe crackles are
consistent with aspiration pneumonia. Wheezes (rhonchi) are continuous musical sounds heard
best on expiration. Wheezes are most commonly heard with diseases of the airways. Cats with
asthma often breathe with their neck extended and may appear to have a "barrel chest."
16. What findings of thoracic auscultation suggest cardiac disease?
In dyspneic cats, crackles may suggest hypertrophic cardiomyopathy. If crackles are due to
cardiac disease, cardiac murmurs and elevated heart rate are usually present concurrently, and af-
fected cats rarely cough.
17. What do muffled or absent breath sounds suggest?
They occur most commonly with diaphragmatic hernia, pleural effusions, pneumothorax,
obesity, consolidated lung lobes, and collapsed lung lobes.
18. What is the differential diagnosis for wet vs, dry cough?
With the exclusion of bacterial bronchopneumonia, cats rarely develop moist or productive
coughs. Dry cough occurs commonly with pharyngeal diseases, laryngeal diseases, tracheal dis-
eases, and low-grade inflammation induced by allergic and parasitic etiologies.
19. Can a tracheal cough help to localize the lesion?
The presence of pharyngeal, laryngeal, or tracheal inflammation does not correlate only with
upper airway disease; lower airway inflammation results in passage of inflammation cells up the
mucociliary apparatus to the mouth, leading to secondary inflammation of the upper respiratory
tract. This possibility precludes the use of a tracheal cough to localize the lesion; tracheal cough
can occur just as readily with bacterial pneumonia as with a tracheal foreign body.
20. What is the initial diagnostic plan for most coughing cats?
After assessment of the signalment, history, and physical examination, diagnostic tests are
commonly performed to identify the primary cause of the cough or dypsnea. Primary causes of
cough in cats include asthma, heartworm disease, bacterial bronchitis, and respiratory para-
sitism. The initial diagnostic plan for coughing cats in a nonendemic area for dirofilariasis gen-
erally consists of a complete blood count (CBC), fecal examination, and thoracic radiographs.
In endemic areas for dirofilariasis, Aelurostrongylus abstrusus, or Paragonimus kellicotti, heart-
worm serology, Baermann assessment of feces, and fecal sedimentation, respectively, are per-
formed as well. Further diagnostic testing depends on the results of these procedures.
21. What is the initial diagnostic plan for most dyspneic cats?
The initial diagnostic plan for evaluation of dyspnea is based on the severity of clinical dis-
ease at presentation combined with signalment, physical examination, and history findings. Most
cases ultimately require thoracic radiographs. Thoracocentesis may be necessary. Arterial blood
gas assessment is indicated in some stable, dyspneic cats with pulmonary parenchymal diseases.
22. Which should be performed first-thoracic radiographs or thoracocentesis?
This is one of the most important clinical decisions made by veterinary practitioners.
Although relatively safe, thoracocentesis is not indicated for most causes of dyspnea. However,
thoracocentesis is diagnostic as well as therapeutic for dyspnea due to pleural effusion or pneu-
mothorax (see Chapters 13-15). The veterinary clinician should evaluate the signalment, history,
and physical examination findings carefully; if evidence consistent with pneumothorax or pleural
effusion is present, thoracocentesis should be performed as the initial diagnostic procedure. If
dyspneic cats exhibit a restrictive breathing pattern and diminished breath sounds, thoracocente-
sis should be performed as soon as possible. If the clinician chooses to perform thoracic radi-
ographs as the initial diagnostic procedure, oxygen should be delivered by facemask and a single
dorsoventral radiograph should be made for evaluation of pneumothorax or pleural effusion.
23. Howshould cats be stabilized before performing diagnostic procedures?
All cats with dyspnea should be stabilized before performing diagnostic procedures. The
minimal stress associated with venipuncture, thoracocentesis, or thoracic radiographs is enough
to induce cardiopulmonary arrest in many cats with severe compromise. Delivery of oxygen by
facemask or, preferably, oxygen cage for 15-20 minutes often stabilizes dyspneic animals ade-
quately to allow performance of minimal diagnostic tests.
24. How can the CBC aid in the diagnosis of cough or dyspnea in cats?
Most cats with upper airway inflammation have normal leukograms. An inflammatory
leukogram with or without a left shift is most common with bacterial pneumonia and pyothorax.
However, the lack of an inflammatory leukogram does not rule out bacterial colonization of the
lower airways. All cats with bacterial inflammation of the lower respiratory tract should be eval-
uated for the presence of an underlying etiology especially FeLV and FlY. Lymphopenia is com-
monly induced by FeLV and FlV and may be present in immunosuppressed cats. Monocytosis is
also a component of a stress leukogram and so can be hard to interpret. Persistent monocytosis is
consistent with chronic inflammation and occurs with many chronic respiratory diseases.
Monocytosis is commonly identified in cats with dirofilariasis. Eosinophilia and basophilia most
commonly occur with asthma, dirofilariasis and respiratory parasites. However, eosinophilia and
basophilia also occur commonly with allergic and parasitic diseases of the skin and gastrointesti-
nal tract. Cats with respiratory disease and eosinophilia or basophilia should be evaluated with
heartworm serology; thoracic radiographs; transtracheal wash for cytology, culture, and sensitiv-
ity testing; fecal flotation and sedimentation (in areas endemic for Paragonimus spp.): and
Baermann examination of feces.
25. When should you perform a serum biochemical panel or urinalysis in cats with cough
or dyspnea?
Occasionally cats with uremic pneumonitis present with cough; azotemia is noted on the bio-
chemical panel. The serum biochemical panel should be used to screen all older cats with bacterial
lower respiratory disease. Hyperglobulinemia occurs with some diseases of the respiratory tract,
particularly, dirofilariasis, chronic bronchitis, neoplasia, and toxoplasmosis. All cats with cough
and hyperglobulinemia should be evaluated for dirofilariasis. Total carbon dioxide is an indirect
measurement of serum bicarbonate and can be used to estimate acid-base status. Hypoalbumi-
nemia can result in a transudative pleural effusion; the biochemical panel can be used to screen
for potential abnormalities. Urinalysis should be performed in any cat for which a serum bio-
chemical panel is justified. Proteinuria occurs most commonly with dirofilariasis, fungal dis-
eases, retroviruses, FIPV, and neoplasia. However. any chronic antigenic stimulation in the
respiratory tract may result in the production of circulating immune complexes. deposition at the
glomerular basement membrane. and induction of proteinuria.
26. What are the major thoracic radiographic abnormalities in alveolar lung disease?
Alveolar lung disease is characterized by air bronchograms that develop as the alveolar sacs
fill with fluid and outline air-filled airways. Air bronchograms occur most commonly with car-
diogenic pulmonary edema. neurogenic pulmonary edema, bacterial bronchopneumonia,
eosinophilic inflammation. and hemorrhage. Air bronchograms are seen occasionally with at-
electatic lungs and granulomatous diseases. In general, a transtracheal wash should be performed
in cats with cough and air bronchograms without physical or radiographic evidence of cardiac
disease. Toxoplasmosis is a cause of alveolar lung disease in neonatal cats.
27. Discuss the significance of bronchial patterns.
Bronchial patterns develop as the peribronchiolar tissues become inflamed. Inflammation of
the peribronchiolar tissues results in "doughnuts," or air-filled circles surrounded by soft-tissue
density. Bronchial patterns develop most commonly with inflammation of the airways. Irritant
gases. allergic disease. viral disease. and some bacterial diseases commonly lead to a bronchial
pattern. Most cats with asthma have a marked bronchial pattern.
28. Discuss the significance of interstitial patterns.
The pulmonary interstitium is the supporting network of the lungs. The pulmonary blood
supply courses through the interstitial space. Interstitial patterns can be divided into the follow-
ing categories:
Diffuse interstitial patterns appear as an increased soft tissue density in the interstitium and
may occur in older cats as a result of normal aging. Interstitial disease develops in the first stages
of cardiogenic pulmonary edema. Mycoplasmal pneumonia can cause a diffuse interstitial pat-
tern. Any cause of vasculitis or coagulopathy can present with a diffuse interstitial pattern.
Miliary interstitial patterns are characterized by 1-5-mm masses and occur most commonly
with fungal disease and metastatic neoplasia.
Nodular interstitial patterns are characterized by O.S-l-cm masses and are most common
with fungal disease. metastatic neoplasia, and primary pulmonary neoplasia.
Tumorous interstitial patterns are characterized by masses> 1 cm and are most common
with primary pulmonary neoplasia.
29. How do you assess for vascular patterns?
In the dorsoventral or ventrodorsal radiograph, the artery is located laterally. followed
medially by the bronchus and vein. Pulmonary venous hypertension occurs most commonly with
hypertrophic cardiomyopathy. Pulmonary arterial hypertension occurs most commonly with
dirofilariasis. In the lateral thoracic radiograph. the cranial lobar artery is most dorsal. fol-
lowed ventrally by the bronchus and vein.
30. What pleural diseases may result in restrictive breathing patterns?
Usually restrictive breathing patterns are associated with pneumothorax, pleural effusions,
mass lesions, or diaphagmatic abnormalities.
31. When should an airway washing be performed?
Airway washings should be performed after assessment of the thoracic radiographs and is
indicated for all coughing cats with interstitial. bronchial. or alveolar lung patterns that are not
suspected to be due to cardiogenic disease or coagulopathy. The goal of transtracheal washing
(TrW) is to collect fluids from the lower airways for cytology, culture, and sensitivity testing.
32. How should airway secretions be collected?
Bronchoscopy with bronchoalveolar lavage is the most sensitive technique but requires gen-
eral anesthesia and a bronchoscope. Because cats commonly develop subcutaneous emphysema
and pneumomediastinum after TTW, it is preferable to use a trans oral approach. Materials
needed include a sterile catheter or feeding tube (6 or 7 French), 2% lidocaine, sterile saline, ster-
ile swab, transport media (Portacul, Bectin-Dickinson Microbiology Systems, Franklin Lakes,
NJ), syringes, needles, and microscope slides.
33. How is transoral TTW performed?
I. Intravenous administration of 10-30 mg of ketamine (100 mg/ml) and an equal volume
of diazepam (5 mg/ml) generally provides enough sedation to intubate the animal successfully
but not to ablate the cough response.
2. After administration of ketamine and diazepam, place 1 drop of 2% lidocaine on each
arytenoid.
3. Place the cat in sternal recumbency, and intubate with a sterile 3.5 tracheal tube, taking
care to avoid contact with the oral cavity.
4. The carina is located approximately at the point where the elbow crosses the midtho-
racic region. Measure from this point up the trachea to estimate how far to insert the TTW
catheter.
5. After intubation and placement of the sterile catheter, instill 2-3 ml sterile saline. As
you are injecting, encourage the cat to cough by tracheal manipulation or thoracic compression.
6. After injection of saline, immediately aspirate with the sterile collection syringe.
Recovered saline should contain respiratory secretions that are easily visualized as flocculent
material.
7. The tracheal washing can be repeated up to 3-4 times until an adequate sample is ob-
tained; 0.5-1.0 ml provides sufficient fluid for most analyses.
8. The washing can be performed in right or left lateral recumbency; if a unilateral lesion is
present, place the diseased side down.
9. After collection of respiratory secretions, place a sterile swab into the fluid; then place the
swab into the Portacul for aerobic culture, mycoplasmal culture, and antibiotic susceptibility testing.
10. The remainder of the respiratory secretions can be used for cytologic evaluation. Direct
smears and cytospins are generally performed. Examine for infectious agents, including intracel-
lular bacteria, white blood cells, and neoplastic cells.
II. Administer 100% oxygen through the tracheal tube while in sternal recumbency until
ready to be extubated.
34. What are the most common abnormalities noted on cytologyof airway washings in cats?
The presence of eosinophils is consistent with asthma, parasitism, and granulomatous dis-
ease. Neutrophils and macrophages are commonly increased with bacterial disease, and intracel-
lular bacteria may be present, indicating bacterial infection. Bacteria can be found in airway
washings from healthy cats because they are commonly present at the carina. The presence of a
positive bacterial culture with no evidence of neutrophils on cytologic examination is difficult to
interpret. Parasitic larvae are commonly identified by TrW. Neoplastic cells are sometimes re-
trieved, and pulmonary involvement of lymphoma can be documented. Fungal elements can be
found in some cases.
35. When is transthoracic aspiration biopsy indicated?
Primary indications for transthoracic aspiration biopsy are interstitial (including masses) or
alveolar diseases that were not diagnosed by cytology of transoral washings. This technique is
more dangerous than TrW because of the increased risk for development of pneumothorax or
hemothorax, particularly in cats with severe cough or dyspnea.
36. What materials are required for transthoracic aspiration biopsy?
Twenty-two-gauge spinal needles, 2% lidocaine, clipper blades, surgical preparation solu-
tions, sterile saline, culturette, transport media, syringes, needles, and microscope slides.
37. Howis transthoracic aspiration biopsy performed?
I. Use the thoracic radiographs or ultrasound to identify the area to be aspirated.
2. Entry through the seventh, eighth, or ninth intercostal space is preferred to avoid great
vessels, large airways, and the liver.
3. Choose a spinal needle of appropriate length.
4. Clip a 3 x 3-cm area over the entry site, and perform a surgical preparation.
5. Administer 0.25-0.5 ml of 2% lidocaine subcutaneously over the entry site.
6. Position the spinal needle so that the entry avoids the periosteum (pain) and caudal area
of the ribs (vessels).
7. Pass the needle on a single plane to the depth calculated for the aspiration.
8. Remove the stylet, place a sterile syringe, and aspirate. It is generally safe to advance
the needle inward on a single plane, but do not move laterally.
9. Remove the needle from the animal.
lO. Place a small amount of the aspirated material on a sterile swab and place in a Portacul;
make thin smears with remainder of the aspirate.
II. Request aerobic, anaerobic, and mycoplasmal culture as well as antibiotic susceptibility
testing from the Portacul and routine cytologic assessment of the thin smears.
12. If a poor yield is obtained, the aspirate can be repeated with injection of 0.5 ml of sterile
saline before aspiration to mobilize respiratory cells and secretions.
38. When is transthoracic biopsy indicated?
Transthoracic biopsies are reserved for cases with nodular to tumorous interstitial lung dis-
ease for which airway washing and transthoracic aspiration fails to give a diagnosis. A primary
indication is to differentiate granulomatous disease from neoplasia. Sedation or anesthesia is re-
quired. Biopsies are generally obtained by passing a small biopsy forceps (Biopty, CR Bard,
Covington, GA) through the intercostal space into the mass. Primary disadvantages include
hemothorax and pneumothorax. The procedure is performed as described for transthoracic aspi-
ration. Ultrasound, fluoroscopy, or thoracoscopy should be used to help guide the biopsy instru-
ment, if available. For solitary masses, surgical excision is often recommended for diagnosis and
potential cure.
39. When should ultrasound be used in the work-up of coughing or dyspneic cats?
Echocardiography is a valuable aid for the diagnosis of cardiac diseases such as cardiomyopathy
or pericardial effusion that may result in dyspnea. Dirofiliaria immitis can be seen in the main pul-
monary artery of many infected cats by ultrasound (see Chapter 10). Ultrasound can be used to iden-
tify diaphragmatic hernia or diaphragmatic-pericardial hernia. Transthoracic biopsy can be guided
by ultrasound. Ultrasonic evaluation of the mediastinum can be used to document mass lesions.
BIBLIOGRAPHY
J. Hawkins EC: Clinical manifestations of lower respiratory tract disorders. In Nelson RW, Couto GC (eds):
Small Animal Internal Medicine, 2nd ed. St. Louis, Mosby, 1998, pp 249-253.
2. Hawkins EC: Diagnostic tests for the lower respiratory tract. In Nelson RW, Couto GC (eds): Small
Animal Internal Medicine, 2nd ed. St. Louis, Mosby, 1998, pp 254-284.
9. SMALL AIRWAY DISEASE
Elisa M. Mazzaferro, M.S., D.V.M.
1. What is feline asthma?
Feline asthma is a syndrome characterized by acute bronchoconstriction leading to cough
and/or respiratory distress. Clinical signs may require immediate therapy or may resolve without
treatment. The exact cause of asthma in cats has not been determined.
2. How does feline asthma differ from chronic bronchitis?
Chronic bronchitis is a condition in which other causes of cough, such as pneumonia,
heartworm infestation, bronchopulmonary neoplasia, and lungworm infection, have been ruled
out. Cats with chronic bronchitis typically cough on a daily basis for at least 2 months of the year.
The cough associated with chronic bronchitis is usually refractory to bronchodilator therapy.
Asthma is a disorder characterized by acute bronchoconstriction that causes signs ranging from
intermittent coughing to life-threatening respiratory distress. The cat with asthma commonly has
asymptomatic periods between episodes of respiratory signs. Usually the signs associated with
asthma in the cat are exquisitely responsive to bronchodilator therapy.
3. What unique features of the feline pulmonary system predispose to asthma?
The feline pulmonary system is unique in that airway smooth muscle can be found distally
as far as the alveolar duct. In addition, the ratio of airway smooth muscle to bronchial wall thick-
ness is greater in cats than in other examined species. Feline bronchioles are abundant in goblet
cells, and inflammatory stimulation results in mucus accumulation. Cilia extend to just beyond
the level of mucus-producing structures.
4. Are certain breeds of cats predisposed to developing asthma?
Feline asthma has been documented in cats of all breeds and ages. The Siamese cat, how-
ever, may have an increased incidence of bronchial disease compared with the general cat popu-
lation, suggesting a genetic predisposition.
5. What predisposing factors may contribute to development of chronic lower airway dis-
ease in cats?
Congenital abnormalities in structure and function of airway cilia
Parasitic infestation of the tracheobronchial tree
Mycoplasmal infection
Viral or bacterial infection
Exposure to noxious substances or inhaled irritants
Immune-mediated or allergic phenomena
Airway hyperreactivity
6. What are the most common presenting complaints in cats with asthma?
Mild-to-moderate cough, wheezing, open-mouthed breathing, exercise intolerance or lethargy,
or acute respiratory distress.
7. What is the pathogenesis of clinical signs in cats with asthma or bronchial disease?
Inflammation probably plays a key role in feline small airway disease. Mast cell degranula-
tion and eosinophil-lymphocyte interactions result in the release of mediators and cationic pro-
teins that affect the epithelium and smooth muscle. The respiratory epithelium responds to
irritating or inflammatory stimuli by hypertrophy, metaplastic change, and erosion or ulceration.
The underlying smooth muscle layer also becomes hyperplastic, and in some cats airway hyper-
reactivity is present. Such changes cause a reduction in the size of the airway lumen. and small
37
38 Small Airway Disease
changes in airway diameter cause tremendous increases in airway resistance. Increased airway
resistance and inflammatory airway disease lead to clinical signs.
8. What are the mediators of bronchoconstriction in cats?
Studies in experimentally induced feline airway disease suggest that serotonin release from mast
cells causes smooth muscle contraction in vitro. This response may result in bronchoconstriction and
respiratory distress in cats with asthma. Stimulation of histamine receptors commonly causes bron-
choconstriction in dogs and humans; however. cats have different histamine receptors within the air-
ways. Activation of histamine receptors in cats may have no effect, cause bronchoconstriction, or
result in bronchodilation. The role of leukotrienes in airway constriction in cats is unclear.
9. What physical examination rmdings are associated with asthma in cats?
Physical examination in cats with acute respiratory distress can be dangerous because han-
dling can easily exacerbate dyspnea. Physical examination findings range from a normal respira-
tory pattern at rest to severe expiratory dyspnea. Tachypnea, adventitious lung sounds, increased
tracheal sensitivity, and crackles or wheezes on auscultation are often present. Marked expiratory
difficulty with an expiratory push may be apparent in severe cases. Some cats may develop a
barrel-shaped appearance to the thorax or show decreased thoracic compressibility.
10. What are the most appropriate emergency treatments for cats with asthma?
Emergency therapy for cats presenting with respiratory distress includes administration of
oxygen and use of minimal restraint or manipulation. Small changes in airway diameter with
bronchodilating agents can cause rapid and marked improvement in the clinical signs of dyspnea
associated with a feline asthmatic crisis. In addition to oxygen, bronchodilator therapy with sub-
cutaneous terbutaline (0.01 mg/kg) or intramuscular aminophylline (4 mg/kg) can be used.
Nebulization of terbutaline (0.01 mglkg in deionized water) in a small oxygen cage also may be
beneficial. If respiratory distress persists after 5-10 minutes of observation, rapidly acting gluco-
corticoids are administered to decrease airway inflammation. When the patient's respiratory pat-
tern is more stable, diagnostic tests such as bloodwork and radiographs can be performed.
Emergency and Long-term Therapy for Feline Asthma
EMERGENCY
DRUG DOSE OR LONG-TERM MECHANISM
Antibiotics
Chloramphenicol
Doxycycline
Enrofloxacin
Bronchodilators
Aminophylline
Terbutaline
Theophylline
Epinephrine
12.5-2OmglkgPO every 12
hr
5 mglkg PO every 12-24
hr
5 rng/kg PO every 24 hr
4mglkgIM
5 rug/kg PO every 8-12 hr
0.01 mglkg SC
0.625 mg PO every 12 hr
50-100 mg/cat PO every
24hr
20 mglkg SC, IV, IM, or
IT
Long-term
(2-4 wk)
Long-term
(2-4 wk)
Long-term
(2-4 wk)
Emergency
Long-term
Emergency
Long-term
Long-term
Emergency
Antibiotic
Antibiotic and anti-inflamma-
tory
Antibiotic
Phosphodiesterase inhibitor;
increased or decreased his-
tamine release, decreased
release of slow-acting
subtance of anaphylaxis,
pulmonary smooth muscle
relaxation
Beta agonist, smooth muscle
relaxation
As for aminophylline
Beta agonist, smooth muscle
relaxation
Small Airway Disease
Emergency and Long-term Therapy for Feline Asthma (Continued)
EMERGENCY
DRUG DOSE OR LONG-TERM MECHANISM
39
Glucocorticoids
Dexamethasone SP 1-2 mg/kgSC, IV,1M Emergency Anti-inflammatory, decreases
eosinophilchemotaxisand
adherence, decreasescyto-
kine production
Dexamethasone 0.25 mg/kgPOevery8-24 Long-term As for dexamethasone SP
hr; thentaperto every48
hrfor 1-2 mo
Prednisolone 1 mg/kgPOevery 12 hrfor Long-term As for dexamethasone SP
10--14days; then taper to
2.5 mg/kgevery48 hr
Prednisonesodium 50--100 mg/cat IV Emergency As for dexamethasone SP
succinate 0.1-0.625 mg/kgPOevery Long-term
12hr
Triamcinolone 0.11 mg/kgPOevery 12-24 Long-term As for dexamethasone SP
hr, then taper; or
0.11 mg/kgSQandrepeat
in 7-14 days if necessary
Others
Cyclosporine-A 10 mg/kgPOevery 12 hr Long-term Decreases activtated T-lympho-
cyte function
Cyproheptadine 2 mg/catPOevery 12hr Long-term Serotonin antagonist, decreases
smoothmusclecontraction,
maycausebronchodilation
Zafirkulase 5 mg POevery12hr Long-term Leukotriene D4 andE4 antag-
onist
PO= orally, 1M = intramuscularly, SC= subcutaneously, IT= intratracheally, IV= intravenously.
11. What diagnostic tests should be performed in cats with asthma?
Complete blood cell count
Serum biochemistry profile
Thoracic radiographs
Occult heartworm test in endemic areas
Fecal flotation and Baerman examination for parasite ova and larvae (see Chapter 11)
Airway sampling for cytology and culture (see Chapter 8)
12. What are the radiographic signs of fetine asthma?
Bronchial markings with "doughnuts" and "tram lines" (see figure on following page)
Hyperlucent lung areas
Flattening and caudal displacement of the diaphragm
Air trapping and hyperinflation
Right middle lung lobe atelectasis with mediastinal shift to the right
13. Define bronchiectasis.
Bronchiectasis is the irreversible dilation of bronchi due to destruction of the airway wall
from inflammation. Occasionally, these airway changes may be visible on radiographs. Bronchi-
ectasis may be secondary to chronic bronchitis in cats.
14. What changes may be observed in airway fluid from cats with asthma?
Cats with airway disease have increased numbers of inflammatory cells in airway fluid, and
the number of cells in bronchial fluid appears to correlate with the severity of clinical disease.
40
A and B. Thoracic radiographs from a cat with bronchial and inter-
stitiallung disease consistent with asthma.
Eosinophils may predominate in some patients with asthma or bronchitis, but a large number of
eosinophils (up to 25% of cells) may be present in airways of normal cats. Therefore, the pres-
ence of eosinophils supports a diagnosis of asthma or bronchitis but does not necessarily prove
that the disease is present. In many studies, nondegenerate neutrophils were the predominant cell
type found in airway cytology from cats with a clinical diagnosis of bronchial disease or asthma.
15. Are infectious agents involved in feline small airway disease?
Flavobacterium. Bordetellabronchiseptica, Streptococcus spp., Acinetobacterspp., Entero-
hacterspp., and lesser numbers of Pseudomonas spp., and Klebsiella spp. have been isolated from
bronchial cultures of healthy cats. Bacteria also have been isolated from 25--42% of cats with
bronchial disease, making it difficult to interpret positive bacterial culture results. Mycoplasma spp.
have been cultured from the airways of approximately 25% of cats diagnosed with feline asthma
but have not been cultured from the airways of healthy cats. Therefore, positive mycoplasmal cul-
tures from airway fluid may indicate involvement of Mycoplasma spp. in clinical disease. Some
cats with bronchopulmonary disease have clinical signs suggestive of upper respiratory tract infec-
tion, but the role of viruses in feline airway disease is unknown. Viral culture is often unrewarding.
16. How can infection with Mycoplasma spp. contribute to clinical signs in cats with small
airway disease?
Experimental investigations in some species indicate that Mycoplasma spp. can degrade a
neutral endopeptidase enzyme that breaks down substance P. Accumulation of substance P in the
airways can cause smooth muscle constriction and edema. Thus, in some cats, doxycycline trea-
ment can be beneficial both for its antimycoplasmal effects and for decreasing inflammation.
17. What are the differential diagnoses in cats with acute respiratory distress (seeChapter 8)?
Lower airway disease
Congestive heart failure/pulmonary edema
Pleural space disease (pleural effusion, pneumothorax, mediastinal masses)
Pain
Fear
Pneumonia
Anemia
Methemoglobinemia (e.g., secondary to acetaminophen toxicity)
Trauma (flail chest, pneumothorax, hemothorax, diaphragmatic hernia)
Smoke inhalation
Carbon monoxide intoxication
41
18. What is the mainstay of long-term therapy for cats with asthma or bronchial disease?
Long-term therapy (see table in question 10) is directed at suppressing inflammation with
sustained administration of glucocorticoids. Most commonly, prednisolone is administered at I
mg/kg orally every 12 hours for 10-14 days. The dose then is tapered gradually to 2.5 mg/kg
orally every 48 hours. The primary benefit of glucocorticoid therapy is inhibition of phospholi-
pase A
z
, that is necessary for metabolism of arachidonic acid to prostaglandins, leukotrienes and
platelet-activating factor. G1ucocorticoids also can minimize airway inflammation by decreasing
eosinophil chemotaxis and epithelial adherence. Some cats that fail to respond to prednisolone
respond to dexamethasone or triamcinolone.
19. When is bronchodilator therapy useful?
In cats with reversible airway constriction, bronchodilator therapy may be added. Terbutaline
(0.625 mg orally every 12 hr) and extended-action theophylline (Theodur, Key Schering-Plough
Corporation, Kenilwirth, NJ; Slo-bid gyrocaps, Rhone Poulenc Rorer, King of Prussia, PA) ad-
ministered orally at 50-100 mg once daily in the evening are used most frequently. In addition,
there are anecdotal reports of some cats tolerating nebulization with terbutaline or aminophylline
diluted in deionized water as a nightly treatment.
20. What other options are available?
In cats that are intolerant of glucocorticoids or have an inadequate response to glucocorti-
coids and bronchodilators, a trial of the antiserotonin drug cyproheptadine (2 mg orally every
12 hr) is recommended. In addition, adjunctive use of serotonin antagonist drugs with glucocorti-
coids may be useful for long-term therapy. Cyclosporine-A decreases activated T-Iymphocyte
function and, in experimentally induced feline airway disease, histologic alterations that may be
responsible for signs of chronic airway disease. Therapy may prove beneficial in selected cases
of severe feline bronchial disease. Trough cyclosporine levels should be 500-1000 ng/ml. Anti-
interleukin-S antibody treatment has been effective in alleviating clinical signs of bronchocon-
striction in cats with experimentally induced asthma. Fish oil supplementation, with high
omega-3 fatty acid concentrations, can decrease the amount of arachidonic acid available for
leukotriene release and may be beneficial in long-term therapy. Finally, there are anecdotal re-
ports of success with the antileukotriene zafirlukast (Accolate, Merck & Co., West Point, PAl
for treating cats with lower airway disease.
21. What effects do beta, agonists have on airways?
Inhibition of cholinergic neurotransmission
Stabilization of mast cell membranes with inhibition of mast cell mediator release
Decreased vascular permeability
Increased mucociliary clearance
22. Are antibiotics beneficial in the treatment of feline asthma?
If a bacterium is grown in pure culture or if Mycoplasma spp. are isolated, antibiotic therapy
should be instituted for a minimum of 3 weeks. Routine use of antibiotics in feline asthma, how-
ever, is controversial. Various bacterial species have been cultured from airways of healthy cats,
42 Small Airway Disease
and tracheobronchial cultures are often negative in cats with airway disease. Most cultured bacte-
ria probably represent colonization secondary to chronic airway inflammation rather than pri-
mary infections. The exception is Mycoplasma spp., which may be a primary pathogen, causing
structural damage to the airway epithelium. The use of doxycycline, enrofloxacin, or chloram-
phenicol is indicated when Mycoplasma spp. are cultured (see table in question 10).
23. Why is N-acetylcysteine contraindicated in the treatment of acute feline bronchocon-
striction?
N-acetylcysteine (Mucomyst, Apothecon, Inc., Princeton, NJ) is a mucolytic agent that
breaks disulfide bonds in proteins present in airway secretions, thereby decreasing the viscocity
of airway mucus. However, aerosol therapy with N-acetylcysteine can promote bronchoconstric-
tion by irritating the airway epithelium.
24. What other drugs are contraindicated in the treatment of feline asthma?
Beta-adrenergic blocking drugs, such as propranolol, are contraindicated because decreasing
adrenergic tone may aggrevate bronchoconstriction and worsen respiratory difficulty. Sedatives
that suppress respiration can exacerbate hypoventilation and hypoxemia. Atropine, as a single in-
jection, may temporarily relieve bronchospasm, but long-term use is contraindicated because it
increases viscocity of airway mucus. Similarly, inappropriate diuretic therapy can dry respiratory
secretions and decrease mucociliary clearance. Because histamine may be beneficial in cats with
asthma by causing bronchodilation, the use of antihistamines may be contraindicated or not
useful in cats with airway disease.
25. What is the long-term prognosis for cats with asthma?
Most cats with asthma experience additional acute episodes. Clients should be instructed
that immediate veterinary attention is necessary as soon as clinical signs develop. In addition,
avoidance of noxious gases, particulate matter (such as aerosol sprays or carpet powders), and
smoke can avoid or delay recurrence. Bronchiectasis may be a long-term sequela of feline lower
airway disease. With time, respiratory function can become severely compromised to such an
extent that humane euthanasia is warranted.
BIBLIOGRAPHY
I. Bauer T: Pulmonary hypersensitivity disorders. In Kirk RW (ed): Current Veterinary Therapy X.
Philadelphia, ws. Saunders, 1989, pp 369-376.
2. Corcoran BM, Foster D1, Fuentes VL: Feline asthma syndrome: A retrospective study of the clinical pre-
sentation in 29 cats. 1 Small Anim Pract 36:481-488,1995.
3. Dye TL, Teague HD, Poundstone ML: Lung lobe torsion in a cat with chronic feline asthma. 1 Am Anim
Hosp Assoc 34:493-495, 1998.
4. Moise NS, Wiedenkeller D, Yeager AB, et aI: Clinical, radiographic, and bronchial cytologic features of
cats with bronchial disease: 65 cases (1980-1986). 1 Am Vet Med Assoc 194:1467-1473, 1989.
5. Moses BL, Spaulding GL: Chronic bronchial disease of the cat. Vet Clin North Am Small Anim Pract
15:929-948, 1985.
6. Padrid P: Chronic lower airway disease in the dogs and cat. Probl Vet Med 4:320-344, 1992.
7. Padrid P: New strategies to treat feline asthma. Vet Forum Oct:46-50, 1996.
8. Padrid P: CVT Update: Feline Asthma. In Kirk RW (ed): Current VeterinaryTherapy XIII. Philadelphia,
W.B. Saunders, 2000, pp 805-810.
9. Padrid, PA, Mitchell RW, Ndukwu 1M, et al: Cyproheptadine-induced attenuation of type I immediate
hypersensitivity reactions of airway smooth muscle from immune-sensitized cats. Am 1 Vet Res
56:109,1995.
10. Wingfield WE: Allergic airway disease (asthma) in cats. In Wingfield WE (ed): Veterinary Emergency
Medicine Secrets, 2nd ed. Philadelphia, Hanley & Belfus, 2000, pp 170-173.
10. DIROFlLARIASIS
Jeff D. Bay, D.V.M.
1. What causes dirofilariasis?
Dirofilaria immitis, a nematode parasite transmitted by mosquitoes, is the causative agent in
both dogs and cats.
2. How does dirofilariasis differ in cats and dogs?
Cats are more resistant hosts than dogs and are less easily infected.
Cats usually are infected with fewer worms (usually 6 or less and commonly 1 or 2) be-
cause of a more aggressive immunologic response.
The heartworm life span in cats is only about 2-3 years compared with 5-7 years in dogs.
Caval syndrome (dirofilarial hemoglobinuria) is rare in cats because of the low worm
burden.
Cats more often exhibit signs associated with aberrant migration of heartworms.
3. What is the prevalence of D. immitisinfection in cats?
Feline heartworm disease (FRD) has been found practically everywhere in the world that it is
seen in dogs, but its incidence is generally lower. A recent survey analyzed the prevalence of posi-
tive heartworm antibody tests in subclinically infected cats from endemic and nonendemic areas of
the United States. This survey suggests regional differences in prevalence, with rates ranging from
4-33%. Of the cats that were antibody-positive, 3% were also positive for heartworm antigen.
However, correlation of antibody and antigen detection test results have varied among studies.
4. Which cats are susceptible to D. immitis infection?
Cats may be infected at any age. In some natural and experimental infections, male cats were
infected more frequently and more heavily. Indoor cats may be at lower risk for encountering in-
fected mosquitoes, but approximately one-third of cats with FHD live totally indoors.
5. Describe the life cycle of D. immitisin cats.
Cats are infected by D. immitis when an infected mosquito injects stage L
3
larvae during
feeding. The larvae develop through an L
4
stage to adult worms (L
s),
which usually arrive in the
pulmonary arteries at approximately 5-6 months after infection. An antibody response is
mounted against migrating larvae, and positive titers may be detected 3 months after infection. If
at least one adult male and one adult female worm are present, microfilaria (L
I
larvae) can be
found between 6 and 8 months after infection, but it appears that occult infections are common in
cats because their immunologic response rids the body of microfilaria. Thus, it is unlikely that
cats serve as a source of L
1
larvae to infect mosquitoes. For undetermined reasons, aberrant mi-
gration of heartworm occurs more commonly in cats than in dogs.
6. Are microfilaria prevalent in cats with FHD?
Cats with FHD are rarely microfilaria-positive. The period in which infected cats demon-
strate microfilaremia is small (approximately 1 month, between 195 and 228 days after infec-
tion). In addition, feline heartworm infection is typified by a low worm burden or infection with
immature worms, thus limiting the number of microfilaria produced. However, heartworm is the
only filarial disease in cats. Therefore, if microfilaria are detected, the diagnosis is confirmed.
7. What are the clinical signs ofFHD?
The most common clinical signs involve the respiratory tract; cough, dyspnea, and tachypnea
are common. Vomiting is also common, either alone or in combination with respiratory signs in
43
44 Dirofilariasis
some cats. Central nervous system signs (e.g., blindness, seizures), probably due to aberrant
worm migration, can be appreciated in rare cases. Sudden death may occur without prior signs
apparent to the owner. A small percentage of infected cats exhibit no clinical signs, apparently
because the infection is cleared before worm maturation or the cat outlives the worm's life span
with inapparent infection.
8. How is FHD diagnosed?
Diagnosing PHD can be difficult. In many cases, the tentative diagnosis is based on a variety
of suggestive findings rather than a single definitive test. Detection of D. immitis microfilaria in
blood confirms the diagnosis of PHD (high specificity) but has poor sensitivity. When concentra-
tion methods such as the modified Knott or filter tests are used, a larger volume of blood (3 ml)
should be used than the amount recommended for dogs (1 ml).
9. What routine laboratory abnormalities may be seen in FHD?
Peripheral eosinophilia and basophilia should increase suspicion of D. immitis infection, but
these findings are not specific because they can be caused by any internal or external parasitic
disease or hypersensitivity reaction. Polyclonal garnmopathy and proteinuria also occur in some
cats but are not specific for PHD.
10. Discuss the role of serologic tests in the diagnosis of FHD.
Positive test results for serum host antibody (i.e., feline heartworm antibody titers) against
D. immitis antigens generally become positive 90 days after infection. These titers are highly sen-
sitive but not specific for PHD because antibodies can develop against larvae that never become
adult heartworms. In addition, antibodies may persist in cats that were exposed to D. immitis but
are not currently infected. Serologic tests detecting female heartworm antigen (i.e., occult heart-
worm tests) are nearly 100% specific, but their sensitivity is lower because of parasite immaturity
at the time of the test or because too few female worms infected the cat. When FHD is suspected,
antibody serology can be used as a screening test; a positive antigen test confirms infection.
However, antibody tests can be negative in cats with FHD. For example, in one study of 25 anti-
gen-positive cats, only 4 or 5 cats were positive for antibody when tested with two different com-
mercially available kits. In addition, a negative antigen test result does not rule out active disease.
Thus, serum tests should not be used alone to make the diagnosis of PHD.
11. What signs of FHD may be seen on thoracic radiographs?
Thoracic radiographs of cats with FHD commonly show enlarged caudal lobar arteries, with
the artery> 1.6 times the width of the ninth rib. This finding is generally evident 6-7 months
after infection. A diffuse bronchointerstitial pattern may be seen, but radiographic abnormalities
can be transient. Radiographic changes in the cardiac silhouette are rarely seen in cats infected
with FHD. Uncommon findings include pleural effusion and lung lobe collapse. Thoracic radi-
ographs are also valuable for assessing the severity of disease and monitoring its progression or
regression over time. (See figure on following page.)
12. Is echocardiography helpful in diagnosing FHD?
Sometimes. Echocardiography is a highly specific test if heartworms are seen in the right
heart. D. immitis typically appear as multiple, parallel, double-linear, hyperechoic objects in the
right ventricle or main pulmonary artery segment. However, because the organism commonly re-
sides in the pulmonary arteries, it may not be visualized by echocardiography.
13. Discuss the role of airway washing procedures in the diagnosis of FHD.
Because other diffuse pulmonary diseases (e.g., asthma, lungworm infection, neoplasia) are
typically on the differential list in a cat with PHD, transtracheal washes or bronchoalveolar lavages
are commonly performed. Airway wash cytology may reveal a preponderance of eosinophils 4-7
months after infection with D. immitis; however, airway eosinophilia is not specific for heartworm
infection. In addition, the absence of eosinophils does not preclude heartworm infection.
Dirofilariasis
Thoracic radiographs consistent with dirofilariasis in cats. Note
the enlarged pulmonary arteries in the VD view (B). (Courtesy of
Dr. Jan Bright, Colorado State University.)
45
14. Can FHD be diagnosed at necropsy?
Unfortunately, some cats with FHD are diagnosed via necropsy, especially those that die
suddenly. Look for intact or fragmented worms in the heart, pulmonary arteries, systemic veins,
and central nervous system (if neurologic symptoms were present). However, some cats that die
from sequelae of PHD may have cleared the infection; in such cases, worms are absent.
15. How is FHD treated?
Supportive care for secondary respiratory tract inflammation is most important; use of adul-
ticide treatment is controversial. Acutely iII cats should be stabilized with appropriate supportive
care such as supplemental oxygen, parenteral fluids, bronchodilators, and glucocorticoids.
Glucocorticoids decrease reaction to the worms in the pulmonary arteries and thus reduce clini-
cal signs. They can be used over the long term in cats with mild-to-moderate symptoms while
waiting for adult worms to die (up to 2-3 years). This approach usually decreases pulmonary ar-
teritis caused by the chronic presence of worms, but acute thromboembolic complications caused
by death of worms are still possible. Supportive treatment protocols are similar to those for
asthma and chronic bronchitis (see Chapter 9).
16. Should adulticide treatment be considered?
Thiacetarsamide was found to be effective in cats with FHD, but its use does not increase
survival rates over the use of glucocorticoids alone, and death has resulted from its administra-
tion in some cats. Thiacetarsamide usually is reserved for stable cats that continue to manifest
clinical signs despite glucocorticoid treatment. The dose is 2.2 mg/kg intravenously twice daily
for 2 days. Cage confinement and close observation are recommended for 3-4 weeks because
pulmonary thromboembolic complications can be expected in about one-third of treated cats.
Aspirin should not be used in cats with PHD.
The safety and efficacy of melarsamine have not been firmly established in cats; therefore,
its use cannot be recommended. One study found that a single intramuscular dose of 2.5 mg/kg
reduced worm burdens by only 30%.
46 Dirofilariasis
17. When should surgical removal of adult worms be considered?
In cats with caval syndrome, surgicalremoval maybe consideredif adult wormsare visual-
ized echocardiographically in the right sideof the heart. However, successrates are largely unde-
tennined becauseof limitedinformation.
18. What preventive measures can be used against heartworms in cats?
Monthlyivermectin at an oral dose of 24 I!glkg is highlyeffective in preventing heartworm
infection in cats. Milbemycinis effectiveat the canine preventivedose (0.5-0.99 mglkg/month
orally) but has not been labeledfor use in cats. Selamectin, a monthlytopical heartworm preven-
tive labeled for cats, is an alternative for cats that refuse oral preventivemedications. Because
even indoor cats are at risk in endemicareas, preventive drugs shouldbe consideredfor themas
well as for cats who live predominantly outdoors. Depending on the product,heartworm preven-
tives havethe addedbenefitof aidingin the control of other helminthparasites.
BIBLIOGRAPHY
I. Atkins C: The diagnosis of feline heartworm infection, J Am Anim Hosp Assoc 35:185-187, 1999.
2. Atkins CE, Atwell RB, Dillon R, et al: American Heartworm Society Guidelines for the diagnosis, treat-
ment, and prevention of heartworm (Dirofilaria immitis) infection in cats. Comp Cont Educ Pract Vet
19:422-429,1997.
3. Atkins CE, DeFrancesco TC, Coats JR, et al: Heartworm infection in cats: 50 cases (1985-1997). J Am
Vet Med Assoc 217:355-358, 2000.
4. Atkins CE, DeFrancesco TC, Miller MW, et al: Prevalence of heartworm infection in cats with signs of
cardiorespiratory abnormalities. J Am Vet Med Assoc 212:517-520, 1998.
5. Dillon R: Clinical significance of feline heartworm disease. Vet C1in North Am Small Anim Pract
28:1547-1565,1998.
6. Dillon AR, Brawner WR, Robertson-Plouch CK, et al: Feline heartworm disease: Correlations of clini-
cal signs, serology, and other diagnostics: Results of a multicenter study. Vet Therapeut 1:176-182,
2000.
7. Goodwin JK: The serologic diagnosis of heartworm infection in dogs and cats. Clin Tech Small Anim
Pract 13:83-87, 1998.
8. Kalkstein TS, Kaiser L, Kaneene JB: Prevalence of heartworm infection in healthy cats in the lower
peninsula of Michigan. J Am Vet Med Assoc 217:857-861, 2000.
9. McCall JW, Dzimianski MT, McTier TL, et al: Biology of experimental heartworm infection in cats. In
Soli MD, Knight DH (eds): Proceedings of the American Heartworm Symposium 1992. Batavia, IL,
American Heartworm Society, 1992, pp 71-79.
10. Miller MW, Atkins CE, Sternme K, et al: Prevalence of exposure to Dirofilaria immitis in cats in multiple
areas of the United States. Vet Therapeut I: 169-175, 2000.
II. Robertson-Plouch CK, Dillon AR, Brawner WR, et al: Prevalence of feline heartworm infections among
cats with respiratory and gastrointestinal signs: Results of a multicenter study. Vet Therapeutics 1:88-
95,2000.
12. Selcer BA, Newell SM, Mansour AE, et al: Radiographic and 2-D echocardiographic findings in eigh-
teen cats experimentally exposed to D. immitis via mosquito bites. Vet Radiol Ultrasound 37:37-44,
1996.
13. Snyder PS, Levy JK, Salute ME, et al: Performance of serologic tests used to detect heartworm infection
in cats. J Am Vet MedAssoc 216:693-700, 2000.
14. Venco L, Calzolari D, Mazzocchi D, et al: The use of echocardiography as a diagnostic tool for detection
offeline heartworm (Dirofilaria immitis) infections. Feline Pract 26:6-9,1998.
11. RESPIRATORY PARASITES
Elizabeth J. Colleran, D.V.M., M.S.
1. What are the most common primary lung parasites?
Paragonimus kellicotti is a trematode in the family Troglotrematids, all of which are lung par-
asites. This lung fluke causes pulmonary disease in the states surrounding the Great Lakes and in
the Midwestern and Southern United States. P. westermani is more common on the West Coast.
Aelurostrongylus abstrusus is a nematode in the family Angiostrongylidae. This small lung-
worm is distributed throughout the United States and is considered the most common respira-
tory parasite.
Capillaria aerophila is a small worm in the superfamily Trichuroidea that contains several
common parasites of domestic animals including C. trichuris, the whipworm found in dogs and
rarely in cats. Capillaria spp. may cause mild cough in cats, but infection is usually subclinical.
2. What are the most common migratory respiratory parasites?
Toxocara cati and Strongyloides stercoralis migrate through the lungs of cats after primary
infection (see Chapter 19). Tissue migration leads to eosinophilic inflammation and cough in some
cats. Infection and visceral larva migrans resulting in cough may be more common in kittens.
3. What are the common polysystemic respiratory parasites?
Toxoplasma gondii and Dirofilaria immitis (see Chapter 10).
4. How are cats infected by Paragonimus spp.?
Paragonimus spp. eggs from a host are passed in feces about 6 weeks after infection. If the
eggs reach water, the miracidia stage develops and hatches in about 2 weeks. These organisms
enter the snail Pomatiopsis lapidaria. Several stages of development take place until the organ-
ism becomes a cercaria. The cercariae leave the snail and encyst in crayfish as metacercariae.
Cats that hunt near water containing crayfish may ingest the encysted cercariae with the crayfish
or consume paratenic hosts that have recently eaten crayfish. The flukes "excyst" from the in-
testines, migrate through the diaphragm, and encyst in lung parenchyma. The adults and eggs
that become trapped in alveoli and airways result in lung pathology.
5. What are the clinical signs of Paragonimus spp. infection?
The primary sign of Paragonimus spp. infection is chronic cough. Clinical signs are associ-
ated with the inflammatory reaction to the parasite, secondary bacterial infection, or cyst rupture.
Lung sounds are often normal, but crackles and wheezes can be auscultated when inflammatory
disease is present and may be confused with feline bronchitis. Acute respiratory distress occurs
when encysted organisms rupture, causing pneumothorax.
6. How is Paragonimus spp. infection diagnosed?
Thoracic radiographic abnormalities include well-defined cystic lesions approximately 1 em
in diameter and pneumothorax may be present if a cyst ruptures. A nodular, interstitial pattern
may result from diffuse inflammation. Definitive diagnosis is made by identification of eggs
either in tracheal washings or feces after fecal sedimentation. Fecal sedimentation can be done by
an outside laboratory or by the following procedure:
I. Mix 5 gm of feces in 200 mI of water in a beaker.
2. Pour the mixture through a tea strainer, and discard the material in the strainer.
3. After 10 minutes, decant approximately 70% of the supernatant, and refill the beaker with
fresh water.
4. Repeat step 3 3-5 times until the supernatant is clear.
47
48 Respiratory Parasites
5. Pour off 90% of the supernatant, and pour the sediment into a petri dish.
6. Examine the sediment under a dissecting microscope (20-30 x) or scanning objective (4
x) of the microscope (total magnification = 40 x) for large, single-operculated eggs.
7. Which cats are most at risk for A. abstrusus infection?
The life cycle of A. abstrusus requires a mollusk (slug or snail) as an intermediate host and a
small mammal or bird as a transport host. Thus, cats that hunt in areas with sufficient moisture
for slugs and snails to thrive are at risk.
8. What are the clinical signs of A. abstrusus infection?
Clinical signs are related to parasite burden. Larvae in feces are an incidental finding in some
subclinically infected cats. Clinical signs range from mild cough to respiratory distress and even
death. Crackles and wheezes may be auscultated, mimicking feline bronchitis. Occasionally, sec-
ondary bacterial pneumonia can complicate the diagnosis.
9. Describe the radiographic appearance of A. abstrusus infection.
On thoracic radiographs, poorly defined nodular densities are observed, particularly in
caudal lung fields. These densities are deposits of egg "nests" in the lung parenchyma. Bronchial
and diffuse interstitial patterns arealso common.
A and B, Thoracic radiographs from a cat with Aeluro-
strongylus abstrusus infection.
10. How is A. abstrusus infection diagnosed?
Diagnosis is made by identifying the parasite in feces or airway washings. Eggs hatch into
first-stage larvae while in the lungs. The larvae are then coughed up and swallowed and appear in
the eat's feces 5-6 weeks after infection. First-stage larvae can be recovered in tracheal wash sam-
ples or by Baermann examination of feces. This test requires a Baermann apparatus, which con-
sists of a ring stand and ring holder and a glass funnel covered by a wire net or cheesecloth with a
piece of rubber tubing on the end. Approximately 3-5 gm of fresh feces are placed on the cheese-
cloth or wire mesh immediately above the water filled funnel. Over several hours, larvae migrate
out of the feces into the fluid and sink to the bottom of a funnel for collection and identification.
Zinc sulfate fecal flotation also can be diagnostic (see Chapter 19). The author has found this
technique useful for the diagnosis of A. abstrusus larvae in clinically ill cats. The larvae are dis-
tinguished from other parasitic infections by the spines on their tails.
Respiratory Parasites 49
Cytologic evaluation of airway washings often demonstrate eosinophilic inflammation sug-
gestive of parasitism, but larvae mayor may not be identified.
11. What is the life-cycleof C. aerophila? How is infection diagnosed?
The life cycle of C. aerophila is unclear but probably involves an earthworm host or ingestion
of eggs from the soil. C. aerophila infects the trachea and large bronchi of cats. Eggs are coughed
up, swallowed, and passed in the feces. Occasionally, clinical signs of cough or wheeze are pre-
sent, but most infected cats are subclinical. Diagnosis is made by identification of eggs in tracheal
wash fluid or in feces after fecal flotation (see Chapter 19). The eggs of C. aerophila are morpho-
logically similar to the double-operculated egg of Trichuris vulpis but are slightly smaller.
12. How are the primary lung parasites treated?
If clinical signs of disease worsen during treatment, prednisolone at 2 mglkg orally every 12
hour may be needed to lessen eosinophilic inflammation.
13. What are the clinical signs of the migratory parasites?
Toxocara cati and S. stercoralis infections of cats may be subclinical. Alternately, gastroin-
testinal signs may occur, including vomiting and diarrhea. Infected kittens may be unthrifty. Mild
cough can occur in some kittens and adult cats.
14. Howare the migratory parasites diagnosed and treated?
Fecal flotation reveals the ova of T. cati, and the Baermann technique can be used to demon-
strate larvae of S. stercoralis. Although drugs such as pyrantel pamoate and fenbendazole (see
Chapter 19) can clear the intestinal tract, it is unknown whether migrating tissue stages can be
treated successfully.
15. Does Toxoplasma gondii infection cause respiratory disease?
Cats are the definitive host for Toxoplasma gondii, and virtually all other warm-blooded an-
imals are intermediate hosts (see Chapters 19 and 84). After primary infection of the host, T.
gondii replicates in most body tissues, including the lungs. In most immunocompetent hosts, pri-
mary infection results in minimal-to-no clinical signs. Thus, T. gondii is rarely diagnosed clini-
cally as a cause of respiratory disease in cats. In some infected cats, particularly young cats with
acute disease, coughing. dyspnea, and polypnea occur. Toxoplasmic pneumonia is most common
in transplacentally or neonatally infected kittens. Proliferative interstitial pneumonia was the
most consistent finding in a study of neonatally induced toxoplasmosis. Of 100 cats with histo-
logically confirmed, fatal toxoplasmosis, 26 had pulmonary lesions. Organisms were found in
76.7% of 86 lungs examined. Other clinical signs may include pyrexia (104-106F,
40.D--4l.1,C), anorexia, anterior uveitis, posterior uveitis, and abdominal discomfort.
16. How is toxoplasmosis diagnosed?
Antemortem diagnosis may be difficult. Thoracic radiographs reveal a patchy, diffuse infil-
trative pattern resembling bacterial or viral pneumonia. Hematologic findings are nonspecific.
Oocysts are small, intermittently shed, and easily overlooked in fecal preparations. Broncho-
alveolar lavage mayor may not contain tachyzoites. Definitive diagnosis is made by a combina-
tion of the following:
Serologic evidence of infection (lgG indicates exposure and IgM active disease)
Clinical signs of toxoplasmosis
Response to treatment
Identification of organism histologically associated with inflammation
17. Howis toxoplasmosis treated?
Because of the minimal number of cases of pulmonic toxoplasmosis, optimal treatment is
undetermined. Clindamycin HCI (Antirobe, Pharmacia and Upjohn Co., Kalamazoo, MI) at
12.5 mg/kg/day orally every 12 hours for a minimum of 4 weeks has been used most frequently
50 Pneumonia
for syndromes other than respiratory disease. Loose stool and emesis have been reported as po-
tential side effects in cats. Potentiated sulfas and azithromycin are effective alternative choices.
In general, pulmonic toxoplasmosis suggests overwhelming tissue replication and carries a
guarded-to-poor prognosis.
BIBLIOGRAPHY
I. Bowman DD, Lynn CR, Georgi JR: Parasitology for Veterinarians, Philadelphia, WB. Saunders, 1999.
2. Dubey JP, Carpenter JL: Histologically confirmed clinical toxoplasmosis in cats: 100 cases (1952-1990).
J Am Vet Med Assoc 203:1556--1566, 1993.
3. Dubey JP, Lappin MR: Toxoplasmosis and neosporosis. In Greene CE (ed): Infectious Diseases of the
Dog and Cat. Philadelphia, W.B. Saunders, Philadelphia. 2nd ed. 1998.pp 493-503.
4. Dubey, JP, Mattix, ME, Lipscomb TP: Lesions of neonatally induced toxoplasmosis in cats. Vet Pathol
33:290-295, 1996.
5. Hawkins EC: Pulmonary parenchymal diseases. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary
Internal Medicine. Philadelphia, WB. Saunders, 2000, pp 1068-1071.
6. Hawkins EC, Davidson MG, Meuten DJ, et al: Cytologic identification of Toxoplasma gondii in bron-
choalveolar lavage fluid of experimentally infected cats. J AmVet Med Assoc 210:648-650, 1997.
7. King L, Drake D, Scott F, et al: Roundtable: Feline respiratory diseases, PI 2. Feline Pract 26:6--10. 1998.
8. Knowlen JR: The coughing cat. In August JR (ed): Consultations in Feline Internal Medicine.
Philadelphia, WB. Saunders, 1991, pp 180-181.
9. Lappin MR, Greene, CE, Winston S, et a1: Clinical feline toxoplasmosis: Serologic diagnosis and thera-
peutic management of 15 cases. J Vet Intern Med 3:139-143,1989.
12. PNEUMONIA
John E. Stein, D.v.M.
1. What is pneumonia?
Pneumonia refers to inflammation of the lung. It is generally due to infectious causes such as
bacteria, viruses, fungi. or parasites, but it also may result from a noninfectious cause such as as-
piration of material into the lower airways. The chemical inflammation induced by aspiration
often results in secondary bacterial pneumonia.
2. What historical findings suggest pneumonia in cats?
Pneumonia in cats may develop from a wide variety of causes. A thorough history provides
valuable clues to the underlying cause. Cats, and in particular kittens, that have recently been
housed in stressful, multicat environments such as shelters are at increased risk of developing
bacterial pneumonia. In sick cats with a history of vomiting or a recent procedure requiring gen-
eral anesthesia, aspiration pneumonia should be considered. Hunting cats are at increased risk of
developing parasitic pneumonia and, during summer months in endemic areas, can encounter
pneumonic plague caused by Yersinia pestis(see Chapter 86). Although serologic tests by them-
selves do not prove immunodeficiency, the retroviral status of all sick cats should be known be-
cause coinfection with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FlV)
may predispose to infectious pneumonia.
3. What clinical signs of illness does pneumonia generally cause in cats?
The most common clinical signs are cough, which may be moist and productive, and dysp-
nea. Some cats demonstrate vague, nonspecific signs, including anorexia, lethargy, dehydration,
and weight loss. Some cats also have a nasal discharge and/or ocular abnormalities, depending on
the underlying cause of pneumonia. Aspiration pneumonia occurs most frequently in cats that
have a history of vomiting, regurgitation, or recent anesthetic event.
Pneumonia 51
4. What physical examination findings suggest pneumonia?
Fever, tachypnea or dyspnea, and weight loss are common physical examination findings in cats
with pneumonia. In addition, thoracic auscultation may demonstrate the presence of increased bron-
chovesicular or adventitial sounds, such as "crackles," that indicate fluid-filled alveoli. The presence
of submandibular lymphadenopathy in a hunting cat during summer months in plague endemic re-
gions should be cause for immediate quarantine until Y. pestis has been ruled out (see Chapter 86).
Generalized peripheral lymphadenopathy may benoted in cats with pulmonary mycoses. A fundic
examination may reveal evidence of uveitis or chorioretinitis with systemic infectious agents such as
Toxoplasma gondii or fungal agents, both of which can cause pneumonia in cats.
5. Which bacterial agents have been associated with pneumonia in cats?
Bacteria can enter and colonize the lower airways of cats via either the inhalation/aspiration or
hematogenous routes, and many possible agents can beinvolved. As with bacterial infection of the
upper respiratory tract, the resident population of bacteria in the oropharynx and trachea can over-
grow under certain circumstances and descend into the distal airways. Careful evaluation for an un-
derlying condition that may predispose the patient to bacterial pneumonia is always indicated.
Many bacteria, whether present as a primary or secondary infection, possess virulence factors that
further disrupt the normal mucociliary apparatus, interfere with local immunity, and/or damage res-
piratory epithelium. Among the more common bacterial agents found in feline bacterial pneumonia
are Pasteurella multocida, Moraxella spp., Klebsiella pneumoniae, Proteus spp., Pseudomonas
aeruginosa, Mycoplasma spp., and Bordetella bronchiseptica, in addition to the ubiquitous
Staphylococcus spp., Streptococcus spp., and Escherichia coli. These infections may represent
overgrowth of resident microflora, opportunistic invaders, or possibly primary pathogens arriving
either via the airway or hematogenously,
6. Which organisms may cause primary bacterial pneumonia in cats?
Although, in general, secondary bacterial pneumonia is more common in cats, the following
organisms are known to cause primary disease:
I. B. bronchiseptica has been shown to be a potential primary pathogen but appears to cause
severe pneumonia only in kittens less than 4-6 weeks of age, particularly those housed in over-
crowded, unsanitary conditions. Overall, B. bronchiseptica is commonly detected in healthy cats
and appears to be an unlikely cause of primary bacterial pneumonia in adult, household cats.
2. Mycoplasma spp. are not normally found in the lower airways of healthy cats and un-
doubtedly may be opportunistic invaders; however, their role as primary bacterial pathogens re-
mains somewhat controversial.
3. In the southwest portion of the United States, from late spring to early fall, pneumonic
plague caused by Y. pestis is an important and zoonotic differential for primary bacterial pneu-
monia in outdoor cats that hunt (see Chapter 86).
7. Discuss the role of canine distemper virus and Chlamydia psittaci in lower respiratory
tract disease.
The role of canine distemper virus and C. psittaci in lower respiratory tract disease was eval-
uated in a retrospective study (1987-1996) of 245 cases of feline pneumonia or conjunctivitis/
rhinitis. Patients were evaluated histologically and by immunohistochemical staining for both or-
ganisms. Neither organism could be demonstrated in the lungs of household cats, suggesting that
they are not involved with feline lower respiratory disease.
8. What other infectious agents may cause pneumonia in cats?
Viral, fungal, and parasitic pneumonia occur in some cats. Secondary bacterial infection may
result from colonization of the damaged airways after the primary infection.
9. What are the most common causes of viral pneumonia in cats?
Viral pneumonia has been noted with calicivirus and, less commonly, feline herpesvirus I
(feline viral rhinotracheitis), almost exclusively in kittens (see Chapter 3). Feline infectious
52
Pneumonia
peritonitis has been reported to result in pyogranulamatous pneumonia with patchy interstitial to
alveolar densities noted radiographically (see Chapter 38). Although not responsible for primary
viral pneumonia, both FeLV and FlV may result in decreased immune function in cats and in-
creased incidence of pneumonia due to infectious agents.
10. What causes mycotic pneumonia in cats?
Mycotic pneumonia is relatively rare in cats compared with dogs. The most common feline
fungal infection, Cryptococcus neoformans, typically results in rhinitis with possible ocular or cen-
tral nervous system manifestations rather than pneumonia (see Chapter 4). Cats with evidence of
pneumonia and concurrent rhinitis should be examined carefully for evidence of cutaneous lesions,
central nervous system signs, and ocular abnormalities, such as exudative retinal detachment, gran-
ulomatous chorioretinitis, or anterior uveitis associated with cryptococcal infection. Blastomyces
dermatitidis, Histoplasma capsulatum, and Coccidiodes immitisare possible, though less common,
causes of pneumonia in cats. Because these organisms often establish systemic infections, cats with
fungal pneumonia may demonstrate abnormalities in multiple body systems, including the eye, cen-
tral nervous system, bones, lymph nodes, intestinal tract, kidneys, and skin. Blastomyces spp. are
found most commonly in soil in the regions of the Mississippi, Missouri, and Ohio River valleys
and may cause anterior uveitis, optic neuritis, and/or retinal hemorrhage as well as dyspnea and po-
tentially draining skin lesions in cats with systemic disease. Histoplasma spp. are also found most
commonly in the central United States and may cause pneumonia as well as lymphadenopathy, he-
patosplenomegaly, and, occasionally, ocular, central nervous system, skin, bony, or gastrointestinal
lesions. Coccidioides spp. are found in the southwestern United States and are more likely to cause
skin lesions than pneumonia in cats; on occasion they also cause bony or ocular lesions.
11. Can respiratory parasites be involved with lung disease in cats?
Multiple parasites are associated with respiratory tract disease in cats. Some, like Toxoplasma
gondii, are polysystemic parasites that may cause pneumonia as well as ocular, central nervous
system, and other multisystemic signs (see Chapter 11). The two most common migratory para-
sites are Toxocaracati and Strongyloidesstercoralis (see Chapter 11). The three most common
primary lung parasites are the lungworms, Aleurostrongylus abstrusus and Capillaria aerophila,
and the lung fluke, Paragonimus kellicotti (see Chapter II). Dirofilaria immitiscan cause severe
lower respiratory disease, but pneumonia is uncommon (see Chapter 10).
12. What causes sterile pneumonia?
Aspiration of gastric secretions results initially in chemical inflammation that is sterile.
However, because of the rich normal flora of the mouth, pharynx, and proximal trachea, bacteria
are usually aspirated as well. Chemical inflammation usually allows secondary bacterial colo-
nization. Aspiration pneumonia should be suspected in cats with a history of vomiting, regurgita-
tion, or recent anesthetic event that develop acute signs of respiratory distress. Examples of
underlying conditions reported in cats include regurgitation and megaesophagus secondary to
congenital or acquired esophageal strictures. Esophagitis with stricture formation has been seen
after esophageal reflux under general anesthesia and also in some cats given oral doxycycline
tablets (see Chapter 26).
13. Howis pneumonia generally diagnosed in cats?
Evaluation of cats with evidence of respiratory disease must be tempered with caution. A pa-
tient that appears stable when initially examined may decompensate rapidly under stress.
Supplemental oxygen therapy is indicated before and during examination of dyspneic cats with sus-
pected pneumonia. In addition, in areas of the country where Y. pestis is endemic, it is vitally im-
portant to minimize exposure to personnel and to take proper precautions until this disease has been
ruled out. In general, a presumptive diagnosis of pneumonia is based on assessment of the signal-
ment, history, and physical examination, along with results of a complete blood count (CBC). tho-
racic radiographs, serum FeLV antigen test, serum FlV antibody test. and fecal examination
Pneumonia 53
techniques, including flotation, sedimentation, or Baermann test, depending on geographic loca-
tion and travel history (see Chapter 8). A definitive diagnosis of pneumonia requires cytologic
evaluation and culture of fluid obtained via transoral airway washings or bronchoalveolar lavage,
although these procedures may not be advisable in unstable, critically ill patients (see Chapter 8).
14. What are the characteristic abnormalities of the CBC?
With bacterial or fungal pneumonia, CBC may demonstrate an inflammatory leukogram with
or without a left shift; however some patients have a norrnalleukogram. In septic cats, neutropenia
with a degenerative left shift may be seen. Eosinophilia may be noted in some cats with parasitic
pneumonia. Normocytic, normochromic, nonregenerative anemia may be noted in response to
chronic inflammation with fungal pneumonia. Total protein can be increased in some cats with
systemic mycoses due to hyperglobulinemia. A macrocytic, normochromic, nonregenerative
anemia may be seen in patients with bone marrow suppression due to concurrent FeLV infection.
Anemia, neutropenia, and lymphopenia are relatively common abnormalities in patients with FlY.
15. What are the characteristic thoracic radiographic findings of pneumonia?
Thoracic radiographic findings vary with the cause of pneumonia. In acute aspiration pneu-
monia, radiographs may be normal. Patients with bacterial pneumonia typically show evidence
of an alveolar pattern characterized by air bronchograms, often distributed in the cranial ventral
lung region. Mycotic pneumonia usually causes a miliary-to-nodular interstitial pattern through-
out the lungs. Viral or mycoplasmal pneumonia often causes a diffuse interstitial pattern, particu-
larly early in the course of disease.
16. Should airway washing be performed?
In stable patients, cytologic evaluation and culture of airway fluids are indicated to aid diag-
nosis and determination of appropriate treatment (see Chapter 8). Washings can be obtained by
either bronchoscopy and bronchoalveolar lavage or transoral wash. Rarely, a transthoracic aspi-
rate may be required when other diagnostic techniques have been attempted without success.
Transthoracic aspiration is most beneficial in cats with interstitial pneumonia (see Chapter 8).
17. Howcan arterial blood gas analysis be used in the care of pneumonia cases?
Arterial blood gas measurements help to determine the severity of pulmonary parenchymal dis-
ease and to monitor response to therapy. Although arterial blood sampling may bedifficult incats, par-
ticular y those in respiratory distress, the changes are more sensitive than those noted on radiographs.
18. What is the alveolar-arterial gradient? Howis it calculated and interpreted?
The alveolar-arterial (A-a) gradient on room air (21%oxygen) is calculated to determine rel-
ative oxygenation with the following formula:
A-a gradient :: Calculated alveolar oxygen - measured PaOz
:: [(Barometric pressure - 47)(0.21) - PaCO
z
/0.8] - Pa02
where PaOz :: partial pressure of oxygen in arterial blood and PaCO
z
:: partial pressure of carbon
dioxide in arterial blood. A normal A-a gradient in a well-oxygenated patient is 0-10. An A-a
gradient of 10-20 is suspicious for impaired oxygenation ability. An A-a gradient of 20-30 indi-
cates oxygenation impairment, and a gradient> 30 indicates severe disease.
19. What formula is used for patients receiving supplemental oxygen therapy?
When the patient is receiving supplemental oxygen therapy, the following formula for the
oxygenation ratio must be used instead:
Oxygenation ratio e PaO/FIO
z
where FlO
z
:: concentration of inspired oxygen. FiO
z
may be presumed to be 40% (0.40) in pa-
tients receiving oxygen supplementation via a face mask and 100% (1.0) in patients receiving
oxygen from an anesthetic machine or ventilator via an endotracheal tube. A patient with an oxy-
genation ratio> 200 mmHg is considered to have normal oxygenation ability.
54
Pneumonia
20. Howdo I treat bacterial pneumonia?
The mainstay of treatment for bacterial pneumonia remains adequate systemic hydration and
antibiotic therapy. Ideally, therapy should be guided by results of bacterial culture and antibiotic sen-
sitivity testing. However, while you are awaiting results, particularly inpatients not stable enough to
undergo respiratory tract fluid collection procedures, empiric antibiotic therapy is usually necessary.
In cats suspected to have severe pneumonia or bacteremia, parenteral administration of four-quadrant
antibiotics is indicated. The combination of a quinolone plus a penicillin or first-generation
cephalosporin provides excellent coverage, but this regimen should be reserved for life-threatening
or resistant infections. The maximal recommended daily dosage of enrofloxacin in cats has recently
been reduced because of reports of sudden blindness in some cats. If toxoplasmic pneumonia is sus-
pected, clindamycin or azithromycin should be considered in lieu of penicillin or cephalosporin.
After initial therapy, cats without evidence of bacteremia may be maintained on penicillin, first-gen-
eration cephalosporin, or clindamycin alone (see table in Chapter 2 for doses and spectrums).
21. What additional therapy is important?
Additional therapy for all patients with pneumonia should include replacement of fluid deficits
and maintenance of adequate hydration to ensure adequate function of the mucociliary apparatus.
For the same reason, diuretics and drugs that interfere with the normal cough response, such as direct
antitussives, should be avoided. Finally, supplemental oxygen therapy may provide some relief to
cats in respiratory distress with poor oxygenation due to significant pulmonary parenchymal disease.
22, Should other adjunct treatments be considered for bacterial pneumonia?
Nebulization and coupage (repeated gentle chest percussion) may facilitate clearance of
mucus and exudates but may not be well tolerated in cats (nebulization is tolerated in a cage or
box, but coupage may not be). Nebulization for 10 minutes 3 times/day may be performed using
3-5 ml of sterile saline, which acts as a mucolytic agent and enhances hydration, alone or in
combination with an aminoglycoside such as gentamycin (25 mg). Drugs such as theophylline
may be of benefit as mild, indirect antitussives and aid in mucociliary apparatus clearance.
23. How is fungal pneumonia diagnosed?
Mycotic pneumonia is suspected based on clinical signs, history, and radiographic findings.
Organism identification by culture, cytology, or histopathology gives a definitive diagnosis.
Serology is of variable usefulness in diagnosing mycotic infections and monitoring response to
therapy, depending on the fungal organism involved. Serology is particularly useful in cases of C.
neoformans because antigen can be detected and may be used to evaluate response to therapy
(see Chapter 4). Serum, cerebrospinal fluid, and aqueous humor can be tested effectively for
cryptococcal antigen. Serology for the other systemic fungal organisms is based on antibody
titers, and a positive result indicates exposure to the organism rather than a definitive diagnosis.
Serologic test results for most cats with blastomycosis or coccidiomycosis are positive. Serologic
test results for cats with histoplasmosis are extremely variable.
24. Howis fungal pneumonia treated?
In general, mycotic pneumonia is a difficult disease to treat, requiring long-term therapy
with expensive, systemic antifungal drugs. Treatment should continue for at least 2 months after
resolution of clinical signs. Although itraconazole has been effective in cats with C. neoformans
infection, fluconazole has superior penetration into the central nervous system and should be
used in cats with central nervous system or ocular involvement (see Chapter 4). Ketoconazole has
serious side effects in cats and is not recommended. Although these drugs are effective in treating
chronic disease, a fungicidal drug such as amphotericin B is indicated in cats with life-threatening
systemic infections. Liposome-encapsulated microsomal amphotericin B is expensive but poten-
tially safer because it is less nephrotoxic. For C. neoformans, monitoring of serum antigen titers
can be beneficial. Ideally, a two-fold decrease in serum titer per month should be detected in a re-
solving case, although at least 10% of cats may remain seropositive despite effective treatment
and resolution of clinical signs.
Pyothorax 55
25. What is the prognosis for pneumonia?
The prognosis for pneumonia depends greatly on theunderlying disease process. Withsecondary
pneumonia, resolution dependson accurately identifying andtreating the primary condition. In gen-
eral, bacterial pneumonia responds well toaggressive antibiotic therapy, as discussed above. Viral and
aspiration pneumoniamayresolve withsymptomatic careandantibiotics to treat secondary bacterial
infections. Fungalpneumonia mayresolve withappropriate therapy, particularly inthecaseof C. neo-
formans. Parasiticpneumoniausuallyrespondswell to antiparasitic therapy, with the exceptionof
severe Toxoplasma gondii-induced pneumonitis, whichwarrants a moreguarded prognosis.
BIBLIOGRAPHY
1. Bart M, Guscetti F, Zurbriggen A, et al: Felineinfectious pneumonia: Ashort literaturereview and a ret-
rospective immunohistological studyon the involvement of Chlamydia spp. anddistempervirus.VetJ
159:3220-3230,2000.
2. Boothe DM: Principles of drug selectionfor respiratoryinfections in cats. Comp Cont Educ Pract Vet
195:5-15,1997.
3. DyeJA, McKiernanB, Rozanski EA, et al: Bronchopulmonary disease in the cat: Historical, physical,
radiographic, clinicopathologic, and pulmonaryfunctional evaluationof 24 affectedand 15 healthy
cats. J VetInternMed 10:385-400, 1996.
4. GreeneCE: Respiratory infections. In GreeneCE (ed): Infectious Diseasesof the Dog and Cat, 2nd edt
Philadelphia, W.B. Saunders, 1998,pp 582-594.
5. HawkinsEC: Disordersof the pulmonaryparenchyma. In NelsonRW, Couto CG(eds): Small Animal
InternalMedicine, 2ndedt St. Louis, Mosby, 1998, pp 297-312.
6. HoskinsJD, WilliamsJ, RoyAF, et al: Isolationand characterization of Bordetellabronchisepticafrom
cats in southernLouisiana. VetImmunolImmunopathoI65:173-176, 1998.
7. Legendre AM,ToalRL:Diagnosis andtreatment of fungal diseases of therespiratory system. InGreeneCE
(ed):Infectious Diseasesof the DogandCat,2ndedt Philadelphia, W.B. Saunders, 1998,pp 815-819.
8. RandolphJF, Moise NS, Scarlett JM, et al: Prevalence of mycoplasmal and ureaplasmal recoveryfrom
tracheobronchial lavagesandof mycoplasmal recoveryfrompharyngeal swabspecimensin cats with
or withoutpulmonary disease.AmJ VetRes 54:897-900, 1993.
9. SpeakmanAJ, DawsonS, Binns SH, et al: Bordetellabronchiseptica infectionin the cat. J SmallAnim
Pract 40:252-256, 1999.
10. WingfieldWE: Acid-basedisorders. In WingfieldWE (ed): Veterinary EmergencyMedicine Secrets.
Philadelphia, Hanley& Belfus, 1997,pp 288-293.
II. WelshRD: Bordetellabronchiseptica infections in cats. JAm AnimHospAssoc32:153-158, 2000.
13. PYOTHORAX
Elizabeth I. Colleran, D.V.M., M.S.
1. Define pyothorax.
An accumulationof purulent material in the pleural space.
2. What causes pyothorax?
Bacterialinfectiongenerallyis involvedwithpyothorax.In cats, the incitingcausefor pyotho-
rax often remains unknown. Infection may result from direct extension due to bite or puncture
wounds, migrating foreign bodies, pneumonia, pulmonary or thoracic trauma, or neoplasia.
Alternately, infectionmay result fromhematogenous spread fromother infectionsites such as an
abscessor gingivitis. Immunocompromised cats may be at higher risk for pleural infection.
3. Which cats are more likely to be affected?
Young cats that roam freely outdoors are at risk for bite wounds and foreign bodies. Older
cats are at increased risk for neoplasia and immunosuppressive disorders. In all cases, other un-
derlyingcauses should be investigated.
56 Pyothorax
4. What are the signs of pyothorax?
Dyspnea, exercise intolerance, and cyanosis are common presenting complaints with dis-
eases of the pleural space (see Chapter 8). Cats also may present with nonspecific signs of
anorexia, lethargy, and depression.
5. What are the common physical examination fmdings in pyothorax?
The cat mayor may not be febrile, but usually an altered breathing pattern is noted because
pleural effusion results in restrictive breathing (rapid and shallow breaths). Auscultation reveals
muffled heart sounds, with decreased respiratory noises ventrally. Thoracic compressibility may
be decreased.
6. What is the role of thoracic radiographs in the diagnosis of pyothorax??
Thoracic radiographs reveal pleural effusion, increased fluid density ventrally that obscures the
cardiac shadow, lung lobes are retracted from the thoracic cage, and rounded lung borders outlining
individual lung lobes. Rarely, a foreign body may be identified with radiographs or ultrasound.
A and B, Thoracic radiographs from a cat with pyothorax
taken before chest tube placement.
7. Explain the role of thoracocentesis in the diagnosis of pyothorax.
In cats with marked respiratory distress, thoracocentesis may be required for stabilization
before chest radiographs are obtained. Thoracocentesis is both diagnostic and therapeutic.
8. How is thoracocentesis performed?
A small area on the ventral portion of the chest at the seventh-to-eighth intercostal space is
clipped and surgically prepared. Thoracocentesis is performed with a syringe connected to a three-
way stopcock, extension set, and needle or catheter. The needle or catheter is inserted behind the
caudal border of the rib to avoid intercostal vessels and nerves. The needle should be directed ven-
trally, with the needle and syringe nearly parallel to the chest wall to minimize lung laceration. This
positioning becomes most important when the lung lobes reinflate as fluid is removed. The extension
set and three-way stopcock should be placed in line and are closed off to the patient when the chest
is entered. Once the needle is in place, connections are opened and fluid is aspirated. In some cases,
fluid may be too thick to be removed via a 22-gauge needle or small catheter, necessitating a
larger-bore catheter or placement of a chest tube. In some cats, the mediastinum is complete. and
Pyothorax 57
thoracocentesis on both sides of the thorax is required. Fluid samples should be analyzed cyto-
logically and submitted for both aerobic and anaerobic culture and susceptibility testing. Fungal
elements may be present but are uncommon.
9. Describe the fluid from a pyothorax.
The fluid is usually a highly cellular exudate, with bacteria visible cytologically in over 90%
of cases. Protein concentrations are high, and the fluid varies in color from amber to red to white.
It may be extremely malodorous, particularly in the presence of anaerobes such as Bacteroides
spp. Nucleated cells in the fluid are usually degenerate neutrophils, macrophages, and mesothe-
lial cells. If active phagocytic cells are present, they normally contain bacteria.
Cytology of a direct smearfroma cat with
pyothorax. Multipledegenerative and non-
degenerative neutrophils arepresent.
10. Are additional diagnostic procedures needed?
Sepsis, moderate-to-severe dehydration, and electrolyte abnormalities may be present in ad-
dition to respiratory signs. Therefore, a complete blood count, chemistry profile, and urinalysis
are generally performed when the cat is stable. Serum tests for feline leukemia virus (FeLY) anti-
gens and feline immunodeficiency virus (FlY) antibodies are usually performed because most
cats with pyothorax roam outdoors and immunosuppression may worsen the prognosis. Fluid
may have obscured underlying causes, such as foreign bodies, lung abscesses, or intrapleural
masses, that alter treatment decisions and prognosis for recovery. Thoracic ultrasound is helpful
in the search for underlying diseases, for detecting the amount of fluid in the pleural cavity, and
for assessing the efficacy of fluid removal.
11. What kind of supportive care is important initially?
Oxygen therapy is started immediately in dyspneic animals, although removal of thoracic
fluid is more advantageous in improving gas exchange. Fluids are given intravenously when the
cat is stable, and parenteral antibiotics effective against gram-positive, gram-negative, aerobic,
and anaerobic organisms (four-quadrant approach) are administered after cultures have been
submitted. A good four-quadrant antibiotic regimen is the combination of a fluoroquinolone
combined with a first-generation cephalosporin, clindamycin, or ampicillin. Adjustments in an-
tibiotic selection should be based on culture and susceptibility results. Many specimens yield
multiple organisms.
12. What treatment course is most likely to be successful?
A chest tube should be placed after diagnosis because drainage and lavage are the mainstays
of successful treatment. Bilateral chest tubes may be necessary. Yigorous monitoring of cytologic
characteristics is important to assess resolution of disease. Radiographs or ultrasound also can be
used to assess drainage and presence of fluid pockets. Long-term antibiotics are needed and are
based on culture results. Antibiotic therapy should continue for at least 4-6 weeks.
58
Pyothorax
13. What materials are needed for chest tube placement?
12-French Sovereign red rubber catheter or feeding tube (Sherwood Medical, St. Louis)
or similar tube from Cook Veterinary Products (Bloomington, IN). In general, a stylet is
not required. If the tube has a closed end, carefully cut it off at an angle, and remove any
sharp edges. Multiple fenestrations can be made in the distal half, taking care not to
weaken the tube. A catheter cap, three-way stopcock, or other closed-end tubing is used to
close the tube.
Sterile gloves
2 Mosquito or Kelly hemostats or other small hemostats with a fairly sharp point
Scalpel and blade
Nonabsorbable suture material
Scissors
Needle holders
Thumb forceps
Sterile antibiotic ointment
Bandaging material
Soft Elizabethan collar (optional but helpful)
14. How is a chest tube placed?
Because cats have more compliant chest walls and less muscle to penetrate, a simpler tech-
nique can be used than that required for dogs. In cats that present with respiratory distress, thora-
cocentesis should be performed first, and as much fluid is removed as is practical. The technique
for tube placement described below applies to a normal-sized adult cat.
I. If one tube is planned, the side most affected should be selected. If the mediastinum is
occluded by fibrin clots, chest tube placement is repeated on the second side.
2. Manual restraint should be kept to a minimum, particularly in cats with signs of respira-
tory distress. Mild sedation can be given intravenously to effect. If the cat is fractious or if strug-
gling continues, general anesthesia is used with a cuffed endotracheal tube.
3. The skin of the lateral chest wall is clipped and aseptically prepared.
4. Local anesthetic can be infiltrated into the intercostal muscles in the dorsal third of the
chest near the tenth rib space and in a second site lower on the thorax at the seventh or eighth rib
space.
5. A small skin incision is made in the dorsal third of the chest by the tenth rib space. The
skin is pulled cranially to the area of the seventh or eighth intercostal space.
6. The tube is tunneled subcutaneously to the region at the seventh or eighth intercostal
space, where it will enter the thorax.
7. A hemostat is used to separate the intercostal muscles gently at the site of insertion.
8. Light, controlled pressure is exerted downward (perpendicular to the table) to penetrate
the thoracic cavity. A low "pop" of air usually is heard as the tube enters the thorax.
9. The hemostat is released, and the tube is advanced gently into the thoracic cavity. About
two-thirds of the tube should lie within the thoracic cavity on the ventral surface.
10. The tube is secured to the skin with nonabsorbable suture. A lightly placed pursestring
suture begins the process.
II. Half of the length of the suture is pulled through the skin so that an even amount of
suture is on either end of the pursestring.
12. A Chinese fingertrap pattern is used to secure the tube to the chest wall. This simple pat-
tern is composed of the first throw of a surgeon's knot in the front.
13. The two ends are then passed around the tube, one in each direction, and another double
throw is made.
14. Continue this pattern for 5-7 throws, and end with a complete surgeon's knot.
15. Cut off the long ends of the suture.
16. Use sterile antibiotic ointment at the thoracostomy site, and wrap the thorax with a light
bandage. Cats often object to thoracic bandages, and minimal material is better tolerated.
Pyothorax 59
17. A soft Elizabethan collar, such as the Recovery Collar (Trim1ine Manufacturing, Boca
Raton, FL), is advised.
18. Radiographs are performed after the procedure to confirm proper placement of the tube.
15. What is the difference between continuous and intermittent suction for pleural lavage?
Continuous suction is considered ideal because it offers the advantage of maximal drainage.
However, intermittent suction is simpler and easier to manage.
16. How do I perform pleural lavage?
1. To a I-L bag of sterile isotonic solution (lactated Ringer's solution or 0.9% sodium chlo-
ride), add 1500 units ofheparin/loo m1of fluid. Heparin may lessen further fibrin formation, The
addition of antibiotics to the lavage fluid is no longer recommended by most authorities.
2. After the fluid is warmed to near body temperature, flush 10 mllkg into each hemi-
thorax and leave for 1 hour, if the cat will tolerate it. Some absorption of fluid occurs during
this time.
3. Aspirate fluid from the pleural space. You should recover 50-60% of the original fluid
volume. Greater recovery is an indication that a pocket of exudate has been aspirated; less may
suggest some pocketing of fluid.
4. A single lavage should not be used as a measure of success or failure; the cumulative
amount of fluid over several intervals indicates the efficacy of therapy. Ultrasound or radiographs
will demonstrate how successful the lavage has been.
17. How often should lavage and suction be performed?
Initially, lavage and suction should be performed every 3-5 hours. As the fluid becomes
clearer and the volume declines, the interval between lavage and suction treatments can be in-
creased. Treatment should continue until the fluid is clear and no organisms are seen cytologi-
cally. Usually this goal is achieved within 4-5 days, although intervals of 3-6 and 5-10 days
have been recommended.
18. Discuss the role of fibrinolytic agents in pleural lavage.
In human cases of pyothorax (empyema), fibrinolytic agents are often added to the lavage
fluid to enhance breakdown of adhesions and improve fluid drainage. Streptokinase is used in pa-
tients who have not responded well to drainage and antibiotics. Some studies demonstrated short-
ening of the duration of treatment, improved drainage, and avoidance of surgical intervention.
The dose of streptokinase varied from 50,000 U in children to 250,000 U in adults. This approach
may be considered when "pockets" of fluid have localized with fibrin adhesions. However, strep-
tokinase is quite expensive, and no studies have been done in cats.
19. How is nutrition managed after pleural lavage?
Nutrition is critical to resolution of pyothorax in cats. Once the cat is afebrile, a good ap-
petite often returns. On the other hand, thoracic bandages, discomfort, and unfamiliar surround-
ings may cause inappetance or anorexia. Warming food, providing a variety of flavors, and
covering the eat's cage for a certain period each day may be helpful (see Chapter 62). Privacy or
quiet or a combination of the two seems to improve appetite. Otherwise, force-feeding or the use
of esophagostomy tubes may be required. It is essential to feed the calculated amount of calories
necessary to maintain a positive nutritional balance.
20. Discuss the role of analgesia after pleural lavage.
Analgesia may speed recovery. Human patients report that chest tubes are uncomfortable,
and some cats seem restless. Therefore, use of a fentanyl patch (25Ilg/1O Ib cat) or intermittent
treatment with oxymorphone or buprenorphine should be considered. The fentanyl patch seems
to offer the best combination of continuous pain relief and ease of administration. If the cat re-
mains in pain after 3 days with a patch, a second patch may replace the first.
60 Pyothorax
21. Summarize proper care of the thoracostomy site.
The thoracostomy site should be checked daily for leaks and cleaned and rewrapped with a
sterile antibiotic ointment at the insertion site, if needed. Take care to avoid entry of bacteria or
air into the thorax during bandage changes.
22. How are patients monitored to determine when the chest tube can be removed?
Fluid pockets are easily visualized with ultrasound. Volume of fluid at each aspiration and
daily volumes of recovered fluid should be recorded. Declining fluid volume and changes in fluid
character indicate successful therapy. Fluid evaluation should begin no later than the third day, if
adequate fluid is recovered. Cellularity decreases, as does bacterial count. The absence of organ-
isms indicates resolution of pyothorax. Fluid aspirated from the chest tube before lavage should
decrease to ~ 2 ml/kg/day before tube removal.
If fluid recovery appears to be inadequate, repeated radiographs help to assess chest tube(s)
position and fluid drainage. Complications of chest tube placement include kinking, occlusion by
fibrin clots, or migration from the ventral thorax. It is sometimes possible to reposition the chest
tube. The site should be aseptically prepared, sutures removed, and the tube withdrawn and
shifted ventrally. A second tube may be required. Surgical intervention may be indicated if fluid
recovery remains poor. Regular assessment of electrolytes is useful throughout treatment. Even
when electrolyte abnormalities are not found on presentation, aggressive IV fluid administration
and pleural lavage may create imbalances that require correction.
23. When is surgical intervention recommended?
If no improvement in clinical signs, fluid recovery, or fluid character is seen after the first 3
days of therapy, surgical intervention is indicated. Thoracotomy is needed when extensive pleural
adhesions prevent adequate drainage and lavage. Pyothorax in conjunction with lung abscessa-
tion, thoracic foreign bodies, and intrapleural masses generally requires surgery. Complications
associated with chest tube placement also may require surgical intervention.
24. What is necessary after the chest tube is removed?
Long-term administration of oral antibiotics is indicated. After discharge, reevaluation
should take place in I week and then I month later. Antibiotic intervals depend on the organisms
isolated but are recommended for a minimum of I month. One week after discontinuation of an-
tibiotics, another reevaluation should be scheduled. Relapse is uncommon if lavage has been suc-
cessful and no underlying cause remains.
25. What are the potential complications of pyothorax?
Lung lobe perforation and pneumothorax can occur if the chest tubes are improperly placed.
Other potential complications of pyothorax include fibrinous pleural adhesions, lung lobe entrap-
ment, pneumonia, and overwhelming sepsis. However, the success rate of intermittent lavage, ag-
gressive antibiotic therapy, careful monitoring, and supportive care exceeds 80% in some studies. In
one study, cats with pyothorax had the best prognosis compared with other types of pleural effusion.
BIBLIOGRAPHY
I. Davies C. Forester SD: Pleural effusion in cats: 82 cases (1987-1995). j Small Anim Pract 37:217-224.
1996.
2. Dunning D, Orton EC: Pulmonary surgical techniques. In Bojrab MJ (ed): Current Techniques in Small
Animal Surgery, 4th ed. Baltimore, Williams & Wilkins, 1998, pp 408-411.
3. Fendin J, abel N: Catheter drainage of pleural fluid collections and pneumothorax. j Small Anim Pract
38:237-242,1997.
4. Fooshee SK: Managing the cat with septic pleural effusion. Vet Med 83:907-913, 1988.
5. FossumTW, Relford RL: Pleural effusion: Physical, biochemical and cytologic characteristics. In August JR
(ed): Consultations in Feline Internal Medicine, 2n ed. Philadelphia, w.B. Saunders, 1994, pp 292-293.
6. Fossum T: Pleural and extrapleural diseases. In Ettinger SJ (ed): Textbook of Veterinary Internal
Medicine, 5th, Philadelphia, WB Saunders, 2000, pp 1106-1107,
7, Fox SM: The best methods of wound drainage in pets. Vet Med 83:462-472, 1988.
Pneumothorax 61
8. Frey Dl, Klapa 1, Kaiser D: Irrigation drainage and fibrinolyis for treatment of parapneumonial pleural
empyema. Pneumologie 53:596-604, 1999.
9. King L, et al: Roundtable discussion: Feline respiratory disease. Feline Pract 26:16-17, 1998.
10. Jerges-Sanchez C, et al: Intrapleural fibrinolysis with streptokinase as an adjunctive treatment in hemoth-
orax and empyema: A multicenter trial. Chest 109:1514-1519, 1996.
II. Rosen H, et al: Intrapleural streptokinase as adjunctive treatment for persistent empyema in pediatric pa-
tients. Chest 103:1190-1193, 1993.
12. Walker AL, lang SS, Hirsh DC: Bacteria associated with pyothorax in dogs and cats: 98 cases. 1 Am Vet
Med Assoc 216:359-363, 2000.
14. PNEUMOTHORAX
Elisa M. Mazzaferro. M.S.. D.V.M.
1. What are the most common causes of pneumothorax in cats?
The most common cause of pneumothorax in cats is trauma, including being hit by a motor
vehicle, bite wounds, penetrating injuries (e.g., bullets, arrows), and high-rise syndrome. Other
documented causes of pneumothorax include barotrauma secondary to anesthetic equipment
malfunction, tracheal rupture, and dirofilariasis. Spontaneous pneumothorax has been docu-
mented in dogs but not in cats.
2. What are the three categories of pneumothorax?
Simple pneumothorax usually is associated with nonpenetrating trauma that damages lung
parenchyma, resulting in leakage of air into the pleural space.
Open pneumothorax results from a penetrating injury to the chest wall that allows commu-
nication between the pleural space and the atmosphere.
Tension pneumothorax occurs when a one-way valve develops in either an airway (bron-
chopleural fistula) or the chest wall (pleurocutaneous fistula). Negative intrapleural pressure
during inspiration aspirates air into the pleural cavity, but air cannot leave during expiration be-
cause the one-way valve closes. Once intrapleural pressure exceeds atmospheric pressure, tension
pneumothorax develops and rapidly leads to a fatal reduction in gas exchange and cardiac output.
3. What are the clinical signs of pneumothorax?
Cats with pneumothorax typically are presented with respiratory distress, tachypnea, open-
mouth breathing, cyanosis or pale pink-to-gray mucous membranes, and a rapid, shallow restric-
tive respiratory pattern. Pneumothorax should be considered in any cat with known trauma.
However, the clinical signs associated with pneumothorax are not pathognomonic and may be
observed with other pleural space problems, including pleural effusion and diaphragmatic hernia.
Auscultation of the thorax usually reveals muffled heart and lung sounds.
4. What is the most appropriate emergency treatment for pneumothorax?
Therapeutic and diagnostic thoracocentesis should be performed to relieve respiratory dis-
tress and stabilize the patient before radiographs are performed. Emergency treatment in patients
displaying signs of pneumothorax or a restrictive respiratory pattern includes immediate oxygen
supplementation in the form of flow-by oxygen. Analgesia and sedation may be required to alle-
viate stress of breathing, anxiety, and pain. Morphine (0.025 mg/kg subcutaneously) decreases
work of respiration and anxiety in patients requiring thoracocentesis.
5. How is a therapeutic and diagnostic thoracocentesis performed?
1. Clip a 4-inch square section of fur from each side of the thorax.
2. Quickly prepare each area aseptically.
62 Pneumothorax
3. Insert a l-inch, 20-22-gauge needle connected to an extension set, three-way stopcock,
and 60-ml into the mid thorax between the seventh-to-tenth intercostal space, carefully avoiding
the caudal border of the rib.
4. After inserting the needle into the pleural space, direct the needle parallel with the tho-
racic wall to avoid penetrating the lung parenchyma.
S. Aspirate air from the chest, and record the volume.
6. If negative pressure is encountered, redirect the needle in several spots, because pockets
of air may persist and restrict breathing or cause lung collapse.
7. Once negative pressure is obtained, the entire procedure should be repeated on the other
side of the thorax.
5. When are radiographs necessary in patients with pneumothorax?
Radiographs should be performed only after the patient's respiratory and cardiovascular
system have been stabilized. Therapeutic thoracocentesis, oxygen therapy, and intravenous fluids
for vascular support are often necessary before radiographs. After successful stabilization, radi-
ographs can be performed to evaluate the patient for continued air accumulation, rib fractures,
pulmonary contusions, and diaphragmatic hernia.
Severe posttraumatic pneumothorax
in a cat. Note the subcutaneous em-
physema.
6. What concurrent injuries are often observed in patients with pneumothorax secondary
to trauma?
When pneumothorax is secondary to trauma, concurrent injuries may include pulmonary
contusions, rib fractures or flail chest, myocardial contusions, and diaphragmatic hernia.
Penetrating wounds into the thorax also may be associated with vessel laceration and hemotho-
rax, myocardial contusion or hemorrhage, and presence of foreign bodies.
7. What treatment is appropriate for simple pneumothorax?
In most cases, the leak is self-limiting, requiring conservative management with thoracocen-
tesis.
8. How is open pneumothorax managed?
If the wound causing the pneumothorax is small relative to the size of the glottis, adequate
ventilation can be maintained. If the wound is large relative to the size of the glottis, severe hy-
poventilation results. Open pleural wounds should be covered immediately with sterile ointment
and bandages. Insertion of a thoracic drain and aspiration of the pleural space can then be done to
stabilize the patient.
9. Describe the appropriate management of tension pneumothorax.
Because respiratory impairment develops rapidly, therapeutic thoracocentesis must be per-
formed immediately. Management then proceeds as for open pneumothorax.
Pneumothorax 63
10. Define flail chest.
A flail chest occurs when three or more contiguous ribs are fractured in two or more spaces,
causing instability of the chest wall. The flail segment often moves paradoxically with respira-
tion: inward during inspiration and outward during expiration. Hypoxemia results from hypoven-
tilation and underlying pulmonary contusions. The pain associated with flail chest contributes
significantly to inefficient gas exchange.
11. What is the most appropriate treatment of flail chest?
Treatment of flail chest is directed at alleviating the pain associated with rib fractures. Local
anesthesia (bupivacaine at 0.10-0.25 ml/site, taking care not to exceed 2 mglkg) should be in-
fused at the caudal aspect of each affected rib proximally and distally. The ribs cranial and caudal
to the flail segment also should be blocked. Typically, the treatment can be performed up to 3
times/day. However, caution must be taken if lidocaine is used for local anesthesia, because ex-
cessive doses have been associated with seizures and hemolytic anemia. In rare cases, external
stabilization of the flail segment may be required.
12. What are the indications for placement of a chest tube in cats with pneumothorax?
A chest tube should be placed in cats that develop respiratory distress due to continued accu-
mulation of air within the thorax and cats that require performance of thoracocentesis more than
2-4 times/day.
13. Is sedation appropriate for placement of a chest tube in cats with pneumothorax?
The chest tube should be placed in a way that minimizes stress. When sedation is needed, a I
Ilglkg intravenous bolus of fentanyl or 2-4 mglkg of intravenous propofol, given to effect, can be
used for sedation and chemical restraint. The skin should be aseptically prepared on the side of the
thorax generating the air. Local anesthetic (0.75 mglkg 2% lidocaine or maximum of 2 mglkg
bupivicaine) is then infused near the tenth intercostal space and at a second site where the chest
tube will enter the mid-thorax (between the seventh and eighth intercostal space).
14. Describe the technique for placement of a chest tube after appropriate sedation.
I. Use an 8- or lO-French trocarized tube.
2. Make a stab incision with a scalpel blade at the tenth intercostal space, and tunnel the
tube under the skin to the seventh or eighth intercostal space. An assistant can pull the skin cran-
ioventrally to aid tunneling.
3. Compress the thorax over the sternum to increase intrathoracic pressure while placing
the trocar through the body wall.
4. Once the trocar enters the pleural space, push the tube rapidly off the trocar in a cran-
ioventral direction.
5. Use a large hemostat to clamp off the chest tube and prevent further leakage of air into
the chest.
6. The tip of the chest tube should lie on the ventral floor of the thoracic cavity at approxi-
mately the third intercostal space, just cranial to the heart.
7. Connect a Christmas tree adapter with extension tubing, three-way stopcock, and 60-ml
syringe to the chest tube, open the hemostat, and begin suctioning immediately.
8. Secure the chest tube to the skin with a horizontal mattress suture around the tube.
9. Use a pursestring suture to close the point of entry of the tube into the skin, and further
secure the tube with a Chinese finger trap.
10. Cover the entrance point of the tube with betadine-soaked sponges, and bandage the
thorax with layers of gauze. The tubing should be incorporated into the bandaging in a way that
covers all connections in the system and discourages withdrawal of the tube with traction.
II. The chest tube can be suctioned intermittently as needed or connected to a continuous
suction system.
12. If patient discomfort continues, 0.75 rug/kg bupivacaine can be flushed into the chest
tube 3 times/day.
64 Pneumothorax
15. Describe an alternate method of chest tube placement if a trocarized tube is not avail-
able.
1. Use a sterile red rubber feeding tube and a sterile polypropylene urinary catheter.
2. Insert the urinary catheter into the feeding tube to provide rigid support while the feeding
tube is placed into the chest.
3. Grasp only the distal end of the red rubber tube with large, curved hemostats.
4. Place the hemostat through the stab incision in the skin and tunnel it with the trocar.
Using blunt force, insert the tips of the hemostat through the chest wall at the seventh intercostal
space.
5. Pass the red rubber tube into the pleural cavity, and direct it cranially and ventrally to the
third intercostal space.
6. Withdraw the urinary catheter, and clamp the red rubber tube with the hemostats.
7. After placement of a Christmas tree adapter, proceed as described for the trocar tube.
8. Take thoracic radiographs after insertion of the chest tube to ensure proper placement
within the chest cavity.
Correct chest tube placement in a
cat with pneumothorax.
16. Are Heimlich valves appropriate for treating pneumothorax in cats?
Heimlich valves require sufficient respiratory excursions and generation of positive in-
trapleural pressure during expiration to force the free air past the one-way Heimlich valve.
Because cats typically do not generate enough pressure during expiration to force air past the
valve, Heimlich valves are contraindicated in feline patients with pneumothorax.
17. Is continuous suction usually required for treatment of pneumothorax in cats?
Most cats with pneumothorax have small volumes of air in the pleural space and can be han-
dled by hand aspiration intermittently.
19. When should surgical intervention be considered in a cat with pneumothorax?
Conservative therapy is successful in the majority of cases with pneumothorax. When a chest
tube is required to alleviate tension pneumothorax or persistent air accumulation, seal of the air
leak is expected within 5 days. If air continues to leak, surgical intervention should be consid-
ered, since devitalized lung tissue, pleural blebs, or bullae may be limiting resolution of disease.
20. What is the pathogenesis of hypotension in patients with pneumothorax?
Accumulation of free air within the thorax impedes venous return to the heart, resulting in
decreased cardiac output and hypotension. With trauma, hypotension is often complicated by
acute hypovolemia secondary to hemorrhage.
Chylothorax
BIBLIOGRAPHY
65
1. Berkwitt L, Berzon JL: Thoracic trauma: Newer concepts. Vet Clin North Am Small Anim Pract
15:1031-1038,1985.
2. Brown DC. Holt 0: Subcutaneous emphysema, pneumothorax, pneumomediastinum, and pneumoperi-
cardium associated with positive-pressure ventilation in a cat. J Am VetMed Assoc 206:997-999, 1995.
3. Caylor KB, Moore RW: What is your diagnosis? Severe cervical trachea and substantial subcutaneous
emphysema in a cat. J Am Vet MedAssoc 205:561-562,1994.
4. EvansAT: Anesthesiacase of the month. Pneumothorax,pneumomediastinum and subcutaneousemphysemain
a cat due to barotraumasafter equipment failureduringanesthesia.J AmVetMed Assoc212:30--32, 1998.
5. Frendin J, Obel N: Catheter drainage of pleural fluid collections and pneumothorax. J Small Anim Pract
38:237-242, 1997.
6. Godfrey DR: Bronchial rupture and fatal tension pneumothorax following routine venipuncture in a
kitten. JAm Anim Hosp Assoc 33:260--263,1997.
7. Hackner SG: Emergency management of traumatic pulmonary contusions. Comp Cont Educ Pract Vet
17:677-686, 1995.
8. Kagan KG: Thoracic trauma. Vet Clin North Am Small Anim Pract 10:641-653, 1980.
9. Kapatkin AS, Matthiesen DT: Feline high-rise syndrome. Comp Cont Educ Pract Vet 13:1389-1396, 1991.
10. Kolata RJ: Management of thoracic trauma. Vet Clin North Am Small Anim Pract 11:103-120, 1981.
II. Malik R, Gabor L, Hunt GB, et al: Benign cranial mediastinal lesions in three cats. Aust Vet J 75: 183-187,
1997.
12. Manning MM, Brunson DB: Barotrauma in a cat. J Am Vet Med Assoc 205:62-64, 1994.
13. McKiernan BC, Adams WM, Huse DC: Thoracic bite wounds and associated internal injury in II dogs
and I cat. J Am Vet Med Assoc 184:959-964, 1984.
14. Murtaugh RJ: Acute respiratory distress. Vet Clin North Am Small Anim Pract 24: I041-1055, 1994.
15. Smith JW, Scott-Moncrieff Je, Rivers BJ: Pneumothorax secondary to Dirofilaria immitis infection in
two cats. J Am Vet Med Assoc 213:91-93, 1998.
15. CHYLOTHORAX
Elisa M. Mazzaferro, M.S., D.V.M., and Davyd Pelsue, D.V.M.
1. Define chylothorax.
Chylothorax is the accumulation of chylomicron-containing fluid within the thoracic cavity.
This fluid typically has a white or pink milky appearance, although if the cat is anorectic or on a
low-fat diet, the fluid may be less opaque.
2. What conditions have been associated with chylothorax in cats?
Conditions associated with chylothorax in cats include right heart failure, cranial mediastinal
mass (lymphosarcoma, thymoma), thrombosis of the jugular vein(s), infection, dirofilariasis,
traumatic diaphragmatic hernia, rupture of the thoracic duct, and lung lobe torsion. In many
cases, however, the cause of chylothorax is unknown (idiopathic chylothorax).
Conditions Associated with Chylothorax
Right heart failure
Persistent atrial standstill
Restrictive pericarditis
Tetralogy of Fallot
Tricuspid dysplasia
Restrictive cardiomyopathy
Hypertrophic cardiomyopathy
Dilative cardiomyopathy
Trauma
Diaphragmatic hernia
Lung lobe torsion
Neoplasia
Lymphoma
Thymoma
Chemodectoma
Metastatic pulmonary
adenocarcinoma
Postoperative disorders
Pulmonary thromboembolism
Thrombosis of cranial vena cava
Jugular catheter placement
Infection
Dirofilariasis
Idiopathic chylothorax
66 Chylothorax
3. What diagnostic tests should be performed in cats with chylothorax?
Complete blood cell count, serum biochemistry profile, urinalysis, and serum tests for feline
leukemia virus antigens and feline immunodeficiency virus antibodies should be performed in all
cats with chylothorax. Echocardiography and thoracic radiographs help to determine whether di-
lated, restrictive, or hypertrophic cardiomyopathy is present. In addition, thoracic radiographs
(horizontal beam) and thoracic ultrasonography help to determine whether the anterior vena cava
is occluded by an intrathoracic mass. Determination of total T4 concentrations can be used to
rule out hyperthyroidism. In endemic areas, serum Dirofilaria immitisantigen and antibody tests
should be performed. In cats with dilated cardiomyopathy, plasma taurine levels should be con-
sidered, because levels < 30 nmol/ml are suggestive of systemic taurine depletion as a cause for
cardiac insufficiency. A fundic examination also should be performed because central retinal de-
generation may occur with taurine deficiency.
4. Does idiopathic chylothorax result from rupture of the thoracic duct?
Numerous studies have documented chylothorax without leakage of the thoracic duct. Positive
contrast lymphangiography often reveals lymphangiectasia of the cranial mediastinal lymphatic
vessels in cats with chylothorax. Although rupture of the thoracic duct has been documented sec-
ondary to blunt trauma, the duct often quickly heals and does not result in chylous effusion.
5. What are the presenting complaints in cats with chylothorax?
The most common presenting complaints from owners include dyspnea (respiratory dis-
tress), tachypnea, cough, anorexia or inappetance, weight loss, dysphagia, regurgitation,lethargy
or weakness, exercise intolerance, depression, salivation, cyanosis, and acute collapse.
6. What are the physical examination findings in cats with chylothorax?
Physical examination findings in cats with chylothorax (or other causes of pleural effusion)
include tachypnea, muffled heart sounds, decreased or absent lung sounds below the effusion, in-
creased bronchovesicular sounds over aerated lung fields, and a rapid shallow respiratory pattern
consistent with restrictive pulmonary disease. Other signs, which depend on the underlying dis-
ease process, may include jugular venous distention (right heart failure, obstruction of the cranial
vena cava), arrhythmias, gallop rhythm, murmurs, noncompliant thorax (due to fluid or an ante-
rior mediastinal mass), dehydration, and cachexia due to chronic weight loss.
7. What are the radiographic findings of chylothorax?
Radiographic findings often include unilateral or bilateral pleural effusion with increased
opacity throughout the thorax, elevation of the trachea (due to effusion or an anterior mediastinal
mass), rounding or scalloping of the lung lobes, loss of the cardiac silhouette, widened interlobar
fissures, and retraction of the lung lobes from the thoracic wall. However, these findings are not
pathognomonic.
8. Howdo you perform thoracocentesis?
Thoracocentesis should be performed bilaterally in patients with a restrictive respiratory pat-
tern, often before radiographs are performed, An ethylenediamine tetraacetic acid (EDTA) tube,
red-top tube, sterile swab for culture, transport media for culture, microscope slides, and collec-
tion bowl should be readily accessible.
I. Clip a 4-inch area over the midthorax on both sides.
2. Prepare the area septically.
3. Use a 21-gauge butterfly catheter, 2Q-22-gauge fenestrated catheter, or 22-gauge needle
for thoracocentesis.
4. An extension set with three-way stopcock and syringe is attached to the tubing of the but-
terfly catheter or should be available to connect to the catheter as soon as the stylet is removed.
5. Insert the needle or catheter between the seventh and ninth intercostal space in the ventral
portion of the thorax, taking care to avoid the intercostal vessels at the caudal aspect of the rib.
Chylothorax 67
6. Gently aspirate fluid from the thorax. The needle may need to be repositioned within the
thorax.
7. Bilateral aspiration is recommended to maximize fluid removal.
9. What are the characteristics of chylous effusions?
Chylous effusions typically are opaque and white to pinkish-white; they have a protein con-
tent of 2.5-6.0 grnldI.The protein content may be increased artifactually by the triglyceride con-
centration. Fibrin content is variable. The fluid is typically nonseptic. Sudan III stain allows
visualization of fat droplets. Nucleated cell count varies, ranging from 500-20,0001111, depending
on the cause and chronicity of the chylous effusion. Early in the course of the disease, lympho-
cytes are typically the predominant cell type, accounting for more than 50% of total nucleated
cells. Lymphocyte morphology should be evaluated closely for characteristics of malignancy (see
Chapter 16). As the chylous effusion becomes more chronic, necessitating repeated thoracocente-
sis, nondegenerate neutrophils or macrophages may predominate. Chylous effusions characteris-
tically have elevated triglyceride levels in comparison to serum concentrations. Therefore, an
accurate diagnosis of chylous effusion is made by measuring pleural effusion triglyceride and
cholesterol levels. A cholesterol:triglyceride ratio in pleural fluid < I: I is found in chylothorax.
Characteristics of Chylous Effusions
Color
Turbidity
Specific gravity
Cell count
Protein content
Fibrin
Triglyceride
Cholesterol
Cholesterol:triglyceride ratio
Bacteria
Milky white, pinkish
Clear to opaque
1.019-1.038
500-20,000
2.5-7.8 gmldl
Variable
Elevated (higher than serum levels)
Normal
<I
Absent
10. How do you distinguish between chylous effusion and pseudochylous effusion?
It is often difficult to distinguish chylous effusions from pseudochylous effusions visually or
cytologically. Triglyceride concentrations are higher in chylous effusion than in serum, whereas
pseudochylous effusions have higher cholesterol concentrations and lower triglyceride concen-
trations than serum.
11. What are the metabolic and pathologic consequences of chronic chylothorax?
Negative consequences of chronic chylothorax include fluid loss and subsequent dehydra-
tion, loss of fat-soluble vitamins, electrolyte imbalances (hyponatremia, hyperkalemia), hypopro-
teinemia, caloric depletion resulting in weight loss and cachexia, and infections secondary to a
compromised immune system, lymphopenia, and repeated thoracocentesis. Chronic chylothorax
in cats can result in life-threatening fibrosing pleuritis, a thickening of the pleura in response to
chronic fluid exudation. Fibrosing pleuritis can occur even after successful management of chy-
lothorax, resulting in restrictive pleural disease and severe respiratory difficulty.
12. What is the most appropriate form of medical management for chylothorax in cats?
Medical management of chylothorax involves repeat thoracic drainage when clinical signs of
tachypnea or respiratory distress are noted. If an inciting cause of chylothorax is established, the
primary disease should be treated. For example, diuretics, beta blockers, angiotensin-converting
inhibitors, and calcium-channel blockers have been used to treat hypertrophic cardiomyopathy
(see Chapter 17). Methimazole, surgical thyroidectomy, or radioactive iodine therapy can be used
to treat hyperthyroidism (see Chapter 53). Surgery, radiation therapy, or chemotherapy can be
used to treat neoplasia of the anterior mediastinum, depending on tissue type (see Chapter t6).
68
Chylothorax
13. How can dietary management assist in the treatment of chylothorax in cats?
A low-fat diet has been used successfully. Commercial diets or homemade diets can be used.
A commonly used homemade diet consists of 1 cup boiled rice, potato, oatmeal or pasta; I cup
low-fat (2%) cottage cheese (or skinned chicken breast or water-packed tuna instead of cottage
cheese), and Yz teaspoon calcium carbonate. Medium-chain triglycerides have been advocated,
with the rationale that they do not enter the lymphatic system and, therefore, do not contribute to
the development of chylothorax. However, medium-chain triglycerides have been documented in
the thoracic duct of humans and dogs with chylothorax. Therefore, their efficacy is questionable.
14. What drugs may be helpful?
Diuretics are not routinely recommended for cats with chylothorax. There is no definitive
proof that they decrease production of chylous fluid, and diuretic therapy may lead to dehydra-
tion. Benzopyrones, such as rutin, have been used with some success to decrease lymph produc-
tion and increase lymph removal.
15. Describe the mechanismof action of rutin in the treatment of chylothorax.
Benzopyrone derivatives, such as the bioflavinoid rutin (25D-500 mg/cat orally every 8 hr), have
been used successfully with low-fat diets in the treatment of chylothorax-with or without surgical
intervention. Bioflavinoids have several proposed mechanisms of action, including decreased leak-
age from blood vessels, increased protein removal from lymphatic vessels, increased phagocytosis
via macrophage stimulation, and increased proteolysis and lymph removal from tissues.
16. Is administration of glucocorticoids beneficial?
Some authoritites have advocated the administration of glucocorticoids to cats with chronic,
idiopathic chylothorax. The rationale is that glucocorticoids decrease inflammation due to pleuri-
tis and may decrease chylous effusion production. However, no controlled studies document the
efficacy of glucocorticoids for this syndrome.
17. Should pleurodesis be attempted?
Chemical pleurodesis achieved by instilling sterile talc or tetracyclines through previously
placed chest tubes has not been documented to be effective for the treatment of idiopathic chy-
lothorax. However, it does increase inflammation and discomfort for the cat.
18. Name several surgical options for treatment of chylothorax.
Ligation of the thoracic duct and its tributaries
Passive pleuroperitoneal shunting, which shunts chyle into the abdomen for absorption by
a large surface area,
Active pleuroperitoneal or pleurovenous shunting
Pleurodesis
Surgery may be more difficult in cats because of their small size. Ligation of the thoracic
duct successfully resolved chylothorax in approximately 53% of cats in which the procedure was
performed.
19. Howis thoracic duct ligation performed?
A thoracic duct Iymphangiogram typically is performed before a left tenth intercostal thora-
cotomy. Alternatively, a transdiaphragmatic approach may be used. Injection of methylene blue
into a mesenteric lymph vessel may improve visualization of the thoracic duct. Once identified, it
is ligated with silk or hemoclips. The lymphangiogram helps to define the anatomy of the tho-
racic duct and demonstrate abnormalities, if present. A postoperative Iymphangiogram may be
performed to demonstrate complete occlusion of the duct.
20. When should I consider surgery for cats with chylothorax?
When clinical signs require thoracic drainage more often than once a week and medical
management does not appear to be reducing chyle formation, surgical intervention should be
Lower Respiratory Tract Neoplasia 69
considered. Cats that have developed significant protein or caloric malnutrition are poor surgical
candidates; therefore, surgery should be considered before the animal becomes debilitated.
21. What is the prognosis for cats with chylothorax?
The prognosis for cats with chylothorax is guarded to poor, unless definitive treatment for an
underlying disease is successful. Spontaneous remission has been reported, and medical therapy
may benefit a certain percentage of cases. Use of rutin may improve management of cats with
chylothorax. In a recent study, 3 of 4 cats treated with low-fat diets and rutin had long-term reso-
lution of chylothorax. Surgery also can be considered for cats with chylothorax. Regardless of
treatment, however, fibrosing pleuritis can decrease quality of life and increase mortality rates.
BIBLIOGRAPHY
I. Birchard SJ, Fossum TW: Chylothorax in the dog and cat. Vet Clin North Am Small Anim Pract 17:271-
283, 1987.
2. Birchard 5J, Smeak DD, McLoughlin MA: Treatment of idiopathic chylothorax in dogs and cats. J Am
Vet Med Assoc 212:652-657, 1998.
3. Davies C, Forrester SD: Pleural effusions in cats: 82 cases (1987-1995). J Small Anim Pract
37:217-224,1996.
4. Fossum TW, Jacobs RM, Birchard SJ: Evaluation of cholesterol and triglyceride concentrations in differenti-
ating chylous and nonchylous pleural effusions in dogs and cats. JAmVet MedAssoc 188:49-51. 1986.
5. Fossum TW, Miller MW, Rogers KS, et al: Chylothorax associated with right-sided heart failure in five
cats. J Am Vet Med Assoc 204:84-89, 1994.
6. Fossum TW, Forrester D, Swenson CL, et al: Chylothorax in cats: 37 cases (1969-1989). J Am Vet Med
Assoc 198:671-678, 1991.
7. Harpster NK. Chylothorax. In Kirk RW (ed): Current Veterinary Therapy IX. Small Animal Practice.
8. Hawkins EC, Fossum TW: Medical and surgical management ofpleura1 effusion. In Kirk RW (ed): Current
VeterinaryTherapy XIIl. Small Animal Practice. Philadelphia, W.B. Saunders, 2000, pp 819-825.
9. Kerpsack SJ, McLough1inMA, Birchard SJ, et al: Evaluation of mesenteric lymphangiography and thoracic
duct ligation in cats with chylothorax: 19 cases (1987-1992). J Am Vet Med Assoc 205:711-715. 1994.
10. Smeak DD, Kerpsack SJ: Management of feline chylothorax. In Kirk RW (ed): Current Veterinary
Therapy XII. Small Animal Practice. Philadelphia, W.B. Saunders, 1995, pp 921-927.
II. Thompson MS, Cohn LA: Use of rutin for medical management of idiopathic chylothorax in four cats. J
Am Vet Med Assoc 215:345-348, 1999.
12. Tyler RD, Cowell RL: Evaluation of pleural and peritoneal effusions. Vet Clin North Am Small Anim
Pract 19:743-768, 1989.
16. LOWER RESPIRATORY TRACT NEOPLASIA
Nicole Leibman, D.v.M.
1. What are the most common tumors in the larynx and trachea of cats?
Neoplasia of the larynx and trachea are rare in cats. The most common histologic types of
tumors in these areas are squamous cell carcinoma, adenocarcinoma, and lymphoma.
2. What are typical clinical signs in cats with laryngeal or tracheal neoplasia?
Voice change Dyspnea
Ptyalism Gagging
Respiratory stridor Anorexia
Dysphagia Hemoptysis
Cyanosis Cough
Affected cats also may carry the neck in an extended position.
70
Lower Respiratory Tract Neoplasia
3. What diagnostic tests should be performed in cats with suspected laryngeal or tracheal
neoplasia?
Radiography often reveals a distinct mass, although sometimes only narrowing of the airway
lumen may be evident. Laryngoscopy, tracheoscopy, computed tomography, and magnetic reso-
nance imaging may be required alone or in combination to determine the extent of disease. A dis-
advantage of these procedures is the need for general anesthesia in a potentially compromised
patient. If obstruction of a large airway is suspected, it is wise to anticipate the need for a tra-
cheotomy. Often anesthesia is reserved for a surgical procedure that is both therapeutic and diag-
nostic. Usually, laryngeal tumors can be visualized intraorally; therefore, they can easily be
biopsied, Surgery or endoscopy is often necessary to gain biopsy samples from tracheal tumors.
Routine blood work generally is performed, depending on the eat's age. Thoracic radiographs
should be performed to rule out metastatic disease and pneumonia. Regional lymph nodes should
be aspirated and cytology examined, regardless of whether or not they are enlarged. If lymphoma
is suspected, chest and abdominal radiographs, complete blood cell count, serum biochemical
panel, urinalysis, serum tests for feline leukemia virus (FeLV) angitens and feline immunodefi-
ciency virus (FlY) antibodies, and cytology of a bone marrow aspirate may be indicated.
4. What are the treatment options for cats with laryngeal or tracheal neoplasia?
Lymphoma is best treated with combination chemotherapy and/or radiation therapy. Benign
tumors on a stalk can be removed via endoscopy. Resection and anastamosis can be used to
remove small tracheal tumors that involve only 3-4 tracheal rings. Laryngeal or tracheal tumors
with metastatic spread are not candidates for curative surgical procedures, although debulking
surgery may prolong life and result in temporary improvement in clinical signs. Palliative surgi-
cal, chemotherapeutic, and radiation treatments also may be used, depending on tumor type.
5. What is the prognosis for cats with tumors of the trachea or larynx?
Because these tumors are so rare, there is little information about prognosis.
6. What is the most common primary lung tumor of cats?
Primary lung tumors are rare, but histologically the most common type is the bronchial or
bronchial-alveolar adenocarcinoma. Tumors of mesenchymal origin are very uncommon.
Conversely, the lung is a common site for metastatic disease.
7. Describe the typical signalment of a cat with a primary lung tumor.
Most cats are 10-12 years of age, and spayed females seem to be overrepresented. Domestic
shorthairs also are overrepresented.
8. What clinical signs are common in cats with primary lung tumors?
Cats often present with dyspnea, coughing, lethargy, and anorexia. Nonrespiratory signs, in-
cluding general lethargy, weight loss, and pyrexia, may be predominant in some cats. Lameness
occurs in some cats because of metastatic disease or hypertrophic osteopathy.
9. What diagnostic tests should be performed to stage suspected pulmonary neoplasia?
Radiographic findings suggestive of a primary lung tumor include a single, circumscribed mass
or marked lobar consolidation. A diffuse, mixed pattern composed of severe peribronchial infiltra-
tion, a reticulonodular pattern, and alveolar filling also can be found with pulmonary neoplasia.
The possibility of metastatic pulmonary neoplasia should be excluded by completing a com-
plete blood cell count, serum biochemical panel, urinalysis, FeLV serum antigen test, FlV serum
antibody test, abdominal radiographs and/or ultrasound, and potentially bone radiographs.
If pleural effusion is present, it is often necessary to remove the fluid to evaluate the lung
parenchma appropriately on radiographs. Cytologic evaluation of the effusion should be per-
formed to help differentiate heart failure, lymphoma, mesothelioma, feline infectious peritonitis,
and thymoma.
Lower Respiratory Tract Neoplasia 71
Fine-needle aspiration (FNA) of pulmonary masses, with or without ultrasound guidance,
can be a useful tool. Neoplastic seeding of the pleura has not been reported, and in one study
FNA was diagnostic for primary lung tumors in 80% of cases. Cytology of primary carcinomas
usually reveals round epithelial cells forming glands or arranged in rows. Other markers of ma-
lignancy include anisocytosis and anisokaryosis, basophilic cytoplasm, and a high nuclear-to-cy-
toplasma ratio. Biopsy may be necessary for definitive diagnosis in some cats. Biopsies can be
obtained through surgical exploratory, thoracoscopy, or ultrasound-guided procedures.
Primary pulmonary adenocarcinoma in the left caudal lung
lobe of a middle-aged cat.
10. What is the most common anatomic site for primary lung tumor in cats?
The left caudal lung lobe is involved in most cases.
11. What are the differential diagnoses for solitary lung masses in cats?
Differential diagnoses include metastatic neoplasia, cyst, infarct, granuloma, localized hem-
orrhage. localized pneumonia, fungal disease, lung lobe torsion, and abscess.
12. What is the treatment of choice for cats with primary pulmonary neoplasia?
Surgery is the treatment of choice if less than 3 nodules are visible on radiographs and the
cat does not demonstrate negative prognostic factors, such as lymph node metastases and distant
metastatic disease.
13. What is the prognosis for cats treated with surgery for primary lung tumors?
In one study, cats with primary lung tumors treated with surgery alone had a median survival
of 115 days. Cats with tracheobronchial lymph node enlargement treated with surgery had a
median survival time of 73 days, whereas cats without tracheobronchial lymph node enlargement
at the time of surgery had a median survival of 412 days. Cats with poorly differentiated tumors
have a worse prognosis after surgery than cats with moderately differentiated tumors (median
survival time of75 days vs. 698 days).
14. What is the most common tumor of the mediastinum in cats?
Lymphoma in the most common mediastinal tumor and is thought to originate from mediasti-
nal lymph nodes or thymic tissue. Differential diagnoses include thymoma, thymic cyst, ectopic
72 Lower Respiratory Tract Neoplasia
thyroid tumors, and chemoreceptor tumors. In general, mediastinal lymphoma affects younger
cats, whereas thymic neoplasia develops in older cats.
15. What clinical signs and physical examination findings are typical in cats with mediasti-
nal disease?
Cats often present with dyspnea, cough, and dysphagia. Because of mass effect or pleural ef-
fusion, most have a restrictive breathing pattern if dyspnea is present. Pleural effusion is sec-
ondary to tumor compression of lymphatics and decreased venous return to the heart, causing
congestion and secondary transudation. Many cats with a mediastinal mass have a cranial tho-
racic cavity that cannot be compressed.
16. What diagnostic tests should be performed when mediastinal disease is suspected?
Radiography, thoracocentesis with cytologic evaluation of pleural fluid, and FNA of mass le-
sions are performed when possible. For staging suspected mediastinal lymphoma, a complete blood
count, serum chemistry profile, urinalysis, abdominal ultrasound, FeLV serum antigen test, FlV
serum antibody test, and cytology of a bone marrow aspiration should be performed, Of cats with
mediastinal lymphoma, 80% are positive for FeLV. These diagnostic tests are also important to rule
out other diseases.
17. How do effusions associated with lymphoma differ from those associated with thymoma?
Both tumors lead to effusions that usually are characterized as modified transudates.
Effusions induced by thymoma contain primarily small, mature lymphocytes, epithelial cells,
and sometimes mast cells. Effusions induced by lymphoma usually contain large lymphoblastic
lymphocytes. However, small lymphocytes are the predominant cell in some cases.
18. What are the chemotherapeutic options for cats with mediastinal lymphoma?
Several chemotherapuetic options have been described in the literature. Historically, the cy-
clophosphamide, vincristine, and prednisone (COP) protocol has been the basis for treatment. In one
study, 12cats treated with a COP protocol attained a 92%complete remission rate, with a median re-
mission duration of 6 months. In another study, cats with mediastinal lymphoma were treated with
vincristine, cyclophosphamide, and methotrexate. Only 45% responded, with a median remission of
2 months. In cats with stage I and II lymphoma treated with combination chemotherapy consisting of
L-asparaginase, vincristine, methotrexate, cyclophosphamide, and prednisone, the median survival
was 7.6 months. Lastly, cats with lymphoma in several anatomic locations that were treated with in-
duction chemotherapy with the COP protocol and maintained with 5 doses of doxorubicin enjoyed a
median remission duration of 281 days. Overall, combination chemotherapy is recommended, al-
though each patient should be evaluated individually. In some cases single agent therapy may be
more appropriate.
19. Can radiation be effective for treatment of mediastinal lymphoma?
Cats with severe respiratory signs secondary to a mediastinal mass can respond favorably to ra-
diation therapy. Because malignant lymphocytes are extremely radiation-sensitive, radiation therapy
can cause a rapid reduction in tumor burden during life-threatening episodes. Chemotherapy should
be administered with radiation treatment because lymphoma is considered a systemic disease.
20. What is the treatment of choice for cats with a thymoma?
Surgery is the treatment of choice. The median survival is 16 months for cats that survive the
perioperative period. Encapsulated tumors seem to have a better prognosis.
21. Are paraneoplastic syndromes associated with thymomas and lymphomas in cats?
Paraneoplastic syndromes, such as myasthenia gravis, polymyositis, and hypercalcemia. are
much more common in dogs. In one study, only 2 of 12 cats developed paraneoplastic syn-
dromes, and both developed acquired myasthenia gravis. Paraneoplastic syndromes associated
with lymphoma have been described in cats, although hypercalcemia associated with mediastinal
lymphoma is rare.
Myocardial Diseases
BIBLIOGRAPHY
73
1. Barr IF, Gruffydd-Jones TJ, Brown PI, et al: Primary lung tumors in the cat. I Small Anim Pract
28: II 15-1125,1987.
2. Bell FW: Neoplastic diseases of the thorax. Vet Clin North Am Small Anim Pract 17:387-409, 1987.
3. Carlisle CH, Biery DN, Thrall DE: Tracheal and laryngeal tumors in the dog and cat: Literature review
and 13 additional patients. Vet RadioI32:229-235, 1991.
4. Carpenter IL, Holzworth J: Thymoma in II cats. I AmVet Med Assoc 181:248-251, 1982.
5. Cotter SM: Treatment of lymphoma and leukemia with cyclophosphamide, vincristine, and prednisone.
II. Treatment of cats. JAm Anim Hosp Assoc 19:166-172, 1983.
6. Elmslie R, Ogilvie G, Gillette E, et al: Radiotherapy with and without chemotherapy for localized lym-
phoma in 10 cats. Vet RadioI32:277-280, 1991.
7. Gores BR, Berg I, Carpenter IL: Surgical treatment of thymoma in cats: 12 cases (1987-1992). I Am Vet
MedAssoc 204:1782-1785,1994.
8. Hahn KA, McEntee MF: Primary lung tumors in cats: 86 cases (1979-1994). J Am Vet Med Assoc
211:1257-1260,1997.
9. Hahn KA, McEntee MF: Prognosis factors for survival in cats after removal of a primary lung tumor: 21
cases (1979-1994). Vet Surg 27:307-311, 1998.
10. Hahn KA, Anderson TE: Tumors of the respiratory tract. In Bonagura ID (ed): Kirk's Current Veterinary
Therapy XIII. Philapelphia, WB Saunders, 2000, pp 500--505.
II. Jeglum KA, Whereat A, Young K: Chemotherapy of lymphoma in 75 cats. I Am Vet Med Assoc 190:
174-178,1987.
12. MelhalfCJ, Mooney S: Primary pulmonary neoplasia in the dog and cat. Vet Clin North Am Small Anim
Pract 14:1061-1075, 1985.
13. Miles KG: A review of primary lung tumors in the dog and cat. Vet RadioI29:122-133, 1988.
14. Mooney SC, Hayes AA, MacEwen EG, et al: Treatment and prognostic factors in lymphoma in cats: 103
cases (1977-1981). J Am Vet Med Assoc 194:696-699, 1989.
15. Moore AS, Cotter SM, Frimberger AE, et al: A comparison of doxorubicin and COP for maintenance of
remission in cats with lymphoma. J Vet Intern Med 10:372-375, 1996.
16. Saik JE, Toll SL, Diters RW, et al: Canine and feline laryngeal neoplasia: A 10 year survey. I Am Anim
Hosp Assoc 22:359-365, 1986.
17. MYOCARDIAL DISEASES
C. Bisque Jackson, V.M.D.
1. Define cardiomyopathy.
Cardiomyopathies represent a heterogeneous class of diseases characterized by primary
structural abnormalities and functional impairment of the heart muscle. Idiopathic or primary
cardiomyopathy excludes conditions that result from valvular, pulmonary, vascular, pericardial,
congenital, or systemic disease. Secondary cardiomyopathy refers to abnormalities of the heart
muscle related to systemic disease. Examples include hypertrophic cardiomyopathy associated
with hyperthyroidism or arterial hypertension.
2. What are the different types of cardiomyopathies?
The primary myocardial diseases in cats can be divided morphologically and functionally
into hypertrophic, restrictive, and dilated cardiomyopathy.
3. What is hypertrophic cardiomyopathy?
Hypertrophic cardiomyopathy (HCM) is the most common feline myocardial disorder. It af-
fects a broad range of ages, although young to middle-aged male cats seem to be affected most
frequently. The hallmark characteristic of HCM is a hypertrophied, nondilated left ventricle in
the absence of other cardiac, systemic, or metabolic diseases. Left atrial or biatrial enlargement
(dilation) is common, and mild-to-moderate right ventricular hypertrophy is often present. The
74
Myocardial Diseases
functional abnormality associated with HCM is diastolic dysfunction due a reduction in both left
ventricular chamber size and distensibility secondary to hypertrophy. Systolic function tends to
be normal to increased. Left ventricular hypertrophy has many morphologic expressions and
variable distributions; hypertrophy may be symmetric, affecting all wall segments proportionally,
or asymmetric, affecting only segments of the interventricular septum, left ventricular free wall,
and/or papillary muscles. Morphologic changes may include septal hypertrophy that leads to nar-
rowing of the left ventricular outflow tract and dynamic outflow obstruction. Systolic anterior
motion (SAM) of the mitral valve also can contribute to outflow obstruction. The typical histo-
pathologic lesion in HCM is ventricular myofiber disorganization.
4. Which breeds are predisposed to HCM?
Domestic shorthair, Maine coon, and Persian cats seem to be predisposed to HCM, and evi-
dence for genetic transmission in these breeds is mounting. Recent studies suggest that HCM is a
familial disorder with an autosomal dominant pattern of transmission. The mutation is thought to
involve a defect in the cardiac ~ - m y o s i n heavy chain gene (the gene that encodes the cardiac sar-
comere protein).
5. Define restrictive cardiomyopathy.
Recently attention has focused on a newly classified feline myocardial disease termed restrictive
cardiomyopathy (RCM). Although RCM shares many structural and functional features with HCM,
its unique feature is severe diastolic dysfunction with Iittle-to-no ventricular hypertrophy. Significant
left atrial or biatrial enlargement is another hallmark. Systolic function is usually well preserved or
only slightly impaired. The disease is not well characterized but seems to result from impaired ven-
tricular compliance and filling due to infiltration of the myocardium or endomyocardium by fibrous
tissue or some other infiltrative process. The disease, however, is frequently classified as idio-
pathic. Histopathologically,extensiveendocardial scar formation and myocardial fibrosis are present.
6. What is dilated cardiomyopathy?
The hallmark characteristic of dilated cardiomyopathy (DCM) is dilation of all chambers of
the heart and severe systolic dysfunction. In 1987, the association between taurine deficiency and
OCM in cats was recognized. At that time, supplemental taurine was added to most commercial
feline diets, and the number of cats affected with OCM markedly declined. Presently, OCM due
to taurine deficiency is a rare disease in cats. The few cats affected tend to be on unsupplemented
homemade diets or some other unconventional food. Idiopathic OCM is diagnosed more com-
monly in cats with systolic myocardial failure. Myocyte degeneration and necrosis are the
common histopathologic findings.
7. Why is taurine important for cardiac function?
Taurine is an essential amino acid for cats. Cats have a low concentration of cysteine-sulfinic
acid decarboxylase, an enzyme required for taurine biosynthesis. As a result, their ability to syn-
thesize taurine from cysteine and methionine is limited. Taurine is essential for normal structural
and functional integrity of the heart and tapetum. Evaluation of the heart and retina should be
performed on cats that are fed noncommercial diets.
8. What are the normal taurine values?
Cats with myocardial failure have plasma taurine concentrations < 30 nmol/ml (normal =>
60 nmoUml) or whole blood taurine concentrations < 100 nmoUmL (normal =>200 nmoUml). In
addition, most of these cats were found to have concurrent retinal lesions, consisting of bilateral
elliptical hyperreflective lesions in the area centralis in the early stages and diffuse retinal degen-
eration and blindness in the later stages.
9. Are myocardial changes reversible with taurine supplementation?
Treatment with oral taurine supplementation probably improves clinical signs, restores myo-
cardial function, and improves survival when taurine deficiency is responsible for DCM.
Myocardial Diseases 75
Echocardiographic improvements can be seen within I month of treatment, and some cats may
be normal after 2-3 months of therapy. The recommended dose of taurine is 250-500 mg/cat!
day. Cats with idiopathic DCM show little-to-no improvement on oral taurine supplementation.
10. What are the common clinical signs in cats with heart disease?
The broad range of clinical abnormalities depends on the severity of the underlying cardiac
disease. Many cats are affected subclinically, and evidence of heart disease is detected during
routine examination. Clinically affected cats tend to have a history of inactivity, depression,
anorexia, and vomiting. Some cats may present for syncope secondary to bradyarrythmias or
tachyarrhythmias, and others present with acute pelvic limb paralysis secondary to a distal aortic
thrombus. Cats with distal aortic thrombus have absent femoral pulses and cool pelvic limbs and
tend to experience significant pain. In addition, some cats display paresis of a front limb associ-
ated with embolization.
11. What are the common physical examination features in cats with heart disease?
Common physical examination findings include tachypnea, dyspnea, and crackles due to pul-
monary congestion from left-sided heart failure. Decreased lung or heart sounds also may be pre-
sent and suggest pleural and/or pericardial effusion. Ascites, hepatomegaly, and jugular venous
distention may be present with right-sided heart failure. Because cats rarely present with exclusive
right-sided heart failure, biventricularfailure is likely if these findings are present. Heart rates can
vary, but typically cats are tachycardic with heart rates> 200beats/min. Systolic murmurs, abnor-
mal heart sounds (gallop rhythms), arrhythmias, and possible pulse deficits are also frequently
present. Other physical examination findings may include hypothermia, pale mucous membranes,
and weak femoral pulses secondary to a low output state due to myocardial dysfunction.
12. What is the initial diagnostic plan for cats with myocardial disease?
After a thorough history and physical examination, the diagnostic work-up for cats with my-
ocardial disease should include a complete blood count, biochemistry profile, urinalysis, total T4
concentration, thoracic radiographs, arterial blood pressure, electrocardiogram, and echocardio-
gram. The diagnostic work-up should not be initiated until the patient has stabilized completely.
13. What are the common laboratory flndlngs in cats with heart disease?
Cats are often mildly azotemic as a result of decreased renal perfusion, decreased water con-
sumption, and fluid sequestration. Mild elevations in liver enzyme activities may be seen from
hypoxia due to decreased liver perfusion. A stress leukogram is usually present, along with hyper-
glycemia. If aortic thromboembolism is present, increased creatine phosphokinase (CPK), lactate
dehydrogenase (LOR), and aspartate aminotransferase (AST) activities usually are detected.
14. How is hyperthyroidism associated with heart disease?
Hyperthroidism results in a high-output cardiac state with low peripheral vascular resis-
tance. The high-output state causes an increase in myocardial metabolic rate (work load) and
oxygen consumption. The resulting cardiac compensatory change is an increase in myocardial
protein synthesis and subsequent hypertrophy. Circulating thyroid hormone also interacts with
the sympathetic nervous system, causing an increase in the number of B-receptors and in their
sensitivity to catecholamines. This change also causes an increase in the metabolic rate of the
myocardium. Reduced peripheral vascular resistance causes volume retention via renal mecha-
nisms that conserve fluid (renin-angiotensin-aldosterone system). The cardiac compensatory
changes seen with increased blood volume lead to chamber dilation.
15. When should hyperthyroidism be considered a possible diagnosis?
Hyperthyroidism should be considered in any cat over 6 years of age that exhibits clinical
signs of hyperthyroidism (tachycardia, weight loss, polyuria, polydipsia, hyperactivity) and heart
disease. Therefore, careful palpation of the cervical region to detect thyroid nodules is recom-
mended for cats with historical or physical exam features consistent with cardiomyopathy.
76 Myocardial Diseases
Cardiomyopathy associated with hyperthyroidism tends to be reversible with appropriate treat-
ment in an otherwise healthy heart.
16. What are the radiographic findings in cats with cardiomyopathies?
The purpose of thoracic radiographs is to evaluate heart size and shape, pulmonary
parenchyma, and pulmonary vasculature. Left-sided heart enlargement or generalized car-
diomegaly are the most common radiographic findings. Pulmonary parenchymal changes can in-
clude an interstitial and/or alveolar pattern that may be diffuse, patchy, or focal in
distribution. Pulmonary venous distension may be present secondary to left-sided heart fail-
ure. Other findings may include pleural effusion, hepatomegaly, or ascites.
Thoracicradiographs of a cat withhypertrophic cardiomyopa-
thy and heart failure. (Courtesyof Dr. Chris Orton, Colorado
StateUniversity.)
17. Are cats with heart disease hypertensive?
Systemic arterial hypertension does not usually occur secondary to heart disease, but hyper-
tension should be considered in the differential diagnoses for any cat with left ventricular hyper-
trophy. Myocardial changes usually result from rather than cause hypertension. Common causes
for systemic hypertension in cats include renal disease, and hyperthyroidism (see Chapter
63). Other less common diseases include pheochromocytoma, primary aldosteronism due to an
adrenal tumor or hyperplasia (Conn's syndrome), and hyperadrenocorticism. Primary (essential)
hypertension is now a recognized disease in cats.
18. What electrocardiographic (EKG) findings are associated with cardiomyopathies?
The EKG of cats with cardiomyopathy is often unremarkable. When present, electrocardio-
graphic abnormalities are highly variable and do not distinguish among the forms of cardiomy-
opathy. The purpose of the EKG is to determine heart rate and to evaluate for the presence and
type of arrhythmias as well as left and/or right-sided heart enlargement. Typically, cats with heart
disease are tachycardic. Some, however, may have normal rates, and others may be syncopal as a
result of severe bradyarrhythrnias.
Among the more common EKG abnormalities are supraventricular tachycardia, atrial pre-
mature contractions, first-degree atrioventricular block,left anterior fascicular block, left bundle-
branch block, ventricular premature contraction, and ventricular tachycardias. Measurement of
EKG complexes helps to determine whether left- and/or right-sided heart enlargement is pre-
sent. Left atrial enlargement is present if the P-wave duration is > 0.04 sec; right atrial enlarge-
ment if the P-wave amplitude is > 0.2mV; and left ventricular enlargement if the QRS duration is
Myocardial Diseases 77
> 0.04 sec and the R wave amplitude is > 0.8mY. Low-voltage QRS complexes can be seen with
severe pleural and pericardial effusion.
19. What echocardiographic findings are associated with cardiomyopathy?
The morphologic patterns encountered on echocardiography are complex and depend on
the type and severity of underlying cardiomyopathy. In brief, HCM is characterized by thicken-
ing of the left ventricular free wall or septum at end-diastole; measured wall thickness is > 6
mm. Typically, cats with RCM demonstrate severe left atrial enlargement in the absence of
severe left ventricular dilation or hypertrophy. Abnormal echogenicity of the left ventricular free
wall may be present. DCM is typified by increased left ventricular end-systolic dimension (> 12
mm) with decreased fractional shortening 30%). Often, all four cardiac chambers are dilated.
20. What cardiovascular emergencies are commonly seen in cats?
The most common medical emergency is left-sided heart failure resulting in pulmonary
edema and, less commonly, pleural effusion. Such cats usually present in severe respiratory dis-
tress with pulmonary crackles. Acute arterial thromboembolism resulting in pelvic limb paralysis
is another frequently encountered emergency. Less common emergencies include biventricular
failure resulting in pulmonary edema and systemic venous congestion (ascites, pericardial effu-
sion) and syncope from brady- or tachyarrhythmias.
21. What other diseases can cause an acute onset of respiratory distress?
Cats that present with an acute onset of respiratory distress (tachypnea, dyspnea, open mouth
breathing) usually have cardiac disease, lower airway disease (asthma), or pleural space disease
(see Chapter 8). Thorough thoracic auscultation can determine accurately whether pleural space
disease is present, requiring thoracocentesis. A history of cough and/or the presence of tracheal
sensitivity indicates that airway disease is more likely, whereas a heart murmur or gallop rhythm
is more typical in cats with cardiac disease. In compromised cats, oxygen should be adminis-
tered, and treatment for both cardiac disease (diruretic) and asthma (glucocorticoids) may be re-
quired to stabilize the cat before diagnostic testing.
22. What are the initial goals of therapy for left-sided congestive heart failure?
Important initial therapy includes cage rest and supplemental oxygen therapy. It is impera-
tive not to stress a cat in severe respiratory distress, because pulmonary edema can be rapidly and
progressively life-threatening.
23. What drugs may be used to treat left-sided congestive heart failure?
Furosemide should be administered intravenously as soon as possible, althoughthe intramus-
cular route is sufficientin a severelycompromisedcat. Furosemide, a loop diuretic, inhibits tubular
reabsorption of sodium, chloride, and potassiumin the ascendingloop of Henle, thereby decreasing
water reabsorption. Decreased water reabsorption reduces vascular volume and preload, thus de-
creasing left ventricular filling pressures and pulmonary edema. The dose of furosemide therapy
ranges from 0.5-2.0 mglkg every 1-12 hr. The goal of diuretic therapy is to resolve congestion
within 24 hours so that the cat can breathe comfortably and oxygen therapy can be
discontinued. At that time, maintenance doses of furosemide can be initiated. Recommended
doses range from 1.1-2.2 mglkg orally every 24-48 hr.
Nitroglycerine ointment (2%) also should be used in the treatment of acute, life-threatening
pulmonary edema. Nitroglycerine is a potent, direct-acting vasodilator that increases venous ca-
pacitance, thus reducing preload. The recommended dose is V2 inch cutaneously to the pinna
every 6-8 hours for the first 24-48 hours. Gloves are worn during application of nitroglycerine to
prevent systemic absorption.
24. Describe the treatments for acute aortic thromboembolism.
Most cats with thromboembolism (TE) have accompanying signs of congestive heart failure;
therefore, treatment for heart failure should be instituted as previously discussed. Judicious use
78 Myocardial Diseases
of analgesics is appropriate for the first 24-48 hours because the ischemic insult is very painful.
Butorphanol (0.05-0.2 mglkg intravenously or intramuscularly every 8 hr) or morphine (0.05-0.1
mg/kg intramuscularly every 8 hr) provides good analgesia. Various medical treatments have
been advocated for the treatment of TE, but most are empirical and no data support any single
treatment. Current therapy is aimed at lysing the existing clot with thrombolytic agents or at pre-
venting new thrombus formation or growth with anticoagulants. The current thrombolytic agents
include tissue plasminogen activator (t-PA), streptokinase, and urokinase. Bleeding, severe reper-
fusion injury, and death are severe complications that can be associated with these drugs, and
they should be used cautiously in cats. The anticoagulants used to impair clotting factor synthesis
or enhance inactivation are warfarin and heparin, respectively. These drugs should be used with
caution because they can result in severe bleeding complications without appropriate monitoring.
Monitoring of bleeding times (one-stage prothrombin time or international normalized ratio for
warfarin and activated partial thromboplastin time for heparin) is imperative if an anticoagulant
is used. Aspirin often is used to retard thrombus formation or growth, because inhibition of
thromboxane production theoretically should block platelet aggregation. The clinical effects of
aspirin therapy are controversial, and most cats reembolize despite aspirin therapy.
25. What are the goals of maintenance therapy for HCM and RCM?
To prevent congestion (diuretic therapy);
To control heart rate and rhythm (beta blockers, calcium channel blockers)
To block the neurohormonal mediators of heart failure, notably angiotensin, aldosterone,
and epinephrine, and thus induce regression of the hypertrophy, (angiotensin-converting
enzyme [ACE] inhibitors, spironolactone, beta blockers)
To reduce the likelihood of TE with anticoagulants (heparin, warfarin, aspirin)
26. What is the recommended therapy for HCM and ReM?
There is no single treatment recommendation for heart disease. Therapy must be tailored to the
particular type, severity, and duration of the cardiomyopathy. Frequent monitoring of patients is ad-
vocated. and drug therapy should be adjusted accordingly. Most cats affected with HCM or RCM
are treated with furosemide, calcium channel blocker or a beta blocker, and an ACE inhibitor.
Drugs Used Frequently in the Management of Cardiac Disease in Cats
DRUG/CLASS INITIALDOSE
ACE inhibitors
Enalopril
Benazepril
Beta blockers
Atenolol
Metoprolol
Calcium channel blocker
Diltiazem (Dilacor XR:
extended release)
Digitalis
Digoxin
Diruetic
Furosemide
Anticoagulants
Aspirin
Warfarin (Coumadin)
Heparin
0.25-5.0 mglkg PO every 12-24 hr
0.50 mg/kg PO every 24 hr
6.25-12.5 mg/cat PO every 12-24 hr
2-15 mg/cat PO every 8 hr
30 mglcat PO every 12 hr
Cats < 3.0 kg: 0.031 mg PO every 48-72 hr
Cats 3.0-6.0 kg: 0.031 mg PO every 24 hr
Cats> 6.0 kg: 0.031mg PO every 12-24 hr
6.25 mg/cat PO every 24--48hr-12.5 mg/cat PO every 8 hr
25 mg/cat PO every 72 hr
0.25--0.5mg/cat PO every 24 hr
100-200 U/kg N once; then 100-300 Ulkg SQ every 8 hr
Myocardial Diseases
Drugs Used Frequently in the Management a/Cardiac Disease in Cats (Continued)
DRUG/CLASS INITIALDOSE
79
Others
Nitroglycerine
Taurine
V2 inch cutaneously to the pinna every 6-8 hr for the first 24-48 hr
ACE= angiotensin-converting enzyme, PO = orally, SQ= subcutaneously,IV = intravenously.
27. Why is the use of ACE inhibitors controversial in cats with HCM?
It has been well documented in dogs that activation of the renin-angiotensin-aldosterone
system negatively affects the natural history of heart failure, primarily mediated by increased an-
giotensin II levels. Despite the many beneficial effects of ACE inhibitors for cardiac disease, their
use in cats with HCM may be controversial. ACE inhibitors cause mild arteriolar dilation by in-
hibiting production of the vasoconstrictor angiotensin II. A decrease in afterioad theoretically may
result in an increased pressure gradient in cats with dynamic outflow obstruction and/orSAMof the
mitral valve. In practice, however, ACE inhibitors are sometimes used in cats with HCM.
28. What are the treatment options and goals of maintenance therapy for DCM?
To prevent congestion (diuretic therapy)
To promote increased forward cardiac output and improve myocardial contractility (posi-
tive inotropy)
29. What is the recommended therapy for DCM?
Most cats affected with DCM are maintained on furosemide and digitalis. Furosemide ther-
apy is the same as for HCM or RCM: 1.2-2.2 mg/kg orally every 24-48 hr. The inotropic effects
of digoxin are mediated through inhibition of the sodium-potassium-adenosine triphosphatase-
pump. By increasing the concentration of sodium in the cell, more calcium enters the cell via the
sodium-calcium exchanger, ultimately producing a more forceful cardiac contraction. Therapy is
based on a calculated dose of 0.005-0.01 mg/kg. The 0.12S-mg tablet is more easily administered
to most cats than the elixir form. The recommended doses are listed in question 26. Serum digoxin
concentrations should be monitored as well as renal values because digoxin is eliminated by the
kidneys. In addition, taurine is administered empirically (2So-S00 mg/cat orally every 12 hr).
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I I. Medinger TL, Bruyette DS: Feline hypertrophic cardiomyopathy. Comp Cont Educ Pract Vet 14:479-
490,1992.
12. Pion PD, Kittleson MD, Rogers QR, et al: Myocardial failure in cats associated with low plasma tau-
rine: A reversiblecardiomyopathy. Science 237:764-768, 1987.
II. Gastrointestinal Problems
Section Editor: L1Jnda Melendez. D.V.M., M.S.
18. OVERVIEWAND DIAGNOSTIC PROCEDURES
Michael R. Lappin, D.v.M., Ph.D.
1. What ditTerentiates vomiting from regurgitation?
Vomiting is the forceful ejection of stomach and proximal duodenal contents through the
mouth. Vestibular, vagal, chemoreceptor trigger zone, or direct input to the emetic center can induce
vomiting. Regurgitation is the passive expulsion of food or fluid from the oral cavity, pharyngeal
cavity, or esophagus (see Chapter 26). Esophageal diseases are rare in cats compared with dogs.
2. Howis diarrhea characterized?
Diarrhea is characterized by increased frequency of defecation, increased fluid content of the
stool, or increased volume of stool. Markedly increased frequency of defecation, small-volume
stools, tenesmus, urgency, hematochezia, and mucus are consistent with large bowel diarrhea.
Slight increase in frequency of defecation, large volume, melena, steatorrhea, and polysystemic
clinical signs are more consistent with small bowel diarrhea. Mixed bowel diarrhea is a com-
bination of characteristics or clinical signs. The clinical differential diagnoses for vomiting and
small bowel diarrheas are similar.
3. What are the major differential diagnoses for vomiting and small bowel diarrhea?
Causes can be grouped as either primary or secondary gastrointestinal (01) tract diseases:
Differential Diagnoses for Vomiting and Small Bowel Diarrhea in Cats
PREDOMINANT SIGN
Primary GI diseases
Obstruction: masses, foreign body, intussusception
Dietary intolerance
Drugs or toxins
Inflammatory gastric and bowel diseases
Neoplasia
Infectious diseases
Parasites
Secondary GI diseases
Renal disease
Hepatic disease
Pancreatitis
Hypoadrenocorticism (rare in cats)
Diabetes mellitus with ketoacidosis
Peritonitis
Central nervous system/vestibular disease
Pancreatic exocrine insufficiency
Vomiting or diarrhea
Vomiting primarily, some diarrhea
See table in question 4
See table in question 4
Vomiting primarily
Vomiting primarily, some diarrhea
Vomiting primarily
Vomiting primarily
Vomiting primariliy
Diarrhea primarily
81
82 Overview and Diagnostic Procedures
4. What are the major differential diagnoses for large bowel diarrbea?
Most causes of large bowel diarrhea involve the GI tract primarily and include inflammatory
disease, neoplasia, obstruction (ileocecocolic valve), spastic disorder (idiopathic), dietary intoler-
ance, infection, and parasitism. Secondary GI diseases usually are not associated with large
bowel or mixed bowel diarrhea Inflammation of the cecum, large intestine, and rectum can result
in vomiting; the mechanism is vagal afferent nerve transmission to the emetic center.
Infectious Disease Differential Diagnosesfor Vomiting and Diarrhea in Cats*
Bacterial agents
Salmonella spp. (S, M)
Enterotoxigenic Escherichia coli (S, M)
Clostridium perfringens (L, rare)
Helicobacter felis and H. heilmannii (V)
Bacterial overgrowth (S)
Bacterial peritonitis (S)
Bacterial cholangiohepatitis (S)
Viral agents
Feline coronaviruses (S)
Feline lymphoma (S, M, L)
Feline immunodeficiency virus (S)
Feline panleukopenia (V only frequently, S)
Fungal
Histoplasma capsulatum (L)
Saprophytic fungi (S, M, L)
Helminths
Ancylostoma/Uncinaria spp. (S, M, L)
Strongyloides cati (S, M, rare)
Dirofilaria immitis (V)
Toxocara cati (V)
Ollulanus tricuspis (V)
Physaloptera spp. (V)
Flagellates
Giardia spp. (S, M)
Trichomonas hominis (L, rare)
Amoeba
Entamoeba histolytica (L, rare)
Coccidian
Cystoisospora spp. (M, L)
Cryptosporidium spp. (S, M)
Toxoplasma gondii (V, S, rare GI diseases)
S = small boweldiarrhea, M= mixedbowel diarrhea, L = largeboweldiarrhea, V=vomiting.
* All diseasesresulting in diarrheaalsocancausevomiting.
5. Is a diagnostic work-up always indicated for cats with vomiting or diarrhea?
Vomiting or diarrhea due to drugs, toxins, and dietary intolerance can be excluded by history
and diet change. Otherwise healthy cats with acute vomiting and normal physical examination
findings often can be managed conservatively by withholding food for 24 hours, followed by in-
troduction of bland food for several days.
6. What is the minimal diagnostic plan for cats with vomiting or diarrhea?
Fecal flotation and complete blood cell count (CBC) are indicated for most cats with vomit-
ing. Although the CBC generally does not lead to a specific diagnosis, the presence of eosino-
philia makes inflammatory bowel diseases and parasitism more likely. If diarrhea is present, wet
mount examination for trophozoites, rectal cytology, and Cryptosporidium screen (fecal enzyme-
linked immunosorbent assay [ELISA] or acid-fast stain of a thin fecal smear) also are indicated.
Fecal fat assessment with Sudan IV stain with and without acetic acid helps to confirm malab-
sorption/maldigestion but is not specific for a single disease.
7, How do you screen for secondary GI tract diseases associated with vomiting and diarrhea?
A serum biochemical profile, urinalysis, feline leukemia virus (FeLV) antigen assay, and
feline immunodeficiency virus (FIV) antibody assay generally are performed in cats with chronic
vomiting and diarrhea (see Chapter 25). The author generally assesses serum total T4 concentra-
tion in all cats with vomiting or small bowel diarrhea that are older than 5 years. Although amy-
lase and lipase are poor predictors of pancreatitis in cats, a trypsin-like immunoreactivity assay
has now been validated (Texas A & M University, College Station, TX). It can be used to support
the diagnosis of acute pancreatitis (increased) or exocrine pancreatic insufficiency (decreased) in
cats (see Chapter 36). If a cat with suspected pancreatitis has abdominal effusion, measure lipase
concentrations in the serum and effusion; if pancreatitis is present, effusion lipase is usually
greater than serum lipase.
Overview and Diagnostic Procedures 83
8. What are the indications for direct smears? What techniques are used?
Liquid feces or feces that contain large quantities of mucus should be microscopically ex-
ami ned immediately for the presence of protozoal trophozoites, including Giardia spp. (fla-
gellate) and Pentatrichomonas hominis (flagellate). A direct saline smear can be made to
facilitate observation of these motile organisms. The amount of feces required to cover the
head of a match is mixed thoroughly with one drop of 0.9% sodium chloride (NaCl). After ap-
plication of a coverslip, the smear is evaluated for motile organisms by examining it under
100 x magnification.
9. How does rectal cytology aid in the diagnostic evaluation of cats with diarrhea?
A thin smear of feces should be made from all cats with diarrhea. Material should be col-
lected by rectal swab, if possible, to increase chances of finding white blood cells. A cotton swab
is gently introduced 3-4 em through the anus into the terminal rectum, directed to the wall of the
rectum, and gently rotated several times. Placing a drop of 0.9% NaCI on the cotton swab facili-
tates passage through the anus but does not adversely affect cell morphology. The cotton swab is
rolled on a microscope slide gently multiple times to give areas with varying thickness; three
slides are usually made. After air drying, one of the slides can be stained with Diff-Quick or
Wright's-Giemsa stains. The slide should be examined for white blood cells and bacteria mor-
phologically consistent with Campylobacter jejuni or Clostridium perfringens. Histoplasma cap-
sulatum or Prototheca spp. may be observed in the cytoplasm of mononuclear cells. Methylene
blue in acetate buffer (pH =3.6) stains trophozoites of the enteric protozoans. Iodine stains and
acid methyl green also are used for the demonstration of protozoans. Acid-fast or monoclonal an-
tibody staining (Meridian Diagnostics, Cincinnati, OH) of a fecal smear should be performed in
cats with diarrhea to aid in the diagnosis of cryptosporidiosis. Cryptosporidium parvum is the
only enteric pathogen of approximately 4-6 f.IIIl in diameter that stains pink to red with acid-fast
stain. Presence of neutrophils on rectal cytology may suggest inflammation induced by
Salmonella spp., C. jejuni, or C. perfringens; fecal culture is indicated in such cases.
10. What fecal flotation solutions sbould be used for cats?
Ability to float parasite ova, oocysts, or cysts is based on the specific gravity of the solu-
tion; most ova, oocysts, and cysts are easily identified after zinc sulfate centrifugal flotation
(see Chapter 19). This procedure is considered by many to be optimal for the demonstration of
protozoan cysts, in particular Giardia spp.; it is a good choice for a routine flotation technique.
Sugar centrifugation can be used for routine parasite evaluation and may be superior to many
techniques for the demonstration of oocysts of Toxoplasma gondii and C. parvum. Giardial
cysts are distorted by sugar centrifugation but can still be easily identified. Fecal sedimentation
recovers most cysts and ova but also contains debris. This technique is superior to flotation pro-
cedures for the documentation of fluke eggs.
Zinc Sulfate Centrifugation Procedure
I. Place I gm of fecal material in a 15-ml conical centrifuge tube.
2. Add 8 drops of Lugol iodine, and mix well.
3. Add 7-8 ml ofzinc sulfate (1.18 specificgravity)," and mix well.
4. Add zinc sulfate until there is a slight positive meniscus.
5. Cover the top of the tube with a coverslip.
6. Centrifugeat 1500--2000 rpmfor 5 minutes.
7. Removethe coverslip, and place on a clean microscopeslide for microscopicexamination.
8. Examinethe entire area under the coverslipfor the presence of ova, oocysts, or larvaeat 100 x
magnification.
*Add330 gmof zincsulfate to670 ml of distilled water.
84
Overview and Diagnostic Procedures
11. If a delay is expected before feces are evaluated, should a preservative be used?
Feces should berefrigerated, not frozen, until assayed. If a fecal sample is to be sent to a diagnos-
tic laboratory for further analysis and will not beevaluated within 48 hours, it should be preserved.
Polyvinyl alcohol, merthiolate-iodine-formalin, and 10% formalin can be used; 10% formalin is com-
monly used because of its routine availability. Add I part feces to 9 parts formalin, and mix well.
12. How can I increase the likelihood of diagnosing Salmonella or Campylobacter spp, in-
fections?
Approximately 2-3 gm of fresh feces should be submitted to the laboratory immediately for
optimal results; however, Salmonella and Campylobacter spp. are usually viable in refrigerated
fecal specimens for 3-7 days. The laboratory should be notified of the suspected pathogen so ap-
propriate culture media are used. Cary-Blair medium (Bectin-Dickinson Microbiology Systems,
Sparkes, MD) is appropriate for transport.
13. Are any of the fecal antigen techniques beneficial in the evaluation of cats with gas-
trointestinal disease?
Parvovirus, C. parvum, and Giardia spp. antigen detection procedures are available for
feces. In a limited number of feline samples assessed at Colorado State University, canine par-
vovirus assays detected feline parvovirus antigen and correlated well with results from electron
microscopy. Sensitivity and specificity of C. parvum and Giardia antigen assays have not been
determined when used with feces from cats. They should be interpreted in conjunction with re-
sults of fecal examination techniques.
14. How can viruses other than parvovirus be detected in feces?
Electron microscopy can be used to detect viral particles in feces of cats with GI signs of dis-
eases. Approximately 1-3 gm of feces without fixative should be transported to the laboratory
(Diagnostic Laboratory, Colorado State University, College of Veterinary Medicine and
Biomedical Sciences, Fort Collins, CO) by overnight mail on cold packs. In some research labo-
ratories, virus isolation can be performed. In addition, reverse transcriptase-polymerase chain re-
action (RT-PCR) can be used to detect coronavirus particles in stool (see Chapter 21).
15. Howcan I assess cats for helicobacteriosis?
Gastric biopsies should be placed on urea slants to assess for urease, which is found in the cell
wall of Helicobacter spp. but not in nonpathogenic spirochetes. A presumptive diagnosis of heli-
cobacteriosis can be based on the identification of inflammatory cells and spirochetes in the gastric
biopsies plus a positive urease test and exclusion of other causes of GI disease (see Chapter 20).
16. What imaging techniques are beneficial in evaluating primary GI tract diseases?
Imaging techniques such as radiographs, contrast radiographs, and ultrasound can aid in the diag-
nosis of diseases resulting in obstruction. Abdominal radiographs should be used to support palpation
findings, particularly to help prove or deny obstructive disease. Contrast radiographs are beneficial to
document obstructive disease and localize lesions. Ultrasound of the GI tract can be difficult to inter-
pret; its value depends on the skill of the operator. However, ultrasound is quite valuable in the diag-
nosis of secondary GI tract diseases such as pancreatitis, renal diseases, and hepatic diseases.
17. When should endoscopy be considered in the work-up of a GI case?
The esophagus, stomach, proximal duodenum, rectum, colon, and distal ileum can be as-
sessed endoscopically. The technique is most valuable to diagnose and retrieve foreign bodies
and to obtain biopsies for evaluation of inflammatory and neoplastic diseases. Because endo-
scopic biopsies are small and lesions may be focal, at least 8-10 biopsies should be made from
the stomach, duodenum, colon, and ileum, if possible. Full-thickness biopsies may be required to
make a definitive diagnosis in some cats. There is no benefit to performing duodenal aspirates for
quantitative bacterial cultures or giardial trophozoite evaluations in cats. The normal bacterial
count range is broad in cats, and Giardia spp. are found in the distal small intestine.
Gastrointestinal Parasites
BIBLIOGRAPHY
85
Lappin MR: Laboratory diagnosis of infectious diseases. In Nelson RW, Couto CO (eds): Small Animal
Internal Medicine, 2nd ed. St. Louis, Mosby, 1998,pp 1240-1252.
19. GASTROINTESTINAL PARASITES
Glenda Taton-Allen, M.S., and John Cheney, D.V.M., M.S.
1. What internal parasites infect the gastrointestinal (GI) system?
Nematodes, cestodes, protozoans, and trematodes can be harbored in the GI tract of cats.
Several of these organisms also infect humans; zoonotic aspects are discussed in depth in
Chapter 84.
Morphologic Characteristics of Feline Gastrointestinal Parasites
ORGANISM UFE STAGEANDDESCRIPTION
Helminths
Toxocara cati
Toxascaris leonina
Ancylostoma cati
Ancylostoma brazitiense
Uncinaria stenocephalia
Spirocerca lupi
Ollulanus tricuspis
Physoloptera spp.
Trichuris spp.
Cestodes
Dipylidium caninum
Taenia spp.
Echinococcus multilocularis
Mesocestoides lineatus
Flukes
Alaria
Protozoans
Coccidians
Toxoplasma gondii
Isospora felis
Isospora rivolta
Sarcocystis spp.
Cryptosporidium spp.
Flagellates
Giardia lamblia
Pentatrichomonas hominis
Egg: 65-75f.1
Egg: up to 80 f.I
Egg: 55-65 f.I x 34-45 f.I
Egg: 55-76 f.I x 35-45 f.I
Egg: 60-75 f.I x 33-50 II
Egg; 12f.1x4011
Egg: 5511 x 30 II; larvated
Larvae: rhabditiform first-stage larva
Adult: 0.7-2.00 mrn long
Adult: 3-6cm
Egg: 30-33 IIx 45-55 II; larvated
Egg: 35-38 II x 75-80 II, bipolar plugs
Proglottid; double pored
Egg packet: 25-40 II x 30-45 II
Proglodttid; single pored
Egg: 37 II x 32 II
Egg: 37 II x 32 f.I
Proglottid: central genital pore
Egg: 22-25 II x 25-30 II
Egg: 70 f.I x 134 f.I; operculated
Oocyst: 10 II x 1211
Oocyst: 21-31 f.I x 38-51 II
Oocyst: 20-26 II x 23-29 II
Oocyst: 12-1611 x 7-911
Oocyst: 4-6 f.I x 4-7 f.I
Cyst: 7-10 II x 8-12 f.I
Trophozoite: 10-12 f.I x 15-18 f.I
Trophozoite: 4-6 f.I x 7-14 J.I
86 Gastrointestinal Parasites
2. What are the most common GI helminthes?
The large roundworms (ascarids) Toxocara cati and Toxascaris leonina and the tapeworms
Taenia taeniaeformis and Dipylidium caninumare very common in cats. T. cati is the most common
parasite of kittens, and T. taeniaeformis and D. caninumare the most common parasites in adult cats.
3. How are cats infected with ascarids?
Adult T. cati live in the small intestine of cats, and eggs are passed with the feces into the envi-
ronment. The eggs become infective in as little as I month, and when the infective eggs are ingested
by another cat, the larvae migrate via the liver and lungs to the small intestine, where they mature.
Rodents can serve as transport hosts, and larvae of the organism can be transmitted lactationally to
kittens. The larval stage does not migrate through tissues when transmitted through milk but goes
directly to the small intestine to mature. Prenatal infection does not occur with T. cati.
T. leonina eggs develop in the environment and become infective in as little as I week. Cats
become infected after ingestion of the egg or infected transport hosts (primarily rodents). Trans-
placental and transmarnmary infection do not occur. Instead of migrating through tissues, the larvae
burrow into the intestinal wall, undergo development, and then return to the lumen to mature into the
adult stage. T. cati but not T. leoninacan cause visceral larva migrans in people (see Chapter 84).
4. What are the clinical signs of ascarid infections?
Ascarid infections in adult cats are usually subclinical. In kittens and young cats, vomiting,
small bowel diarrhea, and abdominal distention are common clinical findings. Kittens may be
listless, fail to thrive, and have a poor hair coat.
5. What hookworms infect the GI tract of cats?
Ancylostoma braziliense, A. tubeforme, and Uncinaria stenocephala infect cats. Prevalence
of hookworm infections varies by region of the United States. Both Ancylostoma spp. prefer
warm, humid climates, whereas U. stenocephalasurvives well in colder climates. Hookworm in-
fections in cats are more common in the southern and southeastern United States.
6. Describe the life cycle of feline hookworms.
The hookworm has a direct life cycle. Eggs passed in the feces larvate and hatch in the envi-
ronment. If the environment is moist and warm, the larvae can hatch in a matter of hours; cats are
infected by skin penetration or ingestion of infective larvae. There is no evidence that feline
hookworms are transferred transplacentally or lactationally. Rodents can act as transport hosts.
7. What are the clinical manifestations of hookworm infection?
Hookworm infection is not nearly as devastating in cats as in dogs. Intestinal bleeding may
occur, but it is usually minimal. Heavy infection must be present to manifest clinical signs such
as poor hair coat, weight loss, and melena. Adult cats are infected more heavily than kittens be-
cause transplacental and lactational transmission do not occur. Infected people can develop cuta-
neous larva migrans (see Chapter 84).
8. What diagnostic techniques best recover hookworm, ascarid, and other nematode eggs?
The centrifugation fecal flotation technique is the best method to recover nematode eggs
from fecal samples (see Chapter 18). The specific gravity of the salt solution used for flotation
should be 1.18-1.25. Zinc sulfate at a specific gravity of 1.18 is a good solution because it is op-
timal for recovery of giardial cysts as well as most helminth eggs.
The prepatent period for Toxocaraspp. is 6-8 weeks; eggs are not present in infected kittens
younger than this age. Eggs of T. cati are large (65-75 u) and dark brown with a thick, roughened
outer (corticate) wall. Eggs of T. leonina are slightly larger than T. cati eggs (up to 80J.l) and have
a light golden brown color with a smooth outer wall and an undulating interior wall. Finding the
unembryonated oval eggs in fresh feces establishes the diagnosis of hookworm infection. The eggs
range from 55-95 J.l in length, depending on the species of hookworm (see table in question I).
Comparison of Toxocara spp. eggs (dark brown eggs with
corticated outer wall) with Toxascaris spp. eggs (lighter,
more diffuse egg with smooth outer wall).
87
9. What stomach worms may infect cats?
Physaloptera spp. is the only common stomach worm of cats but can be found in the small
intestine as well. This parasite requires insects, including crickets, various beetles, and cock-
roaches, as the intermediate host. Transport hosts are primarily mice. Cats become infected when
they ingest the intermediate or transport host. Diagnosis can be difficult because the eggs do not
float well in most salt solutions except in saturated magnesium sulfate (specific gravity =1.30).
Eggs are larvated and measure 30-33 Il x 45-55 Il. Immature or mature worms (1-6 ern) may be
vomited, although these nematodes have small teeth and attach strongly to the gastric mucosa to
suck blood. Endoscopy is a useful diagnostic tool since usually few eggs are found. Clinical ab-
normalities include vomiting and gastric ulcers.
Rare infections with two other parasites, Ollulanus tricuspis and Gnathostoma spinigerum,
have been reported in the United States. The entire life cycle of O. tricuspis can take place within
the stomach of the cat. It is an extremely small worm, only 0.7-1.0 mm long. Cats become infected
from eating vomitus containing L3, L4, or adult nematodes, and the larvae can live in the vomitus
up to 10 days, depending on environmental conditions. Microscopic examination of vomitus or gas-
tric fluids is the primary way to diagnose O. tricuspis infection. G. spinigerum requires two inter-
mediate hosts, first a crustacean and then a freshwater fish, amphibian, or reptile. The cat ingests the
intermediate host. The parasites migrate throughout the body and cause severe ulceration and necro-
sis of the stomach wall, where the adults live. Diagnosis is difficult because few eggs are produced
and usually are not present in feces. There is no treatment, and the infection is often fatal.
10. If adult worms are present in vomitus, how can T. cat; be distinguished from
Physaloptera spp.?
Adult Physaloptera spp. are similar to Toxocara and Toxascaris spp. except that they are
shorter and usually coiled. The head of the ascarid has a small mouth opening surrounded by
three lips. Physaloptera spp. are unique in that adults have two spines at the anterior end and a
"collar" type structure around the head area.
11. What other nematodes are found on rare occasions in the feline GI tract?
Strongyloides stercoralis is an unusual parasite because it has both a parasitic life cycle and
a free-living life cycle. This organism is generally a parasite of younger animals; the finding of
larvated eggs (30 Il x 55 Il) or, more commonly, rhabditifonn larvae in the feces is diagnostic.
The entire life cycle can be completed in cats; diarrhea is the primary clinical sign. The organism
can cause cutaneous larva migrans in people (see Chapter 84).
Spirocerca lupi adults generally live in the esophagus but can be harbored in the stomach. This
organism uses coprophagic beetles as intermediate hosts as well as numerous paratenic hosts. in-
cluding lizards. mice, and chickens. Infection is diagnosed by the finding of small, thick-walled lar-
vated eggs in feces. The eggs measure 121l x 40 Il. Endoscopy is also a useful diagnostic tool to find
esophageal granulomas and make a definitive diagnosis. Clinical signs of disease are rare in cats.
Trichuris campanula and T. serrata infections (whipworms) occur sporadically in cats in the
United States. Adult worms live in the large intestine and cecum. The life cycle is direct; cats can
become infected by ingestion of the eggs that have developed in the environment. Development
of Trichuris spp. eggs takes from 10 days to 2 months. Infections normally do not cause severe
disease in cats. Eggs are recovered using a fecal float and identified by the characteristic barrel
shape and bipolar plugs; they range in size from 35-38 fJx 75-80 fJ. Differentiation from the
lungworm, Capillaria aerophilia, is necessary.
12. What are the principal anthelmintics used for treatment of nematodes infecting cats?
Several anthelmintics are used in cats to treat ascarids, hookworms, and other nematodes.
Pyrantel pamoate, although not approved for use in cats, is extremely safe and efficacious in the
treatment of ascarids and hookworms. It must be given in two doses about 2-3 weeks apart be-
cause the drug kills only parasites in the GI tract, not the tissue migratory stages. Fenbendazole,
also extremely safe, is not approved for use in cats. It is effective for the treatment of ascarids,
hookworms, whipworms, S. stercoralis, and other less common nematodes. The liquid formula-
tion of fenbendazole is usually given for 3-5 days. Treatment must be repeated in 2-3 weeks for
ascarids and hookworms. Treatment needs to be repeated at 4 weeks and 8 weeks for whipworrns.
Fenbendazole also has antigiardial activity (see question 30). The combination of praziquantel and
pyrantel is approved for use in cats and is also effective for the treatment of tapeworms. Piperazine
is approved for use in cats, but efficacy is variable and less than desirable. Selamectin is approved
to treat T. cati and hookworms in cats. Ivermectin is effective for the control of hookworms.
Drugs Used/or Control a/Gastrointestinal Tract Parasites in Cats
GENERIC DRUG COMMONFELINE DOSAGE
Alana marcianae
Praziquantel *
Cestodes
Epsiprantel*
Fenbendazole (Taenia spp. only)
Praziquantel *
Cryptosporidium parvum
Azithromycin
Paromomycin
Tylosin
Isosporaspp.
Trimethoprim-sulfonamide
Sulfadimethoxine
Furazolidone
Amprolium
Paromomycin
Giardia spp.
Metronidazole
Fenbendazole
Furazolidone
Helminths
Fenbendazolet
Ivermectin!
Pyrantel pamoate"
Pyrantel plus praziquantel"!
Piperazine>"
Selamectinv"
5 mglkg/day PO for 2-3 days
2.75 mglkg once PO
50 mglkg/day PO for 3 days
23 rng/cat PO or 56.8 mg/ml SC or 1Monce
7-15 mglkg every 12 hr PO for 5-7 days
150 mglkg every 12-24 hr PO for 5 days
10-15 mglkg every 8-12 hr PO for 21 days
15 mglkg every 12 hr PO for 5 days
50-60 mglkg/day PO for 5-20 days
8-20 mglkg every 12-24 hr PO for 5 days
60-100 mg/day for 5 days
10-25 mglkg every 12 hr PO for 8 days
50 mglkg every 24 hr PO for 3-7 days
50 mglkg/day for 3-5 days PO; repeat in 2-3 wk
Label dose PO monthly
20 mglkg once PO; repeat in 2-3 wk
72.6 mg pyranteVl8.2 mg praziquantel, I tablet PO
110 mglkg once PO; repeat in 2 wk
6 mglkg topically once monthly
Table continuedonfollowing page
Drugs Used for Control of Gastrointestinal Tract Parasites in Cats (Continued)
GENERIC DRUG COMMON FELINE DOSAGE
89
Pentatrichomonas hominis
Metronidazole
Paromomycin
Toxoplasma gondii
Azithromycin
Clindamycin hydrochloride
Clarithromycin
Pyrimethamine
Trimethoprim-sulfonarnide
10-25 mg/kg every 12hr PO for 8 days
150 mg/kg every 12-24 hr PO for 5 days
7-15 mg/kg every 12hr PO for 5-7 day
12.5mg/kg every 12hr PO, 1Mfor 28 days
5-10 mg/kg PO every 12hr for 7 days
Rarely used because of toxicity
15 mg/kg every 12 hr PO for 28 days
IM=intramuscular, IV=intravenous, SC=subcutaneous, PO=oral, NA=not applicable
* Drugs are approved for use in cats
t Effective against hookworms, roundworms, whipworms, andstomachworms.
I Heartgard for cats, Merck,Whitehouse Station, NJ; effectivefor hookworms.
~ Effective against hookworms androundworms.
DrontalPlus, BayerAnimal Health, Shawnee Mission, KS; effective againsthookworms, roundworms, and
tapeworms.
~ Effective against hookworms and roundworms.
Revolution, PfizerAnimalHealth, Exton, PA;effective againsthookworms and roundworms.
13. How do cats become infected with tapeworms?
The most common tapeworms in cats are T. taeniaeformis and D. caninum. Adult tapeworms
live in the small intestine, and both species require an intermediate host to complete their life
cycles. Gravid proglottids containing many eggs are released from adult worms either singly or in
chains attached to each other. These proglottids may rupture in the intestine, liberating the eggs,
or, more commonly, intact proglottids may be expelled in or on the feces. The white proglottids
may crawl out of the anus spontaneously and remain motile for a time. Occasionally, multiple
proglottids still attached to one another are passed in vomitus. The intermediate host must ingest
eggs from proglottids; then the larval stage develops. Rodents (mice) are the intermediate host for
T. taeniaeformis, and dog and cat fleas are the intermediate hosts for D. caninum. Cats become in-
fected with tapeworms by ingesting the intermediate host. The prepatent period is 4-6 weeks.
14. Do tapeworm infections cause clinical manifestations?
Usually no clinical signs are associated with tapeworm infections. Heavy infections occa-
sionally cause anal pruritus, diarrhea, vomiting, or intestinal obstruction. People can be infected
by D. caninum if they ingest infected fleas (see Chapter 84).
15. How are tapeworm infections diagnosed?
Tapeworm proglottid identification is probably the most common way to diagnose infec-
tions. Owners may observe the dried proglottids, which appear as "rice granules" on the perianal
area. A squash mount, which causes release of eggs from the proglottid, facilitates identification.
The proglottid is placed on a microscope slide with a drop of distilled water or saline. A large
coverglass is pressed over the proglottid to force the eggs from the genital pore. Taenia eggs are
mid-sized (30-35 ~ x 35--40 u) and expelled as single, thick-walled, round eggs with the hexa-
canth embryo visible inside. The wall has a striated or "sunburst" effect. Each proglottid has a
genital pore on one side only. Dipylidium eggs are expelled in egg packets with 4-15 oncos-
pheres per packet. Each proglottid has two genital pores, one on each side. Dried tapeworm
proglottids can be hydrated in water first before a squash mount is performed. When fecal sam-
ples are submitted, it is important to look for tapeworm proglottids not only on the feces, but also
on the walls of the container, because the proglottids may crawl off the feces. Eggs of Taenia
spp. can be recovered with the zinc sulfate centrifugation concentration technique, but this tech-
nique is not as common as finding proglottids. Dipylidium egg packets range in size from 25--40
~ x 30--45 ~ and are rarely recovered in a fecal float.
Above. Taenia-type eggs with thick, stri-
ated wall and hexacanth embryo. Right,
Dipylidium caninum egg packet.
16. What other tapeworm infections occur in cats?
Taenia pisiformis and T. hydatigena are transmitted to cats by ingestion of rodents or rab-
bits. Clinical and diagnostic issues are the same as for T. taeniaeformis.
Cats can complete the lifecycle of Echinococcus multilocularis; infection usually is subclin-
ical. E. multi/ocularis is acquired by eating infected rodents, which serve as intermediate hosts.
Tiny proglottids and Taenia-type eggs (32 Il x 37 Il) are passed in the feces after a prepatent
period of about 2 months. The eggs are infective to humans and, if ingested, can invade tissues to
develop into hydatid cysts (see Chapter 84). E. multilocularis is most common in northern and
central parts of North America.
Cats can be the definitive hosts of Diphyllobothrium latum and Spirometra mansonoides.
Both agents require two intermediate hosts; the first intermediate host is a copepod, and the
second a vertebrate. D. tatum uses a freshwater fish for the second intermediate host, whereas S.
mansonoides uses mammals, tadpoles, or water snakes. Eggs rather than gravid proglottids are
passed in feces. Eggs of D. latum are heavy and do not float well in salt solutions except at higher
specific gravity solutions (magnesium sulfate at 1.30 specific gravity). The eggs are operculated
and are 45 Il x 70 11. Spirometral eggs are smaller (30 11 x 60 11) and operculated. Clinical mani-
festations include diarrhea and secondary anemia. Cats and dogs can serve as reservoir hosts for
infections in humans. D. latum occurs in more temperate areas; humans can be a definitive host
and become infected from eating raw fish. S. mansonoides occurs throughout North America,
and humans can become infected from eating pork.
Mesocestoides lineatus occurs worldwide and requires two intermediate hosts. The first host
includes beetles or orbatid mites; the second may be mammals, birds, or reptiles. This tapeworm
is unusual in that cats can be the intermediate or definitive host, and the organism can multiply
asexually in the peritoneal cavity to cause massive infections. The proglottids are about the size
of sesame seeds. Identification is made by examining the proglottid to find the central genital
pore. Eggs (22-25 Il x 25-30 Il) also may be recovered in a centrifugation fecal float.
17. How are tapeworm infections of cats treated?
Praziquantel and epsiprantel are the drugs of choice to treat most tapeworms. Both drugs are
approved for use in cats. Efficacy against Taenia spp. and D. caninum tapeworms is 100% with
either drug in a single treatment. Praziquantel but not epsiprantel has efficacy against
Echinococcus spp. Because of public health concerns in areas where E. mutilocularis is endemic,
cats allowed to hunt may be treated as often as monthly with praziquantel to control shedding of
eggs into the environment.
Gastrointestinal Parasites 91
18. What trematodes infect the GI tract of cats?
Alariamarcianae, Nanophyetus salmincola, and Cryptocotyle linguararely occur in the small
intestine of cats in North America. These parasites require two intermediate hosts and may use
transport hosts. A snail is the first intermediate host, and a fish is usually the second intermediate
host. Cats become infected with trematodes by ingesting the second intermediate host or mice,
frogs, and snakes, which serve as transport hosts. Intestinal fluke infections are usually subclinical
in cats. Eggs are best recovered from the feces by use of sedimentation techniques. The eggs are
dense and do not float well with fecal flotation salt solutions. Fluke eggs are large, ranging from
So-130 11 x 50-SO 11, depending on the species of fluke. In dogs, N. salmincola transmits
Neorickettsia helmintheca (salmon poisoning), but the disease is not transmitted to cats.
19. How are GI trematode infections treated?
Praziquantel is the drug of choice to treat flukes. Usually the same dose is administered as
for tapeworms, but it may need to be given daily for 2-3 days to be fully effective. Albendazole
has shown some efficacy against flukes, but treatment requires 2-3 weeks.This drug is not ap-
proved for use in cats, and it is not as safe to administer to cats as praziquantel.
20. What are the most common protozoan GI parasites in cats?
Coccidians and flagellates commonly infect the GI tract of cats (see table in question I).
The coccidians, Isospora felis and I. rivolta, are the most common protozoans in kittens.
Toxoplasma gondii and Cryptosporidiumparvum are other coccidians of clinical importance.
Infection with Hammondia spp., Besnoitia spp., and Sarcocystis spp. is usually subclinical in
cats. The flagellates Giardia lamblia and Pentatrichomonashominis infect cats and occasion-
ally are associated with clinical illness. Infection of cats with Entamoeba histolytica, an
amoeba, has rarely been reported.
21. What are the clinical rmdings of Isospora spp. infections in cats?
Infections in kittens may be subclinical or cause symptoms ranging from transient diarrhea
to severe hemorrhagic diarrhea. Adult cats tend to be more resistant to clinical coccidiosis be-
cause immunity develops, although stressed or immunocompromised cats occasionally become
clinically ill. Subclinically infected adult cats may shed oocysts sporadically, thus contributing to
environmental contamination. Oocysts sporulate in the environment to become infective. Cats
become infected directly by ingestion of sporulated oocysts or rodents harboring cyst stages.
Enzootic infections are found frequently in catteries where animals are housed together or in
close quarters. Diagnosis is made by demonstrating oocysts in feces after flotation. I. felis
oocysts range in size from 27-3111x 38-5111, and I. rivoltaoocysts range from 20-2611x 23-29
1-1. Because I. felis and I. rivoltacan infect cats directly or indirectly, taxonomists have created a
new genus name, Cystoisospora. Isospora consists of one-host species. Because tissue infections
can occur in mice, rats, hamsters, rabbits, and sheep, Cystoisospora genus better describes these
coccidian species. However, Isosporais still more commonly used.
22. Describe the other enteric coccidians of cats.
Cats serve as the definitive hosts for Besnoitia besnoiti and Hammondia hammondi:cattle
and rodents are intermediate hosts, respectively. Because the oocysts are indistinguishable from
those of T. gondii, animal inoculation is used for definitive diagnosis of T. gondii infection. B.
besnoiti and H. hammondi are considered nonpathogenic in cats. However, because the oocysts
are indistinguishable, T. gondii should always be suspected and precautionary measures taken.
Sarcocystis spp. also use two hosts; the cat can be a definitive host. Several Sarcocystis spp.
use cattle, sheep, mice, and rabbits as intermediate hosts. Cats become infected by ingesting tissue
cysts from the intermediate hosts. The sexual cycle occurs in cat intestinal cells. and fully sporu-
lated oocysts are passed in the feces. Unlike other feline coccidians, Sarcocystis spp. are infective
when passed and require no development in the environment. Sarcocystis spp. usually cause no
illness in cats or other carnivores, but infection of herbivores can result in serious illness. The
sporulated oocyst may be recovered from the feces by use of the centrifugation fecal flotation
method. The oocysts resemble giardial cysts in shape, but Sarcocystis spp. oocysts are slightly
larger (l2-161l x 7-91l), and contain 4 sporozoites.
Isospora (Cystoisospora) [ells unsporulated oocysts
(larger oocysts; I sporoblast), I. felis sporulated
oocysts (larger oocysts; 2 sporocysts), and I. rivolta
oocysts (smaller oocyst; I sporoblast).
23. Does enteric coccidiosis require treatment?
If Isospora spp. oocysts are detected in cats with GI signs, treatment is usually administered.
Sulfa drugs are generally effective (see table in question 12). Treatment of subclinically infected
cats may lessen oocyst shedding and environmental contamination but does not clear infection
because the treatment drugs are coccidiostats. Hammondia spp., Sarcocystis spp., and Besnoitia
spp. infection do not require treatment.
24. Is T. gondii infection associated with GI disease?
Cats are the only known definitife hosts of T. gondii (see Chapter 84) and the only species
known to shed oocysts. However, most cats are subclinically infected when shedding T. gondii
oocysts, Because of rapid development of immunity, oocyst shedding occurs only for 7-14 days. If
diarrhea occurs, it is of short duration (days) and involves the small bowel. The centrifugation fecal
flotation method is the choice for recovery of oocysts (10 Il x 121l) from cat feces, but because the
shedding period is so short, it is uncommon to find them in a routine sample. Clinical illness due to
toxoplasmosis in cats is usually polysystemic. Uveitis (see Chapter 67) and fever (see Chapter 64)
are common manifestations. Clindamycin hydrochloride administered orally at 10-12 mglkg every
12hr is effective for polysystemic toxoplasmosis and may shorten the oocyst shedding period.
25. What are Cryptosporidium spp.?
Cryptosporidium spp. are the smallest of the coccidians found in cats. The organism infects a
large number of animals, including humans. Transmission between other animal hosts and people
occurs with some genotypes; thus the organism is an important zoonotic protozoan parasite (see
Chapter 84). Cryptosporidium spp. are unusual in that they form autoinfective oocyts and can
cause life-threatening infections in immune deficient animals and humans, especially those with
acquired immunodeficiency syndrome.
Cryptosporidium spp. oocysts are sporulated when shed in the feces and thus are infective.
The thick-walled oocysts may remain viable for several months in favorable environments. It
takes extreme temperatures (> 65C and< DoC) to kill the oocysts. Desiccation and strong disin-
fectants also kill the oocysts, but disinfectants require extended contact to be effective. When the
oocysts are ingested, sporozoites invade the microvillous border of the gastric glands (c. muris)
or the lower half of the small intestine (c. parvum). Approximately 20% of oocysts have a thin
wall that breaks open in the 01 lumen. The released sporozoites reinvade host cells, which may
account for chronic shedding of oocysts by some cats. Most clinical infections are probably due
to C. parvum, but evidence of C.felis infection is increasing (see Chapter 84).
26. Does clinical cryptosporidiosis occur in cats?
In a study performed at Colorado State University, Cryptosporidium spp. oocysts or antigens
were detected in 5.4% of the cats with diarrhea. However, oocysts also can be detected in feces of
Gastrointestinal Parasites 93
clinically normal cats. Lymphocytic plasmacytic duodenitis has been detected in some infected
cats. Acute or chronic small bowel diarrhea is the primary clinical sign of cryptosporidiosis in cats.
Cryptosporidium spp. float in salt solutions, but they are difficult to differentiate from small
yeast organisms. The oocysts are very small (4-71.1x 4-61.1). Staining of a thin fecal smear helps
to identify the oocysts; modified acid-fast stain is commonly used. Immunofluorescent staining
techniques are also useful diagnostic tools. Fecal antigen tests used for human cryptosporidiosis
is under evaluation for use with cat feces.
Although no drug is consistently efficacious for treating cryptosporidiosis. tylosin and paro-
momycin apparently have been effective in some infected cats (see table in question 12). Chronic
infection of immunocompetent cats has been documented.
27. Describe Giardia spp. infections.
Giardia spp. are probably among the most commonly diagnosed intestinal protozoan para-
sites in humans and animals. Their distribution is worldwide in tropical and temperate areas, and
the organism does not appear to be host-specific. Giardia spp. can be harbored in virtually any
animal. It is questionable how many species exist. At present three species are accepted: G. duo-
denalis (G. lamblia) in mammals, Giardia muris in mice, and Giardia ranae in frogs. Some
feline isolates are identical genetically to human isolates. However, new genetic information sug-
gests that a feline-specific species may exist (see Chapter 84).
Giardia spp. have a direct life cycle. Cats, other animals, and humans become infected by in-
gestion of cysts shed in the feces, and the cysts are infective when passed. Infection occurs by the
fecal-oral route and occurs most commonly via contaminated drinking water and food.
Excystment takes place in the duodenum, where two trophozoites are released. The trophozoites
attach to the intestine by a sucking disc and multiply by binary fission. In cats, the jejunum and
ileum are the primary areas of multiplication instead of the duodenum. Encystment occurs as the
trophozoites pass through the GI tract. Trophozoites also may be passed in cases of severe diar-
rhea. The cyst stage is resistant in the environment, particularly to cold, and even chlorination
may not be totally effective at killing cysts. Drying kills cysts more rapidly. Trophozoites do not
survive long in the environment and are not the infective stage.
Left. Toxocara cati egg and Giardiaspp. cyst. Right. Giardiaspp. cyst
28. What are the clinical findings of giardiasis?
Giardial cysts are commonly excreted in cat feces. Some cats are subclinically infected,
whereas others may be presented with acute, chronic, or episodic small bowel diarrhea.
Intestinal malabsorption may contribute to persistent diarrhea that is mucoid, soft, and malodor-
ous. Diagnosis is made by the zinc sulfate centrifugation concentration flotation technique,
using Lugol's iodine to stain the cysts. Other salts and sugar distort giardial cysts rapidly.
making them difficult to recognize. The cysts range in size from 8-12 ~ x 7-10 u, If diarrhea is
present, a direct saline fecal smear should be examined to look for trophozoites, which range in
size from 10-12 ~ x 15-18 f.I. In the vast majority of cases, however, diagnosis is made by find-
ing the cysts in a fecal float. Unfortunately, giardial cysts are shed sporadically in the feces;
thus, serial fecal samples over the course of 1 week may need to be collected to rule out giardia-
sis. The fecal antigen ELISA appears to be fairly accurate for diagnosis of giardiasis in cats.
29. How is giardiasis treated?
Commonly used drugs include metronidazole, fenbendazole, and albendazole (see table in ques-
tion 12).Because albendazole has significant hematologic side-effects, it is not recommended. None
of these drugs is approved for use in cats. Repeated treatments may be required. Addition of insolu-
ble fiber may lessen trophozoite adherence to the microvillus. Vaccination is under evaluation as a
therapy. In some chronically infected dogs, administration of 2 subcutaneous vaccines controlled di-
arrhea and lessened cyst shedding. It may be impossible to clear the infection in some cats.
30. How can giardiasis be prevented?
Giardial infection rates may be very high in catteries and difficult to control because the
cysts are infective immediately when passed in the feces. Environmental disinfection helps con-
trol contamination. Dilute solutions of bleach or quaternary ammonium, heat, and drying kill the
cysts. It is important to clean litter trays once or more daily to control reinfection. Environmental
clean-up may be impossible because almost any animal may harbor Giardia spp. and thus conta-
minate water sources. In problem catteries, the combination of treatment of all cats, environmen-
tal disinfection, bathing to lessen cyst transmission, and vaccination may be helpful.
31. What are Trichomonas spp.?
Trichomonas spp. are flagellates occasionally seen in direct wet-mount fecal samples. They
usually are considered to be commensal organisms but have been associated with diarrhea. It is
questionable whether they are the primary cause of diarrhea or opportunistic organisms that mul-
tiply because of the changes in the intestinal environment due to diarrhea. Naturally occurring
trichomonads have been reported in cats, but the organism associated with illness generally is
Pentatrichomonas hominis, the same trichomonad that infects monkeys, dogs, rats, and humans.
Thus it is unclear whether the cat is an accidental host. Large or mixed bowel diarrhea occurs in
most clinically affected cats. The life cycle is direct, by contact or through contaminated food or
water. Trichomonal trophozoites do not live long outside the host. Diagnosis is based on demon-
stration of the 7-14 f.I X 4--6 f.I trophozoite with an anterior flagella, undulating membrane, and
posterior flagellum on fecal wet mount. The organism also can be cultured.
32. Should trichomonal infection of cats be treated?
If Trichomonas spp. are detected in the stool of cats with mixed or large bowel diarrhea and
there is no other explanation for the diarrhea, treatment is indicated. Many drugs, including
metronidazole, fenbendazole, enrofloxacin, and paromomycin, have been used, but none has
been shown to lead to cure. Paromomycin was associated with acute renal failure in 4 cats with
bloody diarrhea and should be used with care. None of these drugs is approved for use in cats.
BIBLIOGRAPHY
I. Arrioja-Dechert A (ed): Compendium of Veterinary Products, 5th ed: Feline anthelmintics and parasiti-
cides. Port Huron, North American Compendium, Ltd., 1999, P 339.
2. Bowman DD: Georgi's Parasitology for Veterinarians, 7th ed. Philadelphia, W.B. Saunders, 1999.
3. Courtney CH, Sundlof SF: Veterinary Antiparasitic Drugs. Gainesville, FL, University of Florida, 1999.
pp 186-205.
4. Finley T: How to Prevent Transmission of Intestinal Roundworms from Pets to People. Atlanta. Centers
for Disease Control and PreventionlDivision of Parasitic Diseases, 1996, publication MSF22.
5. Foreyt WJ: Veterinary Parasitology Reference Manual, 4th ed. Philadelphia. W.B. Saunders. 1997.
6. GrieveRH(ed): Small Animal Practice.Veterinary Clinics of NorthAmerica, vol. 17,no. 6. Philadelphia,
ws. Saunders, 1987.
7. HolzworthJ: Diseasesof the Cat: Medicineand Surgery. Philadelphia, W.H. Saunders, 1987.
8. Sherding RG (ed): The Cat: Diseases and Clinical Management, 2nd ed. NewYork, Churchhill Living-
stone, 1994.
9. UrquhartGM, ArmourJ, Duncan JL, et al: Veterinary Parasitology, 2nded. Oxford, Blackwell Science. 1996.
20. BACTERIAL DISEASES
Margie Scherk, DYM.
1. What bacteria should be considered on a ditTerentiallist for vomiting or diarrhea in cats?
Helicobacter spp. Clostridium perfringens
Salmonella spp. Escherichia coli
Campylobacter jejuni and C. coli
2. Summarize the morphologic characteristics of each.
Morphologic Characteristics ofGastrointestinal Bacterial Pathogens
Campylobacterjejuni
Clostridiumperfringens
Escherichiacoli
Helicobacter spp.
Salmonella spp.
Gram-negative; slender, curved or gull-shaped; motile rods (singles,
pairs, chains of 3-5 spirals)
Gram-positive, spore-forming rods
Gram-negative, medium-sized, short rods
Gram-negative, spiral-shaped, highly motile spirochetes
Gram-negative, non-spore- forming, motile rods
3. Do any of these bacteria pose a potential public health concern?
C.jejuni, C. coli, Helicobacter spp., E. coli, and Salmonella spp. have potential zoonotic im-
plications, especially in immunocompromised people. Thus, a thorough diagnostic work-up is
warranted in cats with vomiting or diarrhea that does not resolve with initial, symptomatic ther-
apy (see Chapter 84).
4. What initial symptomatic therapy is recommended for suspected gastrointestinal bac-
terial infections?
Fluid and electrolyte support, withholding food for 24 hours followed by gradual introduc-
tion of a bland, enteric-type diet are non-specific, supportive measures for the cat who is not seri-
ously ill with vomiting or diarrhea.
5. What antibiotic should be used empirically in cats with diarrhea?
Oral antibiotics should not be administered non-specifically for the treatment of diarrhea in
cats.
6. What tests are usually performed initially on cats with diarrhea?
Because there are multiple infectious and parasitic causes of vomiting and diarrhea in cats,
fecal flotation, fecal wet mount examination, and rectal cytology are usually performed (see
Chapter 18 and 19). Romanowsky and Gram stains of thin fecal smears are simple techniques
used to assess cats with suspected bacterial enteritis (see Chapter 18). With bacterial enteritis,
neutrophils are common and morphologic forms consistent with Campylobaeter spp. and
Clostridium perfringens may be noted. If evidence suggests that a zoonotic pathogen may be in-
volved, culture and antimicrobial sensitivity testing of feces should be recommended.
7. What are the clinical findings of Helicobacter spp. infection?
Since 1984, a pathogenic role has been recognized for some Helicobacter spp. in humans. In
people, H. pylori causes most cases of peptic ulcer disease and type B gastritis; gastric carcinoma
and B cell lymphoma occur secondarily in some cases. Cats are commonly infected by H. felis,
H. heilmannii, H. pametensis, and, rarely, by H. pylori. The failure of one study to isolate H.
pylori from stray cats indicates that in cats it may be an animal infection with a human pathogen.
Because Helicobacter spp. can be found in the stomach of healthy as well as ill cats, it is dif-
ficult to determine a disease association. The organisms may be commensal with opportunistic
tendencies. The prevalence of Helicobacter-like organisms in gastric tissues ranges from 41-
100% of healthy cats and 57-100% of vomiting cats. Transmission is probably by ingestion of
food or water contaminated by vomitus, feces, and possibly saliva.
Chronic lymphocytic or Iymphofollicular gastritis has been detected in some cats, suggest-
ing that infection occasionally results in disease. Clinical signs in infected cats range from none
to intermittent vomiting and weight loss due to chronic gastritis and gastroduodenal ulcers (rare).
In the small number of cats with H. pylori infection, clinical signs were absent despite persistent
colonization and presence of mucosal lesions.
8. How is a diagnosis of Helicobacter spp. gastritis made?
A presumptive diagnosis of Helicobacter spp. gastritis is based on exclusion of other causes
of gastritis as well as the following tests:
o The characteristic endoscopic findings include multifocal mucosal punctate hemmorhages
with rugal thickening.
o Helicobacter spp. produce urease. To screen for urease, mucosal biopsies are placed on a
urea slant medium that contains urea and phenol red indicator. If urease is present, ammo-
nia is liberated, raising the pH and turning the indicator red.
o Cytology of impression smears or mucosal brushings may reveal numerous motile spiral
bacteria.
Histopathology of gastric mucosal biopsies shows lymphocytic gastritis with prominent
lymphoid follicles, fibrosis, erosions, and spiral bacteria in the gastric glands, surface
mucus, and occasionally in the gastric parietal cells. Warthin-Starry silver staining in-
creases visibility of the spiral bacteria in gastric biopsies.
o Culture, mouse inoculation, and polymerase chain reaction are used in research settings.
9. Howis Helicobacter spp, infection treated?
In humans, combinations of antimicrobials and antacids have been used. Amoxicillin or
doxycycline, combined with metronidazole and bismuth subsalicylate, was used most frequently
initially. The combination of c1arithromycin and other antacids, including famotidine or ornepra-
zole), also is frequently prescribed. Because of the difficulty in medicating cats, the clar-
ithromycin protocol may be more practical; both drugs can be given once daily. If a positive
response occurs within 7-10 days, treatment should be continued for a minimum of 3 weeks.
Reinfection and incomplete elimination occur.
Drugs Used in the Treatment ofBacterial Gastrointestinal Diseases
DRUG DOSE INDICATIONS
Amoxicillin
Ampicillin
Ampicillin
Bismuth sub-
salicylate
Cephalothin
10--20 mg/kg PO every 8 hr
10--20 mg/kg POevery 8hr
10-20 mg/kg IV or SCevery 8 hr
17.5 mg bismuth/kgevery 8 hr
(Pepto-Bismol liquid; 17.5 mg/ml
bismuth, 8.7 mg/ml salicylate)
22-44 mg/kg IV or 1Mevery 8 hr
Clostridiumperfringens, Helicobacter spp.
C. perjringens
Anaerobic or gram-positivesepsis (use
with aminoglycosidesor quinolones)
Helicobacter spp,
Anaerobic or gram-positivesepsis (use
with aminoglycosidesor quinolones)
Bacterial Diseases
Drugs Used in the Treatment of Bacterial Gastrointestinal Diseases (Continued)
DRUG DOSE INDICATIONS
97
Chloramphenicol
Clarithromycin*
Erythromycin
Enrofloxacin
Famotidine
Gentamicin
Metronidazole
Omeprazole
Tylosin
10-15 mg/kg PO or SC every 12 hr
7.5 mg/kg PO every 12-24 hr
IOmg/kg POevery 8 hr
5 mg/kg POor SC every 12 hr
0.5-1.0 mglkg POevery 24 hr
2.2 mgikg IVor SC every 8hr
10-15 mg/kg PO every 12 hr
0.7-1.0 mg/kg PO every 24 hr
15 mg/kg PO every 12 hr
Campylobacter spp.
Helicobacter spp.
Campylobacter spp.
Campylobacter spp., gram-negativesepsis
(including Escherichia coli and Sal-
monella spp.), Clostridium difficile
Helicobacter spp,
Gram-negative sepsis (including E. coli
and Salmonella spp.)
C. perfringens, Helicobacter spp.
Helicobacter spp.
C. perfringens, bacterial overgrowth (?)
PO= orally, IV= intravenously, IM= intramuscularly, SC= subcutaneously
* Usually combined witheither famotidine or orneprazole.
10. How common is salmonellosis in cats?
Salmonella spp. have been isolated from feces in up to 18% of healthy cats. The prevalence
is thought to be even higher in cats with diarrhea. However, in a recent study of healthy cats and
cats with diarrhea in Colorado, Salmonella spp. were identified in feces from 0.8% of client-
owned cats and 1.3% of shelter cats with or without diarrhea.
11. How do cats become infected with Salmonella spp.?
The route of infection is almost always oral-fecal; airborne transmission is rare. Contact with
contaminated food (especially raw meat or poorly processed diets). water, or fomites is the common
mode of transmission. Poultry products are commonly contaminated. Moistened food left at room
temperature may pose a risk to cats. Cats should not be fed undercooked meats. Ingestion of in-
fected transport hosts, such as songbirds. may result in salmonellosis in cats; cats should not be al-
lowed to hunt. Animal caregivers are most likely infected with nontyphoid Salmonella strains; these
infections are generally self-limiting and do not pose an anthropomorphic risk.
12. How can salmonellosis in cats be prevented?
The organism is hardy and survives well in the environment in fecal-contaminated material,
including hospital cages and litter trays. endoscopic equipment and sinks. food dishes, and
grooming equipment. Cages and kennels should be cleaned and disinfected between each animal
(see Chapter 80). Hand washing between each patient as well as after contact with feces is cru-
cial. Bedding and clothing contaminated with fecal material should be washed, with bleach
added to the laundry. Clinic resident cats and long-term boarders should not be housed with the
hospital population because they may become infected and shed Salmonella spp. in the future.
13. What are the clinical fmdings of salmonellosis?
Bacteremia and endotoxemia are the most life-threatening form of infection. Acute episodes
may occur as soon as 3-5 days after exposure. and patients may present with fever, anorexia, and
lethargy with subsequent diarrhea. vomiting. and apparent abdominal discomfort. Diarrhea may be
watery to mucoid with the presence of fresh blood. Localized infections, such as abscesses, cellulitis,
osteomyelitis. pyothorax. pneumonia, or meningitis. occur in some cats. Poor reproductive perfor-
mance (genital tract infection. abortions. stillbirths, fading kittens) is of concern in a breeding cattery.
14. What factors determine the clinical form of Salmonella spp, infection?
Salmonella spp. can cause subclinical infection. However, isolation of the organism from
the gastrointestinal tract of diseased animals or normally sterile areas such as blood. urine.
cerebrospinal fluid, joint fluid, tracheal washings, or bone marrow is significant. Repeat shed-
ding occurs in previously infected animals suffering from stress or other illness. The immune
status of the host, the presence of concurrent disorders, and bacterial burden at presentation affect
what form of disease will result.
15. Should salmonellosis be treated?
Parenteral administration of antibiotics should be reserved for treatment of endotoxernia,
bacteremia, or other forms of systemic infection (see table in question 9). Oral administration of
antibiotics not only reduces the host's intestinal resistance to salmonellosis by altering the bal-
ance of normal enteric flora but also has been shown to prolong the disease course in experimen-
tal animals. In addition, the organism may develop plasmid-mediated antibiotic resistance. Thus,
the use of antibiotics is not recommended in uncomplicated gastroenteritis.
16. How is campylobacteriosis transmitted?
As with the other bacterial agents of diarrhea, fecal-oral, water-borne, or food borne routes
of infection are the norm. Most human Campylobaeter infections are due to ingestion of under-
cooked meat (especially chicken). Infected cats may be a source of infection for humans.
Privately owned animals are less likely to contract the disease than animals housed in ken-
nels or catteries, stray animals, and animals in hospitals where nosocomial infections are preva-
lent. In a study from north central Colorado, 0% of cats from a shelter and 1.6% of client-owned
cats with or without diarrhea were culture-positive.
17. What are the clinical findings of Campylobaeter spp, infection?
In many cats, infection with C. jejuni or C. coli is subclinical. Diarrhea usually occurs in cats
younger than 6 months and is usually watery with mucous or blood. Often the development of
clinical signs is associated with coinfection with other enteric pathogens.
18. How is campylobacteriosis diagnosed?
Because the infection is localized to the colon, rectal cytology is helpful in establishing the
diagnosis. Gram-negative, slender, gull wing-shaped organisms may be seen along with neu-
trophils. Confirmation is by fecal culture. It is unknown whether serum antibody titers reflect
current infection.
19. Howis diarrhea due to Campylobacter spp. treated?
Supportive care is administered as indicated. It is unknown whether antibiotics alter the
course of infection. In severe cases, antibiotic therapy is indicated (erythromycin, second-genera-
tion cephalosporins, or enrofloxacin may be considered (see table in question 9). It is important
to base treatment on antimicrobial susceptibility results and to treat for a complete course of 21
days; failure to do so may allow development of an antibiotic-induced carrier state.
20. What are the clinical fmdings of Clostridium perfringens gastrointestinal infections?
Clostridium perfringens is a normal intestinal flora; thus, not all culture-positive cats are dis-
eased. Some types of C. perfringens produce enterotoxin that may induce disease. If diarrhea
occurs, it is usually watery to mucohemmorhagic. Anal tissues may become inflamed, and occa-
sionally colonic epithelium may slough. Diarrhea usually subsides after a few days. However,
some authorities believe that the organism is associated with chronic intermittent diarrhea.
21. Howis C. perfringens-associated diarrhea diagnosed?
Detection of> 5-10 safety-pin shaped spore-forming rods per high-power field, combined
with the appropriate clinical findings, is suggestive. As previously discussed, culture of stool can
document carriage of C. perfringens but does not prove a disease association. Enterotoxin can be
detected in stool by reverse passive latex agglutination or enzyme-linked immunosorbent assay
(ELISA); positive results were previously thought to have the best predictive value for disease.
However, positive results can occur in both healthy and diseased animals. In addition, false-nega-
tive enterotoxin results occur in cats with severely watery diarrhea and cats with chronic disease.
Spore-forming bacteria morphologically
consistent with Clostridium perfringens.
22. Can diet prevent clostridial diarrhea?
Diets high in soluble fiber provide short-chained fatty acids through fiber fermentation.
These acids acidify the colonic environment and alter microbial flora, which may help to reduce
the proliferation of clostridial organisms.
23. Are oral antibiotics indicated in the treatment of suspected clostridial diarrhea?
In acute cases of suspected clostridial diarrhea, withholding food for 24 hours and then feed-
ing small amounts of a high-fiber diet usually results in resolution of clinical signs within 2-3
days. Administration of oral antibiotics with presumed activity against C. perfringens (amoxi-
cillin, tylosin, or metronidazole) may speed resolution of clinical signs. In addition, in some cats
C. perfringens overgrowth may relate to coinfection with other pathogens. Thus, administration of
tylosin tCryptosporidium spp.) or metronidazole (Giardia spp.) may be effective for other reasons.
24. Is Escherichia coli infection associated with disease in cats?
E. coli is most commonly a normal enteric flora in cats. Some strains are true entero-
pathogens and cause inflammation resulting in severe watery diarrhea. Some enterotoxigenic
strains also release toxins in the small intestine that inhibit resorption of sodium and chloride. re-
sulting in water loss. Enteroinvasive forms actively invade the colonic cells and other cells, caus-
ing septicemia and endotoxemia.
25. How is E. coli transmitted?
Most cases of zoonotic E. coli infection result from ingestion of inadequately cooked ground
beef or raw milk products; however, it is possible for people to become infected via fecal material
of cats. E. coli is a hardy organism that survives in fecal material, dust. and water for long periods.
The route of transmission is oral; fomites such as dishes, brushes, hospital equipment and instru-
ments, respiratory equipment, floors, and even disinfectant solutions, may harbor the organism.
26. How is E. coli infection managed clinically?
Routine fecal culture cannot differentiate nonpathogenic E. coli from enteropathogenic
strains; thus, E. coli-associated disease is usually not proven in small animal practice. Treatment
is reserved for cats with systemic signs of infection. Supportive fluid treatment and parenteral an-
tibiotic therapy is indicated in such cases. Because E. coli is a gram-negative organism,
quinolones are appropriate empirical antimicrobial choices.
100 Viral Diseases
27. Do cats develop small intestinal bacterial overgrowth?
The range of quantitative bacterial counts from the duodenum of normal cats varies from 0
to > 10
8
Thus, in contrast to dogs, it is unclear whether small intestinal bacterial overgrowth
occurs as a disease entity in cats.
BIBLIOGRAPHY
I. Deming MS, Tauxe RV, Blake PA, et al: Campylobaeter enteritis at a university: Transmission from
eating chickens and from cats. Am1 Epidemiol 126:526-534, 1987.
2. El-Zaatari FAK, Woo IS, Badr A, et al: Failure to isolate Helieobaeter pylori from stray cats indicated
that H. pylori in cats may be an antroponosis-an animal infection with a human pathogen. 1 Med
MicrobioI46:372-376, 1997.
3. Foley JE, Orgad U, Hirsh DC, et al: Outbreak of fatal salmonellosis in cats following use of a high-titer
modified-live panleukopenia virus vaccine. 1Am Vet Med Assoc 214:67-70, 1999.
4. Greene CEo Fox, IG: Enteric bacterial infections. In Greene CE (ed): Infectious Diseases of the Dog and
Cat, 2nd ed. Philadelphia, W.B. Saunders, 1998, pp 226-248.
5. Hill S, Lappin MR, Cheney 1, et al: Prevalence of enteric zoonotic agents in cats. 1 Am Vet Med Assoc
216:687-692,2000.
6. Kruth SA: Gram-negative bacterial infections. In Greene CE (ed): Infectious Diseases of the Dog and
Cat, 2nd ed. Philadelphia, W.B.Saunders, 1998, pp 217-226.
7. Marks SL, Melli A, Kass PH, et al: Evaluation of methods to diagnose Clostridium perfringens-essoci-
ated diarrhea in dogs. 1 AmVet Med Assoc 214:357-360, 1999.
8. Scott FW: Salmonella implicated as cause of songbird fever. Feline Health Top 3:5, 1988.
9. Simpson K, Neiger R, DeNovo R, et al: The relationship of Helieobaeter spp. infection to gastric disease
in dogs and cats. 1 Vet Intern Med 14:223-227,2000.
10. Papasouliotis K, Sparkes AH, Werrett G, et al: Assessment of the bacterial flora of the proximal part of
the small intestine in healthy cats, and the effect of sample collection method. Am 1 Vet Res 59:48-51
1998.
I I. Zoran DL: Diet and drugs: The keys to managing feline colonic disease. Compend Cont Educ Pract Vet
21:731-748,1999.
21. VIRAL DISEASES
Jordan O. Jaeger, D.v.M.
1. What are the common viral causes of gastrointestinal (GI) disease?
Vomiting or diarrhea has been associated most frequently with feline panleukopenia virus
(FPV), coronaviruses, feline leukemia virus (see Chapter 76), and feline immunodeficiency virus
(see Chapter 77).
2. What causes feline panleukopenia?
Feline panleukopenia is caused by FPV, a small parvovirus. This single-stranded, DNA-type
virus is related closely to canine parvovirus. Cats also can be infected by canine parvovirus and
occasionally have clinical signs of disease. The name was derived from the clinical observation
that many cats develop severe leukopenia, but this finding is not considered pathognomonic. The
disease syndrome also has been called feline distemper. Clinical findings of FPV infection in cats
are similar to those associated with canine parvovirus infection.
3. How is FPV transmitted and maintained in the environment?
FPV is shed in all body secretions; large quantities are present in the feces during active
stages of infection. Cats continue to shed virus in feces and urine for a maximum of 6 weeks after
infection. The virus is ubiquitous in the environment and can survive readily for more than I
year. Susceptible animals are infected via fecal-oral transmission. Fomites are believed to play an
Viral Diseases 101
important role in transmission because the virus can survive for prolonged periods on contami-
nated surfaces. Examples of fomites include clothing, shoes, hands, food dishes, and cages. Flies
and other insects may serve as transport hosts during warmer periods of the year.
4. Which species are susceptible to FPV? What areas of the body does it infect?
All species of Felidae as well as raccoons, coatimundi, and mink are susceptible to the virus.
Feline panleukopenia infects rapidly dividing cells; thus it has a predilection for the GI tract,
lymphoid tissue, and bone marrow. In prenatal and early neonatal infections, the cerebrum, cere-
bellum, retina, and optic nerves are also commonly infected, resulting in clinical abnormalities.
5. Is FPV passed in utero?
The virus is passed from queen to fetus. Infection early in pregnancy results in fetal death
and resorption with infertility, abortions, or birth of mummified fetuses. If infection occurs closer
to term, the kittens are born alive with varying degrees of damage to the late developing neural
tissue. Littermates may be affected to varying degrees.
6. What are the effects of FPV infection on the eNS and other developing neuronal tissue
in late uterine and early prenatal infection?
About 70-80% of small neurons in the cerebellar cortex and granular cell layer of the cere-
bellum do not develop until after birth. FPV inhibits the normal cerebellar cortical development
and migration of cells. The results are the gross pathologic finding of small or hypoplastic cere-
bellum and histologic findings of distorted cell layers and marked depletion of the granular cells
and Purkinje's cells. Less commonly the spinal cord, optic nerve, and retina also may be affected.
7. What is the pathogenesis of FPV-associated GI tract disease?
After oral exposure, the virus induces a plasma viremia. GI disease develops as cells in the
intestinal crypts are destroyed. leading to sloughing of the villi. Increased absorption of bacteria
and bacterial toxins leads to systemic bacteremia or sepsis.
8. What is the typical signalment of cats with clinical feline panleukopenia?
The incidence is highest in cats under I year of age. There is no sex or breed predisposition.
Often there is a seasonal increase in late summer to early fall, when the major annual crop of kit-
tens is at the end of maternal antibody protection. The frequency of clinical disease is much lower
than the actual number of cats infected with the virus. Most adult cats have subclinical infection.
The finding of a high infection rate with low incidence of clinical disease in older cats is sup-
ported by a high prevalence of FPV antibody titers in the adult cat population; up to 75% of pre-
sumably unvaccinated feral cats are seropositive.
9. Describe the clinical presentation of kittens with prenatal or early postnatal FPV infection.
Kittens infected transplacentaly or shortly after birth often appear normal until they start to
walk. At that time, varying degrees of ataxia, incoordination, intention tremors, broad-based
stance, hypermetria, and faIling are frequently observed. Affected kittens have normal mental
status, which is typical of cerebellar hypoplasia. Some may have signs of forebrain involvement,
such as seizures, behavioral abnormalities, or postural reaction deficits accompanied by a normal
gate. The ataxia is nonprogressive.
10. Describe the clinical presentation in kittens with late postnatal FPV infection.
Generalized infection in young unvaccinated cats is the most common form of FPV disease.
Severe disease may result in acute death. In less severe cases, fever (I04-I07F), anorexia, and
depression precede presentation by 3-4 days. At some time during the course of the disease,
vomiting that is not associated with eating often develops. Diarrhea is a common but not consis-
tent finding. The intestines may be painful and feel thickened during abdominal palpation. In
complicated cases, bloody diarrhea, icterus, and severe dehydration may develop.
102 Viral Diseases
11. What laboratory abnormalities are associated with feline panleukopenia?
Specific laboratory abnormalities are found most often in the complete blood count. Severe
panleukopenia is seen often but not in every case. In severe infections, the total white cell count
varies between 50 and 3,000 cells/ul; in more moderate cases, between 3000 and 7000 cells/ill.
Complete blood counts should be repeated because other diseases also may present with pan-
leukopenia. The leukopenia associated with FPV resolves within a few days of recovery from ill-
ness. Thus, it can be differentiated from other causes of chronic leukopenia. If prolonged
panleukopenia exists, other diseases, such as feline leukemia or septic salmonellosis, should be
considered. The severity of the leukopenia often reflects the severity of clinical illness. A mild
decrease in hematocrit and absolute reticulocyte count may be present in cats with viremia but
should not result in marked anemia, unless severe GI bleeding occurs. The anemia remains mild
because of the short course of the disease and the long life span of red blood cells. In cases of
severe infection, thrombocytopenia may develop. Clotting abnormalities consistent with dissem-
inated intravascular coagulation (DIC) also can be detected in severe infection.
Biochemical abnormalities are usually nonspecific. Azotemia due to dehydration is most
often detected. Mild renal damage also may result from viral replication. In rare cases, mild ele-
vations of liver enzyme activities may be detected. Hypoglycemia and hypokalemia result from
sepsis and GI losses, respectively.
12. How is feline panleukopenia diagnosed?
A presumptive diagnosis is based on the presence of appropriate clinical findings in a sus-
ceptible host after exclusion of other diseases that produce acute GI signs or leukopenia. Peracute
and acute cases must be differentiated from intoxication or foreign body ingestion; careful his-
tory taking is vital. Abdominal radiographs as well as fecal examination for parasites should be
performed to rule out intestinal obstruction or extreme parasite burden. Clinical signs also may
be compatible with acute toxoplasmosis. Toxoplasmosis often has accompanying respiratory
signs, which may be helpful in differentiating between the two diseases. Negative feline leukemia
virus status also should be confirmed.
Exposure to FPV can be confirmed by documenting increasing antibody titer on samples
taken at the time of presentation and 2 weeks later. A fourfold rise in titer is supportive of acute
infection. Presence of viral particles in feces on electron microscopy or viral antigens in feces by
enzyme-linked immunosorbent assay (ELISA) also can confirm exposure to FPY. However,
canine parvovirus ELISA has not been validated for use with feline feces, and neither electron
microscopy nor ELISA can distinguish modified live vaccine strains from virulent strains.
13. How is FP treated?
Symptomatic and supportive care are the cornerstones of therapy. Fluid therapy, control of
GI signs, antimicrobial therapy, potassium replacement, maintenance of euglycemia, and control
of oncotic pressure are key components. Specific antiviral treatment is not available. The key is
to support the patient until the immune response is able to overcome the infection.
14. What fluid therapy is suggested?
Fluid deficits and ongoing losses should be corrected parenterally. Use of a jugular catheter is
preferred over other sites because the jugular catheter is usually not positional, can be used to
obtain blood samples, is not likely to be contaminated with feces, is unlikely to develop phlebitis,
and allows monitoring of central venous pressure. The fluid deficit (body wt [kg] x percent dehy-
drated x 1000 =ml) is replaced over 24 hours, along with estimates of ongoing losses and mainte-
nance. Balanced isotonic fluid replacement is used with potassium supplementation. Electrolytes
should be measured intermittently to aid in determining potassium needs; a minimum of 20 mEqlL
should be used. Blood glucose should be monitored and supplemented as indicated. If clinical ev-
idence of decreased oncotic pressure (peripheral or pulmonary edema) is present concurrently
with hypoalbuminemia, plasma or colloids should be administered. Anemia due to severe GI blood
loss may develop in addition to hypoproteinemia; therefore, blood transfusion may be needed.
Viral Diseases 103
Platelet count, fibrin degradation products (FDPs), and clotting times should be assessed in mori-
bund or septic cats to evaluate for possible DIC.
15. How are GI signs of FP managed?
Eliminating oral intake of food and water decreases the amount of vomiting and slows repli-
cation of intestinal cells in the GI tract, which is needed for viral replication. Antiemetics may be
used to control vomiting, if necessary. Anticholinergic medications should not be used because
they produce ileus. First-line antiemetic therapy is metoclopramide, administered subcutaneously
at 0.2-0.5 mg/kg every 6-8 hr. If vomiting persists, a continuous infusion of metoclopramide
(1-2 mg/kglday) is often helpful. Water can be reintroduced no sooner than 24 hours after cessa-
tion of vomiting. Initially, small amounts of water should be offered. If no vomiting occurs for 24
hours, small amounts of a bland food (specifically a commercial GI diet or rice with small
amounts of baby food) may be introduced. If feedings are tolerated, the amount should be in-
creased gradually. After the patient is consuming normal amounts, a slow transition over 4-6
days should be made to regular maintenance diet.
16. What antibiotics should be used if findings of bacteremia or sepsis exist?
Broad-spectrum antibiotics, such as ampicillin (22 mglkg intravenously every 6-8 hr) or a
first-generation cephalosporin (20-25 mg/kg intravenously every 6-8 hr) should be used to help
prevent systemic bacterial infection. If sepsis is suspected, a fluoroquinolone (5-10 mglkg intra-
muscularly or intravenously every 24 hr) or an aminoglycoside (3 mg/kg intravenously every 8hr)
can be added to improve the gram-negative spectrum. Aminoglycosides should not be adminis-
tered until the cat is well hydrated and potassium deficits have been corrected to lessen the chance
of nephrotoxicity. Alternatively, a second-generation cephalosporin can be used. Antibiotic ther-
apy also may decrease bacterial counts in the GI tract, which are known to increase mitotic rate of
intestinal epithelia. In genu-free kittens, the clinical manifestations are not as severe.
17. Is passive immunotherapy of benefit in the treatment of FP?
In dogs, administration of lyophilized serum from hyperimmune dogs decreases morbidity
associated with canine parvovirus infection. Although data from cats are not available, the same
principle probably applies because the pathogenesis is similar to that in dogs. Administration of 1
ml/kg of plasma or serum from a well-vaccinated cat or survivor of feline panleukopenia may be
administered intravenously, intraperitoneally, or subcutaneously.
18. How long do colostral antibodies and maternal virus-neutralizing (VN) antibodies per-
sist in kittens?
Colostral antibodies have a half-life 01'9.5 days. Thus, maternal VN antibodies may interfere
with vaccination until 12-14 weeks of age.
19. When should kittens be vaccinated? With what type of vaccine?
Kittens presented for vaccination before 12 weeks of age should receive either inactivated or
modified live vaccines every 3 weeks until they are 12weeks of age. Kittens presented for vaccina-
tion after 12weeks of age should receive two inactivated vaccines, 3 weeks apart, or I modified live
vaccine. Boosters should be given at 1 year of age and then no more frequently than every 3 years.
In one study, cats vaccinated with two inactivated vaccines had 100% protection when challenged
with virulent FPV 7.5 years later. There is no benefit from use of intranasal products. Queens should
be vaccinated before pregnancy; if vaccinated during gestation, they should receive only inactivated
products because modified live vaccines may infect the fetal or neonatal cerebellum. Kittens born to
naive queens may be vaccinated as soon as 4 weeks of age with inactivated products.
20. How is the virus inactivated once in the environment?
If FP is diagnosed in a household, a I :32 dilution of household bleach should be used on all
cages, bowls, litter pans, and floors. Plastic litter pans should be discarded because of the difficulty
104 Viral Diseases
in disinfecting. New cats with past infection of FPV should not be introduced into the household
without prior vaccination. Other susceptible cats in the household usually show initial signs
(anorexia, lethargy, and vomiting) in 2-6 days. Passive immunity, as described in question 17,
should be considered for exposed susceptible cats that need immediate protection.
21. What are feline coronaviruses? How are they transmitted?
The coronaviruses are ubiquitous RNA viruses transmitted by the fecal-oral route. Some iso-
lates are limited to the intestinal tract, leading to subclinical infection in most (feline enteric coro-
navirus [FECV)). Other isolates have the ability to infect macrophages, disseminate through the
body, and induce the clinical syndrome known as feline infectious peritonitis (see Chapter 38).
22. What are the clinical signs in cats infected with FECV?
When clinical signs occur, mild small bowel diarrhea is usually present. Occasionally, mucus
and fresh blood also may be seen. Occasionally, vomiting, low-grade fever, anorexia, and
lethargy may accompany the diarrhea. Clinical signs often resolve within 2-4 days. Although en-
teric coronaviruses are limited to the Gl tract, spontaneous mutation to feline infectious peritoni-
tis (FIP)-inducing strains can occur in the host.
23, How is a diagnosis of FECV infection made?
FECV infection is often a diagnosis of exclusion. It is important to rule out more common
causes of mild diarrhea and vomiting, such as foreign body ingestion, parasite infestation, dietary
intolerance, intestinal perforation, and other enteric viruses. Documentation of increasing coron-
avirus antibody titers suggests recent infection. FECV can be documented in feces with electron
microscopy or virus isolation. Reverse transcriptase polymerase chain reaction also can be used
to detect RNA of the organism in feces.
24. How is clinical FECV infection treated?
Treatment consists of supportive care (as in feline panleukopenia), but sepsis is less likely.
Fluid therapy and gut rest are the most important components.
25. How is FECV infection prevented?
In crowded environments, most cats are seropositive for coronavirus antibodies. It is esti-
mated that approximately 30% of seropositive cats are shedding coronaviruses in stool at anyone
time. The spread of the virus in catteries is highly efficient, and prevention of spread is essen-
tially impossible. Stress should be avoided if possible, and care should be taken to lessen crowd-
ing of litter boxes. Vaccination with the intranasal coronavirus vaccine is not warranted because
of the mild clinical signs seen in cats and associated low morbidity.
26. Can serology be used to differentiate FECV from FIP.inducing strains?
Currently no serologic test can differentiate antibodies against FECV from those against
FIP-inducing strains (see Chapter 38).
BIBLIOGRAPHY
I. AAFP Vaccination Guidelines: 1998 Report of the American Association of Feline Practitioners and
Academy of Feline Medicine Advisory Panel on Feline Vaccinations. J Am Vet Med Assoc 212:227-
241, 1998.
2. Addie DD, Jarrett 0: Feline coronavirus Infection. In Greene CE (ed): Infectious Diseases of the Dog and
Cat. Philadelphia, W.B. Saunders, 1998, pp 58-59.
3. Barr MC, Olsen CW, Scott FW: Feline viral diseases. In Ettinger SJ, Feldman EC (eds): Textbook of
Veterinary Internal Medicine, 4th ed., Philadelphia, W.B. Saunders, 1995, pp 409-439.
4. Birchard SJ, Sherding RG: Saunders Manual of Small Animal Practice, 2nd ed, Philadelphia, W.B.
Saunders., 2000, pp 115-117.
5. Green CE: Feline panleukopenia. In Greene CE (ed): Infectious Diseases of the Dog and Cat, 2nd ed.
Philadelphia, w.s. Saunders, 1998, pp 52-57.
Fungal and Miscellaneous Diseases 105
6. Harbour DA: Feline enteric viral infections. Feline coronavirus infection. In Greene CE (ed):. Infectious
Diseasesof the Dog and Cat. Philadelphia: W.B. Saunders, 1998, pp 58-59.
7. Willard M: Disorders of the intestinal tract. In Nelson RW, Couto CG, King C: Manual of Small Animal
Internal Medicine. St. Louis, Mosby, 1999,pp 433--467.
8. Scott FW,GeissingerCM: Long-termimmunityin cats vaccinatedwith an inactivated trivalentvaccine[see
comments].AmJVetRes 6 O : 6 5 2 ~ 5 8 , 1999[publishederratumappearsinAmJVet Res 60:763, 1999].
9. Sherding RG: The Cat: Diseases and Clinical Management, 2nd ed. NewYork, Churchill Livingstone,
1994, pp 357-365.
22. FUNGAL AND MISCELLANEOUS DISEASES
Chad Johannes, D.V.M.
1. What is the most common gastrointestinal (GI) fungal disease in cats?
Cats tend to be highly susceptible hosts for Histoplasma capsulatum. This systemic fungal
infection results from inhalation or ingestion (less likely in cats) of infective conidia and subse-
quent hematogenous and lymphatic dissemination. The organism grows best under moist, humid
conditions in nitrogen-rich soil (high in organic material such as bird and bat excrement). It is
most prevalent in the central United States in regions of the Ohio, Missouri, and Mississippi
Rivers as well as in Texas. Clinical histoplasmosis is most commonly seen in cats younger than 4
years of age, although cats of any age can be affected.
2. What signs are typicaUyseen with GI histoplasmosis?
Although GI involvement with systemic histoplasmosis tends to be observed less commonly
in cats than in dogs, it can produce chronic small or large bowel diarrhea. As all layers of the in-
testinal wall are disrupted by granulomatous inflammation, severe chronic malabsorption results
in voluminous watery diarrhea. Protein-losing enteropathy is a potential sequela. If the large
bowel is also affected, tenesmus, hematochezia, and fecal mucus can be seen. Physical examina-
tion often identifies diffusely thickened loops of bowel, along with palpably enlarged mesenteric
lymph nodes. Additional systemic signs may include anorexia, rapidly progressive weight loss,
fever, and lethargy. Intestinal histoplasmosis should be considered in any young cat with in-
tractable large or small bowel diarrhea that has lived in or traveled through an endemic region.
3. How is GI histoplasmosis diagnosed?
Definitive diagnosis requires identification of H. capsulatum organisms (usually within
macrophages) on cytology or biopsies. Although primary intestinal histoplasmosis has been re-
ported, intestinal involvement most often results from systemic infection. Radiographs of the
thoracic cavity may reveal a diffuse interstitial pattern, with infiltrates coalescing to produce a
miliary or nodular interstitial appearance. Other signs of systemic involvement include peripheral
lymph node enlargement, abdominal organomegaly, clinical icterus, and occasionally skin nod-
ules or ulcerated lesions. Therefore, diagnosis is often aided by bone marrow, lung, lymph node,
liver, splenic, or skin nodule aspirates. Ocular involvement is also possible, and physical exami-
nation should include a thorough evaluation of the fundus.
With intestinal involvement, H. capsulatum organisms may be seen on cytology from rectal
mucosal scrapings and impression smears made from intestinal (endoscopic or surgical) or
mesenteric lymph node biopsy samples. The yeasts are round to oval in shape with a distinct wall
and are approximately 2-4 urn in diameter (about one-fourth to one-half the diameter of an ery-
throcyte). With Romanowsky type stains, the interior portion of the organism typically stains pale
to medium blue to purple. In addition, organisms can be visualized on histopathology sections
with appropriate fungal stains. Serologic tests for H. capsulatum antibodies are available, but
their reliability is poor.
106 Fungal and Miscellaneous Diseases
Macrophage containing numerous Histoplasma capsulatum yeasts. (Courtesy of Dr. Steven L. Stockham,
Department of Veterinary Pathobiology, University of Missouri-Columbia.)
4. What laboratory values are commonly seen in disseminated histoplasmosis?
Normocytic, normochromic, nonregenerative anemia is the most common hematologic ab-
normality in cats with disseminated histoplasmosis. The anemia may result from chronic inflam-
matory disease, bone marrow infiltration by H. capsulatum, or intestinal blood loss. Leukocyte
counts are quite variable, but neutrophilia and monocytosis are observed most frequently.
Thrombocytopenia, resulting from increased platelet utilization or destruction, has been reported
in as many as one-third of affected cats. With extensive bone marrow involvement, pancytopenia
may be present. On occasion, H. capsulatum organisms may be visualized within monocytes or
neutrophils on a blood smear.
Hypoalbuminemia, the most consistent serum biochemistry profile finding in cats with sys-
temic histoplasmosis, may result from GI loss or liver dysfunction. Globulins may be elevated
(chronic antigen stimulation), but this finding varies, depending on concurrent intestinal loss.
Hypercalcemia has been reported in several cats and probably is due to systemic granulomatous
disease. Elevations in serum alanine aminotransferase, alkaline phosphatase, and total bilirubin
indicate possible hepatic involvement. Most affected cats that were tested for feline leukemia
virus (FeLV) and feline immunodeficiency virus (FIV) have been negative.
5. What treatment options are available for intestinal histoplasmosis?
Itraconazole is the drug of choice for treatment of disseminated histoplasmosis. Treatment is
initiated at 10 mg/kg orally every 24 hours, and if no signs of hepatotoxicity (elevated liver en-
zymes) develop, dosing can be increased to twice daily. An oral suspension (10 mg/ml) is avail-
able and is more consistently absorbed than the capsules. Combination therapy of itraconazole
with liposome-encapsulated amphotericin B (0.25-0.5 mg/kg intravenously every 48 hr until a
cumulative dose of 4-8 mg/kg is reached) may be necessary in severe or fulminating cases.
Owners should be aware that treatment is needed for at least 4-6 months, sometimes as long as
12 months, depending on response to therapy. The prognosis for intestinal histoplasmosis is fair
to good, depending on the severity of involvement. Relapse several months after discontinuing
oral antifungal therapy is possible.
6. Is histoplasmosis a zoonotic disease?
Although concurrent common-source infections of animals and people have been reported,
direct transmission of H. capsulatum between animals or from animals to humans has not been
shown. Cats and humans in endemic regions are at risk of exposure from infected soil; prevention
lies in minimizing this contact.
Inflammatory Bowel Disease 107
7. What other fungal organisms can cause diarrhea in cats?
Opportunistic fungal organisms that can cause enteritis and diarrhea in cats include
Aspergillus spp., Candida spp., and Mucor spp. FPV, FIP, or FeLV infection, antibiotic therapy,
or glucocorticoid therapy appear to be important predisposing factors that increase susceptibility
to tissue invasion by these fungi. Both small and large bowel are often affected, causing a chronic
mixed bowel diarrhea. Antemortem diagnosis of intestinal mycoses can be quite difficult and re-
quires histopathologic identification of organisms in tissue sections. In some animals with renal
involvement, fungal hyphae may be visualized on routine urine sediment examination.
Most reported cases have been identified on necropsy, providing limited information about
treatment, drug dosages, and length of therapy. Ketoconazole (10 mg/kg orally every 12 hr), itra-
conazole (2.5-5 mg/kg orally every 12 hr), or liposomal amphotericin B (3-5 mg/kg intra-
venously every 48 hr until a cumulative dose of 12 mg/kg is reached) may be options for treating
disseminated aspergillosis. Treatment with an oral imidazole may be needed for months to years,
and long-term prognosis is generally grave. Nystatin (100,000 units/cat orally every 6 hr), keto-
conazole (50 mg/cat orally every 12-24 hr), or itraconazole (5-10 mg/kg orally every 12-24 hr)
may be considered for systemic candidiasis.
8. Do cats develop protothecosis, mucormycosis, or pythiosis?
Pythiuminsidiosum is a water mold associated with GI tract disease in dogs, primarily along
the Gulf Coast. Infection of cats is rare. Infection with Mucorspp. fungi occurs in cats as a systemic
disease. Protothecosis is a disseminated disease in dogs caused by the algae Prototheca zopfii and
P. wickerhamii. Bloody diarrhea is a common manifestation. To date, only cutaneous protothecosis
has been reported in cats.
BIBLIOGRAPHY
1. Baker R, Lumsden JH: Color Atlas of Cytology of the Dog and Cat. St. Louis, Mosby, 2000, p 23.
2. Blischok D, Bender H: What is your diagnosis-15-year old male domestic shorthair cat. Vet Clin Pathol
25:114.
3. Clinkenbeard KD, Wolf AM, Cowell RL, et al: Feline disseminated histoplasmosis. Compend Cont Educ
PractVet 1l:1223-1233.
4. Guilford WG, Strombeck DR: Gastrointestinal tract infections, parasites, and toxicoses. In Strombeck's
Small Animal Gastroenterology. Philadelphia, WB. Saunders, 1996, p 424.
5. Hodges RD, Legendre AM, Adams LG, et al: Itraconazole for the treatment of histoplasmosis in cats. J Vet
Intern Med 8:409-413.
6. Lappin MR: Protozoal and miscellaneous infections. In Ettinger SJ, Feldman EC (eds): Textbook of
Veterinary Internal Medicine. Philadelphia, WB. Saunders, 2000, pp 408-412.
7. Sherding RG, Burrows, CF: Diarrhea. In Anderson NV (ed): Veterinary Gastroenterology. Philadelphia,
Lea & Febiger, 1992, pp 445-449.
8. Taboada J: Systemic mycoses. In Ettinger SJ, Feldman EC (ed): Textbook of Veterinary Internal Medicine.
9. Wolf AM: Histoplasmosis. In Greene CE (ed): Infectious Diseases of the Dog and Cat. Philadelphia, WB.
Saunders, 1998, pp 378-383.
23. INFLAMMATORY BOWEL DISEASE
Alice J. Johns, D.V.M.
1. Define inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a group of idiopathic, chronic gastrointestinal (GI) tract
disorders characterized by infiltration of the lamina propria by inflammatory cells. The cellular in-
filtrate may be lymphocytes, plasma cells, eosinophils, neutrophils, macrophages, or combinations
of these.
108 Inflammatory Bowel Disease
2. What causes mD?
The cause of IBD is probably multifactoral. It appears to involve host hypersensitivity re-
sponses to antigens (food, bacterial, or self) within the bowel lumen or mucosa. Genetic and psy-
chosocial factors also may be involved. Increased permeability allows luminal antigens to cross
the mucosa, leading to inflammation and further mucosal damage, which in tum further increase
permeability. Mucosal inflammation occurs in a diverse group of disorders, including bacterial,
viral, protozoal, and parasitic infections, bacterial overgrowth, metabolic disease, neoplasia, pan-
creatitis, and cholangiohepatitis. These conditions should be excluded from the differential list
before a cat is assumed to have IBD due to dietary hypersensitivity.
3. Describe the pathophysiology of mD.
IBD is an abnormal mucosal immune response, which results in the recruitment of inflam-
matory cells to the intestine. The immune response itself leads to tissue destruction and impair-
ment of digestive and absorptive capabilities. Damage results from the following factors:
Arachidonic acid metabolites
Proinflammatory cytokines
Leukotrienes, produced in the lipoxygenase pathway, that act as chemotactic agents, in-
crease vascular permeability, and induce smooth muscle contraction
Prostaglandins from the cyclo-oxygenase pathway, which result in pain, vasodilation, in-
creased vascular permeability, and increased secretion of water and electrolytes
Platelet-activating factor, which is chemotactic and increases vascular permeability
Interleukins. which regulate the mucosal immune system
Oxygen-derived free radicals and nitric oxide, which damage the mucosa
GI peptides, including substance P, vasoactive intestinal peptide, and somatostatin
Clonal expansion of activated intestinal Band T lymphocytes.
4. Describe the typical signalment for cats with mD.
There is no age, sex, or breed predilection, although purebred cats may be at increased risk
for Iymphocytic-plasmacytic enteritis. Although most affected cats are middle aged (6-8 years)
or older, about one-third of the patients are 2 years old or younger. IBD has been diagnosed as
early as 5 months of age.
5. What are the common clinical signs of mD?
Chronic vomiting and diarrhea are the most common clinical signs and may occur alone or in
combination. Vomiting often is not associated with eating and should bedifferentiated from regur-
gitation (see Chapter 26). Diarrhea may contain mucus or blood, indicating large bowel involve-
ment. Anorexia, weight loss, lethargy, loss of litter training, abdominal pain, and hematemesis also
may be seen. The clinical signs are generally intermittent or cyclical and reflect the predominant
sites of disease. Clinical signs are similar among the various histologic forms. Symptoms vary
from mild to severe. Exacerbations and spontaneous remissions are common.
6. What characteristic abnormalities are found on physical examination?
No physical examination findings are pathognomonic, but several findings may suggest ISO.
Cranial abdominal discomfort may bepresent and is more noticeable in cats with concurrent pancre-
atitis. Intestinal bowel loops may bethickened. Cats with "triaditis"-the combination of inflamma-
tory bowel disease, pancreatitis, and cholangiohepatitis-may beicteric and have a palpable liver.
Many cats are ill kempt, and emaciation may be noted, particularly if malabsorption is occurring.
7. What are the primary differential diagnoses for mD?
Endocrine diseases (hyperthyroidism, exocrine pancreatic insufficiency)
Food intolerance
Bacterial enteritis (Helicobacter spp., Salmonella spp., Campylobacter spp., Clostridium
perfringens, Escherichia coli; see Chapter 20)
Parasites (helminths, cestodes, protozoans; see Chapter 19)
Fungal enteritis (Histoplasma capsulatum; see Chapter 22)
Neoplasia (lymphosarcoma, adenoma, adenocarcinoma; see Chapter 24)
Viral enteritis (feline leukemia virus [FeLV], feline immunodeficiency virus [FlV], feline
enteric coronavirus, feline panleukopenia; see Chapter 21)
Obstruction
8. How is IBD diagnosed?
IBD is diagnosed by combining histologic evidence of inflammation with exclusion of other
causes of 01 inflammation. Baseline laboratory tests should include complete blood count
(CBC), serum biochemical profile, FeLVantigen test, FlV antibody test, serum total T4 concen-
tration (for cats at risk for hyperthyroidism), urinalysis, fecal parasite examination (zinc sulfate
flotation and direct smear), fecal wet mount, Cryptosporidium spp. screening, rectal cytology,
and survey abdominal radiographs (see Chapter 18). Fecal culture is indicated in cats with sus-
pected bacterial enteritis (see Chapter 20).
9. What CBC abnormalities support the diagnosis of IBD?
The CBC may show increased eosinophils. However, parasitic diseases and hypoadrenocor-
ticism also induce this abormormality. Microcytic anemia may develop if IBD is severe and re-
sults in iron deficiency due to chronic blood loss. Plasma protein concentration decreases if
protein-losing enteropathy is present.
10. How do serum biochemical abnormalities aid in the diagnosis of IBD?
The primary benefit of serum biochemical testing is to exclude other causes of vomiting
and diarrhea. Panhypoproteinemia is consistent with protein-losing enteropathy, which may
occur with some forms of IBD. Some cats (25%) with Iymphocytic-plasmacytic enteritis are
reported to have mildly increased serum alanine transferase (ALT), aspartate transferase
(AST), and alkaline phosphatase (ALP) activities. Liver function tests are usually normal; in
some cats, however, histologic examination of the liver reveals periportal inflammatory infil-
trates. Because the pancreatic and biliary ducts are shared in cats and empty into the duode-
num, IBD may result in concurrent pancreatitis and cholangiohepatitis (see Chapters 29 and
36). This syndrome has been called "triaditis" and may explain serum biochemical evidence of
hepatic and pancreatic involvement. Triaditis may be due to translocation of bacteria from the
diseased 01 tract into the portal circulation. Cobalamin, folate, and vitamin K levels may be
decreased as a result of malabsorption.
11. What is the diagnostic benefit of imaging procedures?
Survey and contrast films of the abdomen have a low likelihood of showing abnormalities
(masses or increased small intestinal diameter). Barium studies may show flocculation of barium
contrast material, irregular mucosal-barium interface, delayed transit time, or persistent adher-
ence of barium to mucosa. Ultrasound may show small intestinal abnormalities, including altered
echogenicity, small intestinal wall thickening, or poor small intestinal wall definition. However,
results of imaging procedures are not specific for IBD and are used primarily to exclude other
causes of vomiting or diarrhea.
12. How should tissues be obtained for histologic evaluation?
Endoscopically obtained or full-thickness surgical biopsies may be used for histologic evalu-
ation. Endoscopic mucosal biopsy is less invasive than surgery but provides small samples (usu-
ally 2.8 mm in diameter at most) that include mucosa only. Samples are easily obtained from the
stomach, duodenum, rectum, and colon; the jejunum and ileum are less commonly sampled.
Samples often have crush artifact, which makes histologic characterization difficult. Because
only mucosa is obtained, deeper inflammation or neoplasia may be missed, and it is difficult to
document the presence of Iymphangectasia. It is important to obtain samples even if the mucosal
surface appears normal. Multiple samples should be obtained from each site. In dogs, duodenal
aspirates are performed to assess for Giardia spp. and bacterial overgrowth. In cats, however,
Giardia spp. reside more distally in the small bowel, and normal cats have extremely variable
numbers of bacteria in the duodenum. Thus the diagnostic benefit of these tests is limited. If
gastritis is suspected, samples should be collected from the cardia and placed on a urea slant to
assess for the presence of urease activity, which supports the diagnosis of helicobacteriosis (see
Chapter 20).
If endoscopic biopsies are nondiagnostic in a cat with clinical signs of IBD and other causes
of vomiting and diarrhea have been ruled out, surgical, full-thickness biopsies are warranted.
Surgery has the additional benefit of allowing visualization and biopsy of the pancreas and liver
in cats with suspected triaditis. Because endoscopically obtained biopsies are occasionally falsely
negative, require specialized equipment, and limit testing to the mucosal surface, exploratory la-
parotomy may be the preferred procedure for clients with limited budgets.
13. In what forms does ffiD occur?
IBD is classified by the area of the GI tract that is affected and the predominant type of in-
flammatory cell:
Lymphocytic-pIasmacytic enterocolitis is the most common type of mD diagnosed in cats.
The lamina propria is infiltrated with lymphocytes and plasma cells. The disease may progress to
diffuse intestinal lymphoma.
Eosinophilic enterocolitis and hypereosinophilic syndrome are rare forms of IBD charac-
terized by diffuse or focal infiltration of mature eosinophils into one or more layers of the intesti-
na tract. Usually they are accompanied by peripheral eosinophilia. Although eosinophilic
enterocolitis is confined to the GI tract, hypereosinophilic syndrome may involve the liver,
spleen, lymph nodes, bone marrow, lung, pancreas, adrenal glands, or skin. Hypereosinophilic
syndrome responds poorly to glucocorticoids, is considered a preneoplastic condition, and has a
high mortality rate.
Regional granulomatous enterocolitis is less common. It is characterized by transmural
granulomatous inflammation, usually of the ileum and colon, that causes stenosing, mass-like
thickening of a region of bowel wall. Regional lymph nodes and adjacent mesentery also may be
involved.
Other rare fonns (all treated as lymphocytic-plasmacytic mD) include neutrophilic (suppu-
rative) colitis, granulomatous colitis, histiocytic colitis, necrotic colitis, and angiopathic colitis
with vasculitis and ischemic ulcers.
14. How is ffiD treated?
The basic concepts of treatment are to remove the antigenic source of inflammation and
then suppress the cell-mediated inflammatory response in the GI tract. The goals are remission
of clinical signs, control with dietary management, and use of metronidazole and/or pred-
nisolone. Relapses often occur and require drug therapy. Severe and refractory mD may require
the use of potent immunosuppressive drugs. Some cats require indefinite drug administration
for control.
15. Describe dietary management of IBD.
The diet should contain a single, highly digestible, novel protein (one that the cat has not
eaten before) and reduced amounts of food additives. It also should be gluten-free; use rice or
potato as a carbohydrate source. High-fat diets should be avoided. If colitis is present, consider
high-fiber diets containing either insoluble (cellulose) or soluble (psyllium) fiber. When a
homemade diet is used for initial treatment, many cats find baby rice cereal more palatable than
cooked white rice. Some people advocate a "sacrificial protein" for the first 6 weeks of treat-
ment, on the theory that the cat is more likely to develop dietary sensitivity during the time that
the gut is inflamed. Protein hydrolysates have reduced molecular weights 10,000 daltons)
that should decrease antigenicity.
Inflammatory Bowel Disease
Commercially Available Hypoallergenic Diets
III
Lamb
Hill's Prescription Diet DID (canned)
Innovative Veterinary Diets (dry or canned)
lams Eukanuba Response Formula (canned)
Rabbit
Innovative Veterinary Diets (canned)
Nature's Recipe Rabbit (canned)
Venison
Innovative Veterinary Diets (canned or dry)
Waltham Select Protein (canned)
Duck
Innovative Veterinary Diets (dry)
Hydrolyzed proteins
Hills Prescription Diet'ZJD (dry)
Hill's Pet Nutrition, Topeka, KS; Innovative Veterinary Diet, Nature's Recipe Co., Newport, KY; lams
Company,Dayton, OH; WalthamUSA, Vernon, CA.
16. What dietary supplements are commonly recommended?
Various nutritional deficiencies secondary to IBD require supplementation. In addition,
some nutritional supplements may have anti-inflammatory effects or promote healing of the in-
testinal tract. Controlled studies of these supplements for treatment of feline IBD are lacking.
Vitamin Bl2 (cobalamine) and folate concentrations are often reduced by malabsorption.
Vitamin K deficiency due to malabsorption of fats may be severe enough to cause bleeding
and abnormal hemostasis.
N-acetyl glucosarnine has shown promise in the treatment of inflammatory disorders, in-
cluding IBD, colitis and Crohn's disease in people.
Glutamine can be supplemented as an energy source for mucosal cells of the digestive tract.
Vitamin C scavenges free radicals, enhances immune function, has anti-inflammatory
properties, and may reduce stress.
Lactobacillus acidophilus is a probiotic that may help to restore normal intestinal flora.
Dimethylglycine modulates production of lymphocytes and antibodies. It is theorized to
decrease the allergic response.
Proanthocyanidin complex is a bioflavinoid that theoretically works with vitamin C to
reduce inflammation, strengthen capillaries, scavenge free radicals, and improve immune
function. Antiviral activity also has been proposed.
Vitamin E, vitamin A, and selenium are antioxidants that may protect cells from free
oxygen radical-induced damage.
Zinc is thought to potentiate immune system response and enhance healing.
Dietary Supplements for Management of IBD
SUPPLEMENT
Cobalamine
Dimethylglycine
Folate
Glutamine
N-acetyl glucosamine
Lactobacillus acidophilus
Proanthocyanidin complex
Selenium
Vitamin A
Vitamin C
VitaminE
Zinc
PROPOSED DOSE
125-250 mg/wk SC or 1Mfor 6-8 weeks
50-250 mg/cat PO, indefinitely
0.5 mg/day PO for I month
50-500 million microorganisms/cat PO, until stool returns to
normal consistency
15 J.lg/day PO, indefinitely
1000-5000 IV/day PO as beta caroline, indefinitely
250-300 mg/cat PO, indefinitely.
200 IV/day PO as alpha tocopherol daily, indefinitely.
7.5 mg/day PO, indefinitely
SC", subcutaneously, 1M=intramuscularly, PO=orally.
17. What drugs are used to manage IBD?
DRUG PROPOSEDDOSE
Chlorambucil
Cyclophosphamide
Cyclosporine
Methylprednisolone
Metronidazole
Prednisolone
Azathioprine
Sulfasalazine
2 mg PO every other day or 2 mgt M2/day for 7 days; then I mg/M2/day for 7
days; then taper to lowest effective maintenance dose
50 mg/M' PO 4 times/wk: during remission, use chlorambucil
0.5-8.5 mg/kg PO every 12-24 hr, indefinitely
10-20 mg/cat 1Mevery 2 wk until controlled; then as needed
10-20 mg/kg PO every 8-12 hr for 2-4 wk; then gradually taper off over 1-2 mo
1-2 mg/kg PO every 12-24 hr for 2-4 wk; then reduce dose by half every
2 weeks until lowest effective maintenance dose is found.
0.3 mg/kg PO every 48 hr, indefinitely.
10-20 mg/kg PO every 24 hr for 7-10 days
PO=orally, 1M=intramuscularly.
18. Describe the effects of metronidazole.
This antibiotic is one of the antiprotozoal drugs of choice for Giardia spp. in cats. Because it
has an excellent anaerobic spectrum, it may aid in the treatment of secondary bacterial over-
growth. It is proposed to inhibit cell-mediated immunity and to alter neutrophil chemotaxis and
thus may be an effective adjunct to glucocorticoids. Side effects include salivation (due to bad
taste), anorexia, vomiting, central nervous system abnormalities (seizures), and neutropenia.
19. Discuss the role of glucocorticoids.
Prednisolone is used most frequently, but if the cat cannot or will not take oral medications,
methylprednisolone can be used. Control seems to be more difficult with parenteral depository
glucocorticoids. Transdermal dosing of prednisolone also may be helpful when oral drugs cannot
be administered. Glucocorticoids should not be prescribed until the diagnosis of IBD is con-
firmed by histology. Common side effects include polyuria, polydipsia, polyphagia, skin disease,
weight gain, and type 2 diabetes mellitus (see Chapter 54).
20. How does azathioprine work?
The mechanism of immunosuppression has not been determined, but it is thought to depend
on several factors. Azathioprine antagonizes purine metabolism, resulting in inhibition of RNA,
DNA synthesis, and mitosis. Incorporation into nucleic acids may cause chromosome breaks,
and inhibition of coenzyme function may disrupt cellular metabolism. Azathioprine has a greater
effect on cellular immunity and delayed hypersensitivity than on humoral antibody responses. It
is thought to take at least 1-3 weeks to become fully effective, and clinical response may require
6 weeks. It is used most often in cases of IBD that cannot becontrolled by diet modifications and
glucocorticoids or in cats that glucocorticoids make ill. Side effects may include bone marrow
suppression, pancreatitis, hepatic damage, and anorexia. CBC should bemonitored once or twice
weekly for 10-14 days after starting, then monthly.
21. What is the mechanism of action of sulfasalazine?
The mechanism of action is not known. It is thought that after colonic bacteria cleave sul-
fasalazine into sulfapyridine and 5-arninosalicylic acid (5-ASA), the antibacterial (sulfapyridine)
and anti-inflammatory (5-ASA) activity modify the course of the disease. Levels of both drugs
are higher in the colon when the compound is used than with separate administration. Dosing in
cats may be difficult without compounding. Primary side effects include anorexia, vomiting, and
anemia; in dogs sulfasalazine has induced keratoconjunctivitis sicca.
22. How do cyclophosphamide and chlorambucil work?
The metabolites of cyclophosphamide act as alkylating agents, interfering with DNA replica-
tion, RNA transcription and replication, and nucleic acid function. The phosphorylating activity of
cyclophosphamide also enhances its cytotoxic properties. The mechanism of action for its im-
munosuppressive activity on T-cells and antibody production is unknown. The drug is associated
with bone marrow suppression and hemorrhagic cystitis (rarely). It should not be used over the
long term. If it is effective during the induction phase, the related drug chlorambucil should be
used for chronic management.
The mechanism of action of chlorambucil is cross-linking with cellular DNA. It is cyto-
toxic and cell cycle-nonspecific. Side effects include myelosuppression, resulting in anemia,
leukopenia, and thrombocytopenia. It can also result in anorexia, vomiting, and diarrhea. A
complete blood count with platelets should be done weekly until the cat is stable, then every
other week.
23. Describe the mechanism of action of cyclosporine.
The mechanism of action is impedance of calcium-dependent signal transduction in the cy-
tosol of lymphocytes. Cyclosporine stimulates secretion of transforming growth factor beta,
which inhibits interleukin 2-stimulated T-cell proliferation and generation of antigen-specific cy-
totoxic lymphocytes. The primary side effects in people and dogs include inappetence, GI irrita-
tion, and gingival hyperplasia. Blood levels should be measured 24-48 hours after starting
therapy to ensure adequate levels and periodically during therapy. The goal is a 12-hour whole-
blood trough level of 250-500 ng/m!. Gelatin capsules may be needed for administration because
of the unpleasant taste.
24. What is the prognosis for cats with mD?
The prognosis depends on the form of IBD. In general, although the condition cannot be
cured, the prognosis for control is good.
BIBLIOGRAPHY
I. Davenport OJ, Remillard RL, Simpson KW, et al: Gastrointestinal and exocrine pancreatic disease. In
Hand MS, Thatcher CD, Remillard RL, Roudebush P (eds): SmaII Animal Clinic Nutrition, 4th ed.
Marceline, MO, Mark Morris Institute, 2000, pp 757-763.
2. Diehl KJ: Enteritis, lymphocytic-plasmacytic. In Tilley LP, Smith FWK (eds): The Five Minute
Veterinary Consult, Canine and Feline. Baltimore, Williams & Wilkins, 1997, pp 554-555.
3. Dimski DS: Therapy of inflammatory bowel disease. In Kirk RW, Bonagura JD (eds): Current Veterinary
Therapy XII-SmaII Animal Practice. Philadelphia, W.B. Saunders, 1995, pp 723-727.
4. Jergens AE: Inflammatory bowel disease. In August JR (ed): Consultations in Feline Internal Medicine,
vol. 2. Philadelphia, W.B. Saunders, 1994, pp 75-81.
5. Jergens AE: Inflammatory bowel disease. Vet Clin North Am Small Animal Pract 29:501-521, 1999.
6. Kendall RV: Therapeutic nutrition for the cat, dog, and horse. In Schoen AM, Wynn SG (eds):
Complementary and Alternative Veterinary Medicine: Principles and Practice. St. Louis, Mosby,
1998, pp 5, 61, 64,121-122.
7. Leib MS, Matz ME: Diseases of the large intestine. In Ettinger SJ, Feldman EC (eds): Textbook of
Veterinary Internal Medicine, 4th ed. Philadelphia, WB. Saunders, 1995, pp 1241-1247.
8. Marks SL, Fascetti AJ: Nutritional management of diarrheal diseases. In Bonagura JD (ed): Current
Veterinary Therapy XIII-Small Animal Practice. Philadelphia, WB. Saunders, 2000. pp 654-
655.
9. Meyer DJ, Twedt DC: Effect of extrahepatic disease on the liver. In Bonagura JD(ed): Current Veterinary
Therapy XllI-Smali Animal Practice. Philadelphia, WB.Saunders, 2000, pp 668--671.
10. Plumb DC: Veterinary Drug Handbook, 3rd ed. Ames, lA, Iowa State University Press, 1999.
I I. Sherding RG, Johnson SE: Diseases of the intestines. In Birchard SJ, Sherding RJ (eds): Saunders
Manual of Small Animal Practice. Philadelphia, WB. Saunders, 1994, pp 704-709.
12. Sherk M: mD: A misleading misnomer (inflammatory digestive tract syndrome). In Proceedings of the
16thAnnual ACVIM Forum, San Diego, CA, 1998, pp 537-539.
13. Williams DA: Cobalamin and folate in feline malabsorption. Proceedings of the 16th Annual ACVIM
Forum. San Diego, CA, 1998, pp 534-536.
24. NEOPLASIA AND OTHER FORMS
OFINTESTINAL OBSTRUCTION
Kim Selting, D.v.M.
1. List the possible clinical signs of intestinal neoplasiaand/or obstruction(partial or
complete) in cats.
Vomiting
Anorexia/inappetence
Gagging/dysphagia (linear foreign body anchored in the mouth)
Weight loss/cachexia
Diarrhea
Tenesmus (with lesion in colon or ileum)
Hematochezia (colon or rectum); melena (small intestine)
Lack of stool/constipation
Dehydration
Lethargy/malaise
Ascites and/or carcinomatosis
Central nervous system (CNS) signs and icterus
Palpable abdominal mass (approximately 50% of cases)
Rectal prolapse of ileocecal lymphoma mass
2. Which clinical findings aremostcommon?
In most reports, vomiting, anorexia, and weight loss are by far the most common signs, although
the order of their prevalence varies. Clinical signs do not necessarily correlate with the location of the
tumor in the gastrointestinal (GI) tract with the exception of tenesmus and hematochezia, which
occur with colonic or rectal disease. Palpating an abdominal mass is a consistent finding but depends
on the practitioner's level of palpation skill. The rest of the clinical findings are less common.
Duration of clinical signs before diagnosis can range from days to months. Many cases are treated
for clinical signs conservatively before relapse and definitive diagnosis. CNS signs, icterus, and other
polysystemic signs may occur in cats with feline infectious peritonitis (see Chapter 38).
3. Whatare themost common differential diagnoses for intestinal obstruction?
Intestinal neoplasia, foreign body, and intussusception are common causes of intestinal ob-
struction in cats. Lymphoma is the most common neoplasm. Despite repeated references in cur-
rent texts to mast cell tumor as the second most common feline GI neoplasm, no current studies
focus on this disease. Adenocarcinoma is the most common nonlymphatic/nonhematopoietic
neoplasm. Intestinal obstruction due to adenocarcinoma results from an annular ring of tissue
created by the solitary tumor. Lymphoma and mast cell tumors may be discrete or diffuse.
Uncommonly diagnosed GI tract tumors include lipoma, leiomyosarcoma, leiomyoma, glob-
ule leukocyte tumor, granulated round cell tumor, fibrosarcoma, carcinoid, osteosarcoma, gan-
glioneuroma, gastric extramedullary plasmacytoma, and granulated round cell tumor.
Intussusception most commonly occurs in the ileocecocolic region. Predisposing causes in-
clude parasites, foreign body, previous abdominal surgery, viral enteritis, and mural lesions.
Many cases, however, are idiopathic.
Trichobezoar, volvulus, intestinal torsion, incarceration of bowel in a hernia, adhesions,
stricture, intramural abscess, granuloma or hematoma, congenital malformations, and feline in-
fectious peritonitis (FIP) are less common causes of GI obstruction. Trichobezoars may form in
part because of a lack of interdigestive migrating myoelectric complexes in cats.
114
Neoplasia and Other Forms of Intestinal Obstruction 115
4. How does FIP cause obstructive disease?
Noneffusive FIP can create solitary mural intestinal inflammatory lesions. In one study. this
presentation predominated in approximately 20% of cats with histopathologically documented
FIP. Histologically, the intestine is markedly thickened; multifocal pyogranulomas extend
through the wall with areas of necrosis and fibrosis. Presence of coronavirus was confirmed by
immunohistochemical staining of the tissues (New York State Veterinary Diagnostic Laboratory,
Ithaca, NY). In the 26 cats reported in the study, 76% of obstructions occurred in the colon or at
the ileocecocolic junction. Ragdolls and Himalayans may have been overrepresented, but re-
ported numbers are small. Half of the cats were < I year of age, II of 26 were 1-6 years old, and
only 2 of 26 were 11 years old. Most cats died of the disease within 9 months. A few cats had ef-
fusions at surgery, but the fluid was not typical for effusive FIP (see Chapter 38).
5. What hematologic abnormalities may be seen in cats with intestinal obstruction?
Hematologic abnormalities are common but generally not specific for anyone disease:
Complete blood cell count. Leukocytosis with or without left shift, monocytosis, and lym-
phopenia have been detected in some cats. Eosinophilia. basophilia, and thrombocytosis were de-
tected in a cat with lymphoma. Anemia may result from chronic disease, GI blood loss (anemia
may be microcytic because of iron deficiency in chronic cases), or bone marrow involvement
(feline leukemia virus [FeLV]).
Serum biochemical panel. Panhypoproteinemia may result from GI blood loss. In some
cats, hyperglobulinemia results from chronic inflammatory disease, FIP, or neoplasia. Hyper-
glycemia, increased activities of liver enzymes, and hypercholesterolemia may occur. Hypo-
chloremic metabolic alkalosis may be seen with pyloric outflow tract obstruction.
Serology tests. FeLVserum antigen tests are usually negative with adenocarcinoma and oc-
casionally positive with lymphoma. Positive coronavirus titers indicate only exposure to a coron-
avirus, not PIP (see Chapter 38).
Serum electrophoresis. Monoclonal gammopathy is most consistent with plasmacytoid
neoplasia but is occasionally detected in cats with FIP.
6. What imaging studies may be helpful in evaluating intestinal obstruction?
Plain radiographs may reveal a mass effect, fluid-filled stomach, or intestinal obstructive
pattern characterized by gas-filled loops of bowel. Thoracic radiographs rarely reveal metastasis,
but findings consistent with aspiration pneumonia may be present.
Positive contrast radiographs are used to confirm partial or complete obstruction.
Barium series in a cat with adenocarcinoma of the small intes-
tine. (Courtesy of Dr. David Twedt, Colorado State University.)
116 Neoplasia and Other Forms of Intestinal Obstruction
Ultrasound may be used to document masses localized to the GI tract, thickened bowel
loops, enlarged mesenteric lymph nodes, abnormal peristalsis, and intussusceptions. In addition,
tissue aspirates for cytology also can be guided by ultrasound.
Endoscopy/colonoscopy can be used to visualize mass lesions and to obtain biopsies, de-
pending on the location of the abnormality. Biopsies should be done in all patients because dif-
fuse, microscopic disease may be detected on histopathology. Adenocarcinoma may look like
stricture or fibrous tissue rather than a mass lesion.
7. What other diagnostic techniques may be helpful?
Exploratory laparotomy is used to confirm and relieve obstructive disease and to obtain
tissue for definitive diagnosis.
Cytology obtained before surgery or intraoperatively can help to make a definite diagnosis,
especially of lymphoma. Aspiration cytology is unreliable for adenocarcinoma.
Histology and immunohistochemistry are used to confirm the diagnosis of neoplasia and
PIP.
8. How are intestinal obstructions treated?
For most intestinal obstructions, surgery is the mainstay of treatment. Some foreign bodies
in the pyloric outflow tract can be removed via endoscopy, but disease in other regions requires
surgery. If an intussusception is documented, it should be reduced if the intestine is viable and
the primary disease treatable (e.g., foreign body). If the primary disease is neoplasia or the intes-
tine is not viable, resection and anastomosis are indicated. Enteroplication should be considered
because the recurrence rate for intussusceptions is as high as 27%. When adenocarcinoma is de-
tected, surgery is the primary treatment (see question 14). When lymphosarcoma is detected,
chemotherapy should be used as the primary treatment if possible (see question 18). Most tri-
chobezoars are found in the proximal jejunum to distal ileum.
9. Wbat preventive methods are used after surgical removal?
Administration of emollient laxatives (use petroleum-based products, not mineral oil, to
avoid lipid aspiration pneumonia)
Attempts to prevent overgrooming (brush frequently, control fleas, and address behavioral
problems)
Shaving long hair
Administration of prokinetic drugs (e.g., metocloprarnide)
10. What are adenocarcinomas? How common are they'?
Adenocarcinomas are malignant tumors of glandular epithelium that originate from the
crypts of Lieberkuhn. They are the most common nonlymphoid neoplasia, accounting for
25-30% of all GI neoplasms. Osseous or chondroid metaplasia occurs in some cases. In one
study, luminal stricture occurred in 12 of 44 cats.
11. Describe the typical signalment of cats with adenocarcinoma.
Adenocarcinomas occur most commonly in middle-aged cats (mean age =8-11 years, range
= 2-17 years). Siamese are overrepresented, accounting for 71% of cases (8 times the incidence
in other breeds). The disease is more common in females than males.
12. Wbere are most adenocarcinomas located?
Adenocarcinomas may occur in either the small or large intestine. Up to 70% occur in the
small intestine, especially the jejunum. The tumor is uncommon in the duodenum.
13. How does metastasis occur? Wbat are the most common sites?
Adenocarcinomas spread via the lymphatic system. If metastasis occurs, the mesenteric
nodes are the most common site (50%), followed by carcinomatosis (29%), lung. and liver.
Neoplasia and Other Forms of Intestinal Obstruction 117
14. What treatment is recommended for adenocarcinoma?
Surgical resection and anastomosis are the treatment of choice. In one study, administration
of adriamycin (l mglkg intravenously every 3 weeks for 5-6 treatments) improved median sur-
vival time for colonic adenocarcinoma.
15. Describe the prognosis for cats with adenocarcinoma.
Prognosis varies among studies. A major limitation is the small number of reported cases.
Notable findings of several studies include:
o In the study by Birchard, survival after surgery was 7 days (range = 1-13 day) vs. 3 days
without surgery.
o In the study by Kosovsky, cats that lived for> 2 weeks after surgery had a mean survival
time of 15 months.
o In the study by Cribb, the mean survival time after resection and anastamosis was 2.5
months with a range of 0-24 months.
o In the study by Turk, the mean survival time after surgery was 5 weeks; the median survival
time was 20 weeks with a range of 2 days to 2 years.
o Kosovsky reported survival times of 4.5 and 28 months in two cats that survived surgery
but with carcinomatosis.
o The presence of metastasis is prognostic. According to Cribb, the postoperative mean
survival times for cats with and without metastasis were 5 months and 10 months, re-
spectively.
o Histologic type may be prognostic as in humans. According to Cribb, the mean survival times
for tubular, undifferentiated, and mucinous types were 11,4, and 4 months, respectively.
16. What causes intestinal lymphosarcoma?
Most intestinal lymphosarcomas are of T-cell origin. Feline coronavirus-associated cell
membrane antigen (FOCMA) may be causative after exposure to FeLY.
17. Describe the presentation of intestinal lymphosarcoma.
o The median age is 12 years (range = 3-18 years).
o Discrete and diffuse lymphosarcomas occur with equal frequency in the small intestine.
o Fewer cases occur in the large intestine.
o Affected cats can be either FeLY-positive or FeLY-negative.
o Approximately 13% of feline lymphosarcomas are exclusively in the GI tract.
o Approximately 40% of feline lymphosarcomas metastasize to extra-Gl sites.
o Lymphoblastic lymphosarcoma (59%) is more likely than lymphocytic lymphosarcoma
(24%) to present with an abdominal mass.
18. How are intestinal lymphosarcomas treated?
Recommended treatment is discussed in Chapter 68. Recently, the combination of pred-
nisolone with chlorambucil was reported.
19. Discuss the prognosis for cats with lymphosarcoma.
o The most consistent prognostic factor is response to therapy. Duration of first remission
also correlates directly with survival.
o A positive FeLY serologic test is a negative prognostic indicator in some studies.
o Anatomic location does not predict response rate or survival time.
Survival ranges from 2-2000+ days. The mean survival time ranges from 50 days to 23
months. Survival time is probably prolonged in a subset of cats.
o Histologic grade may be prognostic. In one study, the complete remission rates and
median survival times for lymphoblastic lymphosarcoma were 18% and 2.7 months. re-
spectively; the corresponding values for lymphocytic lymphosarcoma were 69% and
22.8 months.
118 Neoplasia and Other Forms of Intestinal Obstruction
20. How does colonic neoplasia differ from neoplasia in other areas of the GI tract?
Colonic neoplasia accounts for 10-15% of GI neoplasms and <1% of all feline neoplasms.
The mean age for diagnosis of colonic cancer is 12.5 years, and the median age is 13 years. which
is comparable to neoplasia in other areas of the GI tract. Adenocarcinoma is most common, fol-
lowed by lymphosarcoma and then by mast cell tumors. A few cases of neuroendocrine carci-
noma have been reported. Treatment combines surgery and chemotherapy, as discussed for
adenocarcinoma and lymphoma of the small intestine.
21. Summarize the prognosis for cats with colonic neoplasia.
PROGNOSTIC FACTOR
Received
chemotherapy
Type of surgery
Subtotal colectomy
Mass resection
Biopsy
Metastasis
ADENOCARCINOMA
Doxorubicin
with, MST = 280 days
without, MST = 56 days
MST = 138 days
MST= 68 days
MST= 10 days
With: MST = 49 days
Without: MST = 259 days
LYMPHOSARCOMA
Not prognostic
Surgery not prog-
nostic, but I cat
lived 1355 days
Not evaluated
MASTCELLTUMOR
All 4 cats in study
treated with pred-
nisone
All had surgery, but
numbers too small
for assessment
Not evaluated
MST = 199 days
for 4 cats
MST =median survival time.
BIBLIOGRAPHY
I. Barrand KR, Scudmore CL: Intestinal leiomyosarcoma in a cat. J Small Anim Pract 40: 216-219, 1999.
2. Barrs VR, Beatty JA, Tisdall PLC. et al: Intestinal obstruction by trichobezoars in five cats. I Feline Med
Surg I: 199-207, 1999.
3. Bedford PN: Partial intestinal obstruction due to colonic adenocarcinoma in a cat. Can Vet I 39:769-771,
1998.
4. Birchard SJ, Couto CG, Johnson S: Nonlymphoid intestinal neoplasia in 32 dogs and 14 cats. JAm Anim
Hosp Assoc 22:533-537, 1986.
5. Cribb AE: Feline gastrointestinal adenocarcinoma: A review and retrospective study. Can Vet I 29:709-
712,1988.
6. Demetriou IL. Welsh EM: Rectal prolapse of an ileocecal neoplasm associated with intussusception in a
cat. I Feline Med Surg 1:253-256, 1999.
7. Fondacaro IV, Richter KP, Carpenter JL, et al: Feline gastrointestinal lymphoma: 67 cases (1988-1996).
Eur I Comp Gastroenterol 4:5-11, 1999.
8. Gabor LJ, Malik R, Canfield PI: Clinical and anatomical features of lymphosarcoma in 118 cats. Aust
VetI 76:725-732,1998.
9. Harvey CI, Lopez GW, Hendrick MJ: An uncommon intestinal manifestation of feline infectious peri-
tonitis: 26 cases (1986-1993). I Am Vet Med Assoc 209:1117-1120, 1996.
10. Kosovsky lE, Matthiesen DT, Patnaik AK: Small intestinal adenocarcinoma in cats: 32 cases (1978-
1985). I Am Vet Med Assoc 192:233-235, 1988.
II. McEntee MF, Horton S, Blue I, et a1: Granulated round cell tumor of cats. Vet Pathol 30: 195-203, 1993.
12. Slawienski MI, Mauldin GE, Mauldin GN, et al: Malignant colonic neoplasia in cats: 46 cases (1990-
1996). I Am Vet MedAssoc 211:878-881,1997.
13. Turk MAM, Gallina AM, Russell TS: Nonhematopoietic gastrointestinal neoplasia in cats: A retrospec-
tive study of 44 cases. Vet PathoI18:614-620, 1981.
14. Thorn CE, Aubert I: Abdominal mass aspirate from a cat with eosinophilia and basophilia. Vet Clin
PathoI28:139-14I,1999.
15. Zikes CD, Spielman B, Shapiro W, et al: Gastric extramedullary plasmacytoma in a cat. J Vet Intern Med
12:381-383,1998.
25. SECONDARY GASTROINTESTINAL DISEASES
Craig B. Webb, Ph.D., D.V.M.
1. Define secondary gastrointestinal disease.
Secondary gastrointestinal (Gl) diseases are disorders that do not directly involve structures
of the primary Gl tract (oral cavity, esophagus, stomach, small and large intestines) but manifest,
at least in part, with vomiting and diarrhea.
2. What are the secondary GI differentials for vomiting and diarrhea?
Inflammatory, infectious, metabolic, endocrine, and neurologic diseases of organs outside
the gastrointestinal tract can result in vomiting or diarrhea.
Common Secondary Gastrointestinal Causes of Vomiting and Diarrhea
Inflammation
Pancreatitis
Cholangiohepatitis
Nephritis
Peritonitis
Encephalitis
Steatitis
Metabolic/endocrinedisorders
Diabetic ketoacidosis
Hyperthyroidism
Hypokalemia
Hypoadrenocorticism
Uremia (renal failure)
Urinary tract obstruction
Bile duct obstruction
Congestive heart failure
Exocrine pancreatic insufficiency
Drugs/toxins
Antibiotics
Chemotherapeutics
Digoxin
Ethylene glycol
Heavy metals
Plants
Infection
Viral
Bacterial
Pyelonephritis
Cystitis
Pyometra
Cholangiohepatitis
Heartworm disease
Neoplasia
Pancreatic
Hepatic
Central nervous system
Neurologicdisorders
Vestibulardisease
Encephalitis
Hydrocephalus
Trauma
Psychogenic
3. What are the common inflammatory and infectious causes of secondary GI disease?
Hepatic or pancreatic neoplasia, pancreatitis, peritonitis, cholangiohepatitis, bile duct ob-
struction, steatitis, pyelonephritis, heartworm disease, pyometra, and septicemia.
4. What are the common metabolic and endocrine causes of secondary GI disease?
Hepatic lipidosis, lipemia, uremia, hypokalemia, hypercalcemia, urinary tract obstruction.
hyperthyroidism, diabetic ketoacidosis, and hypoadrenocorticism.
5. What primary neurologic disorders are associated with secondary vomiting?
Vestibular disease, dysautonomia, central nervous system neoplasia, encephalitis, hydro-
cephalus, and psychogenic disorders.
119
120 Secondary Gastrointestinal Disease
6. Besides vomiting and/or diarrhea, what are the common presenting signs in cats with
secondary GI disease?
Most of the historical and chief complaints for cats with secondary Gl disease are nonspe-
cific. Examples include thin body condition, anorexia, polyphagia (i.e., hyperthyroidism or dia-
betes mellitus), polyuria, polydipsia, weakness, lethargy, hyperactivity (i.e., hyperthyroidism),
and weight loss.
7. What mechanisms cause vomiting in secondary GI diseases?
Vomiting from secondary Gl diseases can be induced by afferent impulses to the emetic
center, stimulation of the chemoreceptor trigger zone (CRTZ), and altered Gl motility.
8. How do secondary GI diseases stimulate the emetic center?
The emetic center is located in the reticular formation in the lateral medullary region of the
brain. Within the reticular formation, the nucleus of the solitary tract receives convergent input from
the vagus nerve, area postrema, and vestibular and limbic systems. Sources of neural input to the
emetic center include afferents from the Gl tract, abdominal viscera, heart, vestibular system,
CRTZ, and higher brain centers. Within the abdomen, the liver, pancreas, urinary tract, internal gen-
italia, and abdominal mesentery provide input to the brainstem emetic center. Afferent fibers from
the abdomen travel to the emetic center in the medulla via the vagal and sympathetic nerve fibers.
9. What are other potential causes of vomiting in secondary GI diseases?
Fluid and electrolyte imbalances (i.e., hypokalemia, hyponatremia, hypercalcemia) and aci-
dosis (i.e., renal failure, diabetic ketoacidosis) often occur with systemic diseases. These condi-
tions may alter Gl motility or stimulate the CRTZ. Endocrine disease also may produce metabolic
abnormalities that stimulate the CRTZ. The CRTZ is on the floor of the fourth ventricle-specif-
ically, the area postrema. The area postrema is located on the dorsal surface of the medulla ob-
longata, as part of the floor of the fourth ventricle, and lacks the usual blood-brain diffusion
barrier. In this position, the CRTZ can monitor chemical levels in both blood and cerebrospinal
fluid, making it susceptible to many stimuli.
10. What is the initial diagnostic plan for assessment of secondary causes of GI symptoms?
Complete blood cell count, serum biochemical panel, urinalysis, and plain abdominal radi-
ographs are often used to assess for secondary causes of Gl tract signs. Most renal, hepatic, pan-
creatic, and endocrine diseases produce abnormalities that are evident on these tests.
11. What pancreatic diseases result in secondary GI disease?
Vomiting, inappetence, weight loss, and, occasionally, diarrhea can result from pancreatitis
(see Chapter 36). Small bowel diarrhea, polyphagia, and failure to thrive result from exocrine
pancreatic insufficiency (EPI).
12. What chemistry panel abnormalities may suggest pancreatitis in cats?
Elevated activities of the liver enzymes (alkaline phosphatase [ALP], alanine aminotransferase
[ALT, elevated total bilirubin, and azotemia are cornmon. Hypocalcemia and hypoproteinemia
occur in some cats. Histologically confirmed cases of feline pancreatitis may have serum amylase
and lipase activities that are above normal, normal, or below normal; therefore, these tests are not
often helpful.
13. What other diagnostic procedures are used to diagnose pancreatitis?
In some cats with pancreatitis, radiographs reveal a decrease in serosal detail in the cranial
abdomen, displacement of the pyloric antrum and duodenum, and dilated, gas-filled loops of in-
testine, especially the duodenum. Ultrasonographic findings of pancreatitis include hypoechoic
pancreatic parenchyma, dilated pancreatic ducts, hyperechoic peripancreatic fat, and a mild peri-
toneal effusion. An assay for feline trypsin-like immunoreactivity (ITLI) has been developed and
Secondary Gastrointestinal Disease 121
may prove to be a more specific marker of the disease. Several studies have found significantly
elevated ffLllevels in cats with pancreatitis, although one recent report found a poor association
between ffLllevels and pancreatic histopathology (see Chapter 36).
14. What is the most common cause of EPI in cats?
Chronic pancreatitis is the most common cause of exocrine pancreatic insufficiency in cats.
Other causes include pancreatic fluke infestation, pancreatic adenocarcinoma, and possibly con-
genital conditions and idiopathic acinar atrophy.
15. Describe the most common presentation of EPI. How is it diagnosed?
As with dogs, the most common presenting complaints for cats with EPI are polyphagia,
weight loss, diarrhea, and vomiting, with an oily, unkempt haircoat. Patients often produce large
volumes of soft, pale, malodorous stool. Increased neutral fats may be found on Sudan staining
of feces from cats with EPI, but a more sensitive test is the recently developed assay for ITLI.
Significantly decreased ffLI levels are found in cats with EPI.
16. Which hepatic diseases most commonly result in secondary GI tract disease?
Hepatic lipidosis, cholangiohepatitis/cholangitis complex, feline infectious peritonitis, and
hepatic neoplasia (see Chapters 29, 30, 31, and 38).
17. What is "triaditis"?
Triaditis refers to concurrent liver (hepatic lipidosis, cholangiohepatitis), pancreatic (pancre-
atitis), and intestinal disease (inflammatory bowel disease) in cats exhibiting symptoms of pri-
mary GI disease (see Chapter 29).
18. What is the anatomic explanation for concurrent cholangiohepatitis in cats with pan-
creatitis?
In cats, the common bile duct and main pancreatic duct conjoin before entering the duode-
num at the major duodenal papilla. Acute suppurative cholangiohepatitis probably is caused by
an ascending infection from the GI tract to the biliary tree through the bile duct. This ascension
also may affect the pancreas.
19. Which endocrine diseases most commonly cause GI signs and symptoms?
Diabetic ketoacidosis, hyperthyroidism, and hypoadrenocorticism can induce vomiting or
diarrhea.
20. What are the common historical complaints and physical examination rmdings?
The most common historical sign of hyperthyroidism is weight loss; other presenting com-
plaints include polyphagia or anorexia, vomiting, hyperactivity, polyuria and polydipsia, diarrhea,
and muscle weakness (see Chapter 53). Physical examination findings include a palpably en-
larged thyroid gland, thin body condition, tachycardia, and cardiac murmur. Most cats are older.
21. What are the most common serum chemistry abnormalities in cats with hyper-
thyroidism?
Hyperthyroidism is the number-one cause of elevated liver enzyme activities (ALT.ALP, and
aspartate aminotransferase) in cats. Most patients have increased total T4 concentrations. Less
common biochemical abnormalities include elevated blood urea nitrogen, creatinine, blood glu-
cose, and packed cell volume.
22. Why do hyperthyroid cats have diarrhea?
Approximately 45% of hyperthyroid cats have diarrhea. Although the exact cause is un-
known, the most likely candidates are a thyroid hormone-induced increase in GI motility and a
decrease in GI transit time. Increased enterocyte levels of cyclic adenosine monophosphate,
122
Secondary Gastrointestinal Disease
relative deficiency of trypsin secretion by the pancreas, intestinal mucosal edema, and polypha-
gia are also potential contributing factors.
23. What causes emesis in hyperthyroid cats?
There are several possible, but still unproven, causes of vomiting in cats with hyperthy-
roidism. Proposed mechanisms include gastric hypoacidity, hypergastrinemia, superficial gastri-
tis, and esophageal dysfunction. Thyroid hormone may act directly on the CRTZ.
24. What historical, physical examination, or serum biochemistry panel findings may help
to distinguish between cats with or without diabetic ketoacidosis (DKA)?
Anorexia or decreased appetite is more common in cases of DKA (see Chapter 56).
Decreased activity, weakness, thin body condition, and vomiting are also more common in cats
with DKA. Elevated liver enzymes, azotemia, and electrolyte abnormalities (hypokalemia, hy-
ponatremia, and hypochloremia) are more frequent and more significant in cats with DKA.
25. What diseases most commonly accompany DKA?
Hyperthyroidism, inflammatory bowel disease, eosinophilic granuloma complex, urinary
tract infection, and pancreatitis.
26. What historical, physical examination, and chemistry panel findings lead to inclusion
of hypoadrenocorticism on a list of differentials for vomiting cats?
In addition to vomiting, owners may report lethargy, anorexia, weight loss, and polyuria (see
Chapter 55). Physical examination may reveal dehydration, hypothermia, prolonged capillary
refill time, weak pulses, and sinus bradycardia. Hyponatremia and hyperkalemia should be seen
on a chemistry panel. The diagnosis can be confirmed with an adrenocorticotropic hormone stim-
ulation test.
27. What are possible explanations for vomiting and diarrhea in cats with hypoadreno-
corticism?
As in dogs, the cause of these symptoms remains unclear. Physiologic levels of cortisol act
as a trophic factor for the gastrointestinal mucosa. Without that input, there is a decrease in mu-
cosal blood flow. Gastric motility is also decreased in hypoadrenocorticism because of elec-
trolyte imbalances and inhibition of gastric contractions by elevated levels of corticotropin-
releasing factor (CRF).
28. What are the most common presenting clinical signs in cats with heartworm disease?
Vomiting is one of the most frequently reported presenting complaints in cats subsequently
diagnosed with heartworm disease (see Chapter 10). Other common symptoms include cough-
ing, dyspnea, lethargy, anorexia, and weight loss. Vomiting episodes may be intermittent and un-
predictable (i.e., not necessarily related to food ingestion).
29. What causes emesis in cats with heartworm disease?
Although the mechanism is unknown, one possible pathway involves the release of inflam-
matory mediators from diseased lungs that interact with receptors in the CRTZ.
30. What other feline cardiac diseases may be associated with vomiting?
In cases of feline cardiomyopathy (restrictive, dilated, hypertrophic, or idiopathic), vomiting
may proceed cardiopulmonary signs (e.g., dyspnea, cough, lethargy) by 1-3 days.
31. Which classes of drugs are currently used as antiemetics in feline veterinary medicine?
Antiemetics agents include alphaj-adrenergic antagonists (e.g., chlorpromazine, prochlorper-
azine), Dz-dopaminergic antagonists (e.g., rnetoclopramide), histaminergic antagonists (e.g.,
meclizine, diphenhydramine), and 5-HT
rreceptor
antagonists (e.g., ondansetron, rnetocloprarnidc).
Secondary Gastrointestinal Disease 123
32. Is antiemetic therapy for cats different from antiemetic therapy for dogs?
Lesions in the CRTZ of dogs can abolish vomiting in response to oral emetic agents in
almost 80% of trials, whereas similar lesions in cats abolish emesis to the same agents in only
30% of trials. Various explanations are under investigation, including differences in neurotrans-
mitter receptor type, location, and sensitivity.
33. What is the role of metoclopramide as an antiemetic in cats?
Metoclopramide, a Drdopamine receptor antagonist, is a highly effective, centrally acting
antiemetic in dogs. Research suggests that Dz-dopamine receptors are much less important in
centrally mediated emesis in cats; therefore, metoclopramide is significantly less effective as a
central antiemetic agent. As a prokinetic, metoclopramide acts peripherally as a 5-HT
4
receptor
agonist. However, the ability of metoclopramide to enhance gastric emptying of solids (com-
pared to liquids) is questionable.
34. How effective are antihistamines for motion sickness in cats?
Although antihistamines are useful for the treatment of motion sickness in dogs, histamine
receptors have not been demonstrated in the CRTZ of cats, making antihistamine therapy much
less effective for motion sickness. Research suggests that 5-HT
1A
receptor agonists (e.g., bus-
pirone) suppress vomiting secondary to motion sickness in cats.
35. Ondansetron is one of the newest antiemetics in veterinary medicine. What is its mech-
anism of action? In what circumstance does it seem particularly effective?
Ondansetron, a 5-HT
3
receptor antagonist, appears to be particularly effective in the control
of chemotherapy-induced emesis. As with other antiemetics, the receptor location and mode of
action may be different for cats (central) and dogs (peripheral).
BIBLIOGRAPHY
I. Andrews PLR, Naylor RJ, Joss RA: Neuropharmacology of emesis and its relevance to anti-emetic ther-
apy. Support Care Cancer 6:197-203,1998
2. Atkins CE, DeFrancesco TC, Coats JR et al: Heartworm infection in cats: 50 cases (1985-1997). 1 Am
Vet Med Assoc 217:355-358, 2000.
3. Broussard Jl), Peterson ME, Fox PR: Changes in clinical and laboratory findings in cats with hyperthy-
roidism from 1983-1993. JAm Vet MedAssoc 206:302-305,1995.
4. Crenshaw KL, Peterson ME: Pretreatment clinical and laboratory evaluation of cats with diabetes melli-
tus: 104 cases (1992-1994). J Am Vet Med Assoc 209:943-949,1996.
5. Dillon R: Clinical significance of feline heartworm disease. Vet Clin North Am Small Animal Pract
28:1547-1565,1998.
6. Guilford, WG, Center SA. Strombeck DR, et al (ed): Strombeck's Small Animal Gastroenterology, 3rd
ed. Philadelphia, W.B. Saunders, 1996, pp 256-260.
7. Hall lA, Washabau RJ: Diagnosis and treatment of gastric motility disorders. Vet Clin North Am Small
Anim Pract 29:377-395, 1999.
8. King GL: Animal models in the study of vomiting. Can J Physiol PharmacoI68:260, 1990.
9. Miller AD: Central mechanisms of vomiting. Digest Dis Sci 44:39S-43S, 1999.
10. Peterson ME, Greco DS, Orth DN: Primary hypoadrenocorticism in ten cats. 1 Vet Intern Med 3:55-58,
1989.
II. Rosenthal FD, Jones C, Lewis SI: Thyrotoxic vomiting. BMl 2:209-211, 1976.
12. Shaker EH, Zawie DA, Garvey MS, et al: Suppurative cholangiohepatitis in a cat. 1 Am Animal Hosp
Assoc 27: 148-150, 1991.
13. Sleisenger,MH (ed): Gastrointestinal Disease: Pathophysiology, Diagnosis, and Management. Phila-
delphia, W.B. Saunders, 1993, pp 509-523.
14. Steiner 1M, Williams DA: Feline exocrine pancreatic disorders. Vet Clin North Am Small Anim Pract
29:551-575,1999.
15. Steiner 1M, Williams DA: Feline pancreatitis. Comp Cont Educ Pract Vet 19:59Q....60 I, 1997.
16. Swift NC, Marks SL, MacLachlan NJ, et al: Evaluation of serum feline trypsin-like immunoreactivity for
the diagnosis of pancreatitis in cats. 1 Am Vet Med Assoc 217:37-42, 2000.
17. Washabau RJ, Elie MS: Antiemetic therapy. In Bonagura JD, Kirk RW (eds): Current Veterinary Therapy
XII. Philadelphia, W.B. Saunders, 1995, pp 679-684.
26. REGURGITATION
Donald S. Westfall, D.V.M.
1. Define regurgitation, dysphagia, and vomiting.
Regurgitation is the passive expulsion of food or fluid from the oral cavity, pharyngeal cavity,
or esophagus. Dysphagia is regurgitation of oral or pharyngeal origin. Vomiting is the forceful
ejection of stomach and proximal duodenal contents through the mouth. Input into the vestibular
system, vagal nerve, chemoreceptor trigger zone, or emetic center can induce vomiting. Localized
diseases usually cause regurgitation of an esophageal origin, although many of these diseases have
systemic consequences. Esophageal diseases are relatively rare in cats compared with dogs.
2. What pathophysiologic mechanisms can lead to esophageal regurgitation?
Regurgitation can be caused by local obstruction to the passage of esophageal contents,
obstruction at the level of the lower esophageal sphincter, or decreased esophageal peristaltic
activity.
Differential Diagnosesof Regurgitation in Cats
Obstructive causes-esophagus
Foreign bodies
Neoplasia
Intraluminal
Squamous cell carcinoma
Sarcoma
Extraluminal
Mediastinal lymphoma
Thymoma
Heart-based tumors
Lung tumors
Strictures
Doxycycline-associated
NSAID-associated (not reported
in cats to date)
Gastroesophageal reflux
Idiopathic
Postanesthetic
Vascular ring anomaly
Persistent right aorticarch (most common)
NSAID = nonsteroidal anti-inflammatory drug.
Obstructive/structural causes
Hiatal hernia
Gastroesophageal intussusception
Gastric neoplasia
Pyloric stenosis
Decreased esophageal peristalsis
Congenitalidiopathicmegaesophagus (Siamesecats)
Acquired idiopathic megaesophagus
Acquired megaesophagus
Esophagitis
Chronic obstructive esophageal disease
Systemic neuromuscular disease
Feline dysautonomia (Key-Gaskell syndrome)
Myasthenia gravis
Lead toxicity
Polymyositis
Polymyopathies
Polyneuropathies
3. What local esophageal obstructions lead to regurgitation?
Local esophageal obstruction can result from foreign bodies (bones, toys), intra- or extralu-
minal neoplasia (Fig. I), esophageal strictures (Figs. I and 2), or vascular ring anomalies (persis-
tent right aortic arch).
4. Describe the pathophysiology of esophageal stricture formation.
Benign esophageal strictures result from esophageal irritation and cause dysphagia and re-
gurgitation. Specific causes include esophageal trauma secondary to foreign body ingestion,
gastroesophageal reflux leading to esophagitis (idiopathic or postanesthetic), chronic vomiting,
and substances that damage the esophageal mucosa. There have been numerous reports of
124
Regurgitation
Figure 1. Lateral bariumcontrastradiograph from
a cat withesophageal squamous cell carcinoma.
125
tablet-associated esophageal strictures in humans and cats. In humans, nonsteroidal anti-inflam-
matory drugs as well as other medications, including tetracycline antibiotics such as doxycycline,
are most common. The Colorado State University Veterinary Teaching Hospital (CSU- VTH) has
documented 7 cats with doxycycline tablet-induced esophageal strictures. The proposed mecha-
nism is failure of adequate esophageal propagation of the tablet into the stomach, leading to
esophageal retention, focal esophagitis, and subsequent esophageal stricture formation from the
caustic nature of the antibiotic.
5. Howdoyoupreventesophageal stricture formation duringtreatment withdoxycycline?
Cats do not successfully propagate tablets given routinely (dry) through the esophagus into
the stomach, as documented by fluoroscopic evaluation of barium tablet administration. Typically,
the tablets remain lodged in the esophagus for 2: 180 seconds, which can lead to esophageal
trauma and, possibly, esophageal stricture formation. Conversely, when cats are given tablets fol-
lowed by 6 ml of water, tablets easily pass into the stomach within 30 seconds. Based on these re-
sults, CSU-VTH recommends that all cats be given 6 ml of water after tablet administration,
particularly when prescribing doxycycline and NSAIDs.
Figure 2. Lateral (A) and ventrodorsal (B) thoracic
radiograph of a cal with suspected congenital mega-
esophagus.
126 Regurgitation
6. What structural abnormalities or obstructions at the level of the lower esophageal
sphincter (LES) lead to regurgitation?
Diseases affecting the LES include hiatal hernias, gastroesophageal intussusception, gastric
neoplasia, and pyloric stenosis. Hiatal hernias are protrusions of the distal esophagus or proximal
stomach through the esophageal hiatus of the diaphragm into the thorax. Gastroesophageal intus-
susceptions are prolapses of the stomach into the lumen of the distal esophagus. Hiatal hernias
and gastroesophageal intussusception are rare in the cat. Esophageal diverticula also are associ-
ated with regurgitation in cats.
7. What is the normal peristaltic activity of the feline esophagus?
The proximal two-thirds of the feline esophagus is composed of striated muscle; the lower
third, which leads to the LES, is composed of smooth muscle. Innervation of both striated and
smooth muscle and the LES is via the vagus nerve and its branches. Coordination of swallowing
involves three stages: oropharyngeal, esophageal, and gastroesophageal. A bolus of food or
liquid is formed in the oropharyngeal stage; this bolus is perpetuated through the upper
esophageal sphincter. The esophageal stage transports the bolus through most of the esophagus
via a primary peristaltic wave, which is initiated by swallowing. Additional primary peristaltic
waves or secondary peristaltic waves transport any residual volume. The gastroesophageal stage
involves transport of the bolus through the LES. Normally, mechanical, neural, and hormonal
factors allow relaxation of the LES. LES pressure is maintained between boluses to prevent
esophageal reflux.
8. What causes decreased esophageal peristaltic activity?
Primary idiopathic congenital megaesophagus can occur in cats, but is rare compared with
dogs (see Fig. 1). Familial congenital megaesophagus and a gastric emptying disorder occur in
Siamese cats. Acquired megaesophagus may be either idiopathic or secondary. Idiopathic ac-
quired megaesophagus is diagnosed by excluding all other known causes of megaesophagus.
Secondary causes include esophagitis, chronic obstructive lesions, and systemic neuromuscular
diseases. Esophagitis of any cause (reflux esophagitis due to esophageal reflux through the LES,
chemical injury, drugs, trauma, or foreign body ingestion) can lead to esophageal motility disor-
ders. Any metabolic, endocrine, or systemic disease with neuromuscular manifestations can theo-
retically affect the esophagus. Examples include feline dysautonomia (Key-Gaskell syndrome),
myasthenia gravis, lead toxicity, polymyositis, polymyopathies, and polyneuropathies. To the
author's knowledge, megaesophagus associated with hypoadrenocorticism, systemic lupus ery-
thematosus, and hypothyroidism has not been documented in cats.
9. How can signalment help to rank the differential list?
Signalment can give hints as to the underlying cause of regurgitation in many cases. For ex-
ample, the incidence of esophageal neoplasia (squamous cell carcinoma) in younger cats is lower
than in older cats. Mediastinal masses associated with lymphoma are more common in younger
cats, wheras thymoma is more common in older cats. Younger cats may be more likely to ingest
foreign bodies than older cats. Typically, regurgitation associated with a persistent right aortic
arch manifests just after weaning.
10. Howcan the history help to rank the ditTerentiallist?
Systemic illnesses leading to muscle weakness and regurgitation often are associated with
concurrent medical problems. A history of doxycycline administration should alert the clinician
to the possibility of tablet-associated esophageal stricture. Likewise, a history of esophageal
trauma (such as foreign body ingestion) or postanesthetic esophageal reflux should result in a
high index of suspicion for esophageal stricture. An acute onset of clinical signs is most consis-
tent with foreign body ingestion; a more insidious course suggests other causes. Timing of the re-
gurgitation after eating also helps to localize the cause of regurgitation. For example,
regurgitation immediately after ingestion of food implies a problem in the proximal esophagus or
Regurgitation 127
oropharynx, whereas delayed regurgitation implies a problem in the distal esophagus. Regurgi-
tation of both solids and liquids implies a more complete obstruction.
11. Outline a diagnostic planto determine thecauseof regurgitation.
If systemic illness is present, complete blood cell count, serum bichemical panel, and urinaly-
sis should beperformed to search for underlying systemic illness that may lead to muscle weakness
and esophageal hypomotility. The most useful information often is obtained by performing barium
contrast radiography (see Fig. 2). It is important to obtain a radiograph immediately after adminis-
tering the contrast material to ensure a diagnostic study if the source of regurgitation is located
proximally. You should use both solid (food mixed with barium) and liquid barium in performing a
study to identify the source of regurgitation. Fluoroscopy can be used as an adjunct procedure to
identify abnormalities in primary and secondary contractions. Manometry and esophageal scintig-
raphy also have been used to evaluate esophageal motility in cases of megaesophagus. If a localized
problem is identified (such as a stricture), endoscopy can obtain more useful information, such as
exact location, extent of disease, and pathogenesis of the disease process. For example, esophagitis
due to esophageal reflux may be diagnosed by visualizing diffuse ulceration at the distal portion of
the esophagus and by documenting a dilated LES. Barium contrast radiography, fluoroscopy, and
endoscopy are also useful in diagnosis of hiatal hernias or gastroesophageal intussusceptions.
12. What treatment options are available for regurgitation?
The treatment of regurgitation depends largely on the underlying cause. Localized obstruc-
tions such as neoplasia, vascular ring anomalies, and esophageal strictures are best treated with
local therapy. Extraluminal compression of the esophagus with mediastinal lymphoma is best
treated with chemotherapy, whereas thymoma is a surgical disease. Intraluminal masses such as
squamous cell carcinoma are best treated with surgery followed by chemotherapy. A persistent
right aortic arch is best treated with surgery (thoracotomy or thoracoscopy). Esophageal stric-
tures can be managed with endoscopy and balloon dilatation or bougienage. The author prefers
balloon dilatation. Esophagitis is treated with sucralfate in a liquid suspension (Y4 gm crushed
and mixed with 6 ml of water orally every 8 hours or 1.0-2.5 ml of 100 mg/ml commercially
available suspension orally every 12hr), which acts as a diffusion barrier to promote mucosal
ulcer healing and an antacid (Hz blocker or proton pump inhibitor). The author prefers famoti-
dine (0.5-1.0 mg/kg orally or intravenously every 24 hours) or omeprazole (0.7 mg/kg orally
every 24 hours). Omeprazole is available only in a 20-mg sustained-release capsule. For adminis-
tration to cats, mix the contents of the capsule in a strip of melted butter in foil and freeze. The
appropriate dose is easily administered by sectioning the butter/omeprazole mixture. For exam-
ple, a 5.7-kg cat should receive 4.0 mg of omeprazole, which is equivalent to one-fifth of the
butter-mixed strip of medication. If the underlying cause is esophageal reflux, further therapy can
be aimed at promoting LES tone and gastric emptying. Metoclopramide (0.2--0.4 mg/kg orally
every 8 hours) or cisapride (0.1-0.5 mg/kg orally every 8 hours) is used most frequently. The
author prefers cisapride, which is more potent than metocloprarnide at the LES and is superior at
promoting gastric emptying. Systemic diseases should be treated specifically.
BIBLIOGRAPHY
I. Graham JP, Lipman AH, Newell SM, et al: Esophageal transit of capsules in clinically normal cats. Am J
Vet Res 61:655-657, 2000.
2. Hoenig M, Mahaffey MB, Parnell PG, et al: Megaesophagus in two cats. J Am Vet Med Assoc
196:763-765,1990.
3. Johnson JR: Diseases of the esophagus. In Scherding RG (ed): The Cat Diseases and Clinical
Management, 2nd ed. NewYork, Churchill Livingstone, 1994, pp 1153-1179.
4. Joseph RJ, Carrillo JM, Lennon VA: Myasthenia gravis in the cat. J Vet Int Med 2:75-79. 1988.
5. Matz ME: Regurgitation: Diagnosis and management. In August JR (ed): Consultations in Feline Internal
Medicine, 2nd ed. Philadelphia, W.B. Saunders, 1994, pp 65-73.
6. Mears EA, Jenkins CC: Canine and feline megaesophagus. Comp Cont Educ Small Anim Pract
19:313-326,1997.
128
Constipation, Obstipation, and Megacolon
7. Melendez LD, Twedt DC, Weyrauch EA, et al: Conservative therapy using balloon dilation for intra-
mural, inflammatory esophageal strictures in dogs and cats: A retrospective study of 23 cases
(1987-1997). Eur 1 Comp GastroenteroI 3:31-36,1998.
8. Melendez LD, Twedt DC: Esophageal strictures secondary to doxycycline administration in 4 cats. Fel
Pract 28:10--12,2000.
9. Moses L, Harpster NK, Beck KA, et al: Esophageal motility dysfunction in cats: A study of 44 cases. J
Am Anim Hosp Assoc 36:309-312, 2000.
10. Patterson Cl: Suspected cases offeline dysautonomia. Vet Rec 134:123, 1994.
I I. Prymak C, Saunders HM, Washbau RJ: Hiatal hernia repair by restoration and stabilization of normal
anatomy:An evaluation in four dogs and one cat. Vet Surg 18:386-391, 1989.
12. Symonds HW, Me Williams P, Thompson H, et al: A cluster of cases of feline dysautonomia (Key-
Gaskell syndrome) in a closed colony of cats. Vet Rec 136:353-355, 1995.
13. Weyrauch EA, Willard MD: Esophagitis and benign esophageal strictures. Comp Cont Educ Small Anim
Pract 20:203-212, 1998.
27. CONSTIPATION, OBSTIPATION,
ANDMEGACOLON
Elyse M. Kent, D.V.M.
1. What differentiates constipation from obstipation?
Constipation is defined as the infrequent or difficult evacuation of feces. It may be acute or
chronic and does not imply a permanent loss of function. Obstipation is intractable or refractory
constipation that has failed to resolve after several courses of medical and dietary therapy. It im-
plies a permanent loss of function.
2. Define dyschezia, tenesmus, and megacolon.
Dyschezia, a term applied to some cats with constipation, refers to difficult or painful evacu-
ation of feces. Cats with constipation or obstipation may exhibit tenesmus, which is defined as
painful or ineffective straining during defecation. Recurring episodes of either constipation or
obstipation may culminate in megacolon, which is defined as chronic constipation with a marked
increase in the diameter of the colon.
3. What are the two pathologic mechanisms by which megacolon can develop?
Megacolon can develop by hypertrophy or dilation. Hypertrophic megacolon results from
obstructive lesions (e.g., malunion of pelvic fractures causing narrowing of the pelvic canal, for-
eign bodies, tumors) and may progress to dilated megacolon. If unchecked, dilated megacolon is
the end-stage result of colonic dysfunction. Cats with idiopathic dilated megacolon have perma-
nent loss of colonic function and frequently also have loss of colonic structure. Colonic dilation
disrupts the coordinated motility patterns of the distal colon and rectum that allow fecal storage.
Dilation also interferes with the large migrating contractions of the colon and rectum that lead to
the defecation reflex.
4. What causes megacolon?
The list of differential diagnoses includes neuromuscular, pharmacologic, obstructive, di-
etary, environmental, metabolic-endocrine, behavioral, and idiopathic causes. Most cases are or-
thopedic, neurologic, or idiopathic in origin. More than 60% of the cases are idiopathic. Spinal
cord or pelvic nerve injuries account for about 6% of cases. About 5% of all cases occur in Manx
cats as a result of congenital sacral and caudal vertebral defects with malformations of the caudal
spinal cord and cauda equina.
Causes of Constipation
129
Dietary: bones or foreign material mixed with feces
Environmental: decreased exercise, dirty litter box or change in type of litter, change of location or
schedule, hospitalization, introductionof newpets
Traumatic: fractured pelvis or hip, dislocated hip, bite wound, or abscess in perineal area
Obstructive: anal stricture, rectal foreign body or tumor, pseudocoprostasis(hair pasted over anus),
healed pelvic fracture causing a narrowed pelvic canal
Neuromuscular: spinal cord diseaseor congenital spinal anomaly(Manxcat), paraplegia, central ner-
vous systemdysfunction, dysautonomia,idiopathicmegacolon(colonicsmoothmuscle dysfunction)
Metabolic-endocrine: hypokalemia, dehydration, generalizeddebility, muscle weakness secondary to
another disease
Pharmacologic: antihistamines, anticholinergics, diurectics, bariumsulfate
5. What anatomic or physiologic alterations cause colonic dysfunction in cats with idio-
pathic megacolon?
Colonic smooth muscle function appears to be impaired in cats with idiopathic megacolon.
In one study, megacolonic smooth muscle developed less isometric stress compared with healthy
controls in response to neurotransmitters (acetylcholine, substance P, and cholecystokinin), mem-
brane depolarization (potassium chloride), and electrical field stimulation. These changes were
observed in both longitudinal and circular smooth muscle in the proximal and distal colon.
Megacolon probably results from a disturbance in the activation of smooth muscle myofilaments.
Smooth muscle cells and myenteric neurons appear histologically normal.
6. What are the clinical findings of megacolon?
Cats with megacolon typically present with a history of fecal obstruction and show signs includ-
ing dyschezia, depression, anorexia, and vomiting. A small amount of liquid feces (possibly contain-
ing mucus or blood) may ooze around a central colonic or rectal fecal mass. Abdominal palpation
reveals a large amount of abnormally firm feces in an enlarged colon. Other signs suggestive of
spinal cord or pelvic injury may be present, including decreased tone and sensation of the tail, de-
creased or absent anal tone, atonic bladder with urinary incontinence, and paraparesis or paraplegia.
7. Describe the minimal diagnostic plan for cats with obstipation or suspected megacolon.
I. Complete blood count, serum biochemical panel, and urinalysis should be evaluated.
Although changes in laboratory parameters are unlikely to be found, dehydration and hy-
pokalemia may be observed occasionally.
2. Digital rectal palpation should be performed, preferably in an anesthetized cat.
3. Abdominal radiographs should be made in all recurrent cases (Fig. I). Possible predispos-
ing factors such as radiopaque foreign material, intra- or extraluminal colonic masses, pelvic frac-
tures, and spinal canal abnormalities may be seen on radiographs. However, radiographic features
cannot differentiate between constipation, obstipation, and idiopathic megacolon in some cases.
8. What additional studies may be ordered?
I. Abdominal ultrasound, proctoscopy, and colonoscopy are used to defme mass lesions, in-
flammatory lesions, strictures, or diverticula in greater detail.
2. Barium enemas are helpful in delineating masses, strictures, or tumors if colonoscopy is
not available.
3. Cerebrospinal fluid taps, myelograms, computed tomography, or magnetic resonance
imaging should be considered (when financially practical) if the cat has neurologic signs.
4. If masses or lymphadenopathy is suspected, fine-needle aspiration with cytology and ab-
dominal radiographs are recommended. Colonic impaction may be confused with gastrointesti-
nallymphoma. Masses or enlarged mesenteric lymph nodes are often difficult to differentiate
130 Constipation. Obstipation, and Megacolon
Figure 1. Abdominal radiographs of a cat with constipation. A.
Ventrodorsal view. B. Lateral view.
from impacted feces by palpation of the abdomen alone. Megacolon is identified radiographi-
cally by extreme dilation of the colon on survey radiographs (Fig. 2). Obstructive lesions causing
secondary megacolon (e.g., tumors, strictures, or old pelvic fractures) may be visible on survey
abdominal radiographs after multiple enemas, anesthesia, and manual removal of the fecal mass.
9. How should the rrrst episode of constipation be managed?
A solitary episode of constipation may resolve spontaneously. However, most practitioners
administer an enema to provide immediate relief of discomfort. Warmwater enemas are most
often used, but dilute diocytl sodium succinate (DSS; 10% in warm water) is also effective as an
emollient enema. Several other types of enema solutions are commonly used, such as mineral oil,
Figure2. Abdominal radiographs of a cat with idiopathic megacolon.
A. Ventrodorsal view. B. Lateral view
Constipation. Obstipation, and Megacolon 131
mild soap (without hexachlorophene, which is potentially neurotoxic), warm isotonic saline, or
lactulose. The volume of DSS, mineral oil, or lactulose in an enema solution should not exceed
5-10 ml/cat. It is safest to use a well-lubricated, ID-12-French soft red rubber catheter or feeding
tube attached to a 60-ml syringe to administer an enema. The soft tube can be "threaded" inward
gently to reduce mucosal trauma. Do not mix DSS and mineral oil in an enema solution because
DSS increases mucosal absorption of mineral oil. A single episode of constipation does not war-
rant management at home other than observation of defecation by the owner in an effort to detect
any signs of recurrent constipation. Sodium phosphate enemas (prepackaged enemas for humans)
are contraindicated in cats because they induce hypernatremia, hyperphosphatemia, and hypocal-
cemia that may be life-threatening.
10. What therapy is used for recurrent episodes of constipation or idiopathic megacolon?
I. Mild-to-moderate fecal impaction that recurs requires initial relief of the impaction by
enemas and manual evacuation in the hospital. The dangers of having clients administer enemas
to cats at home include the possibility of perforation of the rectum or colon (too much intralumi-
nal pressure) and owner injury due to poor restraint techniques.
2. Take steps to improve both fecal hydration and bulk at home. Advise owners to increase
fiber content in the eat's diet through fiber-enriched food or fiber supplements (cellulose, methyl-
cellulose, psyllium, bran, pumpkin). Fiber helps to prevent constipation by increasing fecal water
content, decreasing intestinal transit time, and increasing the frequency of defecation. All cats
must be well hydrated before initiating fiber supplementation to maximize therapeutic effects
and prevent exacerbation of impaction by mixing of dry fiber with dry feces. Premeasured doses
of powdered psyllium are available in capsule form and as chewable treats (tablets). Bran can be
added to food but is not palatable to most cats. Canned pumpkin is somewhat palatable when
added to food.
3. Periodic enemas may be administered intermittently if a cat shows signs of impaction or
if no bowel movements are observed over several days.
4. Various types of laxatives are recommended, and each should beused singly or in combi-
nation to effect in a given patient.
5. Colonic prokinetic drugs or motility agents (ranitidine, cisapride, nizatidine) help to stim-
ulate colonic propulsive motility, some via stimulation of colonic smooth muscle.
11. Describe the various types of laxatives and their indications.
Emollient laxatives (e.g., DSS), lubricant laxatives (e.g., mineral oil or petrolatum), stimu-
lant laxatives (e.g., bisacodyl), saline laxatives (e.g., magnesium citrate), and hyperosmotic laxa-
tives (lactulose) are effective in some patients. Bisacodyl is classified as a stimulant laxative and
tends to work well in most cats. It is available over the counter and produces its effect by stimu-
lating colonic smooth muscle and the myenteric plexus to cause peristaltic contractions.
Bisacodyl is often the laxative of choice, combined with fiber, for control of mild-to-moderate
constipation. Hyperosmotic laxatives (e.g., lactulose) are effective alone in some cats or in com-
bination with increased fiber and possibly additional laxatives. Osmotic and emollient laxatives
are irritating to colonic mucosa and should not be used before endoscopic procedures. Mineral
oil and flavored petrolatum are helpful only in the mildest cases of constipation. Chronic use of
lubricant laxatives may lead to malabsorption of fat-soluble vitamins. Mineral oil must be admin-
istered orally with caution because it can cause "lipid-aspiration pneumonia" if it is aspirated.
12. What prokinetic drugs are available?
Oral cisapride has been the author's choice for the past several years but currently is not
available because of toxicity in humans. Ranitidine and nizatidine (Hz receptor antagonists) stim-
ulate motility by increasing the amount of acetylcholine available to bind smooth muscle mus-
carinic cholinergic receptors. Erythromycin stimulates colonic motility in dogs but has no such
effect in cats. The prokinetic effect of metoclopramide is seen only in the proximal gastrointesti-
nal tract, not in the colon.
132 Constipation, Obstipation, and Megacolon
13. Summarize the medical therapy for feline constipation and obstipation.
DRUGCLASSIFICATIONANDEXAMPLE
Enemas
Warmtap water
Warmisotonic saline
Dioctyl sodium sulfosuccinate
Mineral oil
Lactulose
Oral laxatives
Bulk laxatives
Psyllium
Canned pumpkin
Coarse wheat bran
Emollient laxatives
Dioctyl calcium sulfosuccinate
Lubricant laxatives
Mineral oil
Petrolatum
Hyperosmotic laxative
Lactulose
Stimulant laxative
Bisacodyl
Prokinetic agents
Ranitidine
Nizatidine
DOSE
5-10 ml/kg
5-10 ml/kg
5-10 mlIcat
250 mg (12 ml) given per rectumas needed (prepackaged)
5-lOmVcat
5-10 rnI/cat
1-4 tsp mixed with food every 12-24 hr
1-4 tbsp mixed with food every 24 hr
1-2 tbsp mixed with food every 24 hr
50 mg/cat orally every 24 hr
50 mg/cat orally every 12-24 hr as needed
10-25 ml/cat orally every 24 hr
1-5 ml/cat orally every 24 hr
0.5 mVkgorally every 8-12 hr as needed
5 mg/cat orally every 24 hr
1.0-2.0 mg/kg orally every 8-12 hr
2.5-5.0 mg/kg orally every 24 hr
Modified from WashabauRJ, Hasler AH: Constipation, obstipation, and megacolon. In August JR (ed):
Consultations in FelineInternalMedicine, vol. 3. Philadelphia, WB. Saunders, 1996, pp 104-111, with per-
mission.
14. How should severe, protracted cases offecal impaction be managed?
Most cats with severe, protracted fecal impaction need to be hospitalized to correct fluid and
electrolyte abnormalities and to allow sufficient time for repeated enemas and multiple manual
evacuations of feces. Fecal concretions can be removed digitally with a well-lubricated, gloved,
hooked index finger or with sponge forceps. General anesthesia is required for manual evacua-
tion in most cases. Rapid administration of an enema may induce vomiting, even in an anes-
thetized cat. To prevent aspiration of vomitus, place the head in a "nose-down" position and
intubate the cat with an inflated cuff on the endotracheal tube. Sometimes it is helpful to instill
40-60 ml of warmwater or dilute DSS (10% solution) and subsequently "knead" the hard feces
through the abdominal wall and then "milk" the softened feces toward the rectum and anus
before attempting to grasp or pull out the feces. Be as gentle as possible while breaking down and
removing fecal concretions. Some colonic and rectal mucosal bleeding is common during this
procedure. In the most severely impacted patients, alternating enemas and manual fecal evacua-
tion are best performed over 1-3 days.
15. Describe the home medical management of severe cases of fecal impaction,
Fiber (preferably in diet)
Hyperosmotic (lactulose) or stimulant laxative (bisacodyl)
Prokinetic agent (ranitidine or others)
Close monitoring for frequency and consistency of bowel movements
Evaluate the status of the cat and palpate for fecal concretions twice monthly at the start of
the medical management program to assess success or failure of therapy.
16. Summarize the approach to management of constipation in cats.
Moderate or
Recurrent
Constipation
133
Figure 3. Therapeutic approach to constipated cats. (Adapted from Washabau RJ, Hasler AH: Constipation.
obstipation, and megacolon. In August JR (ed): Consultations in Feline Internal Medicine, vol. 3. Phila-
delphia, WB. Saunders, 1996, pp 104-111, with pennission.)
17. When should a colectomy be recommended?
Colectomy should be considered in any cat suffering from obstipation or idiopathic mega-
colon that is unresponsive to medical therapy. The objective of the surgery is to remove all of the
colon, except for a short distal segment necessary to reestablish intestinal continuity (Fig. 4).
Preservation of the ileocolic valve is controversial because the valve minimizes access of colonic
bacteria to the small intestine. Removal of the ileocolic valve may lead to bacterial overgrowth in
the small intestine along with steatorrhea and deconjugation of bile salts.
After surgery, most cats initially exhibit tenesmus and have dark, tarry stools. The diar-
rhea gradually changes to soft, formed stool over 6-8 weeks. Occasionally, cats produce semi-
formed feces permanently. Studies have indicated that enteric function is similar in normal
cats and cats that have had a colectomy. The most common complication of colectomy is con-
stipation. Usually, the constipation can be easily managed by a high-fiber diet, laxatives, and
DSS.
Figure 4. Partial colectomy. Vascular
ligations and level of resection with (I)
preservation of the ileocolic valve, or
colocolostomy (squares) and (2) re-
moval of the ileocolic valve and part of
the ileum, or ileocolostomy (circles).
I AOlla
(lIIJdalMtIOl1lMc

134 Hyperbilirubinemia and Icterus: Initial Diagnostic Approach
18. What is the prognosis for cats with chronic constipation or megacolon?
The prognosis is guarded for cats receiving medical treatment alone. Therapeutic success or
failure depends on the severity and stage of disease at first presentation and client compliance in
persisting with ongoing therapy at home. The prognosis for patients treated with subtotal colec-
tomy is good. As soon as it is evident that colonic dysfunction is irreversible, colectomy is the
treatment of choice. Owners perceive the long-term results of colectomy as good to excellent.
Most clients say that the eat's personality improves postoperatively and that behavior returns to
what it was before the onset of constipation.
BIBLIOGRAPHY
1. Burrows CF: Constipation and megacolon. In August lR (ed): Consultations in Feline Internal Medicine,
vol 2. Philadelphia, WB. Saunders, 1994, pp 445-449.
2. Gregory CR, Guilford WG, Berry CR, et aI: Enteric function in cats after subtotal colectomy for treat-
ment of megacolon. Vet Surg 19:216-220, 1990.
3. Hilsenroth R: Medical therapy for diseases of gastronintestinal motility in cats. Feline Pract 27:24, 1999.
4. Holt D, Johnston DE: Idiopathic megacolon in cats. Compend Cont Educ Pract Vet 13:1411-1416, 1991.
5. Rosin E: Megacolon in cats-the role of colectomy. Vet Clin North Am Small Anim Pract 23:587-593,
1993.
6. Washabau RJ, Hall lA: Diagnosis and management of gastrointestinal motility disorders in dogs and
cats. Compend Cont Educ Pract Vet 19:730-734, 1997.
7. Washabau RI, Hasler AH: Constipation, obstipation, and megacolon. In AugustJR (ed): Consultations in
Feline Internal Medicine, vol. 3. Philadelphia, WB. Saunders, 1996, pp 104-111.
8. Washabau RI, Stalis IH: Alterations in colonic smooth muscle function in cats with megacolon. Am J Vet
Res 57:580-587, 1996.
9. Washabau Rl, Holt D: Pathogenesis, diagnosis and therapy of feline idiopathic megacolon. Vet Clin
North Am Small Anim Pract 29:589-601, 1999.
10. Washabau RJ, Holt D: Feline constipation and idiopathic megacolon. In Bonagura ID (ed): Kirk's
Current Veterinary Therapy XIII, Small Animal Practice. Philadelphia, WB. Saunders, 2000, pp
648-652.
I l. Zoran DL: Diet and drugs: The keys to managing feline colonic disease. Compend Cont Educ Pract Vel
21:744-747, 1999.
28. HYPERBILIRUBINEMIA ANDICTERUS:
INITIAL DIAGNOSTIC APPROACH
1. Define hyperbilirubinemia and icterus.
Hyperbilirubinemia is defined as serum total bilirubin concentrations greater than the
normal range. When hyperbilirubinemia is severe enough, a characteristic yellowing of tissues
known as icterus can be detected on physical examination. Icterus generally is detected when
serum bilirubin concentrations are > 2 mg/dl and is most evident on the sclera and mucous mem-
branes. After serum bilirubin concentrations normalize, it may take days for icterus to resolve.
2. What causes hyperbilirubinemia?
Hyperbilirubinemia can be grouped into prehepatic, hepatic, and posthepatic causes.
Hemolysis of red blood cells is the cause of prehepatic hyperbilirubinemia (see Chapter 72).
Multiple primary hepatic diseases result in hyperbilirubinemia. In approximately 90% of cases,
one of the following is found to be the cause; hepatic lipidosis, cholangiohepatitis/cholangitis
syndrome, feline infectious peritonitis virus, or feline leukemia-associated hepatic lymphoma.
Posthepatic hyperbilirubinemia can result from intrahepatic cholestasis or extrahepatic bile duct
Hyperbilirubinemia and Icterus: Initial Diagnostic Approach 135
obstruction. Extrahepatic bile duct obstruction generally results from biliary tract neoplasia. pan-
creatitis, or duodenal disease.
Primary Differential Diagnoses for Hyperbilirubinemia and Icterus
Prehepatic
Haemobartonella felis
FeLV-associated immune-mediated hemolytic anemia
Cytauxzoon felis
Vaccine-induced, drug-induced, or idiopathic immune-mediated hemolytic anemia
Hepatic
Bacterial cholangiohepatitis (suppurative)
Immune-mediated cholangiohepatitis (nonsuppurative)
Hepatic lipidosis (idiopathic or associated with diabetes mellitus)
FeLV-associated lymphosarcoma
Toxoplasma gondii
Hepatic abscessation
Hepatotoxins (acetaminophen)
Epithelial neoplasia
Hyperthyroidism
Posthepatic
Bile duct neoplasia
Pancreatitis
Duodenal disease
Cholelithiasis
Platynosomum concinnum (liver fluke, Florida and Hawaii)
FeLV =felineleukemia virus.
3. How can the signalment help to rank the ditTerentiallist?
Young cats are more likely to have congenital liver diseases such as portosystemic shunts;
old cats are more likely to have hepatic neoplasia. Effusive feline infectious peritonitis (FIP) is
more common in young cats than old cats. Hyperthyroidism is more common in older cats.
4. How can the history help to rank the ditTerentiallist?
Cats with toxoplasmosis have a history of hunting, particularly mice. Cats with haemobar-
tonellosis often have a history of exposure to Ctenocephalides spp. or other cats. Cats with cytau-
zoonosis come from the southern states and may have a history of Dermacentor tick infestation.
Cats with pancreatitis often have vomiting, weight loss, and an intermittent, vague history. Cats
with FIP generally have polysystemic disease. Cats with idiopathic lipidosis are often previously
obese and have had recent stressful events in their lives.
5. How can the physical examination help to rank the differential list?
Most cats with prehepatic disease have pale mucus membranes and elevated heart and respi-
ratory rates. Hepatic neoplasia generally results in hepatomegaly. In addition, cats with acute he-
patic or posthepatic diseases often have hepatomegaly. The liver may become smaller with
chronicity if inflammation leads to fibrosis and cirrhosis. Cats with FIP or toxoplasmosis may
have conconcurrent uveitis. Fever is detected in many cats with bacterial hepatic diseases, FIP,
toxoplasmosis, haemobartonellosis, and pancreatitis. Splenomegaly is commonly palpated in
cats with icterus due to lymphoma, mastocytosis, and haemobartonellosis.
6. Describe the initial diagnostic plan for most cats with icterus.
Packed cell volume is assessed immediately to determine whether prehepatic icterus is
likely. Complete blood count, serum biochemical panel, urinalysis, feline leukemia virus antigen
136 Hyperbilirubinemia and Icterus: Initial Diagnostic Approach
test, feline immunodeficiency virus antibody test, and total T4 concentration (cats> 5 years old)
are indicated for the initial assessment of icteric cats. Fecal flotation or sedimentation should be
included in areas endemic for liver flukes. Urinalysis is important; normal cats do not have biliru-
binuria. Hemolysis of red blood cells due to traumatic collection may cause false increases in
bilirubin concentrations on many blood chemistry machines. If serum bilirubin is elevated but
urine bilirubin is negative, the serum result is probably a laboratory error.
7. How do patterns of hepatic enzyme activities aid in the ranking of differential diag-
noses?
Differences in hepatic enzyme activities have some predictive value. In general, cats with
lipidosis generally have greater activities of alkaline phosphatase (ALP) than alanine aminotrans-
ferase (ALT), whereas cats with the cholangiohepatitis/cholangitis complex generally have
greater activities of ALT (see Chapter 29). Cats with lipidosis generally have increased ALP ac-
tivity but normal gamma-glutamyl transferase (GGT) activity (see Chapter 30).
8. Can routine biochemical testing document posthepatic diseases?
No serum biochemical test can document posthepatic disease. However, if the magnitude of
the hyperbilirubinemia is great (> 10 mg/dl) but clinical signs are minimal, posthepatic disease is
likely. If bilirubin but not urobilinogen is present in urine, posthepatic disease is likely. The
serum total T4 concentration is usually elevated in cats with hyperthyroidism.
9. Is measurement of serum bile acids indicated in cats with hyperbilirubinemia or
icterus?
Measurement of pre- and postprandial bile acids is indicated only in the evaluation of cats
with suspected hepatic disease that have normal serum bilirubin concentrations.
10. Howdo imaging techniques aid in the ranking of differential diagnoses?
Abdominal radiographs can be used to confirm hepatic size, to distinguish between diffuse
or focal disease, to assess peritoneal effusions, and to assess evidence of pancreatitis. Hepatic and
pancreatic ultrasound exams are beneficial for evaluating parenchymal tissues and assessing peri-
toneal fluid, bile duct obstruction, and gallbladder abnormalities. If peritoneal effusion is present,
abdominal pericentesis is indicated. Ultrasound also can be used to guide aspirates or biopsies of
hepatic tissues.
11. When are hepatic aspirates or biopsies indicated? What techniques should be used?
Hepatic aspirates or biopsies can be obtained percutaneously on the basis of landmarks or
palpation or with ultrasound guidance, by laparoscopy, or by exploratory laparotomy. If the
liver is enlarged, percutaneous biopsy by palpation or ultrasound guidance is generally easy. If
the liver is small, laparoscopy or laparotomy is a safer technique. Laparotomy should be per-
formed if extrahepatic bile duct obstruction caused by something other than pancreatitis is sus-
pected. Activated clotting time (ACT) and platelet estimate should be performed in all
hyperbilirubinemic cats before hepatic aspiration or biopsy.
Icteric cats with cholestatic liver disease develop vitamin K absence and subsequently
decreased concentrations of active factors II, VII, IX, and X. If the ACT is prolonged, ad-
minister vitamin K] (I mglkg subcutaneously) and recheck in 12 hours. Cats with coagula-
tion problems due to decreased factor production from hepatic insufficiency do not respond
to vitamin K treatment. Hepatic aspiration can lead to a definitive diagnosis of hepatic lym-
phoma and mastocytosis and a presumptive diagnosis of hepatic lipidosis. Hepatic biopsy is
the optimal procedure for all other hepatic diseases. Biopsies for histopathologic evaluation,
aerobic culture, anaerobic culture, and antimicrobial susceptibility should be performed. If
the bile or gallbladder wall appears thickened on ultrasonic evaluation, bile should be aspi-
rated for culture.
Cholangitis/Cholangiohepatitis Complex
Laparoscopic appearanceof Iymphocytic-plasmacytic hepatitisin a cat.
137
12. Describe the initial treatment plan for icteric cats.
Intravenous fluids as supportive care are indicated in most cats, particularly if dehydration is
occurring. The primary disease should then be treated.
BIBLIOGRAPHY
BunchSE: Clinical manifestations ofhepatobiliary disease. In NelsonRW, CoutoGC(eds): Small Animal
Internal Medicine,2nd ed. Philadelphia, Mosby, 1998, pp 476-486.
2. WeissDJ, ArmstrongPJ, Gagne 1M: Feline cholangiohepatitis. In Bonaguraill (ed): Current Veterinary
Therapy. Philadelphia, W.B. Saunders,2000, pp 672-674.
29. CHOLANGITIS/CHOLANGIOHEPATITIS
COMPLEX
Margie Scherk, D.V.M.
1. Define cholangitis and cholangiohepatitis.
Cbolangitis is inflammation of the biliary tract. Cholangiobepatitis refers to inflammation
of the peribiliary hepatocytes as well as the biliary tract. The biliary tract is composed of the bile
canaliculi, collecting ducts, bile duct, and gallbladder. When both conditions are present, the
term cbolangitislcholangiobepatitis complex (CCHC) is often used.
2. What is unique about the anatomy of the feline biliary tree? Why is it significant?
In cats, the pancreatic duct enters the common bile duct before it opens into the duodenum.
When disease (e.g., inflammation, infection, neoplasia, stasis) is present in the small bowel, it
may ascend into the common bile duct and from there affect the pancreas and the rest of the bil-
iary tree. Similarly, disease in the biliary tree or pancreas may affect the other two regions. This
scenario is termed triaditis.
138 Cholangitis/Cholangiohepatitis Complex
3. What are the most common forms of CCHC?
The most common forms are suppurative and nonsuppurative. Histologically, neutrophils are
the predominant cell infiltrate in the suppurative form, whereas lymphocytes and plasma cells are
the predominant cell infiltrate in the nonsuppurative form.
4. How is a diagnosis of CCHC made clinically?
The clinical presentation includes a vague history of inappetence, anorexia, and lethargy as
well as possible nausea, vomiting, diarrhea, and weight loss. The signs may have a chronic inter-
mittent occurrence. Physical examination may reveal signs of dehydration, weight loss, muscle
wasting, icterus, salivation, palpable liver margins, and cranial abdominal tenderness or firmness.
Suppurative and nonsuppurative CCHC cannot be differentiated on the basis of history and phys-
ical examination alone; both forms mayor may not present with an elevated temperature.
5, What minimal database should be performed to help make the diagnosis of CCHC?
Complete blood cell count, serum biochemical panel, urinalysis, and blood pressure evalua-
tion are indicated initially. These tests help to differentiate CCHC from other conditions but cannot
be used for definitive diagnosis. An inflammatory leukogram increases the likelihood of a suppura-
tive condition. As with any chronic, inflammatory condition, nonregenerative anemia and hyperglob-
ulinemia may be present. Hepatic disease may change red cell morphology, resulting in the presence
of schistocytes, blister cells, elliptocytes, acanthocytes, or keratocytes. If hepatic insufficiency devel-
ops from chronic inflammation, red blood cell microcytosis and thrombocytosis may bepresent.
Cats with CCHC often have hyperbilirubinemia and bilirubinuria, but these findings do not
differentiate the conditions from other hepatic, prehepatic or posthepatic causes of icterus. In pa-
tients with bilirubinuria, lack of urobilinogen should increase suspicion of extrahepatic bile duct
obstruction. Serum alkaline phosphatase (ALP), alanine transferase (ALT), and gamma glutamyl
transferase (GGT) may be increased to varying degrees but do not distinguish between suppura-
tive and nonsuppurative CCHC. Cats with hepatic lipidosis usually have markedly increased ALP
activity compared with ALT activity and nonnal GGT activity (see Chapter 30). In contrast, cats
with CCHC usually have ALP and ALT increases of equal magnitude, or the increase is greater in
ALT than ALP; GGT activity is usually increased as well.
Some patients may have chronic CCHC, resulting in decreased functional liver mass; there-
fore, increases in ALT, ALP, GGT or bilirubin may not occur. There may be variable changes in
albumin, glucose, blood urea nitrogen, and cholesterol. If you believe that liver disease is possi-
ble, a liver function test is indicated. The combination of pre- and postprandial serum bile acid
measurement is used most frequently to assess liver function.
6. What further tests help to make a definitive diagnosis of CCHC?
Ultrasound of the abdomen is ideal before obtaining biopsies of the liver. It allows determi-
nation of the extent of the disease process and determines whether the disease is focal or general-
ized, which helps you advise the client about the best biopsy method and which tissues should be
sampled. Ultrasound also allows visualization of the pancreas and may indicate whether the duo-
denum is involved. Hepatic fine-needle aspiration (FNA) can lead to a definitive diagnosis of he-
patic lymphoma and mastocytosis and a presumptive diagnosis of hepatic lipidosis. Hepatic
biopsy is the optimal procedure for all other hepatic diseases, including CCHC (see Chapter 28).
7. Why is hepatic biopsy preferred over FNA for CCHC?
If you were blind-folded and told to sample an apple pie with a drinking straw, the sample
sucked up through the straw would be limited; you would get mush and liquid that tastes of
apples. With FNA. you are restricted in what you harvest, and the limited sample is mutilated by
the aspiration action and slide preparation. On the other hand, if you were to take a full-thickness
piece of pie, you would recognize the crust, chunks of apples, apple-tasting mush, and cheddar
cheese. Some types of cells do not exfoliate readily (e.g., mesenchymal neoplasias such as fi-
brosarcoma). With FNA you get only a cytologic diagnosis of whatever cells are sampled easily
Cholangitis/Cholangiohepatitis Complex 139
and may not see a real picture of the underlying disease process. In addition, orientation of the
cellular reaction within tissue is critical in differentiating what role neutrophils or lymphocytes
play. For example, peribiliary inflammation and periportal inflammation define different disease
processes and may indicate different therapy and different prognosis.
8. Whathepaticbiopsytechniques are preferred for CCHC?
Before the liver is aspirated or biopsied, a platelet count and factor function test or a PIVKA
(protein induced by vitamin K absence or antagonism) test should be performed (see Chapter
71). Hepatic tissue can beobtained percutaneously using landmarks or with ultrasound guidance
via laparoscopy or laparotomy. Percutaneous techniques usually use Tru-cut needles, which
obtain tissues of superior quality compared with FNA, but often result in the collection of small,
broken samples compared with wedge biopsies. They do not allow direct visualization of the
liver and do not contribute to hemostasis. With laparoscopy, part of the hepatic parenchyma can
bevisualized, large biopsies can bemade, the pancreas can bebiopsied (if indicated), and hemo-
stasis can be applied (if required). However, special equipment is required. Surgically obtained
biopsies have many advantages. The entire biliary tree can be examined, the gallbladder can be
palpated, expressed, and aspirated for culture and sensitivity, and both the duodenum and pan-
creas can be biopsied in cases of suspected triaditis. Tissue obtained through biopsy should be
submitted for histopathologic evaluation as well as aerobic and anaerobic bacterial culture and
antimicrobial susceptibility.
9. Howdo suppurative andnonsuppurative CCHCdifferhistologically?
Changes associated with suppurative CCHC include infiltrates of nondegenerate and degen-
erate neutrophils within dilated intrahepatic bile ducts, canaliculi, and hepatic parenchyma. The
adjacent tissues (duct lining) have varying degrees of fibrosis, but usually it is minimal. In cases
with suppurative cholangitis, Escherichia coli, Clostridium spp., Bacteroides spp., Actinomyces
spp., and alpha-hemolytic Streptococcus spp. are often cultured. Nonsuppurative CCHC has ag-
gregates of inflammatory cells (lymphocytes, plasma cells, eosinophils, and some neutrophils) in
portal regions and around the bile ducts. Fibrosis also may be present.
10. Howis suppurative CCHC treated?
Wherever possible, underlying or concurrent problems, such as inflammatory bowel disease,
pancreatitis, liver flukes, or hepatic lipidosis, should be identified and treated. Suppurative
CCHC requires appropriate antimicrobial therapy. If a culture of liver tissue or bile was obtained,
choice of antimicrobial should be based on the sensitivity profile. While awaiting culture results
or if treating empirically, choose an antibiotic that concentrates in the liver and biliary system
and is tolerated by cats and that the client will be able to administer. Therapy is required for a
minimum of 6-8 weeks and perhaps as long as 6 months. Appropriate choices include penicillins
(ampicillin, amoxiciIIin, or amoxicillin-clavulanate), first- or second-generation cephalosporins.
or a fluoroquinolone. Because anaerobic bacteria are often present, penicillins, cephalosporins,
or metronidazole often is used in combination with fluoroquinolones, particularly if evidence of
sepsis exists. Metronidazole also may be beneficial for its immune-modulating properties, partic-
ularly if inflammatory bowel disease exists concurrently. Glucocorticoids should be avoided
except in cats that fail to respond to antimicrobial therapy.
11. Whatdiet is recommended for nonsuppurative CCHC? ?
Lymphocytic/plasmacytic disorders like nonsuppurative CCHC require elimination of aller-
gens, wherever possible, as well as modulation of the immune response. Thus, an enteric bland
diet, which has limited antigens and low residue and is calorie-dense, is advisable once the pa-
tient is eating well. Some diets may include omega-6 and omega-3 fatty acids in a 5: 1 ratio,
which has an anti-inflammatory effect. Protein restriction is not required unless the patient is
encephalopathic. The fact that the cat is eating is more important than what the cat eats (see
Chapter 62).
140 Cholangitis/Cholangiohepatitis Complex
12. What drugs are used to treat nonsuppurative CCHC?
Glucocorticoids, such as prednisone or prednisolone, are the cornerstone of therapy of lym-
phocytic/plasmacytic disorders in cats. Prednisolone may be more effective because it requires
less hepatic biotransformation than prednisone. As with inflammatory bowel disease, it is impor-
tant to start with a high enough dose to suppress the inflammatory response. Prednisone and
prednisolone, 2-4 rng/kg orally every 12 hours for I month or until clinical remission is
achieved-are commonly used. The dose is then tapered to 0.5 mg/kg orally every 48 hours over
2-3 months, if possible (see Chapter 23).
Metronidazole often is used concurrently for its anaerobic bacterial spectrum as well as its
immune-modulating properties. At oral doses of 7.5 mg/kg every 12 hours, it can be used for
long periods (months) in conjunction with glucocorticoids. Higher doses should be avoided be-
cause metronidazole is metabolized in the liver and has the potential for hepatotoxicity.
Cats with sclerosing CCHS do not respond to prednisolone, metronidazole, and ursodeoxy-
cholic acid alone; thus, adjunctive therapies such as methotrexate may be tried. Although treat-
ment with chlorambucil or azothioprine has not been helpful in sclerotic cases, both agents may
be tried as alternatives or adjunctive therapies in nonsclerotic nonsuppurative CCHC when pred-
nisolone, metronidazole, and ursodeoxycholic acid do not achieve clinical improvement.
Drugs Used in the Management of CCHC
DRUG
Amoxicillin
Amoxicillinlclavulanate
Ampicillin
Azathioprine
Cefoxitin
CephaIexin
Chlorambucil
Enrofloxacin
Methorexate
Metronidazole
Prednisolone
Taurine
Ursodeoxycholic acid
Vitamin BI (thiamine)
VitaminB12 (cobalamin)
VitaminE
Vitamin K
1
STARTING DOSES
11-22 mglkg PO every 8-12 hr
15 mglkg PO every 8 hr
20-40 mglkg PO every 8 hr
0.3 mglkg PO every 48 hr
30 mglkg IV every 6--8 hr
22-35 mg/kg PO every 12hr
5-20 mglkg PO or 1Mevery 24 hr
0.13 mg/cat every 12 hr x 3 doses, repeated once weekly
7.5-10 mg/kg PO every 12 hr
2-4 mglkg PO every 12 hr
250 mg/cat PO every 12-24hr
15rng/kg PO every 24 hr
50-100 J.L'cat PO every 24 hr
100--200 IV/day PO
0.5-1.0 mglkg SC every 24 hr for 3-4 days; then once weekly
PO=orally, IV=intravenously, 1M=intramuscularly, SC=subcutaneously.
13. What treatments are used for both suppurative and nonsuppurative forms of CCHC?
Supportive care Ursodeoxycholic acid
Subcutaneous administration of vitamin K
1
Vitamin E
Water-soluble vitamin B complex
14. What are the essential elements of supportive care?
Supportive care includes fluid therapy to normalize electrolytes and acid base imbalances as
well as to re-hydrate and correct hypovolemia. Inappetant cats are generally hypokalemic, which
should be corrected. Nutritional support cannot be overemphasized (see Chapter 62). Placement
of a feeding tube may be necessary. Cats require approximately 60-80 kcallkg/day. If a cat is
vomiting and antiemetic therapy is ineffective, feeding of smaller meals more frequently over the
24-hour period, continuous trickle feeding through a feeding tube, or total parenteral nutrition
may be required.
Cholangitis/Cholangiohepatitis Complex 141
15. Why is subcutaneous vitamin K
1
recommended?
Vitamin K is absorbed in the small bowel and recycled in the liver. Cats with liver diseases
are often inappetent and do not ingest vitamin K. Because of the severe cholestasis in cats with
CCHC, fat-soluble vitamins, including vitamin K, are not readily absorbed. In addition, cats with
CCHC may have altered mucosal permeability due to bacterial colonization and may have de-
creased or absent vitamin K epoxidase activity in the liver.
16. What is the role of water-soluble vitamin B complex?
Addition of a water-soluble vitamin B complex to intravenous fluids or daily oral adminis-
tration is recommended because B vitamins are minimally stored and inappetence reduces their
availability. In addition, cats with liver failure and polyuria lose water-soluble vitamins in the
urine. Cobalamin deficiency may playa role in hepatic lipidosis; lipidosis often occurs concur-
rently with CCHC (see Chapter 30). Cervical ventroflexion may indicate a deficiency in thi-
amine, which is easily corrected.
17. Discuss the effects of ursodeoxycholic acid.
Ursodeoxycholic acid (Actigall, Ciba-Geigy) is a therapeutic bile acid used to alleviate
sludged bile as well as to ease bile flow in swollen hepatocytes or narrowed canaliculi. It carries
IgA and is believed to have hepatoprotective effects. It should be used in cats with hepatic lipido-
sis or inflammatory liver diseases. It is contraindicated in complete bile duct obstruction; be sure
to check for the presence of urobilinogen. In cats administered ursodeoxycholic acid, taurine
supplementation is advised for conjugation.
18. Why is vitamin E supplementation recommended?
Because of its antioxidative properties.
19. What is the most serious complication of CCHC?
Severe, chronic CCHC can lead to hepatic insufficiency, which may result in hepatic en-
cephalopathy. Treatment of this condition is described in Chapter 35.
20. How is therapeutic response evaluated?
The client's perception and observations of the cat are helpful, although subjective. Physical
examinations help to assess hydration weight gain and overall condition as well as to evaluate
previously noted abnormalities. However, because it is unlikely that the disease "started" exactly
when the client first noticed it and because some degree of illness most likely preceded the first
observable signs, evaluation of previously abnormal serum biochemistries (liver enzymes, liver
function tests) is recommended. Ultrasound or repeat evaluation of liver biopsies is ideal.
21. What is the prognosis for cats with CCHC?
The prognosis for cats with CCHC depends on the extent of histopathologic changes. pres-
ence of fibrosis or cirrhosis, and concurrent disorders. Most cats with suppurative CCHC recover
fully. Most cats with nonsuppurative CCHC recover clinically but have ongoing lymphocyticl
plasmacytic inflammation that must be controlled to avoid development of hepatic insufficiency
and hepatic encephalopathy.
BIBLIOGRAPHY
I. Center SA: The feline cholangitislcholangiohepatitis syndrome. InProceedings of the 15thAnnual Meeting of
the American College of Veterinary Internal Medicine, Lakewood, CO, ACVIM, 1997, pp 409-412.
2. Weiss OJ, Armstrong Pl, Gagne 1M: Feline cholangiohepatitis. In Bonagura lD (ed): Current Veterinary
Therapy XIII. Philadelphia, W.B. Saunders, 2000, pp 672--674.
3. Willard MD, Weeks BR, Johnson M: Fine-needle aspirate cytology suggesting hepatic lipidosis in four
cats with infiltrative hepatic disease. 1 Feline Med Surg 1:215-220, 1999.
30. HEPATIC LIPIDOSIS
Michelle L. Berry, D.V.M.
1. Define hepatic lipidosis.
Hepatic lipidosis (HL), one of the most common hepatobiliary disorders of domestic cats in
North America, is defined as a clinical syndrome in which at least 50% of hepatocellular cytosol
is displaced by triglyceride (TG).
2. What causes HL?
Abnormal fat accumulation in hepatocytes may occur for various reasons. It has been associ-
ated with endocrine conditions, nutritional and metabolic derangements, and some forms of he-
patic disease. As free fatty acids (FFAs) are introduced to the liver, they can be (I) esterified into
TG, packaged as very low density lipoproteins (VLDL), and exported from the liver, (2) esterified
into TG and stored in the hepatocytes, or (3) undergo beta oxidation and be utilized as energy. Any
condition that decreases VLDL synthesis or export or overwhelms the ability to oxidize FFAs for
energy results in increased TG storage. Specific causes include obesity, imbalanced caloric intake,
poor nutrition, hepatotoxins, systemic diseases, and idiopathic disease (approximately 50%).
3. Describe the typical history of a cat with HL.
Typically the owner notes weight loss, lethargy, and anorexia. Feline HL occurs twice as
often in females as males. Cats that are obese may be predisposed. The anorexia usually occurs
for at least 2 weeks, and weight loss often exceeds 25% of original body weight. The cat may
have a history of vomiting, diarrhea, or constipation.
4. What physical examination flndmgs are typical in cats with HL?
Icterus, hepatomegaly, and dehydration often are detected on physical examination. The cat
may exhibit signs of hepatic encephalopathy (HE), such as ptyalism or other neurologic signs,
but they are generally uncommon. Other findings consistent with a primary disease process in-
ducing anorexia may be found (see Chapter 62).
5. What are the differential diagnoses for cats with these findings?
Because icterus is the main clinical presentation with specific diagnoses, the primary differ-
entials include all causes of prehepatic, hepatic, and posthepatic hyperbilirubinemia (see Chapter
28). Because hepatomegaly is common, hepatic and posthepatic causes are higher on the differ-
entiallist than prehepatic causes.
6. Describe the initial diagnostic plan for a cat with suspected HL.
Packed cell volume should be assessed immediately to eliminate prehepatic causes of hyper-
bilirubinemia. Complete blood count (CBC) and serum biochemisty profile, including elec-
trolytes, urinalysis, feline leukemia virus antigen test, and feline immunodeficiency virus antibody
test, are indicated. In cats older than 5 years, total T4 concentration should be determined as well.
A search for underlying diseases should be undertaken, as indicated by other historical and physi-
cal examination findings. Disorders associated with feline HL are listed in the table below.
Disorders Associated with Hepatic Lipidosis in Cats
DISEASE PROPOSEDMECHANISMS
Diabetes mellitus
Intestinal bacterial overgrowthand
inflammatorybowel disease
142
Increased lipolysis of adipose tissue
Formationof endotoxins, impaired gut absorption of
nutrients, formation of toxic bile acids
143 Hepatic Lipidosis
Disorders AssociatedwithHepatic Lipidosisin Cats (Continued)
DISEASE PROPOSED MECHANISMS
Anorexia
Carnitinedeficiency
Poor nutrition
Cholangiohepatitis
Chronicparenteral carbohydrate
Hepatotoxins (various)
Increasedmobilization of FFA,decreased protein; any
illness withassociatedanorexiacanprecipitateHL
Decreasedfattyacidbeta-oxidation
Insufficient protein
Anorexia, liver dysfunction
Increased hepaticsynthesisoftriglycerides, blockingof
beta infusionoxidation of fattyacids
Impairedoxidationof fattyacids, assemblyofVLDL, and
export ofVLDL
FFA =free fatly acids, HL=hepatic lipidosis, VLDL =very lowdensity lipoprotein.
7. Is there a typical pattern of hepatic enzymes in HL?
In most cats with HL, alkaline phosphatase (ALP) activity is higher than alanine transferase
(ALT) activity; gamma-glutamyl transferase activity is usually normal. Approximately 80% of
cats have a twofold or more increase in ALP activity; 55% have a fivefold or more increase.
8. What other abnormalities are often identified on CBC and serum biochemistry profile?
CBC often revealsa mild anemia, whichmay be regenerativeor nonregenerative. Poikilocytosis
is common. The leukogrammay be helpful because cats with idiopathicHLusually do not have an
inflammatoryleukograrn, whereas cats with underlyingdisease leadingto HLoften do.
Serum biochemisty profile changes often reflect cholestasis with hyperbilirubinemia. Some
cats may have a lowalbuminconcentrationwith a normal globulinconcentration.Additional incon-
sistent findings include hypercholesterolemia,decreasedblood urea nitrogen, and hyperglycemia.
Serum electrolyte concentrations are variable. Approximately 30% of cats with HLhave hy-
pokalemia, which is significantly related to failure to survive.
9. What additional diagnostic tests should be performed?
Abdominal radiography is rarely helpful in supporting a diagnosis of HL. Hepatomegalymay
be detected, but usually it is recognized on abdominal palpation during the physical examination.
Abdominal ultrasound in the hands of an experienced ultrasonographercan provide valuable infor-
mation about the cause of liver dysfunction. Cats with HLhave diffuse hyperechoic parenchyma.
Findings consistent with bile duct obstructionor cholangitislcholangiohepatitis, such as gallbladder
wall thickening or bile duct thickening, increase suspicion of other underlyingdisorders.
10. How is HL definitely diagnosed?
Liver tissue must be evaluated microscopically to arrive at a definitive diagnosis of HL. This
goal can be achieved with fine-needle aspirate and cytology or biopsy and histology. Because
liver disease commonly results in coagulopathies, coagulation tests should be performed before
aspiration or biopsy. An activated clotting time (ACT), prothrombin time (PT), or activated par-
tial thromboplastin time (APTT) may help to identify cats with increased risk of bleeding. A test
for proteins induced by vitamin K absence or antagonism (PIVKA) also may be valuable.
Ultrasound-guided percutaneous fine-needle aspiration may be sufficient for a diagnosis of
HL, but it also may miss other underlying hepatic diseases. If an underlying liver disease is sus-
pected, hepatic biopsy should be performed (see Chapter 29).
11. Why are cats with liver disease predisposed to bleeding tendencies?
Because normal liver function and regular flow of bile is necessary to absorb fat-soluble vit-
amins such as vitamin K, cats with abnormal liver function or cholestasis may have a decreased
amount of vitamin K available to activate clotting factors II, VII, IX, and X. The other primary
mechanism is decrease in hepatic production of clotting factors.
12. What should you do if the PT or APTT is prolonged?
The patient shouldbe treatedwith subcutaneous administration of vitaminK
1
at 5 mg/cat,You
shouldwait 12hours beforebiopsyis performed, This therapyshouldtreat vitaminKdeficiency ef-
fectively but does not correct clottingfactor deficiency secondaryto liver insufficiency. In cats sus-
pectedof havinga clottingfactordeficiency, freshfrozenplasmaor freshwholebloodshouldbe given
beforebiopsyto providenecessary clottingfactors. All cats shouldbe blood-typed or cross-matched
beforebiopsyin case bleeding occurs. Manyclinicians preferto treatcats withliverdysfunction with
vitamin K, regardless of coagulation statusbeforebiopsybecausesideeffects are minimal.
13. Describe the initial treatment plan for HL.
Fluid therapy should be initiated immediately to replenish fluid losses and normalize acid-
base status. Normal saline (0.9% sodium chloride) or other polyionic isotonic solutions are ap-
propriate. Because hypokalemia is common, 20 mEq of potassisumchloride should be added per
liter of fluid for maintenance. If hypokalemia is present, more aggressive potassiumsupplemen-
tation may be warranted. Dextrose should not be added to the fluids unless hypoglycemia has
been identified because excessive carbohydrates stimulate hepatic synthesis of triglycerides and
block oxidation of fatty acids, further exacerbating the lipidosis. Because the liver metabolizes
lactate to produce bicarbonate, fluids with lactate added as a buffer (i.e., lactated Ringer's solu-
tion) should be avoidedin patients with liver dysfunction, especially cats with HL.
Aggressive nutritional management is the cornerstone of effective HL therapy. Sufficient
protein must be provided because cats catabolize a set amount of protein for energy to be used for
hepatic triglycerideclearance.
14, What is the best way to provide nutritional support?
Gastrostomy tubes provide the easiest, most reliable method of long-term alimentation. A
self-retaining, 14-20-French catheter with a reinforced mushroom tip (Bardex self-retaining
catheter, Bard Urological Division, Murray Hill, NJ) is commonly used. Some clinicians use
esophagostomy tubes with success (see Chapter 62). Pharyngostomy tubes are poorly tolerated
by cats and should be avoided.
15. When should a gastrostomy tube be placed?
A gastrostomy tube should be placed as soon as possible. If the cat needs to be stabilized
before anesthesia for tube placement, a nasoesophageal or nasogastric tube can be placed to de-
liver nutrition. Becauseof the small size of these tubes, a liquid diet must be used. A commercial
feline liquiddiet (CliniCareFeline Maintenance,Pet Ag Inc., Hampshire,lL) is often sufficientfor
short-termnutritional support. Because liquid formulations do not provide adequate protein, they
are not recommendedfor long-termnutritionaltherapy. Force feeding by the oral route, while suc-
cessful in some cats, is generallyunreliable and not recommended. It is difficult to ensure proper
caloric intake, and cats may developa food aversionbecauseof oral forcedfeeding.
16. What should you do if the cat shows signs of hepatic encephalopathy (HE)?
Cats showing overt signs of HE should be evaluated for conditions known to precipitate
HE, such as gastrointestinal bleeding, hypokalemia, alkalosis, systemic infection, azotemia, and
constipation.
17. How is HE treated?
Treatment is aimed at decreasing production and absorption of alimentary-derived toxins.
The most often implicated toxin associated with HE is ammonia, a breakdown product of pro-
tein. Cats presenting with signs of HE should be treated with warmcleansing enemas of normal
saline to evacuate the colon. Cleansing should be followed with retention enemas containing lac-
tulose (5-10 m1 diluted 1:3 with warmwater) or neomycin.
Hypokalemia should be treated by addition of potassium chloride to intravenous fluids.
Deliveryof potassiumchloride should not exceed a rate of 0.5 mEq/k:g/hr.
Hepatic Lipidosis 145
Once the signs abate, the cat can be managed with a diet containing decreased protein and
orallactulose (see Chapter 35). Oral antibiotics, such as amoxicillin, neomycin, or metronida-
zole, may be beneficial.
18. How should a cat be fed with a gastrostomy tube?
Twenty-four to 36 hours after placement, feeding can begin. Initially, 5 rnl of warm water is
instilled into the tube. If it is tolerated with no signs of nausea or vomiting, small amounts of food
may be given. Caloric requirements should be calculated for each cat. The following formula is
commonly used:
Estimated caloric needs =1.5 x [30 x body wt (kg) +70]
At first, small amounts of food should be given. Caloric requirements usually are introduced in
thirds. On the first day, one-third of the nutritional requirement is given, divided into separate feed-
ings every4-6 hours. As the cat adjusts to the introductionof food, volumesare increasedgradually
in thirds until full caloric requirementsare received.After full caloric requirementsare met, the fre-
quency of feeding can be reduced gradually until the cat is fed every 8 hours. Before each feeding,
the tube should be aspiratedto quantifyresidual stomachcontents. If the amount aspiratedis > 20%
of the previousfeeding, the scheduledfeeding should be skippedand therapywitha prokinetic drug,
such as metoclopramide(0.2-0.5 mglkg every8 hr), should be initiated.Always return the aspirated
fluid to the cat to avoidpotential acid-baseand/or electrolyteimbalances.
Typical Gastrostomy or Esophagostomy Feeding Plan for 4-kg Cat with Hepatic Lipidosis
Estimatedcaloricneeds=1.5 x [(30x 4) + 70] =285 kcal/day
Blenderize food withenoughwaterto make I kcal/ml
Strainthe blenderized mixturetwiceandrefrigerate
Warmthe amountof mixtureto roomtemperature or slightlywarmerbeforefeeding
Day 1
24 hoursafter tube placement,instill 5 ml of warmwater in tube. If no vomiting or signs of nausea
occur, proceedwithfeeding. If vomitingor signs of nauseaoccur, initiateparenteral metoclopramide
therapy.
Offer wet foodorallybeforefeedingthroughthe tube. Do not force the cat to eat.
Beforeadministering food, aspiratethe tube. If> 5 ml of fluid is retrieved, skip the feeding. Givethe
aspirated fluid backthroughthe tube. Initiatemetociopramide therapy. Give 16ml ofblenderized
food mixturethroughthe tube over 20-30 minute. If the cat vomits duringfeeding, stop. Flushthe
tube with5 ml of warmwater,and wait until next feeding. If the cat toleratesthefeeding, finishthe
16ml, and flushthe tube with5 rnl warmwater. Repeatevery4 hoursfor the first 24 hours.
Subsequent feedings throughout the day. Beforeadministering food, aspiratetube. If> 5 ml is aspi-
ratedduringthe first day, skipthe feeding. Givethe aspiratedfluidbackthroughthe tube. Initiate
metociopramide therapy.
Day 2
If the cat has been tolerating the feedings, increasedailytotal amount to two-thirds of total require-
ments.If the food is I kcal/rnl, the total dailyamount increasesto 188ml, givenas 31 ml every4
hours. If aspirateis > 6 ml beforefeeding, skipthe feedingandwait until the next scheduledfeeding.
Day 3
If the cat has been tolerating the feedings, increase daily total amount to full caloricrequirements. If
the food is I kcal/ml, the total daily amountincreasesto 285ml, givenas 48 ml every4 hours. If aspi-
rate is > 10ml beforefeeding,skip the feeding andwait until the next scheduled feeding.
After full caloric requirements are being given
As the cat does better withthe feedings, decreasethe frequency to every6 hoursfor a fewdays, then
every8 hours. For example, if the cat is fed every6 hoursat full caloricrequirements, a total of 71 ml
is givenat each feeding. If the cat is fed every8 hours at full caloricrequirements. a total of 95 ml is
givenat eachfeeding.
19. What kind of food should be fed?
A balanced commercial feline diet is the best choice because it contains all of the necessary
protein and amino acids for cats. Canned food should be blenderized with water to form a slurry
that can be given through the tube with ease. If a homemade diet is used, ensure that adequate
amounts of arginine and taurine are provided.
20. What should be done if the cat vomits?
Vomiting is a common complication in cats with feeding tubes. If vomiting occurs, proki-
netic drugs such as metoclopramide should be used. In the hospital, metoclopramide can be
given parenterally via subcutaneous injection or in a continuous-rate infusion with intravenous
fluids. Alternatively, the medications may be given via the gastrostomy or esophagostomy tube
30 minutes before tube-feeding. Protracted vomiting may signify other underlying disorders,
such as worsening hepatic disease, pancreatitis, or tube problems (e.g., cellulitis or sepsis), and
should be investigated.
21. How should the tube be managed at home?
Give specific written instructions for tube feeding and care at home. Instruct the owner to in-
spect the exit sight daily for exudate or irritation, and call if there is any concern. Tube clogging
is a common problem and usually can be alleviated with a flush of warm water. For more difficult
clogs, about 5-6 ml of a carbonated beverage can be instilled in the tube. Wait 5-10 minutes, then
try flushing again. Before each feeding, the owner should offer the cat a tasty variety of food to
stimulate normal eating. Once the cat is eating spontaneously, tube feedings can be decreased
gradually until the cat is eating all of the nutritional requirements orally. At that time, tube re-
moval should be considered.
22. How long should the gastrostomy tube stay in the cat?
Because all cats are different, the time varies on an individual basis. Many cats require tube
feeding for 4-6 weeks. For appropriate healing, the tube should not be removed before 2 weeks
after placement. Some clinicians remove the tube when the cat is ingesting all nutritional require-
ments with no supplementation from the tube for at least 2 weeks. The cat should gain weight (if
needed) or maintain current weight with oral feeding. A serum biochemistry profile should reveal
normal hepatic enzyme activities and normal total bilirubin.
23. Are additional dietary supplements needed for cats with HL?
Some clinicians prefer to supplement the diets of cats with HL. A list of the most commonly
used supplements and their suspected benefit is included in the table below. To date, no scientific
evidence indicates that these supplements are necessary or beneficial.
Nutritional Supplements for Cats with Hepatic Lipidosis
Arginine
Taurine
Camitine
Thiamine
Vitamin K
J
May be essential for formation of certain apoproteins. Cats can develop hepatic en-
cephalopathy if fed a diet low in arginine. An oral dose of I gm/cat every 24 hr has
been recommended.
Taurine is essential in cats for conjugation of bile acids, among other activities.
Because cholestasis may occur with HL, cats may deplete taurine stores. An oral
dose of 250-500 mg/cat every 12hr has been recommended.
Camitine may help to increase fatty acid beta-oxidation. Anoral dose of 250-500
mg/cat every 24 hr has been recommended.
Supplementation may be needed in anorectic cats. Anoral dose of 50-I 00 mg/cat
every 24 hr has been recommended.
Normal liver function and flowof bile are necessary for absorption of fat-soluble vi-
tamins such as vitamin K. VitaminK is necessary for activationof clotting factors II,
VII, IX, and X. An oral dose of 5 mg/cat every 12 hr for 2-3 days, then every 3
days, is recommended.
Hepatic Neoplasia
Nutritional Supplements for Cats with Hepatic Lipidosis (Continued)
147
VitaminE
Zinc
This fat-soluble vitamin has antioxidant properties. An oral dose of 20--1 00 mg beta
tocopherol/cat every 24 hr is recommended.
Low levels of zinc have been documented in humans with liver insufficiency. Low
levels of zinc are suspected to cause signs of hepatic encephalopathy; therefore, zinc
is supplemented by some clinicians. An oral dose of 7-10 mg/cat every 24 hr has
been recommended.
24. What is the prognosis for cats with hepatic lipidosis?
Identification of underlying causes followed by appropriate and aggressive treatment has im-
proved the prognosis for cats with hepatic lipidosis. Cats that receive the necessary therapy have
a > 60% chance at survival, regardless of whether there is an underlying cause or the lipidosis is
idiopathic.
BIBLIOGRAPHY
I. CenterSA: Hepatic lipidosis. In Guilford WG, CenterSA, Strombeck DR, et al (eds):Strombeck'sSmall
Animal Gastroenterology, 3rded. Philadelphia, W.B. Saunders, 1996, pp 766-782.
2. Cornelius LM, BartgesJW, MillerCC: CVTUpdate: Therapyfor Hepatic Lipidosis. In Bonagura JD (ed):
Kirk's CurrentVeterinary TherapyXIII, SmallAnimalPractice. Philadelphia, W.B. Saunders, 2000, pp
686-690.
3. Roudebush P, DavenportDJ, Dimski DS: Hepatobiliary disease. In Hand MS, Thatcher CD, Remillard
RL, Roudebush P (eds): SmallAnimal ClinicalNutrition, 4th ed. Topeka, KS, MarkMorris Institute,
2000, pp 826-827.
31. HEPATIC NEOPLASIA
Timothy M. Fan, D.V.M.
1. What is the difference between a primary hepatic neoplasm and a secondary or
metastatic hepatic neoplasm?
A primary hepatic neoplasm is a tumor that originates from the hepatic parenchyma or as-
sociated structures, whereas a secondary or metastatic hepatic neoplasm arises from another
source and spreads or invades into the liver parenchyma as a consequence of disease progression.
2. Name the most common malignant primary hepatic neoplasms of the feline liver.
The most common primary feline hepatic neoplasms may be of epithelial or nonepithelial
origin. Hepatobiliary epithelial neoplasms include hepatocellular adenocarcinoma, biliary duct
carcinoma, and biliary duct adenoma. Hepatobiliary nonepithelial neoplasms include heman-
giosarcoma, fibrosarcoma, and leiomyosarcoma.
3. What are the most common metastatic hepatic neoplasms in cats?
Lymphosarcoma, infiltrative mast cell tumors, pancreatic carcinoma, intestinal carcinoma,
and carcinoids are the most common metastatic neoplasms affecting the feline liver. The term
visceral mastocytosis describes infiltrative mast cell tumors involving the internal organs, such
as the liver and intestines. Most metastatic hepatic neoplasms are characterized by diffuse infil-
tration of the liver, resulting in generalized hepatomegaly.
4. Which are more common, primary hepatic neoplasms or metastatic hepatic neoplasms?
Metastatic neoplasms of the liver are more common than primary hepatic neoplasms.
Hepatic lymphosarcoma and visceral mastocytoma typically cause generalized hepatomegaly;
148 Hepatic Neoplasia
however, metastatic pancreatic or intestinal carcinoma generally produces multiple discrete nod-
ules involving more than one liver lobe. The most cornmon primary hepatic neoplasm of epithe-
lial origin in cats is bile duct adenoma, followed by bile duct adenocarcinoma.
S. What are the common clinical manifestations of hepatobiliary neoplasia?
Most affected cats are presented for vague nonspecific signs of illness, including anorexia,
vomiting, diarrhea, weight loss, and lethargy. Some are overtly icteric. Icterus associated with
feline hepatic neoplasia is caused most commonly by intrahepatic biliary duct occlusion, re-
sulting in posthepatic hyperbilirubinemia. In extreme cases, advanced neoplastic infiltration
may compromise liver function, resulting in hepatic icterus. A minority of cats with hepatobil-
iary neoplasia have peritoneal effusion. Potential causes of peritoneal effusion include in-
creased vascular permeability due to the release of inflammatory cytokines, occlusion of
hepatic lymphatics from neoplastic infiltration, and decreased oncotic pressure secondary to
hypoalbuminemia.
6. Name common hematologic and biochemical abnormalities that may be supportive of
hepatobiliary neoplasia.
Hematologic abnormalities may include nonregenerative anemia and leukocytosis. Degree
of leukocytosis can be variable and should not be automatically attributed to infectious causes of
hepatic disease. Profound leukocytosis (> 80,000 cells/ul) can be a paraneoplastic syndrome as-
sociated with neoplastic production and release of granulocyte colony-stimulating factor.
Biochemical abnormalities may include increased serum activities of alanine aminotransferase
(ALT), aspartate aminotransferase (AST), garnma-glutamyl transferase (GGT), and alkaline
phosphatase (ALP), hyperbilirubinemia, and abnormal coagulation tests. The absence of bio-
chemical abnormalities does not exclude the possibility of hepatobiliary neoplasia. If hepatic
function is severely compromised by advanced neoplastic disease, biochemical abnormalities as-
sociated with liver failure, such as hypoalbuminemia, hypoglycemia, low blood urea nitrogen,
and hypocholesterolemia, may be identified.
7. Describe potential radiographic and sonographic findings associated with hepatobiliary
neoplasia.
Abdominal radiographs may identify diffuse hepatomegaly or a cranial abdominal mass
effect. Significant abdominal effusion may impede visualization of normal anatomic structures be-
cause of diminished radiographic contrast and detail. Sonographically, primary and metastatic he-
patobiliary neoplasms may produce variable patterns of echogenicity. Diffuse hepatomegaly, a
solitary hepatic mass, or multiple hepatic nodules may be identified, depending on the location
and type of hepatobiliary neoplasm. Imaging studies are helpful in supporting the diagnosis of he-
patobiliary neoplasia; however, definitive diagnosis is based on cytologic or histologic findings.
8. How is a liver biopsy obtained in cats?
Definitive diagnosis of hepatic neoplasms other than lymphosarcoma and mastocytosis tradi-
tionally requires a liver biopsy for histologic evaluation. Methods for obtaining an adequate
amount of tissue include percutaneous ultrasound-guided liver biopsy, laparoscopic biopsy. or
exploratory laparotomy with biopsy. Risk for hemorrhage is greatest with percutaneous, ultra-
sound-guided liver biopsy; this technique also yields the smallest amounts of tissue. During ex-
ploratory laparotomy, large biopsies can be taken and hemorrhage can be controlled, but general
anesthesia is required and there is risk of poor wound healing in severely affected patients.
Percutaneous ultrasound-guided and laparoscopy-obtained biopsies have the benefits of not re-
quiring a significant surgical incision, and both techniques can be performed with sedation.
Although histopathologic evaluation is the only definitive method for diagnosing some malig-
nancies, cytologic confirmation of malignancy can be obtained by fine-needle aspiration of the
liver or, in some cases, evaluation of peritoneal effusions and can be performed instead of biopsy
for the benefit of compromised patients.
Hepatic Neoplasia 149
9. Howcan surgery aid in the treatment of hepatic neoplasia?
Surgical resection may prove to be curative in dealing with solitary primary hepatocellular
adenocarcinomas or adenomas. In general, primary tumors affecting one or two lobes should be
excised by hepatic lobectomy. Unfortunately, most epithelial and nonepithelial hepatobiliary
neoplasms involve multiple liver lobes, precluding complete surgical excision. Surgical resection
of biliary duct adenocarcinomas is rarely curative because of anatomic limitations for complete
surgical resection, as welI as the aggressive metastatic behavior of the tumor. Approximately
75% of hepatobiliary adenocarcinomas at time of diagnosis have already metastasized to the
lungs, regional lymph nodes, and intestinal serosa.
10. When should I use systemic chemotherapy in the treatment of hepatic neoplasia?
Systemic chemotherapy should be considered as a primary therapeutic modality for hepatic
lymphosarcoma or visceral mastocytoma. Systemic chemotherapy should be recommended in an
adjunctive setting for the control of micrometastatic disease after surgical debulking of primary
hepatobiliary neoplasms. At this point in veterinary oncology, the effective use of radiation ther-
apy or immunotherapy for the treatment of hepatobiliary neoplasia remains poorly explored.
11. How successful is systemic chemotherapy in the treatment of hepatobiliary neoplasms?
In general, when treating hepatobiliary neoplasms with systemic chemotherapy, response
rates, remission duration, and survival times remain disappointing. One postulated explanation
for the poorer response rates concerns the expression of P-glycoprotein by hepatocytes. For a
chemotherapeutic agent to be effective in killing a tumor cell, several requirements must be met,
including a high enough concentration of the agent within the tumor cell to induce apoptosis
(programmed cell death). Certain tumor cells protect themselves from reaching this lethal thresh-
old concentration by upregulating an intrinsic cellular efflux pump known as P-glycoprotein.
Activation of P-glycoprotein enhances the ability of tumor celIs to export chemotherapeutic
agents, thereby circumventing cellular death. Normal tissues involved with xenobiotic metabo-
lism and excretion, such as the liver and kidney, have higher inherent expressions of P-glycopro-
tein. Neoplasms originating from the liver or kidney tend to express very high levels of
P-glycoprotein, making them more resistant to the effects of systemic chemotherapy.
12. In treating an icteric cat with systemic chemotherapy for hepatobiliary lymphosar-
coma, which chemotherapy drugs should be used with caution?
Most traditional chemotherapeutic regimens for the treatment of lymphosarcoma include the
use of adriamycin, vincristine, cyclophosphamide, prednisone, and L-asparaginase (See Chapter
68). Both adriamycin and vincristine rely on hepatobiliary excretion and at the very least should
be dose-reduced, if not completely avoided, in the treatment of icteric patients. If the patient does
not have evidence of icterus, standard dosing of adriamycin and vincristine may be recommended.
Cyclophosphamide and prednisone are prodrugs requiring hepatic transformation to their respec-
tive active metabolites, 4-hydroxycyclophosphamide and prednisolone. There are no contraindica-
tions for the use of cyclophosphamide or prednisone in icteric cats, but if hyperbilirubinemia is
secondary to synthetic liver failure, biotransformation of cyclophosphamide or prednisone to its
active metabolite may be incomplete. L-asparaginase degrades endogenous L-asparagine to L-as-
partie acid and ammonia, depriving malignant lymphoid cells of necessary L-asparagine for rapid
protein synthesis and growth. There have been no reported contraindications for the use of L-as-
paraginase in the treatment of feline hepatic lymphosarcoma, but hyperammonemia with subse-
quent hepatic encephalopathy has been reported in humans treated with L-asparaginase.
13. What is visceral mastocytosis? How can you manage the clinical signs associated with
visceral mast cell degranulation?
Visceral mastocytosis describes the diffuse infiltration of neoplastic mast cells within a vis-
ceral organ. Visceral mastocytosis may affect the liver, spleen, or intestines. Systemic signs of ill-
ness are caused not only by neoplastic infiltration into organ sites but also by mast cell
150 Hepatic Neoplasia
degranulation. Mast cells contain numerous cytoplasmic granules that are released by immuno-
logic (lgE or complement-mediated) and nonimmunologic (temperature, pressure, drug expo-
sure) mechanisms. The process of cytoplasmic granule release is termed degranulation. One
major component responsible for many of the clinical signs associated with mast cell degranula-
tion is histamine. Histamine can activate H
2
receptors on the parietal cell, resulting in excessive
hydrochloric acid production and subsequent vomiting, anorexia, melena, and gastric ulceration.
In addition, histamine can activate HI receptors found on vascular endothelium, resulting in pro-
found vasodilation and increased capillary membrane permeability. The use of an HI blocker
(diphenhydramine) and an H
2
blocker (famotidine, ranitidine, or cimetidine) may ameliorate sys-
temic signs attributed to mast cell degranulation.
14. What chemotherapeutic protocol is used for visceral mastocytosis?
Visceral mastocytosis tends to be a highly aggressive disease, with common involvement of
the intestine, liver, and spleen. Even with multiorgan involvement, splenectomy has proved to be
beneficial in prolonging survival times of cats. The use of systemic chemotherapy should be
viewed at best as palliative, with a low probability of providing a definitive cure for systemic vis-
ceral mastocytosis. Adjunctive medical therapies with histamine blockers (diphenhydramine and
famotidine) should be implemented in attempts to improve quality of life scores. Effective
chemotherapy protocols for the treatment of visceral mastocytosis in cats have yet to be critically
evaluated in a prospective manner. The concurrent use of lomustine and prednisone provides a
relatively cost-effective and rational means of treating visceral mastocytosis. If hematologically
tolerable,lomustine may be dosed at 60 mg/m'' by mouth every 21 days, and prednisone may be
dosed at 20 mg/m? by mouth daily. Vinblastine and cyclophosphamide used together or as single
agents also may be effective in treating visceral mastocytosis.
BIBLIOGRAPHY
I. Alexander RW, Kock RA: Primary hepatic carcinoid (APUD cell carcinoma) in the cat. J Small Anim
Pract 23:767,1982.
2. Carr BI. Flickinger JC, Lotze MT: Hepatobiliary cancers. In Devita VT (ed): Cancer: Principles and
Practice of Oncology, 5th ed. Philadelphia, Lippincott-Raven, 1997, pp 1087-1114.
3. Day DG: Diseases of the liver. In Sherding RG (ed): The Cat: Diseases and Clinical Management, 2nd
4. Feeney DA, Johnston GR, Hardy RM: Two-dimensional, gray-scale ultrasonography for assessment of
hepatic and splenic neoplasia in the dog and cat. J Am Vet Med Assoc 184:68-81, 1984.
5. Feldman BF, Strafuss AC, Gabbert N: Bile duct carcinoma in the cat: Three case reports. Feline Pract
6:33, 1976.
6. Fondacaro JV, Guilpin VO, Powers BE, et al: Diagnostic correlation of liver aspiration cytology with
histopathology in dogs and cats with liver disease. In Proceedings of the 17th Annual Veterinary
Medical Forum, June 10--13, 1999, P 719.
7. Lawrence HJ, Erb HN, Harvey HJ: Nonlymphomatous hepatobiliary masses in cats: 41 cases (1972 to
1991). Vet Surg 23:365-368,1994.
8. Morrison WB: Primary cancers and cancer-like lesions of the liver, biliary epithelium, and exocrine pan-
creas. In Morrison WB (ed): Cancer in Dogs and Cats: Medical and Surgical Management.
Philadelphia, Lippincott Williams & Wilkins, 1998, pp 559-568.
9. Patnaik AK: A morphologic and immunocytochemical study of hepatic neoplasms in cats. Vet Pathol
29:405-415, 1992.
10. Post G, PatnaikAK: Nonhematopoietic hepatic neoplasms in cats: 21 cases (1983-1988). J Am Vet Med
Assoc 201: 1080--1082, 1992.
1I. Scavelli TD, Patnaik AK, Mehlhaff CJ, et a1: Hemangiosarcoma in the cat: Retrospective evaluation of
31 surgical cases. J Am Vet Med Assoc 187: 817, 1985.
12. Straw RC: Hepatic tumors. In Withrow SJ, MacEwen GE (eds): Small Animal Clinical Oncology, 2nd
13. Strombeck DR, Guilford GW: Hepatic neoplasms. In Guilford GW (ed): Strombeck's Small Animal
Gastroenterology, 3rd ed. Philadelphia, w.B. Saunders, 1996, pp 847-859.
14. Trout NJ, Berg RJ, et al: Surgical treatment ofhepatobiliary cystadenomas in cats: Five cases (1988-
1993). J Am Vet Med Assoc 206:505-507,1995.
32. HEPATIC INFECTIONS
Timothy M. Fan, D.V.M.
1. What infectious agents are associated with hepatic disease in cats?
Infectious causes of hepatic disease include viruses (feline infectious peritonitis. feline
leukemia virus), parasites (Toxocara cati, Platynosomum concinnum. Toxoplama gondii,
Cytauxzoon felis), bacteria (suppurative cholangitis/cholangiohepatitis complex), and fungi
(Mucor spp., Aspergillus spp).
2. What is the most common hepatic infection?
The bacterial cholangitis/cholangiohepatitis complex is most common (see Chapter 29).
3. Which protozoans are associated with hepatic infections?
At least four different protozoal organisms have been associated with hepatic infections:
Toxoplasma gondii; a coccidia-Iike organism from the protozoan family Eimeriidae; a protozoan
parasite similar to Hepatozoon canis; and Cytauxzoonfelis (see Chapter 75). T. gondii is the most
frequently encountered protozoan parasite causing cholangitis/cholangiohepatitis.
4. How does hyperbilirubinemia due to toxoplasmosis develop?
Cats are infected by T. gondii by ingestion of sporulated oocysts or tissue cysts or transpla-
centally or lactationally from primary infection of the queen. Clinical toxoplasmosis is most
severe in transplacentally infected or neonatally infected kittens; the type and severity of clinical
illness depend on the degree and localization of tissue injury. The organism infects the gastroin-
testinal epithelium and disseminates through the blood. Intracellular replication of T. gondii
tachyzoites results in destruction of infected cells and necrosis. Replication is common in hepato-
cytes and the pancreas and can result in hyperbilirubinemia from either hepatic disease or pan-
creatic disease. Hepatic disease seems to be uncommon in chronically infected cats. Clinical
signs in acutely infected cats include anorexia, depression, fever, abdominal distension, crying.
dyspnea, central nervous system signs, icterus, and death.
5. How is hepatic toxoplasmosis diagnosed?
A diagnosis of T. gondii infection can be made by various testing procedures. Tachyzoites
may be detected cytologically in various tissues and body fluids (pleural and peritoneal effu-
sions) during acute infection. Fecal examination for T. gondii oocysts may be beneficial 1-2
weeks after initial exposure. Serologic testing has become the most practical and accepted means
of diagnosing T. gondii infection. Serologic evidence of recent or active infection consists of
high IgM titers, or a fourfold or greater increase in IgG titers. However, these findings document
only recent infection, not clinical disease due to infection.
6. How is hepatic toxoplasmosis treated?
Drugs attempted for the treatment of acute extraintestinal toxoplasmosis include clin-
damycin (10-12.5 mglkg orally every 8-12 hr), pyrimethamine (0.25--0.5 mglkg orally every 12
hr), and trimethoprim-sulfonamide (15 mglkg orally every 12 hr). If pyrimethamine is used, it is
generally combined with one of the other drugs; it is rarely given to cats because of the high inci-
dence of side effects.
7. How does Cytauxzoonfelis cause hyperbilirubinemia?
Cytauxzoon felis results in severe disease in most infected domestic cats (see Chapter
75). Hyperbilirubinemia in infected cats is probably due to two mechanisms: (I) red blood
151
152 Hepatic Infections
cell destruction from the piroplasm stage and (2) hepatic dysfunction or cholestasis from hepatic
infiltration by schizont-infected macrophages.
8. What trematode parasites cause hyperbilirubinemia in cats?
The liver fluke, Platynosomum concinnum, has been reported to infect cats in tropical to
semitropical climates. Infestation with this trematode is uncommon but has been reported in cats
living in or with a history of travel to Hawaii, Florida, Polynesia, Malaysia, New Guinea,
Australia, Nigeria, Brazil, Bahamas, and Puerto Rico. Other species of trematodes that have been
identified in the livers of cats include Amphimerus pseudoflineus, Opisthorcus tenuicollis, and
Metorchus conjunctus; infestation with these species is rare.
Platynosomum concinnum requires two intermediate hosts to complete its life cycle: a land
snail and a reptile (gecko, lizard, or skink) or amphibian (toad). Embryonated eggs are ingested
by the land snail and hatch within the snail's intestinal tract. The miracidia then penetrate the
host's tissues and transform into sporocysts. The second intermediate host ingests oocysts shed
by the snail, and the cat becomes infected when it ingests an infected second intermediate host.
Infective flukes migrate up the common bile duct into the gallbladder and bile ducts.
Although most cats are subclinically infected, some cats with a high, chronic fluke burden
may manifest weight loss, vomiting, diarrhea, icterus, and hepatomegaly ("lizard poisoning").
The presence of the flukes within the biliary system incites an inflammatory process that eventu-
ally may lead to bile duct fibrosis and biliary epithelial hyperplasia.
9. How are liver fluke infections diagnosed?
Diagnosis of P. concinnum can be difficult because most cats are subclinically infected.
Identification of the parasite by fecal examination has poor sensitivity because of the small number
and variable morphology of P. concinnum eggs. Observe for the double-operculated eggs after fecal
sedimentation. Cholecystocentesis is a more definitive means of diagnosing P. concinnum infection
in cats; however, given the invasive nature of the procedure, it should be reserved for cases in which
the index of suspicion for fluke infestation is high and the cat is clinically symptomatic.
10. How are liver fluke infections treated?
Effective treatment of P. concinnum infection remains poorly defined. Current recommenda-
tions are to administer albendazole (50 mglkg/day) until fluke eggs disappear from feces or fen-
bendazole (50 mglkg orally every 12 hr) for 5 consecutive days. Albendazole may cause bone
marrow toxicity in cats treated for more than 5 consecutive days; therefore, the risk-benefit ratio
must be considered with chronic administration of albendazole.
11. Is toxocariasis a common cause of liver disease in cats?
Toxocara cati migrates through the liver of cats after ingestion of larvated eggs or infected
transport hosts (see Chapter 19). However. clinical findings consistent with liver disease are usu-
ally not detected.
12. What are the clinical rmdings of liver disease due to feline infectious peritonitis?
Feline infectious peritonitis (PIP) is thought to result from infection by a mutated variant of the
universally prevalent feline enteric coronavirus (FECV). PIP can manifest as either effusive (wet) or
noneffusive (dry), depending on predominant type (humoral or cell-mediated) and efficacy of the
host's immune response (see Chapter 38). Hyperbilirubinemia has been associated most commonly
with the noneffusive form of PIP. A primary mechanism for hyperbilirubinemia due to PIP is the for-
mation of perivascular pyogranulomas within the hepatic parenchyma and bile duct system severe
enough to cause either synthetic liver failure, intrahepatic biliary obstruction, or extrahepatic biliary
obstruction. In addition, the hyperbilirubinemia associated with PIP can result from hepatic lipidosis
induced by anorexia. The definitive diagnosis of hepatic involvement with the PIP virus requires a
liver biopsy to document the characteristic lesions and to perform immunohistochemistry. Classical
lesions include perivascular infiltration (arterioles and venules) of proliferating macrophages, lym-
phocytes, plasma cells. and neutrophils. Treatment responses are variable and prognosis is guarded.
Hepatic Infections 153
13. How does feline leukemia virus infection result in hyperbilirubinemia?
Feline leukemia virus (FeLV) is the other principal viral cause of hepatic disease in cats.
Although FeLV infection may cause multisystemic illness, the mechanism for liver disease usu-
ally is not associated with synthetic liver failure but rather with FeLV-induced malignant cell
transformation leading to the development of hepatic lymphosarcoma. Hepatic lymphosarcoma
causes hyperbilirubinemia as a result of malignant lymphocyte invasion into the hepatic
parenchyma with subsequent intrahepatic cholestasis (see Chapters 24 and 31). Other mecha-
nisms for FeLVassociated hyperbilirubinemia include:
Direct viral induction of hemolytic anemia and subsequent hyperbilirubinemia (see
Chapter 76).
Induction of immunosuppression and subsequent predisposition to H. felis-associated he-
molytic anemia (see Chapter 75), FIP, or toxoplasmosis.
Induction of anorexia and subsequent hepatic lipidosis
14. What are the clinical findings of liver disease associated with fungal infection?
Cats with systemic fungal disease are occasionally presented for evaluation of clinical find-
ings consistent with hepatic disease. Anorexia, wasting, lethargy, diarrhea, and icterus are the
most common clinical manifestations. In one report, Mucor spp. and Aspergillus spp. were the
two reported isolates. A presumptive diagnosis is based on cytologic or histopathologic evidence
of fungal infection; definitive diagnosis is based on culture. In the one large case series, all cats
were diagnosed on necropsy; therefore, definitive treatment recommendations cannot be made.
BIBLIOGRAPHY
I. Addie DO, Jarrett 0: Feline coronavirus infection. In Greene CE (ed): Infectious Diseases of the Dog
and Cat, 2nd ed. Philadelphia, WB. Saunders, 1998, pp 58-69.
2. Bielsa LM, Greiner EC: Liver flukes (Platynosomum concinnum) in cats. JAm Anim Hosp Assoc
21:269-274.1985.
3. Center SA: Hepatobiliary infections. In Greene CE (ed): Infectious Diseases of the Dog and Cat. 2nd ed.
Philadelphia, WB. Saunders, 1998. pp 615-625.
4. Center SA: Diseases of the gallbladder and biliary tree. In Stombeck DR (ed): Stombeck's Small Animal
Gastroenterology, 3rd ed. Philadelphia, WB. Saunders, 1996, pp 860--888.
5. Chock E, Wolfe BM, Matolo NM: Acute suppurative cholangitis. Surg Clin North Am 61:885-892.
1981.
6. Cotter SM: Feline viral neoplasia. In Greene CE (ed): Infectious Diseases of the Dog and Cat. 2nd ed.
7. Dubey Jp, Carpenter JL: Histologically confirmed clinical toxoplasmosis in cats: 100 cases. J Am Vet
Med Assoc 203:1556-1566,1993.
8. Dubey JP, Lappin MR, Thulliez P: Diagnosis of induced toxoplasmosis in neonatal cats. J Am Vet Med
Assoc 207:179-185,1995.
9. Dubey JP, Zajac A, Osofshy SA, et al: Acute primary toxoplasmic hepatitis in an adult cat shedding
Toxoplasma gondii oocysts. JAm Vet MedAssoc 197:1616-1618, 1990.
10. Ewing GO: Granulomatous cholangiohepatitis in a cat due to a protozoan parasite resembling
Hepatoroon canis. Feline Pract 7:37-39, 1977.
11. Hirsch VM. Doige CEo Suppurative cholangitis in cats. J Am Vet Med Assoc 182:1223-1226. 1983.
12. Hitt HE: Liver fluke infection in South Florida cats. Feline Pract I 1:26-29, 1981.
13. Jorgensen LS, Pentlarge VW, Flanders JA, et al: Recurrent cholelithiasis in a cat. Comp Cont Educ Pract
Vet 9:265-267, 1987.
14. Neufeld JL, Brandt RW: Cholangiohepatitis in a cat associated with a coccidia-like organism. Can Vet J
15:156-159, 1974.
15. Ossent P: Systemic aspergillosis and mucormycosis in 23 cats. Vet Rec 120:330--333, 1987.
16. Shaker EH, Zawie DA, Garvey MS, et aI: Suppurative cholangiohepatitis in a cat. J Am Anim Hosp
Assoc 27:148-151,1991.
17. Smart ME. Downey RS. Stockdale PHG: Toxoplasmosis in a cat associated with cholangitis and progres-
sive pancreatitis. Can Vet J 14:313-316, 1973.
18. Taylor 0, Perri SF: Experimental infection of cats with the liver fluke Platynosomum concinnum. Am J
Vet Res 38:51-54. 1977.
33. BILIARY DISEASES
Lynda Melendez, D.V.M.. M.S.
1. Which diseases typically affect the biliary system of cats?
Inflammatory diseases such as cholecystitis, choledochitis, and cholangiohepatitis/cholangi-
tis complex (CHCC) occur, as do obstructive processes, Platynosomum concinnum infestation
(see Chapter 32), and neoplastic disorders. Other than CHCC (see Chapter 29), most of these
conditions are uncommon in cats.
2. What clinical signs are seen in cats with biliary disorders?
As with most liver diseases, the clinical signs of biliary disorders are often nonspecific. Cats
can be subclinically affected for quite some time. Anorexia, lethargy, vomiting, fever, and varying
degrees of icterus may be seen. If the condition is subacute or chronic, weight loss also may be de-
tected. Some cats may exhibit signs of abdominal pain, but this can be difficult to assess. With
severe cholestatic disease, acholic feces may be noted. If rupture of the bile duct or gallbladder has
occurred or if concurrent hepatic disease has resulted in increased portal pressure or severe hy-
poalbuminemia, abdominal effusion may be present and detected on physical examination.
3. Which laboratory tests are helpful in diagnosing biliary tract disease in cats?
In icteric cats or cats with other signs that may be attributed to the liver, gastrointestinal
system, or pancreas, a complete blood count (CBC), serum biochemistry panel, and urinalysis
should be performed.
4. Describe the typical CDCfmdings.
CBC findings are often variable. Septic inflammation of the biliary tract often results in a
neutrophilia with or without an increase in the number of band neutrophils in circulation. A stress
leukogram also may be found. Cats with liver fluke infestation often have eosinophilia. With
chronic disease, nonregenerative anemia may be present as a result of chronic inflammation or
gastrointestinal blood loss.
5. What abnormalities may be seen on the serum biochemistry panel?
The serum biochemistry panel reveals an increase in the activities of cholestatic liver enzymes
alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) along with varying degrees
of hyperbilirubinemia. If cholestasis is severe or concurrent liver disease is present, serum concen-
trations of hepatocellular enzymes alanine transferase (ALT) and aspartate transferase (AST) also
are elevated. Hypercholesterolemia is usually associated with bile duct obstruction.
6. What does urinalysis reveal?
Urinalysis reveals bilirubinuria and, in cases of complete bile duct obstruction, lack of uro-
bilinogen.
7. What other biochemical tests may be useful?
Coagulation times should be assessed in cats with hyperbiliubinemia or other clinical evi-
dence of cholestasis. Because bile is necessary for the absorption of fat-soluble vitamins, cats
with chronic cholestatic disease often have prolonged clotting times secondary to vitamin K defi-
ciency. Fluid analysis should be performed in any cat with abdominal effusion.
8. Which imaging techniques can assist in the diagnosis of biliary tract disease?
Abdominal radiographs are often nonspecific but may reveal mineralized densities within
the biliary tree, representing either dystrophic mineralization from chronic inflammation or
cholelithiasis. Hepatomegaly or a mass in the region of the gallbladder, liver or pancreas may be
154
Biliary Diseases 155
evident. Gas within the biliary system or parenchyma of the liver is diagnostic for emphysema-
tous cholecystitis or a hepatic abscess caused by gas-forming bacteria such as Clostridium spp.
This problem is recognized most frequently in diabetic patients or patients who have a disease
process resulting in ischemia of the liver and/or gallbladder.
In the hands of a skilled ultrasonographer, abdominal ultrasound is more reliable than radi-
ographs for evaluating the biliary structures and finding both radiodense and radiolucent stones.
The gallbladder wall can be evaluated for thickness and irregularities as well as the presence of
polyps or other discrete masses. Common bile duct enlargement can be recognized with ultra-
sound, and the region surrounding the common bile duct (e.g., pancreatic region, hepatic
parenchyma, intestines) can be evaluated as well. In some cases, small amounts of abdominal ef-
fusion may be detected and aspirated for evaluation. Bile can be collected via ultrasound-guided
fine-needle aspiration for cytology, anaerobic culture, aerobic culture, and antimicrobial suscep-
tibility testing. Hepatic nuclear scintigraphy using technetium-labeled organic anions that are
excreted in the bile can be used to help diagnose bile duct occlusion, gallbladder malfunction,
and small-volume bile leakage into the peritoneal cavity.
9. What causes cholecystitis and choledochitis?
Cholecystitis (inflammation of the gallbladder) and choledochitis (inflammation of the
common bile duct) are uncommon as primary diseases in cats. They generally are the sequelae of
other inflammatory or infectious disease processes affecting the liver, duodenum, and/or pan-
creas. Because the feline common bile duct forms an anastomosis with the pancreatic duct before
emptying into the proximal duodenum, pancreatic and intestinal diseases can cause the extension
of inflammation up the biliary system to the gallbladder. Reflux of duodenal juices often intro-
duces gastrointestinal flora into the biliary system, resulting in septic inflammation. Other dis-
ease processes that result in prolonged anorexia, which may cause bile stasis and sludging, also
can result in inflammation or infection of the biliary system.
10. How are cholecystitis and choledochitis diagnosed?
Clinical signs are consistent with any cholestatic disease in cats. Abdominal ultrasound may
show a thickened irregular gallbladder wall or dilated, tortuous common bile duct with varying
degrees of bile sludging and stasis. With emphysematous cholecystitis, gas accumulation within
the gallbladder may be evident on plain abdominal radiographs. Severe necrotizing cholecystitis
may result in biliary rupture and bile peritonitis. Because cholecystitis and choledochitis in cats
are often secondary to another disease process, every effort should be made to identify underly-
ing or coexisting problems. Surgical biopsies are the best method for diagnosis of cholecystitis
and choledochitis; abdominal exploratory surgery also provides the opportunity to evaluate for
underlying disease. A portion of the gallbladder wall or a sample of bile should be submitted for
anaerobic culture, aerobic culture, and antimicrobial susceptibility testing. With severe disease,
cholecystectomy or biliary diversion procedures may be necessary.
11. Describe the treatment of cholecystitis and choledochitis.
Treatment should be directed primarily at any underlying condition. Fluid and electrolyte
balance and nutritional support should be addressed. Colloidal support should be instituted for
patients with hypoalbuminemia. While you are waiting for culture and sensitivity results, a
broad-spectrum antibiotic regimen should be implemented. The author prefers ampicillin (22
mg/kg intravenously every 8 hr) combined with a fluorinated quinolone (enrofloxacin, 2.5-5
mg/kg intravenously every 12-24 hr). Vitamin K
1
(2.5 mglkg subcutaneously or intramuscularly,
divided every 12 hr) should be administered to all patients with evidence of chronic cholestatic
disease and/or increased coagulation times, especially before going to surgery.
12. How common is cholelithiasis in cats?
Cholelithiasis (gallstone formation) is uncommon in cats. Although it has been associated
with CHCC as well as cholecystitis, in many cats it is an incidental finding. The exact cause of
156 Biliary Diseases
cholelithiasis is unknown, but bile stasis and abnormal composition of bile are thought to con-
tribute. Only about 50% of choleliths are radiodense, making abdominal ultrasound better for di-
agnosis than plain or contrast films. For cats with mild clinical signs, medical treatment with
ursodeoxycholic acid (10-15 mg/kg orally every 24 hr) can be attempted for dissolution.
Clinically ill cats with cholecystitis or bile duct occlusion should be explored surgically. A por-
tion of the gallbladder and a sample of bile or a stone should be submitted for anaerobic culture,
aerobic culture, and antimicrobial susceptibility testing. Long-term antibiotic therapy should be
guided by susceptibility results. In the short term, broad-spectrum antibiotic coverage should be
initiated as described in question 11.
13. What causes extrahepatic bile duct obstruction (EHBDO) in cats?
Pancreatitis, masses involving the common bile duct, cholelithiasis, and trematode infesta-
tion may cause EHBDO in cats. Other causes include extrinsic compression from regional lymph
nodes and pancreatic masses, stricture formation as a sequela to severe inflammation, blunt
trauma, or previous bile duct surgery, polycystic liver disease, and choledochitis. Diagnosis of
EHBDO is based on clinical signs, biochemistry abnormalities, and confirmation with abdominal
ultrasound, nuclear scintigraphy, and/or exploratory surgery. Treatment is aimed at identifying
and correcting the underlying cause. In some cases, rerouting of the biliary system is required.
Distended bile ducts (A) and dis-
tended gallbladder and bile ducts
(8) in a cat with EHBDO.
14. What causes bile peritonitis?
Leakage of bile into the abdominal cavity may result from traumatic rupture of the biliary
system. Any disease process that interferes with the integrity of the gallbladder wall or biliary
tree also may result in bile leakage (e.g. necrotizing cholecystitis, neoplasia). Iatrogenic damage
to the biliary system may occur during surgery or percutaneous hepatic biopsy or aspiration. A
small amount of sterile bile leaking into the peritoneal cavity is usually benign. Because bile is
Biliary Diseases 157
caustic, however, a large amount of bile accumulation or a continuous leak leads to an inflamma-
tory response and subsequent abdominal effusion. Slow leakage of bile into the abdomen from a
small defect may result in the loculation of fluid by the omentum (focal bile peritonitis) and be an
incidental finding during abdominal ultrasound or exploratory laparotomy in evaluating an icteric
patient. A large accumulation of bile results in diffuse abdominal effusion, which is usually evi-
dent on physical examination. Because marked inflammation of the peritoneal cavity can com-
promise the integrity of the intestinal wall, animals with diffuse bile peritonitis are at an increased
risk of developing sepsis secondary to bacterial translocation from the gastrointestinal tract.
15. How is bile peritonitis diagnosed?
Diagnosis is based on analysis of the abdominal effusion. The fluid is often turbid and
golden-brown or golden-green. Cytology reveals a marked inflammatory reaction containing
many neutrophils and macrophages with intra- and extracellular particles of bile. Sepsis also can
be determined from cytology. However, a sample of fluid should be submitted for culture and
sensitivity to help direct long-term antibiotic therapy. The clinician also may compare concentra-
tions of bilirubin in the fluid to serum bilirubin concentrations (with bile peritonitis, abdominal
fluid has a markedly higher concentration of bilirubin).
16. How is bile peritonitis treated?
The patient should be fully assessed with CBC, serum biochemistry panel, and coagulation
status in an attempt to identify any underlying or coexisting problems. Hypovolemic patients
should be stabilized with adequate fluid therapy, and endotoxic shock should be addressed. Close
attention should be given to electrolyte status. For patients with hypoalbuminemia or coagulation
disorders, fresh or fresh frozen plasma should be administered. Once the animal is stabilized, sur-
gical correction of the bile leakage is necessary. Collection of abdominal fluid in the area closest
to the bile leak for cytologic evaluation and Gram stain for initial antimicrobial therapy as well as
submission for culture and sensitivity for long-term antimicrobial therapy should be performed.
Once the leak is repaired, copious lavage of the abdominal cavity with warm, physiologic saline
should be done until the abdomen is free of bile-stained fluid.
17. What causes hepatobiliary cysts?
Hepatobiliary cysts may be congenital or acquired. Congenital cysts may be single or multi-
ple and are thought to arise from embryonic bile ducts that lack communication with the biliary
system. Polycystic disease often affects both the liver and the kidneys. Often the cysts affecting
the liver are discovered incidentally during evaluation of a cat with evidence of renal insuffi-
ciency. Acquired cysts are usually solitary and may result from recent trauma, inflammation, or
neoplasia. Although most cysts are incidental findings, they may become apparent if large
enough to cause abdominal distention, impingement on normal surrounding tissues, or impaired
movement of the diaphragm.
18. Howare hepatobiliary cysts treated?
When a cat becomes symptomatic for an enlarged cyst, two options are available. The cyst
can be aspirated with ultrasound guidance to relieve pressure. Fluid analysis should be performed
to rule out other causes of fluid accumulation. The other option is surgical removal, which is per-
formed if the cyst is causing biliary obstruction or if aspiration of the cyst has to be repeated mul-
tiple times to decrease pressure on neighboring structures.
BIBLIOGRAPHY
I. Center SA: Diseases of the gallbladder and biliary tree. In Strombeck's Small Animal Gastroenterology.
3rd ed. Philadelphia, w.s, Saunders, 1996, pp 860-888.
2. Day DG: Diseases of the liver. In Sherding RG (ed): The Cat: Diseases and Clinical Management, 2nd ed.
New York, Churchill Livingstone, 1994, pp 1297-1340.
3. Tams TR: Hepatobiliary parasites. In Sherding RG (ed): The Cat: Diseases and Clinical Management. 2nd
ed. NewYork. Churchill Livingstone, 1994, pp 607-611.
Cholestasis
Erythromycin
Methy ltestosterone
Trimethoprim-sulfa
34. DRUG.. INDUCED HEPATIC DISEASE
Marcella D. Ridgway, Y.M.D., M.S.
1. Define drug-induced hepatopathy.
Any abnormality of liver function or structure resulting from the action of a drug or its
metabolites on liver cells may be termed drug-induced hepatopathy. Lesions may be obvious, such
as massive hepatic necrosis, or minute, such as changes in hepatocellular plasma membrane per-
meability that allow increased levels of cytosolic enzymes to leak into the systemic circulation.
2. What types of hepatic disease result from adverse drug reactions?
Adverse drug reactions produce either acute or chronic hepatic disease. Acute hepatic dis-
ease is more common and is associated histologically with hepatocellular necrosis. Acute disease
may range from mild and inconsequential to massive hepatic necrosis and fulminant hepatic fail-
ure. Medications that cause acute hepatic disease also can cause chronic hepatic disease if the
acute disease is mild and undetected while drug administration is continued. Chronic hepatic dis-
ease is associated histologically with mild degenerative changes and hepatic lipidosis.
3. Which drugs have been implicated in causing hepatic disease in the cat?
Hepatotoxicity of individual drugs varies significantly among species. Agents known to be
hepatotoxic in other species cannot be assumed to be hepatotoxic in cats. Likewise, agents may
cause hepatic injury in cats but not in other species. Drugs associated with acute hepatic disease
(hepatocellular necrosis), chronic hepatic disease, or cholestasis are listed below. For drugs with
no reported hepatotoxicity in cats, a high index of suspicion should be maintained for drugs with
known hepatotoxicity in other species and drugs metabolized by the liver.
Acute hepatic necrosis Chronic hepatic disease
Acetaminophen Anabolic steroids
Aspirin Corticosteroids
Diazepam Colchicine
Iron-containing supplements Megestrol acetate
Glipizide Tetracycline
Griseofulvin Valproic acid
Ketarnine
Ketoconazole
Methimazole
Phenazopyridine
Propylthiouracil
Tetracycline
Thiacetarsamide
Tiletamine/zolazepam
4. Describe the mechanisms by which drugs cause acute hepatic disease.
Acute hepatic injury may be caused by a direct toxic effect of the drug or its metabolites on the
hepatocyte, producing a predictable dose-dependent effect (acetaminophen, thiacetarsarnide), or by
idiosyncratic drug reactions, which occur unpredictably in a small number of cats exposed to a par-
ticular drug (diazepam, griseofulvin, glipizide, methimazole, others). Idiosyncratic drug reactions
probably result from preexisting abnormalities of drug-metabolizing pathways, which are due to
genetic differences or previous hepatic injury. Individual differences in drug metabolism may result
in an inability to metabolize the drug to a nontoxic form or in transformation of a normally nontoxic
drug to a toxic form via an atypical metabolic pathway. Most drug-related hepatotoxicities are due
158
Drug-induced Hepatic Disease 159
to idiosyncratic reactions. In either direct toxicity or idiosyncratic reactions, the toxic form of the
drug, usually a metabolite, causes cell damage by oxidative injury, depletion of intracellular com-
pounds or binding cellular components, resulting in impaired cell function or cell death. The hepa-
tocyte is usually the affected cell, although biliary epithelium may be affected concurrently. Chronic
hepatic disease may result from continued administration of drugs that cause mild acute hepatic
injury or with use of medications that alter metabolic pathways but do not usually cause hepatocel-
lular necrosis. Tetracycline impairs fat mobilization by the liver by inhibiting synthesis of apopro-
tein or interfering with dispersal of very-low-density lipoprotein, leading to accumulation of
triglycerides and hepatic lipidosis. Corticosteroids increase mobilization of free fatty acids to the
liver by increasing lipolysis of peripheral fat stores; this process may result in hepatic lipidosis if
hepatic fat metabolism is already compromised by anorexia or other abnormalities.
5. Howfrequently do drug-induced diseases occur?
The true incidence of drug-induced hepatic disease is unknown. Clinical signs and labora-
tory test results are nonspecific and do not differentiate drug-induced from other causes of he-
patic disease. Consequently, drugs known to have hepatotoxic potential may be wrongly blamed
for hepatic disease in a patient receiving the medication and subsequently found to have evidence
of hepatic injury. This error may delay determination of an accurate diagnosis and lead to overes-
timation of the prevalence of drug-related hepatopathy. Conversely, failure to recognize the po-
tential hepatotoxicity of a drug may delay measures to minimize exposure and the amount of
resulting hepatic damage and also lead to underestimation of the prevalence of drug-related he-
patopathy. Although the overall incidence of drug-induced hepatic disease is uncertain, severe
drug-associated hepatotoxicity is uncommon.
6. What determines the severity of hepatic disease resulting from drug administration?
The degree of hepatic damage caused by a drug may range from mild degenerative changes
and hepatic lipidosis to massive hepatic necrosis. Dose of the medication, route of administra-
tion, frequency and duration of administration, and physiologic condition of the individual
animal affect the degree of liver damage. Administration of drugs at high doses, at greater fre-
quency, or for longer periods or failure to recognize the onset of hepatic damage early in the
course of therapy (i.e., greater total amount of drug to which a cat is exposed) may result in more
severe hepatic injury if an adverse drug reaction occurs. Oral administration may potentiate hepa-
totoxicity because hepatocytes are exposed first and at higher drug concentrations via portal
blood flow. Likewise, drugs undergoing enterohepatic circulation may have enhanced potential
for hepatotoxicity. Host-related factors govern the response of an individual animal to a particu-
lar medication and the tendency to develop drug-associated hepatopathy.
7. What host factors may predispose to drug-induced hepatic disease?
Host factors such as age, sex, individual genetic constitution, nutrition, disease status, and
prior or concomitant use of other medications can affect the likelihood and severity of drug-in-
duced hepatic disease. Reduced protein binding in very young animals may alter the hepatotoxic
potential of highly protein-bound agents. The rate of metabolism of some drugs may be decreased
in younger animals because of lower hepatic enzyme activities. Older animals are more likely to
have preexisting disease and alterations in hepatic blood flow that affect rates of drug metabolism
and ability to compensate for hepatic injury. Females may be predisposed to drug-induced hepatic
disease because of higher drug-metabolizing hepatic enzyme activities and increased capacity to
generate toxic metabolites. Genetic make-up is important in determining hepatic enzyme activi-
ties, and inherited enzyme defects may significantly alter drug metabolizing capacity.
8. How may preexisting disease influence the hepatotoxic potential of a drug?
Malnutrition, especially protein deficiency, adversely affects hepatic enzyme and protein carrier
systems and is of great significance in cats, which depend on dietary protein intake to meet energy as
well as protein requirements. Any condition that alters hepatic blood flow, including cardiovascular
160 Drug-induced Hepatic Disease
disease, portosystemic shunting, and even dehydration, also alters drug metabolism by the liver. In
animals with preexisting liver disease, reduced populations of functional liver cells as well as archi-
tectural changes and acquired portosystemic shunting limit the capacity of the liver to metabolize
drugs and compromise its ability to compensate for additional hepatic damage. Cholestasis increases
the toxic potential of drugs normally excreted in bile. Concurrent exposure to other medications that
share high levels of protein binding or utilize the same carrier or enzyme systems can influence the
hepatotoxicity of a drug. Many drugs and chemicals are metabolized via cytochrome P450 enzyme
systems; prior administration of agents metabolized via this system may induce increases in P450
enzyme activities and result in increased capacity to metabolize other drugs, enhancing hepatotoxic-
ity of drugs biotransformed by the P450 enzyme system to more toxic forms.
9, What species differences in metabolism may predispose cats to drug-induced hepato-
toxicity?
Cats are true carnivores and have higher protein requirements than most other species.
Energy is derived largely from dietary protein and fat rather than carbohydrate, and the cat has
high levels of hepatic enzymes that deaminate amino acids for energy production. Metabolic
adaptation or downregulation of these enzyme systems to compensate for changes in dietary pro-
tein does not occur; cats are unable to curtail metabolism of proteins for energy in the face of de-
creased protein intake. If dietary protein intake is inadequate, cats rapidly become deficient in
important cellular proteins, including carrier proteins and enzymes that are necessary compo-
nents of drug metabolic pathways. Another species variation affecting drug metabolism in cats is
a relative deficiency of glucuronyl transferase, which mediates conjugation of various drugs to
glucuronide for elimination. The inability to form glucuronide conjugates predisposes cats to toxi-
city with drugs dependent on glucuronide conjugation, such as aspirin, acetaminophen, morphine,
and phenols. Some of these agents, such as aspirin, may be administered safely by increasing
dosing intervals. Others, such as acetaminophen and phenolic compounds, should not be used at
all in cats, yet exposure may occur when uninformed owners administer acetaminophen or apply
phenolic dermal preparations (keratolytics, coal tar products, hexachlorophene) to their pets.
10. What clinical signs are associated with drug-induced hepatopathy in cats?
Clinical manifestations range from subclinical to chronic disease to acute hepatic failure.
Subclinical mild acute hepatic injury may remain undetected unless serum chemistry profiles are
obtained. In patients with clinical disease, presenting signs are nonspecific but may suggest he-
patic disease. The severity of signs varies with the severity of the hepatic damage. Clinical signs
consistent with drug-induced hepatic disease include depression, anorexia, ptyalism, vomiting,
weakness, jaundice, and, less commonly, fever, hepatomegaly, cranial abdominal pain, and diar-
rhea. In severe cases, hemorrhage or petechiation may be noted, and neurologic signs of hepatic
encephalopathy may be present. Ascites may develop but is relatively uncommon in cats. Most
cases of drug-induced hepatopathy are mild and present with vague signs of lethargy and
anorexia with or without vomiting or jaundice.
11. What laboratory findings are consistent with drug-induced hepatopathy?
Laboratory abnormalities reflect hepatic injury and are nonspecific for drug-induced vs. other
causes of hepatic disease. Elevations in alanine aminotransferase (ALT) and aspartate aminotrans-
ferase (AST) activities are the most consistent finding. Serum alkaline phosphatase and gamma-
glutamyl transferase activities also may be increased. Bilirubinuria and hyperbilirubinemia occur
more commonly in cats than in dogs. Abnormalities in hepatic function tests (serum bile acid and
ammonia testing) and reduced levels of hepatic synthetic products (glucose, albumin, cholesterol)
are seen in more severe cases and roughly parallel the severity of the hepatic damage. Clotting
factor deficiencies may arise as a result of synthetic failure or disseminated intravascular coagula-
tion secondary to severe hepatic insult; coagulation profiles should be assessed before liver aspi-
rate or biopsy procedures are performed. Electrolyte imbalances (hypokalemia, hyponatremia)
and acid-base disturbances (metabolic acidosis) may occur. Patients with hepatic encephalopathy
Drug-induced Hepatic Disease 161
may develop respiratory alkalosis and hypophosphatemia. Complete blood count may show mild
nonregenerative anemia, reduced platelet numbers, and either neutrophilia or neutropenia.
12. How is drug-induced hepatopathy diagnosed?
Because no clinical signs, laboratory profiles, or histopathologic changes are pathognomonic
for drug-induced hepatic disease, diagnosis depends largely on recognition of the hepatotoxic po-
tential of therapeutic agents, historical association of exposure to a drug coincidental with onset
of hepatic disease, and diagnostic evaluation to rule out other causes of hepatic disease. Drug-in-
duced hepatopathy should be considered as a differential in all cases of hepatic disease. A pre-
sumptive diagnosis of drug-induced hepatopathy may be based on the following findings:
History of drug exposure
Clinical signs and/or laboratory abnormalities consistent with hepatic damage due to ad-
ministration of the drug
Resolution of clinical signs and laboratory abnormalities (within a few days to a few
weeks) when drug administration is discontinued.
Liver biopsy may help to rule out other potential causes of hepatic disease, but histopatho-
logic changes seen in cases of adverse drug reactions are nonspecific and not diagnostic of drug-
induced hepatopathy. Often, if a patient improves after withdrawal of the drug, a biopsy is not
performed. Definitive diagnosis by resuming administration of the implicated drug and evaluat-
ing for recurrence of hepatic disease is usually contraindicated.
13. Howare cats with drug-induced hepatic disease treated?
Immediate withdrawal of the drug is indicated in all patients with suspected drug-induced
hepatopathy. With the exception of acetaminophen, phenol, or iron toxicity, there are no specific
treatments or antidotes to counteract the effects of hepatoxic drugs. Treatment, therefore, is di-
rected at limiting exposure to the drug and providing supportive care proportionate to the level of
hepatic dysfunction. In subclinical cases, identified only by elevations of hepatic transaminases,
simply discontinuing the drug may be sufficient. In clinical cases, additional measures of general
supportive treatment for acute hepatic disease are initiated and may include intravenous fluids,
electrolyte supplementation, correction of acid-base status, glucose supplementation, antibiotics,
and management of coagulopathies and hepatic encephalopathy. Use of medications that affect
cytochrome P450 enzyme activity are best avoided. Cats showing clinical signs of hepatic dis-
ease usually require aggressive nutritional support to meet caloric and protein needs.
14. What additional treatments are available for specific therapy of hepatic disease caused
by acetaminophen, phenol, or iron toxicity?
In addition to general supportive care, cats with acetaminophen-induced hepatic necrosis are
treated with N-acetylcysteine to help to restore hepatic glutathione, which is depleted rapidly in
cats exposed to acetaminophen or phenacetin. When given within the first 8-10 hours after expo-
sure, N-acetylcysteine may limit formation of toxic metabolites. A 5% solution is administered
initially at an intravenous or oral loading dose of 140 mglkg, followed by 5-7 additional treat-
ments of 70 mglkg intravenously or orally every 4 hours. Treatment with N-acetylcysteine is also
used in cases of phenol intoxication to limit hepatic injury, which occurs within the first 12-24
hours of phenol exposure. Iron toxicity is treated with desferroxarnine, which chelates iron and
enhances urinary excretion. Desferroxarnine is administered by constant-rate infusion of 15
mg/kglhr intravenously or 40 mglkg intramuscularly every 4-8 hours until serum iron levels drop
below 300 Illldi.
15. Describe the main characteristics of diazepam-associated hepatic disease.
Severe acute hepatic necrosis and failure occur sporadically in cats treated with routine doses
of diazepam prescribed for behavioral or micturition problems. Diazepam-associated hepatotoxi-
city is most likely due to an idiosyncratic drug reaction, occurring in only a few of the cats re-
ceiving the medication, and requires no prior sensitization. Affected cats show anorexia, lethargy,
162 Drug-induced Hepatic Disease
and ataxia within 4 days of starting therapy and jaundice within I I days. Marked elevations of
serum ALT and AST activities are consistently found; hypoglycemia, hypocholesterolemia, and
abnormal coagulation tests also may be present. Most affected cats die of fulminant hepatic fail-
ure. Because of this hepatotoxic potential, cats placed on diazepam should be monitored for in-
creases in ALT and AST. If hepatic enzyme abnormalities arise, drug therapy should be
suspended and supportive care provided.
16. What is the prognosis for recovery from drug-induced hepatic disease?
Clinical outcome depends on the extent of hepatic damage. In most cases, the degree of liver
injury is mild; with discontinuation of the drug and supportive therapy, complete recovery is
likely. The liver has tremendous regenerative capacity. Even in severe cases, recovery of adequate
hepatic function is possible if the patient can be supported through the initial period of acute he-
patic necrosis and if the liver retains the ability to regenerate (adequate remaining cell popula-
tions and intact reticular framework). However, most cats that develop acute fulminant hepatic
failure do not survive.
17. Are drug-induced hepatic diseases preventable?
Awareness of potential hepatotoxicity and predisposing factors as well as early detection of
hepatic injury are key to selecting therapeutic agents and preventing clinically significant hepatic
disease. Patients receiving drugs with hepatotoxic potential should be monitored for evidence of
hepatic injury on serum chemistry profiles. Baseline chemistry values should be determined
before treatment to serve as a reference point for monitoring and to help identify preexisting dis-
ease conditions. Avoid exceeding recommended dosing levels and frequency, and limit duration
of therapy to the minimum required for effectiveness. Maintaining an index of suspicion of drugs
as potential hepatotoxins and early evaluation of patients that develop clinical signs after receiv-
ing any drug for evidence of hepatic injury help to limit the degree of liver damage.
BIBLIOGRAPHY
J. Bunch SE: Acute hepatic disorders and systemic disorders that involve the liver. In Ettinger SJ, Feldman
EC (eds): Textbook of Veterinary Internal Medicine Volume, vol. 2, 5th ed. Philadelphia, WB.
Saunders, 2000, pp 1326-1340.
2. Bunch SE: Hepatotoxicity associated with pharmacologic agents in dogs and cats. Vet Clin North Am
Small Anim Pract 23:659--670, 1993.
3. Center SA: Acute hepatic injury: Hepatic necrosis and fulminant hepatic failure. In Guilford WG, Center
SA, Strombeck DR, et aI (eds): Strombeck's Small Animal Gastroenterology, 3rd ed. Philadelphia,
WB. Saunders, 1996, pp 654-704.
4. Center SA: Hepatic Lipidosis. In August JR: Consultations in Feline Internal Medicine 2. Philadelphia,
WB. Saunders Co., 1994, pp 87-101.
5. Center SA, Elston TH, Rowland PH, et a1: Fulminant hepatic failure associated with oral administration
of diazepam in I I cats. J Am Vet Med Assoc 209:618--625, 1996.
6. Hooser SB: Hepatotoxins. In Bonagura 10 (ed): Kirk's Current Veterinary Therapy xm Small Animal
Practice. Philadelphia, WB. Saunders, 2000, pp 217-219.
7. Johnson SE: Diseases of the liver. In Ettinger SJ, Feldman EC(eds): Textbook of Veterinary Internal
Medicine Volume, vol, 2, 4th ed. Philadelphia, WB. Saunders., 1995, pp 1313-1326.
8. Kaufman AC, Greene CE: Increased alanine transaminase activity associated with tetracycline adminis-
tration in a cat. J Am Vet Med Assoc 202:628--630, 1993.
9. Nelson RW, et al: Effect of an orally administered sulfonylurea, glipizide, for treatment of diabetes mel-
litus in cats. J Am Vet Med Assoc 203:821-827, 1993.
10. Papich MG, Davis LE: Drugs and the liver. Vet Clin North Am Small Anim Pract 15:77-95, 1985.
I I. Peterson ME, Kintzer PP, Hurvitz AI: Methimazole treatment of 262 cats with hyperthyroidism. J Vet
Intern Med 2:150-157,1988.
12. Wilke JR: Idiosyncrasies of drug metabolism in cats: Effect on pharmacotherapeutics in feline practice.
Vet Clin North Am 14:1345-1354, 1984.
35. PORTOSYSTEMIC SHUNTS
Margo L. Menl, D.V.M.
1. Define portosystemic shunt.
A portosystemic shunt (PSS) is an abnormal vascular communication between the portal
venous system and the systemic venous system. The portal system normally drains blood from
the abdominal viscera to the liver for removal of toxins. A PSS diverts normal portal blood flow
around the liver and directly into systemic circulation.
2. What is the difference between intrahepatic and extrahepatic portosystemic shunts?
The ductus venosus is a normal fetal structure that allows umbilical venous blood to bypass
the liver; during gestation or shortly thereafter, it is stimulated to close. Intrahepatic shunts occur
more commonly in dogs than cats and typically are congenital. singular shunts that represent
failed closure of the ductus venosus. Extrahepatic shunts may be congenital or acquired. In cats,
extrahepatic shunts are more common than intrahepatic shunts, and most shunt vessels arise from
the left gastric vein and empty into the abdominal vena cava.
3. What is the difference between congenital and acquired portosystemic shunts?
A congenital shunt is present at birth and usually remains as a single intra- or extrahepatic
shunt. An acquired shunt results from sustained portal hypertension, most often secondary to
chronic liver disease. Most acquired shunts are multiple and extrahepatic; they are rare in cats.
4. Are portosystemic shunts hereditary?
Portosystemic shunts have not proven to be hereditary. However, they are recognized more
frequently in male cats of mixed breeding (approximately 70%) that are < 3 years of age. Of the
remaining 30% of purebred cats, 23% are of Himalayan and Persian breeds. Acquired PSS re-
sults from chronic liver disease and therefore can occur in any breed.
5. What are the common clinical findings of portosystemic shunts?
Physical examination findings and clinical abnormalities associated with PSS usually result
from central nervous system disease, liver insufficiency, or urinary tract disease. Affected ani-
mals are usually thin and undersized. Ptyalism is the most frequently reported clinical sign in
cats. In addition, copper-colored irises have been reported in cats with PSS.
Clinical Signs Associated with Portosystemic Shunt
Central nervous system
Behavior changes
Blindness
Seizures
Dementia
Liver insufficiency
Anorexia
Depression
Polyuria
Weightloss
Urinary system
Hematuria
Pollakiuria
Deafness
Aggression
Stupor/coma
Tremors
Lethargy
Polydipsia
Pica
Stuntedgrowth
Stranguria
Urethral obstruction
Pacing
Ataxia
Weakness
Disorientation
Diarrhea
Ptyalism
Nausea
Vomiting
163
164 Portosystemic Shunts
Isosthenuria
Hematuria
Anemia
Microcytosis
Hypochromasia
6. Why do patients with portosystemic shunts have decreased liver function?
Portal venous blood supplies 50% of oxygen delivery to the liver and contains hepatotrophic
(liver-supportive) growth factors such as insulin. These factors are necessary for hepatocyte
growth and function. When a substantial PSS is present, these growth factors bypass the liver, re-
sulting in atrophy, atresia, hypoplasia, and dysfunction. Hepatic hypertrophy, hyperplasia, regen-
eration, and glycogen storage are impaired.
7. Define hepatic encephalopathy.
Hepatic encephalopathy (HE) is abnormal mentation and neurologic function induced by ab-
sorbed intestinal toxins that have not been removed by the liver. To date, the exact mechanism of
HE is not clear. HE is believed to result from diversion of portal blood flow around the liver, al-
lowing ammonia, encephalotoxins, and endotoxins into systemic circulation. These toxins di-
rectly affect the cerebral cortex.
8. What fmdings of routine bloodwork and urinalysis support a diagnosis of PSS?
Laboratory findings are often nonspecific. The most common abnormalities include micro-
cytic anemia, low blood urea nitrogen, hypoalbuminemia, hypoglycemia, hypocholesterolemia,
and mild-to-moderate elevations in alanine aminotransferse (ALT) and alkaline phosphatase
(ALP) activities. In any patient with a typical history, supportive clinical findings, and presence
of ammonium biurate crystalluria, further liver function testing is recommended.
Laboratory Abnormalities Associated with Portosystemic Shunt
Hematologicflndings
Neutrophilicleukocytosis
Poikilocytosis
Target cell formation
Serum biochemicalpanel
Lowblood urea nitrogen Hyperarnmonemia
Increasedalkaline phosphatase Increasedalanine aminostransferase
Hypoglycemia Hypocholesterolemia
Hypoproteinemia Hypematrernia
Hyperchloremia Hypokalemia
Urinalysis
Ammoniumbiurate crystalluria
9. How is PSS diagnosed?
Liver insufficiency is suggested by the combination of history, physical examination find-
ings, and both hematologic and serum biochemical abnormalities. Results of pre- and post-
prandial measurements of serum bile acid concentration and ammonium tolerance tests are
more sensitive than serum biochemical tests for detecting hepatic dysfunction but are not spe-
cific for PSS.
10. What imaging modalities are used to diagnose PSS?
Various imaging modalities are used to determine the extent and location of PSS.
Abdominal radiographs often detect a small liver. Ultrasonograhy is a noninvasive way to evalu-
ate liver architecture and vessels but is highly operator-dependent. Ultrasound also can be used
intraoperatively to locate an intrahepatic PSS. Nuclear scintigraphy is a sensitive and specific
technique to detect PSS but is not consistent in differentiating intra- and extrahepatic shunts.
Angiography can be used to visualize the portal venous system, diagnose a shunt, and determine
its location. Laparoscopy may allow visualization of an extrahepatic PSS. Most patients with
PSS undergo exploratory laparotomy for diagnosis, determination of location, and potential sur-
gical correction.
TECHNIQUE
Portosystemic Shunts
Imaging Modalities Used in the Diagnosis of Portosystemic Shunt
SUPPORTIVEFINDINGS DISADVANTAGES
165
Radiology
Ultrasonography
Nuclear scintigraphy
Angiography
Laparoscopy
Microhepatica
Renomegaly
Microhepatica
Undetectable portal or hepatic
veins
Initially greater fraction of radio-
activity in heart than in liver
Visualization of portal blood flow
Direct viewing of extrahepatic
shunting vessel or lack thereof
and obtaining of liver biopsy
Not specific
Highly operator-dependent, less sen-
sitive for extrahepatic shunts
Unable to determine location of shunt
Unable to distinguish between single
and multiple shunts
Invasive, requires general anesthesia
Unable to see within liver parenchyma
or to perform surgical correction
11. What differential diagnoses should be considered?
Other differential diagnoses refer to the organ system affected; gastrointestinal system, central
nervous system, or urinary tract. Typical examples include liver failure due to other causes (hepa-
totoxins, infection, autoimmune disorder, neoplasia, or lipidosis), congenital urea cycle enzyme
deficiency, other hepatic vascular disorders, and other causes of seizures in young animals.
12. How are most cases oCPSSmanaged?
A combination of medical and surgical management is often used. The goal of medical man-
agement is to prevent the production and slow the absorption of central nervous system toxins
produced by bacteria in the intestinal tract. Medical management alone has been successful in
supporting some cases for more than 2 years. However, surgery should be performed, if possible.
to redirect portal blood flow to the liver and potentially reverse hepatic atrophy and alleviate clin-
ical signs. If surgery is performed, medical management typically is continued for 2-4 weeks
beyond the resolution of clinical signs. Medical management includes a high-carbohydrate, low-
protein diet to reduce the dietary source of ammonia, cathartics to decrease ammonia production
and absorption. colonic pH modifiers to trap NH
4
+ in the colon, and oral antibiotics to reduce
urease-producing intestinal bacteria.
Long-term Medical Management ofPortosystemic Shunt and Hepatic Insufficiency
Dietary modifications
The goals of dietary modifications are to decrease the amount of protein available for ammonia produc-
tion. increase fiber concentration, and promote fecal nitrogen excretion. Diets with protein requirements
of at least 16% to 30% protein on a dry matter basis with easily digestible carbohydrate sources should
be used. Diets used for the management of renal insufficiency (see Chapter 40) may be effective.
Oral antibiotics
Oral antibiotics are administered to decrease numbers of urease-producing bacteria in gastrointestinal
tract. Urease-producing bacteria hydrolyze urea to ammonia in the intestine, thereby causing high am-
monia levels.
Neomycin, 10-20 mglkg orally every 8-12 hr
Metronidazole, 7.5 mglkg orally every 8 hr
Ampicillin, 22-33 mglkg orally every 8hr
Cathartics
Lactulose is a disaccharide that is converted in the colon to organic acids that lower colonic pH, re-
sulting in conversion ofNH
3
to NH/, which is not as readily absorbed. In addition, lactulose in-
creases intestinal transit time, thereby decreasing time for production and absorption of toxins.
Dosage is empirical, starting with 0.25-0.5 mJlkg orally every 8-12 hr.
166 Portosystemic Shunts
13. What considerations must be given to drug therapy and anesthetic use in patients with
PSS?
In selecting anesthetic agents, hepatic metabolism, cardiovascular effects, and effects of the
anesthetic agent on portal venous and hepatic arterial blood flow need to be considered.
Barbiturates, acepromazine, and diazepam should be avoided because they are highly protein-
bound and require liver metabolism. In addition, halothane is potentially hepatotoxic and should
not be used. Isoflurane is the anesthetic agent of choice for induction and maintenance but has
been reported to produce hypotension in some cases. An alternative for induction is fentanyl in
small boluses (0.01-0.03 mg/kg intravenously) or as a constant-rate infusion (0.7 ~ g / k g / h r ) .
However, narcotics can result in prolonged recovery time and may require administration of
naloxone (0.02--0.04mg/kg intravenously) as a reversal agent.
14. What parameters should be monitored postoperatively in cats with PSS?
Postoperatively cats should be monitored closely for signs of portal hypertension, including
diarrhea, vomiting, distention of the abdomen or ascites, and abdominal pain as well as hypov-
olemia. Blood glucose should be monitored postoperatively. Cats with PSS also require close
monitoring for seizures, which have been reported to occur up to 3 days postoperatively.
15. What are the complications of PSS?
The primary complications of medical management relate to progressive worsening of
clinical disease associated with liver atrophy. Complications of preoperative anesthesia may
include hypotension, hypothermia, and hypoglycemia. Portal hypertension during or after
surgery, hemorrhage at liver biopsy site or during dissection, postsurgical sepsis, seizures,
and recurrence of clinical signs are also possible. The most common complication after PSS
ligation is abdominal distention, which may not need treatment if it is the only clinical abnor-
mality.
16. What are the most common signs of postoperative portal hypertension? How should it
be treated?
Clinical signs associated with portal hypertension include cardiovascular collapse, severe
abdominal pain and distention, and delayed recovery from anesthesia. If clinical signs of portal
hypertension occur after surgery, the patient requires supportive care and immediate surgical in-
tervention to remove the ligature.
17. How is hepatic encephalopathy treated?
High-protein meals, constipation, infection, gastrointestinal hemorrhage, hypovolemia, hy-
pokalemia, alkalosis, and hypoglycemia exacerbate neurologic signs in animals with PSS.
Treatment, therefore, is aimed at correcting fluid deficits and electrolyte and or acid-base ab-
normalities, minimizing formation and absorption of ammonia and other toxins, and treating
seizures. Administration of 0.9% sodium chloride with potassium supplementation helps to cor-
rect metabolic alkalosis and hypokalemia. Lactulose and either neomycin or metronidazole
should be administered to conscious animals to increase intestinal transit time and to trap am-
monium ions in the bowel. In comatose cats, lactulose or 10% povidone-iodine enemas should
be given. Cats with seizures at the time of presentation should be treated parenterally to slop
seizure activity.
18. What is the prognosis for a patient with PSS?
Although several different patterns of abnormal portosystemic vasculature connections have
been described in dogs, the most common anomaly in cats is a single extrahepatic shunt. A single
extrahepatic shunt in canine patients carries a good prognosis with surgical correction, but in cats
this does not appear to be the case. Because of postoperative complications and decreased ability
of the liver to accommodate the increased hepatic blood flow, the prognosis for PSS with surgery
is less favorable in cats than in dogs.
Pancreatic Diseases
BIBLIOGRAPHY
167
I. Holt D: Critical care management of the portosystemic shunt patient. Comp Cont Educ Pract Vet
16:879-889, 1994.
2. Holt DE, Schellin CG, Saunders MH, et al: Correction of ultrasonographic findings with surgical, porto-
graphic, and necropsy findings in dogs and cats with portosystemic shunts: 63 cases (1987-1993). J
Am Vet Med Assoc 207:1190--1193,1995.
3. Koblik PD, Homorf WJ: Transcolonic sodium pertechnetate Tc 99m scintigraphy for diagnosis of
macrovascular portosysternic shunts in dogs, cats, and potbellied pigs: 176 cases (1988-1992). J Am
Vet MedAssoc 207:729-732,1995.
4. Lamb CR, Forester-van Hijfte MA, White RN, et al: Ultrasonographic diagnosis of congenital portosys-
ternic shunt in 14 cats. J Small Anim Pract 37:205-209,1996.
5. Leveille-Webster CR: Disease of the hepatobiliary system. In Morgan RV (ed): Handbook of Small
Animal Practice, 3rd ed. Philadelphia, W.B. Saunders, 1997, pp 383-401.
6. Martin RA: Congenital portosysternic shunts in the dog and cat. Vet Clin North Am 23:609-623, 1993.
7. Moon M: Diagnostic imaging ofportosysternic shunts. Semin Vet Med Surg (Small Animal) 5:120--126,
1990.
8. Payne IT, Martin RA, Constantinescu GM: The anatomy and embryology of portosystemic shunts in
dogs and cats. Sernin Vet Med Surg (Small Animal) 5:76-82,1990.
9. Swalec TK, Besser TE: Evaluation of leukocytosis, bacteremia, and portal vein partial oxygen tension in
clinically normal dogs and dogs with portosystemic shunts. J Am Vet MedAssoc 211:715-718,1997.
10. Swalec T, Karen M, Rawlings CA: Surgical techniques for extravascular occlusion of intraltepatic shunts.
Comp Cont Educ Prac Vet 8:745-754,1996.
11. Swalec T, Karen M, Seguin B, et al: Surgical approaches to single extraltepatic portosystemic shunts.
Comp Cont Educ Prac Vet 20:593-601, 1998.
12. VanGundy TE, Boothe HW, Wolf A: Results of surgical management of feline portosystemic shunts. J
Amr Anim Hosp Assoc 26:5-62, 1990.
13. Vogt JC, Krahwinkel DJ, Bright RM, et a1: Gradual occlusion of extrahepatic portosystemic shunts in
dogs and cats using the arneroid constrictor. Vet Surg 25:495-502, 1996.
14. White RN, Trower ND, McEvoy FJ, et a1: A method for controlling portal pressure after attenuation of
intraltepatic portacaval shunts. Vet Surg 25:407-413, 1996.
15. Whiting PG, Peterson SL: Portosystemic shunts. In Slatter (ed): Textbook of Small Animal Surgery, vol.
I, 2nd ed. Philadelphia, w.s. Saunders, 1993, pp 660-677.
36. PANCREATIC DISEASE
Margie Scherk, D.V.M.
1. Which pancreatic diseases occur in cats?
For years, feline pancreatic diseases were assumed to be similar to those in dogs. Currently, it
appears that pancreatic disorders are quite different in cats. Overall, acute septicemic pancreatitis
and exocrine pancreatic insufficiency (EPI) are much less common in cats than in dogs. Chronic
nonsuppurative and suppurative pancreatitis are the most common forms. The most common pan-
creatic neoplasms include primary pancreatic adenocarcinoma as well as metastatic lymphosar-
coma and mast cell tumor. Pancreatic abscesses are occasionally found. Toxoplasma gondii,
Eurytrema procyon is (liver fluke), feline infectious peritonitis, feline parvovirus, and herpesvirus
I can infect the pancreas. However, more than 90% of cases of feline pancreatitis are idiopathic.
2. What forms of pancreatitis are seen in cats?
Both acute and chronic pancreatitis are reported. Although both can be mild or severe, acute
cases tend to be more severe than chronic cases. Mild pancreatitis generally results in minimal
clinical signs, minimal necrosis, and low mortality rates In severe pancreatitis (necrotizing, hem-
morhagic), extensive pancreatic necrosis and multiple-organ involvement with or without organ
failure lead to a poor prognosis. Fortunately, this form is rare in cats.
168 Pancreatic Diseases
Pancreatitis in cats is usually either suppurative (neutrophilic) or nonsuppurative (lympho-
cytic/plasmacytic or eosinophilic). These disorders may be discrete or occur in conjunction with
idiopathic inflammatory bowel disease, cholangitis/cholangiohepatitis complex, or both (triadi-
tis). See Chapters 23 and 29 for a further discussion of triaditis.
3. What are the clinical fmdings of pancreatitis?
Presenting complaints are vague and may include lethargy, inappetence, weight loss, vomit-
ing, diarrhea, abdominal pain, and ataxia. On physical examination, dehydration, hypothermia,
weight loss, lethargy, icterus, and abdominal pain, which may be localized to the right anterior
quadrant, are often detected. Pleural and peritoneal effusion rarely occur but can result in abdom-
inal distention or dyspnea.
4. What is the initial diagnostic plan for cats with suspected pancreatitis?
Complete blood cell count with differential, serum biochemical panel, urinalysis, and blood
pressure evaluation are usually performed in sick cats but do not show pathognomonic changes
for pancreatic disease. An inflammatory leukogram, which indicates inflammation, infection, or
an immune-mediated process, may be present, depending on the form of pancreatitis and degree
of chronicity. In addition, mild, nonregenerative anemia (anemia of chronic disease) and hyper-
proteinemia occur in some cats with chronic inflammation. Changes in liver enzyme activities
and other serum biochemical abnormalities vary, depending on predisposing diseases and pres-
ence of cholangiohepatitis.
5. Can imaging techniques aid in the diagnosis of pancreatitis?
Abdominal radiographs may show decreased serosal detail in the right anterior quadrant and
bunching of small bowel loops in cases of acute pancreatitis. Sonographic evaluation of the pan-
creas by an experienced ultrasonographer may help to identify pancreatic changes, to interpret
active inflammation or fibrosis of the pancreas, and to note other changes in adjacent viscera.
Ultrasound may detect small amounts of fluid, which can aspirated for fluid analysis.
6. Are concurrent disorders common?
Many cats with pancreatitis have other diseases. Hepatic lipidosis, cholangitis/cholangiohep-
atitis, idiopathic inflammatory bowel disease, enteritis, diabetes mellitus, and vitamin Kj-respon-
sive coagulopathy are common. Cats with hepatic lipidosis and pancreatitis have a poorer
prognosis than cats with lipidosis alone.
7. Are serum amylase and lipase concentrations predictive of pancreatitis?
Not really. Amylase is a nonspecific gastrointestinal (GI) enzyme in cats; it may be elevated
because of disease in other parts of the GI tract. In addition, amylase is excreted by the kidneys;
decreased renal clearance (dehydration, concurrent renal disease) causes elevations of serum amy-
lase. Thus, increased amylase activity does not correlate with the presence of pancreatic inflam-
mation. Lipase is similar to amylase, but an elevated level is usually significant. The pancreas
should be assessed with other tests, such as ultrasound or serum trypsin-like immunoreactivity
(TLI). Unfortunately, many cats with pancreatitis have normal amylase and lipase activities.
8. Can abdominal effusion aid in the diagnosis of pancreatitis?
If abdominal effusion is present, routine cytologic evaluation should be performed. Most effu-
sions are nonseptic suppurative exudates with increased protein concentrations and a mixture of
degenerate neutrophils, nondegenerate neutrophils, and macrophages. It has been proposed that if
lipase or amylase activities are greater in abdominal effusion than in serum, pancreatitis is present.
9. How does serum TLi aid in the diagnosis of pancreatic diseases?
Theoretically, serum TLI concentrations increase with inflammatory diseases of the pan-
creas and are decreased with EPI. However, serum TLI frequently fails to correlate with presence
of chronic pancreatitis in cats.
Pancreatic Diseases 169
10. Howcan suppurative and nonsuppurative pancreatitis be differentiated?
Histopathologic evaluation of pancreatic tissues is the only way to confirm and classify pan-
creatitis. Because triaditis is common, liver and small intestinal biopsies are often obtained at the
same time (see Chapters 23 and 29). Pancreatic biopsies can be obtained via laparotomy or la-
paroscopy. The pancreas should be isolated gently, and 3-4-mm wedge samples should be taken
from abnormal-appearing areas or from both left and right poles of the pancreas with small, sharp
scissors such as iris scissors. Overall, Iaparoscopy-obtained biopsies are less invasive, but the
areas of the pancreas that can be sampled are limited.
11. Howis the pain associated with pancreatitis treated?
Regardless of the type, pancreatitis is painful. Use an opioid such as oxymorphone, hydro-
morphone, or morphine. Butorphanol is less effective for visceral analgesia. If the patient appears
to benefit from a test dose of opioid, consider application of a transdermal fentanyl patch
(Duragesic, Janssen Phamaceutical, Titusville, NJ). Analgesia is required for a number of days,
and the continuous release by a transdermal patch avoids peak and trough levels of opioid. Do
not make patients show you that they are in pain.
Analgesics Used in the Treatment ofPancreatitis
GENERIC NAME TRADE NAME DOSE
Butorphanol
Hydromorphone
Morphine
Oxymorphone
Torbugesic
Dilaudid
Morphine sulfate
Numorphan
0.1-0.8 mglkg every 4 hr IV, 1M, SQ
0.1-0.4 mglkg every 4hr IV, 1M, SQ
IV=intravenously, 1M =intramuscularly, SQ=subcutaneously.
12. What antiemitics should be used?
Antiemetics should be used as indicated clinically; in cats with concurrent hepatic dysfunction,
doses should be reduced accordingly. Antiemetics commonly used in the cat include metoclopramide
and clorpromazine. Each has its side effects. Central nervous system sedation, frenzied behavior, or
disorientation may be associated with metoclopramide, and chlorpromazine has a hypotensive effect.
While costly, ondansentron is quite beneficial in the patient with intractable vomiting.
Antiemetics Used in the Treatment of Pancreatitis
GENERIC NAME
Chlorpromazine
Prochlorpromazine
Diphenhydramine
Dimenhydrinate
Prochlorpromazine
+ isopropamide
Metoclopramide
Ondansentron
TRADE NAME
Thorazine, Largactil
Compazine
Benadryl
Dramamine
Darbazine
Reglan
Zofran
DOSE
0.5 mglkg every 8hr 1M
0.1 mg/kg every 6 hr 1M
2.0-4.0 mg/kg every 8hr PO
2.0 mglkg every 8 hr 1M
8.0 mglkg every 8 hr PO
0.5-0.8 rug/kg every 12 hr 1M, SQ
1-2 mg/kg constant-rate IV infusion over 24 hr
0.1-0.15 mglkg slowIVpush every6-12 hr, as needed
1M =intramuscularly, PO=orally, SQ=subcutaneously, IV=intravenous.
Adapted from Ogilvie G: Presentation at the Fall Meeting of the American Association of Feline
Practitioners, 1997,withpermission.
13. Describe the approach to nutritional support in cats with pancreatitis.
Nutritional support is critical even in the acute phase. In acute pancreatitis, total or par-
tial parenteral nutrition may be required. If exploratory laparotomy for biopsies and lavage is
performed, jejunal and gastric feeding tubes should be placed. Jejunal feeding should be given during
the acute phase (see Chapter 62) because stimulation of pancreatic secretion is less likely than with
use of a gastrostomy tube.
I 70 Pancreatic Diseases
14. What other nonspecific treatments are used for acute pancreatitis?
Fluid therapy with appropriate electrolyte adjustments and water-soluble vitamins is essential.
If hypoalbuminemia develops, colloid support is indicated.
Dopamine administered at a constant-rate infusion of 3 Ilglkg/min improved pancreatic
perfusion in a model of alcoholic pancreatitis in cats.
15. How is suppurative pancreatitis treated?
A quinolone combined with a penicillin or metronidazole should be administered empiri-
cally while you wait for bacterial culture and antimicrobial susceptibility results. Antimicrobial
choices are then based on the results and administered for at least 6-8 weeks.
16. How is nonsuppurative pancreatitis treated?
1. Prednisolone or another glucocorticoid is the cornerstone of therapy for lymphocytic/
plasmacytic disorders in cats. As with inflammatory bowel disease, it is important to start with a
high enough dose to suppress the inflammatory response. A reasonable starting dose of pred-
nisolone is 2-4 mglkg orally every 12 hours for 1 month or until clinical remission occurs. The
dose is then tapered to once every 48 hours for 2-3 months (see Chapter 23).
2. Metronidazole can be used concurrently for its anaerobic spectrum as well as its immune-
modulating properties. At oral doses of 10 mglkg every 12 hours, it can be used for long periods
(months).
3. With lymphocytic/plasmacytic disorders, it is best to eliminate allergens whenever possi-
ble as well as to modulate immune response. Thus, an enteric bland diet, which has limited anti-
gens and low residue and is calorie-dense, is recommended once the patient is eating well. Some
of these diets may include omega-6 and omega-3 fatty acids in a 5:1 ratio, which has an anti-in-
flammatory effect. Protein restriction is not required unless the patient is encephalopathic. The
fact that the cat eats is more important than what the cat eats (see Chapter 62).
17. Describe the treatment of pancreatitis induced by Toxoplasma gomiii.
Pancreatitis induced by T. gondii is almost never documented on antemortem evaluation.
Increasing IgG titers or high IgM titers suggest acute infection. The organism can be identified
on histologic examination of pancreatic tissue. If it is suspected, clindamycin (10-12 mglkg
orally every 12 hr) may be an effective treatment (see Chapter 36).
18. Describe the treatment of pancreatitis induced by Eurytremaprocyonis and Amphimerus
pseudofelineus,
E. procyonis may infest the pancreatic duct, whereas A. pseudofelineus may infest the pan-
creas itself. The diagnosis is made by finding the eggs on examination of fresh feces using forma-
lin-ethyl sedimentation. Fenbendazole (30 mglkg orally every 24 hr for 6 days) is recommended
for treatment of E. procyonis; praziquantal has been used at a very high dose (40 mglkg orally
every 24 hr for 3 days) to treat A. pseudofelineus. E. procyonismay be considered when cats are
exposed to raccoons or foxes.
19. How is therapeutic response monitored?
Cessation of vomiting and diarrhea are obvious signs of improvement. If lesions were ini-
tially present, repeat ultrasound examination can provide objective evidence of disease resolu-
tion. If CBC or biochemical abnormalities were present, resolution suggests improvement. Client
and clinician evaluations are subjectively valuable; concrete assessments of body weight, muscle
tone, coat condition, activity level, attitude, and appetite are also helpful.
20. What is the prognosis for cats with pancreatitis?
Prognosis depends on the type of pancreatitis as well as duration and severity. Many cats have
chronic, low-grade smoldering pancreatitides and live long lives, but they do better with diagnosis
and appropriate therapy.
Pancreatic Diseases 171
21. Does chronic pancreatitis predispose to other clinical syndromes?
Untreated nonsuppurative pancreatitis has the potential to develop into acute necrotizing
pancreatitis.
Type I diabetes mellitus may develop as a result of loss of beta cells.
Exocrine pancreatic insufficiency (EPI) may result from loss of acinar tissue.
Chronic lymphocytic plasmacytic inflammation may progress to small cell lymphoma in
some patients (controversial).
22. Is EPI common in cats?
Congenital EPI is rare in cats compared with dogs. Occasionally EPI results from chronic
pancreatitis.
23. Describe the clinical findings of EPI.
If active pancreatitis is not present, most cats have polyphagia with failure to thrive or weight
loss and poor coats. The stool is often voluminous and may appear as undigested food; diarrhea
may be present.
24. How is EPI diagnosed?
Increased neutral fats are present when stool is evaluated microscopically with Sudan IV
stain. Fecal trypsin, as assessed by gel digestion, should be decreased, but this finding is not spe-
cific for EPI. Serum TLI concentrations should be decreased, but this parameter has not been
used to assess large numbers of cats with EPI. Serum cobalamin and folate levels are expected to
be subnormal in most cases.
25. How is EPI treated?
High-fat foods should be avoided. Pancreatic enzyme replacement is added to food to effect.
Preincubation with the food for 15-30 minutes before feeding may be beneficial.
26. What is the prognosis for cats with pancreatic neoplasms?
The management and prognosis of pancreatic lymphosarcoma are similar to those described
for alimenteric lymphosarcoma (see Chapter 24). Because there is no effective therapy for adeno-
carcinoma, the prognosis is guarded.
BIBLIOGRAPHY
I. Akol KG, Washabau Rl, Saunders HM, et a1: Acute pancreatitis in cats with hepatic lipidosis. 1Vet Intern
Med 7:205-209, 1993.
2. Hill RC, Van Winkle Tl: Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat: A
retrospective study of 40 cases (1976-1989).1 Vet Intern Med 7:34--39,1993.
3. Mathews KA: Pain assessment and general approach to management. Vet Clin North Am Small Animal
Pract 30:729-755, 2000.
4. Parent C, Washabau RI, Williams OA, et al: Serum trypsin-like immunoreactivity, amylase and lipase in
the diagnosis of feline pancreatitis. Proceedings of 13th Annual Forum of the American College of
Veterinary Internal Medicine, 1995.
5. Pascoe PI: Opioid analgesics. Vet Clin North Am Small Animal Pract 30:757-772, 2000.
6. Steiner 1M, Williams OA: Feline pancreatitis. Compend Contin Educ Pract Vet 19:590-603, 1997.
7. Steiner 1M, Williams DA: Feline exocrine pancreatic disorders. Vet Clin North Am Small Anim Pract
29:551-575.1999.
8. Stewart AF: Pancreatitis in dogs and cats: Cause, pathogenesis, diagnosis, and treatment. Compend
Contin Educ Pract Vet 16:1423-1430, 1994.
9. Swift NC, Marks SL, MacLachlan N1, et al: Evaluation of serum feline trypsin-like immunoreactivity for
the diagnosis of pancreatitis in cats. 1 Am Vet Med Assoc 217:37--42, 2000.
10. Washabau R: The vomiting cat. Presented at the Waltham Feline Medicine Symposium, 1997.
II. Weiss 01, Gagne 1M, Armstrong PJ: Relationship between inflammatory hepatic disease and inflarn-
matory bowel disease, pancreatitis, and nephritis in cats. 1 Am Vet Med Assoc 209: 1114-1116.
1996.
37. ABDOMINAL DISTENTION AND ASCITES
1. Define abdominal distention.
Abdominal distention is defined as a sudden or gradual increase in the size of the abdomen.
2. What causes abdominal distention?
Major differential groups include fluid accumulation, organomegaly, masses in the peri-
toneal cavity not involving organs (including obesity), and muscle weakness (usually associated
with hyperadrenocorticism).
3. What are the principal fluid accumulations resulting in abdominal distention?
The most common abnormal fluid accumulations include blood, urine, ascites, exudates, and
chyle (rare).
4. Define ascites.
Ascites is an abnormal accumulation of a transudate (low protein concentration) or modified
transudate (high protein concentration) in the peritoneal cavity.
5. What are the primary differentials for hemoabdomen?
Organ or vessel ruptures are common causes of hemoabdomen and usually result from
trauma, tumors, or torsions of the stomach and spleen. Although tumors (mainly of the liver
and/or spleen) and trauma are possible causes of hemoabdomen in cats, torsions are extremely
rare. The other major differential diagnosis for hemoabdomen is coagulopathy. Factor deficien-
cies such as those associated with warfarin toxicity are most common (see Chapter 71).
Thrombocytopenia, platelet function abnormalities, vasculitis, and systemic arterial hypertension
usually do not cause hemoabdomen.
6. What are the primary differentials for uroabdomen?
Uroabdomen results most commonly from rupture of the bladder due to trauma, neoplasia.
or obstruction. Diseases associated with urine leakage from the kidneys, ureters, or urethra result
in retroperitoneal leakage of fluid; if the peritoneum is also damaged, uroabdomen results.
7. What causes transudative ascites?
Transudates have low protein concentrations 2.5 gmldl) and small numbers of cells
1000/I.tI). Abdominal effusions in this category are associated most commonly with decreased
oncotic pressure due to hypoalbuminemia. Hypoalbuminemia is associated most frequently with
renal loss, decreased hepatic production, gastrointestinal loss, starvation, and third spacing into
tissues or body cavities. In rare cases, sustained portal hypertension from chronic liver diseases
results in transudative ascites.
8. What causes ascites due to modified transudates?
Modified transudates have moderate protein concentrations (2.5-6.0 grn/dl) and moderate
numbers of cells (250-20,000/1.11). Right-sided congestive heart failure is a common cause in
dogs but a rare cause in cats. Pericardial disease or obstruction of the caudal vena cava or hepatic
vein can lead to vascular congestion of the liver and leakage of high-protein fluid from hepatic
lymph vessels. In some cases, neoplasia, chyloperitoneum, and inflammatory diseases such as
feline infectious peritonitis are classified as modified transudates based on cell and protein con-
centrations. However, other findings usually support the primary diagnosis. For example, neo-
plastic cells are often detected cytologically; triglycerides are elevated in chylous effusions.
172
Abdominal Distention and Ascites 173
9. What are themost common causesof exudative peritoneal etTusion?
Exudates have high protein concentrations (> 3.5 gmldl) and high numbers of cells (>
3D,OOD/IlI). Most cases result from infectious inflammatory diseases (feline infectious peritonitis
[FIPJ, bacterial peritonitis from penetrating wounds, bowel rupture) or from diseases resulting in
chemical irritation (pancreatitis, leakage of bile, leakage of urine).
10. Whattypesof diseases resultin organomegaly?
Organs can become enlarged when masses develop. Tumors, abscesses, granulomas, cysts,
and hemotoma are the most common mass lesions. Congestion of the liver and spleen can cause
organomegaly. Gastric or intestinal distention due to ileus, parasites, or obstructive diseases are
other causes of organomegaly. Torsion of the stomach or spleen also may result in abdominal
distention.
11. Howis the initialditTerentiailist for abdominal distention determined?
Signalment, history, and physical examination are used initially. For example, young inbred
cats from crowded environments most commonly develop effusive PIP; uveitis and fever may bede-
tected. FIP, neoplasia and pancreatitis are the most likely causes of concurrent pleural effusion.
Uroabdomen and hemoabdomen are commonly associated with trauma and are usually acute.
Hypoalbuminemia associated with gastrointestinal (GI) loss is most often chronic and accompanied
by a history of GI signs such as vomiting or diarrhea. Hypoalbuminemia associated with hepatic fail-
ure usually is chronic and has other signs, including hepatic encephalopathy and weight loss.
Trauma, pancreatitis, exudates, and torsions usually have abdominal pain. A fluid wave can generally
be ballotted when abdominal distention is severe enough to bevisible. Extreme abdominal distention
with a fluid wave in a cat with minimal other clinical signs is more likely ascites than hemoperi-
toneum, uroabdomen, or exudates. Increased respiratory rate may result from diaphragmatic im-
pingement. Polysystemic signs such as fever (exudates), pain (trauma, exudates), weakness (blood
loss, heart failure), dermatologic changes (hyperadrenocorticism), and polyuria/polydipsia (hypera-
drenocorticism) may help to differentiate causes of abdominal distention.
12. Describe theinitial diagnostic planfor evaluating cats withabdominal distention.
Abdominal pericentesis is the logical first diagnostic procedure if a fluid wave is ballot-
ted. Because a large volume of fluid is required to result in abdominal distention, a single,
midline aspirate is adequate. Four-quadrant abdominal pericentesis is indicated when a single
midline tap is negative. It is better to use the linea alba for needle penetration because fewer
sensory nerve endings are involved and, if a coagulopathy is present, hematomas are less
likely to develop than if muscle is penetrated. Fluid should be placed onto a sterile swab and
into transport media for possible culture and sensitivity and into an EDTA tube for fluid
analysis; for cytologic assessment, it should be applied to a microscope slide in a thin smear.
If the fluid is red, packed cell volume and total protein assessment should be performed and
compared with peripheral blood to assess whether a vessel was hit or whether hemoabdomen
exists. Remove only enough fluid for diagnostic testing and to relieve diaphragmatic impinge-
ment if dyspnea is present. If it is unclear whether fluid is present, abdominal radiographs
should be taken.
13. Whatadditional diagnostic testsare usedfor cats withorganomegaly?
Additional tests depend on which organ is enlarged and the primary diseases suspected. For
renal, splenic, and hepatic masses, complete blood count (CBC), serum biochemical panel, and
urinalysis are usually performed. Ultrasound is often performed to evaluate enlarged parenchy-
mal organs. Barium series are indicated if obstructive GI tract disease is suspected but cannot be
confirmed by usual assessment of plain abdominal radiographs. Fecal examination is indicated in
some animals, particularly kittens with possible toxocariasis. Laparoscopy or exploratory laparo-
tomy can be used to evaluate enlarged organs and to obtain biopsies. Exploratory laparotomy
should be performed if the mass can be excised.
174 Abdominal Distention and Ascites
14. Describetheadditional diagnostic work-up for cats withtransudates.
CBC, serum biochemical panel, and urinalysis should be performed to determine whether
hypoalbuminemia is present and to assess for a site of potential loss. If hypoalbuminemia is pre-
sent, assessment of serum globulin concentrations can be beneficial. Renal loss usually results in
proteinuria with normal serum globulin concentrations. The further diagnostic plan usually in-
cludes the urine protein/creatinine ratio, renal ultrasound, and a search for potential causes of
glomerulonephritis. Potential tests may include an antinuclear antibody titer, Dirofilaria immitis
antigen and antibody testing, and renal biopsy. Decreased hepatic production of albumin usually
has normal-to-increased serum globulin concentrations. Pre- and postprandial bile acid measure-
ment, hepatic ultrasound, and hepatic biopsy are used for further assessment of hepatic diseases
associated with transudative ascites. When GI diseases result in hypoalbuminemia, serum globu-
lin concentrations are usually decreased as well. Rectal cytology, fecal examination, fecal fats,
trypsin-like immunoreactivity, barium series, endoscopy, and exploratory laparotomy for biop-
sies are examples of tests used to evaluate causes of protein-losing enteropathies. If hypoalbu-
minemia is not present, the liver should be evaluated for potential causes of protracted portal
hypertension by use of bile acid assessment, ultrasound, and, potentially, biopsy.
15. Whatadditional diagnostic testsare usedfor cats withmodified transudates?
Modified transduate should be examined cytologically to rule out neoplasia. If chyloperi-
toneum is suspected, triglyceride concentrations should bemeasured. Most cats with disease cranial
to the liver have hepatomegaly. If cardiac tamponade is occurring, jugular pulses and jugular disten-
tion may be present; thoracic radiographs, cardiac ultrasound, and measurement of central venous
pressure are indicated. If cardiac causes of the modified transudate are eliminated, CBC, serum bio-
chemical panel, and urinalysis are indicated to evaluate other possible primary causes. Abdominal
ultrasound, laparoscopy, or exploratory laparotomy often is needed to identify the primary cause.
16. Describe the additional diagnostic work-up for cats withexudates.
If an exudate is detected, CBC, serum biochemical panel, and urinalysis often are performed
to evaluate for primary causes. Peritoneal effusion and serum lipase activities should be com-
pared; the abdominal fluid lipase activity is usually greater if pancreatitis is present. If uroab-
domen is suspected, creatinine and urea nitrogen concentrations in the abdominal fluid should be
measured and compared with serum concentrations. Abdominal ultrasound often is indicated if a
cytologic diagnosis cannot be made. If the exudate is septic or contains bile, immediate ex-
ploratory laparotomy is indicated. If the fluid has high protein concentration but only moderate
increases in mature neutrophils and macrophages, PIP is likely. The albumin-to-globulin ratio of
the fluid should be evaluated. Values <0.4 suggest PIP, whereas values> 0.8 suggest that another
disease is present.
17. What additional diagnostic tests are usedfor cats withhemoabdomen?
If trauma is not obvious, coagulopathy should be excluded by measuring an activated clot-
ting time (or other factor tests, such as prothrombin time or activated partial thromboplastin time)
and platelet count. Organ-associated bleeding is evaluated by ultrasound, laparoscopy, or ex-
ploratory laparotomy.
18. What additional diagnostic tests are usedfor cats withsuspected myopathy associated
withhyperadrenocorticism?
Exogenous glucocorticoid administration should be excluded by history. Naturally occurring
hyperadrenocorticism is excluded by a combination of blood tests and imaging techniques (see
Chapter 54).
19. Howshouldabdominal distention be treated?
The treatment plan is based on the primary diagnosis. Palliative treatments include rest, de-
livery of oxygen, and therapeutic abdominal pericentesis to relieve diaphragmatic impingement.
Feline Infectious Peritonitis
BIBLIOGRAPHY
175
I. Cornelius LM: Abdominal distension. In Lorenz MD, Cornelius LM (eds); Small Animal Medical
Diagnosis, 2nd ed. Philadelphia, J.B. Lippincott, 1993, pp 73-77.
2. Kruth SA: Abdominal distention, ascites, and peritonitis. In Ettinger 11, Feldman EC (eds): Textbook of
Veterinary Internal Medicine, 5th ed. Philadelphia, W.B. Saunders, 2000, pp 137-139.
38. FELINE INFECTIOUS PERITONITIS
Michelle L. Berry. D.v.M.
1. Define feline infectious peritonitis.
Feline infectious peritonitis (FIP) is a disseminated disease caused by feline coronaviruses
(FCoV). Field strains of FCoV vary in disease-inducing potential. Some isolates cause FIP
(feline infectious peritonitis virus [FIPV]), and some isolates cause a more localized gastroin-
testinal disturbance that often results in diarrhea (feline enteric coronavirus [FECV]). These two
strains cannot be distinguished from one another morphologically or antigenically. FECV can
mutate spontaneously in the host to become a PIP-inducing stain.
2. How do cats become infected with FCoV?
Cats usually become infected with FCoV by ingestion of virus, but inhalation may provide
viral entrance. Because cats shed viral particles in feces, litterbox exposure and mutual grooming
are probably the most important sources of infection. Cats living in multiple cat households or
having exposure to multiple cats are at a greater risk of contracting FCoV and, as a result, FlP, in
part because of higher levels of virus exposure and probably a higher level of stress.
3. Why is disease limited to enteric signs in some cats, whereas others develop FIP?
Both viral strain factors and host factors may playa role. FECV attaches to an enzyme in the
intestinal brush border and replicates in enterocytes. This process causes the villous tips to
slough, and diarrhea ensues, which usually is self-limiting. If the cat is exposed to FIPV or if
FECV mutates to FIPV, the organism is able to replicate in enterocytes and macrophages.
Disseminated infection can then occur. Genetic predispositions also are suspected. Host-derived
immunity also may playa role in resistance to development of FlP.
4. Describe the typical presentation for a cat with FIP.
Cats with FIP can present for evaluation of many clinical syndromes. Anorexia is
common, but some cats have a normal appetite. Ascites may be the only clinical sign.
Historically, the cat is usually young, lives in a multicat household or cattery, and has been re-
cently stressed with a new environment, surgery, or illness. The history may include diarrhea,
lethargy, weight loss, or inappetence. Many cats present with a low-grade fever unresponsive
to antibiotics. The clinical disease of FIP has two primary clinical forms, the effusive (wet)
form and the noneffusive (dry) form. The most common historical and physical examination
findings of noneffusive FIP relate to organomegaly and resultant organ failure. Hepatic, ocular,
renal, alimenteric, and central nervous system dysfunction are common. Clinical manifesta-
tions of the effusive form relate to the development of body cavity effusions. A distended ab-
domen due to ascites and dyspnea and muffled heart and lung sounds due to pleural effusion
are common. Although these distinctions are useful in diagnosing the disease and recognizing
signs, they are not mutually exclusive; an individual cat can have manifestions of both forms.
Some cats may initially have manifestations most consistent with the noneffusive form and
later become effusive or vice versa.
176 Feline Infectious Peritonitis
Clinical Abnormalities Suggestive of Feline Infectious Peritonitis
Signalment and history
Cats < 3 years of age or > 10 years of age
Purebred cat
Purchase from a crowded cat environment
Previous history of gastrointestinal or upper respiratory disease
Serologic evidence of infection by feline leukemia virus
Nonspecific signs of anorexia, weight loss, or depression
Seizures, nystagmus, or ataxia
Acute, fulminant course in cats with effusive disease
Chronic, intermittent course in cats with noneffusive disease
Physical examination
Fever
Weight loss
Pale mucous membranes with or without petechiae
Dyspnea with a restrictive breathing pattern
Muffled heart or lung sounds
Abdominal distention with a fluid wave with or without scrotal swelling
Icterus with or without hepatomegaly
Chorioretinitis or iridocyclitis
Multifocal neurologic abnormalities
Irregularly marginated kidneys with or without renomegaly
Mesenteric lymphadenopathy
Splenomegaly
Clinicopathologic abnormalities
Nonregenerative anemia
Neutrophilic leukocytosis with or without a left shift
Lymphopenia
Hyperglobulinemia characterized as a polyclonal gammopathy with increases in alpha, and
gammaglobulins; rare monoclonal gammopathies
Nonseptic, pyogranulomatous exudate in pleural space, peritoneal cavity, or pericardial
space
Increased protein concentrations and neutrophilic pleocytosis in cerebrospinal fluid
Positive coronavirus antibody titer
Pyogranulomatous or granulomatous inflammation in perivascular location on histologic
examination of tissues
Positive results of immunofluorescence or polymerase chain reaction performed on pleural
or peritoneal exudate
5. What are the neurologic manifestations of FIP?
Some studies estimate that 12-35% of cats with FIP have neurologic signs. These numbers
vary widely among institutions and possibly are affected by a skewed population. Some cats may
show only central neurologic signs. The most common neurologic signs associated with FIP are
ataxia, followed by nystagmus and seizures. Other neurologic signs depend on the location of the
granuloma or whether the virus is causing meningitis.
6. What are the most common ocular manifestations of FIP?
Uveitis can be detected in cats with either form of disease, but it is thought to be more
common in cats with noneffusive F1P. The most common ocular sign in FIP is iritis, which mani-
fests as a color change (see Chapter 67). Keratic precipitates also may be seen because large
numbers of inflammatory cells settle on the back of the cornea. Chorioretinitis due to vasculitis is
recognized in some affected cats.
Feline Infectious Peritonitis 177
7. Why do effusions form in some cases of FIP?
When the organism is disseminating in infected macrophages, the body responds with anti-
body production, resulting in complement activation. It is hypothesized that the combination of
viral particles or antigens bind to antibody, resulting in complement fixation and circulating
immune complexes, which attach to blood vessels and cause severe vasculitis. It is also possible
that complement is fixed to immune complexes in tissues. Vasculitis results in leakage of high
protein fluids from affected organs; common sites of leakage are the peritoneum. kidney, and
uvea. Exudation of fluid and plasma proteins occurs primarily in body cavities, resulting in as-
cites and pleural effusion. Cats developing the effusive form of disease may have poor cell-medi-
ated immune responses.
8. Describe the pathophysiology of the noneffusive form of FIP.
It is hypothesized that the noneffusive form of FIP occurs in cats that are capable of mounting
a partial cell-mediated immune response that does not totally contain the infection. Effusion may
be less likely because less virus is available for the formation of immune complexes, resulting in
less severe vasculitis. When circulating or tissue-associated immune complexes fix complement,
neutrophils and macrophages are attracted to the involved organs and pyogranulomatous inflam-
mation develops. Pyogranulomatous inflammation may become severe enough to cause organ
dysfunction or failure.
9. At what age are cats more likely to develop FIP?
FIP is said to be a disease of the very young and the very old. Newborn kittens usually are
protected by maternal antibodies that last for the first few weeks of life. As maternal antibody
protection fades, the kittens are susceptible to infection. The most common age range for cats
with FIP is 3 months to 3 years. Another peak in susceptibility occurs in cats older than 10 years.
presumably because of an age-related decline in immune responses.
10. What is the relation between FIP and feline leukemia virus?
Previously it was believed that feline leukemia virus (FeLV) compromised the immune
system and facilitated development of FIP. If this were true, it seems likely that the dramatic de-
crease in the incidence of FeLV would be accompanied by a parallel decrease in the incidence of
FIP. Because the incidence of FIP has remained the same despite a decrease in the incidence of
FeLV, the correlation between the two viruses is much weaker than once imagined.
11. How is FIP diagnosed?
Histology of affected tissues is considered the only way to reach an indisputable diagnosis of
FIP. Immunohistochemical staining of tissues allows identification of viral antigen associated
with inflammation and therefore provides a specific diagnosis.
12. How can effusions be used to aid in the diagnosis of FIP?
If the cat has ascites or pleural effusion, centesis and fluid analysis are valuable diagnostic tools.
Typically the fluid is pale yellow and has increased viscosity. Evaluation of protein content yields a
total protein> 3.5 gm/dl, over 50% of which is composed of garmnaglobulins. Cytology of the fluid
reveals an exudate with cellularity 5000 cells/ul) consisting primarily of nondegenerative neu-
trophils. In rare cases, the effusion is pink and chylous. With a combination of the above protein con-
tent, globulin predominance, and cytology, the positive predictive value for diagnosis of FIP based
on fluid analysis is > 90%. In addition, the albumin-to-globulin ratio of the effusion is usually < 0.8;
a ratio < 0.45 is usually predictive of effusive FIP. Documentation of coronaviral RNA by reverse
transcriptase polymerase chain reaction (see question 15) supports the diagnosis of effusive FIP.
13. Can nonefTusive FIP be diagnosed without obtaining tissue?
Clinicians strive to arrive at a diagnosis with less invasive methods because of the patient's
often compromised condition. The noninvasive approach to diagnosis can prove to be difficult.
Currently no single test of serum or effusion fluid can give a definitive diagnosis of PIP; there-
fore, the clinician must rely on careful history and observation, thorough physical examination,
and multiple diagnostic tests. If the history and physical examination are suggestive of FIP, diag-
nostic tests can aid in confirmation.
Cats with clinical signs consistent with FIP and the combination of lymphopenia 1.5 x
103 cells/ul). FCoV antibody titer> I :160, and hyperglobulinemia (> 5.1 gmldl) have an 88.9%
probability of having FIP. If the cat has clinical signs of FIP but does not have all three of the
above diagnostic criteria, there is a 98.8% probability that the cat does not have FIP. Therefore,
these tests can be quite helpful in excluding the diagnosis of PIP.
In cats with neurologic FIP, cerebrospinal fluid (CSF) analysis can provide helpful informa-
tion to aid in diagnosis. CSF analysis in cats with neurologic PIP usually reveals increased protein
concentrations and neutrophilic pleocytosis. Detection of coronavirus antibodies in CSF has not
correlated consistently with a diagnosis of PIP and does not seem to correlate with serum titers.
14. What kind of serologic tests are available? How reliable are they in diagnosing FIP?
No available serologic test can differentiate between strains of FCoV. A positive test result
reveals that the cat has been exposed to a coronavirus but does not predict that the cat will de-
velop FlP. One study reported that cats with high coronavirus antibody titers had only a 38.9%
probability of having FlP. In addition, cats that have been vaccinated for FIP can become
seropositive. Although negative titers strongly suggest that the cat does not have FIP, some stud-
ies have reported negative antibody titers in cats with histologically confirmed FIP. A possible
explanation is that, with widespread immune complex formation, the antibody may be bound in
the complex and prevented from reacting in the test. Alternatively, the cat may have had fulmi-
nant FIP and died before mounting a humoral response. For these reasons, clinicians are urged
not to rely on serology as a single diagnostic test. Many cats have been euthanized because of
misconceptions about the validity of serologic tests as the sole determinant of disease.
15. What other tests are available for FIP?
Reverse transcriptase polymerase chain reaction (RT-PCR) test is available. Because coron-
aviruses are RNA viruses, reverse transcriptase is used first to convert RNA to DNA. The DNA is
then amplified in the polymerase chain reaction. Positive results of this test on whole blood may sup-
port the diagnosis of FIP in a clinically ill, seronegative cat. However, as with serologic tests, RT-
PCR does not distinguish between FCoV strains; a positive test indicates only exposure to a
coronavirus. In one study, cats with enteric coronavirus infections were just as likely to be PCR-pos-
itive as cats with PIP. In addition, false positives and false negatives have been reported. Whether RT-
PCR performed on aqueous humor or CSF aids in the diagnosis of PIP is currently unknown.
16. What is the prognosis for cats with FIP?
Clinical PIP is almost always a fatal disease with a mortality rate> 95%. Cats with the effu-
sive form of FIP usually progress more quickly and often die within 2 months of initial clinical
signs. The noneffusive form may run a slower course; some cats live for months to years.
17. What treatment is recommended for FIP?
Because PIP is an immune complex disease, immunosuppression is the mainstay of treatment.
High doses of glucocorticoids are commonly used for their immunosuppressive and antiinflamma-
tory properties. Cytotoxic drugs such as cyclophosphamide and chlorambucil have been used in con-
junction with glucocorticoids. Success is greater with noneffusive PIP. Cats with effusive FIP are
thought to have poor immunity and heavy viral load; glucocorticoid administration may exacerbate
disease. In addition, although these drugs are needed to help control the immune response associated
with clinical FIP, they also may cause susceptibility to bacterial infections due to myelosuppression
and general immunosuppression. Therefore, broad-spectrum antibiotic therapy may be necessary as
a prophylactic treatment. Reasonable choices include amoxicillin and cefadroxil. If an infection is
documented, antibiotic selection should be based on culture and sensitivity.
Feline Infectious Peritonitis 179
18. What other drugs are used for treatment of FIP?
Antiviral drugs and immune-modulating drugs have been evaluated for the treatment of FIP.
Recombinant human interferon-alpha has been given to cats in experimental settings and has
slowed progression of disease. For debilitated cats with the effusive form, recombinant human
interferon-alpha at high doses has been recommended. For cats with the noneffusive form. lower
doses have been recommended. To date, no antiviral drugs have proved effective that can be tol-
erated by cats without severe side effects.
Treatment Recommendations for Feline Infectious Peritonitis
DRUG DOSE
Immunosuppressive drugs
Prednisolone 2-4 mglkg orally every 24 hr
Cyclophosphamide 200-300 rng/m- orally every 2-3 wk or
2.2 mglkg every 24 hr for 4 consecutive days each week
or
Chlorambucil 20 mg/m?orally every 2-3 wk
Antibiotic therapy
Amoxicillin/clavulanic acid 10-20 mglkg orally every 12 hr
or
Cefadroxil 20 mglkg orally every 12 hr
Immune-modulatingdrugs
Recombinant human interferon-alpha
Effusive form 2 x 10"IVlkg intramuscularlyor subcutaneouslyevery 24 hr for up to 3 wk
Noneffusive form 30 IV orally every 24 hr for life
19. What measures should be taken to aid in prevention of FIP?
Prevention strategies should be based on the housing and exposure possibilities of each pa-
tient. Cats living in a single cat household need a much less rigid prevention protocol than cats in
a cattery or multiple cat household.
20. What prevention strategies are appropriate for seronegative single cat households?
Seronegative cats living in a single cat household are at low risk for developing FIP (inci-
dence =I in 5000). Prevention is aimed at limiting exposure to other cats. Any new cat to be in-
troduced to this household should be seronegative 30 days before entrance. Optimally, new cats
should be quarantined for 3 weeks, then retested before free access to the household is given.
Kittens should be tested after 12 weeks of age to allow time for clearance of lactationally derived
antibodies and to allow seroconversion if they have been naturally exposed.
21. What prevention strategies are appropriate for seronegative multiple cat households?
Prevention is geared toward the same goal as the single cat seronegative household-limit-
ing exposure. New additions to the household should be seronegative 30 days before entrance
and should be quarantined for 3 weeks, then retested before gaining access to other cats in the
household. Kittens should be tested at 12 weeks of age. Fecal contamination should be mini-
mized by keeping food away from Iitterboxes and cleaning Iitterboxes daily.
22. Describe the appropriate prevention strategies for seropositive multiple cat house-
holds.
Decreasing stress and fecal-oral contamination are main concerns. Care should be taken to
decrease fecal contamination of food by keeping food bowls and Iitterboxes in separate areas.
Litterboxes should be cleaned daily and disinfected with a 1:32 dilution of bleach week1y. There
should be one Iitterbox for every I or 2 cats. Cats should be kept in stable groups of three or four
to decrease stress. In boarding or rescue facilities, cats should be housed singly.
23. Describe the appropriate prevention strategies for catteries.
In catteries or other breeding colonies, cleanliness guidelines should be enforced without ex-
ception. The kitten room should be kept separate from other rooms in the cattery, and exposure to
other cats should be eliminated. The room should be cleaned with 1:32 dilute bleach solution
before the queen is introduced into the room before parturition. Seropositive queens should be
separated from their kittens at 5 weeks to limit exposure to the kittens. Kittens that are seronega-
tive at 12-14 weeks of age can be assumed to be FoCV-naive.
24. When should vaccination for FIP be used?
Vaccination with the commerically available intranasal FIP vaccine is not recommended for
all cats. Because cats from one- or two-cat households have such a low risk for development of
FIP, vaccination is not recommended. In multicat households where FCoV is enzootic, vaccina-
tion of resident or incoming seronegative cats potentially decreases the incidence of FIP.
Vaccination in these settings has been shown to decrease the incidence only in cats that were
seronegative before vaccination.
BIBLIOGRAPHY
I. Addie DD, Jarret 0: Feline coronavirus infection. In Greene CE (ed): Infectious Diseases of the Dog and
Cat, 2nd ed. Philadelphia, W.B. Saunders, 1998, pp 59-67.
2. Foley JE, Lapointe JM, Koblik P, et al: Diagnostic features of clinical neurologic feline infectious peri-
tonitis. J Vet Intern Med 12:415-423,1998
3. Gunn-Moore DA, Gruffydd-Jones TJ, Harbour DA: Detection of coronaviruses by culture and reverse
transcriptase-polyrnerase chain reaction of blood samples from healthy cats and cats with clinical
feline infectious peritonitis. Vet Microbiol 62: 193-205, 1998.
4. McReynolds C, Macy D: Feline infectious peritonitis. Part I: Etiology and diagnosis. Comp Cont Educ
PractVet 19:1007-1014,1997.
5. McReynolds C, Macy D: Feline infectious peritonitis. Part II: Treatment and prevention. Comp Cont
Educ Pract Vet 19:1111-1116,1997.
6. Paltrinieri S, Parodi MC, Cammarata G, et al: In vivo diagnosis of feline infectious peritonitis by com-
parison of protein content, cytology, and direct immunofluorescence test on peritoneal and pleural ef-
fusions. J Vet Diagn Invest 11:358-361, 1999.
7. Polland AM. Vennema H, Foley JE, et al: Two related strains of feline infectious peritonitis virus isolated
from immunocompromised cats infected with a feline enteric coronavirus. J Clin Microbiol 34:3180-
3184,1996.
8. Shelly SM, Scarlett-Kranz J, Blue JT: Protein electrophoresis on effusions from cats as a diagnostic test
for feline infectiouis peritonitis. J Am Anim Hosp Assoc 24:495-500, 1988.
9. Sparkes AH, Gruffydd-Jones Tl. Harbour DA: Feline infectious peritonitis: A review of clinicopathologi-
cal changes in 65 cases and a critical assessment of their diagnostic value. Vet Rec 129:202-212, 1991.
10. Sparkes AH, Gruffydd-Jones T'I, Harbour DA: An appraisal of the value of laboratory tests in the diagno-
sis of feline infectious peritonitis. JAm Anim Hosp Assoc 30:345-350, 1994.
III. Urinary Problems
Section Editor: India F. Lane, D.V.M., M.S.
39. POLYURIA AND POLYDIPSIA:
OVERVIEWAND DIAGNOSTIC PLAN
1. Define polyuria and polydipsia.
Polyuria is increased urine production, and polydipsia is increased water consumption. In
dogs and cats, polydipsia is defined as water consumption> 100mIlkg/24 hours; polyuria is de-
fined as urine production> 50 mllkg124 hours. There are primary causes of each condition, but
clinical manifestations of both occur in most affected cats. For example, cats with polydipsia uri-
nate larger volumes to clear the body of excessive fluids; polyuric cats dehydrate themselves and
drink excessively to compensate.
2. What diseases are commonly associated with polyuria and polydipsia?
The multiple causes of polyuria/polydipsia in cats can be grouped into four major categori-
ers: renal, endocrine, metabolic, and miscellaneous. By far, the most common causes of polyuria/
polydipsia in cats are renal failure, diabetes mellitus, and hyperthyroidism.
PrimaryCausesof Polyuriaand Polydipsiain Cats
Renal
Acute renal failure
Chronic renal failure
Pyelonephritis
Primary renal glycosuria (rare)
Glomerulonephritis
Idiopathic or congenital nephrogenicdiabetes insipidus
Endocrine
Diabetes mellitus
Hyperthyroidism
Hypoadrenocorticism(rare)
Hyperadrenocorticism(rare)
Central diabetes insipidus
Metabolic
Hepatic failure
Hypercalcemia
Hypocalcemia
Miscellaneous
Gram-negativeendotoxins
Drugs
Hyperviscositysyndromes
Psychogenicpolydipsia (rare)
3. Describe the signalment most commonly associated with causes of polyuria/polydipsia.
Acute renal failure and pyelonephritis can occur in cats of any age. Chronic renal failure is
most common in older cats; exceptions include breeds with congenital renal diseases (see
Chapters 40 and 42). Endocrine and metabolic disorders are most common in older cats; an ex-
ception is hepatic insufficiency due to congenital liver disease. Breed associations are seen with
some causes of polyuria/polydipsia. For example, Persian cats commonly have polycystic kidney
disease, and Abyssinian cats commonly have amyloidosis. Pyometra is most common in intact
female cats.
181
182 Polyuria and Polydipsia: Overview and Diagnostic Plan
4. What historical findings are commonly associated with causes of polyuria/polydipsia?
Clients generally report excessive urine in the litterbox, inappropriate urination, increased
water consumption, or clinical signs reflecting the primary problem. Water intake may be from
unusual sources (e.g., tubs, sinks, toilets, plant water containers). Drugs and toxins (nephrotoxi-
cants) often can be excluded by history. Cats with pyelonephritis or chronic renal failure may
have had recurrent episodes of lower urinary tract disease preceding polyuria/polydipsia. Cats
with hepatic insufficiency commonly have protracted history of doing poorly and may have had
weight loss, anorexia, vomiting, or icterus consistent with hepatic disease. Cats with hypoadreno-
corticism usually have a history of intermittent gastrointestinal signs as well as polyuria/polydip-
sia. Polyphagia with polydipsia/polyuria is most common in cats with hyperthyroidism or
diabetes mellitus. Cats with hyperthyroidism or hyperadrenocorticism often have a history of ag-
gression; hyperadrenocorticism is commonly associated with dermatologic problems.
5. What physical examination findings are most commonly associated with causes of
polyuria/polydipsia?
Cats with polyuria/polydipsia associated with renal diseases may have several different physical
examination abnormalities. For example, large kidneys occur with acute renal diseases, obstructive
nephropathy, and lymphoma. Cats with chronic renal failure usually have small, irregularly mar-
ginated kidneys with evidence of weight loss and may have soft bones or retinal lesions. Thyroid
nodules often can bepalpated in the ventral cervical region of cats with hyperthyroidism. Cats with
hepatic failure usually are thin and may have evidence of ascites, icterus, or neurologic dysfunction.
The uterus may be palpated in cats with pyometra. Many cats with diabetes mellitus have palpable
hepatomegaly. Most cats with hyperadrenocorticism have alopecia and thinning of the skin.
6. How can I confirm polyuria/polydipsia?
Performance of a 24-hour water consumption study at home is best for determining whether
a cat has polydipsia/polyuria. All faucets should be turned off, and the toilet lids placed in the
down position so that a single water source can be used to determine consumption. Normal cats
should drink < 100 ml/kg/24 hr and urinate < 50 ml/kg/day. In the absence of an accurate quanti-
tated water consumption measurement, dilute urine on a urinalysis is supportive of polyuria.
7. What is included in the initial diagnostic plan for cats with polyuria/polydipsia?
In cats with documented polyuria/polydipsia, the combination of complete blood cell count,
serum biochemical panel, urinalysis, serum osmolality, and total T4 (cats older than 5 years) is a
good initial diagnostic plan that proves or eliminates most differential diagnoses.
8. How does the urinalysis aid in the ranking of the differential diagnoses?
The urine specific gravity is usually < 1.035 in cats with polyuria/polydipsia. Proteinuria is
usually detected in cats with glomerular or tubular lesions in the kidneys. In cats with diabetes
mellitus, glycosuria with or without ketonuria is detected. Glucosuria may be detected with tubu-
lar disease such as primary renal glycosuria, but the cat is euglycemic. Ammonium biurate crys-
tals may be detected in cats with hepatic insufficiency; other crystal types may be detected in cats
with other forms of obstructive uropathy. Pyuria and bacteriuria are common in cats with
pyelonephritis. Cats with hyperadrenocorticism may have bacteriuria without pyuria; excessive
urinary cortisol lessens inflammation while promoting infections. Cats with central or nephro-
genic diabetes insipidus have the lowest urine specific gravity measurements (e.g., 1.001-1.008).
9. How does the serum osmolality aid in the ranking of differential diagnoses?
Most cats either have polydipsia with compensatory polyuria or polyuria with compensatory
polydipsia. Cats with primary polydipsia dilute the serum osmolality and urinate excessively to
clear the extra volume. Cats with polyuria dehydrate, increasing serum osmolality and resulting
in compensatory polydipsia. Serum osmolality values < 280 and> 310 are most consistent with
polydipsia and polyuria, respectively. Because of chronicity and compensatory mechanisms,
however, a normal serum osmolality is observed in most cases.
Acute and Chronic Renal Failure 183
10. What specialized blood tests are commonly used in the diagnostic work-up of cats with
polyuria/polydipsia?
Diabetes mellitus is confirmed in cats with hyperglycemia. glycosuria, and three of the fol-
lowing clinical signs: polyphagia. polyuria, polydipsia. and weight loss. A baseline fructosamine
concentration usually is determined after diagnosis and is used to monitor therapy (see Chapter
56). Cats with hepatic insufficiency resulting in polyuria/polydipsia usually have low albumin,
low blood urea nitrogen. low glucose. low cholesterol. and high bilirubin concentrations on rou-
tine blood chemistries. Pre- and postprandial serum bile acids can be used to document hepatic
insufficiency in cases with questionable results (see Chapter 28). Measurement of multiple serum
total T4 concentrations, a T3 suppression test, or a technecium scan may be required to confirm
hyperthyroidism (see Chapter 53). The adrenocorticotropic stimulation test can be used to ex-
clude hyperadrenocorticism and hypoadrenocorticism (see Chapters 54 and 55). Most cats with
hypoadrenocorticism have elevated potassium and low sodium concentrations. Protein elec-
trophoresis determines the type of gammopathy in cats with hyperviscosity syndromes.
11. How do imaging techniques aid in the diagnosis of polyuria/polydipsia?
Radiographs and ultrasound are commonly used to aid in the evaluation of hepatic, renal or uter-
ine causes of polyuria/polydipsia. Thoracic and abdominal radiographs usually are reviewed in cats
with hypercalcemia to assess for evidence of neoplasia. Nuclear scintigraphy can be used to docu-
ment glomerular filtration rate or to confirm hyperthyroidism. Computed tomography or magnetic
resonance imaging of the brain may berequired to evaluate causes of central diabetes insipidus.
12. When should a water deprivation test be performed?
Other than idiopathic nephrogenic diabetes insipidus, central diabetes insipidus, and psy-
chogenic polydipsia, most causes of PUIPD in cats can be excluded as described above. Because
these conditions are rare in cats, water deprivation testing is almost never required.
BIBLIOGRAPHY
Grauer GF: Clinical manifestations of urinary disorders. In Nelson RW, Couto CG (eds): Small Animal
Internal Medicine, 2nd ed. St. Louis, Mosby, 1998, pp 581-584.
40. ACUTE AND CHRONIC RENAL FAILURE
He!en Tuzia, D.V.M., M.S.
1. Define renal failure.
It is the inability of the kidneys to perform hemodynamic, filtration, and excretory functions.
resulting in the accumulation of uremic toxins and deregulation of fluid, electrolyte, and acid-
base balance. Clinically, it is defined as azotemia (elevated concentrations of blood urea nitrogen
[BUN] or creatinine) and concurrent decrease in urine-concentrating ability (urine specific grav-
ity [USG] < 1.040).
2. Define azotemia.
Azotemia is an excess of urea and other nitrogenous compounds in the blood. It results from
increased protein catabolism or reduced excretion capabilities and may be divided into renal. pre-
renal, and postrenal causes.
3. What causes renal azotemia?
Renal azotemia, defined as persistent azotemia with suboptimal urine concentrating ability
in the absence of nonrenal factors, is due to a functional loss of nephrons (at least 75%).
184 Acute and Chronic Renal Failure
4. What causes prerenal azotemia?
Increases in blood urea nitrogen (BUN) occur with factors other than renal failure, including de-
hydration, high protein diet, starvation, fever, burns, blood loss (especially gastrointestinal ulceration),
and glucocorticoid administration. Creatinine may be falsely elevated if the sample is hemolyzed. In
these nonrenal causes of azotemia, urine specific gravity (USG) is usually> 1.040. The kidneys re-
ceive 25% of cardiac output and do not have collateral circulation. As a result, ischemia can occur
whenever renal blood flow is reduced. One of the most common prerenal causes of kidney failure is
prolonged anesthesia. Other common causes are diuretics, thromboembolism, malignant hyperten-
sion, trauma, and hemorrhage. Conditions such as hypotension, circulatory collapse, prolonged renal
vasoconstriction, disseminated intravascular coagulation, shock, pancreatitis, hypoproteinemia, and
heat stroke also can produce hypovolemia or hypoperfusion. If left untreated, ischemia from reduced
blood flow can produce intrinsicrenal damage and subsequent acute or chronic renal failure.
5. What causes postrenal azotemia?
Azotemia also can occur with urinary tract obstruction (mucous plugs, uroliths, neoplasia)
and leakage of urine into tissues (ruptured bladder, ureter or urethra), which result in failure to
excrete uremic waste.
6. How does acute renal failure differ from chronic renal failure?
Acute renal failure (ARF) usually is associated with a sudden onset of clinical signs, rapid
(hours to days) increases in BUN and serum creatinine, and electrolyte and acid-base distur-
bances. All of these manifestations result from tubular dysfunction and reduction in glomerular
filtration rate. Chronic renal failure (CRF) is a long-term condition caused by a decrease in the
number of functioning nephrons that can last for months to years. ARF that persists for 2 weeks
or longer is considered chronic.
7. Does it make a difference whether renal failure is acute or chronic?
Unlike CRF, ARF is potentially reversible, especially if diagnosed early and treated appro-
priately. However, if therapy is delayed, ARF can produce irreparable kidney damage and subse-
quent death of the patient.
8. What causes intrinsic renal failure?
Diseases that directly or indirectly affect the vasculature, glomeruli, tubular epithelium, or
interstitium of the kidney cause intrinsic renal failure. Glomerulonephritis, pyelonephritis. feline
infectious peritonitis, lymphoma, and nephrotoxicants (e.g., ethylene glycol, nonsteroidal anti-
inflammatory drugs [NSAIDs], arninoglycosides) are common causes.
9. Describe the progression of ARF.
ARF progresses sequentially through three phases:
I. In the initiation phase, the parenchyma and tubular epithelium are injured.
2. In the maintenance phase, the damage to the epithelium becomes irreversible.
3. During the recovery phase, repair occurs and some or all of the renal function is regained.
The initiation phase may last from hours to days. If treatment is instituted before the patient
enters the maintenance phase, further progression of the disease can be prevented.
10. How common is renal failure in cats?
A study completed at the University of Minnesota between 1980 and 1990 found an overall
prevalence of 3.05%. However, this figure annually increased from 0.5% to 4.5% over the lO-year
period. Because detection techniques, client knowledge, and clinician awareness of renal disease
have improved significantly since 1990, the prevalence of renal failure may be far greater today.
ll. How does age affect the prevalence of renal failure?
The incidence of renal failure increases with advancing age. Studies of age distributions have
shown that cats younger than 10 years account for 37% of cases; cats between 10 and 15 years old
are 5 times more likely to have renal failure than cats of other age groups and account for 31% of
cases; and 32% of cats older than 15 years are diagnosed with renal failure. Cats older than 15years
are 20 times more likely to have renal failure than other age groups. According to published reports,
the mean age of cats with CRF is 12.6 years, whereas the mean age at diagnosis is 7.4 years.
12. What other factors may predispose to renal failure?
Factors leading to the development of CRF may be inherited or acquired. The tendency to
develop polycystic renal disease, for instance, appears to be familial (see Chapter 42). A higher
incidence of renal failure has been identified in Abyssinian, Burmese, Maine coon, Russian blue,
and Siamese cats. Acute renal insults, if left untreated, can lead to CRF by irreparably damaging
the renal parenchyma, resulting in loss of functional nephrons. However, ARF may not be recog-
nized in some cases. A study of cats with primary renal disease found that chronic tubulointersti-
tial nephritis was the most common (70.4% of 47 cats) histopathologic finding. It has been
suggested that chronic pyelonephritis or glomerulonephritis may be inciting factors for chronic
nephritis, although the etiology is most often undetermined.
13. What are the chief complaints associated with ARF?
With ARF, the main signs noted by the owners are nonspecific; anorexia, listlessness, weak-
ness, and vomiting are common complaints. In advanced renal failure, ataxia, dyspnea, syncope and
seizures are possible. Patients with ARF generally have a history of illness of < I week and may
have had exposure to nephrotoxicants, administration of medication, recent surgery, or blood loss.
14. Describe the chief complaints associated with CRF.
CRF is usually slow in onset; the owner usually notices a general decline over weeks to
months. Some cases may exhibit the classic uremic syndrome, which is characterized by de-
pression, anorexia, lethargy, and vomiting. Weight loss, halitosis, inappropriate urination, consti-
pation, and increased shedding may occur. Occasionally, owners report sudden onset of
blindness, or hematemesis. Polyuria and polydipsia occur but are not as common in cats as in
dogs. Cats with CRF may decompensate and present in an acute uremic crisis at any time.
15. What physical examination abnormalities are common in cats with renal failure?
Common findings in most cats with renal failure are lethargy and evidence of dehydration.
In moderate-to-severe cases, hypothermia, uremic breath, tachypnea, bleeding tendency, muscle
fasciculations, and altered mental status may be noted. Tachycardia may be detected in dehy-
drated or hypovolemic patients, bradycardia may be detected in hyperkalemic patients with ARF,
and other cardiac arrhythmias may arise from uremic myocarditis. Ocular abnormalities due to
systemic hypertension include reduced pupillary light reflexes, tortuous retinal vessels, hypherna,
anterior uveitis, glaucoma, retinal hemorrhage, retinal detachment, and papilledema.
16. Can physical examination findings distinguish ARF from CRF?
Cats with ARF are usually in good body condition with normal haircoat and body weight.
Weakness, mental dullness, and seizure activity may be noted. Abdominal pain and enlarged kid-
neys may be found on palpation. Lameness, back pain, icterus, discolored urine, and dysuria may
be present in cats with infectious causes. Body temperature is usually normal but may be low be-
cause of uremia or elevated because of infection or severe inflammation. Uremic stomatitis may
develop with ARF or CRE
Cats with CRF are usually unkempt on initial examination. Dehydration, significant weight
loss, and muscle wasting may be evident. Oral ulceration, fetid breath, tongue discoloration, or
sloughing may be observed. Fundic examination may reveal findings consistent with hyperten-
sion. Mucous membranes may be pale (from anemia) and dry (from dehydration) or moist from
vomiting (due to uremic gastritis). Petechial or ecchymotic hemorrhages may be noted. Heart
murmurs or arrhythmias may be found on thoracic auscultation. Small, irregularly marginated,
nonpainful kidneys are typically found on abdominal palpation; however, conditions such as neo-
plasia, pyelonephritis, nepholithiasis, and polycystic renal disease may produce renomegaly.
17. What is included in the diagnostic plan for suspected renal failure?
The initial database generally includes complete blood count (CBC) with differential, serum
biochemistry profile (which should include concentrations of urea nitrogen, creatinine, sodium,
potassium, chloride, bicarbonate or total carbon dioxide, calcium, and phosphorus), complete
urinalysis (urine collected before fluid therapy is initiated), urine culture and antimicrobial sus-
ceptibility, plain abdominal radiographs, arterial blood pressure, and, in cats older than 6 years,
total T4 concentration. In cats allowed outdoors and cats with bilateral renornegaly, a serum
feline leukemia virus antigen test and serum feline immunodeficiency virus antibody test should
be performed because of the potential for renal lymphoma. Kits for measurement of ethylene
glycol or its toxic metabolites should be used if indicated by history and laboratory findings. If
bladder rupture is suspected, abdominocentesis and fluid analysis should be performed. The fluid
typically has a creatinine concentration that exceeds the serum creatinine concentration.
18. How do results of the CDC and serum biochemical panel help to differentiate ARF
fromCRF?
Nonregenerative anemia is characteristic of CRF, whereas cats with ARF have normal or in-
creased red blood cell count, hematocrit, and hemoglobin concentration. In some cases of ARE
regenerative anemia, thrombocytopenia, and stress or inflammatory leukogram may be noted.
Hematocrit and total protein measurements are affected by hydration status.
Increased BUN, creatinine, and phosphorus concentrations occur in both ARF and CRF.
Serum potassium levels are generally increased in ARF and decreased in CRF but tend to vary
with the extent of vomiting and anorexia and the degree of acidosis. Serum bicarbonate concen-
trations decrease with severity of the renal failure, which results in metabolic acidosis; the most
dramatic acidosis is usually seen in ARF. Serum calcium concentrations may be normal, in-
creased, or decreased with renal failure. Acute ethylene glycol toxicity often induces hypocal-
cemia and hyperglycemia. Total serum calcium> 3.4 mmol/L (13.2 mg/dl) may induce ARF.
Measurement of ionized calcium may aid in determining whether hypercalcemia is the cause or
the result of renal failure. Most cats with CRF have ionized hypocalcemia, even though total cal-
cium levels may be increased. Only ionized hypercalcemia promotes renal failure; if it is present.
the cat should be evaluated for a primary cause of hypercalcemia (see Chapter 57).
19. What information is likely to be provided by urinalysis?
Cats with prerenal azotemia should have USG > 1.040; cats with renal azotemia have USG <
1.040. A decrease in urine concentrating ability may be the first indicator of impending renal fail-
ure. Although cats have the potential to develop azotemia before losing urine concentrating abil-
ity. this scenario is not common. In evaluating urine specific gravity, nonrenal causes of dilute
urine (e.g., hyperthyroidism, diabetes mellitus, hypercalcemia, severe hepatic disease, diabetes
insipidus, diuretics) must be kept in mind.
Proteinuria is common in uremic patients and generally indicates tubular or glomerular injury.
although it can be caused by hematuria or inflammation (see Chapter 43). Urine sediment exami-
nation is imperative. In pyelonephritis, cellular casts and inflammatory cells may be observed and
may be accompanied by bacteria or yeast. Granular or hyaline casts indicate active renal injury
with possible epithelial necrosis. Presence of crystalluria may help to rank differential diagnoses.
20. Howare imaging techniques used to evaluate cats with renal failure?
Intravenous urography may be beneficial in some cases (e.g., bladder rupture), but con-
trast studies are not recommended in ARF because of their hypertonicity and potential to create
additional renal damage.
Detection of changes in renal parenchyma by use of ultrasonography may help to rank dif-
ferential diagnoses. Hyperechoic renal cortices are the most common finding in ARF but also
may be associated with other causes such as pyelonephritis, ethylene glycol toxicity, renallym-
phoma, and pyogranulomatous nephritis secondary to feline infectious peritonitis (FIP). Focal le-
sions that may be detected include masses, cysts, abscesses, or hematomas. Dilation of renal
pelves may indicate excessive diuresis, obstruction, or pyelonephritis. In cases of CRF, the typi-
cal ultrasonographic findings are increased echogenicity and reduced renal size. Irregular con-
tours or renal mineralization may also be visualized. Ultrasound can be used to guide renal
aspirates (lymphoma) or biopsies if indicated.
Nuclear scintigraphy can be used to estimate glomerular filtration rate of each kidney indi-
vidually and to assess for obstructive disease of the ureters and pelves.
21. Is renal biopsy necessary?
Fine-needle aspiration of a kidney is usually sufficient for documentation of renal lymphoma.
Renal biopsy is indicated primarily to assess excessive proteinuria (see Chapter 43), to document
neoplasms other than lymphoma, to confirm noneffusive FlP, and to evaluate and determine a prog-
nosis in cats with severe uremia, hyperkalemia, or oliguria that persists despite therapy. In cases of
suspected ARF, evidence of intact tubular basement membranes and tubular regeneration indicates a
good prognosis, whereas interstitial mineralization, disrupted basement membranes, and extensive
tubular necrosis indicate a poor prognosis. Renal biopsy is contraindicatedin most cats with CRF, in-
cluding those with severe debilitation, anemia, one kidney, hydronephrosis, renal cysts, perirenal ab-
scess, pyelonephritis, or coagulopathies, and should not be used indiscriminately. Histopathologic
studies have shown that the most common finding in CRF is chronic generalized nephritis.
22. What causes the common complications of renal failure?
Because the kidneys have excretory, metabolic, and endocrine functions, patients in renal
failure are at risk for various complications, including electrolyte, blood pressure, fluid, and acid-
base disorders, which in tum may create neuromuscular, cardiovascular, respiratory, and immune
system compromise.
23. List the most common complications of renal failure.
Hypertension Platelet and leukocyte dysfunction
Peripheral neuropathy Metabolic acidosis
Uremic encephalopathy Hyperphosphatemia and renal secondary
Uremic pneumonitis hyperparathyroidism
24. How common is hypertension? What are the consequences?
Hypertension is diagnosed in nearly two-thirds of cats with CRF (see Chapter 63 and ques-
tions 60-62). Encephalopathies and ocular abnormalities may result.
25. How common is peripheral polyneuropathy? What are the typical signs?
Peripheral polyneuropathy (abnormal motor responses) associated with uremia has been de-
scribed in up to 65% of cats with CRF and generally is characterized by sensory changes and
sluggish reflexes in the distal limbs.
26. What are the typical signs of uremic encephalopathy? When does it occur?
Uremic encephalopathy is characterized by confusion, ataxia, sluggishness, and disorienta-
tion. It occurs with decreased GFR and may be exacerbated by increased cerebral calcium con-
centration, systemic hypertension, and electrolyte abnormalities.
27. What are the typical signs of uremic pneumonitis?
Dyspnea and alveolar lung disease.
28. Describe the platelet and leukocyte dysfunction associated with renal failure.
Platelet and leukocyte dysfunction occurs in the presence of urea, resulting in bleeding
diatheses and reduced cellular immunity.
29. Is metabolic acidosis common? What are its adverse effects?
A large number of cats with CRF develop metabolic acidosis. Chronic acidosis has a number
of adverse effects:
Reduction of cardiac output and hepatic and renal blood flow
Induction of cardiac arrhythmias, directly or indirectly, by influencing serum potassium
concentration
Enhancement of protein catabolism and possible inhibition of protein synthesis, which
cause anorexia, nausea, and vomiting, all of which increase the risk of malnutrition
Promotion of bone demineralization
Enhancement of potassium and taurine depletion.
30. What are the possible consequences of hyperphosphatemia?
Hyperphosphatemia alone has no clinical signs; however, it predisposes patients to metastatic
calcification, primarily affecting the stomach, kidneys, myocardium, lung, and liver. It may be
used as a prognostic indicator because phosphorus does not usually become elevated unless 85%
of the nephrons are nonfunctional. As hyperphosphatemia develops, hypocalcemia causes a reduc-
tion in calcitriol and an increase in circulating parathyroid hormone (renal secondary hyper-
parathyroidism). This syndrome directly affects the bones, kidneys, brain, heart, smooth
muscles, lungs, erythrocytes, lymphocytes, pancreas, adrenals, and testes. Results may be im-
paired function of platelets, cardiac muscle, and skeletal muscle, increased number and severity of
infections due to immunodeficiency, mental fatigue, and lethargy. It can produce nephrocalcinosis,
leading to further renal deterioration. Renal osteodystrophy with demineralization of bone and
proliferation of connective tissue has been documented but is uncommon. The resulting skeletal
decalcification and associated pathological fractures, "rubber jaw," and pain seem rare in cats.
Renal secondary hyperparathyroidism is said to occur in 84% of cats with spontaneous CRF and
100% of cats with end-stage CRE
31. What are the goals and management issues in ARF?
The goals of therapy should be to correct hemodynamic changes, fluid volume abnormali-
ties, and biochemical irregularities; to eliminate uremic toxins; to supply adequate nutrition,
and to allow repair of renal damage. Treatment recommendations are primarily supportive and
need to be initiated as early as possible to improve the chance of recovery. The inciting cause
of ARF should be identified and eliminated when possible, and therapy should be targeted to
the sequelae of acute uremia.
The first step in therapy is to address the acute crisis; this principle applies to ARF, decom-
pensated CRF, and acute-on-chronic renal failure. Life-threatening abnormalities (e.g., hyper-
kalemia, hypovolemia, metabolic acidosis) should be noted and controlled. Patients with ARF
must be stabilized by return to normal renal function or establishment of compensated chronic
renal failure, which can be treated conservatively.
32. Outline the primary treatment plan for cats with ARF.
Most cats with ARF are oliguric or anuric. A patient is considered oliguric if urine output is
< 0.27-0.5 ml/kg/hr; after rehydration, output < 1-2 ml/kg/hr is still inadequate. Evidence sug-
gests that the efficacy of treatments for the promotion of diuresis may be negligible if they are ad-
ministered more than a few hours after initiation of ARE The following general steps are
recommended:
I. A jugular catheter should be placed to allow monitoring of central venous pressure and
repeated blood sampling.
2. Placement of a urinary catheter should be considered to allow accurate measurement of
urine production.
3. Fluids should be administered intravenously at a rate that corrects dehydration within the
first 4-6 hours of therapy and induces diuresis.
4. If oliguria is persistent, mannitol is the initial treatment of choice to increase renal blood
flow, reverse cellular swelling, increase solute excretion, and discharge tubular debris. Other op-
tions include hypertonic glucose and furosemide.
5. The patients should be monitored appropriately (see question 37).
Acute and Chronic Renal Failure
Therapeutic Guidelinesfor Cats in Renal Failure
189
I. Rehydrate and reestablish fluid and electrolyte balance.
Buffered, balanced electrolyte solution or 0.9% sodium chloride (NaC]); replacement volume ad-
ministered within 4-{) hr
Replacement volume (m]) = [BW (kg)] x [estimated deficit (%)] x 1000
Maintain fluid and electrolyte balance.
0.45% NaCI with 2.5% dextrose or buffered, balanced electrolyte solution; rate based on rate
of loss
Volume (ml) = [20 mllkg/day] + [urinary + GI losses}
2. Promote urine production (primarily of concern in ARF).
Rehydrate with fluids (see above)
20% mannitol, 0.25-1.0 gmlkg, administered over 20 minutes; use only after rehydration
Furosemide: 2-6 mglkg IV every 6-8 hr; use in hydrated patient, alone or with mannitol
3. Reestablish potassium balance.
Hyperkalemia
K+ up to 6.0 mEq/L (fluid therapy)
K+ 6-8 mEq/L (fluid therapy, diuresis); if persistent:
Sodium bicarbonate, 0.5-2.0 mEqlkg IV over 30 min, or
Regular insulin, 0.1-0.25 Ulkg, + dextrose, 1-2 gmIU insulin IV
K+ > 8.0 mEq/L: 10% calcium gluconate, 0.5-1.0 mllkg IV over 15 min, + fluid therapy
Hypokalemia: potassium chloride, 0.5 mEqlkg/hr by IV infusion (see table in question 52)
Maintenance: potassium gluconate, 2-6 mEq/catlday PO
4. Correct metabolic acidosis.
Fluid therapy alone for mild-to-moderate cases
If pH < 7.1, sodium bicarbonate, 0.5-2.0 mEq/kg IV over 60 min, + fluid therapy
5. Correct hyperphosphatemia.
Limit dietary phosphorus
Phosphate binders given with meals:
Aluminum hydroxide, 30-100 mglkg/d divided PO, or
Calcium acetate, 20-30 mglkg every 8 hr PO, alone or with aluminum-based binder
6. Control uremic gastroenteritis.
Famotidine, 0.5 mglkg/day PO, SC, or 1M
Metoclopramide, 0.2-0.5 mglkg every 8 hr PO, SC, or IV if vomiting
Sucralfate, 0.25-0.5 gmlcat every 8-12 hr PO if gastric or oral ulceration
7. Provide adequate nutrition.
Meet energy requirements as fat or carbohydrates:
RER (kcaIlday) = 70 + [30 x (BW (kg) x 1.2)]
Meet protein requirements:
Minimal protein requirement = 3.8-4.4 glkg/day, 20-25 % protein on ME basis
B vitamins
8. Control hypertension.
Amlodipine, 0.625-1.25 mg/cat/day PO
9. Correct anemia
Monitor fluid therapy
Erythropoietin, 50-100 Ulkg SC 3 times/wk,+ iron dextran, 50-100 mg/day PO
10. Control hyperparathyroidism
Calcitriol, 2.5-3.5 nglkg every 24 hr PO, if serum phosphorus concentration s 6.0 mg/dl
May need to use in conjunction with dietary phosphorus restriction and intestinal phosphorus
binders
BW = body weight. or = gastrointestinal. ARC = acute renal failure, IV = intravenously. PO = orally, SC =
subcutaneously. 1M= intramuscularly. RER =renal energy requirement. ME = metabolizable energy.
33. How should fluids be replaced?
The replacement volume may be calculated using the clinical estimate of dehydration ac-
cording to the formula in the preceding table. Ideally, the replacement fluid should resemble the
type of fluid lost. In the absence of severe blood loss, buffered, balanced electrolyte solutions are
used initially. [f replacement of the fluid deficits does not result in diuresis (urine production> 1
mllkg/hr), an additional fluid volume (equal to 3-5% body weight) may be administered to pro-
duce mild volume expansion and stimulate urine production. Use care in animals with a history
of cardiovascular disease.
34. How is mannitol administered?
Administer mannitol as a slow intravenous (IV) bolus of 0.25-1.0 gmlkg. [f significant diuresis
is established within 60 minutes, mannitol administration may be continued for 24-48 hours either
as intermittent intravenous boluses of 0.25-0.5 g/kg every 4-6 hours or as a constant-rate infusion
at 1-2 mglkg/min. If diuresis is inadequate 60 minutes after the initial IV bolus, an additionallY
bolus of 0.25-0.5 glkg may be administered with caution. Potential complications associated with
volume overexpansion (e.g., pulmonary edema) are more likely to occur with a repeat bolus. The
most favorable results are obtained when mannitol is administered early in the course of ARF.
35. Describe the roles of hypertonic glucose and furosemide.
Hypertonic glucose can be used in place of mannitol to increase urine production and
supply metabolizable energy; however, it does not have many of the protective effects (vasodila-
tion, free-radical scavenging) of mannitol. Solutions of 10-20% dextrose may be formulated and
administered as a slow (over 1-2 hours) IV bolus of 25-50 mllkg 2 or 3 times daily.
Furosemide may be used alone or with mannitol to promote urine formation and facilitate
management of overhydration. Before it is used, the patient must receive adequate fluid replace-
ment. Furosemide is dosed initially at 2-6 mglkg IV. If diuresis occurs within 30 minutes, the dose
may be repeated every 6-8 hours or may be given as a constant-rate infusion at 0.25-1.0 mglkg/hr
for 24-48 hours. If diuresis is not achieved within the first 30 minutes, the dose should be repeated.
36. Why is dopamine usually not recommended for cats?
Dopamine, although widely used with furosemide in dogs, is not strongly recommended for
use in cats. Although the drug induces diuresis, it probably acts via alpha-adrenergic receptors;
effective doses for cats may create deleterious pressor effects on the kidney that worsen the initial
problem. If used, dopamine should be administered at 3 Ilglkg/min as a constant-rate IV infusion.
37. How should the patient be monitored during diuresis?
Patients undergoing diuresis should be monitored closely by measuring urine output, body
weight, packed cell volume, serum total protein and electrolyte concentrations, and central
venous pressure. In addition, they should be observed for signs of overhydration, which include
restlessness and tachycardia, chemosis, bronchovesicular sounds, or serous nasal discharge.
Auscultation of crackles and wheezes is indicative of pulmonary edema.
38. What should be done once the dehydration is corrected?
Once fluid volume is restored and urine production is adequate, IV fluid diuresis is contin-
ued until azotemia, acidosis, and electrolyte abnormalities have stabilized during the mainte-
nance and recovery periods. The fluid rate should be based on insensible, urinary, and
gastrointestinal losses (ins and outs). Insensible losses (e.g., through respiration) may be calcu-
lated as 20 ml/kg/day. Urinary output should be measured and the gastrointestinal losses esti-
mated by the volume of vomiting and diarrhea. Buffered, balanced electrolyte solutions or 0.45%
sodium chloride with 2.5% dextrose should be used.
39. What type of potassium imbalance typically develops with ARF?
Hyperkalemia is the most common potassium disorder in cats with ARF. Severity varies
greatly depending on the degree of anorexia and vomiting. Hyperkalemia has a direct effect on
the mycocardium that can be life-threatening. If potassium concentrations are unknown, an elec-
trocardiogram should be monitored. Mild hyperkalemia produces peaked T waves, short R
waves, and prolonged P-R intervals. Moderate hyperkalemia produces bradycardia. flat P waves,
prolonged Q-T intervals. and wide QRS complexes. Severe hyperkalemia causes sinoventricular
rhythms and ventricular fibrillation and may induce cardiac arrest. Cats with ARF or urinary ob-
struction frequently become hypokalemic during and after diuresis, particularly if the fluids used
are low in potassium. or after insulin administration for correction of acidosis.
40. Howis hyperkalemia treated?
Use of 5% dextrose or 0.9% sodium chloride solutions has been suggested because both are
potassium-free. However, they are not buffered and may worsen acidosis. Therefore, unless hy-
perkalemia exceeds 10 mEqlL, buffered. balanced electrolyte solutions are reasonable choices.
even though they contain small concentrations of potassium. Mild hyperkalemia 6.0 mEq/L)
or moderate hyperkalemia (6.0-8.0 mEqlL) generally resolves with initial fluid therapy. In refrac-
tory cases, furosemide may be used in addition to fluid therapy to promote potassium excretion.
41. What additional measures may be needed for severe hyperkalemia?
Severe hyperkalemia (> 8.0 mEq/L) needs to be addressed immediately because of its life-
threatening electrocardiac and neuromuscular disturbances. Calcium gluconate (10% solution,
dosed at 0.5-l.0 ml/kg) should be administered intravenously over 10-15 minutes to stabilize
heart rhythm directly and immediately. Because calcium has no effect on the serum potassium
concentration, the patient should be given bicarbonate or insulin and glucose, as described below,
once the cardiotoxic effects of hyperkalemia have been controlled. If the patient develops ar-
rhythmia, bradycardia, or hypotension, calcium administration should be stopped immediately.
If hyperkalemia remains uncontrolled despite diuresis, sodium bicarbonate (0.5-2.0
mEq/kg) may be administered intravenously over 20-30 minutes to increase the intracellular pH
and force an exchange between intracellular hydrogen and extracellular potassium. Bicarbonate
therapy should not be used in patients with metabolic alkalosis, volume overload, or hypocal-
cemia (often seen with urinary obstruction).
In patients that cannot be given sodium bicarbonate, glucose or insulin may be used to stimu-
late cellular uptake of potassium. Intravenous glucose (20%) alone may be administered at 1.5g/kg.
Alternatively, regular insulin (0.1-0.25 U/kg) may be administered intravenously with dextrose at
1-2 g/U of insulin. Monitor closely for hypoglycemia for several hours after insulin administration.
42. Howis metabolic acidosis managed?
Mild-to-moderate metabolic acidosis generally responds to diuresis. More severe cases of aci-
dosis (blood pH < 7.10 or total carbon dioxide [C0
2
] < 10 mEqlL) should be treated with sodium
bicarbonate. In acute patients, the dose can be calculated using one of the following formulas:
MEq bicarbonate = body weight (kg) x 0.3 x (desired bicarbonate - measured bicarbonate)
or
MEq bicarbonate = 20 - total CO
2
or
0.5-2 mEq/kg slow IV
Half of this dose should be given over 20-30 minutes; the remainder is mixed with IV fluids
and administered over 2-4 hours. Bicarbonate therapy is usually conservative; the goal is to bring
the serum pH to 7.2. Severely uremic patients may require ongoing bicarbonate supplementation up
to S0-90 mEq/kglday. Bicarbonate supplementation must be monitored closely because of poten-
tially severe effects of rapid correction of acidemia (pulmonary and cerebral edema. hypertension,
hypovolemia, hypokalemia, hypocalcemia. hypercapnia, and paradoxical cerebral acidosis).
43. How is intractable vomiting managed?
Oral ingestion should be avoided for approximately 24 hours. H
2
receptor antagonists such
as cimetidine, ranitidine, or famotidine are administered parenterally to lessen uremic gastritis.
Antiemetics may be administered parenterally by injection until the vomiting is controlled.
Metoclopramide is often used initially as constant-rate infusion because it promotes gastric empty-
ing; uremia induces gastric stasis. Because it is excreted by the kidneys, however, this dose should
be reduced by 50% in severely uremic animals. High doses may produce neurologic complications
(altered behavior, disorientation). Cats with intractable vomiting unresponsive to metocloprarnide
may be given phenothiazine antiemetics (acepromazine, chlorpromazine, or prochlorpromazine).
provided they are well hydrated and normotensive and can safely tolerate the side effects of vasodi-
lation, hypotension, and sedation.
44. Summarize the drugs commonly used in the management of renal failure.
Drugs Commonly Used in the Management ofRenal Failure
DRUG NAME DOSE COMMENTS
Acepromazine
Aluminum carbonate
(Basalgel)
Aluminum hydroxide
(Amphogel)
Amlodipine (Norvasc)
Calcitriol, vitamin D
Calcium acetate
(Phosl,o)
Calcium carbonate
(Turns)
Calcium gluconate 10%
Calcium phosphate
Chlorpromazine
Cimetidine (Tagamet)
Cyproheptadine
Dextrose (lD-20%
solution)
0.01-0.05 mg/kg every 8-12
hrIM, SC
3D-120 mg/kg/day divided,
with meals
3D-IOOmg/kg/day divided,
with meals
0.625-1.25 mg/cat PO every
24 hr
2.5-3.5 ng/kg every 24 hr PO
Pulse dose at 20 ng/kg PO
2 times/wk
2D-30 mg/kg every 8-12
hr PO, with meals
3D-50 mg/kg every 8 hr PO,
with meals
0.5-1.0 mg/kg IV over ID-
15 min
0.5-2.0 mmollkg/day PO
0.2-0.5 mg/kg every 6-8 hr
IM,SC
5-I0 mg/kg every 6-8 hr
PO, 1M, IV
25-50 ml/kg over 1- 2hr IV
and repeat every 8-12 hr
Used for vomiting; patient must be hy-
drated and normotensive
Phosphate binders; use with dietary
phosphorus restriction, dose to effect;
potential for aluminum toxicity; do not
use with citrate salts
Calcium channel blocker for systemic
hypertension
Give at night on empty stomach; dose
should not exceed 6.6 ng/kg; not for
use in patients with serum phosphorus
> 6 mg/dl; use with caution if giving
calcium-based phosphorus binders
Most effective calcium-based phosphate-
binding agent
Phosphate binder; use with dietary
phosphorus restriction; dose to effect;
potential for hypercalcemia
Used for severe hyperkalemia; monitor
patient for bradycardia, hypertension.
cardiac arrhythmias, ECG disturbances
Used for hypophosphatemia
Hz receptor antagonist; give slowly if IV;
administer at least 30 min apart from
metoclopramide, sucralfate, antacids;
various drug interactions; reduce dose
in hepatic or renal disease (by 10-25%
if patient is severely uremic)
Appetite stimulant
Osmotic diuretic; test urine for glucose.
and continue to monitor urine output;
adjust maintenance fluid therapy ad-
ministered between boluses to supply
total daily calculated requirements; dis-
continue if glucosuria is not present or
if urine output is not adequate after half
of recommended dose is given
Table continued Oil [ollowiru; page
Drugs Commonly Used in the Management of Renal Failure (Continued)
193
DRUGNAME
Diazepam (Valium)
Enalapril (Vasotec,
Enacard)
Erythropoietin
(Epogen)
Ethanol 20%
Famotidine (Pepcid)
Ferrous sulfate
Furosemide (Lasix)
Glucose 20%
Magnesium chloride
Magnesium sulfate
Mannitol ( 10-25%
solution)
Metoclopramide
(Reglan)
Nitroprusside (Nipride)
Oxazepam (Serax)
Potassium citrate
(Urocit-K)
DOSE
0.2-0.3 mg/kg every 12 hr
SQ
0.25-0.5 mg/kg every 12-24
hrPO
50-100 U/kg SC 3 times/wk
5 ml/kg IVevery 6hr for 30 hr.
then every 8 hr for 30 hr
0.5 mg/kg every 24 hr PO.
SC,IM
50-100 mg/cat every 24 hr PO
2--6 mg/kg every 6-8 hr IV;
incrementally increase dose
every I hr up to 6 mg/kg if
urine output remains poor
1.5 gm/kg IV
0.75-1.0 mEq/kg every 24 hr
IV for 3-5 days. mixed with
5% dextrose in water
0.25-1.0 gm/kg; give as slow
IV bolus over 15-20 min;
may repeat every 4--6 hr
0.2-0.5 mg/kg every 8 hr PO.
SC.IV
1-2 mg/kg CRI
3-10 mg/kg/min IV
0.2-0.4 mg/kg every 12 hr PO
2-6 mEqlcat every 24 hr PO
40--60 mglkg every 12 hr PO
COMMENTS
Used as appetite stimulant; causes hypo-
tension and hypovolemia that may ex-
acerbate renal failure
Angiotensin-converting enzyme inhibitor
for hypertension; may cause nausea
Start when hematocrit reaches 18'*';
administer with iron; decrease dose by
50% if hypertensive; increase dose in-
terval when hematocrit reaches 35%
Used for ethylene glycol toxicity
H
2
blocker for uremic gastropathy; may
cause hemolysis if given IV; give at
least 30 min apart from metoclopra-
mide, sucralfate, antacids; renal excre-
tion: reduce dose by 10-25% in debili-
tated patients with renal failure
Iron supplement
Loop diuretic; may produce dehydration,
hypokalemia. aminoglycoside toxicity
Used to treat hyperkalemia
Used for hypomagnesemia
Osmotic diuretic; may be given as CRr
of 8-10% solution; may cause dehydra-
tion, cardiopulmonary insufficiency.
overhydration, elevated central venous
pressure, intracranial hemorrhage
Antiemetic; acts at CRTZ; enhances
gastric ernpyting and cimetidine ab-
sorption; avoid in epileptics and
hypertensives, incompatible with cal-
cium gluconate, ampicillin sodium.
penicillin G potassium. sodium bicar-
bonate and other drugs; high doses may
cause mental disturbances; contraindi-
cated with GI bleeding; excreted by
kidneys: reduce dose by 50% if patient
is severely uremic
Vasodilator
Appetite stimulant; causes hypotension
and hypovolemia that may exacerbate
renal failure
Potassium supplement; may enhance
intestinal absorption of aluminum
Drugs Commonly Used in the Management of Renal Failure (Continued)
DRUG NAME DOSE COMMENTS
Potassium gluconate
(Kaon, Tumil-K)
Potassium phosphate
Prochlorperazine
Ranitidine (Zantac)
Regular insulin
Sodium bicarbonate
Sucralfate (Carafate)
2-6 mEq/cat every 24 hr PO
O.OI-o.Q3 mmol/kg/hr IV,
mixed with 0.9% saline
0.1-0.5 mg/kg every 8-12 hr
IM,SC
2.5 mg/kg ql2hr IV (admini-
ster slowly)
2-4mglkg every 12 hr PO
0.1-0.25 Ulkg IV; with dex-
trose, 1-2 gmIU of insulin
0.5-2.0 mEqlkg IV over 20-
30 min
5-10 mglkg PO every 8-12 hr
0.25-0.5 gmlcat every 8-12 hr
PO
Potassium supplement
Used to treat hypophosphatemia; check
phosphorus levels every 6 hr
H
2
antagonist; reduce dose in renal disease
(by 50-75% if patient is debilitated)
Used to treat hyperkalemia
Used to treat moderate hyperkalemia:
tailor PO dose to individual
GI protectant; give 30-60 min before ad-
ministration of antacids or cimetidine;
may cause constipation, impair absorp-
tion of other drugs
IV =intravenously, PO =orally, 1M=intramuscularly, SC =subcutaneously, CRI =constant-rate infusion,
CRTZ=chemoreceptor trigger zone, GI = gastrointestinal.
45. Why is nutrition important in ARF?
Maintaining adequate nutrition is mandatory in ARF to control muscle protein catabolism.
Metabolic acidosis also serves as a major stimulus for catabolism in acute uremic patients, which,
in tum, worsens azotemia, hyperkalemia, and hyperphosphatemia. Anorexia, nausea, vomiting,
and uremic toxins worsen nutritional inadequacies that lead to muscle weakness, an impaired
immune system, and delayed wound healing.
46. Describe a strategy for nutrition management in ARF.
Nutritional maintenance may be difficult in ARF patients due to persistent anorexia or vomit-
ing as well as existing gastritis or gastrointestinal ulceration. There are no easy and reliable meth-
ods of assessing nutritional status, but weight loss, reduction in serum albumin or total protein,
anemia, and muscle wasting are clinical indicators of poor nutrition. Once metabolic abnonnali-
ties associated with renal failure (dehydration, hypokalemia, anemia) have been corrected, and
drug-associated (enalapril, antibiotics) anorexia been eliminated, uremic gastroenteritis should be
considered and the patient treated accordingly, usually with an H
2
receptor antagonist and proki-
netic agent.
Severely depleted animals may require periods of total parenteral nutrition, which is admin-
istered through a dedicated central intravenous catheter. Alternatively, peripheral parenteral nutri-
tion with isotonic fluids may be used up to 5 days and then continued as a supplement to oral
feeding. Appetite stimulants may be sufficient in animals that are anorexic but not vomiting.
Inappetent cats unresponsive to appetite stimulants should be fed a nonrestricted diet or may re-
quire feeding via nasoesophageal, esophageal, or percutaneous gastric tube (see Chapter 62). See
Chapter 50 and question 50 for a discussion of dietary recommendations.
47. Howshould patients with ARF be monitored?
Resolution of clinical signs, increase in appetite, and reversal of abnorrnallaboratory values are
used to monitor response to therapy. Obviously, the patient with ARF needs to be monitored more
closely than the patient with CRE At minimum. urine output should be measured hourly, body
weight and hematocrit 2 or 3 times/day, and BUN and creatinine once daily, at least in the initial
phases of therapy. Ideally, potassium and blood gases should be assessed once or twice daily.
48. What are the key management issues in CRF?
Maintaining adequate hydration
Maintaining normal potassium concentrations
Stabilizing azotemia
Controlling metabolic acidosis
Maintaining normal phosphorus concentrations
Controlling uremic gastritis and
ulcers
Stabilizing anemia
Controlling systemic hypertension
49. What fluid support is indicated for stable patients with CRF?
Because patients with CRF have obligatory polyuria, adequate fluid intake is extremely
important to maintain fluid balance. Clear, fresh drinking water should always be available.
canned foods should be fed, and tuna broth or other flavored liquids may be offered to increase
fluid consumption. Prepared broths should be used with caution becaues of their high sodium
content; milk should be used sparingly because of its high concentration of phosphate (0.029
mmol/ml).
If oral intake is insufficient, dehydration and renal hypoperfusion occur, possibly resulting in
full uremic crisis and/or additional renal injury. Additional buffered, balanced electrolyte solu-
tions can be given subcutaneously by the owner; the volume and frequency of administration are
tailored to the individual patient's needs.
50. What diet should be fed to cats with CRF?
Diets designed for cats in renal failure usually have reduced protein, phosphorus. and
sodium concentrations; higher potassium, vitamin B, and caloric content; and a neutral
acid-base effect (see Chapter 50). Reduced protein intake minimizes hyperphosphatemia, hy-
pertension, hypokalemia, and signs of uremia, but little evidence suggests that it alters the pro-
gression of the disease. Phosphorus restriction helps to minimize hyperphosphatemia and
renal secondary hyperparathyroidism. Decreased sodium intake may help to control sys-
temic hypertension. Vitamin B supplementation helps to restore supplies depleted by
polyuria and anorexia. High caloric content helps to improve palatability and counter the ef-
fects of decreased food intake. Potassium supplementation helps to reduce the incidence of
hypokalemia, to which cats with CRF are vulnerable.
51. What are the signs of hypokalemia in cats with CRF?
Hypokalemia is the most frequent electrolyte abnormality in cats with CRF. Hypokalemia
causes generalized muscle weakness and cardiac rhythm disturbances, the hallmark sign being
ventroflexion of the neck. In addition, hypokalemia reduces renal function, worsens dysfunction
caused by metabolic acidosis, and causes polyuria as a result of nephrogenic diabetes insipidus
(unresponsiveness to antidiuretic hormone) as well as weight loss and dull haircoat because it in-
terferes with protein synthesis. Severe hypokalemia can cause death due to myocardial depres-
sion or paralysis of respiratory muscles.
52. Describe the management of hypokalemia.
Clinically stable cats with serum potassium concentrations < 4.0 mEqlL should be supple-
mented with oral potassium. Potassium gluconate is well tolerated by cats when administered
orally at a dose of 2-6 mEq/cat/day. Potassium citrate (30 mgllb/day, in divided doses every 8-12
hr orally) provides a beneficial alkalinizing side effect. Potassium chloride is an acidifier and not
recommended. When serum potassium reaches 4.0 mEqlL, the oral dosage may be reduced to a
maintenance level of 2 mEq/cat/day. Acidifying diets and diets low in magnesium should be
avoided in cats with CRF because they promote hypokalemia.
Diuresis can potentiate hypokalemia. Oral potassium supplementation should be continued,
if possible, and potassium should be added to fluids using the following formula:
Serum potassium concentration (mEq/L)
<2.0
2.0-2.5
2.6-3.0
3.0-3.5
3.5-4.0
Potassium chloride/liter of fluid (mEq)
80
60
40
30
20
53. How should acid-base disturbances be treated?
For patients with moderate-to-severe acidosis (serum bicarbonate concentration :0; 17
mliq/L), oral supplementation may be indicated. Sodium bicarbonate should be administered
orally at 8-12 mg/kg every 8-12 hours; the final dose should be tailored to the individual.
Alternatively, potassium citrate may be given orally (40-60 mglkg every 12hr); it has the benefit
of aiding in the management of both acidosis and hypokalemia. Treatment of metabolic acidosis
without concurrent treatment of hypokalemia may not be effective.
54. How is hyperphosphatemia treated?
Hyperphosphatemia should be controlled to prolong survival time and limit renal secondary
hyperparathyroidism. Control is achieved by limiting dietary intake of phosphorus and adminis-
tering phosphorus-binding agents. Although phosphorus-restricted diets are usually implemented
when serum phosphate levels are elevated, evidence suggests that they should be started much
earlier, because hyperparathyroidism may occur long before serum phosphate levels are affected.
Because most dietary phosphorus is obtained from protein sources, reduced-protein diets are rec-
ommended (see Chapter 50).
55. When should phosphorus-binding agents be given?
When serum phosphorus concentrations remain elevated 2-4 weeks after implementing di-
etary restrictions, intestinal phosphorus-binding agents should be administered. They limit the
absorption of phosphorus in the diet and inhibit resorption of phosphorus contained in saliva,
bile, and intestinal fluids. Phosphorus-restricted diets should be used concurrently because there
is less phosphorus to bind and reduced risk of toxic side effects when a lower dose can be used.
Phosphate binders usually are dosed to effect based on serial blood measurement of phosphorus
concentration; recommended dose ranges are intended simply to guide initial therapy.
56. Which phosphorus-binding agents are recommended?
Aluminum hydroxide, aluminum carbonate, or aluminum oxide is commonly used.
Sucralfate, an aluminum relative given to many patients with CRF to treat gastrointestinal ulcera-
tion, also may be useful as a phosphorus-binding agent. Inappetence and constipation may result.
Encephalopathies, microcytic anemia, and osteomalacia are toxic side-effects in humans but have
not yet been documented in cats.
Calcium acetate, calcium carbonate, and calcium citrate avoid the risk of aluminum toxicity
but may induce significant hypercalcemia. Calcium acetate is least likely to produce hypercal-
cemia and is a more effective binding agent than the others. Either calcium acetate or calcium
carbonate may be combined with an aluminum-based binding agent to reduce the risks of alu-
minum toxicity and hypercalcemia. Calcium citrate should not be used with an aluminum-based
phosphorus-binding agent. Serum calcium and phosphorus concentrations should be measured
approximately 10-14 days after starting therapy and the dose adjusted accordingly.
57. How are the gastrointestinal side effects of uremia managed?
Uremic gastritis and ulcers cause inappetence, vomiting, and, in some cats, blood loss. H
2
re-
ceptor antagonists such as ranitidine, cimetidine, and famotidine can be adminstered parenterally
until the cat is eating; at that point, they are administered orally. Because of renal clearance, ran-
itidine and famotidine doses should be reduced if the patient is severely ill. Many clinicians de-
crease the dosing frequency (in lieu of decreasing the dose) to every 48 or 72 hours. Gastric
ulceration may be treated with the coating agent sucralfate. Oral ulcers can be treated with oral
rinses of 0.1-0.2% chlorhexidine 3 or 4 times/day to reduce bacteria, prevent additional ulcer for-
mation, and relieve discomfort. Very painful necrotic lesions may be treated with topical lido-
caine. Metoclopramide can be given orally to improve gastric motility and lessen nausea.
58. Can the anemia of CRF be controlled?
It is important to try to identify the cause of anemia and to control other potentiating prob-
lems.
Uremia and gastric ulceration should be corrected first.
Malnutrition, protein and vitamin deficiencies, and hyperphosphatemia can lead to anemia
and should be corrected.
Iron deficiency is fairly common in cats with CRF and may be treated with iron sulfate.
Iron therapy also should be instituted in animals treated with recombinant erythropoietin.
Transfusion with whole blood or packed red blood cells may be warranted in severely
anemic patients with CRF, particularly those that are thought to be inappetent because of
hypoxemia. This therapy is only used when necessary because of associated risks (i.e.,
transfusion reaction with multiple treatments, transfer of infectious agents), high cost, lim-
ited availability, and reduced life span of transfused cells in patients with uremia. Ideally,
blood typing or cross-matching should be performed before transfusion to minimize com-
plications. The target hematocrit should be at the low end of the normal range.
59. What strategies may be used to treat persistent anemia?
Persistent anemia (hematocrit < 20%) resulting in clinical signs such as weakness and inap-
petence often can be managed with recombinant human erythropoietin (rHuEPO). The usual
starting dose is approximately 100 U/kg subcutaneously 3 times week. In hypertensive cats, a
subcutaneous dose of 50 U/kg 3 times/week is suggested. The hematocrit should be monitored
weekly and the dose adjusted accordingly. Resolution of the anemia usually takes 2-8 weeks.
Because use of rHuEPO places a high demand on the body's iron stores, patients receiving hor-
mone replacement therapy also should be given iron supplements. In addition to increased hema-
tocrit, most treated cats exhibit improvements in appetite, energy, and body weight. The most
common complications of rHuEPO administration are polycythemia and formation of anti-
rHuEPO antibodies, resulting in refractory anemia. On rare occasions, cutaneous allergic reac-
tions (which resolve when therapy is discontinued and often do not recur when therapy is
reinstituted) and seizures (primarily in severely debilitated animals) have been noted.
60. When should systemic hypertension be treated?
Systolic pressure consistently exceeding 170 mmHg indicates systemic hypertension (see
Chapter 63). Cats with systolic pressure> 200 mmHg can develop retinal detachment or neuro-
logic signs and require immediate therapy. With acute retinal detachment or edema surrounding
the optic disc, hospitalization and rapid reduction of blood pressure (15-20%) with intravenous
sodium nitroprusside may be instituted.
61. Discuss the role of sodium restriction for chronic management of hypertension.
No conclusive studies document the effects of dietary sodium restriction on blood pressure
in cats. Suggestions for the restriction of sodium have been extrapolated from studies in other
(primarily human) species that link sodium with promotion of arterial hypertension. However,
sodium restriction may result in prerenal azotemia by decreasing extracellular fluid volume. In
addition, diets low in sodium may be less palatable. At this point inadequate data are available to
suggest that sodium restriction is beneficial or harmful to cats. However, most renal diets are for-
mulated with restricted sodium.
62. What drugs are used to control chronic hypertension?
The calcium channel antagonist amlodipine (0.625 mg/cat/day orally) is currently the drug
of choice for systemic hypertension because of its ability to reduce blood pressure without caus-
ing fluid retention. Blood pressure measurements should be repeated every 2-4 weeks, with
subsequent dosage adjustments, until systolic pressure is just below 170 mmHg. Hypotension ac-
companied by lethargy, weakness, or anorexia suggests that the dosage should be reduced.
whereas a partial response to therapy suggests that the dosage may be increased.
If there is no response to a higher dose of amlodipine, a second drug should be added; an-
giotensin-converting enzyme inhibitors and beta antagonists are used most frequently (see
Chapter 63). Patients undergoing hypertensive therapy also should be monitored closely for ele-
vations in serum urea nitrogen and creatinine because hypotension can create prerenal azotemia
and induce uremic crisis.
63. How common are drug interactions in cats with CRF?
Because of reduced renal clearance, changes in distribution, altered protein binding, and ab-
normal hepatic biotransformation, some medications may produce changes in therapeutic effects
(both increased and decreased), resulting in increased incidence of adverse drug reactions in pa-
tients with CRE In addition, some drugs are nephrotoxic even at normal doses and must be used
with extreme care. Changes in binding capacity may promote toxicity of some drugs while less-
ening the therapeutic effect of other drugs administered within the normal dose range. Effects of
reduced renal clearance must be taken into consideration before any therapy is changed.
Drugs Affected by Renal Failure
DRUG
Amikacin
Aminoglycoside
antibiotics
Amoxicillin
Amphotericin B
Ampicillin
Antacids containing
magnesium or
phosphorus
Carbenicillin
Cephalexin
Cephalothin
Chloramphenicol
Cimetidine
Cis-platinum
Digoxin
Doxycycline
Enrofloxacin
Famotidine
Furosemide
Gentamicin
Glucocorticoids
PROBLEM
Nephrotoxic
Nephrotoxic
Renal excretion
Nephrotoxic
Renal excretion
Hypermagnesemia, hyper-
phosphatemia
May promote acidosis, renal
excretion
Renal excretion
Nephrotoxic (?), renal excre-
tion, slow elimination
Partial renal excretion
Increased binding, reduced
renal clearance
Nephrotoxic
Renal excretion
Nephrotoxic (?), partial renal
excretion
Renal excretion
Renal excretion
Nephrotoxic (?), renal excre-
tion, hypokalemia
Nephrotoxic, renal excretion
May worsen proteinuria,
increase BUN and protein
catabolism
DOSE CHANGE
Reduce dose interval*
Avoid
Use half dose or double dose interval in
severely ill patients
Use half dose or double dose interval
Avoid
Reduce doset
Reduce dose" or use half dose or double dose
interval
Normal dose; avoid in advanced renal failure
Reduce dose by 10-25% in severe disease
Contraindicated
Normal dose
Reduce dose interval* or reduce dose"
Normal dose
Avoid
DRUG
Drugs Affected by Renal Failure (Continued)
PROBLEM DOSECHANGE
199
Insulin
Kanamycin
Methoxyflurane
Metoclopramide
Neomycin
Nitrofurantoin
NSAIDs
Orbifloxacin
Penicillin
Procainamide
Propranolol
Ranitidine
Streptomycin
Sulfonamides
Tetracycline
Tobramycin
Trimethoprim-sul-
famethoxazole
Urinary acidifying
agents (methana-
mine mandelate,
nalidixic acid)
Slow elimination
Nephrotoxic
Renal excretion
Nephrotoxic
Renal excretion, may pro-
mote acidosis
Decreased binding
Renal excretion
Renal excretion
Renal excretion
Slow to rapid renal clearance
Renal excretion
Nephrotoxic
Nephrotoxic, renal excretion,
may increase BUN
Nephrotoxic
Promote acidosis
Avoid
Reduce dose by 50% in severe disease
Contraindicated in renal failure
Contraindicated in renal failure
Avoid
Reduce dose interval* or reduce dose"
Normal dose to start
Reduce doset
Reduce doset
Contraindicated
Reduce dose: avoid in advanced renal failure
Avoid
* Normal intervalx normal creatinineclearance/patient creatinineclearanceor normal intervalx patient cre-
atinine/normal creatinine.
t Normal dose x patient creatinine clearance/normal creatinine clearance or normal dose x normal creati-
nine/patientcreatinine.
64. How is the progress of a patient with renal failure monitored?
Once the cat is stabilized, evaluations should be performed 3 or 4 times/year. More frequent
rechecks (every 2--4 weeks) are recommended when therapeutic alterations are made. Physical ex-
amination and serial blood and urine tests are the best methods of determining treatment response.
Body weight, indirect blood pressure, packed cell volume and total protein, total carbon dioxide.
and serum levels of BUN, creatinine, potassium, calcium (preferably ionized), and phosphorus
should be measured; in addition, a complete urinalysis and urine culture should be performed.
65. Is dialysis available for cats?
Hemodialysis to remove uremic toxins is offered at a limited number of facilities across the
nation. Hemodialysis is highly effective for ethylene glycol intoxication and for supporting renal
function and reducing azotemia in both ARF and CRE However, one study indicates that, al-
though hemodialysis has proved effective and beneficial in ARF, complications and chronic de-
bilitation limit its efficacy in CRE Peritoneal dialysis is simpler to perform but is labor-intensive
and requires a large owner and veterinarian commitment, including 24-hour facilities and care.
Medical complications commonly encountered include peritonitis and hypoproteinemia.
66. When should dialysis be considered?
Dialysis should only be considered for short-term therapy in the following settings:
Persistent oliguria despite appropriate fluid, diuretic, or vasodilator therapy
Life-threatening electrolyte or acid-base disturbances that are nonresponsive to other treat-
ments
BUN> 100 mg/dl or serum creatinine> 10 mg/dl that is nonresponsive to other treatments
Severe fluid overload, pulmonary edema, or congestive heart failure
Acute poisoning or drug overdose
Stabilization of renal transplant recipients before transplant or during episodes of acute re-
jection.
67. Is renal transplantation a viable option?
Renal transplantation can be considered if the patient is in early decompensation; has lost no
more than 20% of healthy body weight; has no evidence of cardiac disease, urinary tract infec-
tion, or secondary illness; and is negative for feline retroviruses. In addition, the owner must be
cooperative, able to medicate the recipient, willing to adopt the donor cat, and both willing and
able to undertake the expense of surgery (estimated at $3000-$7000) and aftercare (which may
be as high as several hundred dollars per month). Recipients must be placed on long-term im-
munosuppressive therapy (prednisolone and cyclosporine) postoperatively and monitored regu-
larly. Researchers at the University of California College of Veterinary Medicine have reported a
79% survival rate in transplanted cats.
68. What is the prognosis for patients with ARF?
Prognosis depends on etiology and timely and aggressive administration of appropriate ther-
apy. Cats with ARF due to prerenal or postrenal factors have an excellent prognosis if the inciting
cause is removed before structural damage to the kidneys occurs. ARF due to infectious agents
generally has a better chance of reversal than ARF due to nephrotoxic agents, although nephro-
toxic ARF has a better prognosis than ischemic ARF. In general, polyuric renal failure has a
better prognosis than oliguric or anuric renal failure. Magnitude of azotemia is not a good predic-
tor of outcome. Cats that survive to the recovery phase frequently do not recover full renal func-
tion and should be observed for evidence of renal insufficiency or failure.
Studies have shown that hemodialysis has extended lives in severe cases of RF. In one study,
60% of cats with pyelonephritis or ethylene glycol toxicity that did not respond to conventional
therapy recovered sufficiently that further dialysis was unnecessary, and 44% of cats with ethyl-
ene glycol toxicity, severe azotemia, and oliguria or anuria also survived with hemodialysis.
69. What is the prognosis for patients with CRF?
Because loss of renal function is permanent in CRF, prognosis depends on the extent or prob-
ability of abatement of clinical signs. Long-term prognosis should be based on a number of fac-
tors, including severity of clinical signs, likelihood of improving renal function, severity of
impaired renal function, type and rate of progression of disease, and age of the patient.
Severity of clinical signs is usually a good short-term prognostic indicator, except in cases of
acute-on-chronic renal failure when the patient may be in a temporary uremic state. Severity of
renal dysfunction also may be useful in establishing long-term prognosis. Hydrated, well-fed cats
with serum creatinine concentrations < 4.5 mg/dl typically fare rather well, whereas cats with
concentrations> 10mg/dl do not respond as favorably. Similarly, hyperphosphatemia is indica-
tive of advanced disease and a guarded prognosis.
Many cats with CRF can be maintained with a good quality of life for months to years. However,
CRF is a progressive disease, and no therapeutic strategies to date have been shown to alter markedly
its progression in cats. The best method of predicting long-term prognosis is to assess progression
and response to management with serial examinations and laboratory evaluations.
CONTROVERSIES
70. Can renal failure be prevented?
Potentially inciting factors should be avoided. Increasing natriuresis, urine volume, and solute
excretion by saline diuresis before administration of nephrotoxic agents may help to prevent ARE
Chronic metabolic acidosis due to acidifying diets may lead to bone demineralization as well
as taurine and potassium depletion. Studies also suggest that hypokalemia may be a cause and
not only a result of CRF in some cats.
Systemic hypertension may lead to chronic progression of renal failure. For the most part. it
is unknown whether hypertensive cats with CRF develop systemic hypertension secondarily or
whether chronic systemic hypertension causes CRF. Blood pressure measurement should be part
of the yearly health assessment for middle-aged and geriatric cats.
71. Is calcitriol supplementation indicated?
Reduced calcitriol production may develop as renal tubular function declines, contributing to
renal secondary hyperparathyroidism and increased levels of circulating parathyroid hormone.
Calcitriol rapidly and effectively controls secondary hyperparathyroidism without requiring renal
activation like other forms of vitamin D therapy. Some evidence suggests that calcitriol supple-
mentation benefits patients with CRF; favorable results (improved appetite. brighter attitude.
more active. longer life span) have been reported by clinicians. However, controlled clinical trials
have not been conducted in cats.
72. When and howshould calctriol administration be initiated?
Calcitriol administration may be initiated after dietary phosphorus restriction has been im-
plemented and serum phosphorus is controlled 6 mg/dl). The recommended initial dose range
is 1.5-3.5 nglkg orally every 24 hours, but this recommendation should be amended for the indi-
vidual patient, preferably not to exceed 6.6 nglkg. Calcitriol is best administered at night on an
empty stomach because of its propensity to increase intestinal absorption of both calcium and
phosphorus. Calcitriol should be used with caution in patients receiving calcium-based phos-
phate binders, particularly calcium carbonate.
The onset of action and half-life of calcitriol are short ( ~ 24 hrs); BUN, creatinine, cal-
cium, and phosphorus measurements should be evaluated I week after initiating calcitriol ad-
ministration. Ideally, the concentration of calcium times phosphorus product should be between
42 and 50. If the product exceeds 60, calcitriol therapy should be discontinued. If hypercal-
cemia develops, calcium carbonate administration should be discontinued or replaced with an
aluminum-based phosphorus-binding agent. If calcium carbonate is not administered, calcitriol
treatment should be discontinued, then reinstituted at a lower dose when serum calcium levels
return to normal.
73. Does magnesium imbalance occur in patients with renal failure?
Patients with CRF have the potential to be hypermagnesemic because the kidneys cannot ex-
crete magnesium. Hypermagnesemia is not considered clinically significant unless it is accompa-
nied by hypocalcemia. Magnesium-containing antacids are contraindicated.
More commonly, protein catabolism, peritoneal dialysis, use of diuretics, and aggressive
fluid therapy produce abnormally low magnesium levels that may result in muscle weakness,
tremors, and seizures. In addition, insufficient magnesium may leave the kidneys vulnerable to
further insult, because magnesium may be renoprotective in some types of toxicity. If severe hy-
pomagnesemia is documented ( ~ 1.2 rng/dl), supplementation should be administered intra-
venously by the addition of magnesium chloride or magnesium sulfate to 5% dextrose in water,
using an initial dose of 0.75-1.0 mEq/kg/day for 3-5 days. In the case of life-threatening ven-
tricular fibrillation, 0.15-0.3 mEq (50-100 mg) per kg may be added to a solution of 5% dextrose
or 0.9% saline and administered intravenously over 5-15 minutes.
74. Are anabolic steroids indicated in anemic patients with CRF?
Anabolic steroids, once widely used, are no longer recommended because of their limited ef-
ficacy. prolonged onset of action, and adverse side effects. A recent study suggests that stanazolol
can be hepatotoxic to cats. Although the effects may be reversed once therapy is discontinued,
there still is no clear indication for the use of anabolic steroids in feline CRE
202
75. When should diet therapy be instituted?
For reasons mentioned above, diet therapy should be instituted as soon as chronic renal dis-
ease is indicated. Patients are more likely to tolerate a change in diet before gastrointestinal effects
of CRF occur, and early in renal disease it may be possible to control hyperparathyroidism by di-
etary intervention alone. However, protein restriction in patients whose serum creatinine concen-
tration is < 5 mgldl is controversial. Until we achieve a better understanding of the role of dietary
protein in such patients, a reasonable compromise may be the gradual reduction of dietary protein
in relation to the increase in serum creatinine. Morraillon suggests the following guidelines:
Serum Creatinine (mgldl) Dietary Protein (%DM)
3.5 25
4n 19
4.5 14
5.0 10
5.5 7
76. Should fatty acid supplements be used?
Studies in people suggest that fatty acids may alter the progression of renal failure. However,
human studies cannot be directly extrapolated to cats because, unlike in people, both linoleic and
arachidonic acids are essential fatty acids in cats, and the conversion of one fatty acid to the other
is limited. As a result, further studies of the benefits and risks of dietary supplementation with
fatty acids are necessary before recommendations can be made.
BIBLIOGRAPHY
I. Barber PJ, Elliott J: Feline chronic renal failure: Calcium homeostasis in 80 cases diagnosed between
1992 and 1995. J Small Anim Pract 39: I08-166, 1998.
2. Bartges JW, Willis AM, Polzin DJ: Hypertension and renal disease. Vet Clin North Amer Small Anim
Prac 26:1331-1345,1996.
3. Burkholder WJ: Dietary considerations for dogs and cats with renal disease. J Am Vet Med Assoc
216:1730-1734,2000.
4. Cowgill LD, Elliott DA: Acute renal failure. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary
Internal Medicine. Philadelphia, W.B. Saunders, 2000, pp 1615-1633.
5. Grooters AM, Duypers MD. Partington BP. et a1: Renomega1y in dogs and cats. Part II: Diagnostic ap-
proach. Comp Cont Educ Pract Vet 19:1212-1229. 1997.
6. Harkin KR, Cowan LA, Andrews GA, et al: Hepatotoxicity of stanozolol in cats. J Am Vet Med Assoc
2000.
7. Hurley KJ: Acute renal failure. Waltham FOCUS on the Urinary Tract. Presented at the 1998 British
Small Animal Veterinary Association Conference. Waltham USA, Inc.. 1998, pp 7-17.
8. Lane IF, Grauer GF. Fettman MJ: Acute renal failure. Part I: Risk factors, prevention, and strategies for
protection. Comp Cont Ed Pract Vet 16:15-29, 1994.
9. Lane IF, Grauer GF, Fettman MJ: Acute renal failure. Part II: Diagnosis, management, and prognosis.
Comp Cont Educ Pract Vet 1994.
10. Lulich JP, Osborne CA, O'Brien TD, et al: Feline renal failure: questions, answers, questions. Comp
Cont Educ PractVet 14:127-152.1992.
II. Macintire DK: Disorders of potassium, phosphorus, and magnesium in critical illness. Comp Cont Educ
PractVet 19:41-48, 1997.
12. Nagode LA, Chew D. Podell M: Benefits of calcitriol therapy and serum phosphorus control in dogs and
cats with chronic renal failure. Vet Clin North Amer Small Anim Prac 26:1293-1330, 1996.
13. Neel JA, Grindem CB: Understanding and evaluating renal function. Vet Med 95:555-565,2000.
14. Norsworthy GD: Managing chronic renal failure in geriatric cats. Vet Med 95:11-18, 2000.
15. Polzin DJ. Osborne CA. Jacob F. et al: Chronic renal failure. In Ettinger SJ, Feldman EC (eds): Textbook
of Veterinary Internal Medicine. Philadelphia, W.B. Saunders, 2000, pp 1634--1662.
16. Rubin SI: Chronic renal failure and its management and nephrolithiasis. Vet Clin North Am Small Anim
Pract27:1331-1354.1997.
17. Sparkes AH: Diagnosis and management of chronic renal failure in cats. Waltham FOCUS 011 the
Urinary Tract. Waltham USA, Inc.. 1998, pp 25-31.
41. PYELONEPHRITIS
Helen Tuzlo. D.v.M.. M.S.
1. Define pyelonephritis.
Pyelonephritis refers to inflammation of the renal pelvis and parenchyma, especially the ad-
jacent medulla, with potential extension into the cortex. The disease may be unilateral or bilat-
eral, acute or chronic.
2. What causes pyelonephritis?
Pyelonephritis is a manifestation of bacterial infection of the kidneys. Usually bacteria
ascend from the lower urinary tract, but they also may spread to the kidneys via the bloodstream
(hematogenous route) from distant foci such as dental disease, bacterial endocarditis, or disko-
spondylitis. The most frequently implicated organisms include Escherichia coli, Staphylo-
coccus aureus, Streptococcus spp., Klebsiella pneumoniae, Pseudomonas aeruginosa,
Enterobacter spp., and Proteus spp. Rarely are anaerobes identified as the cause of urinary tract
infections (UTIs).
3. What types of conditions predispose patients to pyelonephritis?
Normal voiding is a natural defense against UTI, effectively washing out bacteria from the
urinary bladder. Therefore, disorders that decrease the frequency and/or volume of voided urine
or that result in an increased urine residual volume (such as urethral stricture or urachal remnant)
are predisposing factors. Damage to mucosal barriers of infection by uroliths, neoplasia, or even
palpation leaves the patient susceptible to infection. Other anatomic anomalies, such as an ec-
topic ureteral termination, may allow ascending migration of bacteria.
Conditions that weaken the immune system, such as retroviral infection or hyperadrenocorti-
cism, may predispose cats to pyelonephritis. Patients with diabetes mellitus generally have defi-
cient immunity as well as a greater likelihood of lower UTI due to glucosuria. Conditions that
result in dilute urine or extremes of urine pH reduce its antibacterial properties. making infection
easier. Iatrogenic factors such as glucocorticoid administration, urinary catheterization, and sur-
gical diversions (e.g., perineal urethrostomy) also predispose cats to kidney infection.
Other predisposing factors include decreased urine volume and decreasing frequency of
voiding (from decreased water consumption or vomiting and diarrhea), voluntary retention of
urine, vesicoureteral reflux, herniated bladder, and spinal diseases such as vertebral fractures, in-
tervertebral disk disease, and spinal neoplasia.
4. What are the most commonly observed signs of pyelonephritis?
In the acute form, the most common signs are recent-onset lethargy, anorexia, fever, vomiting,
and dehydration. Patients may demonstrate polyuria and polydipsia and have pain in the lumbar
area. Signs of lower UTI (pollakiuria, strangiuria, dysuria, frank hematuria) also may bepresent.
The chronic form is subtle and may not be noticed by the owner. Patients may show weight
loss or reduced appetite; some may be polydipsic and polyuric. Another common scenario sug-
gesting upper UTI is a bacterial UTI that recurs when antibiotics are discontinued. In many cats,
pyelonephritis is subclinical.
5. What may be found on physical examination?
Diagnosis usually is based on history, physical examination, and laboratory findings. In the
acute form, fever and abdominal discomfort may be detected on physical examination. One or
both kidneys may be enlarged or painful on palpation. Cats with the more subtle chronic form
may have none of these physical indicators, and only a loss of weight may be noted.
203
204 Pyelonephritis
6. What kind of laboratory tests should be done if pyelonephritis is suspected?
The minimum database should include complete blood count (CBC). serum biochemical
panel, and urinalysis. In suspected cases, when the urine sediment is active or when the specific
gravity is low (below 1.035), quantitative urine culture and sensitivity also should be performed.
7. What is typically found on urinalysis?
The simple and most sensitive diagnostic test of renal function, especially for diseases, such
as pyelonephritis, that affect the medulla is a measure of the kidneys' concentrating ability, par-
ticularly in the face of dehydration or azotemia. The urine sample should be collected, preferably
by cystocentesis, before drugs are administered. Urinalysis findings may include evidence of uri-
nary tract inflammation (proteinuria, pyuria, and hematuria) as well as low specific gravity and
bacteriuria. However, failure to detect bacteria in the sediment does not exclude the possibility of
infection. Especially in patients with dilute urine, the sediment may be nonreactive.
8. When should urine be cultured?
In suspect cases or in cases of isosthenuria, the urine should be cultured qualitatively and
quantitatively, even if no bacteria are observed in the sediment. Although ideally the culture
should be initiated within 30 minutes of collection, the sample may be refrigerated for 6-8 hours
before plating. Although the lower limit of bacterial growth in feline urine indicative of infection
is thought to be lower than for dogs or people, the actual figure has yet to be determined. The
consensus at present is that bacterial growth> 1000 bacterialml of sample collected by catheteri-
zation or any growth in a cystocentesis sample is indicative of UTI.
9. Howis a kidney infection differentiated from a lower UTI?
The lower urinary tract is presumed to be involved in all cases of UTI, but in some cases it is
difficult to determine whether the infection also involves the kidney(s) (see Chapter 46). In gen-
eral, systemic signs such as fever, polyuria, polydipsia, depression, anorexia, vomiting, and dehy-
dration are not seen with disorders limited to the bladder, urethra, or prostate. Granular casts (>
1IIpt), cellular casts, or renal epithelial cells in a urine sample help to localize the infection to the
upper urinary tract; their absence, however, does not rule out the possibility of pyelonephritis.
Upper UTI should be considered when infection recurs after initial therapy or when the infection
is documented without concurrent lower urinary tract symptoms. In addition, a positive culture in
dilute urine is suggestive of pyelonephritis.
Some cases of pyelonephritis are associated with concurrent changes in the hemogram
and/or biochemistry referable to kidney disease. Hemogram (CBC and differential) abnormalities
may include a neutrophilic leukocytosis with left shift (more likely in acute disease). The chronic
form can result in a nonregenerative anemia. Serum biochemistry profile alterations observed
during active infection may include azotemia and hyperphosphatemia, especially in patients with
renal failure. Patients with azotemia typically have metabolic acidosis. In some cases serum bio-
chemistry may be normal.
10. What other disorders may resemble pyelonephritis?
The nonspecific signs of systemic illness usually seen with pyelonephritis are also indicative
of a myriad of other diseases, particularly those that affect both kidneys, such as polycystic
kidney disease, feline infectious peritonitis, amyloidosis, bilateral hydronephrosis. renal lym-
phoma, and perinephric pseudocysts. Renomegaly may be identified in cases of hypertrophy, py-
onephrosis, renal abscessation, and acute ureteral obstruction. Acute renal failure may resemble
pyelonephritis but usually has a rapid onset. It is possible for a patient to have acute and/or
chronic renal failure along with pyelonephritis (see Chapter 38).
11. What imaging tests help to confirm the diagnosis?
In some instances, imaging of the kidneys may be necessary to confirm the diagnosis or to
identify predisposing factors. The normal feline kidney is 2.5-3.5 times the length of L2 on a
Pyelonephritis 205
right lateral radiograph (3.0-4.3 em on sonogram) and is located ventral to Ll-L4 with the right
kidney slightly cranial to the left. In cases of pyelonephritis, one or both kidneys may be enlarged,
especially in the acute form of the disease. On abdominal ultrasound or excretory urogram, di la-
tion of the renal pelvis(es) and ureter(s) may be seen. Incomplete filling of the diverticula may be
evidence of an acute process, whereas blunting of the pelvic diverticula may be indicative of
chronic pyelonephritis. A decrease in opacity of contrast media in the collecting system is sugges-
tive of pyelonephritis, or good initial opacification may be followed by persistence of a dense
nephrogram. Hyperechoic or asymmetrical cortices and hypoechoic or mixed echogenic renal
pelves may be noted on abdominal ultrasound. However, diagnostic imaging is limited in that a
normal study does not exclude the possibility of infection. In addition, neither imaging technique
can quantify renal function or determine whether the disease process is reversible.
12. How is pyelonephritis treated?
Treatment consists of antibiotic administration to eradicate infection, correction of predis-
posing factors, and fluid therapy as needed. Animals that are acutely ill, anorexic, or azotemic
benefit from intravenous fluid therapy and parental antibiotics until the systemic signs abate.
13. Which antibiotic should be administered?
The primary therapy consists of administration of the appropriate antimicrobial, based on
urine culture and susceptibility results determined by minimum inhibitory concentration (MIC)
of antimicrobials for the infecting organism. The preferred antibiotics are those that can penetrate
the renal medulla, such as nitrofurantoin, trimethoprim, chloramphenicol, and enrofloxacin. The
medication should be administered at the correct dosage for a minimum of 6-8 weeks. When the
bacteria cannot be positively identified, penicillin should be used for gram-positive organisms;
gram-negative organisms respond well to trimethoprimlsulfa or enrofloxacin. Because
Escherichia coli is the most commonly isolated organism in feline UTI, patients with rods in the
urine sediment may be treated with amoxicillin combined with c1avulanic acid, trimethoprim-
sulfa, or a quinolone until the sensitivity results are obtained. If cocci are identified, you may
start the patient on ampicillin or amoxicillin while awaiting MIC results. In the absence of sensi-
tivity testing, the following antibiotics are the drugs of choice for the most common infections:
enrofloxacin for E. coli and Klebsiella spp.; arnoxicillin-clavulanic acid for Proteus spp.,
Staphylococcus spp., and Streptococcus spp.; and tetracycline for Enterobacter spp. and
Pseudomonas spp. Tetracyclines (except doxycycline) and aminogIycosides should be avoided in
cases of renal insufficiency. In addition, the dosage of quinolones and cephalosporins should be
reduced or the interval extended.
14. How are drug dosages adjusted in patients with renal failure?
I. Formula to adjust the dose of cephalosporins and quinolones:
Current dosage x (normal creatinine/patient's creatinine)
2. Formula to adjust the interval:
Current dosage x (patient's creatinine/normal creatinine)
15. How is the patient's progress monitored?
The urine should be cultured approximately 7-14 days after treatment is initiated to deter-
mine antimicrobial efficacy and then recultured I week after the therapeutic course is completed.
If either culture is positive, a different antimicrobial should be selected (based on antimicrobial
susceptibility testing) and the follow-up regimen repeated. If both cultures are negative, monthly
cultures are recommended for several months to detect persistent infection. Ideally, the patient
should not be considered recovered until three consecutive urine cultures are negative.
16. What causes "recurrent" UTls?
A second episode may be due to relapse with the same infecting bacteria or to reinfection
with a new strain of bacteria.
206 Pyelonephritis
17. When does relapse usually occur? What are the typical causes?
Relapse usually occurs days to weeks after ending treatment and usually is caused by failure
to clear the initial infection. Relapses are generally associated with a higher degree of antimicro-
bial resistance than original infections. The most common causes of relapse are as follows:
Insufficient or inaccurate therapy
Lack of owner compliance
Failure to eliminate predisposing causes
Impaired drug absorption from the gastrointestinal tract
Bacterial sequestration or failure to multiply
Mixed infections with only one pathogen eliminated by therapy
Emergence of drug-resistant pathogens
18. When does reinfection occur? What are the typical causes?
Reinfection implies that the urinary tract again became infected after the initial infection was
cleared. The time interval between reinfections is usually longer than that between relapses.
Reinfections most frequently are due to the following causes:
Failure or inability to relieve the predisposing factors
Iatrogenic causes (catheterization)
Sequelae to surgical techniques affecting host defenses (urethrostomy)
Reinfection with less invasive (opportunistic) bacteria, such as Pseudomonas aeruginosa or
Klebsiella pneumoniae, usually suggests a compromised immune system.
19. What should be done for patients with frequent recurrences of UTI?
The first step should be a thorough effort to identify and eliminate predisposing factors. such
as uroliths, anatomic defects, endocrinopathies, or other characteristics that interfere with the
body's protective mechanism. Excretory urography and/or ultrasonography, if not previously per-
formed, are recommended. In addition, a longer course of therapy (up to 6 months), should be in-
stituted. If infection recurs after 6 months of full-course therapy, if reinfection occurs more than 4
times/year, or if predisposing factors are noncorrectable, suppressive therapy consisting of contin-
uous low-dose administration of an antimicrobial should be initiated once the initial infection is
cleared. Such patients usually do well on one-third to one-half the normal daily dose of antibiotic
given once every 24 hours, preferably at night. Urine should be cultured monthly. If a positive cul-
ture is obtained, the patient is treated as though the infection were acute (full dose for 4-6 weeks)
before returning to low-dose therapy; if the culture is negative, suppressive therapy should be con-
tinued. Most cases do well after 6 months of bacteria-free urine. However, in patients prone to re-
infection, urine should be examined and cultured periodically, preferably at least 3 times/year.
20. What is the prognosis for cats with pyelonephritis?
The status of the host's defense mechanisms is the most important factor in assessing proba-
ble outcome of treatment for UTI. Pyelonephritis in both severe acute and chronic forms can lead
to renal failure. Cats diagnosed early in the acute form and treated aggressively appear to do well.
The prognosis is also good if predisposing factors are eliminated and treatment begun before the
onset of endstage renal disease. Cats in which treatment is delayed or inadequate to eradicate in-
fection often suffer permanent kidney damage and chronic renal failure.
CONTROVERSIES
21. What is the role of pyelocentesis and kidney biopsy in the diagnosis pyelonephritis?
Although culture of a pyelocentesis sample and histopathologic findings are necessary for
definitive diagnosis of pyelonephritis, there are varying schools of thought about performing
these procedures in the face of infection. Fine-needle aspiration can be performed with ultra-
sound guidance and may provide an ideal sample for culture of the upper urinary tract, but some
Pyelonephritis 207
experts believe that renal sampling is contraindicated in cases of infection because of the poten-
tial for creating leakage into the abdomen and subsequent peritonitis. Renal biopsies also may
contribute to progressive renal deterioration in cats. A good rule of thumb is that any cat with
UTI and azotemia or dilute urine should be assumed to have pyelonephritis. With this principle in
mind, few cases of UTI should require renal biopsy.
22. Are any adjunct treatments helpful in pyelonephritis?
Recent studies in rats treated with antibiotics have suggested that supplementation with vita-
mins A and E may help to decrease the extent of renal inflammation in acute bacterial
pyelonephritis. However, these preliminary data have not yet been explored in cats.
23. In cats with unilateral disease, should the affected kidney be surgically removed?
Nephrectomy as a treatment for pyelonephritis is not recommended and rarely performed. It
should be done only as a last resort, and only if (1) the diseased kidney appears grossly abnormal
on excretory urogram; (2) the contralateral kidney appears normal on excretory urogram; and (3)
the patient is not azotemic. Quantitative renal scintigraphy can be completed at referral centers to
document individual kidney function before nephrectomy is performed.
BIBLIOGRAPHY
l. Barsanti JA: Genitourinary infections. In Greene CE (ed): Infectious Diseases of the Dog and Cat. 2nd
2. Bennett RT, Mazzaccaro RJ, Chopra N, et al: Suppression of renal inflammation with vitamins A and E
in ascending pyelonephritis in rats. J Urol 161:1681-1684, 1999.
3. Cuypers M, Grooters AM, WiIliarns J, et a1: Renomegaly in dogs and cats. Part I: Differential diagnosis.
4. DiBartola SP: Renal diseases of the cat. Proceedings from the American Board of Veterinary Practi-
tioners Symposium. Chicago, 1998, pp 197-214.
5. Feeney DA, Barber DL. Johnston GR, et al: The excretory urogram. Part II: Interpretation of abnormal
findings. Compendium Collection: Renal Disease in Small Animal Practice. Trenton, NJ, Veterinary
Learning Systems, 1994, pp 255-263.
6. Forrester SD, Lees GE: Diseases of the kidney and ureter. In Birchard SJ, Sherding RG (eds): Saunders
Manual of Small Animal Practice. Philadelphia, W.B. Saunders, 1994, pp 807--808.
7. Grauer GF: Urinary disorders. In Nelson RW, Couto CG (eds): Manual of Small Animal Internal
Medicine. St. Louis, Mosby, 1999, pp 355-408, 790.
8. Grauer GF: Complicated urinary tract infections. Scientific Proceedings of the American Animal
Hospital Association, Chicago, 1998, pp 44-47.
9. Grooters AM, Cuypers M, Partington BP, et al: Renomegaly in dogs and cats. Part II: Diagnostic ap-
proach. Comp Cont Educ Small Anim Pract 19:1213-1229, 1997.
10. Lulich JP, Osborne CA, O'Brien TD, Polzin DJ: Feline renal failure: Questions. answers, questions.
Comp Cont Educ Sm Anim Pract 14:127-152, 1992.
II. Osborne CA: Three steps to effective management of bacterial urinary tract infections: Diagnosis, diag-
nosis, and diagnosis. Comp Cont Educ Small Anim Pract 17:1233-1248, 1995.
12. Polzin DJ: Recurrent urinary tract infections. Scientific Proceedings of the American Animal Hospital
Association, Seattle, WA, 1993, pp 461-464.
13. Rubin SI: The procedures that confirm and localize a urinary tract infection. Vet Med 85:352-364.
1990.
14. Senior DF: Bacterial urinary tract infections: Invasion, host defenses, and new approaches to prevention.
Compendium Collection: Renal Disease in Small Animal Practice. Trenton, NJ, Veterinary Learning
Systems, 1994, pp 160-168.
42. POLYCYSTIC KIDNEY DISEASE
Julie R. Fischer, D.V.M.
1. Define polycystic kidney disease.
Polycystic kidney disease (PKD) is an autosomal dominant condition that occurs most
commonly in Persian and Persian crossbred cats, but it has been documented in many other
breeds as well as in mixed-breed cats. Affected cats develop fluid-filled cysts in the renal
parenchyma; cysts compress the normal renal tissue as they expand. The disease is progres-
sive, and in most cats parenchymal compression and consequent interstitial nephritis eventu-
ally result in renal failure.
2. What historical findings support the diagnosis of PKD?
Because the clinical signs of PKD are due to renal failure, which may take years to develop,
cats are usually subclinically affected and considered normal by their owners until the later stages
of the disease. Once renal insufficiency or failure occurs, historical findings are the same as for
other causes of chronic renal failure. Common examples include polyuria, polydipsia, inappe-
tence, weight loss, vomiting, and weakness (see Chapter 40). Cats with PKD may be predisposed
to develop urinary tract infections because the cysts can serve as a nidus for bacterial growth.
Culture of cyst fluid may be necessary to document infection.
3. Describe the classic physical examination findings.
Cats with PKD may have renomegaly on physical examination. The kidneys usually have a
palpably irregular surface and in severely affected cats can feel like small bunches of grapes. In
the early stages of PKD, changes in renal structure are likely be the only abnormal physical ex-
amination finding. Physical examination performed in the late stages of the disease may reveal
signs consistent with chronic renal failure; poor body condition, pallor, dehydration, and weak-
ness are common. Uremic breath and oral ulceration are consistent with decompensated renal
failure (see Chapter 40). Renal hemorrhages or retinal detachment may be seen in cats with con-
current systemic arterial hypertension.
4. What laboratory abnormalities are seen with PKD?
No blood or urine abnormalities are specific for PKD. The serum biochemical and urinalyses
in an otherwise healthy cat are unremarkable before renal insufficiency occurs; afterward they
are typical of this condition (see Chapter 40).
5. When should PKD be suspected?
Any Persian or Persian crossbred cat with historical, physical examination, or laboratory
findings consistent with chronic renal failure or with persistent or recurrent bacterial urinary tract
infection should be screened for PKD. In addition, any cat whose kidneys feel irregularly mar-
ginated on physical examination should be screened.
6. What is the best diagnostic test for PKD?
Ultrasonographic examination of the kidneys reliably detects PKD. The fluid-filled cysts are
readily apparent as hypoechoic, usually spherical regions scattered through both kidneys. Cysts
vary greatly in size (from < I mm to > I ern). Only a few cysts may be present, or cysts may
occupy most of the renal parenchyma. Ultrasonography differentiates PKD from renal neoplasia
and feline infectious peritonitis, both of which also can cause palpably irregular, lumpy kidneys.
Excretory urography is also helpful in differentiating PKD from other causes of renomegaly. The
nephrogram phase in a cat with PKD shows numerous, sharply demarcated radiolucencies in the
208
Polycystic Kidney Disease 209
Longitudinal ultrasonographic image of the left kidney of a 4-year-old Persian cat with PKD. Note the multi-
ple, varied, rounded, anechoic regions throughout the renal parenchyma. The other kidney was similarly af-
fected. (Image courtesy of David S. Biller, D.V.M., Kansas State University.)
renal parenchyma, because the cysts do not fill with contrast media. Late in the disease, survey
radiographs may detect bilateral renomegaly and irregular renal silhouettes.
7. What should I do if a client asks me to "screen" a cat for PKD?
If the cat is Persian or Persian crossbred, agree to it! Ultrasonographic examination can
detect renal cysts noninvasively in kittens as young as 7 weeks of age. In one study, ultrasono-
graphic findings in cats at least 36 weeks of age had a 91% sensitivity and 100% specificity for
the detection of PKD. Sensitivity was 75% (but specificity was still 100%) in kittens 16 weeks of
age or less. However, sensitivity and specificity are operator-dependent; experienced ultrasonog-
raphers should perform PKD screening examinations. A clinically normal cat of non-Persian
breeding has a relatively low likelihood of having cystic renal disease (14% in one study), and, if
present, the disease may not behave like PKD.
8. How can PKD affect the health of an affected cat?
PKD is a progressive disease. Cats with PKD develop renal insufficiency and eventual renal
failure when cystic enlargement and interstitial nephritis destroy more than 67-75% of the renal
parenchyma. Cats so affected should be treated like cats with chronic renal failure for any other
reason (see Chapter 40). In addition, the cysts can become infected.
9. How are cyst infections diagnosed and treated?
Cyst infections may be difficult to diagnose and to clear. Cyst fluid can be aspirated with ul-
trasound guidance, and culture of the fluid gives the most solid basis for antimicrobial selection.
If infected cysts are suspected or confirmed, lipid-soluble antimicrobials, which penetrate the
cyst wall, should be used for therapy. Fluoroquinolones and potentiated sulfonarnides have been
shown to achieve excellent penetration into renal cysts in humans, and should be used for at least
4-6 weeks. Documented cyst infections should be treated as complicated urinary tract infections,
with monitoring and reculturing as indicated (see Chapters 39 and 48).
10. How quickly does PKD progress?
The rate of progression to renal failure varies tremendously from cat to cat. Renal failure
usually occurs between the ages of 3 and IO years, with an average age at onset of 7 years.
Occasionally, a cat will live a normal life span despite the presence of PKD.
210 Feline Glomerular Diseases
11. What can be done to prevent PKD?
Because PKD is an autosomal dominant condition, it is theoretically possible to eliminate it
from the Persian breed by careful screening and exclusion of affected cats from the breeding
pool. Owners should be informed that PKD is heritable. Cats with PKD should be sterilized or
otherwise prevented from reproducing.
BIBLIOGRAPHY
I. Biller DS, Chew DJ, DiBartola SJ: Polycystic kidney disease in a family of Persian cats. J Am Vet Med
Assoc 196:1288-1290, 1990.
2. Biller DS, OiBartola SP: Familial renal disease in cats. In Bonagura JO, Kirk RW (eds): Current
VeterinaryTherapy xn. Philadelphia, W.E. Saunders, 1995, pp 977-979.
3. Biller OS, DiBartola SP, Eaton KA: Inheritance of polycystic kidney disease in Persian cats. J Hered
87:1-5,1996.
4. OiBartola SP: Autosomal dominant polycystic kidney disease. In Proceedings of the 18th Annual
Veterinary Medical Forum, Seattle, WA, 2000, pp 438-439.
5. Eaton KA, Biller DS, DiBartola SP, et al: Autosomal dominant polycystic kidney disease in Persian and
Persian-cross cats. Vet PathoI34:117-126, 1997.
43. FELINE GLOMERULAR DISEASES
Craig B. Webb, D.V.M., Ph.D.
1. What are the two major categories of glomerular disease?
Glomerulonephritis and amyloidosis.
2. How prevalent is glomerular disease in cats?
Confirmed cases of feline glomerular disease are rare. In two separate surveys of 160 and 333
sick cats, only one suspected case of glomerulonephritis was identified. One review of published
reports of feline amyloidosis uncovered 20 cases over a 20-year time span. However, reports of
glomerular disease in cats have increased in prevalence with the advent of electron microscopy
and the ability to discern changes in basement membrane and podocyte foot process morphology.
3. Describe the pathogenesis of glomerulonephritis.
Glomerulonephritis results from one of two immunologic mechanisms: immune complex
deposition or formation of antibodies to glomerular basement membrane components. Soluble,
circulating antigen-antibody complexes may become localized in glomerular capillary walls. or
in situ immune complexes may be formed in response to antigens within the glomerular base-
ment membrane and capillary walls.
4. What glomerular changes result from immune complex deposition?
The glomerular response to immune complex deposition is glomerular cell proliferation and
glomerular capillary wall thickening. Associated findings are cellular and mesangial matrix pro-
liferation and glomerular basement membrane thickening.
5. Describe the pathologic progression of glomerulonephritis.
Antibody-antigen complexes within the glomerulus activate complement, stimulate platelet
adhesion and aggregation, signal neutrophil infiltration, and activate the coagulation system.
Complement activation triggers an inflammatory response, including the release of proteolytic
and lysosomal enzymes by neutrophils, followed by fibrin deposition. Aggregated platelets re-
lease thromboxane, which further promotes inflammation.
Feline Glomerular Diseases 211
6. What clinicopathological abnormalities are consistent with glomerulonephritis?
The hallmark abnormality of glomerulonephritis is proteinuria. In addition, an inactive urine
sediment is usually present, and both hyaline and granular casts may be observed. Progression of
the disease and response to treatment can be monitored by serial measurement of the urine pro-
tein:creatinine (UPC) ratio. Hypoalbuminemia and hypercholesterolemia may occur if nephrotic
syndrome develops.
7. What is a normal UPC ratio?
A UPC ratio < I is considered by many to be normal. However, some clinicians consider a
UPC > 0.5 significant in cats. A moderately elevated UPC ratio (i.e., > I; < 20) is consistent with
glomerulonephritis.
8. What nonspecific clinical rmdings are consistent with glomerulonephritis?
Nonspecific clinical findings associated with glomerulonephritis include anorexia, vomiting,
weight loss, and lethargy; edema or ascites (rare in cats) secondary to hypoalbuminemia;
azotemia; polyuria and polydipsia secondary to renal failure; hypertension; and hypercoagulabil-
ity. Evidence of nephrotic syndrome (proteinuria, hypoalbuminemia, ascites or edema, and hy-
percholesterolemia) should alert the clinician to the possibility of glomerulonephritis. As
glomerulonephritis is often secondary to another primary disease process, the clinical presenta-
tion may be dominated by the primary disease.
Primary Disease Processes That May Result in Secondary Feline Glomerular Disease
Bacterial pyoderma or chronic skin inflammation
Dental disease (e.g., chronic gingivitis)
Dirofilariasis
Ehrlichial infections
Endocarditis
Feline leukemia virus, feline immunodeficiencyvirus, feline infectious peritonitis,
and associatedconditions (e.g., lymphoma)
Immune-mediateddiseases
Neoplasia
Pancreatitis
Pyometra
Systemic lupus erythematosus
9. Summarize the diagnostic plan for cats with suspected glomerulonephritis.
Complete cell count, serum biochemical panel, urinalysis with protein/creatinine ratio, and
systemic blood pressure are recommended for all cats with glomerulonephritis. Renal ultrasound
may be used to evaluate for morphologic renal diseases. Thoracic and abdominal radiographs
may be used to evaluate for occult infections or neoplasia. Feline leukemia virus serum antigen
test and feline immunodeficiency virus serum antibody test are indicated in most cases. Other
specialized testing, such as serum coronavirus antibody titers, Ehrlichia spp. antibody titers, and
Dirofilaria immitis serum antigen and antibody tests, are indicated in some cats.
10. How is glomerulonephritis diagnosed?
The definitive diagnosis of glomerulonephritis requires histologic examination of renal
biopsy specimens.
11. How can renal tissues be collected? What are the risks?
Because of the availability of ultrasound and the potential for complications, it is no longer
advisable to attempt biopsy of renal tissue "blindly." Ultrasound guidance or direct visualization
212
Feline Glomerular Diseases
with laparoscopy or exploratory laparotomy can be used to obtain samples of renal tissue.
Excessive bleeding from the biopsy site is a potential complication, especially in animals that are
hypertensive. Assessment of platelet count, activated clotting time or other clotting factor assess-
ment, and arterial blood pressure is highly recommended before the procedure is performed.
Laparoscopy offers the advantage of being able to apply direct pressure or Gel-foam to the
biopsy site if persistent bleeding occurs.
12. What necropsy changes are seen with glomerulonephritis?
Any progressive destruction of nephrons results in gross and microscopic changes in the
kidney that appear similar, regardless of the underlying cause. On gross inspection, kidneys are
slightly smaller than normal, firm and pale, with irregular pitting and linear fibrosis.
13. Describe the histologic appearance of glomerulonephritis.
Histologic examination of renal tissue confirms medullary and glomerular deposition of
eosinophilic hyaline material. In hematoxylin- and eosin-stained sections, glomerular capillary
walls are diffusely thickened and intensely eosinophilic. Papillary necrosis, tubular dilatation,
lymphocytic-plasmacytic cellular infiltration, and interstitial fibrosis also are seen. The glomeru-
lar walls are often thickened and eosinophilic. The periodic acid-Schiff stain is used to highlight
small glomerular basement membrane projections consistent with immune complex deposition.
Mesangial matrix and cell proliferation can be observed. Continued necrosis and glomerular at-
rophy lead to end-stage nephron destruction, scarring, fibrosis, and sclerosis.
14. What happens if glomerulonephritis is left untreated?
Without treatment, glomerulonephritis leads to irreversible damage from fibrin deposition and
glomerulosclerosis. The loss of nephron function eventually leads to renal insufficiency and failure.
15. What are the treatment objectives for cats with glomerulonephritis?
The first objective of treatment is to identify and treat any underlying disease (i.e., removal
of the offending antigen). Unfortunately, this goal is often impossible.
16. Are glucocorticoids appropriate for treatment of glomerular disease in cats?
Unless the primary disease process is a glucocorticoid-responsive condition. glucocorticoids
are not recommended for the treatment of glomerular disease. Although cats are considered resis-
tant to most side effects of long-term glucocorticoid use, treated dogs have demonstrated an in-
crease in proteinuria and azotemia as well as loss of body condition. Elevated endogenous or
exogenous glucocorticoid levels also predispose the animal to thromboembolic events. Other im-
munosuppressive drugs used to treat glomerular disease in dogs include azathioprine, chlorambu-
cil, cyclophosphamide, and cyclosporine, but few controlled studies have investigated their
efficacy in dogs. Several of these agents may be too toxic for use in cats (e.g., azathioprine).
17. What other treatments should be considered for glomerular disease in cats?
Thromboxane synthetase inhibitors, angiotensin-converting enzyme (ACE) inhibitors,
prostaglandin analogs, leukotriene antagonists, and dietary omega-3 fatty acid supplements have
been investigated for their ability to reduce glomerular inflammation and associated symptoms
(e.g., proteinuria, hypertension). Antiplatelet therapy with low-dose aspirin is a mainstay of treat-
ment for dogs with glomerular disease, but thromboembolic events secondary to glomerular dis-
ease are rare in cats. If edema or ascites is present, treatment may include a reduced sodium,
protein-restricted diet in addition to an ACE inhibitor. For treatment of significant hypertension
(systolic blood pressure> 170-180 mmHg), the calcium antagonist amlodipine (0.625 mg/cat
once daily) is the drug of choice (see Chapter 63). Blood pressure should be rechecked at 2--4-
week intervals at the start of therapy. The ACE inhibitor enalapril (0.25 rug/kg once daily) or a
beta antagonist such as atenolol (6.25 mg/cat once daily) may be added if monotherapy is inef-
fective, but extreme caution and diligent follow-up are required to monitor for progressive
azotemia and renal failure.
Feline Glomerular Diseases 213
18. Define renal amyloidosis.
Amyloidosis is the deposition of fibrillar proteins in various tissues. These proteins assume a
beta-pleated sheet configuration, which makes them insoluble and resistant to proteolysis.
Amyloid impairs the function of the organ in which it is deposited. Renal amyloidoisis is usually
secondary (reactive) to some infectious, inflammatory, or neoplastic disease process.
19. How does renal amyloidosis differ in cats and dogs?
Renal amyloidosis in cats is rare. Feline amyloidosis usually affects the medulla of the
kidney. whereas in dogs renal amyloidosis is usually a glomerular disease. Amyloid deposit in
the feline kidney results in medullary fibrosis and papillary necrosis. Unlike dogs, severe protein-
uria is uncommon in cats because amyloid deposition is interstitial (sparing the glomeruli).
20. In what breed of cat does renal amyloidosis have a genetic basis?
Renal amyloidosis has been diagnosed in a number of related Abyssinian cats. The cats
had marked medullary interstitial and glomerular amyloid deposition, interstitial fibrosis, and
papillary necrosis. Siamese and Oriental shorthair breeds also have an increased incidence of
amyloidosis.
21. What clinical and clinicopathologic abnormalities are associated with renal amyloidosis?
Cats are usually quite sick and often uremic, with nonregenerative anemia, hyperphos-
phatemia, metabolic acidosis, isosthenuria, and proteinuria. Concurrent amyloid deposits in the
liver of Siamese and Oriental shorthair breeds may lead to hepatic rupture and severe, acute hem-
orrhage.
22. Describe the typical progression of renal amyloidosis.
Amyloid deposits interfere with the blood supply (vasa recta) to the renal medulla, resulting
in papillary necrosis. The progressive loss of nephrons leads to renal failure and uremia. Feline
amyloidosis carries a grave prognosis. Both dimethylsulfoxide (DMSO) and colchincine have
been used to treat canine amyloidosis, but the results are equivocal, and similar studies have not
been performed in feline amyloidosis. Both drugs may result in significant gastrointestinal side
effects, and neither drug is likely to be of benefit once renal failure is established.
BIBLIOGRAPHY
I. Arthur JE, Lucke VM, Newby TJ, et al: The long-term prognosis of feline idiopathic membranous
glomerulonephropathy. 1AmAnimal HospAssoc 22:731-737, 1986.
2. B1unden AS, Smith KC: Generalizedamyloidosisand acute liver hemorrhagein four cats. 1 Small Anim
Pract 33:566-570, 1992.
3. Boyce 1T, OiBartola SP, Chew 01, et al: Familial renal amyloidosis in Abyssinian cats. Vet Pathol
21:33-38, 1984.
4. Center SA, Smith CA, WilkinsonE, et al: Clinicopathologic,renal immunofluorescent, and light micro-
scopic features of glomerulonephritis in the dog: 41 cases. 1AmVetMed Assoc 190:81-90, 1987.
5. Chew 01, OiBartola SP, Boyce 1T, et al: Renal amyloidosis in related Abyssinian cats. 1 Am Vet Med
Assoc 181:139-142, 1982.
6. Glick AO, Hom RG, Holscher M: Characterizationof feline glomerulonephritis associatedwith viral-in-
duced hematopoieticneoplasms.Am 1 Pathol92:321-332, 1978.
7. Grauer GF: CVT update: Canine glomerulonephritis In Bonagura 1 (ed): Kirk's Current Veterinary
Therapy XIII (Small Animal Practice). Philadelphia,W.B.Saunders, 2000, pp 851-853.
8. NashAS, Wright NG, Spencer A1,et al: Membranousnephropathy in the cat: Aclinical and pathological
study. Vet Rec 105:71-77, 1979.
9. Osborne CA, Vernier RL: Glomerulonephritis in the dog and cat: A comparative review. 1 AmAnirn
HospAssoc9:101-124, 1973.
10. Slauson 00, Lewis RM: Comparative pathology of glomerulonephritis in animals. Vet Pathol
16:135-164.1979.
44. POLLAKIURIA: OVERVIEW
AND DIAGNOSTIC PLAN
Michael R. Lappin. D.V.M., Ph.D.
1. Define poUakiuria, stranguria, and dysuria.
PoUakiuria is the passage of small amounts of urine frequently. Stranguria and dysuria are
straining to urinate and difficulty with urination, respectively. These problems indicate inflamma-
tion or obstruction of the bladder or urethra and mayor may not be accompanied by hematuria.
2. What are the major causes of poUakiuria?
Most causes of pollakiuria are local diseases of the bladder or urethra. In most cats, the cause
of the disease is unknown. but uroliths, neoplasia, and infections occur in some (see Chapters
45-49). Extraluminal obstruction and neurologic causes also occur.
PrimaryDifferentialDiagnosesfor Pollakiuria in Cats
Urinary tract disease
Idiopathicor sterile (interstitialcystitis ?)
Urolithiasis
Neoplasia
Bacterial infection
Neurologic disease
Extraluminal obstruction
Viral infection(?)
Fungal infection
Parasiticinfestation
3. Define reflex dysynnergia.
Reflex dyssynergia (or detrusor-urethral dyssynergia) is a syndrome that develops when neu-
rologic conditions result in a failure of coordination between detrusor contractions and urethral
relaxation. It generally occurs with upper motor neuron lesions. In most cats, overt neurologic
disease is noted on physical examination. Other types offunctional urinary obstruction lead to in-
complete emptying and are attributed to neurologic or nonneurologic disorders (see Chapter 49).
4. What signalment findings are commonly associated with causes of pollakiuria?
Lower urinary tract disorders can occur in cats of any age. Ranking of differential diagnoses
varies with the signalment. For example, urate calculi are detected most frequently in young cats
with portosystemic shunts and resultant hepatic insufficiency. Idiopathic cystitis most often starts
in young adult cats. Bacterial urinary tract infections (UTIs) are rare in cats, but queens are more
predisposed than toms because their urethra is shorter and has less muscular tone. Toms with per-
ineal urethrostomy, however, are predisposed to bacterial UTIs compared with normal toms.
Bacterial UTI and neoplasia become more common in older cats.
5. Describe the historical findings commonly associated with causes of pollakiuria.
Owners usually complain of inappropriate urination or excessive time in the litterbox. It can
be difficult for the owner to differentiate stranguria from constipation. Depending on the cause of
pollakiuria, hematuria also may be noted. In cases of total obstruction, vocalization or clinical
signs of uremia (e.g., inappetence, depression, vomiting) also may be present.
6. What physical examination findings are commonly associated with causes of pollakiuria?
Cats with reflex dyssynergia often have decreased proprioception to the limbs, hyperactive
reflexes, ataxia, and a variably distended, taut urinary bladder. Cats with idiopathic cystitis and
2\4
Pollakiuria. Overview and Diagnostic Plan 215
infections commonly have small thickened bladders on palpation. Cats with inflammatory dis-
eases generally urinate when minimal pressure is placed on the bladder. Blood may be noted in
the urine or in the perineal region with some diseases. Occasionally, masses or calculi in the
bladder can be palpated through the body wall. With complete obstruction, the urinary bladder is
palpably distended. Extraluminal obstructive lesions and urethral calculi in the pelvic urethra can
sometimes be detected by rectal palpation. The penis of toms with inflammatory disease or ob-
structive uropathy may be darker red in color than normal or may be inflamed.
7. Describe the initial diagnostic plan for cats with poUakiuria.
Urinalysis should be performed on urine collected by cystocentesis. It may be difficult to
collect urine using this method because most affected cats maintain a small bladder or urinate
immediately on gentle palpation. Mid-stream, free-catch urine or urine collected by catheteriza-
tion may need to be evaluated. Abdominal radiographs also should be performed and evaluated
for radiodense calculi. Because it is not always possible to estimate accurately the duration and
frequency of clinical signs, abdominal radiographs are recommended in all cats with pollakiuria.
8. How does urinalysis aid in ranking of the ditTerential diagnoses?
Hematuria is the most consistent finding with most causes of pollakiuria. Crystalluria may
be detected in cases with calculi. Struvite (alkaline pH) and calcium oxalate (acidic pH) are the
most common crystals (see Chapter 45). Pyuria and bacteriuria are detected in most cats with
bacterial cystourethritis; aerobic infections are most common (see Chapter 48). Aerobic culture
and antimicrobial susceptibility testing are indicated in cats with pyuria or elevated urine pH,
whether or not bacteriuria is noted. Hematuria without significant pyuria or bacteriuria is the
most common finding in cats with idiopathic cystitis (see Chapter 47).
9. What imaging techniques are most beneficial in the evaluation of cats with pollakiuria?
Because most uroliths in cats are radioopaque, abdominal radiographs are a useful screening
technique. Ultrasound is effective for evaluation of cystic diseases, including masses, radiolucent
uroliths, blood, and mineral debris; urine in the bladder serves as contrast. However, contrast ure-
thrography is required to evaluate the urethra adequately.
10. Does endoscopy aid in the work-up of cases with pollakiuria?
Rigid cystoscopes can be used to evaluate the bladder lumen of queens or toms with perineal
urethrostomies. Small flexible cystoscopes are available for use in other toms. Calculi, neoplasia,
urachal remnants, ureteral orifices, and glomerulations consistent with interstitial cystitis can be
visualized. In addition, the urethral lumen can be visualized. Unfortunately, most cats are too
small for use of cystoscopes with biopsy sleeves.
BIBLIOGRAPHY
I. Grauer GF: Clinical manifestations of urinary tract disorders. In Nelson RW, Couto GC (eds): Small
Animal Internal Medicine, 2nd ed. SI. Louis, Mosby, 1998, pp 572-588.
2. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part I: Clinical man-
ifestations. Comp Cont Educ Pract Vet 21: 15-26, 1999.
3. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part 2: Potential
causes. Comp Cont Educ Pract Vet 21:148-154, 1999.
4. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part 3: Diagnosis.
5. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part 4: Therapeutic
options. Comp Cont Educ Pract Vet 21:15-26, 1999.
45. URINARY CALCULI
Cynthia L. Bowlin, D.V.M.
1. What urinary calculi occur in cats?
Struvite (magnesium ammonium phosphate) urinary crystals, microcalculi, or uroliths are
found in approximately 35% of affected cats. In contrast, 20 years ago approximately 80-90% of
urinary calculi in cats were struvite. Calcium oxalate calculi are becoming increasingly common
in cats and now account for more than 50% of calculi. Urate, calcium phosphate, silica, and cys-
tine calculi also have been identified in cats but with much less frequency. Decreased water
intake resulting in concentrated urine influences the saturation level of mineral components and
promotes crystal and calculi formation. Thus, dry kibble diets may be associated with an in-
creased incidence of calculi. Why some cats form calculi when others do not, even when the
same diet and feeding practices are used, has yet to be determined.
2. What clinical signs suggest urinary calculi in cats?
Cystic calculi cause inflammation of the bladder and possibly the urethra. Inflammation may
result in pollakiuria (increased frequency of urination), hematuria (blood in the urine), dysuria (diffi-
cult urination) and stranguria (straining to urinate). The other primary differential diagnoses are idio-
pathic cystitis and neoplasia; lower urinary tract inflammation is rarely caused by a primary bacterial
infection in cats (see Chapter 44). With urate uroliths, clinical findings consistent with hepatic insuf-
ficiency may be present (see Chapter 35). If calcium oxalate uroliths are due to hypercalcemia, clini-
cal signs of the primary disease may occur (see Chapter 57). Nepholiths are often subclinical unless
concurrent lower urinary tract disease or obstructive uropathy resulting in azotemia is also present.
3. What factors influence formation of struvite calculi in cats?
Struvite calculi are detected most frequently in younger cats. Struvite calculi form primarily in
the bladder, most often in neutral-to-alkaline urine (pH> 6.5), when the mineral components reach
a saturation level that allows crystallization. Diets that provide adequate mineral components such
as magnesium and phosphorous may influence struvite calculi formation. The decrease in the inci-
dence of struvite calculi in the past two decades is attributed at least partially to the change in min-
eral composition and acidification of feline diets. In addition to the moisture content and
alkalinizing potential of the diet, other dietary risk factors associated with struvite calculi formation
include low-fat dry diets, high magnesium levels, and high phosphorous levels (see Chapter 50).
4. What factors influence formation of calcium oxalate calculi in cats?
Calcium oxalate calculi are seen most commonly in middle-aged to older cats. Acidifying
diets and acidic urine may enhance formation of calcium oxalate calculi; an increased incidence
has been noted since feline diets formulated to promote urine acidity have been widely fed.
Calcium oxalate nephroliths are more common than struvite nephroliths and usually do not cause
clinical signs until they pass or form in a ureter or the bladder. Other than moisture content and
acidifying potential of the diet, dietary risk factors associated with calcium oxalate urolith forma-
tion in cats are feeding ad libitum, excessive vitamin D and C content, excessive calcium restric-
tion, and low fiber levels in dry food. Epidemiologic studies have shown that overweight, 4-8-
year-old, indoor cats of the Himalayan and Persian breeds that eat dry diets are most likely to
have calcium oxalate urolithiasis.
5. What physical examination findings suggest urinary calculi?
Any cat with signs of lower urinary tract inflammation should be evaluated for calculi. Cats
with cystic calculi may have palpably thickened bladder walls due to chronic irritation, but this
216
Urinary Calculi 217
finding also occurs with other urinary tract diseases. If multiple, large calculi are present in the
bladder, they may be palpated through the abdominal and bladder walls. If a large urinary bladder
is present but difficult to express, cystic or urethral calculi are high on the differential list.
Changes in renal size are variable, but the affected kidney is usually enlarged when obstruction is
due to nephroliths. Discomfort on palpation of the bladder or kidneys is detected in some cats
with urinary calculi.
6. Describe the initial diagnostic plan for documentation of urinary calculi.
Cats with clinical signs consistent with urinary tract disease should be assessed with urinaly-
sis and abdominal radiographs (see Chapter 44). A urine sample should be obtained and exam-
ined immediately to ensure an accurate assessment of crystalluria. Crystal formation can readily
occur in vitro (outside the cat) because of cooling or delayed analysis of the urine. In vivo crys-
talluria mayor may not be clinically significant, but it does indicate oversaturation of minerals in
the urine and suggests an increased risk for stone formation. If calcium oxalate or urate calculi
are suspected, a serum biochemical panel should be performed to assess for hypercalcemia and
hepatic disease, respectively.
7. How does imaging aid in the diagnosis of urinary calculi?
The most common urinary calculi of cats are radioopaque and readily seen on survey radi-
ographs. However, small and radiolucent calculi (urate and cysteine) may be overlooked. Double-
contrast cystography or ultrasonography should be performed if calculi or neoplasia are suspected
but not documented by survey radiographs. Ultrasonographic evaluation of the lower urinary tract
can be inaccurate if there is no urine in the bladder to act as contrast (a common occurrence in cats
with pollakiuria). Contrast radiography has the advantage of screening the entire lower urinary
tract and can be more accurate than ultrasound for quantifying the total number and location of
calculi-particularly if calculi are located in the urethra, which is poorly imaged with ultrasound.
Nuclear scintigraphy can be used to assess degree of obstruction associated with ureteroliths and
nephroliths as well as function of the contralateral kidney if surgical removal is contemplated.
8. What are the treatment options for cystic calculi?
Treatment options for cystic calculi include medical dissolution (some calculi), voiding uro-
hydropropulsion, and surgical removal via cystotomy. Treatment options for nephrolithiasis in-
clude medical dissolution (some calculi) and surgical removal by pyelotomy, nephrotomy, or
nephrectomy.
9. Which calculi can be dissolved medically?
If struvite calculi are suspected, medical management can be considered. A specially formu-
lated diet (Prescription Diet Feline SID; Hills Pet Nutrition, Inc., Topeka, KS) has been shown to
dissolve struvite calculi in the bladder after 1-3 months (see Chapter 50). If dissolution has not
occurred after 3 months, other forms of management should be instituted. The advantages of this
method are avoidance of a surgical procedure and easy administration if the cat will accept the
new diet. The disadvantage of this method is that the cat often continues to be painful, dysuric,
and pollakiuric until dissolution is complete. House soiling outside the litterbox can continue to
be a problem for the owner. Because most nephroliths are calcium oxalate, medical dissolution is
ineffective.
10. How is urohydropropulsion performed?
Lower urinary calculi of any type small enough to pass through the female urethra may be re-
moved by urohydropropulsion. Voidingurohydropropulsion involves catheterizing an anesthetized
or sedated cat, distending the bladder with saline, and then (while holding the cat in an upright po-
sition) applying manual pressure to the urinary bladder to "force" the fluid and, hopefully, the ac-
companying stones out through the urethra. Multiple catheterizations and expulsions may be
necessary to remove the stones. If this method is successful, surgical intervention is avoided.
218 Urinary Calculi
11. When is cystotomy indicated?
If medical management is not indicated or unsuccessful and if calculi are too large for uro-
hydropropulsion, cystic calculi should be removed surgically. About 20-80% of surgeons leave
one or more calculi in the bladder during surgical removal. Thus, postoperative radiographs are
always indicated. Nephroliths may move into the bladder at any time; if they are present, the
owner should be advised that cystic uroliths also may recur from this source. Cystic calculi can
be an incidental finding in cats with no obvious clinical signs of urinary discomfort. Surgical in-
tervention in subclinically affected cats is a decision best left to the clinician and owner, but reg-
ular monitoring for infection or change is indicated. Cystic calculi also may obstruct the urethra.
12. When is surgical management of nephroliths considered?
Pyelolithotomy or nephrotomy is generally performed only in cats with evidence of obstruc-
tive uropathy based on contrast studies, ultrasonic evaluation, or nuclear scintigraphy. Surgical
procedures on the feline renal pelves have a large degree of postsurgical morbidity from urine
leakage and ureteral scarring. Nephrectomy should be performed only if the affected kidney is
considered nonfunctional and function of the contralateral kidney is adequate to control azotemia.
13. Define lithotripsy.
Lithotripsy is the breaking up of stones, usually with shock waves. Shock waves may be gen-
erated at the tip of an instrument placed directly on a stone (intracorporeallithotripsy) or by an
electrohydraulic or electromagnetic source outside the body and transmitted to the stone via a
water interface (extracorporeal shock-wave lithotripsy [ESWL)).
14. Can lithotripsy be nsed to treat uroliths in cats?
Protocols for safely treating nephroliths in cats have not been determined. The feline kidney
appears more sensitive than other species to potentially damaging effects of the shock waves. In
addition, feline upper tract uroliths appear more difficult to fragment with ESWL than canine
uroliths. However, attempts to fragment feline nephroliths and ureteroliths are limited; some types
of ESWL may be effective and safe in cats. The procedure may be best considered for obstructive
ureteroliths. Centers providing lithotripsy can be contacted for specific recommendations.
ESWL is not widely recommended for treatment of bladder stones because mobile stones
can move out of the shock-wave path within the bladder lumen. Treatment may be considered for
larger or multiple bladder stones and for patients that have had multiple surgeries. are poor surgi-
cal candidates, or are being treated concurrently for upper urinary tract stones, Multiple cys-
touroliths have been fragmented using ESWL in at least one cat; the composition of these stones,
unfortunately, was not known.
15. What else can be done to aid in the management of urinary calculi?
Preventing recurrence of calculi is often more difficult than initial diagnosis and treatment. All
calculi should undergo quantitative analysis to determine mineral composition, which aids in insti-
tuting a program to prevent reformation. At removal, bladder tissue and calculi should be submitted
for bacterial culture and sensitivity. Appropriate long-term antibiotic therapy should be adminis-
tered to eliminate infection, if present (see Chapter 48). Treatment of confirmed infection should
continue for 2 weeks after medical dissolution is complete or 4 weeks after surgical removal. For
susceptible cats with a history of urinary calculi formation, urine should be evaluated at least every
3-6 months to look for crystal formation, evaluate urine pH, and monitor urine concentration.
16. Howcan recurrence of urinary calculi be avoided?
Dietary management is the mainstay of preventative therapy (see Chapter 50). Increasing
water intake to reduce urine specific gravity and urine saturation is also important in preventing
calculi reformation. Canned food diets and flavored waters have been advocated for this purpose.
Flavored waters (beef or chicken bouillon cubes, tuna water, or clam juice) should be used as a
supplement and not in place of regular fresh water.
Urinary Calculi 219
17. What specific recommendations may help to prevent struvite calculi?
A diet formulated to be low in magnesium and to create a urine pH around 6.5-6.8 is indi-
cated to prevent recurrence of stuvite calculi. Treating and preventing struvite crystalluria and
calculi formation, however, does not prevent recurrent episodes of idiopathic feline lower urinary
tract disease (see Chapter 45).
18. What specificie recommendations may help to prevent calcium oxylate calculi?
Acidifying diets should be avoided and a more neutral urine pH (6.5-7.5) maintained. If
urine pH remains below 6.5, potassium citrate (50-75 mg orally every 12 hr) can be used to raise
urine pH. If a primary cause of hypercalcemia is identified, it should be corrected if possible (see
Chapter 57).
19. What is the prognosis for cats with urinary calculi?
The prognosis for cats with cystic calculi is good. Because of difficulties associated with
nephric and ureteral surgery in cats, the prognosis for nephroliths and ureteroliths is more
guarded. Unfortunately, except for struvite uroliths, the chance for recurrence of other types of
uroliths remains high despite the best preventive recommendations.
CONTROVERSIES
20. What is the ideal dietary regimen for cats?
We often talk about "acidifying diets" because in the past 15 or 20 year pet food manufactur-
ers have reformulated cat foods to maintain a urine pH at 6.2 --6.5 for most cats. In fact, cats fed
a diet exclusively of rats and mice maintain a urine pH around 6--6.2. A diet of corn, corn gluten,
and meat byproducts creates a urine pH of about 7. By reformulating these foods to reduce urine
pH, the pet food industry has simply corrected a problem that it created. Cats are true carnivores,
but largely we continue to recommend and provide dry cereal grain diets, tweaked and supple-
mented in an attempt to meet the species' unique nutritional requirements. Worse yet, indoor,
well-tended cats have been victims of the professional advise to feed one brand and only one
brand ("Changing foods is bad"). In the author's opinion, probably the worse thing you can do
for a cat, nutritionally or medically, is to feed one diet exclusively for years and years. Offering a
commercially available feline diet, supplemented with various other meats, fish, grain products,
fruits, and vegetables may help to reduce the incidence of urolithiasis and other disorders.
BIBLIOGRAPHY
1. AllenTA: Colloquiumon urology. Fel Pract 25:5-32, 1997.
2. BuffingtonCAT, ChewDL, Kendall MS, et a1: Clinical evaluationof cats with nonobstructive urinary tract
diseases. J AmVetMed Assoc210:46-50, 1997.
3. FossumTW: Surgeryof the kidneyand ureter. In FossumTW (ed): SmallAnimal Surgery. SI. Louis, MO,
Mosby-YearBook, Inc., 1997,pp 461-480.
4. Grauer GF: Feline Lower Urinary Tract Inflammation. In Nelson RW, Couto CG (eds): Small Animal
Internal Medicine, 2nd ed. Mosby,SI. Louis, Mo, 1998, pp 650-657.
5. Lulich JP, Osborne CA: Voiding Urohydroprpulsion: A nonsurgical technique for removal of urocys-
toliths. In BonaguraJD, editor: Current Veterinary TherapyXII, Philadelphia, 1995,WBSaundersCo..
pp 1003-1006.
6. Osborne CA, Kruger JM, Lulich JP, et al: Disorders of the feline lower urinary tract. In Osborne CA,
Fineo DR (eds): Canine and Feline Nephrology and Urology. Philadelphia, Williams and Wilkins,
1995,pp 665-674.
7. Osborne CA, Lulich JP, Thumchai R: Feline Calcium Oxalate Urolithiasis. In Bonagura JD, editor:
Current Veterinary TherapyXll, Philadelphia, 1995, WBSaunders Co., pp 989-992.
8. Polzin OJ, Osborne CA: Dysuria, hematuria, pollakiuria, and urethral obstruction in cats. Proc Waltham
Feline Medicine Symposium,Vernon,California, 1996, pp 29-32.
9. Thumchai R. Lulich JP, Osborne CA, et al: Epizoologic evaluation of urolithiasis in cats: 3498 cases
(1982-1992). J AmVetMed Assoc 208:547-551, 1996.
46. URINARY TRACT NEOPLASIA
Tammy Anderson, DYM.
1. Howcommon are urinary tract neoplasms in cats?
Urinary tract neoplasms are rare in cats. Primary renal tumors reportedly constitute 1.6-2.5%
of all neoplasms in cats. Primary bladder tumors account for> I%of all reported neoplasms in cats.
2. Describe the biologic behavior of urinary tract neoplasms in cats.
Most urinary tract neoplasms in cats are malignant. Renal tumors most commonly metasta-
size to the lungs, liver, brain, and bone. Bladder tumors most commonly metastasize to the lungs,
regional lymph nodes, kidney, and liver. The disease is often advanced at the time of diagnosis.
3. What clinical signs and physical examination findings are associated with upper uri-
nary tract neoplasia?
Clinical signs often are nonspecific and include anorexia, weight loss, and lethargy.
Abdominal distention may be present. Abdominal palpation may detect a mass or enlarged kid-
neys or elicit pain.
4. What laboratory findings are associated with upper urinary tract neoplasia?
Hematuria, proteinuria, and pyuria unassociated with lower urinary tract signs may be pre-
sent. Anemia of chronic disease may be detected on complete blood count. Renal failure mayor
may not be evident. Lymphosarcoma, which often affects both kidneys, is the tumor type most
likely to cause renal failure. Paraneoplastic syndromes are rare in cats, but polycythemia sec-
ondary to increased erythropoeitin production by a renal tumor has been reported. Hypertrophic
osteopathy also has been reported in a cat with a renal papillary adenoma.
5. Describe the signalment of cats with renal neoplasia.
The mean age of cats with renal neoplasia exclusive of lymphosarcoma is 9 years. Males are
slightly more likely to be affected. Cats with renal lymphosarcoma tend to be younger (median
age =6 years), and 50% of affected cats test positive for feline leukemia virus (FeLV).
6. What are the most common upper urinary tract neoplasms in cats?
Most renal tumors are primary and malignant. Lymphosarcoma is the most common upper
urinary tract tumor in cats and often represents an extension of alimentary lymphosarcoma.
Adenocarcinomas. adenomas, nephroblastomas, and other tumor types are less commonly re-
poned. Primary ureteral tumors have not been reported in cats.
7. What other disorders should be considered in the differential diagnoses?
The differential diagnoses are based on clinical signs. physical examination findings, and lab-
oratory results. Palpation of a mass may indicate neoplasia of other abdominal organs. Hematuria
may be due to lower urinary tract disease, trauma, or coagulopathy. Pyuria and proteinuria may be
due to lower urinary tract disease. Proteinuria also may be caused by a protein-losing nephropathy.
Abdominal distention and pain may be due to ascites, peritonitis, or organomegaly. Enlarged kid-
neys may be secondary to ureteral obstruction, pyelonephritis, or renal pseudocysts,
8. What ancillary tests are recommended in cats with renal neoplasia?
Complete blood count, serum biochemistry panel, urinalysis, serum FeLV antigen test. and
serum feline immunodeficiency virus (FIV) antibody test are recommended to determine the
general health of the cat and aid in prognosis. Because most tumors are malignant, thoracic and
220
Urinary Tract Neoplasia 221
abdominal radiographs and abdominal ultrasound are indicated to detect metastatic disease.
Before nephrectomy is performed, function of the contralateral kidney should be evaluated with
an excretory urogram or glomerular filtration rate, as estimated by nuclear scintigraphy.
9. How are tumors of the upper urinary tract diagnosed?
Tumor type may be determined by fine-needle aspiration or biopsy. Fine-needle aspiration is
especially useful in cases of lymphosarcoma because the cells easily exfoliate. Percutaneous
(blind, ultrasound guided, or laparoscopy obtained) or surgical biopsies may be obtained.
Laparoscopy has the benefits of allowing accurate biopsy site selection and hemorrhage control,
if needed. Contraindications to renal biopsy include untreated coagulopathy, acute pyelonephri-
tis, systemic arterial hypertension, and solitary kidney. Platelet count, activated clotting time (or
other factor function test), and systemic arterial blood pressure should be assessed before biopsy.
10. What are the treatment options for upper urinary tract neoplasms in cats?
For tumors other than lymphosarcoma, surgical excision is the treatment of choice in cats
with no evidence of metastatic disease and adequate function of the contralateral kidney. With the
exception of lymphosarcoma, most tumor types respond poorly to chemotherapy. Lymphoma
may be treated with various chemotherapy protocols. In Mooney's study, a protocol that included
vincristine, L-asparaginase, prednisone, cyclophosphamide, methotrexate, and cytosine arabi-
noside, achieved a 61% complete remission rate.
11. Describe the prognosis for upper urinary tract neoplasms in cats.
In Mooney's study, the mean survival time was> 408 days, and the median survival time
was 169 days. Azotemia and stage of lymphosarcoma have not been shown to be accurate predic-
tors of prognosis; however, positive FeLV status affects survival negatively. Central nervous
system signs are detected in 40% of cats dying of renal lymphoma.
12. What clinical signs and physical examination findings are most commonly associated
with neoplasms of the lower urinary tract?
Clinical signs are typical of any lower urinary tract disease and include hematuria, dysuria,
stranguria, and pollakiuria. Physical examination findings may include a palpably thickened
bladder wall or thickened urethra. Painful and enlarged kidneys may be present in cats with
ureteral or urethral obstruction. A mucoid urethral discharge also may be present.
13. What laboratory findings are associated with lower urinary tract disease?
Hematuria, proteinuria, and pyuria are common. Recurrent or unresponsive urinary tract in-
fections also may occur. Azotemia and signs consistent with renal failure may be evident in cats
with bilateral ureteral obstruction.
14. Describe the signalment of cats with bladder tumors.
Cats with bladder tumors tend to be older (average age = 9 years). Males are affected more
often than females.
15. What are the most common lower urinary tract neoplasms in cats?
Most bladder tumors are primary and malignant. Transitional cell carcinoma is the most
common tumor type; squamous cell carcinoma, adenocarcinoma, and others have been reported.
At the time of diagnosis, 30-50% of lower urinary tract neoplasms have metastasized to the sub-
lumbar lymph nodes, pelvic or lumbar vertebrae, or lungs.
16. Howdo bladder tumors differ in cats and dogs?
Bladder tumors in cats often originate in the apex of the bladder or are widespread in the
bladder wall, whereas bladder tumors in dogs often involve the trigone region. This difference
makes bladder tumors more amenable to surgery in cats than in dogs. In general, bladder tumors
are less common in cats than in dogs.
222 Urinary Tract Neoplasia
17. What other disorders should be considered in the differential diagnoses for bladder
disease in cats?
Differential diagnoses include other lower urinary tract diseases such as idiopathic feline
lower urinary tract disease, cystic calculi, and bacterial urinary tract infection (see Chapter 44).
Hematuria may be caused by trauma or coagulopathies.
18. Howare tumors of the lower urinary tract diagnosed?
Mass lesions are documented by ultrasound or double-contrast cystourethrography.
Cytology of urinary sediment or fine-needle aspiration of the tumor may help with diagnosis.
Histopathology may be preferred because neoplastic cells often are difficult to differentiate from
reactive transitional cells on cytologic evaluation. Biopsy samples may be obtained by cys-
toscopy or open surgery. There is a potential risk of tumor cell transplantation during surgery if
the tumor is incised or manipulated with the same instruments that are used to close the surgical
site. Therefore, changing surgical packs before closure is recommended.
Double-contrast cystogram revealing a
mass in the urinary bladder.
19. What ancillary tests are recommended in cats with lower urinary tract neoplasia?
Complete blood count, serum biochemical panel, urinalysis, serum FeLV antigen test, and
serum FIV antibody test should be completed to evaluate the general health of the cat. Abdominal
and thoracic radiographs and abdominal ultrasound are recommended to evaluate for metastasis.
Contrast cystourethrography or ultrasound is useful to evaluate the extent of tumor. An excretory
urogram is indicated if azotemia or renomegaly is present.
20. What are the treatment options for lower urinary tract neoplasms in cats?
Traditional chemotherapy protocols are generally not effective. Carboplatin has been sug-
gested as a chemotherapeutic option in cats, although its efficacy is unknown. Radiation therapy
is not recommended because of its significant side effects, including bladder or colon rupture, in-
continence, and urinary fibrosis. Surgical resection may be considered if no metastasis is present
and the mass does not involve the trigone. If the tumor is at the apex, up to 75-80% of the blad-
der may be removed. Surgical margins of at least 2 em are recommended.
21. Does piroxicam work in cats?
Piroxicam, a nonsteroidal anti-inflammatory drug, has been used anecdotally for transitional
cell carcinomas. Piroxicam should be used only in well-hydrated animals with normal renal func-
tion because it can be nephrotoxic. It is frequently combined with misoprostol because it may
cause gastrointestinal ulceration in dogs and humans. The safety and efficacy of piroxicam in
Idiopathic Lower Urinary Tract Disease 223
cats have not been evaluated. The drug has been administered at 0.3 mglkg orally every 48-72
hours without side effects in some cats.
BIBLIOGRAPHY
I. CrowSE: Urinarytract neoplasmsin dogs and cats. CompContinEduc Pract Vet7:607-618, 1985.
2. KlausnerJS, CaywoodDD: Neoplasmsof the urinarytract. In OsbourneCA, Finco DR(eds): Canineand
Feline Nephrology and Urology. Philadelphia, LippincottWilliams & Wilkins, 1995, pp 903-916.
3. MooneySC, HayesAA, Matus RE, et al: Renal lymphomain cats 28 cases (1977-1984). J AmVet Med
Assoc 191:1473-1477, 1987.
4. MorrisonWB: Cancersof the urinary tract. In MorrisonWB(ed): Cancer in Dogs and Cats: Medical and
Surgical Management. Philadelphia, LippincottWilliams& Wilkins, 1998, pp 569-579.
5. Ogilvie GK, Moore AS: Tumors of the urinary tract. In Ogilvie GK, Moore AS (eds): Managing the
VeterinaryCancer Patient: A Practice Manual. Trenton, NJ, VeterinaryLearning Systems. 1995. pp
403-414.
6. Phillips BS: Bladdertumorsin dogs and cats. CompContin Educ Pract Vet21:540--547, 1999.
7. Schwartz PD, Greene RW. Patnaik AK: Urinary bladder tumors in the cat: A reviewof 27 cases. j Am
AnimHospAssoc21:237-245, 1985.
47. IDIOPATHIC LOWER URINARY
TRACT DISEASE
Tina S. Kalkstein, D.V.M., M.A.
1. What are the signs of feline lower urinary tract disease?
Feline lower urinary tract diseases (LUTDs) manifest clinically with similar symptoms, re-
gardless of cause. Hematuria, pollakiuria, dysuria, inappropriate urination, and/or urethral ob-
struction are the clinical signs associated with LUTD in cats (see Chapter 44).
2. What diseases affect the feline lower urinary tract?
Idiopathic LUTD is the most common cause of hematuria, dysuria, pollakiuria, inappropri-
ate urination, and urethral obstruction in male and female cats. Other common causes of feline
LUTD are urolithiasis and urethral plugs. Uncommon causes ofLUTD in cats include infectious,
iatrogenic, or traumatic disorders. Rarely, anatomic abnormalities (congenital or acquired), neo-
plasia, or neurologic disorders may affect the bladder and/or urethra of cats.
3. Define idiopathic LUTD.
Idiopathic LUTD is a diagnosis reserved for male and female cats with clinical signs of
LUTD for which the specific cause cannot be determined after an appropriate and thorough di-
agnostic evaluation. The exact cause of idiopathic LUTD remains unknown, but various theo-
ries have been suggested, including bacterial and viral infections, autoimmune disease, urinary
toxins, leaky bladder transitional epithelium, stress, neurogenic, and mast cell-mediated in-
flammation. Rather than one single cause, multiple factors probably interact to result in idio-
pathic LUTD.
4. Are crystals a cause of idiopathic LUTD?
Crystalluria naturally occurs in cats in the absence of clinical disease. In one study, the
prevalence of crystalluria was not significantly different in cats with nonobstructive idiopathic
LUTD and unaffected control cats. The signs of idiopathic LUTD also occur commonly in the
absence of crystals on urine sediment exam. Together, these findings suggest that crystals are not
the cause of idiopathic LUTD.
224
Idiopathic Lower Urinary Tract Disease
5. Is idiopathic LUTD of cats synonymous with interstitial cystitis in humans?
Interstitial cystitis refers to an idiopathic LUTD of humans that bears many clinical and di-
agnostic similarities to feline idiopathic LUTD. In addition, both disorders are characterized by
an elusive cause and unknown effective therapy. Because of these similarities, it has been sug-
gested that feline idiopathic LUTD and human interstital cystitis represent the same disease in
different species. However, considering that the lower urinary tract of any species has a limited
ability to react to a number of different diseases, the similarities between feline idiopathic LUTD
and human interstitial cystitis may be coincidental. Future studies of both disorders may reveal
significant differences or similarities between the human and feline diseases. Additional informa-
tion is needed to define more clearly the relationship between the two disorders.
6. Are bacterial infections the cause of idiopathic LUTD?
Results of urine culture for aerobic bacteria and other less common bacterial organisms (e.g.,
anaerobes, mycoplasmas, ureaplasmas, spirochetes) are consistently negative in cats with idio-
pathic LUTD, supporting the conclusion that bacteria are not the cause. Using novel diagnostic
techniques, however, recent research has identified bacteria and bacterial nucleic acid sequences
in some humans with interstitial cystitis. These findings do not define a causative role for bacte-
ria in the etiopathogenesis of human interstitial cystitis but have led to the development of new
hypotheses about the role of bacteria in human interstitial cystitis. The new hypotheses suggest
that in people with interstitial cystitis active infection may occur with atypical. difficult-to-cul-
ture, or nonculturable organisms or that, in the absence of active infection, bacterial products
may stimulate pathology leading to clinically significant disease.
7. Can viruses be the cause of idiopathic LUTD?
In laboratory settings, viral agents can provoke feline LUTD. Recently, calicivirus and virus-
like particles have been identified in the urine and urethral plugs, respectively, of cats with natu-
rally occurring idiopathic LUTD. As with bacterial pathogens, these findings do not define a
causal relationship. Furthermore, little evidence demonstrates that viruses cause naturally occur-
ring feline idiopathic LUTD. Nonetheless, the new information about bacterial and viral
pathogens reinforces the need to continue evaluation and development of more sensitive micro-
bial detection methods. Armed with new information, researchers may be able to define more
clearly the role of uropathogens in development of idiopathic LUTD.
8. Which cats get idiopathic LUTD?
The typical cat with nonobstructive idiopathic LUTD is a young to middle-aged male or
female of any breed; however, any age can be affected. Obstructive idiopathic LUTD (idiopathic
urethral obstruction) occurs primarily in male cats.
9. Describe the usual clinical course of idiopathic LUTD.
Most cats with idiopathic LUTD have acute, nonobstructive signs of a few days' duration.
Fortunately, clinical signs resolve spontaneously within 3-7 days in most cats. Episodes of hema-
turia, dysuria, pollakiuria, and inappropriate urination may recur at unpredictable intervals but
tend to decrease in severity and frequency as the cat ages.
Some cats present with frequently recurring episodes or a more prolonged duration of
nonobstructive symptoms (weeks to months). Signs may eventually subside without therapy and
recur unpredictably. Urethral obstruction may occur in male cats with or without a prior history
of nonobstructive disease.
10. How is idiopathic LUTD diagnosed?
The clinical signs of idiopathic LUTD are identical to symptoms of other feline LUTDs.
Because no diagnostic test is specific for idiopathic LUTD, the syndrome is diagnosed after a
thorough evaluation in which other known causes of feline LUTD have been excluded. The
choice of individual tests depends on several factors:
Idiopathic Lower Urinary Tract Disease
Duration of clinical signs and frequency of recurrence
Abnormalities identified on initial examination or diagnostic tests
Presence of urethral obstruction or concurrent disease
225
11. Which diagnostic tests are recommended for cats presenting for the first time with
acute nonobstructive LUTO?
Thorough history and physical examination. Prior episodes of LUTD should be noted, in-
cluding episodes of urolithiasis or urethral obstruction that may have predisposed the cat to ure-
thral stricture formation from a previously lodged urethral stone or iatrogenic causes (e.g.,
urethral catheter placement).
Survey abdominal radiographs should be obtained to rule out the presence of radiopaque
uroliths and crystalline-matrix urethral plugs. The entire perineum should be included on the lat-
eral radiographic view to evaluate the entire length of the urethra.
Urinalysis should be done to evaluate for chemical and sediment examination.
Cystocentesis should be performed to obtain a urine sample for aerobic culture.
12. Which diagnostic tests are recommended for cats with hematuria but no other signs of
LUTO?
Diagnostic evaluation should include assessment of the upper urinary tract, reproductive
tract, and coagulation cascade.
13. Which diagnostic tests are recommended for cats presenting with prolonged or recur-
rent episodes of LUTD?
In cats with prolonged or frequently recurring LUTD, a more thorough evaluation is indi-
cated. In addition to the tests listed in question 11, diagnostic evaluation should include:
Contrast cystourethrography to rule out radiolucent or small 3 mm) radiopaque uroliths,
anatomic abnormalities, or neoplasia.
Cystoscopy may be pursued if appropriate equipment is available to identify mass lesions,
uroliths, or anatomic abnormalities. In clinical practice, however, high-quality contrast cys-
tourethrography usually is sufficient.
Complete blood count (eBC) and biochemistry profile may be indicated in some cats for
exclusion of systemic illness and before anesthesia for contrast cystourethrography or cys-
toscopy.
14. Is ultrasound useful in the evaluation of cats with LUTO?
Ultrasound is a useful, noninvasive imaging technique to evaluate the urinary bladder and
kidneys in cats. Ultrasound examination of a fully distended urinary bladder may identify radi-
olucent or radiopaque uroliths, mass lesions, echogenic urine sediment, and diffuse or focal mu-
cosal irregularities. Significant limitations of sonographic exam of the lower urinary tract in cats
with LUTD include (1) the need for a fully distended urinary bladder (many cats with pollaki-
uria have a contracted urinary bladder) and (2) the inability to evaluate the entire urethra (ure-
thral lesions may be overlooked if ultrasound is used as an alternative to survey and contrast
radiography).
15. Are cystotomy and biopsy indicated in the diagnostic evaluation of cats with LUTD?
Cystotomy and biopsy are not necessary to establish the diagnosis of idiopathic LUTD or
most other feline LUTDs. Less invasive methods are sufficient.
16. What findings of CRC and serum biochemical profile are consistent with idiopathic
LUTD?
CBC and serum biochemical profile are normal in cats with nonobstructive idiopathic LUTD
in the absence of other illness. Cats with idiopathic urethral obstruction may have biochemical
abnormalities such as postrenal azotemia, metabolic acidosis, and hyperkalemia.
226 Idiopathic Lower Urinary Tract Disease
17. What urinalysis and urine culture fmdings are common in cats with idiopathic LUTD?
Common urinalysis findings include well-concentrated and acidic urine, hematuria, and usu-
ally the absence of pyuria or bacteriuria. False-positive reactions may occur on the leukocyte pad
of urine dipsticks; microscopic urine sediment exam is imperative to evaluate for white blood cells
in feline urine. In addition, the observation of bacteria in urine sediment is suggestive but not con-
clusive evidence of bacterial urinary tract infection. Bacteria may appear in urine samples via con-
tamination during collection (common with catheter-obtained or voided samples because of
commensal flora of the distal urethra) or storage. In addition, many components of urine sediment,
such as fat droplets and cellular debris, appear morphologically similar to and may be mistaken for
bacteria in unstained urine preparations. Urine cultures are negative in cats with idiopathic LUTD.
18. What imaging abnormalitites may be seen in cats with idiopathic LUTD?
Survey abdominal radiographs are usually normal in cats with idiopathic LUTD.
Double-contrast cystogram and retrograde positive contrast urethrogram may be normal or
may expose bladder wall thickening, mucosal irregularities, vesicoureteral reflux, andJor
vesicourachal diverticula.
Cystoscopy may reveal submucosal petechiae and increased vascularity.
19. Is an effective therapy for idiopathic LUTD available?
An effective and safe therapy for idiopathic LUTD has not been identified. However, few
therapies have been the subject of controlled clinical studies. At this time, only symptomatic ther-
apy for idiopathic LUTD is available, and controversy surrounds most, if not all, of the recom-
mended symptomatic therapeutics.
20. What therapies for idiopathic LUTD have been studied?
Controlled studies have been performed to evaluate the efficacy of chloramphenicol, propan-
theline (an antispasmodic), subcutaneous fluid administration, and prednisolone. None of these
therapeutics were effective in reducing the duration or severity of clinical signs in cats with
nonobstructive idiopathic LUTD.
21. In the absence of an effective therapy, how are cats with idiopathic LUTD managed?
Management protocols for cats with idiopathic LUTD should be based on the following:
Thorough diagnostic evaluation to exclude causes of feline LUTD with known effective
and specific therapy
Client education about the self-limiting nature and short duration of symptoms in most cats
and the lack of studies proving the efficacy of recommended therapies
Protocols to minimize risk factors associated with urethral obstruction
Protocols to prevent iatrogenic disease (e.g., urinary catheter complications such as stric-
ture or infection, diet-induced uroliths or metabolic complications, adverse drug reactions)
Consideration of pharmacologic management of persistent or recurrent clinical signs
22. Is stress reduction helpful for cats with idiopathic LUTD?
Stressful events such as extreme weather conditions, residential moves, diet change, and major
holidays have been associated with recurrent episodes ofLUTD in cats. Although it is unlikely that
stress is a primary cause of idiopathic LUTD in cats, its etiopathogenic role is unclear. Stress-in-
duced immune, endocrine, and inflammatory responses may induce or aggravate signs of idiopathic
LUTD, regardless of the underlying cause. Potential stressful aspects of the eat's home environment
should be identified and eliminated or at least minimized. Possible feline stressors may include
changes or disruptions in the home population (people or other animals), diet, or feeding schedule;
changes in litter type, location, or cleanliness; and lack of toys and hiding places.
23. Is amitriptyline helpful for cats with idiopathic LUTD?
Amitriptyline has been recommended for the symptomatic relief of cats with acute and
chronic forms of idiopathic LUTD. Amitriptyline is a tricyclic antidepressant and anxiolytic drug
with other potentially beneficial properties, including anticholinergic, antihistaminic, anti-alpha
adrenergic. anti-inflammatory, and analgesic effects. The exact mechanism of action is unknown
but may be related to the relief of neurogenic and mast cell-mediated inflammation. Ongoing
studies are evaluating the safety and therapeutic value of amitriptyline in managing cats with id-
iopathic LUTD.
24. How should amitriptyline be used?
Dose, frequency, and duration of amitriptyline therapy are empirical. Dose recommenda-
tions range from 2.5-12.5 mg/cat orally every 24 hours at bedtime. The goal is to produce a mild
calming effect. Adverse reactions may include urine retention, blood dyscrasias, and liver
enzyme elevations. If amitriptyline is chosen for use in the symptomatic management of cats
with idiopathic LUTD, caution should be exercised. Clients should be educated about its empiri-
cal use, and routine monitoring should include CBC and liver enzyme evaluation before com-
mencing therapy as well as regularly during therapy (monthly at first. then every 3-6 months).
25. Are glycosaminoglycans helpful for cats with idiopathic LUTD?
The transitional epithelium of the urinary tract is lined by a layer of glycosaminoglycans
(GAGs) that function to prevent microbial and crystal adherence to the bladder epithelium and
minimize the movement of urine solutes and proteins through the bladder epithelium. One hy-
pothesis in the pathogenesis of idiopathic LUTD suggests that cats with a deficient or defective
GAG layer develop increased bladder wall permeability. Chronic exposure of the bladder epithe-
lium to urine constituents may result in sensory nerve stimulation, mast cell activation, and/or in-
duction of immune-mediated or neurogenic inflammation. Research has shown that some cats
with idiopathic LUTD have increased bladder permeability, but it is not known whether this find-
ing is a cause or an effect of idiopathic LUTD.
26. Which GAG has been used in cats?
Pentosan polysulfate sodiumis a semisynthetic, low-molecular-weight heparin GAG analog used
with some success in the management of human interstitial cystitis and recently considered for use in
cats with idiopathic LUTD. The empirical dose of pentosan polysulfatefor use in cats with idiopathic
LUTD is 2-10 mg/kg orally every 12hours. Adverse effects reported in humans include bleeding dis-
orders, alopecia, abdominal pain, diarrhea, and nausea. The safety and efficacy of pentosan polysul-
fate or other GAG replacement therapy in feline idiopathic LUTD has not been reported.
27. Are antimicrobial agents helpful for cats with idiopathic LUTD?
Antibiotics are not recommended for the following reasons:
1. Bacterial urinary tract infections are rare (1-3%) in young to middle-aged cats with LUTD.
2. Urine cultures are negative in cats with idiopathic LUTD.
3. Antibacterial drugs are not beneficial to abacteriuric cats with LUTD.
4. Bacterial resistance may be induced by the arbitrary use of antibiotics
28. Are acidifying diets recommended for cats with idiopathic LUTD?
Acidifying diets are designed to minimize or prevent struvite crystals, struvite uroliths, or
struvite crystalline matrix urethral plugs (see Chapter 50). Because crystals are not believed to be
a cause of idiopathic LUTD and most cats with idiopathic LUTD have acidic urine without sig-
nificant crystalluria. acidifying diets do not appear to offer a therapeutic advantage for most cats.
However, some male cats with heavy crystalluria may benefit from dietary therapy designed to
minimize crystalluria, crystalline matrix plug formation, and potential urethral obstruction.
29. How should an appropriate diet be selected?
Urine sediment and chemical examination should be used as a guide for the choice of an ap-
propriate diet because not all male cats with idiopathic LUTD will benefit from an acidifying diet.
For example, cats with acidic urine and heavy calcium oxalate crystalluria may develop calcium
oxalate uroliths or calcium oxalate crystalline urethral plugs. An acceptable urine pH and sediment
228 Idiopathic Lower Urinary Tract Disease
composition should be defined, and follow-up urinalysis should be performed after a few weeks of
consuming the new diet to evaluate the desired effect. Urinalyses should be evaluated at regular in-
tervals to ensure maintenance of the desired effect or early recognition of adverse effects.
Acidifying diets are contraindicated in immature cats and in the presence of disorders that may
predispose cats to metabolic acidosis, such as renal or postrenal azotemia. New diets should be in-
troduced gradually and should be fed for long periods to minimize stress related to diet change.
30. Are glucocorticoids useful in the symptomatic management of idiopathic LUTD?
Mononuclear inflammation is a common histopathologic finding in the urinary bladder of cats
with idiopathic LUTD. The cause of the inflammation is unknown. Anti-inflammatory dosages of
glucocorticoids have been used in attempts to decrease symptoms attributed to inflammation, such as
hematuria and dysuria. A small (n := 12), double-blind, placebo controlled, pilot study of untreated
cats with idiopathic LUTD has shown that prednisolone therapy at an anti-inflammatory dose (I
mglkg orally every 12 hours for IOdays) did not minimize clinical signs compared with placebo. In
cats treated with either prednisolone or placebo, clinical symptoms and urinalysis findings of hema-
turia and dysuria subsided within 2-5 days. Because glucocorticoids do not appear to produce a clin-
ically favorable effect and are associated with clinically significant adverse effects, they are not
recommended for use in cats with either obstructive or nonobstructive idiopathic LUTD.
31. How is obstructive idiopathic LUTD managed?
Cats with obstructive idiopathic LUTD should be managed like cats with any other cause of
urinary obstruction. Urethral catheterization is necessary to relieve the obstruction in most cases.
The priorities of management are to determine the presence and extent of metabolic derangements
(e.g., postrenal azotemia, metabolic acidosis, hyperkalemia), to address these complications, and
to relieve urethral obstruction. Intravenous access should be obtained as soon as possible to ad-
minister fluid therapy, other medications, and injectable anesthetic agents, if needed. The lower
urinary tract should be evaluated radiographically before catheterization and flushing, if possible.
32. Is sedation or general anesthesia necessary in cats with urinary obstruction?
Sedation or general anesthesia is necessary in most male and female cats with urinary ob-
struction. However, severely depressed cats with postrenal azotemia may allow urethral manipu-
lations with manual restraint, possibly including a small amount of topical anesthetic solution.
Urinary obstruction is occasionally due to a distal penile urethral plug. In these cases, penile
massage may facilitate expulsion of the plug and negate the need for sedation and catheterization
altogether. This simple technique should be attempted in all obstructed male cats. In noncompli-
ant cats, the risk of sedation or general anesthesia may be acceptable considering that iatrogenic
trauma to or infection of the urinary tract may be an even greater risk.
33. Which sedative or anesthetic agents should be used?
Agents that do not undergo renal metabolism, such as short-acting barbiturates, diazepam,
midazolam, propofol, or inhalation agents, are common choices. Combinations of ketarnine and
diazepam or midazolam also have been used. Because ketarnine is metabolized and eliminated
via the kidneys, however, intubation and maintenance with inhaled anesthestics should be
strongly considered instead of additional doses if the initial dose of ketamine is unsuccessful. In
uncooperative patients that are not good anesthetic risks at the time of presentation, careful de-
compressive cystocentesis can be performed to "buy time" for stabilization before anesthesia.
34. What types of catheters should be used?
The urethral lumen of most male and female cats is large enough to fit a 5-French catheter.
Catheters of smaller diameter may be necessary in some cats, but they become kinked or plugged
more easily than larger catheters, especially if they are maintained as an indwelling system.
Polyvinyl chloride (red-rubber) catheters are preferred over polypropylene catheters because (hey
are softer and more pliable and have been found to induce much less uroepithelial injury.
35. Describe the technique for catheter insertion.
Aseptic and nontraumatic technique with sterile aqueous lubricant should be used during all
attempts to pass a urethral catheter. If the obstruction is within the distal urethra, short catheters
such as a l-inch, 22-gauge intravenous catheter with the needle removed, may be passed initially.
Once the urethral catheter is advanced to the level of the obstruction, reverse flushing with 0.9%
saline or lactated Ringer's solution is performed to dislodge, soften, or retropulse a urethral plug.
Large volumes (several hundred milliliters) of lavage solutions are sometimes needed to manipu-
late the plug or move a urolith (if a urolith is present, the obstruction is not due to idiopathic dis-
ease). Physiologic solutions such as normal saline or lactated Ringer's solution are preferred over
other solutions because they are isotonic and nonirritating to the mucosal membranes of the uri-
nary tract. After relieving the obstruction, the bladder and urethra should be lavaged to remove cel-
lular, proteinaceous, and/or crystalline debris. If the obstruction cannot be relieved, decompressive
cystocentesis should be performed, and another attempt to pass a urethral catheter should be made
at a later time rather than risk additional trauma to the urethra. Urethral catheterization may be un-
successful in obstructive idiopathic LUTD because of a stubborn and firm urethral plug, urethral
edema or spasm, blood clots. or sloughed mucosal fragments. Concurrent diseases may prevent
easy catheterization. such as urolithiasis or an intraluminal, mural, or extramural mass.
36. What are the most common risks of urethral catheterization? Howare they minimized?
The most common risks of urethral catheterization include iatrogenic trauma to and infec-
tion of the lower urinary tract. Iatrogenic trauma can be prevented or minimized with gentle tech-
nique, pliant catheters, copious amounts of lubricant, and use of sedation or anesthesia in
uncooperative patients. The risk of infection can be minimized with the use of sterile materials
(including sterile gloves, flush, and catheters), nontraumatic technique, minimal use of in-
dwelling catheters, use of sterile, closed collection systems when indwelling catheters are
deemed necessary, and removal of the catheter as soon as possible. The risk of infection increases
with the duration of catheterization.
37. What are the indications for an indwelling catheter?
Not all cats with recent obstruction require an indwelling catheter. Indications for an in-
dwelling urethral catheter after obstruction include a narrowed urethral lumen, persistent debris in
the urinary tract, and detrusor atony. These findings are risk factors for reobstruction during the first
few days after urethral patency is reestablished. Cats with severe postrenal azotemia as a conse-
quence of obstructive idiopathic LUTD also may benefit from an indwelling catheter. Antibiotics
and/or glucocorticoids should not be substituted for aseptic, nontraumatic technique and closed col-
lection systems. Repeat obstruction occurs after catheter removal in some cats due to functional
urethral spasm. See Chapter 49 for a discussion of pharmocologic agents that may be of benefit.
38. When should I consider a perineal urethrostomy?
Because of the increased risk for bacterial urinary tract infections (see Chapter 48). perineal
urethrostomy is no longer routinely performed. However, if urethral scarring has resulted from
multiple episodes of idiopathic LUTD or repeated urethral catheterization, surgery may be indi-
cated. Perineal urethrostomy does not resolve idiopathic LUTD; it only lessens the odds of devel-
oping an obstructive uropathy.
39. What is the prognosis for cats with idiopathic LUTD?
The prognosis for most cats with idiopathic LUTD is good. The disease is usually self-limit-
ing and of short duration. Symptoms may recur at unpredictable intervals but again subside in
about I week without therapy. Only a small population of cats with idiopathic LUTD develop
frequently recurring or persistent symptoms. However, as the cat ages, episodes tend to become
less frequent and severe. Unfortunately, male cats with idiopathic LUTD are at increased risk of
urethral obstruction due to the formation of urethral plugs. Recognition of certain risk factors for
urethral obstruction in some male cats may help to prevent urethral obstruction but will not pre-
vent nonobstructive episodes.
230
Urinary Tract Infections
BIBLIOGRAPHY
I. Buffington, CAT, Chew DJ: CVT update: Idiopathic (interstitial) cystitis in cats. In Bonagura 10 (ed): Kirk's
Current VeterinaryTherapy XIII (Small Animal Practice). Philadelphia, W.B. Saunders, 1999, pp 894-896.
2. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part I: Clinical man-
ifestations. Comp Cont Educ Pract Vet 21: 15-26, 1999.
3. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part 2: Potential
causes. Comp Cont Educ Pract Vet 21:148-154,1999.
4. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part 3: Diagnosis.
Comp Cont Educ Prac Vet 21:387-394, 1999.
5. Kalkstein TK, Kruger JK, Osborne CA: Feline idiopathic lower urinary tract disease. Part 4: Therapeutic
options. Comp Cont Educ Pract Vet 21:497-509,1999.
6. Lees GE: Use and misuse of indwelling urethral catheters. Vet Clin North Am26:499-505, 1996.
7. Osborne CA, Kruger JM,Lulich JP, et al: Prednisolone therapy of idiopathic feline lower urinary tract dis-
ease: A double-blind clinical study. Vet Clin North Am26:563-570, 1996.
48, URINARY TRACT INFECTIONS
Laurie). Blanco, D.V.M.
1. Howcommon are bacterial urinary tract infections in cats?
Bacterial urinary tract infections are uncommon in young cats. In one prospective study of
141 young cats with lower urinary tract disease, the incidence of infections was < 2%. The mean
age of the cats studied was 56.6 months. In one retrospective study, 25% (341 of 1380) of feline
urine cultures submitted in a university hospital had positive bacterial urine cultures. The mean
age of these cats was 8.2 years. In another retrospective study of cats older than 10 years of age
with lower urinary tract disease, urinary tract infections were documented in 36 of 81 cats (45%).
2. Why are urinary tract infections so uncommon in young cats?
Many factors prevent bacterial colonization in the lower urinary tract of cats. One of the most im-
portant defenses is the normal flushing action of micturition. Normal flora that reside in the distal ure-
thra and penis or vagina prevent colonization of pathogenic bacteria. In addition, the bladder mucosa
has a layer of glycosaminoglycan (GAG) that is hypothesized to bind water and form a barrier to pre-
vent contact of bacteria with the mucosa. Urine is also a relatively bacteriostatic medium. High osmo-
lality, low pH, high urea concentration, and organic acids contribute to its bacteriostatic properties.
The high urine osmolality of cats may be the major factor for the low incidence of infections. Finally.
local and systemic immune responses also contribute to the prevention of urinary tract infections.
3. What are predisposing factors for developing an infection?
Any problem that disrupts the natural barriers of the urinary system predisposes cats to infec-
tions. Uroliths can create a nidus for bacterial infection. Cats with perineal urethrostomies are at a
greater risk for introduction of bacteria than cats without perineal urethrostomies. Urinary
catheters also disrupt the normal urethral barriers and introduce bacteria from the distal urethra
and genital area. In a retrospective study of older cats with urinary tract infections, two-thirds of
the cats had concurrent renal failure. and diagnoses in other cats included hyperthyroidism, feline
immunodeficiency infection, feline leukemia virus infection, urinary incontinence, and neoplasia.
4. Howcan urinalysis help in the diagnosis of urinary tract infection?
A significant number of white blood cells in the sediment suggests an infection. Unfortu-
nately, the leukocyte assay on urine dipsticks is highly unreliable for cat urine. Rod-shaped bacte-
ria may be seen in the sediment if there are > 10,000 bacteria/ml. Cocci usually are not seen unless
there are > 100,000 bacteria/ml. The absence of observable bacteria does not rule out an infection.
Alkaline urine may be caused by urease-producing bacteria; however, many factors influence urine
Urinary Tract Infections 231
pH, and a high urine pH is not necessarily indicative of infection. The presence of white blood cell
or bacterial casts indicates renal involvement. Although urinalysis results help to increase the suspi-
cion for infection, urine culture is the gold standard for diagnosis of urinary tract infection.
5. What is considered significant bacteriuria in a urine culture?
Because the urinary bladder is considered sterile, any sample collected via cystocentesis
should be devoid of bacteria unless there is contamination in vitro. Bacterial growth> 1,000
colony-forming units per milliliter (cfu/ml) in a urine sample obtained by cystocentesis or
catheterization is considered significant. Because normal cats can have up to 100,000 cfu/ml on
voided samples, this method of collection is not recommended if an infection is suspected.
6. What are the most common urinary pathogens in cats?
Escherichia spp., Staphylococcus spp., Streptococcus spp., Proteus spp., Klebsiella spp.,
Pseudomonas spp., and Enterobacter spp.
7. While you are waiting for urine culture results, what empiric therapy can be instituted?
Urinalysis with a sediment exam can be helpful for selecting empiric therapy. If the urine is
alkaline, Staphylococcus or Proteus spp. are likely. Nearly 100% of Staphylococcus spp. and
80% of Proteus spp. are susceptible to beta-lactam antibiotics (penicillin, amoxicillin, or amoxi-
cillin/clavulanic acid). If cocci are present in the sediment, one should suspect Staphylococcus
or Streptococcus spp.; both are also susceptible to the beta-lactams. If rods are present, it can be
more difficult to select an effective antibiotic because various rod-shaped bacteria have distinct
susceptibility patterns. Because Escherichia coli is the most common rod-shaped bacteria in uri-
nary tract infections, empirical treatment with a potentiated sulfa or quinolone is appropriate
until susceptibility results are available.
8. What is the appropriate duration of antibiotic therapy?
In an uncomplicated lower urinary tract infection, 10-14 days of treatment is usually suffi-
cient. In most cats, however, urinary tract infections are considered complicated (e.g, asssociated
with a concurrent abnormality of the urinary tract or host defenses). The length of treatment de-
pends on the type of host defense abnormality. If the abnormality can be corrected, the infection
should be treated until the urinary tract has healed. If the abnormality cannot be corrected, treat-
ment should extend 2-3 weeks after clinical signs have resolved. If signs recur soon after discon-
tinuing treatment, the duration may need to be longer or daily preventive therapy may be
necessary. Cats with pyelonephritis should be treated for at least 4-6 weeks (see Chapter 39).
9. Describe the ideal monitoring plan for cats with urinary tract infections.
Urine culture and sensitivity should beobtained via cystocentesis 3-5 days after starting antibi-
otic therapy. If the culture is positive, a different antibiotic should beselected based on susceptibility
results. Another urine culture should beobtained 7-10 days after discontinuing antibiotic therapy. If
this culture is positive, relapse or reinfection has occurred (see Chapter 39). Ifthe posttreatment urine
culture is negative, urinalyses and urine cultures can bemonitored every 3--6months.
BIBLIOGRAPHY
I. Bartges JW, Barsanti JA: Bacterial urinary tract infections in cats. In Bonagura JD (ed): Current Veterinary
Therapy XIII (Small Animal Practice). Philadelphia, W.B. Saunders, 2000, pp 88G-882.
2. Davidson AP, Ling GV, Stephens E, et al: Urinary tract infections in cats: A retrospective study,
1977-1989. Calif Vet 46:32-34,1992.
3. Kruger JM, Osborne CA, Goyal SM, et al: Clinical evaluation of cats with lower urinary tract disease. J
Am Vet MedAssoc 199:211-216, 1996.
4. Lees GE: Epidemiology of naturally occurring feline bacterial urinary tract infections. Vet Clin North Am
14:471-479, 1984.
5. Lees GB, Simpson RB, Green RA: Results of analysis and bacterial cultures of urine specimens obtained
from clinically normal cats by three methods. J Am Vet Med Assoc 184:449-454, 1984.
6. Lees GB, Rogers KS: Treatment of urinary tract infections in dogs and cats. J Am Vet Med Assoc
189:648--652. 1986.
49. FUNCTIONAL URINARY OBSTRUCTION
Julie R. Fischer, D.V.M., and India F. Lane, D.v.M., M.S.
1. Define functional urinary obstruction.
Functional urinary obstruction refers to the inability to urinate because of excessive resis-
tance in the bladder neck or urethra in the absence of an intraluminal or extraluminal anatomic
obstruction. Normal elimination of urine requires coordinated relaxation of the bladder neck and
urethra during detrusor contraction. In functional obstruction, the detrusor may contract, but in-
appropriate urethral or bladder neck contraction prevents effective or complete voiding of urine.
Reflex dyssynergia, detrusor-sphincter dyssynergia, and urethrospasm also have been used to de-
scribe functional urinary obstruction in veterinary medicine.
2. What historical fmdings are common in cats with functional urinary obstruction?
Cats with functional urinary obstruction usually have a history of a predisposing medical
condition, such as recent anatomic urethral obstruction or spinal injury. Idiopathic functional ob-
struction is rare in cats. If the condition is acute, owners may report straining (some think that the
cat is constipated), vocalizing while voiding, and decreased amounts of urine in the litterbox.
They may notice that the eat's abdomen is painful and may report nonspecific signs of illness,
such as decreased food or water intake, lethargy, or hiding behavior. Cats with chronic partial ob-
struction may not be painful and may cease to strain. Overflow incontinence may develop. lead-
ing to a wet perineal area or urine scald. In hospitalized cats, persistent dysuria, stranguria, and
distended urinary bladder are usually observed.
3. Howshould you focus the physical examination if functional urinary obstruction is sus-
pected?
In the course of the physical examination, careful attention should be focused on the size and
turgidity of the urinary bladder, external genitalia, and neurologic status.
4. What questions should be asked about the genitourinary system?
Is the urinary bladder palpably enlarged? Is bladder tone soft or firm?
Does the cat resent urinary bladder palpation?
If the bladder is moderately enlarged, can urine be expressed with gentle, judicious pressure?
Manual expression is somewhat difficult in a conscious, healthy male cat; however, it is pos-
sible to rupture a bladder with manual pressure, especially a diseased one. Be cautious!
Is the abdomen distended (e.g. uroabdomen)?
Is there evidence of self-trauma, swelling, urine scald. or inflammation of the external gen-
italia?
5. What questions should be asked to evaluate neurologic status?
Are the car's mentation and gait normal?
Are hind limb reflexes normal?
Does the cat have any areas of pain on firm palpation of the spinal column?
Is tail carriage normal?
Is perineal sensation intact? You should be able to elicit an anal "wink" with perineal stim-
ulation. and there should be good anal tone when a rectal thermometer is passed.
6. What are common causes of functional urinary obstruction in cats?
Functional urinary obstruction in cats commonly occurs after a physical obstruction (usu-
ally a mucoprotein plug or stone) has been relieved by catheterization. Irritation caused by the
physical obstruction and by the procedures required to remove the obstruction can result in a
232
Functional Urinary Obstruction 233
hypercontractile or "spastic" urethra. Spasm of the urethral musculature can be sufficient to pre-
vent urine flow, despite repeated voiding attempts by the cat. In fact, repeated straining and in-
creased sympathetic tone due to pain and irritation may stimulate further contraction of the
urethra and bladder.
Injury to the spinal cord (most commonly from trauma, tumor, or disk disease) above the
level of the sacral segments can disinhibit urethral sphincter reflexes and lead to continuous
sphincter contraction. Cats with upper motor neuron bladders usually have firm bladders that are
difficult to express manually. Sometimes even a cord lesion in the sacral region can produce
dyssynergic voiding that mimics a suprasacrallesion. Prolonged bladder distention resulting
from a neurologic lesion can lead to detrusor atony, which may further complicate management.
Less common causes of functional urinary obstruction include surgery or trauma of the
caudal abdominal region, perineal region, or urogenital tract.
7. Do cats with functional urinary obstruction have characteristic laboratory abnormalities?
If a cat has had complete urinary obstruction for an extended period, azotemia, hyper-
kalemia. and metabolic acidosis may be detected. Hematuria, pyuria, or bacteriuria may be ob-
served on urinalysis, reflecting bladder wall pathology, inflammation, or infection secondary to
urine retention and urinary bladder distention. Because of these potential sequelae to partial or
complete urinary obstruction, a minimal laboratory database should include complete blood
count, serum biochemical profile with electrolytes, and urinalysis with sediment examination and
culture. Serum feline leukemia antigen testing and feline immunodeficiency virus antibody test-
ing are indicated if spinal cord compression is suspected in cats with no history of trauma; cats
with spinal lymphoma often are infected with a retrovirus.
8. How is functional urinary obstruction diagnosed?
Functional urinary obstruction is characterized by a distended urinary bladder that is difficult
to express and absence of anatomic obstruction. A cat that has just urinated should have minimal
(a few milliliters) urine left in the bladder. The bladder should be small or nondetectable radi-
ographically and on palpation. If the bladder is radiographically or palpably much larger than a
small plum after voluntary urination, urethral catheterization is the next diagnostic and therapeu-
tic step. A well-lubricated, 3.5-French polypropylene, red rubber, or silicone urinary catheter
should pass relatively easily and smoothly through the urethra of a sedated or anesthetized male
cat. Feel for areas of resistance or grittiness as you pass the catheter. Do not forget the curve in
the male feline urethra; pulling the penis straight caudally should facilitate atraumatic catheteri-
zation. Female cats can be catheterized with the use of a tiny speculum or by passing the catheter
along the floor of the vestibule.
9. Discuss the role of imaging modalities.
Survey radiography and abdominal ultrasonography can be helpful in ruling out the presence
of small or mobile stones that are not detected via catheterization. A retrograde cystourethrogram
can show urethral strictures and radiolucent stones. Urodynarnic studies (such as urethral pres-
sure profilometry, cystometrography, or electromyography) are available at selected referral in-
stitutions and are sometimes helpful in documenting detrusor and urethral muscle dysfunction in
confusing cases.
10. What are the other common causes of voiding difficulty after relief of urethral obstruc-
tion?
Reobstruction (anatomic)
Mucoproteinaceous urethral plug material
Mobile urolith
Blood clot
Crystalline material
Detrusor atony
234 Functional Urinary Obstruction
11. How should functional urinary obstruction betreated?
If the cat has a treatable cause of spinal trauma or urethral disease. management of these dis-
orders is the most valuable component of treatment. Cats with spinal injury, postobstructive dis-
orders, or idiopathic functional urinary obstruction may benefit from short- or long-term
medication to provide urethral relaxation. The selective alpha-l antagonists (e.g., prazosin, doxa-
zosin, alfuzosin) have been shown to decrease urethral pressures in anesthetized male cats.
Because of the greater percentage of skeletal muscle in the feline urethra compared with the
canine urethra, skeletal muscle relaxants (diazepam, dantrolene) often are added to the therapeu-
tic regimen. Bladder care and monitoring are important. The bladder should be kept relatively
small (i.e., after micturition or expression it should be smaller than a small plum).
Most urethral relaxant medications are safe for long-term use. The exception is diazepam-
long-term use is not recommended because of the possibility of idiopathic hepatic necrosis. If ef-
fective, the medications can be slowly tapered over a few weeks to determine continued need.
Medications are usually tapered more quickly when urethral obstruction has been cleared.
Agents Used as Urethral Relaxants in Cats
RECOMMENDED POSSIBLE CONTRAINDICATIONS
DRUG MECHANISM DOSAGE ADVERSEEFFECTS ORCOMMENTS
Acepromazine Skeletal muscle Up to 0.1 mglkg IV Hypotension Hypovolemia
relaxation via every 12-24 hr Sedation Cardiac disease
neuroleptic effect (doses as low as Exacerbation Seizure disorder
Smooth muscle 0.02 mg/kg IV of seizure
relaxation via may be effective) disorder
alpha antago- 1.1-2.2 mg/kg PO
nism every 12-24 hr
Dantrolene Skeletal muscle 0.5-2.0 mglkg PO Weakness
relaxation via every 8 hr Hepatotoxicity
direct effects 1.0 mg/kg IV
Diazepam Skeletal muscle 0.2--{).5 mglkg IV Sedation Cardiopulmonary
relaxation via every 8 hr or PRN Paradoxic disease
central effects (doses as low as excitation
(benzodiaze- 0.1 mglkg IV may Idiopathic hepa-
pine) be effective) tic necrosis
2.5-5.0 mg/cat PO (with PO use
every 8 hr or PRN only)
Polyphagia
Phenoxybenzamine Smooth muscle 1.25-7.5 mg/cat PO Hypotension Cardiac disease
relaxation via every 8-12 hr Tachycardia Hypovolemia
nonspecific GI upset Glaucoma
alpha antago- Renal failure
nism Diabetes mellitus
(type II)
Prazosin Smooth muscle 0.25--{).5 mg/cat PO Hypotension Cardiac disease
relaxation via every 12-24 hr Mild sedation Renal failure
alpha-I antag- 0.03 mglkg IV Ptyalism
onism
Alprazolam Centrally acting 0.125--{).25 mg/cat As for diazepam, May be good alter-
anxiolytic ben- PO every 12 hr except idio- native if oral therapy
zodiazepine pathic hepatic is needed
necrosis has
not been docu-
mented
IV =intravenously, PO =orally, PRN =as needed.
Functional Urinary Obstruction 235
12. What are the advantages and disadvantages of using an indwelling urinary catheter in
functionally obstructed cats?
Cats that are functionally obstructed after relief of a mechanical obstruction usually require
replacement of an indwelling urinary catheter for 1-3 days to maintain urine flow and prevent
further urinary bladder damage. Unfortunately, urethral catheterization may contribute to urethral
inflammation and spasm. The following suggestions may reduce the risk of creating or exacer-
bating functional urinary obstruction during indwelling urinary catheterization:
I. Use soft, nonirritating catheters for indwelling placement in the urethra. Less irritating
catheter types include silicone, Teflon, and soft infant feeding-tubes. Polypropylene catheters
(tom-cat catheters) are extremely irritating when left in contact with the bladder or urethral
mucosa. The use of pharmacologic urethral relaxants during and after the period of catheterization
should be considered (see table in preceding question). Diazepam and acepromazine also may
have an anxiolytic effect, which reduces stranguria while the catheter is in place. Acepromazine is
contraindicated in dehydrated or hypotensive patients.
2. Consider the one-time use of a nonsteroidal anti-inflammatory drug (NSAID), such as
ketoprofen, at the time of catheterization or catheter removal. NSAIDs may be contraindicated in
azotemic animals.
3. Ensure patency of the indwelling catheter at all times so that the urinary bladder remains
empty and urine flows freely when the catheter is in place.
13. What is the prognosis for a cat with functional urinary obstruction?
Prognosis for functional urinary obstruction depends on the cause. The vast majority of cats
who have postobstructive dysfunction recover normal urinary function if given adequate time and
supportive care. Rarely do cats require longer than I week of in-hospital management in this sce-
nario. Cats with suprasacral spinal injuries usually recover urinary function as they recover motor
function to the limbs; recovery may be prolonged. Most cats with complete sacrococcygeal ("tail-
pull") lesions never recover normal urinary function and may require lifelong treatment. Initially
such cats usually have an easily expressed,lower motor neuron bladder, but sphincter hypertonic-
ity eventually develops.
BIBLIOGRAPHY
I. Bartges JW, Finco DR, Polzin OJ, et al: Pathophysiology of urethral obstruction. Vet Clin North Am Small
Anirn Pract 26:255-264, 1996.
2. Fletcher TF: Applied anatomy and physiology of the feline lower urinary tract. Vet Clin North Am Small
Anim Pract 26:181-196, 1996.
3. Frenier SL, Know1en GG, Speth RC, et al: Urethral pressure response to alpha-adrenergic agonist and an-
tagonist drugs in anesthetized male cats. Am J Vet Res 53:1161-1165,1992.
4. Marks SL, Straeter-Knowled 1M, Moore M, et al: Effects of acepromazine maleate and phenoxybenza-
mine on urethral pressure profiles of anesthetized, healthy, sexually intact male cats. Am J Vet Res
57:1497-1500,1996.
5. Lane IF: Diagnosis and management of urinary retention. Vet Clin North Am Small Anim Pract 30:25-57,
2000.
6. Lane IF: Disorders of micturition. In Osborne CA, Finco DR (eds): Canine and Feline Nephrology and
Urology, 2nd ed. Baltimore, Williams & Wilkins, 1995, pp 693-717.
7. Osborne CA, Kruger JM, Lulich JP, et al: Feline lower urinary tract diseases. In Ettinger SA, Feldman EC
(eds): Textbook of Veterinary Internal Medicine. Philadelphia, WB. Saunders, 2000, pp 1738-1739.
8. Straeter-Knowlen 1M, Marks SI, Rishniw M, et a1: Urethral pressure response to smooth and skeletal
muscle relaxants in anesthetized, male cats with naturally acquired urethral obstruction. Am J Vet Res
56:919-923, 1995.
50. COMMON DIETARY QUESTIONS
Joseph W. 8artges, 8.S., D.v.M., Ph.D., and India F. Lane, D.v.M., M.S.
1. How is a nutritional plan formulated?
A nutritional plan is formulated using a two-step iterative process:
I. Assessment of the animal (signalment. history, physical examination, laboratory results,
and nutritional factors related to the life stage andlor disease process), diet (current diet), and
feeding method (frequency and amount of meals).
2. Formulating and implementing a feeding plan, including selecting a diet formulated to
meet the nutritional factors identified in the assessment process (the diet that the animal is
currently consuming or a different diet) and providing the diet (meal feeding, free-choice
feeding, tube feeding, or parenteral feeding). Included in the nutritional plan is a reassess-
ment of the implemented feeding plan; changes are made as indicated by the two-step itera-
tive process.
2. What urinary tract diseases may respond to dietary modification?
Most information about dietary considerations of dogs and cats with urinary tract disease is
limited to chronic renal failure and urolithiasis; however, nutritional modification has a role in
management of all diseases, including other urinary tract diseases. Dietary modification may fa-
vorably alter urine composition, thereby aiding in the treatment or prevention of urinary tract dis-
eases (see table on following two pages).
3. What are the key features of dietary modification for specific diseases?
Chronic renal failure: reduced protein, reduced phosphorous, alkalinization, and adequate
potassium.
Protein-losing nephropathy: reduced protein.
Hypertension: reduced sodium.
Struvite calculi: reduced protein, reduced phosphorous, reduced magnesium, acidification,
and induction of diuresis.
Calcium oxalate calculi: reduced protein, reduced sodium, adequate magnesium and phos-
phorous, and alkalinization; or increased fiber
Urate calculi: reduced protein and alkalinization.
Cystine calculi: reduced protein, reduced sodium, and alkalinization.
Idiopathic lower urinary tract disease: reduced protein, reduced phosphorous, reduced
magnesium, acidification, and induction of diuresis.
4. Define chronic renal failure.
Chronic renal failure is defined as irreversible destruction of nephrons with resultant loss of
renal function; the condition is stable on a short-term basis but ultimately progressive (see
Chapter 40). Usually the cause of chronic renal failure is not known; therefore, specific therapy
cannot be implemented to reverse the condition.
5. What are the goals of dietary treatment for chronic renal failure?
Reduced renal function results in excesses or deficiencies related to nutritional status, elec-
trolyte concentrations, acid-base balance, hydration status, retention of waste products, inade-
quate metabolism or excretion of exogenous substances, and neuroendocrine balance. The goal
of treatment is to minimize these excesses and deficiencies. Furthermore, chronic renal failure is
a dynamic process; therefore, routine monitoring and adjustment are necessary. The mnemonic
NEPHRONS is based on these goals:
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Common Dietary Questions
N = Nutrition (adequately provide)
E Electrolytes (maintain normal concentrations)
P pH of blood (normalize)
H Hydration (maintain adequate level)
R Retention of wastes (remove or reduce)
o = Other renal insults (avoid)
N Neuroendocrine parameters (normalize)
S Serial monitoring (essential)
239
6. Describe the caloric requirements of cats with chronic renal failure.
Caloric requirements are presumed to be similar to those of healthy cats; however, energy
intake decreases with decliningrenal function because of anorexia and nausea. In general, calcula-
tion of caloric requirements(maintenanceenergyrequirements[MER]) with either of the following
formulas is adequate:
MER =1.5[(30BW
kg)
+70] or MER =lOO(BWkgo.75)
where BW
kg
= body weight in kilograms. Ideally, however, energy intake should be adjusted in
individual cats to maintain optimal body condition.
7. How can uremic anorexia be minimized?
Several strategies may be attempted to minimize uremic anorexia, the cause of which is mul-
tifactorial. Most cats with chronic renal failure have increased concentrationof gastrin and benefit
from Hrreceptor antagonist therapy (see Chapter 40). Correcting metabolic acidosis, hypo-
kalemia, and potential B-vitamin deficiencyand decreasing retention of metabolic waste products
(urea nitrogen, creatinine, and organic acids) may increase appetite. Maintaining hydration status,
treating anemia, and correcting systemic arterial hypertension are also beneficial. However, drug
administration may result in anorexia in individual cats with chronic renal failure. Use of feeding
tubes may be necessary.
Strategies That May Minimize Uremic Anorexia
I. Correct underlying abnormalities.
Minimize deficitsandexcesses in:
Hydration status
Serumconcentrations of nitrogenous wastes
Serumelectrolyte andmineral concentrations (sodium, potassium, phosphorus, calcium)
Serumhydrogen ion concentration (pH)
Serumconcentrations of hormones (parathyroid hormone, erythropoietin, renin, angiotensin)
Others
2. Enhance palatability of diet.
Whenchangingdiet:
Switchfoodsslowly.
Use food witha texture to whichthecat is accustomed.
Tryflavoring agentssuchas clamjuice, tunajuice, andchicken broth.
Attemptto add waterto dryfoods (thisstrategy usuallydoes not workwithcats).
Tryliquidenteral diets: RenalCare (Pet-Ag), Impact(Sandoz), other humanliquidenteral diets.
Warm moist foodto, but not above, bodytemperature.
The smellof foodis important for cats; keepnasal passages open.
Cats preferhigh-protein foods
3. Modifyfeeding patterns.
Emphasize frequent small meals.
Offer rewards (favorite foods; maintenance foods).
Handfeed.
Avoid adverse associations witheating(medications, injections, others).
Preventfoodaversion. Do not offer dietsfor long-term management of chronic renal failure during
periods of nausea and vomiting
240 Common Dietary Questions
Strategies ThatMay Minimize Uremic Anorexia(Continued)
4. Minimize vomiting.
Correct underlying abnormalities (see suggestions under I).
Use pharmacologic antiemetic agents:
Cimetidine (2.5-5 mg/kg every 8-12 hr IV or PO)
Ranitidine (2.5 mglkg every 12 hr IV; 3.5 mglkg every 12 hr PO)
Metocloprarnide (0.2-0.5 mg/kg every 6-8 hr IV, 1M. or PO; 1-2 rng/kg every 24 hr by continu-
ous IV infusion)
Omeprazole (0.7 mg/kg PO every 24 hr)
Chlorpromazine (0.25-{).5mg/kg 1M, SQ, or PO every 6-8 hr)
Prochlorperazine (0.1-{).5mglkg 1M or SQ every 6-8 hr)
Use gastrointestinal coating agents and protectants:
Antacids
Sucralfate (0.25-1 gmlkg PO every 8-12 hr)
Bismuth subsalicylate (2 mlIkg PO every 6-8 hr)
Kaolin-Pectin (1-2 mlIkg PO every 4-6 hr)
5. Implement pharmacologic appetite stimulation:
Diazepam (1-2 mg/cat PO, as needed, or 0.05-{).1 rug/kg IV, as needed)
Oxazepam (0.3-{).4mg/kg PO or 2-2.5 mg/cat PO, as needed)
F1urazepam (0.1-{).5mg/kg PO, as needed)
Cyproheptadine (2 mg/cat PO every 8-12 hr)
Androgens
6. Useenteral feeding:
Hand feeding
Nasoesophageal, esophageal, and/or gastrostomy feeding tubes.
IV=intravenously. PO =orally, SQ =subcutaneously, 1M=intramuscularly.
Modified from Lulich JP, Osborne CA, O'Brien TD, Polzin DJ. Feline renal failure: Questions, answers,
questions. Compen Contin Educ Pract Vet 14:127-153, 1992.
8. Is alteration of dietary lipid content or type beneficial in cats with chronic renal failure?
Studies in dogs with experimentally induced chronic renal failure have shown that a diet
with 15% fat (dry matter basis) containing menhaden fish oil (high in omega-3 fatty acids) was
associated with greater glomerular filtration rate and longer survival times compared with diets
containing similar amounts of beef tallow or safflower oil. Similar benefits, however, have not
been documented in cats.
9. Why does hypokalemia occur in cats with chronic renal failure?
Hypokalemia has been reported in approximately 20% of cats with naturally occurring
chronic renal failure. Decreased dietary intake of potassium, increased urinary losses due to
polyuria, increased fecal losses, and consumption of high-protein, low-potassium, acidifying
diets may contribute to hypokalemia. Hypokalemia may result in metabolic acidosis, worsening
renal failure, anorexia, and muscle weakness.
10. How is hypokalemia treated?
A dietary intake of 0.18 gm ofpotassium/JOO kcal of metabolizable energy (ME) or 0.9% of
the diet (dry matter basis) is recommended to maintain serum potassium concentration above 4
mEqlL. If diet alone does not maintain the desired serum concentration, supplementation with
potassium gluconate should be instituted (see Chapter 40).
11. Is dietary sodium restriction beneficial in cats with chronic renal failure?
Sodium is important in fluid balance and blood pressure regulation. Although serum sodium
concentrations are not usually abnormal in cats with chronic renal failure, dietary sodium restric-
tion is important for maintaining normal extracellular fluid volume and systemic arterial blood
pressure. Concomitant dietary chloride restriction also is important. Chloride may act as a direct
Common Dietary Questions 241
renal vasoconstrictor, and tubular chloride also stimulates release of renin by the juxtaglomerular
cells. Renin increases renal sodium retention and stimulates angiotensin II production, promoting
expansion of extracellular volume and increased systemic arterial blood pressure.
12. What are the recommended daily intakes for sodium and chloride'?
Recommended daily sodium intake for cats with chronic renal failure is 10-40 mg/BWkg or
0.2-0.35% of the diet (dry matter basis). Appropriate dietary chloride requirements of cats with
chronic renal failure are not known; however, a chloride level at least 1.5 times the sodium con-
tent is recommended. Because of obligatory renal sodium excretion in some animals, adaptation
to a lower sodium- and chloride-containing diet should be gradual.
13. What is the most common acid-base abnormality in cats with chronic renal failure?
Metabolic acidosis occurs in at least 80% of cats with chronic renal failure. Acidosis results
from dietary as well as nondietary factors. Dietary acid is derived from sulfur-containing amino
acids; organic acids produced during intermediary metabolism from partial oxidation of carbohy-
drates, fats, protein, and nucleic acids; phosphoric acid used as a palatability enhancer; and min-
eral salts. In general, protein metabolism is the major source of hydrogen ions and thus acidosis.
Metabolic acidosis may result in anorexia, weakness, increased muscle catabolism, hypokalemia,
worsening of renal failure, and stimulation of parathyroid hormone production.
14. Howis metabolic acidosis treated?
Potassium citrate is often included in diets formulated for management of renal failure as an al-
kalinizing agent as well as a source of potassium. The therapeutic goal is to maintain a serum total
carbon dioxide concentration (or serum bicarbonate concentration) between 17 and 22 mEqlL. If diet
alone does not achieve this goal, additional alkalinization using sodium bicarbonate or potassium cit-
rate supplementation may be required (see Chapter 40). Potassium citrate may bea better choice in
cats with chronic renal failure because the added potassium intake helps to offset hypokalemia. and
the additional sodium load associated with sodium bicarbonate administration is avoided.
15. Describe the fluidrequirements in cats with chronic renal failure.
Water balance occurs when the sum of water intake and metabolic water produced equals
output. Water intake is composed of drinking water, water contained in food, and water formed
during metabolism. The kidneys represent the major system involved in water output regula-
tion. Renal failure is associated with polyuria, and the maximal urine osmolality approaches
that of plasma (300 mOsmlkg or a specific gravity of 1.007-1.014). Dehydration and hypov-
olemia may result in worsening of renal failure; therefore, both should be prevented. Feeding a
canned formulated diet provides water (most canned diets contain approximately 75% water
compared with dry formulated diets, which contain approximately 10% water). If cats will not
eat canned formulated diets, adding water to dry food may increase water intake (although cats
are often resistant to this maneuver). Many cats require supplemental water in the form of sub-
cutaneously administered fluids (glucose-free balanced electrolyte solutions, 1OG-150 mllcat
every 1-3 days). Water also may be administered through nasoesophageal or gastrostomy feed-
ing tubes if either is used.
16. Is dietary protein restriction beneficial in chronic renal failure?
Dietary protein restriction is associated with decreased accumulation of waste products de-
rived from protein, including urea and other nitrogenous compounds. Clinical experience con-
firms that dietary protein restriction is associated with amelioration of uremia. However, the
influence of dietary protein restriction on progression of renal failure is controversial. In addition
to decreasing nitrogenous compounds, dietary protein restriction is associated with a decreased
acid load, decreased phosphorous intake, and less solute that failing kidneys must excrete. Diets
formulated for management of renal failure should contain 19-23% of calories as high biologic
value protein or 28-30% of the diet (dry matter basis).
242 Common Dietary Questions
Another beneficial effect of protein restriction relates to decreasing ammoniagenesis.
Urinary ammonia is derived primarily from renal metabolism of glutamine. Urinary ammonia ex-
cretion increases with metabolic acidosis. Increased urinary ammonia may result in tubulointer-
stitial disease through activation of complement and other mechanisms. Because the majority of
excreted acid is produced from metabolism of dietary protein (in particular, animal-derived pro-
tein), dietary protein restriction is associated with decreased generation of metabolic acids and,
consequently, decreased urinary ammonia excretion.
17. What is the major risk of protein restriction?
Although uncommon, a potential side effect of dietary protein restriction is protein defi-
ciency. Worsening anemia, hypoalbuminemia, loss of muscle mass, or a dry, unthrifty haircoat
may be manifestations of protein deficiency. If signs of protein deficiency occur, increasing di-
etary protein intake may be attempted; however, care should be taken to avoid creating an imbal-
anced diet or worsening uremia.
18. What is renal secondary hyperparathyroidism?
Phosphorous retention and secondary hyperparathyroidism have been incriminated as causes
of progressive renal failure. Phosphorous plays a critical role in energy metabolism, cell mem-
brane integrity, acid-base balance, oxygen delivery to tissues, and carbohydrate metabolism.
Secondary hyperparathyroidism is an inevitable consequence of chronic renal failure, although it
is often not present until late in the course of the disease.
19. What dietary modifications may improve hyperparathyroidism?
In a study involving experimentally induced chronic renal failure in cats, a dietary phosphorous
intake of 1.56% (dry matter basis) was associated with significant renal mineralization and tubu-
lointerstitiallesions. In comparison, a dietary intake of 0.42% (dry matter basis) resulted in minimal
lesions. Appropriate dietary phosphorous restriction prevents and reverses preexisting renal hyper-
parathyroidism. An intake of 0.4-0.6% phosphorous (dry matter basis) is recommended for cats
with chronic renal failure. If dietary phosphorous restriction alone does not normalize serum phos-
phorous concentration, administration of phosphate binders (see Chapter 40) should be instituted.
20. What dietary treatments are helpful in managing the anemia of chronic renal failure?
Normocytic, normochromic nonregenerative anemia may occur with chronic renal failure and
is believed to be due, in part, to decreased erythropoietin production by failing kidneys. Poor nu-
tritional status and gastrointestinal blood loss secondary to uremic gastroenteropathy may further
exacerbate anemia. Anemia is treated by maintaining a good nutritional plane, minimizing gas-
trointestinal hemorrhage, and administering erythropoietin (see Chapter 40). By providing ade-
quate calories while minimizing uremia, a good nutritional plane can be maintained. Ameliorating
metabolic acidosis decreases gastric acid secretion, thereby minimizing uremic gastroenteropathy
and blood loss. If erythropoietin therapy is instituted, iron supplementation also should be pro-
vided. Iron sulfate (50--100 mg/cat/day orally initially) is the preferred therapy for iron deficiency
and prevention of iron-deficient erythropoiesis in patients beginning therapy with recombinant
human erythropoietin. Because iron supplementation may be associated with gastrointestinal
upset and diarrhea, small divided doses may be preferable.
21. Describe the role of diet in management of systemic arterial hypertension.
Systemic arterial hypertension is common in cats with chronic renal failure (see Chapters 40
and 63). Dietary sodium restriction, dietary phosphorous restriction, and amelioration of meta-
bolic acidosis may decrease systemic arterial blood pressure.
22. What other nutrients may be of interest in cats with chronic renal failure?
Soluble fiber may have a role in management of chronic renal failure. Soluble fiber causes bac-
terial proliferation in the large intestine. Bacterial growth requires a source of nitrogen that is de-
rived primarily from blood urea, which diffuses into the large intestine. Colonic bacteria degrade
Common Dietary Questions 243
urea, and the nitrogen is used for bacterial protein synthesis. Bacteria and these proteins are ex-
creted in feces. The net effect is increased fecal urea excretion, reduced serum urea nitrogen con-
centration, and reduced urinary urea excretion. Although fecal excretion of urea may decrease
serum urea nitrogen concentration, metabolic acids are generated from dietary protein, and if di-
etary protein is not reduced, the kidneys still must excrete an added acid load.
23. When should dietary modification be instituted in cats with chronic renal failure?
Dietary modification should be instituted at the time of diagnosis of chronic renal failure in
cats. Dietary modification decreases the clinical signs and biochemical consequences of chronic
renal failure and also is associated with a longer median survival time in cats with spontaneously
occurring chronic renal failure. Dietary modification should not be attempted while animals are
uremic because it may result in food aversion. Instead, a gradual dietary change should be at-
tempted after initial management of uremia when the cat is eating voluntarily. Dietary change is
easily accomplished early in chronic renal failure but becomes progressively more difficult as the
disease progresses.
24. What nutrients are of concern in cats with proteinuria?
Protein-losing nephropathy is not common in cats unless it is associated with chronic renal
failure or familial amyloidosis (see Chapter 43). Therefore, little information is available about
its treatment in cats. Dietary modifications that may of benefit include protein restriction and
other modifications appropriate for chronic renal failure.
25. Can dietary modification aid in treatment or prevention of urinary tract infections?
Bacterial urinary tract infections are uncommon in young cats but common in cats older
than 10 years (see Chapters 40, 41, and 48). Induction of aciduria has been recommended in
treatment of bacterial urinary tract infections; however, most cats cannot achieve a urine pH <
5.5. Most bacteria are able to propagate in urine with pH values ranging from 5.0 to 9.0; there-
fore, urinary acidification probably offers little benefit. Furthermore, because the incidence of
bacterial urinary tract infection is greater in older cats and cats with renal failure, an acidifying
diet may induce or exacerbate renal failure.
Fungal urinary tract infections are uncommon in cats; however, in cats with subclinical
funguria, induction of alkaluria may clear the infection. Urinary alkalinizing agents such as
sodium bicarbonate or potassium citrate or an alkalinizing diet to induce a urine pH ~ 8.0 may be
adequate for treatment of funguria if clinical signs are absent or minimal. Antifungal drugs may
be necessary in symptomatic or ill cats with funguria.
26. Are there different forms of struvite uroliths?
Struvite (magnesium ammonium phosphate hexahydrate) forms in alkaline urine (see
Chapter 45). Alkaluria may result from a urease-producing bacterial urinary tract infection (in-
fection-induced struvite uroliths) or from diet (sterile struvite uroliths). Sterile struvite uroliths
occur most commonly in cats; however, infection-induced struvite uroliths occur occasionally in
kittens and older cats predisposed to bacterial urinary tract infections.
27. How are struvite uroliths managed?
Sterile struvite uroliths can be dissolved by inducing undersaturation of urine with magne-
sium, ammonium, and phosphate ions and by inducing alkaluria (see Chapter 45). These goals
can be accomplished by feeding a diet that, compared with adult cat maintenance diets, is lower
in protein, magnesium, and phosphorous and induces aciduria. Currently, only one feline diet is
marketed to induce struvite urolith dissolution (SID diet; see table on pages 237-238). On aver-
age, sterile struvite uroliths can be dissolved in 2-4 weeks by feeding this diet exclusively; disso-
lution of infection-induced struvite uroliths requires 8-10 weeks. Once sterile struvite uroliths
are dissolved or removed, prevention involves dietary modification. Diets formulated to mini-
mize recurrence of sterile struvite uroliths are lower in protein, phosphorous, and magnesium and
244
Common Dietary Ouestions
induce aciduria. The struvite dissolution diet should be used cautiously in kittens or adult cats
with chronic renal failure.
28. Howare calcium oxalate uroliths managed?
Currently there are no medical protocols that induce dissolution of calcium oxalate uroliths
in cats; therefore, symptomatic uroliths must be physically removed. Preventive measures in-
clude dietary modification.
29. What nutrients are of interest in the prevention of calcium oxalate uroliths?
Dietary modifications demonstrated or thought to be beneficial include moderate restric-
tion of protein, restriction of calcium and oxalic acid, provision of adequate magnesium and
phosphorous, increased moisture, and inducing neutral to alkaline urine pH. Currently three
diets are formulated for management of calcium oxalate uroliths in cats (see table on pages
237-238). Consumption of these diets by healthy cats results in lowering of urine saturation to
a state of undersaturation, which theoretically should be sufficient to minimize recurrence of
calcium oxalate formation. Hypercalcemic cats (approximately 35% of cats with calcium ox-
alate uroliths) appear to respond better to higher-fiber diets supplemented with potassium cit-
rate for alkalinization.
30. How are purine uroliths (ammonium urate and xanthine) managed?
Xanthine and uric acid are metabolic products in purine metabolism. Purines are derived pri-
marily from protein sources, endogenous as well as dietary. They often form in acidic urine.
Management of purine uroliths involves feeding a protein-restricted, alkalinizing diet similar to
diets used in management of chronic renal failure. Although ammonium urate uroliths may form
because of a portosystemic shunt, most purine uroliths in cats are not associated with the presence
of a shunt.
31. What dietary modifications may be beneficial in managing cystine uroliths?
Cystine is a sulfur-containing amino acid composed of two cysteine molecules attached by a
disulfide bond. Cystine uroliths tend to form in acidic urine because their solubility is low at low
urine pH values; solubility increases exponentially in alkaline urine. Feeding a protein-restricted,
alkalinizing diet is beneficial in managing cystine uroliths. These diets also are used in manage-
ment of chronic renal failure.
32. Does dietary modification have a role in treating idiopathic feline lower urinary tract
disease?
Idiopathic feline lower urinary tract disease refers to a complex of clinical signs due to un-
known cause(s) (see Chapter 47). Cats with this syndrome have clinical signs of lower urinary
tract disease (e.g., pollakiuria, stranguria, hematuria) and may have urethral obstruction due to
urethral matrix-crystalline plug formation (males only), but they do not have a definable cause
for the clinical signs. Male cats with matrix-crystalline urethral plugs may benefit from dietary
modification to control the crystalline component of the plug. The most common mineral in-
corporated into urethral matrix-crystalline plugs is struvite (usually sterile struvite); however,
other minerals have been reported in isolated urethral plugs.
A large proportion of affected cats (55-70%) have nonobstructive idiopathic lower uri-
nary tract disease. The role of dietary modification in this setting is less clear. One clinical
study of young adult cats with nonobstructive lower urinary tract disease reported fewer
episodes of clinical signs when a struvite preventative diet was used compared with cats
whose diets were not changed. A diet that induces production of a larger volume of urine may
be beneficial. Canned food diets may be preferred. In addition, idiopathic lower urinary tract
disease is more common in obese cats than nonobese cats; therefore, weight reduction may be
beneficial.
Inappropriate Urination
BIBLIOGRAPHY
245
I. Allen TA, Polzin OJ, Adams LG: Renal disease. In HandMS, Thatcher CD, RemillardRL, Roudebush P
(eds): Small Animal Clinical Nutrition, 4th ed. Topeka, KS, Mark Morris Institute, 2000, pp 563---Q04.
2. Bartges JW: Calcium oxalate urolithiasis. In August J (ed): Consultations in Feline Medicine, 4th ed.
Philadelphia,W.B. Saunders, 2000.
3. LulichJP, OsborneCA, O'Brien TO, PolzinOJ: Feline renal failure: Questions, answers. questions. Comp
Contin Educ PractVet 14:127-153, 1992.
4. Osborne CA, Lulich JP, Thumchai R, et al: Feline urolithiasis: Etiology and pathophysiology. Vel Clin
NorthAm Small AnimPract 26:217-232, 1996.
5. Thatcher CD, Hand MS, RemillardRL: Small animal clinical nutrition:An iterativeprocess. In HandMS,
Thatcher CD, RemillardRL, RoudebushP (eds): SmallAnimal Clinical Nutrition,4th ed. Topeka, KS,
Mark Morris Institute, 2000, pp 1-19.
51. INAPPROPRIATE URINATION
Hazel C. Carney, M.S., D.V.M.
1. Define inappropriate urination.
The cat voluntarily deposits urine in one or more locations that are unacceptable to the
owner.
2. Why do cats urinate inappropriately?
Cats urinate in different locations as a way of giving social information to other cats. as a
way of releasing anxiety, or as a response to physiologic changes in the body.
3. How common is inappropriate urination by cats?
Inappropriate urination is the most common behavior problem in cats. Approximately 10%
of all pet cats at some time in their lives are presented to a veterinarian with a complaint of inap-
propriate urination.
4. What steps are included in a diagnostic evaluation offeline inappropriate urination?
Complete history, physical examination, and urinalysis provide the basis for a presumptive
diagnosis of the cause of the inappropriate urination and allows the clinician to begin a therapeu-
tic regimen (see algorithm on following page).
5. What questions are important in the history of a case of inappropriate urination?
Questions about the eat's background and urination habits, characteristics of the eat's litter
box, and the owner's personality and expectations for the cat are important in a thorough history
of inappropriate urination.
6. If the owner is unsure which cat in a multicat household is urinating inappropriately,
how do you determine the culprit?
Roll three fluorescein eye dye strips into each of two size 0 gelatin capsules. Give one cat in
the family these capsules orally. Have the owner use a black light to scan the litter pan and the
areas of inappropriate urination for the next 24-72 hours. The dye-containing capsules can be
given to each cat sequentially until the culprit is determined.
7. What clues from the history may help to explain the cause of inappropriate urination?
Dry stool or owner complaints of constipation may suggest early renal compromise.
A history of difficulty in jumping up onto the couch or bed may suggest musculoskeletal
pain.
246 Inappropriate Urination
Painor
Disease
Related
House
Soiling
Litter
Box
Related
Soiling
Anxiety
Based
Soiling
Anxiety
Related
Marking
Urine Volume
Stress
Urinalysis Resnlts
Surface
Location
Posture Standing Squatting

/\ \
Category of Urine House Urinary System
Inappropriate Marking Soiling or otber
Urinadon / \ \\
Working S yin
Diagnosis pra g
History, physical examination findings, and urinalysis are used to formulate a working diagnosis,
8. What clues from the physical examination may help to explain the cause?
o Uneven hind leg length when the hind legs are extended, a difference in the rotation of the cox-
ofemoral joints, resentment of the cat to the manipulation of its hind legs, unequal hind nail
lengths, or "pointing" with one leg when the cat stands may suggest musculoskeletal pain.
o Abnormal or disparate kidney size, rough or poorly compressible kidneys, or chalky white
stripes on the dorsal surfaces of the eat's nails suggest declining renal function.
o If palpation of the eat's bladder (unless it is very full), causes the eat's prepuce or vulva to
"wink," the cat has some bladder tenderness.
o Spines on the penis of a supposedly neutered male cat suggest occult cryptorchidism.
o Moist or chapped external genitalia or evidence of urine staining at the perineum suggests
incontinence or lower urinary tract disease.
o Resentment to compression of the lumbosacral spine may suggest pain when the cat pos-
tures to urinate,
o Poor eyesight may contribute to a eat's unwillingness to use its litter box consistently.
Inappropriate Urination 247
9. What basic characteristics of feline behavior and behavioral modification do you and
your client need to understand?
The cat is a creature of habit. The more the client is a creature of habit during therapy of the
cat, the greater the chance of success.
The cat learns most quickly by constant, frequent repetition and reward but remembers the
longest if trained with intermittent rewards.
The best plan of behavior therapy establishes situations in which the cat can only succeed
and blocks the chances of repeating the offending behaviors.
All previous sites of inappropriate urination must be cleaned so that noresidual urine smell
remains.
Modification of the environment, positive reinforcement, play therapy, aversion training,
and negative reinforcement may be necessary components of the treatment plan.
10. Describe the proper technique for urine clean-up.
Urine Clean-up
I. Dilute white vinegar I to I with water, and saturate the soiled area. If carpet padding has urine in
it, the pad also must be saturated with the vinegar water. Vinegar is cheaper than commercial odor
eliminators for the initial clean-up.
2. Let set for 30 minutes.
3. Blot up all vinegar water and urine with old terry towels. Blot up any residual dampness with paper
towels. Let area dry while washing the towels in x-a Odor Neutralizer (X-O Corporation, Dallas.
TX) as instructed on the bottle.
4. Get close to the spot, and sniff deeply. Repeat process as many times as necessary until you can
smell no urine odor. Fairly fresh spots usually take 3-4 cleanings, whereas old spots may require
8-10 cleanings. Repeat process once more, this time using plain water only. Let the area dry com-
pletely.
5. Apply one of the following urine clean-up products mixed as instructed on the label: X-O Odor
Neutralizer or Nature's Miracle (Nature's Miracle, Pens 'n' People, lnc., Rolling Hills Estates,
CAl. If the carpet pad had any urine in it, the pad must be saturated with the odor neutralizer.
Leave product in contact with surface to be cleaned as long as the label recommends.
6. Blot up odor neutralizer as you did the vinegar wash. Let dry thoroughly. For heavy, thick carpet-
ing, you may have to put dry towels atop the carpet and weight them to help absorb absolutely all
of the dampness.
11. What features of the eat's environment do owners need to evaluate?
The owner may need to increase the space that an individual cat has in its environment or
change the environment to make a cat feel safer. An indoor cat may be less stressed if the owner
builds a screened porch, deck, or patio to which the cat has access. The porch keeps the cat safe
from most outdoor dangers and increases the eat's visual stimulation. The spraying cat may mark
the perimeter of the porch; outside spraying "protects" the resident cat from intruders and proba-
bly is less offensive to the owners.
The owner may need to increase the vertical space available to cats by building cat trees or
allowing them on top of bookcases. This strategy decreases the stress in multicat households.
12. Howcan the eat's carrier be used for training?
The eat's carrier can be its friend instead of an enemy. Have the owner place the open carrier
in a quiet comer of the room in which the cat is most at ease and allow the cat to go in an out of
the carrier whenever the cat chooses. The carrier can then be used as a haven when the cat is
being trained. The cat can be confined to the carrier without feeling stressed when the owner is
not home to supervise the eat's urination behavior.
13. Describe the ideal litter box.
The more the owner mimics the eat's ideal litter box, the more likely the cat is to use the
litter box consistently. The ideal litter box is scrupulously clean, contains litter of a texture that
the cat prefers, and is in a safe, quiet location.
14. Explain the "scrambled egg theory of litter box number."
In multicat households, the ideal number of litter boxes is I for each cat plus I for the house.
15. Give examples of positive reinforcement for cats.
o The tone of the owner's voice is important to a cat. Praise spoken in a soothing voice when
the cat is seen using the litter box encourages the cat to choose the litter box again.
o Making the litter box attractive to the cat is the best positive association an owner can give
for the cat. Cleanliness is next to godliness for cats.
o Grooming can be a positive reinforcement for some cats; so can stroking a cat gently under
the chin, at the base of the left ear, or down the top of the head.
16. Howshould the litter box be maintained?
The owner should remove urine and stool every day and never stir wet litter into dry. A cat
stepping into a litter box wants to step into a dry area. If nonclumping litter is used, the owner
should empty the entire contents of the litter box once weekly. Then the box should be washed in
hot, soapy water, using a soap that has no ammonia base, no pine base, and no strong odor. The
box must be rinsed thoroughly; chemists say that 12 rinses with clear water are required to
remove all residual odor of cleansers. The box should be dried before new litter is added. For
clumping litters, this process should be repeated at least monthly. Although covered litter boxes
are great for owners, cats probably equate them with an outhouse maintained by the forest ser-
vice in a Southern swamp. Unless they are scooped and cleaned more often than an open box,
they stink! Liners for litter boxes are convenient, but holes in liners allow urine to seep under the
liner and create a source of odor that is not removed until the entire box is washed. Because of
their dislike for slippery surfaces, some cats will not use a litter box with a liner.
17. Explain play therapy and give examples.
The owner should actively play with the cat each day to build its self-confidence and provide
exercise. Play therapy also bonds the cat to new people. The owner can start with a few minutes
at a time and then gradually increase the playtime to 15 minutes twice daily. Owners should find
whatever the cat likes to do for play:
o Drag a string or a panty hose leg.
o Toss a ping-pong ball.
o Dangle a soft piece of denim tied to the end of a "fishing pole" (a good starter toy for a
timid cat).
o Move a laser light pointer; mimic a scared mouse that stops, starts, and darts in several di-
rections rather than in a straight line.
o Leave out an empty large paper grocery sack when the cat is alone; most cats cannot resist
playing in them.
18. Explain aversion training and give examples.
Aversion training uses a remote-controlled device to deter a cat from urinating in an inappro-
priate location. It is effective only if the cat does not associate the aversion device with the owner;
otherwise, the aversion device is effective only if the owner is present. Simple and effective aver-
sion devices include the following:
o Lightweight magazines, such as Reader's Digest, can be tossed at a urinating cat.
o Water pistols can be squirted at a urinating cat.
o Unusual noise, such as that made by fog horns, whistles, pop cans partially filled with pen-
nies and taped shut, a child's finger-controlled cricket noise maker, hissing noise, or clap-
ping of hands. Owners should use these sounds when they catch the cat in the act of
inappropriate urination. The owner may have difficulty making sufficient noises without
the cat seeing the owner as the source; fortunately, small devices such as a whistle or
cricket toy can be carried at all times.
Food bowls placed over areas where the cat has inappropriately urinated deter most cats be-
cause they do not like to urinate near food and water sources.
A butter tub containing cotton balls scented with lemon or orange oil and taped shut, with
small holes poked into the lid and sides, deters most cats because they do not like citrus scents.
Slick aluminum foil, shelf paper, butcher paper, and shower curtain liners placed over areas
that the owner wants the cat to avoid deter most cats because they dislike slick surfaces.
19. Should you punish a cat?
As cartoons and jokes suggest, punishment is not effective in cats unless the cat is "caught in
the act" The cat perceives delayed punishment as a threat to its safety. If an owner swats a cat
with his or her hand, the cat becomes afraid of the owner's hand and will resist petting also. If an
owner punishes a cat near the litter box or forcibly moves the cat into the litter box, the cat may
become afraid of the litter box.
20. When are drugs added to the treatment regimen?
Because almost all drugs for treatment of inappropriate urination are not approved for use in
cats and because many have significant side effects, behavioral modification and changes in the
eat's environment are the initial options. If inappropriate urination persists after 1-3 weeks of be-
havioral therapy. medication should be considered. The longer a cat urinates in any location. the
more likely the cat will continue to urinate there because the presence of its own urine makes the
cat feel more at home and in control. Specific drugs that have been used for treatment of inappro-
priate urination are discussed under each working diagnosis.
21. When can pharmacologic treatment be discontinued?
If you see no response to a particular drug after 3 weeks. the drug or starting dosage is likely
ineffective and should be changed. Drugs generally require 1-5 weeks to affect the eat's neuro-
logic and behavioral chemistry. Urination behavior should be consistently acceptable for a mini-
mum of 3 weeks before an attempt to discontinue the drugs is made. Therefore, once drugs are
started, they are given for at least 1-2 months before they are slowly tapered. At that time. the
dosage usually is reduced by one half every week until a minimal effective maintenance dose is
determined or no drug is needed. Sudden stoppage of the medication may cause rebound exacer-
bation of the undesirable behavior.
22. How do you manage suspected spraying?
1. Explain characteristics of spraying behavior to the owner.
2. Describe the characteristic posture of the spraying cat
3. Discuss surgical treatment options.
4. Discuss behavior modification techniques.
5. Discuss possible pharmacologic therapy.
23. Why do cats spray?
The behavior communicates territoriality. possession, and sexual availability to other cats. It
says, "I'm here," "It's mine," or "I'm available." The most common way that a cat marks territory
is by spraying. Male cats spray more often than female cats; toms spray more often than neutered
males, and queens spray more often than spayed females. In a one-cat household the chance that
one cat, regardless of sex, will spray is 25%; in a household with 11or more cats. the chance that
anyone cat will spray increases to 100%.
24. Describe typical spraying behaviors.
1. The cat stands with tail fully erect; there is no curve, even in the tip of the tail.
2. The cat squirts out a small amount of urine onto a vertical surface.
3. A small, anxious, intact female, especially one purchased from a large cattery, may uri-
nate in small or normal volumes beside the litter box or near doors or windows only when she is
coming into estrus; she is too timid to spray but still wants to tell male cats that she is "available,"
25. What surgical options are available for spraying cats?
Gonadectomy. Within 2 months after surgery, 80-90% of cats that are spayed or castrated
will no longer spray urine. The chance of spraying after gonadectomy increases if the cat had
sexual experience before surgery.
Olfactory tractotomies and ischiocavernosus myectomy. Both techniques suppress spray-
ing, but because they are technically more difficult, they are rarely used.
26. List specific behavior modification techniques for spraying cats.
1. Thoroughly clean the sprayed areas on the inside and outside of the house, using the
technique described in question 10.
2. Actively engage the cat in play therapy at least 15 minutes daily (see question 17).
3. Increase available indoor vertical space for the cat.
4. Determine why the cat feels it must mark territory:
5. If a new adult is the cause, have the person take over feeding and other activities that the
cat considers to be pleasant.
6. If the cause is new furniture or recent remodeling, limit the eat's access to times when
the owner can be with the cat in the room with the new items. The owner should sit near the new
items and pet or play with the cat. Let the cat rub its face on the new items, but if the cat backs up
toward any item, immediately use an aversion device or pick up the cat, gently say "No," and take
the cat to an area of the house where the cat is completely at ease and has not sprayed. Just before
the cat is allowed into the new area, use a hormone spray (Feliway, Abbott Laboratories) daily on
the new items.
7. Remove outside competitor cats if possible.
8. Block view of outside cats.
9. Cover windows with aluminum foil or vinyl view blockers for bathrooms.
10. Restrict cats to interior rooms that have no view of outside cats.
11. Decrease competition among inside cats.
12. Separate antagonistic cats.
13. Allow the spraying cat to become an indoor-outdoor cat.
14. Build a screened porch for the culprit.
I S. Block sprayed areas with aluminum foil or slick shower curtain liners; the sound of
sprayed urine hitting these surfaces is sometimes offensive or scary to the cat.
16. Try a "Scat Mat" type device rolled from the floor upward toward the article being
sprayed. Enough of the mat should be on the floor so that the eat's hind feet contact it and trigger
the alarm when the cat backs up to spray.
17. Use other invisible noise detractors whenever the cat is seen to sniff and turn its rear
toward an item.
18. Use food aversion techniques.
19. If the cat sprays only one or two areas repeatedly and cannot be deterred, the owner
should make an L with two litter boxes. Put one box on the floor and the second vertically inside
the horizontal box. This strategy does not stop the spraying, but it contains the sprayed urine and
may be acceptable to some owners.
27. What pharmacologic therapy may be used in spraying cats?
Buspirone is a good drug to try in multicat households.
Cyproheptadine is a safe alternative; it is the first choice if the spraying cat is cryptorchid.
Amitriptyline, diazepam, and synthetic progestins have associated risks and should be of-
fered only if preliminary serum chemistries and a lead II electrocardiogram (for amitripty-
line) are within normal limits. The owner must be fully informed about the potential risks,
Paroxetine may be especially useful if the spraying is territorial and motivated by aggres-
sion-dominance.
Pheromone spray (Feliway) eliminates or decreases the frequency of spraying in 30% and
60% of treated cats, respectively.
Flower Essences Vine and Mimulus (available at health food stores) decrease dominance-
and fear-motivated spraying when given as oral drops or in drinking water and have no
known adverse side effects.
28. How do you do manage suspected anxiety-based house soiling?
1. Explain to the owner the causes of anxiety in cats.
2. Describe the characteristic posture.
3. Convince the owner that cats do not urinate spitefully.
4. Discuss behavior modification plans.
5. Discuss pharmacologic therapies that help to decrease anxiety.
29. What are the common causes of anxiety in cats?
Because cats are creatures of habit, any change in routine may cause anxiety, especially if
the cat is genetically predisposed to shyness or as a kitten did not stay with the queen long
enough to be well socialized. New babies, adults, furniture, cats, puppies, walls, plants, or litter
boxes can frighten a cat. Other possible causes include the following:
Separation from its owner for different intervals
Strained interpersonal relationships among people in the household
Placement of the litter box in an area that is noisy or busy
Placement of the litter box in an attic, basement, or other unpleasant setting
The act of urinating outside the litter box is also stressful to the cat because the cat is going
against its own naturally fastidious nature.
30. Describe the characteristic posture associated with anxiety-related house soiling.
The cat squats to urinate.
The cat deposits urine on horizontal surfaces.
The cat usually "rakes earth" before and sometimes after it urinates.
Urine volume varies with how scared the cat may be, whether another cat or person is pre-
sent, and how recently the cat previously urinated.
31. How do you convince the owner that cats do not urinate spitefully?
1. A cat deposits urine so that something or some place will smell more like itself and thus
be less threatening. This principle explains why the cat may urinate on the belongings of a person
that the cat dislikes.
2. A cat urinates on the owner's bed or clothes because the owner's smell is strongest there.
An anxious cat urinates on these items because only there does the cat feel safe.
32. Summarize the behavior modification plan for anxiety-related house soiling.
1. Thoroughly clean all areas where the cat has urinated outside the litterbox (see question 10).
2. Attempt to determine the cause of the eat's anxiety:
Location of litterbox Separation anxiety
Multicat household Dislike of specific person(s)
3. Discuss pharmacologic therapies that help to decrease anxiety.
33. What specific behavior modification techniques are helpful for location anxieties?
I. Analyze both the history and the house plan to determine the locations in the house that
are the quietest and most comfortable for the cat.
2. If the cat has chosen a spot that the owner does not like, the owner should camouflage the
spot and place a litter box near it. When the cat is consistently using the litter box, the owner
should move the box slowly by l-inch. increments toward the preferred location.
34. What specific techniques may alleviate anxiety related to multicat thresholds?
I. Meet the "scrambled egg theory" of litter box number (see question 14).
2. Practice all aspects of litter box cleanliness.
3. Institute play therapy (see question 17).
4. Increase vertical space in the house or build screened porches to allow more separation
among cats.
5. Physically separate unfriendly cats for 10-14 days, then gradually reintroduce them.
35. Describe behavior techniques for dealing with separation anxiety.
1. Have the owner stay away from the cat for gradually increasing intervals.
2. Have the owner develop a leave-taking ritual to use initially, even if just leaving the house
to take out the garbage.
3. If the cat urinates on the owner's bed, lock the cat out of bedroom or cover the bed with a
clear plastic shower curtain until the cat is retrained. Sometimes a litter box placed atop the
shower curtain can be moved in l-inch increments per week toward the ideal litter box location.
36. What behavior techiques are used for anxiety related to dislike of specific people?
1. Have the person assume the pleasant activities in the eat's life, such as feeding, grooming.
and play.
2. Put away items belonging to the disliked person until the cat is at ease with the person.
Then gradually allow the cat access to the person's belongings.
37. What drugs are available to decrease anxiety in cats?
Buspirone may be the drug of choice for multicat households.
Clomipramine may be better in a single cat household or when the cause of the inappropri-
ate urination is separation anxiety.
Pheromone spray (Feliway; see question 26) may be beneficial.
In multicat households, consider flower essence therapies after doing personality profiles
of each resident cat.
38. How do you manage suspected litter box-related house soiling?
1. Explain to the owner that the cat is house soiling because the cat dislikes something about
the litter box or has a preference for the site that the cat has chosen to soil. If the cat has chosen
multiple locations, the cat probably dislikes the box shape, location, or litter substrate. If the cat
has chosen just one or two sites, the cat probably prefers this particular location or substrate.
2. Describe the posture that the cat uses in the inappropriate location: the cat has a normal uri-
nation posture, passes normal volumes of normal urine, and rakes earth before and after urination.
3. Look for behaviors that may suggest that the cat dislikes something about the litter box.
4. If the cat appears to dislike the litter box, try to determine why.
5. Remove or change the aspects of the litter box that the cat dislikes.
6. Thoroughly clean all areas of inappropriate urination (see question 10).
7. Try confinement therapy (see question 42).
39. List behaviors that suggest dislike of the litter box.
The cat shakes its paws after leaving the box.
The cat straddles the sides of the box or keeps only one or two feet in the box.
The cat runs away from the box after using it.
The cat does not dig in the box or cover its excrement.
The cat starts in a squatting posture and stands up before it finishes urinating.
40. What aspects of the litter box may be displeasing to the cat?
The cat may dislike the texture of the litter. Cats that dislike rough litter may choose soft,
carpeted surfaces or fine textured material for urination.
The cat may dislike the depth of litter in the box. Kittens and long-haired cats may prefer
more shallow litter.
The cat may dislike the smell of the litter, especially if the box is not cleaned frequently or
is used by multiple cats. Cats with a smell aversion may display the Flehman response
before entering the box.
The cat may dislike the size, depth, or configuration of the box (e.g., kittens and arthritic
senior cats may have difficulty with jumping into a tall box).
The cat may dislike the location of the litter box. Cats prefer quiet, low-traffic, low-noise
areas away from their food and water bowls. Some cats want two potential exits from the
box so that they cannot be trapped by another animal.
41. Explain confinement therapy.
The cat is confined with its litter box in a large carrier or a small room such as a powder room.
The cat is allowed out of isolation only to eat and only when owner is available to supervise the
eat's activity. The goal of confinement and strict supervision is not to let the cat "make another
mistake" because any mistake reenforces inappropriate behavior. One expert states that a cat must
repeat a correct behavior 300 consecutive times before the new behavior replaces the old behavior
in the eat's thought processes. Even without higher mathematics, one can see that the cat must uri-
nate in the correct location for many months before it has forgotten about the old location!
42. What have you learned if the cat uses the box in confinement?
The type of litter and box size and shape are probably not the problem. The location of the
box may be what the cat dislikes.
43. What if the cat does not use the litter box in conf'mement?
The cat probably dislikes something about the type of litter or the litter box.
44. How do you determine what the cat dislikes about the litter?
Fill separate litter boxes with a different type of litter (a substrate "smorgasbord" test). Use
at least one unscented, clumping, sand type litter, one of clay, one of pellets, one lined with
carpet, and one of garden soil. Put all of the boxes in the confined area with the cat and let the cat
choose its favorite. Continue the test for several days. If the cat uses the same type of litter every
day, the cat prefers this brand. If the cat chooses several of the boxes, the cat may need only a
cleaner litter box, less litter volume, or different side height.
45. What do you do next?
If the cat uses the litter box in confinement, place the cat in confinement with the litter that
the cat chose during the substrate smorgasbord test. If the cat chose carpet, use scraps of carpet
initially and gradually add litter over the carpet. Some cats that rake the sides of the litter box will
eliminate in a litter box with sandy litter on the bottom and carpet along the walls. Again confine
the cat with the new litter until the cat has been using the box consistently for at least 2 weeks.
Then gradually enlarge the area of confinement.
46. Howdo you prevent the cat from returning to former areas of inappropriate urination
after it is let out of confinement?
I. Initially allow the cat outside the confinement area only under supervision.
2. Block access to previous sites of inappropriate urination, especially if the cat has chosen
numerous places in which to urinate.
3. Divide the total meal volume among a number of food bowls equal to the number of
places at which the cat inappropriately urinates. Place one food bowl over each site of inappro-
priate urination. Leave the food bowls in place even after they are empty each day.
4. If the cat goes one full week without inappropriately urinating, remove the food bowls
one at a time. If the bowls are near a litter box, take away the innermost bowl first. Take away the
bowl for only IS minutes or so the first day; then replace it. For each day that the cat does not uri-
nate in the area uncovered by removing the bowl, leave the bowl away from the area for gradu-
ally increasing intervals until the cat has not inappropriately urinated in that spot for 7 days. Then
take away that one bowl permanently.
5. Begin removing a second bowl, again for only IS minutes on the first day and so on until
the cat is no longer urinating inappropriately at any location.
6. If the cat used only a few areas for inappropriate urination, place litter boxes at these lo-
cations. If the cat urinates in the boxes, move them at the rate of I inch per week toward the pre-
ferred locations.
47. How do you manage pain- or disease-associated house soiling?
1. Explain why the cat quits using its litter box when it has cystitis or other diseases.
2. When the cat experiences pain during urination, it begins to associate the litter box with
pain and leaves the box. If the pain continues at the next urination, the cat will move to a new
spot again and again until the pain stops.
3. Once treatment of the primary disorder removes the pain, the cat will return to its litter
box unless inappropriate urination has become a chronic habit.
4. Retrain the cat to use its litter box again after the pain is diminished with treatment of the
primary condition. Consider short-term confinement (see question 42) until the cat seems to be
using the litter box consistently. Gradually allow the cat unlimited access to the house.
BIBLIOGRAPHY
I. Alani MM: The Body Language and Emotion of Cats. NewYork, William Morrow, 1987.
2. Bateson P, Turner DC: Questions about cats. In Turner DC, Bateson P(eds): The Domestic Cat: The
Biology of Its Behavior. Cambridge, MS, Cambridge University Press, 1999, pp 193-201.
3. Beaver BV: Eliminative behavior development. In Beaver BV (ed): Feline Behavior: A Guide for
Veterinarians. Philadelphia, w.s. Saunders, 1992, pp 63-85.
4. Dodman NH: The writing on the wall. In Dodman NH (ed): The Cat Who Cried for Help. New York,
Bantam Books, 1997, pp 101-120.
5. Graham H,Vlamis G: Bach Flower Remedies for Animals. Tallahassee, FL, Findhorn Press, 1999. pp
1-126.
6. Halip lW, McKeown DB, Luescher UA: Inappropriate elimination in cats. Part I. Feline Pract20: 17-21.
1992.
7. Halip lW, McKeown DB, Luescher UA: Inappropriate elimination in cats. Part 2. Feline Pract 20:25- 29,
1992.
8. Hunthausen W: Evaluating a feline facial pheromone analogue to control urine spraying. Vel Med
95:151-155,2000.
9. Overall KL: Feline elimination disorders. In Overall KL (ed): Clinical Behavioral Medicine for Small
Animals. St. Louis, Mosby, 1997, pp 160-194.
10. Overall KL: Diagnosing feline elimination disorders. Vet Med 93:350-382, 1998.
52. URINARY INCONTINENCE
India F. Lane, D.v.M., M.S.
1. Define urinary incontinence.
Urinary incontinence is the involuntary loss of urine. Urine leaks through the urethra, often
while the cat is resting. Urinary incontinence must be differentiated from inappropriate (volun-
tary) urination, pollakiuria, and urine spraying in cats.
2. What mechanisms commonly lead to urinary incontinence?
Urinary incontinence results from abnormal anatomy of the ureters, urinary bladder, or ure-
thra; poor urine storage by the urinary bladder; or weak urethral outlet tone. Functional abnor-
malities are caused by neurogenic and nonneurogenic disorders.
3. Is urinary incontinence common in cats compared with dogs?
Urinary incontinence is rare in cats.
4. When urinary incontinence is observed in cats, what are the common causes?
The most common causes of urinary incontinence in cats are neurologic lesions (sacral or
sacrococcygeal), feline leukemia virus (FeLV)-associated urinary incontinence, and idiopathic
urethral incompetence.
Causes of Urinary Incontinence in Cats
Neurologic lesions(sacral spinal cord)
Spinal malformation
Trauma
Neoplasia
Anatomicabnormalities
Congenital urethral hypoplasia
Congenital bladder hypoplasia
Ectopic ureter
Patent urachus
Ureterovaginal fistula
Perineal urethrostomy
Functional or idiopathic disorders
Idiopathic bladder hypercontractility
Feline leukemia virus-associated urinary incontinence
Acquired urethral incompetence
Urinary tract infection or inflammation
Urinary bladder neck or urethral neoplasia
Overflowurinary incontinence
Neurologic lesion (upper or lower motor neuron)
Dysautonomia
Detrusor atony (postobstructive)
Partial urethral obstruction (paradoxical incontinence)
5. What should be included in the physical examination of cats with urinary inconti-
nence?
In addition to a general physical examination, attention to neurologic function, urinary blad-
der size, and expressibility of urine are important. Mental status, hindlimb proprioception. anal
255
256 Urinary Incontinence
tone, perineal sensation, tail tone, and tail function are indicators of sacral spinal cord and higher
nervous center integrity. Pupil size should be assessed. Anisocoria is often detected in cats with
FeLV- associated polyganglionopathy, whereas mydriasis is a common finding in idiopathic
dysautonomia.The causes of urinary incontinence are sometimes categorized by resting urinary
bladder size. With a small, nondistended bladder, urinary incontinence usually is attributed to
bladder hyperactivity or urethral incompetence. When incontinence occurs with a distended blad-
der, causes of overflow incontinence are likely. The ease of bladder expression can be used to es-
timate urethral outlet tone.
6. What tests are included in the initial evaluation of cats with urinary incontinence?
Urinalysis, urine culture, FeLV serum antigen testing, and abdominal radiographs are indi-
cated in all cats with urinary incontinence. Abdominal radiographs are needed to detect uroliths
or gross abnormalities of the urinary tract or spinal column. Complete blood count and serum
biochemistry panel should be evaluated in cats with concurrent polyuria, urinary tract infection,
or other signs of systemic illness.
7. When are additional imaging procedures indicated?
Abdominal ultrasonography may be indicated in young cats with urinary incontinence to
evaluate the kidneys, ureters, and urinary bladder conformation. Excretory urography and con-
trast cystourethrography are indicated for further evaluation of urinary tract anatomy in cats that
exhibit urinary incontinence at a young age or after surgery or trauma. Vaginourethrography also
is indicated in kittens with urinary incontinence, because vaginal anomalies often accompany
congenital urethral incompetence in cats.
8. What specialized diagnostic procedures are available for the evaluation of incontinent
cats?
Insome complex cases or cases that respond poorly to trial therapy, urodynarnic or electrodiag-
nostic tests may be indicated to define more clearly functional and neurologic abnormalities.
Urinary bladder capacity, compliance, and contractile function can be assessed with cystometry (in-
travesical pressure measured as the bladder is slowly distended with air, fluid, or contrast media) or
specialized voiding studies. Urethral resistance can be assessed by recording urethral pressures
along the length of the urethra (urethral pressure profilometry). Concurrent measurement of elec-
tromyographic activity from the perineal area adds qualitative evidence of striated urethral muscle
innervation and activity during cystometric or urethral studies. Other electrodiagnostic procedures,
such as spinal evoked potential and pudendal reflex recordings, may be available at teaching hospi-
tals for more sophisticated evaluation of neurologic input to the lower urinary tract.
9. What are the distinguishing clinical features of congenital urinary incontinence in cats?
Affected kittens are female domestic short-haired cats with severe urinary incontinence, es-
pecially when resting. The urethra is anatomically hypoplastic or essentially absent. Concurrent
vaginal aplasia is common; the uterine horns empty into the dorsal bladder wall. Urinary bladder
hypoplasia, ectopic ureteral terminations, and renal dysplasia or aplasia also may accompany the
developmental anomaly.
10. Howdoes the presentation of ectopic ureters differ in cats and dogs?
Whereas most dogs with ectopic ureteral terminations are presented for evaluation of severe
or continuous urinary incontinence, some affected kittens may exhibit minimal or no inconti-
nence. The ectopic ureter is found during diagnostic evaluation for recurrent bacterial urinary
tract infections or chronic hematuria, dysuria, or pollakiuria. At surgery, most feline ectopic
ureters bypass the bladder completely, whereas most ectopic ureteral terminations in dogs tunnel
through bladder or urethral mucosa. The prognosis for continence after surgical repair in cats is
generally good unless overt abnormalities of the urethral and bladder are evident. Up to two-
thirds of dogs with ectopic ureteral terminations continue to have some degree of urinary inconti-
nence postoperatively.
Urinary Incontinence 257
11. What treatments are recommended for congenital urinary incontinence in cats?
Surgical correction by a specialist is recommended for congenital urinary anomalies in cats.
The limited size of cat ureters necessitates command of microsurgical techniques for ureteral
transplantation or neoureterostomy. Some cases of ectopic ureter with severe hydronephrosis,
renal dysplasia, or pyelonephritis are managed by ureteronephrectomy as long as contralateral
renal function is adequate.
Bladder neck reconstruction may be attempted in cats with urethral hypoplasia; the proce-
dure is designed to create a longer, resistant "urethral tube." In experienced surgical hands, this
procedure significantly reduces urinary incontinence. Adjunct medical treatment with phenyl-
propanolamine is required in some cases.
12. Summarize the mechanism of action, dosage, side effects, and contraindication of drugs
used for the management of urinary incontinence in cats.
MECHANISM RECOMMENDED POTENTIAL CONTRA-
AGENT CLASS OFACTION DOSE SIDEEFFECTS INDICATIONS
Phenylpropa- Alpha-adrenergic Increases urethral 1.1-2.2 mg/kg Hyperactivity Hypertension
nolamine agonist tone PO every 8- Tachycardia Renal failure (?)
12hr Anorexia Arrhythmias
Ephedrine Alpha-adrenergic Increases urethral 2--4 mg/cat PO As above
agonist tone every 8-12 hr
Oxyhutynin Anticholinergic Decreases hladder 0.5 mg/cat PO Ileus
Antispasmodic contractility every 12 hr Vomiting
Urine retention
Ptyalism
Propantheline Anticholinergic Decreases bladder 5-7.5 mg/cat As above
contractility PO every 24-
12hr
Bethanechol Cholinergic Increases bladder 1.25-7.5 mgt Ptyalism Urinary ob-
agonist contractility cat PO every Vomiting struction
8-12 hr
PO =orally.
13. Define dysautonomia.
Dysautonomia is a diffuse autonomic polyganglionopathy described primarily in cats in
Great Britain (Key-Gaskell syndrome) but occasionally encountered in dogs or cats in the mid-
western United States. The urologic disturbance is characterized by a distended urinary bladder
and overflow urinary incontinence. The urinary bladder is easily expressed and contractility may
improve with administration of prokinetic or parasympathomimetic agents such as bethanechol.
Other clinical signs include mydriasis, prolapsed third eyelids, constipation or diarrhea, regurgi-
tation or vomiting, and anorexia. The diagnosis is established by documenting inappropriate re-
sponses to provocative autonomic testing.
14. What treatments are recommended for FeLV-associated urinary incontinence?
FeLV-associated urinary incontinence may be caused functionally by urinary bladder over-
activity or urethral incompetence. Unstable detrusor contractions at low bladder volume (also
called detrusor instability) were documented in one FeLV-positivecat that responded well to ad-
ministration of the anticholinergic, antispasmodic agent oxybutynin. Trial treatment with anti-
cholinergic agents seems warranted in affected cats. If response is minimal, pharmacologic
management for urethral incompetence may be considered.
15. What treatments are recommended for urethral incompetence in cats?
Although reproductive hormones are useful in the management of urethral incompetence in
many dogs, they are not recommended in cats. Estrogens can induce signs of estrus or bone
258 Urinary Incontinence
marrow suppression in female cats, and testosterone preparations have been minimally effective
in male cats. Alpha-adrenergic agonists (phenylpropanolamine, ephedrine compounds), which
stimulate urethral smooth muscle receptors, may be effective in the management of urethral in-
competence in both dogs and cats.
16. When are other pharmacologic treatments indicated?
Additional pharmacologic manipulation of bladder emptying (i.e. bethanechol) may be indi-
cated in cats with a distended urinary bladder and overflow incontinence (see also chapter 47).
Manual expression or intermittent urethral catheterization may be required to maintain a small
urinary bladder.
17. What is the prognosis for acquired urinary incontinence in cats?
Response to pharmacological treatments for urinary incontinence is much less reliable in
cats when compared to dogs. Although some cats with feline leukemia-associated urinary incon-
tinence may respond to anticholinergic agents, long-term prognosis is guarded. Management of
lower urinary tract dysfunction associated with neurologic lesions or idiopathic urethral incom-
petence often is unrewarding.
BIBLIOGRAPHY
1. Baines Sl, Speakman AI, Williams 1M, et al: Genitourinary dysplasia in a cat. 1 Small Anim Pract
40:286-290,1999.
2. Barsanti lA, Downey R: Urinary incontinence in cats. 1 Am Anim Hosp Assoc 20:979-982, 1984.
3. Holt PE: Feline urinary incontinence. In Bonagura 1 (ed): Kirk's Current Veterinary Therapy XII (Small
Animal Practice). Philadelphia, W.B. Saunders, 1995, pp 1018-1022.
4. Holt PE: Surgical management of congenital urethral sphincter mechanism incompetence in eight female
cats and a bitch. Vet Surg 22:98,1993.
5. Lane IF, Barsanti lA: Urinary incontinence. In August lR (ed): Consultations in Feline Internal Medicine,
2nd ed. Philadelphia, W.B. Saunders, 1994, pp 373-382.
6. Lane IF: Pharmacologic management of feline lower urinary tract disorders. Vet Clin North Am Small
Anim Pract 26:515-533,1996.
7. Lappin MR, Barsanti lA: Urinary incontinence secondary to idiopathic detrusor instability; Cystometro-
graphic diagnosis and pharmacologic management in 2 dogs and a cat. 1Am Vet Med Assoc 191:1439-
1442,1987.
8. Sackman IE, Sims MH: Electromyographic evaluation of the external urethral sphincter during cystome-
try in male cats. Am J Vet Res 51:1237-1241,1990.
IV. Endocrine Problems
Section Editor: Ellen N. Behrend, V.M.D., M.S., Ph.D.
53. HYPERTHYROIDISM
James K. Olson, D.V.M.
1. Howcommonis feline hyperthyroidism?
Feline hyperthyroidism is the most common feline geriatric endocrinopathy, even though the
first cases were described in the late 1970s.
2. Describe the pathophysiologyof feline hyperthyroidism (thyrotoxicosis).
In 99% of cases, the cause is benign nodular adenoma(s). These nodules autonomously se-
crete the thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) in excess, resulting in multi-
systemic disease. The excessive secretion has negative feedback to the pituitary, suppressing
thyroid-stimulating hormone (TSH) secretion. Normal thyroid tissue atrophies because of lack of
TSH from the pituitary gland and ceases secretion ofT4 and T3. Inthe other rare I% of cases, the
cause is a mild to moderately malignant thyroid carcinoma.
3. What causes hyperthyroidism?
What initiates the hyperplasia/tumor formation is unknown, but possible risk factors have
been identified and are under study. Theories of the cause of feline hyperthyroidism suggest that
dietary changes (canned foods), preservatives and food additives, environmental exposures (cat
litter, toxins, and pollution), increased exposure to allergens, genetic mutation (altered TSH re-
ceptor gene and G protein), and abnormal immunologic responses may be involved.
4. Describe the normal anatomyof the thyroidglands.
Most of the normal thyroid tissue is located as a single gland that is divided into two lobes
located ventral to the trachea in the mid-portion of the neck between the larynx and xiphoid
process. One lobe is on either side of the trachea, with no connection between them. Small
amounts of ectopic thyroid tissue may be scattered throughout the ventral neck and mediastinum.
The thyroid gland cannot be palpated in normal cats. Enlarged thyroid tissue in the chest cannot
be palpated and can be difficult to locate at exploratory surgery.
S. What is the typical signalment of cats with hyperthyroidism?
Hyperthyroidism is a geriatric disease seen in cats aged 4-22 years, with a median age of 13
years. Hyperthyroidism is extremely rare under the age of 7 years. There is no sex or breed
predilection, but Siamese and Himalayan cats have a lower incidence.
6. Whathistorical andclinicalfindingsare typically associated withfelinehyperthyroidism?
Weight loss or emaciation (93%) Polydipsia/polyuria (36%)
Enlarged thyroid lobes (80-90%) Increased activity (33%)
Behavioral changes (80%) Diarrhea (15%)
Polyphagia (49%) Gallop rhythm (15%)
Tachycardia (42%) Vocalization (10%)
Vomiting (44%) Poor hair coat (10%)
259
260 Hyperthyroidism
Other clinical signs seen in 5-10% of cases include dyspnea, panting, large fecal volumes,
and the apathetic (sick) form of hyperthyroidism characterized by decreased activity, lethargy.
anorexia. depression, and weakness.
7. Howdoes hyperthyroidism affect the body as a multisystemic disease?
A human analogy for feline thyrotoxicosis is the "stressed out speed freak" or an "adrenaline
junkie."
Systemic Effects of Feline Hyperthyroidism
SYSTEM
Neuromuscular
Gastrointestinal
Hepatic
Cardiac
Respiratory
Renal
EFFECTS
Behavioral changes. hyperactivity, muscle loss, weakness, aggression, vocali-
zation, pacing, restlessness
Changes in appetite, vomiting, diarrhea, maldigestion/malabsorption, large
fecal volumes, vitamin and nutritional deficiencies.
Elevated serum enzyme activities, hepatic lipidosis
Systolic murmurs, tachycardia, gallop rhythm, cardiac hypertrophy, hyper-
tension, congestive heart failure
Hyperventilation, dyspnea, pulmonary edema/congestive heart failure
Hypertension-induced renal damage, polydipsia/polyuria
8. Can hyperthyroid cats be diagnosed on physical examination?
Enlarged thyroid glandes) can be palpated in 80--90% of cases. In published studies, approx-
imately 25-30% are unilateral, 70% are bilateral, and 3-5% are ectopic.
9. What abnormalities can be detected on routine laboratory testing?
On the complete blood count, increased packed cell volume and mean corpuscular volume are
seen in approximately one-third to one-half of hyperthyroid cats. Increased activities of liver en-
zymes are common; approximately 90% of hyperthyroid cats have increased activity of alanine
transaminase (ALT), alkaline phosphatase (ALP), and/or aspartate transaminase (AST). Increased
ALP activity is the most common (approximately 80% of cases), but ALT and AST increases occur
in approximately 55%. Other less common biochemical abnormalities are elevated blood urea ni-
trogen (BUN) and creatinine (approximately 20%) and hyperglycemia (approximately 20%).
10. Howis hyperthyroidism diagnosed?
Clinical signs (the first and most reliable is weight loss) give a clue to the diagnosis, and if
enlarged thyroid nodules are palpated, hyperthyroidism is likely. Palpation may be the earliest
and most reliable way to detect the disease, but the presence of enlarged nodules does not neces-
sarily mean that the cat is hyperthyroid. Definitive diagnosis requires thyroid testing. The total
T4 (TT4) concentration should be the first test. If the TT4 is above normal, there is a 98-100%
chance that the cat is hyperthyroid. Cats with enlarged thyroid glands but normal TT4 concentra-
tions should be considered thyroid suspects and monitored closely for hyperthyroidism.
11. Is it possible for a hyperthyroid cat to have a TT4 in the normal range?
In some hyperthyroid cats, the TT4 is in the upper half of the normal range. Total T4 concen-
trations fluctuate between normal and elevated levels in many mildly hyperthyroid patients. Non-
thyroidal disease also may suppress TT4 into the normal range in hyperthyroid cats (i.e ..
euthyroid sick syndrome). If the TT4 is in the upper half of the normal range in a cat suspected of
hyperthyroidism, a free T4 (fT4) level should be measured by equilibrium dialysis. Alternatively,
a T3 suppression test can be done, but it is more difficult and time-consuming.
12. How is the T3 suppression test used to aid in the diagnosis of hyperthyroidism?
In borderline cases of hyperthyroidism with clinical signs but normal TT4 levels, the T3 sup-
pression test can be used to define the condition more accurately. To perform the test. a baseline
Hyperthyroidism 261
blood sample is taken, and seven 25-mg doses ofT3 are administered orally every 8 hours, start-
ing on the morning of day I. Two to four hours after the seventh dose is administered (day 3), a
blood sample is drawn. T3 should be measured before and after T3 administration, and the con-
centrations should increase to ensure administration of the drug. Hyperthyroid cats have a post-
test TT4 that does not suppress; the values are > 1.5 ug/dl (20 nmol/L), In normal cats or cats ill
from other causes, the TT4 is suppressed below this level.
13. Does an elevated IT4 necessarily mean that the cat is hyperthyroid?
Free T4 can be elevated in up to 12% of sick, euthyroid cats. Free T4 should be measured in
combination with TT4. If the fT4 is high and TT4 is in the upper half of the normal range or
above, the cat is probably hyperthyroid. If the fT4 is high and TT4 is in the lower half of the
normal range, the cat is probably not hyperthyroid.
14. How can a pertechnetate scan help in the diagnosis of hyperthyroidism?
In a pertechnetate or technetium scan, radiolabeled pertechnetate is injected intravenously
and is concentrated by the thyroid gland. The scan can help to confirm a diagnosis of hyperthy-
roidism, raise the suspicion of malignant disease, and locate all abnormal tissue (even intratho-
racic). For definitive diagnosis of malignancy, histopathology is required.
15. What are the three most important factors to assess in hyperthyroid patients?
Hyperthyroidism, if left untreated, eventually kills the patient. The two major organ systems
most affected are the heart and kidneys. Another factor to assess, which has been underappreci-
ated in thyrotoxicosis, is systemic hypertension.
16. How does hyperthyroidism affect the heart?
In cats with mild hyperthyroidism, the heart may be normal or have a slightly increased rate.
As the disease progresses, tachycardia, gallop rhythms, myocardial hypertrophy, or, in rare cases,
dilation develops. Congestive heart failure may be seen in some cats. Echocardiography cannot
differentiate between hypertrophic changes due to hyperthyroidism and primary hypertrophic
cardiomyopathy. Hyperthyroidism-induced hypertrophic changes revert to normal in the majority
of treated patients within 6 months.
17. How does hyperthyroidism affect the kidneys?
The kidneys are a common site of geriatric disease in general, and a "normal" progressive loss
of renal reserve occurs as the cat ages. Hypertension secondary to hyperthyroidism speeds the loss
of nephrons. In the early stages of hyperthyroidism, increased cardiac output from hyperdynamic
cardiac function increases glomerular blood flow and glomerular filtration rate (GPR). This im-
proved function can mask low-grade renal insufficiency, and azotemia may not be detected until
the cat is euthyroid. Renal disease in the aged patient can be insidious and difficult to detect accu-
rately by laboratory testing, and hyperthyroidism can mask renal disease. Many cats with hyper-
thyroidism present with normal kidney laboratory values but are bordering on kidney failure.
Hyperthyroidism can mask renal disease by increasing cardiac output and systemic blood pres-
sure, thus abnormally increasing renal perfusion and GPR. If a cat treated for hyperthyroidism
(medically, surgically, or with radioiodine) has "masked" kidney disease, renal failure may result
when blood pressure and renal blood flow return to normal and can be life-threatening.
18. Howcan underlying renal disease be detected?
A methimazole challenge (administration of therapeutic doses of methimazole for 30 days)
may be a reversible way to assess cats with suspected renal disease (see questions about treat-
ment). Many cats have an increase in creatinine or BUN with correction of hyperthyroidism but
show no clinical signs of renal disease; therefore, clinical status as well as blood and urine para-
meters must be assessed after the trial. No factors that predict whether renal failure will occur
have been identified. However, some authorities believe that a urine specific gravity < 1.035
before treatment may be predictive. The hyperthyroid condition must be addressed, but kidney
262
Hyperthyroidism
disease must be givenequal importancein the therapeuticplan. If surgeryor radioiodinetherapy
unmasks renal disease and failure occurs, low levels of L-thyroxine supplementation (0.1-0.2
mg/cat orally every 24 hr) can be used to increase renal perfusion and GFR to a safer, higher
level. Other kidneysupport measures also shouldbe part of the overall treatment.
19. How common is hypertension in hyperthyroidism?
Systemic hypertension is detected in up to 87% of hyperthyroidcats and may be one of the
most significant pathophysiologic factorsin hyperthyroidism. Useof newbloodpressuredetection
systems may better define the importanceof high blood pressure in cats as clinicians obtain both
diastolic and systolic pressures in a more reliable and convenient manner (see Chapter 63). This
manifestation appearsto be causedby a combination of a hyperdynamic cardiac state, sodiumre-
tention, glomerularcapillaryandarteriolarscarring,lowlevelsof renal vasodilators, lossof the au-
toregulation of glomerularbloodpressure, and activation of the renin-angiotensin system.
20. How is hyperthyroidism treated?
Radioiodine, surgery, and medical management are options. But it is also important to prac-
tice a high level of geriatric medicinewhen a treatment protocol for hyperthyroidismis designed.
Hyperthyroid cats are commonlyover 13years old, which makes treatment of the whole cat as a
senior patient a priority.
21. How does radioiodine work? How successful is it?
Radioiodine(1
31
1) is highly selectivein killing adenomatousor hyperplastictissue wherever
it is located, and response rates are high (> 95%). The abnormal tissue concentrates the radioio-
dine and is killed by the radioactivity, whereas normal, atrophied tissue does not take up the ra-
dioiodineand is spared. Normal thyroid function returns in most patients within 30-90 days, but
up to 6 monthsmay be required.A second treatmentis neededin only about 2%of patients. Even
compromisedpatients, when given supportivecare to address concurrent disease, respond favor-
ably to
131
1. Length of stays for radioiodinevary becauseof individual interpretationof the radia-
tion safety policy by each state and federal regulatory agencies. The shortest stay is 2 days in
Florida, and the longest stays are up to 4 weeks. The averagestay is 7-10 days in most states. The
cost for the procedure ranges from $750-$1,600+, depending on the length of stay and what is
includedin the treatment protocol.
22. Does previous medical treatment interfere with
131
1therapy?
Effectiveuptake of radioiodineby the abnormal thyroidtissue determines the efficacyof the
treatment. Because hyperthyroidmedicationmay interfere, it should be stopped 3-5 days before
radioiodine treatment. Recent evidence suggests that it may be possibleto continue methimazole
until the time of 131I administration. However, if the cat is not compromisedby discontinuanceof
antithyroid medication, stopping for a few days before radioiodine treatment is prudent until
more informationis gained. After methimazoleis discontinued, thyroid hormone returns to high
concentrationsin 24-72 hours.
23. What adverse effects and complications may be seen with
131
1therapy?
Side effects of treatment are few, rare, and transient; dysphagia and voice change have been
documented. Clinical hypothyroidismmay occur in about 2% of I3II-treated cases.
24. Can surgery be used for treatment of hyperthyroidism?
If radioiodineis not available, surgeryis the only other option for definitivetherapy in stable
patients. Success depends on the competence of the surgeon, the stability of the patient, and a
provensurgical protocol. Surgery misses ectopic hyperthyroidtissue, and the only recourse is to
treat either medically or with radioiodine. Because ectopic tissue is relatively uncommon,
surgeryleads to remissionin approximately 95%of cases. The recurrencerate after surgeryis ap-
proximately5-10%, dependingon the technique used.
Hyperthyroidism 263
25. What risks are associated with surgery?
Surgery and anesthesia in a compromised hyperthyroid patient have inherent risks and may
cause iatrogenic injury to vital tissues (e.g. damage to the recurrent laryngeal nerve(s), leading to
laryngeal paralysis, or removal of all parathyroid tissue, leading to hypocalcemia). With experi-
enced surgeons, the rate of side effects is low 10%). Ideally, patients should be treated med-
ically to resolve the hyperthyroidism before surgery to make them better anesthetic and surgical
candidates. A thorough physical examination and evaluation of cardiac status are paramount. Do
not use atropine in the anesthetic protocol! If the heart rate is dramatically elevated, medications
such as propanolol (2.5-5 mg/cat every 8-12 hr to effect) or atenoiol (6.25 mg/cat every 12-24 hr
to effect) may be needed to prevent arrhythmias and help contol heart rate and hypertension.
26. Does a low serum TT4 after radioiodine therapy or surgery necessarily mean that the
cat is hypothyroid?
The diagnosis of clinical hypothyroidism must be made by a combination of thyroid testing
and clinical signs such as lethargy, obesity, nonpruritic seborrhea sica, poor hair coat, hypother-
mia, and bradycardia. Only if these clinical signs are seen in combination with a low TT4 or, ide-
ally, ff4 should thyroid supplementation (L-thyroxine, 0.1 mg orally every 24 hr) be initiated.
27. Can hyperthyroidism be treated medically?
In general, antithyroid medications are used in three scenarios:
1. As long-term therapy when
131
1treatment and surgery are not possible.
2. As short-term therapy preoperatively or before J31I treatment to make the patient a better can-
didate for surgery or prolonged hospitalization. Because anesthesia can worsen hyperthyroidism-in-
duced cardiac abnormalities, cats should be rendered euthyroid before surgery, if possible.
3. As short-term therapy to create a temporary euthyroid state in order to judge the effect of
permanent correction of hyperthyroidism.
28. How effective is medical therapy?
Methimazole, which lowers circulating thyroid hormone concentrations by blocking T3 and T4
synthesis, is used most frequently. Medical therapy with methimazole is successful if the patient is
stable, the client is compliant, the clinician is vigilant inperforming routine blood testing (CBC, blood
chemistry, and TT4levels) to make medication adjustments, and the patient tolerates the medication.
Unfortunately, if any of the above criteria are not met, treatment may not be ideal. Methimazole is ef-
fective in approximately 87% of cats. Giving pills to feline patients and lack of follow-up testing seem
to be the biggest challenge to this life-long therapy. Short-term therapy is relatively inexpensive, but
long-term therapy and lab tests performed for the life of the patient can be quite expensive.
29. What methimazole treatment regimen should be used?
For mild hyperthyroidism (cats that have mild clinical signs and normal or mildly elevated
TT4 values), administer methimazole at 2.5-5 mg orally every 24 hr for 7-10 days. TT4 concen-
tration, liver enzyme activities, and CBC are rechecked at that time. Timing of the post-pill TT4
determination does not matter. Ideally, the TT4 value should be in the lower half of the normal
range. An increase to twice-daily dosing may be needed. During the initial 3 months, CBC, liver
enzymes, and TT4 should be monitored every 2-3 weeks to assess control and monitor for seri-
ous hematologic side effects. For severe hyperthyroidism (cats with severe clinical signs and ele-
vated TT4 usually twice the high-normal value), administer methimazole at 5 mg orally every 12
hr for 7-10 days. The first recheck should be at that time, with subsequent rechecks every 2-3
weeks as for mild disease. Increasing the dose and frequency to every 8 hr depends on the reduc-
tion of the TT4 value and clinical signs.
30. After the initial 2-3 months, how should methimazole therapy be monitored?
After the initial period, a TT4 should be measured every 3-6 months to assess control and
adjust methimazole dosage as necessary. Unless clinical signs indicate the possible presence of a
264 Hyperthyroidism
blood dyscrasia or hepatopathy, CDC and liver enzymes no longer need be reassessed because
the likelihood of developing serious hematologic adverse effects at this point is small.
31. What clinical adverse effects are seen with methimazole? How common are they?
Clinical side effects occur in approximately 18% of cats overall and include anorexia (II %),
vomiting (II %), lethargy (9%), excoriation of the face and neck (2%), bleeding (2%), and icterus
(1.5%). Anorexia, vomiting, and lethargy typically occur during the first month and tend to re-
solve despite continuing drug administration. Treatment with methimazole should be perma-
nently stopped in cats that develop hepatopathy or bleeding tendency or excoriate their face or
neck. Myasthenia gravis has been reported after methimazole treatment in 4 cats.
32. What kind of hematologic adverse effects may be seen? How common are they?
Eosinophilia (11% of cats), lymphocytosis (7%), leukopenia (5%), thrombocytopenia (3%),
and agranulocytosis (2%) may occur. The milder adverse effects-eosinophilia, lymphocytosis,
and leukopenia-are usually noted within 1-2 months of initiation of treatment and are transient
despite continued therapy. The more serious complications (thrombocytopenia, agranulocytosis)
typically occur within the first 3 months of therapy and require discontinuation of methimazole.
33. What immunologic adverse effects may occur? How significant are they?
Immunologic effects, including positive antinuclear antibodies (ANA) and positive direct
antiglobulin test (Coombs' test), have been noted. The risk of developing a positive ANA appears
to increase with length of therapy and dose. Despite the presence of these abnormalities, how-
ever, no cat has shown clinical signs of a lupus-like syndrome (e.g., dermatitis, polyarthritis,
glomerulonephritis, thrombocytopenia, fever) or hemolysis.
34. What other medical therapies are available?
Calcium ipodate, a radiopaque organic iodine agent, was used with some success but is no
longer available. Carbimazole is metabolized to methimazole. When used at the same doses de-
scribed for methimazole in question 29, carbimazole is sometimes tolerated by cats showing gas-
trointestinal signs when treated with methimazole. Cats that have immunologic reactions to
methimazole probably will react also to carbimazole. The drug must be formulated for use. The
beta-adrenergic blockers (e.g., propranolol) have no effect on thyroid hormone concentration but
decrease the neuromuscular and cardiovascular effects of hyperthyroidism, such as hyperex-
citability, hypertension,and cardiac hypertrophy. These agents can be used in combination with
an antithyroid drug or alone if a patient cannot tolerate antithyroid medications. They can be
helpful in preparing a patient for thyroidectomy or radioactive iodine by making the cat a better
candidate for surgery or hospitalization.
35. What is the prognosis of treated hyperthyroidism?
With any type of treatment for hyperthyroid disease, the patient must be assessed thoroughly.
Geriatric-related disease must be evaluated and treated along with hyperthyroidism. Hyper-
thyroidism is a killing disease and must be treated.
Medical treatment: guarded to very good, depending on medication regulation and drug
side effects.
Surgical treatment: guarded to very good, depending on surgical protocol, competency of
the surgeon, and follow-up care.
Radioiodine: excellent with a few exceptions. The quality of the
131
1protocol and hospital-
ized patient support is important. A 95% cure rate has been reported with one treatment.
BIBLIOGRAPHY
I. Atkins CE: Thyrotoxic heart disease. In August JR (ed): Consultations in Feline Internal Medicine. 3rd
ed. Philadelphia. WB. Saunders. 1997. pp 279-285.
2. Behrend EN: Medical therapy offeline hyperthyroidism. Comp Cont Educ Pract Vet 21:235-244, 1999.
Hyperadrenocorticism 265
3. Broussard JD, Peterson ME, Fox PR: Changes in clinical and laboratory findings in cats with hyperthy-
roidism from 1983 to 1993. J Am Vet Med Assoc 206:302-305, 1995.
4. Kass PH, Peterson ME, Levy J, et al: Evaluation of environmental, nutritional, and host factors in cats
with hyperthyroidism. J Vet Intern Med 13:323-329, 1999.
5. Mooney CT, Thoday KL, Doxey DL: Carbimazole therapy of feline hyperthyroidism. J Small Anim
Pract 33:228-235,1992.
6. Peterson ME, Becker DV: Radioiodine treatment of 524 cats with hyperthyroidism. J Am Vet Med Assoc
207:1422-1428,1995.
7. Peterson ME, Kintzer PP, Hurvitz AI: Methimazole treatment of 262 cats with hyperthyroidism. J Vet
Intern Med 2:150-157, 1988.
8. Peterson ME: Hyperthyroidism. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal
Medicine, 5th ed., Phildelphia, W.B. Saunders, 2000, pp 1400-1419.
9. Peterson ME. Update on feline hyperthyroidism. Proceedings of the 18th Annual Veterinary Medical
Forum, ACVIM, Seattle, 2000, pp 654-656.
10. Peterson ME, Graves TK, Gamble DA: Triiodothyronine (TJ) suppression test: An aid in the diagnosis of
mild hyperthyroidism in cats. J Vet Intern Med 4:233-238, 1990.
I I. Welches CA, Scavelli TD, Matthiesen, et al: Occurrence of problems after three techniques of bilateral
thyroidectomy in cats. Vet Surg 18:392-396, 1989.
54. HYPERADRENOCORTICISM
Ellen N. Benrend, V.M.D., M.S., pn.D.
1. What is feline hyperadrenocorticism?
Classically, feline hyperadrenocorticism has been synonymous with Cushing's syndrome,
which is caused by excessive secretion of cortisol from the adrenal glands. Technically, hypera-
drenocorticism also applies to adrenocortical tumors that secrete any hormone. Tumors that se-
crete aldosterone and progesterone have been reported.
2. How common is feline hypercortisolism? Describe the pathophysiology.
Confirmed, naturally occuning hypercortisolism is rare and has been reported in approximately
88 cats since 1975. Hypercortisolism can be caused either by a pituitary tumor that excessively se-
cretes adrenocorticotropin (ACTH), which stimulates secretion of cortisol, or an adrenal tumor that
autonomously secretes cortisol. Pituitary-dependent hypercortisolism (PDH) is more common, ac-
counting for approximately 85% of cases; the remaining 15%are due to adrenal tumors.
3. What types of pituitary and adrenal disease can be present?
Pituitary microadenomas, macroadenomas, and carcinoma (I case) have been reported.
Because clinical signs such as anorexia and disorientation, which frequently are associated with
macroadenomas in dogs, are rare in cats, the majority of pituitary tumors probably are microade-
nomas. Approximately 50% of adrenal tumors are benign, and 50% are malignant.
4. What is the common signalment for cats with hypercortisolism?
There is no known breed or sex predisposition. Hypercortisolism is a disease of older cats;
the average age is 10 years with a reported range of 4.5-15 years.
5. What historical findings are commonly associated with hypercortisolism?
Polyuria/polydipsia, polyphagia, weight loss, and lethargy are the most common historical
findings. Hypercortisolemic cats without diabetes mellitus can be polyuric/polydipsic.
Inappetence in hypercortisolemic dogs suggests the presence of a pituitary macroadenoma;
whether the same is true in cats remains unclear.
266 Hyperadrenocorticism
Clinical Findings in Cats with Spontaneous Hyperadrenocortisolism
ANDING NUMBEROF CATS(%)
History
Polyuria/polydipsia
Polyphagia
Weight loss
Lethargy
Weight gain
Depression
Abnormal gait
Constipation
Decreased appetite
Panting
Diarrhea
Vomiting
Physical examination
Enlarged abdomen
Alopecia
Thin skin
Muscle atrophy
Rough or dry haircoat
Obesity
Hepatomegaly
Easily tom skin
Seborrhea
Palpable abdominal mass
Cutaneous hyperpigmentation
Folded pinnae
52/58 (90)
40/58 (69)
20/58 (34)
18/58 (31)
6/58 (10)
3/58 (5)
3/58 (5)
2/58 (3)
2/58 (3)
2/58 (3)
2/58 (3)
1/58 (2)
41/55 (75)
34/58 (59)
25/55 (45)
24/58 (41)
17/55 (31)
17/58 (29)
16/55 (29)
15/58 (26)
4/55 (7)
3/55 (5)
2/55 (4)
1/55 (2)
* This informationreflects a summaryof availbledata fromapproximately 58 cats. In at least one instance,a
few cats were included in two reports. Because it was not always possible to determine whicb data per-
tained to which cat in the reports, some cats may have been included twice. Because this duplication ap-
plies to 2 or 3 cats, the data shouldnot be greatlyskewed.
FromBehrendEN, Kemppainen RJ: Felineadrenocorticaldisease. InAugustJR (ed): Consultations in Feline
Internal Medicine,4th edition. Philadelphia, WBSaunders, 2001.
6. What are the common physical examination fmdings associated with hypercortisolism?
An enlarged abdomen is the most common finding, followed by alopecia (spontaneous) and
thin skin (see table above). Overall, skin changes of some form are a prominent finding. Besides
spontaneous alopecia, hair may fail to regrow after clipping. Easily tom skin can be a dramatic
finding, and routine hospital or grooming procedures can cause large wounds. The presence of
infections or abscesses can be a historical or physical examination finding; affected sites include
the upper and lower urinary tract, upper and lower respiratory tract, skin, and oral cavity. Unusual
infections such as disseminated candidiasis and disseminated toxoplasmosis may occur.
7. What abnormalities of hypercortisolism are commonly noted on complete blood cell
count and serum biochemical panel?
Based on experiences with dogs, a stress leukogram might be expected but is not common. Of
the typical changes on stress leukogram, lymphopenia is the most consistent. Hyperglycemia is
the most common biochemical change, and the majority of cats (82%) are diabetic. However, al-
though cortisol can antagonize the actions of insulin, not all diabetic, hypercortisolemic cats are
insulin-resistant. Elevations in liver enzyme activities occur in just under 50% of cases and may be
seen with or without concomitant diabetes mellitus. Elevations in alkaline phosphatase activity are
not as common as in dogs, because cats are believed not to have a corticosteroid-induced isoen-
zyme. Hypercholesterolemia is also a common finding, perhaps occurring in as many as 50%.
Hyperadrenocorticism
Clinicopathologic Results in Cats with Spontaneous Hyperadrenocortisolism
TEST NUMBEROFCATS(%)
267
Completebloodcount
Lymphopenia
Eosinopenia
Neutrophilia
Monocytosis
Anemia
Leukocytosis
Neutropenia
Lymphocytosis
Biochemical profile
Hyperglycemia
Diabetes mellitus
Elevated alanine aminotransaminase
Elevated aspartate aminotransaminase
Elevated alkaline phosphatase
Decreased total thyroxine
Elevated blood urea nitrogen
Elevated total bilirubin
Hypocalcemia
Elevated creatinine
Hypercalcemia
23/36 (64)
14/36 (39)
14/36 (39)
6/36 (17)
4/32 (13)
4/33 (12)
2/36 (6)
l/36 (3)
49/53 (92)
47/57 (82)
17/34 (50)
4/9 (44)
12/38 (32)
3/10 (30)
7/32 (22)
3/17 (18)
3/24 (13)
3/25 (12)
1/24(4)
FromBehrendEN, Kemppainen RJ: Felineadrenocortical disease.InAugustJR (ed): Consultations in Feline
Internal Medicine, 4th edition.Philadelphia, WBSaunders,2001.
8. How can abdominal radiography help in the diagnosis?
Hepatomegaly is a common finding, occurring in approximately 75% of hypercortisolemic
cats. If an adrenal tumor is present, it may be seen. Adrenal calcification may be visualized in
adrenal tumors, but since it can be seen in up to 30% of normal cats, its detection does not mean
that an adrenal tumor is present.
9. What about other means of abdominal imaging?
On abdominal ultrasonography, bilaterally enlarged adrenal glands are consistent with PDH.
However, feline adrenal glands can be difficult to image, and enlargement has not always been
noted in cats with PDH. An adrenal tumor, if present, may be detected. Computed tomography
also can be used to image the pituitary gland or the adrenal glands.
10. What tests are available for the diagnosis of hypercortisolism?
Definitive diagnosis requires adrenal testing. Screening tests used to determine whether the
disease is present are the urine cortisol:creatinine ratio (DCCR), low-dose dexamethasone suppres-
sion test (LDDST), high-dose dexamethasone suppression test (HDDST), ACTH stimulation test,
and the combination test. An ultra-high-dose dexamethasone suppression test, endogenous ACTH
level determination, or CT scan can beused to differentiate between PDH and adrenal tumor.
11. Why are results of these tests difficult to interpret?
First, results in normal cats and cats with hypercortisolism appear to be more variable than in
dogs. Second, few studies have been published examining the specificity and sensitivity of these
tests in cats.
12. How accurate is VCCR in cats?
Measurement of VCCR has received little study in cats. A ratio within the normal range rules
out hypercortisolism with high accuracy, possibly close to 100%. In contrast, determination of an
268 Hyperadrenocorticism
elevated ratio is nondiagnostic because cats with hypercortisolemia or nonadrenal illness may
have an elevated ratio. When an elevated ratio is found in a suspect cat, more definitive screening
tests should be performed.
Screening and Differentiating Testfor Hypercortisolism*
TEST PROTOCOLS tNTERPRETATION
VCCR
ACTHstimula-
tion test
LODST
HDDST
VHDDST
Combination
test
Endogenous
ACTHmea-
surement
Collect urine by free catch
or cystocentesis. Centrifuge
sample and submit super-
natant.
Administer O. I25 ug of synthetic
ACTHt IV. Draw blood samples
before and I hr after injection.
Administer dexamethasone at 0.01
mglkg IV. Collect blood samples
before and 4 and 8 hr after injection.
Perform like LDDST, but administer
O. I mglkg dexamethasone.
Perform like LDDST, but administer
1.0 mg/kg dexamethasone.
Take blood sample, and administer
1.0 mglkg dexamethasone IV. Take
blood sample 4 hr later, and imme-
diately performACTHstimulation
test as above.
Proper sample handling is critical.
Collect sample in EDTA, add
trasylol.f and spin within 15 min.
Place plasma in plastic tubes and
mail cold sample overnight on ice.
Sample can be stored with refrigeration
for < I day; it should be frozen for
longer storage.
Normal ratio 30) rules out hyper-
cortisolism; with elevated ratio,
diagnosis of hypercortisolism must
be confirmed with another test.
Normal serum cortisol concentration at
baseline = 10- I 10nmollL; after ACTH,
normal value = 21D-330nmollL. A
post-ACTHlevel> 330 nmollL is con-
sistent with hypercortisolism.
After dexamethasone, serum cortisol con-
centration should be < 30 nmol/L.
Normal suppression rules out diagnosis
of hypercortisolism.
Lack of suppression at 8 hr is consistent
with hypercortisolism. Suppression at
4 hr with lack of suppression at 8 hr is
consistent with PDH.
Suppression at 4 or 8 hr to < 30 nmollL
or to < 50% baseline is consistent with
PDH.
Diagnosis of hypercortisolismis based on
ACTHstimulation portion, as above.
Suppression to < 30 nmollL or < 50%
baseline after dexamethasone is con-
sistent with PDH. If no suppression
is seen, another differentiation test
must be done.
Plasma ACTHconcentrations should be
in mid to above-normal range (> 15
pg/ml) in cats with PDH and low in
cats with adrenal tumors 10 pg/ml).
VCCR =urinarycortisol:creatinine ratio, ACTH =adrenocorticotropin, LDDST=low-dose dexamethasone
suppression test, HODST = high-dose dexamethasone suppresssion test, VHODST = ultra-high-dose dexam-
ethasonesuppression test, PDH=pituitary-dependent hypercortisolism, IV=intravenously, EDTA =ethyl-
enediamine tetraacetic acid.
*The valuesgivenfor interpretation are thoseusedbythe Auburn University Endocrine Diagnostic Service.
Checkwithyour ownlaboratory for their normalvalues. Toconvert cortisolto rng/dl, divideby 27.6.
t Cosyntropin, Organon, Inc., West Orange, NJ.
t Aspecialpreservative available from someendocrine diagnostic laboratories.
13, How should I use the ACTH stimulation test?
An elevated post-ACTH cortisol concentration (see table above) is consistent with a diagno-
sis of hypercortisolism, but it is present in only about 81% of affected cats. Repeat testing in a
previously negative cat may provide a positive result. The ACTH stimulation test has been shown
to give exaggerated results in some ill cats with nonadrenal disease, and false-positive test results
are possible. The ACTH stimulation test cannot be used to differentiate PDH from adrenal tumor.
14. Can a low-dose dexamethasone suppression test be used in cats?
After administration of a low dose of dexamethasone (see table in question 12),95% of hy-
percortisolernic cats fail to suppress (positive result). However, some ill cats with nonadrenal dis-
ease also have inadequate suppression on an LDDST. The chance for false-positive test results
limits the usefulness of LDDST in cats. However, because most hypercortisolemic cats have a
positive LDDST, the negative predictive value of the test can be valuable. If the LDDST is
normal, it is highly unlikely that the cat has hypercortisolism.
15. What is the diagnostic utility of the high-dose dexamethasone suppression test?
Because of the low specificity of the LDDST, the use of a higher dose of dexamethasone (see
table in question 12), which causes suppression more reliably in cats with normal adrenal function,
is recommended for screening purposes. When used as a screening test, a positive HDDST occurs
in about 80% of hypercortisolernic cats. False-negative results may occur because a high dose of
dexamethasone can cause cortisol suppression in some cats with early or mild hypercortisolism,
This test appears to be more specific than the LDDST, but extensive studies have not been done.
16. How can the ultra-high-dose dexamethasone suppression test be used?
An ultra-high dose can be used to differentiate PDH and adrenal tumor (see table in question
12). This test is used once a diagnosis of hypercortisolism has been confirmed by a screening
test. Suppression is consistent with the presence of PDH, but lack of suppression is consistent
with either PDH or ATand another differentiation test must be used.
17. Can determination of an endogenous ACTH concentration be used to differentiate AT
from PDH?
Once hypercortisolism is confirmed, plasma ACTH concentrations should be in the mid- to
above-normal range in cats with PDH and low in cats with adrenal tumor. This test has been
highly reliable in cats.
18. What is the combination test?
The combination of a high-dose dexamethasone suppression test and an ACTH stimulation
test (see table in question 12). Each part should be interpreted as if the test were done alone. with
the attendant caveats. In dogs, the combination test is hoped to be a screening test on the basis of
the ACTH stimulation test and a differentiation test on the basis of the high-dose dexamethasone
blood sample. Because most hypercortisolemic cats do not suppress after this dose of dexametha-
sone, the combination test is less likely to provide differentiation than it is in dogs. However, if
both limbs of the test are positive-lack of suppression and an increased ACTH response-the
diagnosis of hypercortisolism can be made with greater confidence.
19. What may be the ideal screening method for feline hypercortisolism?
Because feline hypercortisolism is an infrequent diagnosis and each test has potential for
both false-positive and false-negative results, confirmation of the diagnosis is best made by
demonstrating both an exaggerated cortisol response to ACTH and failure to suppress serum cor-
tisol on an HDDST.
20. What medications are used to treat hypercortisolism?
Mitotane, ketoconazole or metyrapone may be used. Experience with all 3 is limited in cats.
21. What is the mechanism of action of mitotane? How effective is it in cats?
Mitotane (Lysodren, Bristol-Meyers Oncology, Princeton, NJ) causes selective necrosis of
adrenocortical cells that secrete cortisol. Early reports suggested that mitotane was not as effective
270
in normal cats or cats with hypercortisolism as it is in dogs. However, mitotane therapy may be
successful with higher doses and/or longer induction periods than typically used for dogs.
22. Can ketoconazole therapy be used for this syndrome in cats?
Ketoconazole (Nizoral, Janssen, Titusville, NJ) decreases adrenal synthesis of cortisol
through inhibition of numerous enzymes and also may antagonize glucocorticoid receptors.
Ketoconazole has had mixed success in cats and commonly causes toxicity. In dogs with hyper-
cortisolism, ketoconazole is estimated to be efficacious in < 50% of cases; successful use in cats
also seems unlikely.
23. What is the mechanism of action of metyrapone? How effective is it?
Metyrapone (Metopirone, Novartis, E. Hanover, NJ) affects cortisol synthesis through inhi-
bition of an adrenal enzyme. Its use has been highly limited and has shown
mixed success, but currently it is the medical therapy of choice.
24. Can surgery be used for treatment of hypercortisolism?
Because of difficulties with medical therapy, the treatments of choice for adrenal tumor and
PDH are unilateral and bilateral adrenalectomy, respectively. Surgical management appears to be
highly effective overall; approximately 80% of patients survive for longer than 1 month.
25. What is the cause of postoperative mortality in cats with adrenalectomy? Howcan it be
prevented?
Death occurred within the first month in 5 cats, 4 that underwent bilateral adrenalectomy for
PDH, and 1 that underwent unilateral adrenalectomy for adrenal adenocarcinoma. Suspected
causes of death included hypoadrenal crisis, renal failure, development of chylothorax secondary
to extensive thrombosis of the cranial vena cava, severe pancreatitis and septic peritonitis. and
sloughing of large regions of skin. Administration of metyrapone to stabilize patients preopera-
tively and strict adherence to postoperative medical protocols may decrease mortality rates.
26. How should cats be treated intraoperatively?
Diabetic cats should receive 50% of their usual insulin dose on the morning of surgery. With
unilateral or bilateral adrenalectomy, treatment with glucocorticoids during and after surgery is
required. In cats with an adrenal tumor, the contralateral adrenal gland is atrophied because con-
stant negative feedback by the tumor to the pituitary gland decreases ACTH secretion. At the
time of anesthetic induction, a continuous intravenous infusion of hydrocortisone (625 mglkg/hr)
should be initiated and continued for 24--48 hours postoperatively. At that time, prednisone (2.5
mg/cat orally every 12 hr) should be instituted.
27. Describe long-term postoperative treatment.
In cats with unilateral adrenalectomy, recovery of the unaffected gland is expected with time,
and glucocorticoid therapy can be withdrawn slowly. Cats undergoing bilateral surgery should be
treated as for spontaneous hypoadrenocorticism. Mineralocorticoid replacement therapy should
be instituted when the hydrocortisone infusion is discontinued. Because some cats have died
postoperatively from suspected hypoadrenal crisis, the importance of continuing therapy must be
communicated to the owner.
28. What is the long-term prognosis for cats that survive the postoperative period?
For cats that live past the first month postoperatively, reported survival times range from 3 to
> 60 months. The cause of death is varied, including suspected hypoadrenal crisis, renal failure,
and expansion of a pituitary mass in cats that develop neurologic abnormalities.
29. Does diabetes mellitus resolve with treatment of hypercortisolism?
Whereas in dogs therapy for hypercortisolism alleviates insulin resistance but diabetes
mellitus typically persists, the disease resolves with successful treatment of hypercortisolism
in approximately 50% of cats. If the diabetes mellitus does not resolve, amelioration of the hy-
percortisolism should decrease insulin requirements.
30. How quickly sbould the clinical signs of bypercortisolism resolve once control is ob-
tained?
Clinical signs typically resolve 2-4 months after control of hypercortisolism.
31. Can adrenal tumors secrete bormones besides cortisol?
Progesterone-secreting and aldosterone-secreting adrenal masses have been reported in I
and 3 cats, respectively.
32. What clinical signs and pbysical examination findings may be seen with byperproges-
teronemia?
Clinical signs are similar to those of hypercortisolism: nonpruritic, bilaterally symmetrical
alopecia; polyuria/polydipsia; and aggression. Physical examination may reveal alopecia, a
greasy unkempt coat and scale, comedones at the oral commissures, thin skin with easily visible
blood vessels, and bruising at venipuncture sites.
33. Howcan a diagnosis of byperprogesteronemia be made?
The diagnosis is based on results of sex hormone concentration measurement before and
after a standard ACTH stimulation test (see table in question 12). Progesterone will be above
normal, at least in the post-ACTH sample.
34. Howshould a progesterone-secreting tumor be treated?
Adrenalectomy is the treatment of choice. No information is available about medical man-
agement. Postoperatively, glucocorticoid therapy may be required, at least temporarily. Pro-
gesterone can inhibit pituitary ACTH secretion, leading to atrophy of the normal gland.
Glucocorticoids need to be given until the gland recovers.
35. What bistorical complaints, clinical signs, and physical examination findings occur
with byperaldosteronism?
Polyuria, polydipsia, nocturia, generalized weakness, collapse, anorexia, weight loss, pendu-
lous abdomen, and blindness are reported by some owners. On physical examination, bilateral
retinal detachment, hypertension, pendulous abdomen, or heart murmur may be found.
36. Wbat abnormalities may be seen on a complete blood count and serum biochemical
profile?
The complete blood cell count is generally normal. Hypokalemia is a consistent serum bio-
chemical abnormality. Hypernatremia, increased serum bicarbonate, and elevated creatine phos-
phokinase (CPK) activity may be detected. Diabetes mellitus may result from the effect of
hypokalemia on insulin secretion. Glycosuria despite normoglycemia also has been observed.
37. How is the diagnosis ofbyperaldosteronism made?
Diagnosis of primary hyperaldosteronism is based on marked hyperaldosteronemia (at least
6 times higher than normal) in conjunction with hypertension, hypokalemia, inappropriate kali-
uresis (urinary fractional excretion of potassium at least 6 times normal), normal plasma renin
activity, ultrasonographic confirmationof an adrenal mass, or cytologic or histopathologic con-
formation of adrenal cortical neoplasia. Currently, a validated renin assay is not available for
cats. Without such an assay, diagnosis of primary hyperaldosteronism requires that all sec-
ondary causes (e.g., states associated with peripheral edema or liver failure) be ruled out. The
presence of renal failure presents a particular dilemma, because renal failure itself can lead to
this constellation of abnormalities. The magnitude of aldosterone elevation may be the key to
differentiation in such cats.
272 Hypoadrenocorticism
38. How is hyperaldosteronism treated?
Medical therapy has been only partially successful. Potassium supplementation should be
provided (2-6 mEq/day) to keep the serum potassium concentration in the normal range, if possi-
ble. The best initial medication for treatment of hypertension is the aldosterone antagonist spirono-
lactone (1-2 mglkg orally every 12hr), but it may not provide full control. Other antihypertensive
agents may be required in combination (see Chapter 63). Unilateral adrenalectomy to remove the
tumor is possible. All three cases reported have been due to carcinoma; cure may not be possible.
39. What is the prognosis?
It is difficult to make definitive statements based on results of only 3 cases, but medical ther-
apy was not highly successful in any cat. The one cat treated by adrenalectomy survived I year.
BIBLIOGRAPHY
1. Ahn A: Hyperaldosteronism in cats. Semin Vet Med Surg (Small Anim) 9:153-157,1994.
2. Behrend EN, Kemppainen RJ: Feline adrenocortical disease. In August JR (ed): Consultations in Feline
Internal Medicine, 4th ed. Philadelphia, W.B. Saunders, 2001.
3. Boord M, Griffin C: Progesterone secreting adrenal mass in a cat with clinical signs of hyperadrenocorti-
cism. J Am Vet Med Assoc 214:666--669, 1999.
4. Duesberg CA, Nelson RW, Feldman EC, et al: Adrenalectomy for treatment of hyperadrenocorticism in
cats: 10 cases (1988-1992). J Am Vet MedAssoc 207:1066-1070,1995.
5. Duesberg CA, Peterson ME: Adrenal disorders in cats. Vet Clin North Am Small Anim Pract 27:321-
348,1997.
6. Feldman EC, Nelson RW: Hyperadrenocorticism in cats. In Feldman EC, Nelson RW (eds): Canine and
Feline Endocrinology and Reproduction, 2nd ed. Philadelphia, W.B. Saunders, 1996, pp. 256-261.
7. Flood SM, Randolph JR, Geizer ARM, et al: Primary hyperaldosteronism in 2 cats. J Am Anim Hosp
Assoc 35:411-416,1999.
8. Jensen J, Henik RA, Brownfield M, et al: Plasma renin activity and angiotensin I and aldosterone concentra-
tions in cats with hypertension associated with chronic renal disease. Am J Vet Res 58:535-540, 1997.
9. Peterson ME, Randolph JR, Mooney CT: Endocrine diseases. In Sherding RG (ed): The Cat: Diseases
and Clinical Management, 2nd ed. New York, Churchill Livingstone, 1995, pp 1403-1506.
10. Schwedes CS: Mitotane (o,p'-DDD) treatment in a cat with hyperadrenocorticism. J Small Anim Pract
38:520--524,1997.
55. HYPOADRENOCORTICISM
Ellen N. Benrend, V.M.D., M.S., pn.D.
1. What constitutes the hypothalamic-pituitary-adrenal axis?
The hypothalamus secretes corticotropin-releasing hormone (CRR), which stimulates the
anterior pituitary to release adrenocorticotropin (ACTH). ACTH, in turn, causes the adrenal
glands to secrete cortisol. Cortisol then gives negative feedback to the hypothalamus and anterior
pituitary, inhibiting CRR and ACTH release, respectively.
2. Define hypoadrenocorticism.
Hypoadrenocorticism is the failure of the adrenal glands to produce adequate concentrations
of mineralocorticoids, glucocorticoids, or both. Spontaneous hypoadrenocorticism can be either
primary or secondary. With primary hypoadrenocorticism (Addison's disease), adrenal gland dys-
function causes glucocorticoid and mineralocorticoid deficiency. Spontaneous secondary hypoad-
renocorticism, due to reduced secretion of ACTH from the pituitary, has not been reported in cats.
Iatrogenic secondary hypoadrenocorticism can be caused by treatment with either glucocorticoids
or progestins, which lessen ACTH secretion by negative feedback. In spontaneous or iatrogenic
Hypoadrenocorticism 273
secondary hypoadrenocorticism, reduced circulating ACTH concentrations lead to atrophy of the
glucocorticoid-secreting zones of the adrenal cortex; aldosterone secretion is not affected.
3. How common is spontaneous primary hypoadrenocorticism? What causes it?
Naturally occurring hypoadrenocorticism is rare in cats, with 26 confirmed cases and 2 sus-
pected cases reported since 1983. Most cases are idiopathic, but 2 were traumatically induced,
and 2 were secondary to lymphoma. In 2 of 5 cases of idiopathic disease that went to necropsy.
lymphocytic infiltration of the adrenals was noted. This finding suggests that in some cats hypoa-
drenocorticism results from immune-mediated destruction of adrenal tissue.
4. What signalment findings are commonly associated with spontaneous primary hypoad-
renocorticism?
In 12 cats, the average age at presentation was approximately 5-6 years (range = 1.5-14
years), all were of mixed breeding, 7 were castrated males, and 5 were spayed females.
5. What historical findings are commonly associated with primary hypoadrenocorticism?
Anorexia and lethargy are the most common signs. Weight loss is also common; vomiting, a
waxing and waning course, previous therapeutic response, and polyuria/polydipsia are noted Jess
frequently. Clinical signs may be present for up to 100 days before diagnosis.
Clinical Findings in Cats with Spontaneous Hypoadrenocorticism
FINDING NUMBER OF CATS (%)
Historical complaints
Anorexia
Lethargy/depression
Weight loss
Vomiting
Waxingand waning course
Previous response to therapy
Polyuria/polydipsia
Sudden collapse/weakness
Physical examination findings
Dehydration
Weakness
Hypothermia
Increased capillary refill time
Weak pulse
Inability to rise
Painful abdomen
Bradycardia
Cool extremities
14/14 (100)
13/14 (93)
12/14 (86)
5/14 (36)
4/14 (29)
3/14 (21)
3/14 (21)
1114(7)
12/13 (92)
11/13 (85)
10/13 (77)
5/13 (38)
5/13 (38)
3/13 (23)
3/13 (23)
2/13 (15)
1/13 (8)
FromBehrend EN, Kemppainen RJ: Felineadrenocortical disease. InAugustJR(ed): Consultations in Feline
Internal Medicine, 4th ed. Philadelphia, w.B. Saunders, 2001.
6. What physical findings are commonly associated with primary hypoadrenocorticism?
On physical examination, dehydration, weakness and hypothermia are detected in the major-
ity of cases. Increased capillary refill time, weak pulses, inability to rise, painful abdomen, brady-
cardia, and cool extremities also have been observed (see table above).
7. What abnormalities of primary hypoadrenocorticism are commonly noted on complete
blood cell count and serum biochemical panel?
Routine blood work abnormalities may suggest hypoadrenocorticism but cannot be used to
make the definitive diagnosis. The most consistent abnormalities, as in dogs, are azotemia with
electrolyte changes, including hyperkalemia, hyponatremia, hypochloremia. and acidosis.
274
Hypoadrenocorticism
Hyperkalemia is typically mild and may not be detected until days after initial presentation. The
highest reported potassium value to date is 6.2 mEqlL. Hyponatremia ranges from mild to
marked. Although detection of eosinophilia and lymphocytosis (i.e., lack of a stress leukogram)
may be a clue to the presence of hypoadrenocorticism in a sick, stressed cat, these findings are
not common. An increased red blood cell count, if seen, is most likely a result of dehydration.
Clinicopathologic Results in Cats with Spontaneous Hypoadrenocorticism*
TEST NUMBEROFCATS(%)
Complete blood count
Anemia
Lymphocytosis
Eosinophilia
Biochemistry profile
Hyponatremia
Hyperkalemia
Azotemia
Hypochloremia
Decrease in total carbon dioxide
Elevatedalanine aminotransferase
Elevatedalkaline phosphatase
Increasedtotal bilirubin
Increased serumcalcium
4/14 (29)
2/13 (15)
1/13(8)
15/15 (100)
15/16 (94)
14/15 (93)
11/14 (79)
6/14 (43)
2/12 (17)
1/12 (8)
1/12 (8)
1/12 (8)
*Includes twoseparate presentations of the samecat.
FromBehrend EN, Kemppainen RJ: Felineadrenocortical disease. InAugust JR (ed): Consultations in Feline
Internal Medicine, 4th ed. Philadelphia, W.B. Saunders, 2001.
8. Many cats with primary hypoadrenocorticism have dilute urine. What is the signifi-
cance of this finding?
Of I I cats for which urine specific gravity was determined at presentation, 7 had inappropri-
ate urine concentration. Whether this finding represents true renal disease is unknown. Hypo-
natremia can cause poor urine concentrating ability by potentially leading to renal medullary
washout. Urine specific gravity and renal function must be evaluated after sodium repletion to
determine the true urine concentrating ability.
9. Can radiography or electrocardiography help in the diagnosis of primary hypoadreno-
corticism?
As with blood work, the changes found may suggest hypoadrenocorticism but are not diag-
nostic. Radiography may reveal decreased lung opacity and vascular markings, suggesting hy-
poperfusion, and microcardia. Electrocardiographs are often normal; bradycardia and atrial
premature contractions have been detected in some cats. In contrast to dogs with primary hypoa-
drenocorticism, tall, peaked T waves or diminished P waves due to hyperkalemia have not been
detected in cats, possibly because the degree of hyperkalemia is relatively mild.
10. How is the diagnosis of hypoadrenocorticism made?
Definitive diagnosis is based on results of an ACTH stimulation test. To perform the test, ad-
minister 0.125 mg of synthetic ACTH (Cosyntropin, Organon Inc, West Orange, NJ) intra-
venously. Blood samples are drawn before and I hour after the injection. Serum cortisol
concentration before and after ACTH are very low or nondetectable. Differentiation between pri-
mary and secondary hypoadrenocorticism can be made on the basis of endogenous ACTH con-
centrations (see Chapter 54 for sample handling). Increased endogenous ACTH confirms adrenal
failure with lack of negative feedback on the pituitary; with secondary hypoadrenocorticism, en-
dogenous ACTH is very low or non-detectable. However, differentiation is rarely necessary in
cats because only iatrogenic secondary hypoadrenocorticism has been described.
Hypoadrenocorticism 275
11. Howis hypoadrenocorticism treated?
Treatment depends on whether a hypoadrenal crisis is present or whether the patient is rel-
atively stable.
12. What abnormalities need to be addressed therapeutically if a patient is in crisis?
Which is the most important?
Therapy for a hypoadrenal crisis is directed at expanding fluid volume, supplying exogenous
glucocorticoids, and correcting electrolyte abnormalities and acidosis. Fluid replacement is the
most important aspect of treatment. Fluids should be given intravenously at an approximate rate
of 40 ml/kg over 2--4hours. The fluid of choice is 0.9% sodium chloride (NaCI), which provides
both sodium and chloride but is potassium-deficient. However, if 0.9% NaCI is not available,
Ringer's solution or lactated Ringer's solution is acceptable because potassium concentrations
are low and administration dilutes serum potassium concentrations. Correction of hyponatremia
should be slow to avoid neurologic sequelae.
13. What glucocorticoidshould be administered to a patient with a hypoadrenal crisis?
Prednisolone sodium succinate (4-20 mglkg IV) or dexamethasone (0.1-2.0 mglkg IV) may
be used. Prednisolone sodium succinate is the quickest-acting, followed by dexamethasone
sodium phosphate and then dexamethasone. If dexamethasone sodium phosphate is used, make
sure that the dose is calculated on the basis of the active ingredient. One milliliter of dexametha-
sone sodium phosphate usually has a total concentration of 4 mg/rn1but only 3 mg/ml of dexam-
ethasone. The 3 mg/ml figure should be used in calculations. Because prednisolone crossreacts
with cortisol on most assays, an ACTH stimulation test should not be performed for 12 hours
after its administration. The decision of which glucocorticoid to use depends on patient status.
Because prednisolone is the most rapidly acting, it is the glucocorticoid of choice in severe crisis.
Adrenal testing can be performed once the patient is stabilized.
14. What other treatments may be necessary for a hypoadrenal crisis?
Hyperkalemia may need to be addressed specifically, but this is unlikely given the mild alter-
ations in potassium typically seen in cats with spontaneous primary hypoadrenocorticism.
Intravenous administration of fluids alone causes rapid lowering of the potassium. If the potas-
sium concentration is > 8.5 mEqlL, specific treatment options include:
10% calcium gluconate (0.5-1.0 mglkg IV, given slowly over 10-20 minutes);
Sodium bicarbonate (2-3 mEqlkg IV over 30 minutes or dose based on serum bicarbonate
deficit to correct acidosis); or
Combination of glucose and insulin (0.5 unitslkg regular insulin IV followed by 1-1.5 gm
dextrose per unit insulin added to the IV fluids and administered over 4-6 hours).
Calcium protects the heart from the effects of the potassium, whereas the others shift potas-
sium from the serum into cells. Sodium bicarbonate also helps to correct acidosis but is rarely re-
quired because the acidosis is usually mild and responds well to fluid therapy.
15. Compare the response of dogs and cats to treatment.
Dogs respond rapidly whereas cats usually remain weak, lethargic and depressed for 3-5
days despite institution of appropriate therapy.
16. What long-term treatment is needed in the stable patient?
Any combination of a glucocorticoid and mineralocorticoid can be used, but complications
of glucocorticoid therapy, such as diabetes mellitus, may be more likely if injectable glucocorti-
coids are used. Of 4 cats treated with a combination of f1udrocortisone (Florinef, Apothecon, The
Netherlands) at 0.1 mg/cat/day orally and prednisone at 1.25mg/cat/day orally, one cat died sud-
denly of unknown causes after 47 days and the other 3 cats survived for at least 3 months. A com-
bination of desoxycorticosterone pivalate (DOCP; Percorten-V, Novartis Animal Health, Inc,
Greensboro, NC) at 10-12.5 mg/cat/month intramuscularly and methylprednisolone acetate at 10
276
Diabetes Mellitus
mg/cat/month intramuscularly also has been used. Approximately 50% of dogs receiving f1udro-
cortisone may not require further exogenous glucocorticoids, but whether this finding applies to
cats is unknown. Although some dogs taking DOCP have not received glucocorticoid therapy.
this practice is not recommended because DOCP has no glucocorticoid activity and the patient
will always be glucocorticoid-deficient.
17. Are treatment adjustments needed during times ofstress?
During times of stress, glucocorticoid requirements increase. On days of planned increased
stress, the daily glucocorticoid dose should be doubled or, if the cat is not receiving glucocorti-
coids or is receiving an injectable form, prednisone should be administered at a dose of 0.2-0.4
mglkg orally every 24 hr.
18. What is the prognosis for cats with hypoadrenocorticism?
For 6 cats that received long-term treatment with either DOCP or f1udrocortisone for con-
firmed, idiopathic primary hypoadrenocorticism, the median survival was 34 months. In one cat
with confirmed, traumatically induced hypoadrenocorticism, medication was eventually discon-
tinued after adrenal recovery.
BIBLIOGRAPHY
I. Behrend EN, Kemppainen RJ: Feline adrenocortical disease. In August JR (ed): Consultations in Feline
Internal Medicine, 4th edition, Philadelphia, WB Saunders, 2001.
2. Chastain CB, Graham CL, Nichols CE: Adrenocortical suppression in cats given megestrol acetate. Am J
Vet Res 42:2029-2035, 1981.
3. Hypoadrenocorticism in cats. In Feldman EC, Nelson RW (eds): Canine and Feline Endocrinology and
Reproduction, 2nd edition, Philadelphia, WB Saunders, 1996, pp 302-306.
4. Myers NC, Bruyette OS: Feline adrenocortical diseases: Part 11- hypoadrenocorticism. Seminars Vel Med
Surg (Small Animal) 9:144-147,1994.
5. Parnell NK, Powell LL, Hohenhaus AE, et al: Hypoadrenocorticism as the primary manifestation of lym-
phoma in 2 cats. J Am Vet Med Assoc 214:1208-1211, 1999.
6. Peterson ME, Greco OS, Orth ON: Primary hypoadrenocorticism in ten cats. J Vet Int Med, 3:55-58, 1989.
56. DIABETES MELLITUS
Jill Lurye, D.V.M., and Ellen N. Behrend, V.M.D., M.S., Ph.D.
1. What is diabetes mellitus?
Diabetes mellitus (DM) is a metabolic disease characterized by an absolute or relative insulin
deficiency that results in abnormal fuel metabolism, particularly of glucose and fat. Prolonged hy-
perglycemia is the most obvious consequence of insulin deficiency, but ketoacidosis and other
manifestations of accelerated catabolism also occur. Because all cells require energy utilization,
OM can result in abnormalities in most body systems, some of which can be fatal if untreated.
2. What are the forms of primary diabetes mellitus in humans?
Diabetes mellitus is classified as type I or type 2. Type 10M. also commonly called juve-
nile-onset diabetes because typically it is first evident in childhood, results from destruction of
> 80-85% of pancreatic islet beta cells. It is typically immune-mediated but may be idiopathic.
Type 2 OM results from three concomitant abnormalities:
I. lmpaired pancreatic insulin secretion
2. Resistance of peripheral cells to insulin
3. Increased hepatic glucose production.
Diabetes Mellitus 277
3. How does the human classification system apply to veterinary medicine?
Human nomenclature cannot be applied to veterinary species with complete accuracy.
Evidence suggests that both type I and type 2 OM occur in veterinary species, but variations and
overlaps in pathophysiology are likely. The presence of autoantibodies and the suggestion of au-
toimmune destruction of pancreatic beta cells have been occasionally reported in diabetic cats,
but the presence of type I OM has not been established as a major pathophysiologic mechanism.
It may explain the rare occurrence of OM in kittens. Most diabetic cats probably have a disease
process most similar to human type 2 OM.
4. What is meant by insulin-dependent or non-insulin-dependent DM?
In the past, type 1 has been called insulin-dependent OM (IDOM) and type 2 non-insulin-de-
pendent OM (NIDOM). This terminology is confusing when applied to veterinary patients be-
cause approximately 60-70% of diabetic cats require insulin therapy at the time of diagnosis,
regardless of the underlying pathophysiology. Cats also may alternate between requiring and not
requiring insulin; as many as 10-20% of insulin-dependent cats become non-insulin-dependent.
5. What is glucose toxicity?
Cats are highly sensitive to glucose toxicity. Prolonged hyperglycemia, which may be pre-
sent before the diagnosis of OM, results in an additional decline in the ability of pancreatic beta
cells to sense and respond to glucose concentrations. This decline further reduces insulin secre-
tion and perpetuates the disease. Glucose toxicity also may playa role in increasing peripheral
insulin resistance.
6. How can DM resolve in some cats?
Glucose toxicity may be the reason. After reduction of hyperglycemia via exogenous insulin,
beta cells may regain the ability to sense glucose and secrete insulin; thus, exogenous insulin is
no longer required.
7. What is secondary DM?
Secondary OM, usually called type 3, results from beta-cell dysfunction or insulin resistance
caused by an unrelated disease process (e.g., acromegaly, hyperadrenocorticism) or drug admin-
istration (e.g., progestins). If the primary problem or drug administration is eliminated, type 3
OM that has not progressed beyond initial stages will resolve.
8. How common is DM in cats?
The incidence of feline DM is estimated at 0.25-0.5% (l in 200-400 cats). It is one of the
most common endocrinopathies of cats, second only to hyperthyroidism.
9. What is the typical signalment of cats with DM?
OM can develop in cats of any breed, age, or sex; however, older (> 10 yr), obese, neutered
males appear to be at increased risk.
10. What are the historical and clinical signs ofDM?
In uncomplicated OM, weight loss with normal-to-increased appetite, polyuria, and polydip-
sia are common. Because of the insidious onset of these signs, owners may miss them until
changes become severe. A poor, unkempt hair coat also may be noted. In rare instances, a gait
change or plantigrade stance associated with a peripheral neuropathy may be seen. In cases of
complicated OM (e.g., ketosis, hyperosmolar state, or concomitant disease, such as hepatic lipi-
dosis), other symptoms may be seen, including anorexia, vomiting and diarrhea, lethargy. depres-
sion, and icterus.
11. Howis DM diagnosed?
The diagnosis is achieved by documenting fasting hyperglycemia> 200 mg/dl and glucosuria
in a cat with appropriate clinical signs. The presence of ketonuria further confirms the diagnosis.
278 Diabetes Mellitus
12. Does the presence of hyperglycemia mean that a cat is diabetic?
As a result of a physiologic response to acute or chronic stress, nondiabetic cats can be hy-
perglycemic. Blood glucose concentration can even exceed 300 mg/dI.
13. How can DM and stress hyperglycemia be differentiated?
If the stress is acute (e.g., induced by handling or restraint), glucosuria is usually absent. If
glucosuria is observed and stress is still suspected, resampling or serial sampling of blood and
urine after acclimatization may be tried. Urine glucose also can be measured in a nonstressful,
home environment using urine dipsticks, if needed.
14. Can measurement of glycosylated proteins aid in the differentiation?
With hyperglycemia of days to weeks in duration, certain plasma proteins (albumin and he-
moglobin) become bound to glucose (glycosylated). In theory, the concentration of glycosylated
protein is proportional to the blood glucose over time. The concentrations of these altered pro-
teins can be measured in a laboratory as fructosamine or glycosylated hemoglobin, and they typ-
ically are elevated in untreated diabetic cats. However, not all diabetic cats have elevated levels;
conversely, elevated levels may be seen in nondiabetics. Thus measurement of glycosylated pro-
teins is not 100% accurate in differentiating stress from DM.
15. What other clinicopathologic changes may be seen in diabetic cats?
Other common clinicopathologic changes include hypercholesterolemia and elevations in one or
more liver enzymes, ranging from mild to severe. When hyperosmolar, ketoacidotic, or concomitant
disease states are present, various other laboratory findings, including evidence of hemoconcentra-
tion, hyperosmolality, acidemia, electrolyte abnormalities, and hyperbilirubinemia, may be noted.
16. How is DM treated?
Therapy consists of various combinations of weight and dietary modification, insulin ther-
apy, and administration of oral hypoglycemic agents.
17. Why is weight correction important? How should it be done?
Correction of obesity or malnutrition diminishes insulin resistance and, in type 2 DM, im-
proves insulin secretion. For weight loss, caloric intake should be restricted to approximately
75% of the maintenance caloric requirements of 60-70 kcal/kg/day. Underweight cats should be
fed maintenance caloric requirements to achieve ideal body weight. Any attempts to alter body
weight should be made gradually. Blood glucose values should be monitored closely because in-
sulin requirements change with body condition.
18. Describe an appropriate diet for diabetic cats.
An appropriate diet and feeding schedule are important parts of diabetic control. A well-bal-
anced diet containing adequate protein and reduced fat content is recommended most commonly,
but new evidence suggests that high protein also may be beneficial. Sugars should be complex
carbohydrates with minimal amounts of simple sugars. Increased dietary fiber may improve
glycemic control by minimizing postprandial fluctuations in blood glucose. Diets should take
into consideration any concomitant diseases.
19. Describe the ideal feeding schedule.
Consistency in amount and schedule is crucial. Insulin therapy is more successful when diet
and feeding schedule are regular. Feeding schedules should minimize postprandial fluctuations in
blood glucose and coordinate with the peak physiologic effects of exogenously administered in-
sulin, if possible. The ideal schedule to minimize postprandial hyperglycemia includes multiple
smalI meals throughout the day, but this schedule is usually impractical. Because the ideal is usu-
ally not possible, it is suggested that meals be given immediately before insulin injections. if
given twice daily. If once-daily insulin is used, one meal can be given before the morning injec-
tion and one in the late afternoon or early evening.
20. What about free-choice feeding?
Free-choice feeding can be used if a cat refuses to eat scheduled meals, but the amount
should be restricted to maintenance caloric requirements. The problem with this approach is that
it may be difficult to tell whether the cat is eating well, and insulin may be given inappropriately.
21. What medical therapies are available?
Treatment of DM in cats can be approached by administration of either exogenous insulin or
oral hypoglycemic agents, which increase insulin secretion, decrease peripheral insulin resis-
tance, or decrease absorption of glucose from the intestinal tract.
22. When should medical therapies be used?
Insulin is the required initial therapy in ketotic patients or patients with significant systemic
illness. Oral hypoglycemic agents may be used as the initial mode of therapy in relatively healthy
cats with uncomplicated diabetes. Once initial glucose toxicity is resolved with insulin therapy, it
may be possible to substitute oral hypoglycemic agents for insulin injections in some cats.
23. How is insulin classified?
Various insulin formulations are available. Insulin can be categorized according to source
(e.g., beef, pork, or human recombinant) or type (based on onset and duration of action: short-
acting, intermediate-acting, or long-acting.). Insulin is a 51-amino acid protein molecule.
Several amino acid residues vary between species. Feline insulin is most similar to bovine (1-
amino acid difference), followed by porcine (3-amino acid difference), and finally human (4-
amino acid difference).
24. How may insulin source affect efficacy?
Variations in amino acid residues between exogenous and endogenous insulin may cause
immune stimulation. Although believed to be rare, significant antibody formation against admin-
istered insulin can lead to insulin resistance. Formation of a low antibody titer, however, may ac-
tually help prolong the duration of insulin action, a desirable effect. In most situations, clinically
important differences are not observed when using various sources of insulin in diabetic cats.
25. What types of insulin are available?
Characteristics of Insulin Types and Insulin Requirements for Diabetic Cats
AVERAGE
TIME
ONSET OF OF PEAK DURATION
TYPE PRODUCTS' SOURCE UIML ROUTE ACTION EFFECT OFACTlON
Short-acting
Regular HumulinR Human 100 IV,IM, 10-30 min 1-5 hr 4-10 hr
Novolin R Human SQ
Velosulin R Human
Intermediate-acting
Lente HumulinL Human 100 SQ < I hr 2-8 hr 6-14 hr
NovolinL Human
NPH HumulinN Human 100 SQ 0.5-3 hr 2-8 hr 4-12 hr
Novolin N Human
Long-acting
PZI PZI Beef/pork 40 SQ 1--4 hr 3-12 hr 6-24 hr
Ultralente HumulinU Human 100 SQ 1-8 hr 4-16 hr 8-24 hr
IV=intravenous, 1M=intramuscular, SQ=subcutaneous, NPH =neutral protamine Hagedorn, PZl =prota-
minezincinsulin. Humulin (Eli Lilly, Indianapolis, IN), Novolin andVelosulin (Novo Nordisk, Princeton,
NI), PZI(Blue Ridge Pharmaceuticals, Greensboro, NC).
From Feldman EC, Nelson RW (eds): Canine and Feline Endocrinology and Reproduction. 2nd ed.
Philadelphia, W.B. Saunders, 1996, p 360,withpermission.
26. When should short-acting insulin be used?
Short-acting insulin generally is reserved for sick diabetic cats when immediate reduction of
blood glucose is desired, especially if ketoacidosis is present. Regular insulin can be adjusted fre-
quently without significant concern for overlapping or prolonged effects of a single dose.
Because intensive monitoring generally is required, its use is limited to hospitalized patients. If
ketoacidosis or other complications are present at the time of diagnosis of DM, therapy with
longer-acting insulin should beinitiated only after resolution or stabilization of these problems.
27. When should intermediate- or long-acting insulin be used?
If no significant complications are present at diagnosis, long-term therapy with longer-acting
insulins can be initiated. The choice between an intermediate- or long-acting type is based most
commonly on personal preference. The classification as intermediate- or long-acting is based on
humans, and both types of insulin are typically required twice daily in cats. All of these insulins
have been used successfully in cats, but individual responses vary. Ultralente insulin may be as-
sociated with inconsistent absorption in approximately 33% of cats. If use of Ultralente leads to a
poor response, another type of insulin may be more effective.
28. Can insulin mixtures be used to treat diabetic cats?
Occasionally insulin mixtures are used to treat human diabetics. Commercially available
mixtures usually contain a combination of regular and NPH insulin in various percentages.
Insulin mixtures may be useful when the onset of action of an intermediate-acting insulin alone is
too slow, allowing periods of unacceptable hyperglycemia, but this requirement is rare in cats.
Administration of insulin mixtures is often associated with hypoglycemia in veterinary patients.
29. How should insulin therapy be initiated?
The recommended starting dose of intermediate- and long-acting insulin ranges between I
and 3 units (about 0.25 U/kg) subcutaneously once or twice daily (see table in question 25). In
general, intermediate-acting insulins are more potent than long-acting insulins; thus the recom-
mended starting dose of intermediate-acting insulins is lower. It is always better to err on the side
of underdosing when therapy is started than to cause hypoglycemia with an overdose. If insulin
therapy is to be started while the cat is in the hospital, blood glucose should be measured during
the period when peak insulin effect is predicted to detect hypoglycemia if it develops. Using the
lower end of the dosing range and once-daily therapy in the case of long-acting insulins may be a
safer method of instituting therapy at home.
30. When does the insulin dose need to be changed?
Changes in insulin therapy are almost always needed, especially during initial management.
Weight changes and resolution of glucose toxicity often play an important role during early
stages of therapy. The need for changes in therapy is best determined by performing a blood glu-
cose curve. No changes in insulin dose should be made sooner than 4-6 days after starting a
given dose unless hypoglycemia occurs. This period is required for equilibration of blood glu-
cose concentration.
31. When should a blood glucose curve be performed?
A blood glucose curve is performed after modification of insulin therapy and after an appro-
priate equilibration period. Glucose curves also are used as a routine monitoring tool every few
months for long-term management of diabetic patients or at any time if clinical signs recur.
32. How is a blood glucose curve performed?
A blood glucose curve is made by measuring blood glucose concentration every 2 hours for
a duration equal to or greater than the insulin administration interval (usually 12 or 24 hours).
Blood samples may be obtained via a large-bore catheter placed at the beginning of the monitor-
ing period or multiple venipunctures.
33. How are blood glucose curves interpreted?
The parameters that need to be assessed include the time required after injection for peak: in-
sulin effect to occur, the blood glucose nadir at the time of maximal effect, and the duration of in-
sulin action. Blood glucose nadir values determine whether changes in insulin dosage are needed.
The duration of insulin action determines the frequency of insulin administration.
34. How should insulin dose be changed with regard to blood glucose curve results?
Ideally, blood glucose values should be maintained between 100 and 200 mg/dl during any
24-hour period. This goal is rarely achieved. In most instances, it is hoped that blood glucose can
be maintained under 300 mg/dl to help limit disease complications. Dosage changes should be
based on blood glucose nadir values. An ideal glucose nadir is between 80 and 150 mg/dl. Nadirs
above this range require increases in insulin dose. In most cases, incremental increases of 0.5-1
U per dose of insulin are appropriate. Values < 80 mg/dl require decreases in insulin dose of
10-25%. Remember that stress from hospitalization and procedures may cause blood glucose
concentrations to be higher than during a eat's normal routine at home. Hypoglycemia can be
life-threatening and always should be avoided.
35. How should the insulin dosing interval be determined?
Duration of insulin action is estimated by determining the period from insulin administration
through the blood glucose nadir to the time when blood glucose concentration exceeds approxi-
mately 200-250 mg/dl. Once-daily insulin administration is used if the duration of insulin action
is between 22 and 24 hours. If the duration of action is 10-14 hours, twice-daily insulin therapy is
given, or a longer-acting insulin, if available, may be tried. For durations of action between these
ranges (i.e., 15-20 hours), changes in insulin type or dose may be needed. If a long-acting insulin
such as Ultralente or PZI is used, twice-daily administration of an intermediate-acting insulin,
with an initial 10-25% decrease in dose, may be ideal. If a 12-hour dosing interval is not an option
for owners, a small dose of regular insulin 16-18 hours after the morning dose may be tried.
Caution should be used with this type of protocol because of the increased risk of hypoglycemia.
36. What is the Somogyi phenomenon?
When blood glucose levels fall below normal, counterregulatory hormones such as epineph-
rine and glucagon are released, quickly causing a marked hyperglycemia that can persist for
hours. The hypoglycemia and subsequent physiologic response resulting in hyperglycemia are
known as the Somogyi phenomenon. Prolonged hyperglycemia during a glucose curve or clinical
signs of continued polyuria and polydipsia at home may be consistent with either an inadequate
insulin dose or excessive insulin administration and rebound hyperglycemia. It is important to
differentiate between the two before increasing insulin dosage by documentation of the blood
glucose nadir. Because blood glucose values can change very quickly in response to counterregu-
latory hormones, excessively low blood glucose nadirs can be missed when performing a stan-
dard curve with blood glucose measurements every 2 hours. It may be necessary to perform extra
glucose measurements around the time of peak insulin effect.
37. What special considerations are needed for interpreting or performing a glucose curve?
Because of the stress and associated physiologic response during hospitalized blood glucose
curves, some cats are hyperglycemic throughout the testing period, falsely giving the appearance
of poor diabetic control. Unnecessary increases in insulin doses may be made, putting the patient
at risk for hypoglycemia. If stress-induced alterations of blood glucose curve values are sus-
pected, hospitalization and catheter placement 24 hours before starting a glucose curve allow
time for environmental adjustment and minimize handling during the glucose curve.
38. What is the best use for measurement of glycosylated proteins?
Because poorly controlled diabetic cats can have normal levels of glycosylated proteins and
well-controlled diabetic animals can have elevated concentrations, they may best be used to
monitor trends in an individual patient. Concentration of one of the glycosylated proteins can be
measured when a cat is first diagnosed, and changes in the protein levels can be used to help
assess control.
39. What period of glycemic controldo glycosylated proteinsreflect?
The period of glycemic control reflected by glycosylated proteins is a factor of the life span
of the measured protein. In cats, glycosylated hemoglobin and fructosamine reflect glycemic
control over the previous 1-2 months and 1-2 weeks, respectively.
40. Whatshouldbe donefor a previously well-controlled cat whentherapy is no longeref-
fective?
Insulin source, administration, and handling as well as feeding practices should be evalu-
ated. Recent changes in insulin vials and vials more than 2 months old are suspect. Site of in-
sulin administration also may playa role; absorption may be suboptimal in the interscapular
region as compared with the lateral thorax or flank. If these factors are not a problem, a glucose
curve should be performed to rule out insulin-induced hyperglycemia and to gauge insulin ef-
fectiveness. Changes in body weight, introduction of drugs such as corticosteroids or megestrol,
endogenous sources of progesterone in intact females, and concomitant disease, especially uri-
nary tract, skin, and respiratory infections, can alter diabetic control. The presence of other dis-
eases, such as hyperthyroidism, renal disease, hyperadrenocorticism, and acromegaly, may need
to be considered.
41. Whatis insulinresistance?
Insulin resistance is defined as the need for an insulin dose> 2.2 U/kg to maintain adequate
glycemic control. Most well-controlled animals require insulin doses of < 1 U/kg. Insulin resis-
tance should be suspected when hyperglycemia persists throughout the day despite doses> 1.5
U/kg. When insulin resistance is suspected, the same steps used to determine the cause of lack of
control apply. True insulin resistance can be caused by many factors.
Causes ofInsulin Resistance
Drugs: glucocorticoids, progestins
Endocrinedisorders: acromegaly, hyperadrenocorticism, hyperthyroidism
Hyperlipidemia
Infection
Insulinantibodies
Ketoacidosis
Malnutrition
Neoplasia
Obesity
42. Howis insulinresistance treated?
The best treatment is to remove the underlying cause. If this solution is not feasible, large
doses of insulin may be necessary to maintain euglycemia, if control is possible at all.
43. Whatare oral hypoglycemic agents?
Oral hypoglycemic agents consist of several categories of drugs used for treatment of type 2
DM in humans. They include sulfonylureas (glipizide, glyburide, glimepiride), biguanides (met-
formin), thiazolidinediones (troglitazone, rosiglitazone), alpha-glucosidase inhibitors (acarhose),
and transition metals (chromium, vanadium). Several of these agents have been tried in feline di-
abetics with variable success.
Diabetes Mellitus
Oral Hypoglycemic Agents
283
Pioglitazone (Actos)
Biguanides
Inhibithepaticglucose Metformin(Gluco-
production phage)
Thiazolidinediones (gIitazones)
Increaseinsulinreceptor Rosiglitazone (Avandia)
sensitivity
PROPOSED
MECHANISM OFACTION
Sulfonylureas
Increaseinsulinsecretion
and sensitivity
Reducehepaticglucose
production
GENERIC DRUG
(BRAND NAME)
Glipizide(GlucotroI)
Glyburide(Micronase,
Diabeta)
Glimiperide(Amaryl)
DOSE
2.5-5.0 mg/cat PO 2-3
times/day
0.625 mg/catPO every
24hr
Unknown (humandose:
1-4 mg/day)
Unknown (humandose:
500-750 mg/day)
Unknown (humandose:
4-8 mg/day)
Unknown (human dose:
15-45 mg/day)
SHOWNTOBE
POTENTIAL EFFECTIVE IN
SIDE EFFECTS SOME CATS
Hepatotoxicity Yes
Hypoglycemia
Vomiting
Sameas above No?
Same as above No
Anorexia No
Vomiting
Hepatotoxicity No
Cardiacfailure
Sameas above No
Alpha-glucosidase inhibitors
Impair glucoseabsorption Acarbose(Precose)
fromGl tract
Transition metals
Increaseinsulinreceptor Vanadium
sensitivity
Chromium
12.5-25 mg/cat with Flatulence Yes
meals Soft stool, diarrhea
0.2 rug/kg/day in food Anorexia Yes
or water Vomiting
Diarrhea
Renal disease
200ug/ca; POevery24 hr Unknown No
PO =orally.
Glucotrol and Micronase: Pfizer, New York; Diabeta and Arnaryl: Aventis, Bridgewater, NJ; Glucophage:
Bristol-Myers Squibb, NewYork; Avandia: SmithKline Beecham, Philadelphia: Actos: Takeda, Lincolnshire,
IL; Precose: Bayer, Pittsburgh.
44. How do oral hypoglycemics work?
Sulfonylureas increase pancreatic insulin secretion. Thiazolidinediones sensitize tissues to
the effects of insulin. Biguanides are believed to act primarily by inhibiting hepatic glucose re-
lease as well as improving peripheral insulin sensitivity. How transition metals reduce blood glu-
cose remains unclear. Possibilities include increasing insulin responsiveness at postreceptor sites,
increasing insulin receptor numbers, or functioning as an insulin cofactor. Alpha-glucosidase in-
hibits dietary fiber digestion, decreasing postprandial glucose absorption.
45. What types of oral hypoglycemic agents have been shown to be useful in diabetic cats?
The sulfonylurea glipizide is used most commonly; it is the only oral hypoglycemic agent
tested in a large number of diabetic cats. Little information is available about the efficacy and
safety of other hypoglycemic agents in cats. Reports of the use of troglitazone and biguanides
suggest that they may not be efficacious. The a-glucosidase inhibitor acarbose appears to have
mild glucose-lowering effects and may be a useful adjunct to insulin therapy. Gastrointestinal
side effects are common, however, and may outweigh the benefits. Vanadiummay alleviate clini-
cal signs of early type 2 DM.
46. Which cases are appropriate for trial therapy with glipizide?
Glipizide therapy may be most ideal in stable, nonketotic diabetic cats with mild clinical
signs and normal body weight. Debilitated or ketoacidotic cats are not good candidates for glip-
izide. Glipizide should be tried if owners refuse to give insulin injections. Many owners who ini-
tially refuse to administer insulin subsequently agree to try insulin treatment after glipizide
therapy has failed.
284
Diabetes Mellitus
47. How is glipizide used in diabetic cats?
An initial dose of 2.5 mg per cat twice daily with food is recommended. Clinical signs, body
weight, and medication side effects, including vomiting and icterus, should be monitored. Blood
glucose, urine glucose and ketones, and liver enzyme concentrations should be checked after 1-2
weeks. If no problems have occurred, the dose may beincreased to 5 mg twice daily. After 2 weeks,
the cat should be reexamined and a lQ-12-hour glucose curve performed. Blood glucose values <
200 mg/dl and absence of glycosuria indicate a therapeutic response. Hypoglycemia may occur in
cats receiving glipizide. If response is inadequate, therapy can becontinued and re-assessed every 4
weeks as long as ketoacidosis or significant weight loss and clinical signs do not develop. Response
to therapy can take as long as 12 weeks. Some cats respond only when the dose is increased to 7.5
mg 2 or 3 times/day. If no response occurs after 12 weeks, glipizide administration should be dis-
continued and insulin therapy started. If a clinical response occurs, glipizide therapy should be
stopped, and the serum glucose reevaluated in I week. If hyperglycemia recurs, glipizide therapy
should be reinstituted, starting at half the previous dosage. If normoglycemia persists, appropriate
dietary therapy should be continued and the cat routinely monitored for recurrence of clinical signs
and hyperglycemia. Normoglycemia may be maintained for 12-14 months or longer.
48. What should be done if side effects occur with initiation of therapy?
Clinical signs of vomiting or icterus are usually transient. If they occur, medication should
be discontinued for 5 days. If problems resolve, glipizide can be reinstituted with a gradually in-
creasing dose. A dose of 1.25 mg twice daily can be given for 7 days. If no problems occur, the
dose can be increased to 2.5 mg once daily for 7 days followed by 2.5 mg twice daily for 14 days.
If problems are still absent, a dose of 5 mg twice daily can be given. If problems recur, glipizide
should be stopped and insulin therapy instituted.
49. Clinical signs resolve with glipizide therapy, but blood glucose values remain consis-
tently > 200 mg/dl. What may be the cause?
Partial responses to glipizide do occur, but stress hyperglycemia is also a possibility.
Glycosylated hemoglobin or fructosamine should be measured or urine glucose assessed at
home. If therapy appears to be adequate, glipizide can be continued. If control is inadequate,
glipizide should be discontinued and insulin therapy started.
50. How effective is glipizide treatment?
Approximately 35-45% of cats respond to long-term therapy. Which cats will respond
cannot be predicted.
51. What serious complications may occur in diabetic cats?
Diabetic ketoacidosis (DKA), hyperosmolar diabetes mellitus (HDM), and insulin overdose
resulting in serious hypoglycemia can be life-threatening complications.
52. How does DKA occur?
Insulin deficiency results in an inability of peripheral tissues to utilize glucose. A relative excess
of insulin counterregulatory hormones (glucagon, cortisol, catecholamines, growth hormone) occurs,
perpetuating hyperglycemia. Without adequate amounts of insulin, peripheral tissues must use
nonglucose energy sources, and adipose stores are mobilized. Free fatty acids undergo transforma-
tion in the liver to triglycerides or ketone bodies (including acetoacetate, and
acetone). Because of the relative excess of counterregulatory hormones, particularly glucagon,
ketone production predominates. Normally, peripheral tissues metabolize ketones, and their acidic
nature is buffered primarily by bicarbonate. In diabetics, production can exceed utilization, and
buffering systems are overwhelmed. The result is ketosis, ketonuria, and metabolic acidosis.
53. What clinical abnonnalities are observed in DKA?
Vomiting, anorexia, lethargy, and depression are often reported. In previously undiagnosed di-
abetic patients, prior history may include clinical signs typical of DM. On physical examination.
dehydration, weakness, tachypnea, and a strong acetone odor on the breath may be noted. When
metabolic acidosis is severe, slow deep breathing (Kussmaul respiration) may be observed.
Pathology findings usually support dehydration, metabolic acidosis, hyperglycemia, ketonemia,
ketonuria, and electrolyte deficiencies, especially of sodium and potassium. Elevated liver en-
zymes and azotemia (usually prerenal) are also common.
54, How is DKA typically treated?
Treatment of DKA requires fluid replacement, restoration of electrolyte and acid-base bal-
ance, and reduction of hyperglycemia. Appropriate fluid and insulin therapy and identification
and treatment of any underlying disease that may have precipitated the DKA are critical in
achieving these goals.
55. What fluid and electrolyte therapies are used in DKA?
Adequate fluid should be administered to resolve dehydration within the first 24 hours of
treatment. Normal saline is the fluid of choice. Potassium supplementation is required in patients
with DKA, even if serum potassium concentration is normal to elevated on initial blood work,
unless contraindicated by the presence of another disease. Because insulin therapy and correction
of acidosis cause extracellular potassium to move into cells, therapy may cause severe, life-
threatening hypokalemia. Typically 20-40 mEq of potassium are added to each liter of fluids, but
higher levels may be needed. Potassium concentrations should be monitored as frequently as
every 2-4 hours during initial therapy. Treatment of acidosis with bicarbonate therapy is not typ-
ically needed unless the acidosis is severe (arterial pH < 7.1). Replacement of circulating fluid
volume and initiation of insulin therapy, which promotes metabolism of ketoacids, typically re-
sults in rapid normalization of acid-base balance. Like potassium, total body phosphorus levels
also may be low despite normal levels on initial blood work; with treatment, phosphorus shifts
into cells. Although development of severe hypophosphatemia is uncommon, it can be life-threat-
ening. Phosphorus levels should be monitored regularly during initial therapy, and supplementa-
tion should be given if serum levels drop to < 2.0 mg/dl.
56. How is insulin therapy given in DKA?
Regular crystalline insulin is recommended. Because patients are dehydrated, insulin is admin-
istered intramuscularly or intravenously rather than subcutaneously to ensure absorption. If given
intramuscularly, the initial starting dose is 0.2 U/kg with subsequent hourly doses of 0.1 U/kg as
needed. Blood glucose levels should be monitored hourly. Because rapid reductions in blood glu-
cose may result in cerebral edema, blood glucose levels should be maintained above 250 mg/dl for
at least the first 4-6 hours. When blood glucose concentrations fall to 250 mg/dl or less, 2.5% or
5% dextrose should be added to the fluids. Insulin administration is then reduced to every 4-6 hours
with dose adjustments, as needed, to control blood glucose values while avoiding hypoglycemia.
57. How is insulin administered intravenously?
Insulin can be given intravenously via continuous rate infusion (CRt) at a dose of 1.1 U/kg per
24 hours, allowing easy dose adjustments and avoiding problems with parenteral insulin absorption.
A simple method of approximating this dose is to add the number of units equivalent to the body
weight in kilograms to a 250-rnl bag of normal saline and administer the fluid at a rate of 10 rnl/hr
(e.g., for a 4-kg cat, 4 units of regular insulin are added to 250 rnl of fluid and administered at 10
rnl/hr). When blood glucose concentration is < 250 mg/dl, the administration rate should bereduced
as needed. Once clinical signs and ketonuria resolve, longer-acting insulin therapy is instituted.
58. How does HDM occur?
As in DKA, hyperglycemia results in osmotic diuresis with water and electrolyte distur-
bances. However, decreased renal excretion of glucose occurs in HOM, resulting in extreme hy-
perglycemia (usually> 600 mg/dl). Severe hyperglycemia causes an increase in serum osmolality,
altering the osmotic gradient between extracellular and intracellular compartments and shifting
286
Diabetes Mellitus
water into the extracellular space. Severe tissue dehydration results from renal water loss as well
as the shift of water out of the cells.
59. What clinical abnormalities are seen in HDM?
Neurologic abnormalities, including ataxia, disorientation, seizures, and coma, may be ob-
served in HDM because of severe dehydration of neurologic tissue. Other historical findings sim-
ilar to those noted for uncomplicated DM and DKA may be reported. Laboratory abnormalities
usually include severe hyperglycemia, glycosuria (typically without ketonuria), azotemia, meta-
bolic acidosis, and hyperosmolality (typically> 350 mOsm; normal =285-310 mOsm). Serum
osmolality can be estimated with the following formula:
Serum osmolality =2(Na +K) +glucose/18 +BUN/2.8.
where Na =sodium, K =potassium, and BUN =blood urea nitrogen. Potassium abnormalities as
seen with DKA also may occur with HDM.
60. Howis HDM treated?
Treatment goals of HDM are similar to those for DKA. Treatment requires replacement of
body fluids, reduction of excessive hyperglycemia, and restoration of electrolyte and acid-base
balance. Appropriate fluid and insulin therapy is critical. The major difference between treating
HDM and DKA is the increased risk of cerebral edema. During development of HDM, the brain
accumulates idiogenic osmoles, osmotically active substances, as a mechanism to prevent dehy-
dration of neurologic tissue. If serum osmolality decreases suddenly as a result of rapidly declin-
ing blood glucose, idiogenic osmoles do not have time to dissipate. The resultant osmotic
gradient shifts water intracellularly, causing cerebral edema. Therefore, fluid deficit replacement
and lowering of serum blood glucose concentration should be done slowly over a period of 24-48
hours by using smaller insulin doses than for DKA and adding dextrose to the fluids as necessary.
61. What happens with insulin overdose?
Overdosage of insulin results in hypoglycemia, which, in turn, can cause lethargy, depres-
sion, weakness, ataxia, seizures, or coma.
62. How is insulin overdose treated?
Owners should be educated about the clinical signs of hypoglycemia and instructed to apply
corn syrup to oral mucous membranes if they are observed. In the hospital, an initial intravenous
bolus of 50% dextrose (0.5-1 mg/kg), diluted at least I: 1 with normal saline or a balanced elec-
trolyte solution, should be given slowly. A maintenance drip of 5% dextrose should then be
started. Insulin therapy should not be reinitiated until hyperglycemia is maintained without dex-
trose therapy. This process may take several days, depending on the severity and duration of the
hypoglycemia. Insulin therapy should be modified to prevent further episodes.
63. What is the prognosis for cats with DM?
The prognosis for cats with DM depends, in part, on owner commitment to treatment, con-
current diseases, and ease of glycemic control. In general, a guarded long-term prognosis has
been suggested.
64. What important factors should owners be aware of in regard to treatment?
Owner education is critical for successful treatment. The commitment and costs required to
maintain a diabetic pet should be made clear. Consistency in insulin injections or medication
and feeding schedule is essential. The likelihood that dysregulation problems will be encoun-
tered during treatment should be discussed. Insulin handling and administration should be
demonstrated. It is often helpful to observe the client handle and administer insulin to ensure
that directions are clear and mistakes are not made. Owners should be educated about the clini-
cal signs of hypoglycemia as well as dysregulation and be given instructions for intervention
and the need for reevaluation.
Diabetes Mellitus
65. What is acromegaly?
Acromegaly is a condition of excessive growth hormone (GH) production and secretion.
287
66. What causes acromegaly?
Acromegaly in cats results from a functional pituitary tumor, of which approximately 90%
are macroadenomas (i.e., > 1 em in diameter). Excessive GH has anabolic effects that may result
in overgrowth of connective tissue, bone, and viscera. These effects are mediated by growth hor-
mone-stimulated production of insulin-like growth factor-I (IGF-I) or somatomedin by the liver.
Catabolic effects of GH result primarily from insulin antagonism and subsequent abnormalities
in carbohydrate and fat metabolism. The net effect is promotion of hyperglycemia and ketogene-
sis. DM has developed in all acromegalic cats.
67. Describe the common signalment, clinical signs, and pathologic abnormalities.
Acromegaly typically occurs in older, castrated male cats. Clinical signs associated with the
catabolic effects of GH tend to predominate. Typical clinical signs include polyuria, polydipsia, and
polyphagia. Increases in body size with enlargement of the head, interdental spaces, and abdomen
may be seen. Frequently, prognathism is present. Other abnormalities may include degenerative
arthropathies; organomegaly of the heart, kidney, liver, or tongue; hypertrophic cardiomyopathy;
and neurologic signs related to the presence of a pituitary mass. Hyperglycemia and glycosuria are
due to DM. Hypercholesterolemia, hyperphosphatemia, elevated liver enzymes, hyperproteinemia,
renal azotemia, and mild erythrocytosis also may be observed.
68. How is acromegaly diagnosed?
Feline acromegaly can be diagnosed with computed tomography or magnetic resonance imag-
ing for visualization of a cranial mass. Documentation of increased serum GH or IGF-I levels also
may be useful (Animal Health Diagnostic Laboratory, Endocrine Diagnostic Section, Michigan
State University, East Lansing, MI). A commercial GH assay, however, is not currently available in
the U.S. Compatible pathologic abnormalities and clinical signs also support the diagnosis.
69. How is acromegaly treated?
Radiation therapy has had short-term success in some cases. Administration of a synthetic
somatostatin (octreotide) as a means of counteracting the effects of IGF-I has not been promis-
ing. Dopamine agonists have been used successfully in human acromegalies but have not been
evaluated in cats.
70. What is the prognosis of acromegaly in cats?
Long-term prognosis of cats with acromegaly is poor. Because of the typically slow-growing
nature of pituitary tumors in this disease, short-term prognosis may be good to guarded with re-
ported survival times of 4-42 months. However, control of DM in cats with acromegaly is diffi-
cult; insulin doses as high as 100-200 U/day are required if the acromegaly is not controlled.
BIBLIOGRAPHY
I. Behrend EN, Greco DS: Treatment of feline diabetes mellitus: Overview and therapy. Comp Cont Educ
Pract Vet 22:423-439, 2000.
2. Behrend EN, Greco DS: Treatment of feline diabetes mellitus: Evaluation of treatment. Comp Cont Educ
Pract Vet 22:440-452, 2000.
3. Feldman EC, Nelson RW: Disorders of growth hormone. In Feldman EC, Nelson RW (eds): Canine and
Feline Endocrinology and Reproduction, 2nd ed. Philadelphia, WB. Saunders, 1996, pp 38--66.
4. Feldman EC, Nelson RW: Diabetes mellitus. In Feldman EC, Nelson RW (eds): Canine and Feline
Endocrinology and Reproduction, 2nd ed. Philadelphia, W.B. Saunders, 1996, pp 339-391.
5. Feldman EC, Nelson RW: Diabetic ketoacidosis. In Feldman EC, Nelson RW (eds): Canine and Feline
Endocrinology and Reproduction, 2nd ed. Philadelphia, W.B. Saunders, 1996, pp 392-421.
6. Feldman EC, Nelson RW, Feldman MS: Intensive 50-week evaluation of glipizide administration in SO
cats with previously untreated diabetes mellitus. J Am Vet Med Assoc 210:772-777, 1997.
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Hypercalcemia and Hypocalcemia
7. Goossens MMC, Feldman EC, Nelson RW, et al: Cobalt 60 irradiation of pituitary gland tumors in three
cats with acromegaly. 1 Am Vet Med Assoc 213:374-376, 1998.
8. Goossens MMC, Nelson RW Feldman EC, et al: Response to insulin treatment and survival in 104 cats
with diabetes mellitus (1985-1995). 1 Vet Intern Med 12:1-6, 1998.
9. Lutz TA, Rand 1S: Pathogenesis of feline diabetes mellitus. Vet Clin North Am Small Anim Pract 25:
527-552, 1995.
10. Peterson ME, Taylor RS, Greco OS, et al: Acromegaly in 14 cats. 1 Vet Intern Med 4:192-201, 1990.
II. Whitley NT, Drobatz KJ, Panciera OL: Insulin overdose in dogs and cats: 28 cases 1 Am

57. HYPERCALCEMIA AND HYPOCALCEMIA
Rebecka S. Hess, D.v.M.
1. What are the physiologic roles of calcium?
Intracellularly, calcium mediates numerous hormonal actions and is involved in the secretion
of some hormones. In addition, it is involved in muscle contraction, nerve conduction, blood coag-
ulation, and bone formation. Because calcium has many important physiologic roles, its concen-
tration is tightly maintained throughout the body. Ionized calcium (Ca
2
+) is the physiologically
active form.
2. Which three hormones regulate serum Ca
2+
concentration? From what tissue are they
secreted?
I. Parathyroid hormone (PTH), which is produced by chief cells in the parathyroid gland.
2. 1,25-Dihydroxycholecalciferol (calcitriol, vitamin D
3
) , which is produced by sequential
hydroxylation of vitamin D first in the liver and then in the kidney.
3. Calcitonin, which is produced primarily by C (parafoIlicular) cells in the thyroid gland.
3. Howdo these hormones control serum Ca
2+?
The three major target organs of these hormones are bone, kidneys, and gastrointestinal tract.
PTH increases plasma Ca
2
+ concentration mainly by stimulating bone resorption but also by in-
creasing renal reabsorption of Ca
2
+ and stimulating production of calcitriol. Calcitriol increases
plasma Ca
2
+ concentration mainly by increasing Ca
2
+ absorption from the intestine but also by
stimulating bone resorption and increasing renal calcium reabsorption. Calcitonin is the only one of
the three hormones that lowers Ca
2
+concentration; it acts mainly by inhibiting osteoclast action and
promoting Ca
2
+ retention in bone. Calcitonin also increases urinary excretion of calcium. The role
of calcitonin in adult animals is not completely understood but appears to be minimally important.
4. How is calcium transported in blood?
Approximately 50% of calcium in blood is ionized and biologically active. Approximately
40% is protein-bound, and the remaining 10% is bound to other serum factors such as phosphate
or citrate.
5. What nonhormonal factors affect serum calcium concentration?
Acid-base status and concentrations of serum phosphorus and albumin may affect serum cal-
cium concentration. Acidosis increases plasma concentration of total and ionized calcium. As hydro-
gen (H+)ions increase in acidosis, they bind plasma proteins, displacing Ca
2+.
This process increases
ionized plasma Ca
2
+ concentration. Total serum calcium also changes with acid-base status. Ionized
Ca
2
+ concentration is affected by phosphorus concentration, because some Ca
2
+ is bound to phos-
phorus. An increase in plasma phosphorus, therefore, may result in decreased plasma ionized Ca
2
+
concentration. Total calcium concentration is affected by albumin concentration because
Hypercalcemia and Hypocalcemia 289
approximately 50% of calcium is bound to albumin. Therefore, an increase in albumin concentra-
tion results in increased total calcium concentration. Conversely, hypoalbuminemia can lead to
lowered total serum calcium concentration.
6. Define hypercalcemia and hypocalcemia.
In cats a total calcium concentration> II mg/dl is typically consistent with hypercalcemia
but varies with the laboratory; a total calcium concentration < 6.5 mg/dl is consistent with signif-
icant hypocalcemia. However, ionized Ca
z
+ concentration is a more accurate and physiologically
significant measure. For example, it is possible to have an abnormal total calcium measurement
and normal ionized calcium concentration; if ionized calcium is normal, calcium balance overall
is considered normal. Therefore, whenever possible, calcium concentration should be assessed
by measurement of ionized Ca
z
+.
7. Since serum proteins affect total calcium concentration, can total calcium concentra-
tion be corrected for serum protein concentration as in dogs?
Unlike dogs, no formula in cats can be used to correct the total serum calcium concentration
for serum protein concentration.
8. Howdoes hypercalcemia affect the kidneys?
Hypercalcemia has a profound effect on the kidneys. It may be associated with calcium de-
position in any soft tissue but is particularly important in the kidneys (nephrocalcinosis). Renal
tubular epithelial cells, damaged from mineralization, slough into the tubular lumen, resulting in
cast formation and tubular obstruction. Renal injury is further propagated by hypercalcemia-as-
sociated vasoconstriction, which results in ischemic damage. Hypercalcemia also results in ex-
cessive secretion of calcium in urine (hypercalciuria), which predisposes animals to formation of
calcium-containing uroliths.
9. Does hypercalcemia affect any other organs adversely?
Hypercalcemia usually is associated with bone resorption, which may lead to loss of normal
bone architecture and pathologic fractures. Hypercalcemia also can cause polyuria with com-
pensatory polydipsia by interfering with the response to antidiuretic hormone. Cardiac arrhyth-
mias due to decreased intraventricular conduction may develop in some cases and are
characterized by prolonged PR interval, atrioventricular block, and QRS-complex prolongation.
Experimentally hypercalcemia has induced acute pancreatitis in cats by facilitating activation of
pancreatic enzymes and causing pancreatic hypersecretion, but the clinical significance of these
experimental findings is not known. In humans, hypercalcemia is associated with hypertension,
increased platelet aggregation, thrombosis, and atherosclerosis, but whether these effects occur
in cats has not been determined.
10. What clinical signs are associated with hypercalcemia in cats?
Clinical signs associated with hypercalcemia may be mild and nonspecific. The most
common clinical signs in cats are gastrointestinal and include vomiting (observed most fre-
quently) and diarrhea or constipation. Polyuria, polydipsia, neurologic signs (mainly mental dull-
ness), anorexia, and lethargy are also common. If cystic calculi are present, clinical signs
associated with the lower urinary tract (i.e., hematuria, stranguria) may be expected. If renal fail-
ure has developed, appropriate clinical signs may be present.
11. Describe the physical examination findings in cats with hypercalcemia.
Physical examination findings are usually nonspecific but may be related to the cause of hy-
percalcemia. For example, in one report of cats with primary hyperparathyroidism, 3 of 7 cats
had a palpable parathyroid mass. A thorough physical examination should be performed in every
cat with hypercalcemia to assess the parathyroid glands and kidneys, to detect palpable tumors,
and to determine whether concurrent diseases are present.
290 Hypercalcemiaand Hypocalcemia
12. What are the differential diagnoses for hypercalcemia?
The numerous possibilities can be remembered by the mnemonic GOSH DARN IT:
G = Granulomatous disease, in which activated macrophages can produce calcitriol
o = Osteolytic disease, which, if severe, can cause mild hypercalcemia.
S =Spurious result, due to artifactual elevation of serum calcium measurement by lipemia
or hemolysis (depending on laboratory technique)
H = Hyperparathyroidism
D = Vitamin D toxicosis, which is seen after ingestion of cholecalciferol rodenticides
A = Addison's disease, in which hypoadrenocorticism affects renal calcium excretion and
gastrointestinal calcium absorption.
R = Renal failure
N = Neoplasia
I = Idiopathic disease
T = Temperature; severe hypothermia may cause hypercalcemia
13. Which are the most common causes of hypercalcemia in cats?
Neoplasia, chronic renal failure, and primary hyperparathyroidism.
14. How does malignancy cause hypercalcemia?
Hypercalcemia of malignancy may result from various neoplasms, but the most common in
cats are lymphosarcoma and squamous cell carcinoma. Other neoplasias associated with hyper-
calcemia in cats include leukemia, osteosarcoma, fibrosarcoma, undifferentiated sarcoma, and
bronchogenic carcinoma. Perianal apocrine gland adenocarcinoma, multiple myeloma, thyroid
adenocarcinoma, and mammary tumors are common causes of malignant hypercalcemia in dogs
but not cats. Hypercalcemia of malignancy is often due to excessive secretion of parathyroid hor-
mone-related peptide (PTHrP), a peptide that can bind to PTH receptors and mimic PTH.
Alternatively, various osteoclast-activating factors may be secreted from neoplastic cells.
15. How does renal failure cause hypercalcemia?
Hypercalcemia of chronic renal failure is incompletely understood, but it may be due to lack
of renal phosphorus excretion. Hyperphosphatemia results, and the phosphorus can complex with
the calcium, resulting in a transient decrease in plasma Ca
2
+concentration and compensatory sec-
ondary hyperparathyroidism. Another possible explanation for hypercalcemia of chronic renal
failure is that loss of renal mass results in decreased calcitriol production. Because calcitriol in-
hibits PTH synthesis, decreased calcitriol concentration results in secondary hyperparathyroidism.
16. What is the underlying cause of primary hyperparathyroidism? How is it diagnosed?
Primary hyperparathyroidism in cats is usually due to a PTH-secreting parathyroid adenoma.
Diagnosis is made by measurement of serum PTH concentration. With hyperparathyroidism,
PTH is in the upper end of or above the normal range.
17. What other diseases have been associated with hypercalcemia?
Nonparathyroid endocrine disorders, such as diabetes mellitus, hyperthyroidism, and,
rarely, hypoadrenocorticism
Infectious diseases, such as feline infectious peritonitis, toxoplasmosis, actinomycosis,
atypical mycobacteriosis, nocardiosis, and cryptococcosis
Lower urinary tract disease
Liver disease
Bone marrow disease, such as myelodysplasia and myelofibrosis
Whether some of these actually cause the hypercalcemia (e.g., liver disease) is unclear.
Furthermore, urolithiasis is a common condition reported in association with hypercalcemia, but
it is the result rather than the cause. In addition, mild hypercalcemia may be a normal finding in
young animals.
Hypercalcemia and Hypocalcemia 291
18. How does measurement of serum phosphorus concentration aid in ranking differential
diagnoses?
Primary hyperparathyroidism, vitamin D toxicosis, and neoplasia can be difficult to distin-
guish. With a neoplasm that secretes PTHrP or primary hyperparathyroidism, serum phosphorus
is in the low-normal to below-normal range, because PTH and PTHrP increase renal phosphorus
excretion. With vitamin D toxicosis, serum phosphorus is in the high-normal to above-normal
range because vitamin D increases gastrointestinal phosphorus absorption.
19. How is hypercalcemia treated?
The most important component of treatment for hypercalcemia is treatment of the underly-
ing disease. For example, if the hypercalcemia is secondary to lymphosarcoma, the most effec-
tive approach is treatment of the neoplasia. Similarly, if the cat has primary hyperparathyroidism,
a parathyroidectomy is recommended. However, symptomatic treatment of hypercalcemia is
warranted when clinical signs associated with hypercalcemia are severe and must be addressed
before establishing the diagnosis and treating the primary cause of hypercalcemia.
20. What is the commonly used symptomatic treatment for hypercalcemia?
The most common modes of symptomatic treatment are correction of fluid deficits, saline
diuresis, and furosemide administration. The sodium load that occurs with saline diuresis pro-
motes increased renal calcium excretion. Once the cat is well hydrated, furosemide may be
added. By inhibiting the sodium-potassium-chloride cotransporter in the thick ascending limb of
the loop of Henle, furosemide decreases sodium reabsorption, which, in turn, causes increased
calcium excretion.
21. What other options are availabc1efor symptomatic therapy of hypercalcemia?
Other modes of treatment for hypercalcemia include administration of prednisone or calci-
tonin. Prednisone should be given only after a diagnosis has been confirmed. Prednisone may ob-
scure a diagnosis of lymphosarcoma, potentially for weeks to months. Glucocorticoids increase
urinary calcium secretion, possibly by decreasing tubular calcium reabsorption, and decrease
gastrointestinal absorption. Calcitonin promotes hypocalcemia by increasing calcium retention in
bone and by increasing urinary excretion of calcium.
22. Describe the pathophysiology associated with hypocalcemia.
The most important changes observed with hypocalcemia are due to increased neuromuscu-
lar excitability, which causes spontaneous skeletal muscle contraction, tetany, and possibly
seizures. Effects of hypocalcemia on other organs are less dramatic and less important clinically.
23. What clinical signs are associated with hypocalcemia?
The most obvious clinical signs are neuromuscular, and the most common of these are ner-
vousness, seizures, and tetany. Other neuromuscular signs include tense or aggressive behavior,
depression, facial or foot pruritus, muscle spasms, cramping, pain, twitching, tremors, stiff gait,
weakness, and disorientation. Inappetence, weight loss, vomiting, and diarrhea also may occur.
24. Describe the physical examination rmdings in cats with hypocalcemia.
Physical examination findings also are related mostly to neuromuscular disturbances and
may include seizures or muscle fasciculations. Other nonspecific findings, such as weakness, de-
pression, fever, hypothermia, and dehydration, may be present. Lenticular cataracts are common
in humans with hypoparathyroidism and have been reported in hypoparathyroid cats.
25. What are the differential diagnoses for hypocalcemia?
Overall, the most common form of hypoparathyroidism in the cat is iatrogenic, subsequent
to thyroidectomy. The most common cause of spontaneous hypocalcemia is chronic renal fail-
ure. Spontaneous hypoparathyroidism is rare. Hypocalcemia also occurs in cats with acute pan-
creatitis, intestinal malabsorption of vitamin D or other causes of vitamin D deficiency,
292
eclampsia, ethylene glycol toxicity, or malnutrition and in cats that have received phosphate-
containing enemas or transfusion with a large volume of citrated blood. Because calcium binds
to serum proteins, hypoalbuminemia can cause a low total serum calcium measurement.
However, the biologically active ionized calcium is normal and the total serum calcium mea-
surement insignificant.
26. How is hypocalcemia treated on an emergency basis?
Emergency treatment consists of intravenous administration of calcium in the form of 10%
calcium gluconate (5-15 mg/kg given slowly over 10-30 minutes). The electrocardiogram should
be monitored during administration. If bradycardia, premature ventricular complexes, or prolon-
gation of the PR interval or QRS complex is observed, calcium administration should be discon-
tinued until the problem resolves; infusion should then be reinitiated at a slower rate. If oral
supplementation with vitamin D and calcium is needed (e.g., primary hypoparathyroidism), a
continuous rate intravenous infusion or subcutaneous administration of calcium is necessary to
maintain adequate serum calcium concentration until oral supplementation takes effect.
27. Does hypocalcemia always need to be treated as an emergency?
Hypocalcemia should be treated if clinical signs are present, but mild hypocalcemia does not
always cause clinical signs.
28. How should hypocalcemia be treated on a long-term basis?
Some causes of hypocalcemia are self-limiting (e.g., pancreatitis, eclampsia) and resolve
with the underlying disease. If long-term therapy is required (e.g., spontaneous hypoparathy-
roidism), oral vitamin D and calcium supplementation are required initially. Vitamin D prepara-
tions include vitamin D
2
(ergocalciferol), the synthetic form of vitamin D (dihydrotachysterol
[DHTJ), and vitamin 0
3
(calcitriol). Ergocalciferol has the longest onset of action and time re-
quired for toxicity relief, followed by DHT and calcitrioI. However, calcitriol is the most expen-
sive and requires compounding; ergocalciferol is the least costly. Oral doses of vitamin 0 and
calcium supplementation vary with the type of preparation and must be tapered to effect in each
patient. If supplementation is used, close monitoring of blood urea nitrogen, creatinine, calcium,
and phosphorus is imperative-usually every 2-3 days until the dose is titrated. Hypercalcemia
and hyperphosphatemia may occur with oversupplementation. Depending on the vitamin 0
preparation, toxicity can last for weeks. Because it is safer, calcitriol is the treatment of choice.
Calcium supplementation usually can be discontinued once the effect of supplemental vitamin 0
is complete. Iatrogenic hypoparathyroidism secondary to thyroidectomy may be transient, lasting
from days to months. If parathyroid tissue was damaged but not removed during surgery, func-
tion may be decreased only temporarily. In such cases, vitamin 0 therapy can be discontinued
when the parathyroid recovers.
Recommended Starting Doses of Compounds Usedfor Treatment ofHypocalcemia'
COMPOUND DOSE COMMENTS
10%Calciumgluconate
Calciumcarbonate
Calcitriol (vitamin0
3
)
capsule or
formulate)
5-15 mg/kggivenslowlyIV
over 10-30 min if clinical
signs are present
0.5-1 gmof calciuml24hr orally
0.03-0.06 hr orally
Effectiveimmediately
Effectivewithin 1-3 days; may
cause inappetence
Effectivewithin 1-4 days; toxicity
resolutionin 1-14 days
Dose is basedon therapeutic
recommendations for humans;
no studies of dosing in cats
BIBLIOGRAPHY
293
I. Cotran RS, Kumar V, Collins T: The endocrine system. In Cotran RS, Kumar V, Collins T (eds): Robbins
Pathologic Basis of Disease. Philadelphia, W B. Saunders, 1999 pp 1121-1169.
2. Feldman EC, Nelson RW: Hypercalcemia and primary hyperparathyroidism. In Feldman EC, Nelson RW
(eds): Canine and Feline Endocrinology and Reproduction. Philadelphia, WB. Saunders, 1996, pp
455-496.
3. Feldman EC, Nelson RW: Hypocalcemia and primary hypoparathyroidism. In Feldman EC, Nelson RW
(eds): Canine and Feline Endocrinology and Reproduction. Philadelphia, WB. Saunders, 1996, pp
497-516.
4. Flanders lA, Scarlell JM, Blue IT, et al: Adjustment of total serum calcium concentration for binding to
albumin and protein in cats: 291 cases (\986-1987). 1 Am Vet Med Asoc 194:1609-1611, 1989.
5. Ganong WF: Hormonal control of calcium metabolism and the physiology of bone. In Ganong WF (ed):
Review of Medical Physiology. NewYork, Simon & Schuster, 1999, pp 365-377.
6. Kallet AI, Richter KP, Feldman EC, et al: Primary hyperparathyroidism in cats: Seven cases
(1984-1989).1 AmVet MedAssoc 199:1767-1771,1991.
7. Kruger 1M, Osborne CA: Canine and feline hypercalcemic nephropathy. Part I: Causes and conse-
quences. Comp Cont Educ Pract Vet 16:1299-1315, 1994.
8. Kruger 1M, Osborne CA: Canine and feline hypercalcemic nephropathy. Part II: Detection, cure and con-
trol. Comp Cont Educ Pract Vet 16:1445-1458, 1994.
9. Layer P, Hotz 1, Schmitz-Moormann HP, et al: Effects of experimental chronic hypercalcemia on feline
exocrine pancreatic secretion. Gastroenterology 82:309-316, 1982.
10. McClain HM, Barsanti lA, Bartges JW: Hypercalcemia and calcium oxalae urolithiasis in cats: A report
of 5 cases. 1 Am Anim Hosp Assoc 35:297-301, 1999.
II. Peterson ME, lames KM, Wallace M, et al: Idiopathic hypoparathyroidism in 5 cats. J Vet Intern Med
5:47-51, 1991.
12. Saul M, Genuth D: Endocrine regulation of calcium and phosphate metabolism. In Berne RM, Levy MN
(eds): Physiology. St. Louis, Mosby, 1998, pp 848-871.
13. Savary KCM. Price GS, Vaden SL: Hypercalcemia in cats: a retrospective study of71 cases (1991-1997).
1 Vet Intern Med 14:184-189,2000.
14. Waters CB, Scott-Moncrieff lCR: Hypocalcemia in cats. Comp Cont Educ Pract Vet 14:497-506. 1992.
Urinary incontinence
Urinary tract infection
v. Reproductive Problems
Section Editor: Deb Greco, D.V.M.
58. PYOMETRA AND VAGINAL DISCHARGES
Davyd Pelsue. D.v.M.
1. What causes vaginal discharge in cats?
There are many potential causes of vaginal discharge in cats. The character of the discharge,
combined with history, clinical presentation, cytology, urinalysis, other laboratory results,
vaginoscopy, and diagnostic imaging, can be used to achieve a definitive diagnosis in most cats.
DifferentialDiagnosesfor VaginalDischargein Cats
Serous to mucoid discharge (cornified cellson cytology)
Proestrus to estrus
Mucopurulent discharge
Primary bacterial infection
Mycoplasma spp.
Coxiella burnetii
Secondary bacterial infection
Pyometra
Endometrititis
Vaginitis/vestibulitis
Foreign body
Neoplasia
Stricture
Hemorrhagic discharge
Trauma
Neoplasia
Coagulopathy
2. How do I perform vaginal cytology?
A sterile cotton swab should be introduced gently into the vestibule by directing it dorsally
first, above the clitoral fossa, and then cranially. Placing a drop of sterile 0.9 sodium chloride aids
in the passage of the swab. The swab then is rolled along a microscope slide several times to pro-
vide areas of varying thickness, air-dried, stained, and examined microscopically. Attention
should be given to the type of epithelial cell, presence of red blood cells or neutrophils, and pres-
ence or absence of bacteria. Material draining from the vulva can be examined but does not allow
accurate determination of epithelial changes.
3. What is the significance of a mucopurulent vaginal discharge?
In cats, presence of a mucopurulent vaginal discharge is usually consistent with a secondary
bacterial infection. Primary infections with Coxiellaburnetii (see Chapter 88) and Mycoplasma
spp. are thought to be unusual. Because C. burnetii is a significant public health risk, care should
be taken when attending to the reproductive tract of cats.
295
296 Pyometra and Vaginal Discharges
4. Define pyometra and endometritis.
Pyometra is the abnormal accumulation of purulent material in the uterus. Endometritis is
inflammation involving only the endometrial lining of the uterus.
5. What is the difference between closed and open pyometra?
These distinctions relate to the state of the cervix. A closed cervix leads to greater accumu-
lation of purulent material within the uterus. Such patients, therefore, have a greater chance of
developing secondary complications such as renal dysfunction, hepatic dysfunction, anemia,
cardiac arrhythmias, coagulation abnormalities, peritonitis, and septic shock. An open cervix
allows more drainage of the purulent material from the uterus, leading to a greater degree of
vaginal discharge. It is not known what specific factors lead to the development of open vs.
closed pyometra.
6. How does pyometra develop in cats?
Because cats are induced ovulators, pyometra develops less frequently in cats than in dogs.
In cats, ovulation is required for the formation of corpora lutea, which subsequently secrete prog-
esterone. The influence of progesterone on the uterus can lead to cystic endometrial hyperplasia.
In addition, progesterone suppresses leukocyte activity in the uterus, which may allow accumula-
tion of mucus and inflammatory exudate to build up in the uterus. Bacterial infection is thought
to ascend from the vagina while the cervix is open during proestrus and estrus.
7. Does pyometra occur only in bred cats?
Pyometra can occur in bred or unbred cats. Adequate stimulation can lead to ovulation in
some unbred cats. In others, use of progesterone-containing therapeutics may be the culprit.
8. What are the clinical signs of pyometra?
Vaginal discharge occurs in just over one-half of cases. Other common signs are anorexia,
lethargy, vomiting, abdominal distention, and polydipsia/polyuria. Dehydration, a palpably en-
larged uterus, and fever are frequently detected on physical examination. A large proportion of
cases have been in estrus within the previous 4 weeks.
9. How is pyometra diagnosed?
A presumptive diagnosis often is based on history and clinical signs. In approximately 80%
of cases, the uterus is visible as a tubular fluid/soft tissue structure on survey abdominal radi-
ographs. Ultrasound can be used to distinguish between a fluid-filled and a gravid uterus.
Cytology of the vaginal discharge, if present, generally reveals the presence of large numbers of
neutrophils with intracellular bacteria. Extracellular bacteria may be present as a result of conta-
mination from the lower urinary tract.
Ultrasound of an enlarged, pus-filled uterus in a cat with
pyometra.
Pyometra and Vaginal Discharges 297
10. Are serum biochemical analysis and hematologic evaluation necessary in making the
diagnosis?
Although these tests are not required, they are important in evaluating the whole patient.
Common biochemical abnormalities associated with pyometra include hyperproteinemia,
azotemia, and hypokalemia. Increases in liver enzyme activities also may be observed. The most
common hematologic abnormality is leukocytosis with a regenerative left shift. These findings
help to guide fluid and drug therapy and also act as baselines to monitor response to therapy.
Cystocentesis should not be attempted in patients suspected of having pyometra.
11. What are the most common bacterial isolates associated with pyometra?
Escherichia coli, Streptococcus spp., and Staphylococcus spp. are isolated most commonly.
However, the putrid odor and mixed flora commonly noted on cytologic exam suggest anaerobic
involvement in many cats.
12. How is open pyometra treated in nonbreeding cats?
For nonbreeding cats, ovariohysterectomy (OHE) should be performed. Septic shock should
be treated as indicated. A sample of the uterine discharge should be submitted for culture and an-
timicrobial susceptibility.
13. What alternative is available for breeding cats?
A dose of 0.1-0.25 mglkg of natural prostaglandin F
2a
(PGF
2a
) administered subcutaneously
every 12-24 hours has proved to be effective. Before institution of therapy, a culture and antimicro-
bial susceptibility test of the vaginal discharge is submitted. Concurrent broad-spectrum antimicro-
bial therapy is instituted until antimicrobial susceptibility results return. Appropriate antimicrobial
choices include beta-lactams (such as amoxicillin and cephalexin), potentiated penicillins (such as
amoxicillin-c1avulanic acid), and sulfonamides. Adverse reactions to PGF
2n
are common, especially
with the first dose. These reactions, which relate to PGF
2a
actions in many tissues throughout the
body, include vocalization, panting, restlessness, grooming, tenesmus, salivation, diarrhea, kneading,
mydriasis, emesis, urination, and lordosis in decreasing frequency. PGF
2n
is effective because it
causes uterine contractions, thereby draining the pus-filled uterus. Therapy usually requires 3-5
days. Because of the common adverse reactions, hospitalization is recommended. This therapy has
been shown to be 95-100% successful in returning queens to a normal estrous cycle, with 80% de-
livering normal litters. PGF
2a
should be reserved for young, otherwise relatively healthy queens. It
should not be used in sick animals because of delayed improvement of the patient.
14. Howis closed pyometra treated?
OHE is the treatment of choice. Be careful to avoid the enlarged uterus when entering the
peritoneal cavity to prevent rupture and spillage of uterine contents. Obtain a urine sample via
cystocentesis at surgery for aerobic culture and antimicrobial susceptibility before abdominal
closure. A culture of the uterine contents should be submitted for aerobic culture, anaerobic cul-
ture, and antimicrobial susceptibility. Empirical antimicrobial therapy is instituted until the re-
sults return. Appropriate choices include combination therapy with enrofloxacin and ampicillin
or the use of a single-agent second-generation cephalosporin. These protocols have been used
successfully in our hospital; they provide aggressive broad-spectrum coverage. Placement of
drains through the cervix has been moderately successful in treating bitches with closed-cervix
pyometra. This technique is more difficult in queens because of their smaller size, and results
have not been reported in the veterinary literature. Therefore, their use is not recommended.
15. What are the complications of pyometra?
Death is the most serious complication, occurring in approximately 8% of cases. Causes of
death include sepsis, bacterial peritonitis, renal dysfunction, and liver disease. Other complica-
tions include anorexia, lethargy, anemia, fever, vomiting, anesthetic problems, hemorrhage, de-
hiscence, recurrent estrus, fistulous tract formation, and urinary incontinence. Most of these
complications resolve with appropriate symptomatic therapy.
298
Failure to Conceive
16. Can cats develop "stump" pyometra?
Cats occasionally develop pyometra of the remnant of the uterus after OHE C'stump" py-
ometra). History, clinical signs, physical examination findings, and diagnosis are similar to
those for open- or closed-cervix pyometra. The requirements for this condition are twofold: (I)
remaining uterine tissue and (2) residual ovarian tissue. Treatment consists of laparotomy to
remove the remaining uterine tissue and residual ovarian tissue. The incidence of stump pyome-
tra has not been reported in the veterinary literature. At our hospital, few cases have been diag-
nosed. Cats can also develop "stump" granulomas, a condition that can mimic stump pyometra.
In this case, the uterine stump forms a granuloma secondary to inflammatory reaction to the
suture material. Treatment consists of removing suture material, if identifiable, or removal of
residual uterine tissue, if needed.
BIBLIOGRAPHY
I. Davidson AP, Feldman EC, Nelson RW: Treatment of pyometra in cats, using prostaglandin F
2a
: 21 cases
(1982- I990). J Am Vet Med Assoc 200: 825-828, 1992.
2. Hedlund CH: Surgery of the reproductive and genital systems. In Fossum (ed): Small Animal Surgery. St.
Louis, Mosby, 1997, pp 544-549.
3. Kenney KJ, Matthiesen DT, Brown NO, et al: Pyometra in cats: 183 cases (1979-1984). J Am Vet Med
Assoc 191:1130-1132, 1987.
4. Manetta SM, Matthiesen DT, Nichols R: Pyometra and its complications. Probl Vet Med 1:50-62. 1989.
5. Potter K, Hancock DH, Gallina AM: Clinical and pathological features of endometrial hyperplasia, py-
ometra, and endometritis in cats: 79 cases (1980-1985). J Am Vet Med Assoc 198:1427-1431, 1991.
6. Stone EA, Cantrell CG, Sharp NJH: Ovary and uterus. In Slatter (ed): Textbook of Small Animal Surgery.
59. FAILURE TO CONCEIVE
Sara Stephens, D.v.M.
1. At what age do queens begin to cycle?
Female cats go through puberty, defined by onset of first estrus, at an average age of 5-10
months (range = 4-21 months). Longhaired breeds, Manx, and Persians may enter puberty later
in life than shorthaired breeds. A body weight of 2.3-2.5 kg (5.G-5.5 pounds) usually must be
achieved for a female cat to cycle. Cats reaching an appropriate age during the seasonal anestrus
do not go though their first estrus until the breeding season begins.
2. Describe the seasonal cycle of the queen.
Cats are seasonally polyestrous, cycling for an average of 5.8 3.3 days every 2-3 weeks
from January through mid-October. The seasonal anestrus from mid-October through December
is caused by day length: cats maintained under artificial lights for 12 continuous hours daily will
cycle year round (13 4.9 times/year) and may exhibit increased fertility. At least 10 hours of
daylight (50 footcandles/hour) is necessary for cycling to occur. Fourteen to 16 hours of light
(8-10 hours of dark) maximizes the number of cycling queens in a colony. Longhaired breeds
tend to be more seasonal than shorthaired breeds.
The corpus luteum persists for about 30-40 days in the queen that ovulates and is not preg-
nant (pseudopregnancy). The next cycle may begin any time thereafter and usually does so within
10 days. The postpartum estrus usually occurs 2-3 weeks after weaning and is shorter in duration
and less fertile. Anovulatory estrous cycles occur every 2-3 weeks during the breeding season if
the queen is not bred, and it has been suggested that interestrous periods may lengthen during
times of warm temperatures.
Failure to Conceive 299
3. What hormonal factors are involved in estrus?
Gonadotropin-releasing hormone (GnRH) secreted by the hypothalamus stimulates the re-
lease of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary
gland. FSH stimulates the secretion of from the ovarian follicle. The increasing
serum concentration of estrogen triggers the follicular phases of proestrus and estrus.
4. What behavioral changes characterize proestrus and estrus?
Proestrus and estrus in the queen are not physically discernible by changes in genitalia or dis-
charges from the reproductive tract but are recognized by behavioral changes. Proestrus is character-
ized by an increase in affectionate behavior and rubbing, treading with the rear feet, vocalizing, and
decreasing hostility toward the male. Proestrus may not be noticed but typically lasts up to 2 days.
Estrous behaviors include monotonous vocalization, increased affection, lordosis (elevation of the
hindquarters with lateral deviation of the tail), and rolling. Estrus usually lasts about 6 days. Some
studies suggest a shortening of estrus in bred cats, whereas others show no effect of breeding.
Estrous behavior has been observed in pregnant queens, but true superfetation has not been proved.
S. How can estrus be determined?
A positive correlation has been shown between estrous behavior and cornified vaginal cytol-
ogy. Cytologic studies may be useful in defining estrus in queens that exhibit no overt estrous be-
havior. Moistened sterile swabs should be passed quickly up to the end of the cotton, twirled,
removed, and smeared. Individual cornified epithelial cells on a clear background ("clearing") in-
dicate estrus. Cytology is also helpful in diagnosing ovarian remnant syndrome because the ovar-
ian remnant produces estrogen.
6. What factors influence progesterone levels?
Bred cats or estrus cats that were induced to ovulate undergo a prolonged luteal phase (high
serum levels of progesterone produced by the luteinized follicle). Serum progesterone concentra-
tions rise 24-48 hours after ovulation and peak 25-30 days later.
The feline placenta either does not secrete progesterone or does so in amounts insufficient to
maintain pregnancy. Apparently pregnancy-specific luteotropic hormones from the feline pla-
centa or pituitary influence the life span of the corpus lute urn. During pregnancy the corpora
lutea continues to produce progesterone throughout gestation; serum concentrations gradually
decline during the second half of pregnancy.
7. How does age affect reproduction in queens?
If the first pregnancy occurs after 3 years of age, litter size and neonatal survival remain
poor. Reproductive performance declines after 6 years of age. Queens should be retired from
breeding after 8 years of age.
8. What is the duration of pregnancy in queens? What are the reported conception rates?
The duration of pregnancy is 56-69 days (average 66 days). If pregnancy is defined as the
first day on which serum progesterone concentration exceeds 2.5 ng/ml, the duration of preg-
nancy is 63-66 days. Reported conception rates in queens range from 68-83%.
9. When do queens ovulate?
Cats are induced ovulators; ovulation requires coital stimulation of the vagina. Lions are the
only felid that are not induced ovulators. An external trigger, usually coitus, stimulates release of
GnRH from the hypothalamus, which in tum stimulates release of LH from the pituitary within
2-4 hours. The LH causes ovulation in 1-3 days. The amount of LH released depends on the
number of copulations and the time during the estrous cycle when copulation occurs. Queens bred
only once exhibit great variability in serum LH concentrations, and fewer than 50% will ovulate.
In one study, more than 4 copulations were required to ensure enough LH release to induce ovula-
tion. More than 90%of normal domestic shorthair cats ovulate if bred 3 times daily for the first 3
days of estrus. Although cats are considered induced ovulators, several investigators have shown
300
Failure to Conceive
that 35-60% of colony cats spontaneously ovulate without coital stimulation or direct physical
contact of any kind.
10. When does the tom reach puberty?
Toms go through puberty, defined by first appearance of sperm in the ejaculate, at 8-12
months of age. Penile spines are androgen-dependent. appearing at 6-7 months of age and disap-
pearing after castration. The testes usually are descended at birth.
11. What are the accessory sex glands in the tom?
The prostate on the dorsolateral urethra at the neck of the urinary bladder and the bul-
bourethral glands, located craniolateral to the base of the penis.
12. When are mature toms capable of mating?
Mature toms are capable of mating repeatedly over a 4-5-day period without a decrease in
sperm numbers. Males maintained in 12 hours of continuous light daily show no seasonal change
in breeding behavior or semen quality.
13. Howis serum quality assessed?
Retrograde ejaculation (movement of spermatozoa into the urinary bladder during ejacula-
tion) occurs in normal toms. Collection of a urine sample by cystocentesis immediately after
breeding, with centrifugation and examination of the sediment, may allow gross evaluation of
semen quality.
14. Summarize the characteristics of normal feline semen.
Semen volume varies from 0.01-0.77 ml with an average of 0.5 ml. Volume is larger with
electroejaculation (EE) because of excessive stimulation of the accessory sex glands. Total
number of spermatozoa in the ejaculate averages 50-60 million, with a reported range of 3-143
million, and is larger with manual collection than with EE. Motility is variable. Over 60% of the
spermatozoa should have normal morphology.
15. Describe feline copulation.
Copulation consists of mounting of the queen by the tom. positioning of the tom and erec-
tion of the penis, intromission and ejaculation by the tom. dismounting the queen, and the "after-
reaction" by the queen. The "after-reaction" consists of striking out at the male (76.5%), vulvar
licking (92.3%), and frantic rolling (100%). The entire copulation sequence is reported to take
from 0.5-9 minutes. and the pair may copulate as many as 6 times in each of the first 2 hours.
Copulation frequency then decreases. It is probably stimulation of the posterior vagina, not the
cervix, that triggers ovulation.
16. Can artificial insemination be performed in cats?
Semen collection techniques include manual collection with an artificial vagina (AV) and
EE. The use of xylazine as an anesthetic in the EE process should be avoided because it may pro-
mote retrograde ejaculation of spermatozoa into the urinary bladder. Artificial insemination,
either vaginal or intrauterine, is best performed 24-50 hours after medical induction of ovulation.
Ovulation can be induced with GnRH administered intramuscularly at 25 ug or human chorionic
gonadotropin (hCG) administered intramuscularly at 100 IV on the third day of estrus.
Anesthesia of the queen before oocyte release may compromise ovulation. A pregnancy rate of
50% is reported for insemination at the time of hCG administration, with an increase to 75% if
insemination is repeated 24 hours later.
17. Wbat is infertility?
Infertility is a broad term that refers to failure of the queen to breed. conceive. or carry a litter
to term, Infertility is not a diagnosis, but a sign of one or more problems. A helpful approach to in-
fertility in queens is to determine at which point in the breeding process the problem occurs:
1. Was estrus exhibited?
2. Was there a failure during the copulation process?
3. Did ovulation occur after copulation?
4. Was there a failure to conceive?
If the queen exhibits estrus < 18 days after being bred, no ovulation occurred. If the queen
exhibits estrus at 36-40 days after breeding, she ovulated but was not fertilized. If the queen ex-
hibits estrus after 60 days, abortion or resorption of the fetus occurred.
18. What are the three forms of anestrus in cats?
Seasonal anestrus, related to decreasing day length (seen in most cats and considered
normal)
Primary anestrus (queens who have never exhibited estrus)
Secondary anestrus (queens that have had at least one estrus cycle and then cease cycling)
19. What are the causes of anestrus in queens?
I. Queens housed with minimal lighting may enter a prolonged anestrus. Apparent lack of
cycling may occur in queens with silent heat (normal ovarian follicular development in the ab-
sence of estrous behaviors). Silent heat may be more common in cats low in the social hierarchy.
In one colony of 14 queens, 2 (14.3%) exhibited silent heat. Queens in silent heat diagnosed in
estrus by weekly vaginal cytology will stand for breeding and are fertile.
2. True lack of cycling has been reported in cats with karyotypic abnormalities (38, XO),
and in male pseudohermaphrodites (retained testes, female external genitalia). Cats that have
errors in chromosomal sex may have gonads that are small, lack oocytes, or have both ovarian
and testicular tissue (true hermaphrodites). Intersex cats may have normal karyotypes.
3. Ovarian dysfunction may result in persistent corpora lutea or luteal ovarian cysts that se-
crete progesterone (> 2 ng/ml). Such cats may not exhibit estrus. Luteal cysts should be con-
firmed with progesterone levels for several months before treating with prostaglandin F
2lX
Older
queens may cycle less frequently.
4. Lack of cycling during false pregnancy (ovulation without conception) and nursing (lac-
tational anestrus) is normal for cats. Lack of cycling also has been reported in cats infected with
feline leukemia virus.
20. Howcan estrus be induced?
I. Housing a queen with other cycling queens and increasing day length to 12-14 hours may
help to induce estrus.
2. FSH administered intramuscularly at 2 mg/day for 5 days should induce estrus in 4-5
days. Lower doses of FSH also may be effective: administer 2 mg on the first day, I mg on days
2 and 3, and 0.5 mg on days 4 and 5.
3. The GnRH analog, Decapeptyl (Organon, West Orange, NJ), may be administered subcu-
taneously at I ug/kg every 8 hours for 10 days or until signs of estrus behavior are noted.
4. Ultrapurified porcine FSH, divided into 5 daily subcutaneous doses for a total dose of 2.5
IU, followed on days 6 and 7 by 1.25 IU porcine FSH and 250 IU hCG given together intramus-
cularly, has resulted in supraovulation and an ovulation rate of 73%.
21. Do assays of pituitary and hypothalamic hormones help to diagnose anestrus?
The pituitary hormones, FSH and LH, and the hypothalamic hormone, GnRH, are persis-
tently elevated in cats with ovarian/testicular aplasia or hypoplasia and after ovariohysterectomy
and castration. The secretion of all three hormones is pulsatile. Because of their difficulty, assays
are rarely attempted.
22. Can estradiol levels be used to diagnose anestrus?
Serum concentrations of estradiol are about a thousandfold less than those of progesterone
and are often at or below the limits of detection of the assays used by many commercial endocrine
laboratories. Estradiol concentrations also fluctuate widely and rapidly; thus measurement often
302
Failure to Conceive
does not yield diagnostic results. However, estrogen levels may differentiate a queen with persis-
tent anestrus from one with unexpressed estrus. During follicular phase (proestrus and estrus),
the plasma estradiol concentrations are > 20 pg/ml. During anestrus and interestrus, the estrogen
levels are < 20 pg/ml.
23. Describe the role of progesterone in the diagnosis of anestrus.
Progesterone may be assayed to differentiate pseudopregnancy from anestrus. Luteal phase
serum progesterone concentration is > 2 ng/ml. If the progesterone level is < I ng/ml, no luteal
tissue exists. The use of hormonal challenge testing may induce elevated progesterone. Blood is
drawn 2-3 weeks after intramuscular administration of one 25-flg dose of progesterone. Less
than 2 ng/ml indicates presence of functional luteal tissue and functional ovaries. Progesterone
can be assayed to determine whether ovulation actually occurred after estrus induction with FSH-
and GnRH-induced ovulation.
24. How is GnRH used to diagnose anestrus?
Intramuscular administration of a single 2 5 - ~ g dose of GnRH causes a 20-fold increase in
LH in anestrous queens and a loo-fold increase in estrous queens. Failure of serum LH to in-
crease after GnRH administration indicates a possible pituitary problem. Failure of progesterone
to increase after GnRH administration indicates prior ovariohysterectomy or gonadal dysfunction.
25. Discuss the role of vaginal cytology in the diagnosis of anestrus.
Vaginal cytology for detection of estrogen can be assessed every 1-2 weeks to detect queens
in silent heat.
26. What causes persistent, nonovulatory estrus?
1. The queen may appear to be in constant heat because follicles form in overlapping waves.
Persistent estrus may be behavioral rather than physiologic, and breeding may still lead to preg-
nancy.
2. Abnormally long estrus (> 16 days) and high serum estrogen levels may be due to func-
tional cystic ovaries, functional granulosa cell tumors, or portosystemic shunts.
3. Granulosa cell tumors are the most common ovarian tumor in queens. These large unilat-
eral tumors often are palpable; they may cause abdominal distention and produce signs of hypere-
strogenism, including persistent estrus. Granulosa cell tumors are commonly malignant.
4. Ovarian rerrmant syndrome (ORS) is defined as the presence of functional ovarian tissue in a
previously ovariohysterectomized queen. The interval between ovariohysterectomy and the first ap-
pearance of estrous behavior caused by ORS is variable, with a reported range of 2 weeks to 9 years.
Individual cats may possess accessory lobes of the ovaries, but they are rare in domestic animals. All
reported ovarian rerrmants have been found at the pedicle; in one study, 27% were bilateral.
27. Describe the diagnostic plan for cats with suspected persistent nonovulatory estrus.
I. Vaginal cytology is easily performed and is an inexpensive, accurate way to detect the
presence of estrogen.
2. Ultrasound may demonstrate the presence of follicles or tumors, and serum estrogen con-
centrations may be elevated in queens with persistent estrus.
3. Intramuscular administration of hCG at 250 IU/day for 2-3 days or GnRH at 2.2
ug/ml/day for 3 days may luteinize follicular cysts.
4. Ovariohysterectomy is recommended if the queen does not respond quickly and ovulate.
28. What may cause copulation failure?
Because of the speed with which copulation occurs and the aggressive attitude of the cats
during the process, it may be difficult to know whether copulation in fact has occurred. The
queen's scream may be the only evidence that breeding has occurred. The queen should be intro-
duced to the tom in his territory several days before estrus. Cats exhibit partner preference and
may refuse to mate with one cat but mate with another. If female dominance precludes mating,
the queen can be lightly sedated, a different male can be used, or 25 IJg GnRH may be adminis-
tered intramuscularly 1 hour before mating to increase the tom's sexual determination.
Vulvar, vaginal, and vestibular barriers, such as persistent hymenal remnants, annular stric-
tures, hypoplasia, septal defects, and reproductive tract neoplasia, may exist in the queen. A
vulvar stricture may develop in queens with a history of dystocia and preclude copulation.
Contrast vaginography may be used to identify strictures and malformations.
29. What test determines whether ovulation has occurred?
Serum progesterone concentrations rise 24-48 hours after ovulation. A serum progesterone
level> 2.5 nglml 48 hours after copulation confirms ovulation. Because progesterone is the same
substance in all species, any progesterone assay may be used.
30. What causes ovulation failure?
More than 90% of normal domestic shorthair cats ovulate if bred 3 times/day for the first 3
days of estrus. Causes of ovulatory failure include breeding too late in the follicular cycle while
follicles are regressing, too few breedings, and low male libido resulting in too few copulations.
The queen and tom should be allowed to breed repeatedly, and the frequency of the copula-
tory cry should be noted if it occurs. Ovulation may be induced physically by vaginal insertion of
a metal or glass probe after breeding or medically by intramuscular administration of hCG at 250
lU on days 1 and 2 of estrus or GnRH at 25 Ilg on day 2 of estrus.
31. How can infertility in toms be recognized?
I. A sterile mating that induces ovulation causes the queen to enter the luteal phase (pseudo-
pregnancy) for 45-50 days. This scenario should raise suspicion of infertility of the tom.
2. Testosterone concentrations may be nondetectable in normal intact male cats, and levels
may need to be checked several times because of pulsatile secretion. Testosterone is best mea-
sured after challenge testing with either GnRH, administered intramuscularly at 25 Ilg with blood
drawn I hour later (normal values = 17.3-41.6 nmol/L) or hCG at 250 lU/cat with blood drawn 4
hours later (normal values =10.4-31.2 nmol/L). Testosterone levels should be greatest in intact
toms, less in cryptorchid toms, and negligible in castrated toms.
32. How common are cryptorchidism and monorchidism in toms?
Of 1,345 cats in one study, 23 (1.7%) were cryptorchid and 2 (0.1%) were monorchid.
Persian cats (29%) were overrepresented compared with other breeds (1.48%). Monorchid toms
had bilateral ductus deferens, testicular arteries and veins, and cremaster muscles.
33. What are the characteristic features of cryptorchidism in toms?
All toms with bilateral cryptorchidism have abdominally located testes.
In toms with unilateral cryptorchidism, no predisposition for side has been noted. Of af-
fected toms, 61% had abdominal and 39% had inguinal testes.
A polygenic mode of inheritance for cryptochidism has been suggested, although in most
species cryptorchidism has an autosomal recessive cause.
34. Howshould cryptorchid toms be managed?
All cryptorchid toms should be castrated bilaterally.
35. Does administration of exogenous testosterone stimulate spermatogenesis?
Testicular levels of testosterone are 50-100 times higher than serum levels. These high local
levels produced by the Leydig cells stimulate spermatogenesis. Administration of testosterone
does not increase spermatogenesis, however, because exogenous testosterone causes an increase
in serum levels, which gives negative feedback to the pituitary to decrease LH levels. Decreased
LH levels signal the Leydig cells to decrease the local production of testosterone and inhibit sper-
matogenesis.
304
Failure to Conceive
36. What causes smaU testes in toms?
Small testes may be congenital in toms with an abnormal karyotype or acquired after fetal or
neonatal panleukopenia infection. Calico and tortoiseshell male cats are often infertile. White coat is
carried on an autosome. The gene for black or orange coat is carried on the X chromosome. Normal
male cats with one X chromosome can exhibit either black or orange. but not both. Calico/tortoise-
shell males must have two X chromosomes either as triploidy (39, XXV) or mosaicsimlchimerism
(XXlXY, XXY!XY). Azoospermia is common because of seminiferous tubule dysgenesis.
37. What factors may contribute to poor libido in toms?
Age and timing may be factors in toms with low libido. Spermatogenesis begins at 5 months
of age, and sexual maturity is completed by 9 months of age. Spermatogenesis and epididymal
maturation take approximately 75 days. The quality of sperm decreases with age. Chronic infec-
tion can cause decreased sperm counts. Effusive feline infectious peritonitis can cause scrotal en-
largement and associated testicular infection.
Diphallia, penile hypoplasia, and persistent penile frenula have been reported in cats.
Adhesion of the penis to the prepuce may be a congenital lesion or result from inflammation.
Hair may become impacted in rings at the base of the penis, precluding copulation after a normal
mount, and can cause priapism (persistent erection). Prostate disease is uncommon in male cats.
38. How may poor libido in toms be managed?
If the tom is exhibiting poor libido, he should be housed separately from the queens. All
toms should be allowed to breed within their established territories. Artifical insemination also
may be used.
39. What tests are appropriate in all infertile toms and queens?
Serum biochemical panel, urinalysis, feline leukemia virus antigen test, feline immunodefi-
ciency virus antibody test, and total T4 concentration. In appropriate situations, karyotyping may
be informative.
40. How is early embryonic death differentiated from failure to conceive?
Pregnancy loss in the first 3 weeks of gestation is also called early embryonic death and
cannot be distinguished from failure to conceive. Until an early pregnancy test becomes available
for cats, early embryonic death is unlikely to be diagnosed or treated effectively.
41. What causes conception failure in the queen?
Insufficient luteal phase due to premature luteolysis may cause a decline in progesterone <
I ng/ml at 2-4 weeks after breeding. Serum progesterone concentrations < 2 ng/ml indicate
lack of the luteal tissue necessary to continue pregnancy.
Conception failure after copulation and ovulation may be due to cystic endometrial hyper-
plasia (CEH), subclinical uterine infection. lack of patency of the reproductive tract in the
queen, or poor semen quality in the tom.
Pyometra (CEH with overlying infection and subsequent development of purulent in-
trauterine fluid) occurs most commonly during the luteal phase of increased progesterone
secretion in nonpregnant cats that were induced to ovulate. Bacteria ascend from the vagina
more easily during this time. The organisms are usually from the normal vaginal flora;
Escherichia coli is the most common isolate, but other organisms have been cultured.
42. Define CEH. What causes it?
CEH is a progressive, irreversible, proliferative change of the uterine lining. It is common in
cats older than 5 years. CEH results from repeated exposure of the endometrium to estrogen and
progesterone, and it cannot be induced experimentally with either hormone alone. Repeated ovu-
latory cycles that do not result in pregnancy can increase the risk of pyometra in older queens.
Cats with CEH may be asymptomatic or infertile. Hyperactivity and pacing have been associated
with infertility and CEH in I cat.
43. Describe the signs and symptoms of CEH and pyometra.
In one study of 25 cats with CEH or pyometra, 20 had corpora lutea on the ovaries at the
time of ovariohysterectomy, despite no recent history of breeding or exposure to male cats.
Cats with pyometra present with variable signs, depending on the degree of cervical patency.
Clinical signs reported in 183 cats with CEH/pyometra included vaginal discharge (59%),
anorexia (40%), lethargy (32%), abdominal distention (17%). vomiting (16%), and polyurialpoly-
dispia (9%). Leukocytosis and a left shift occur less commonly than in dogs; one study reported an
incidence of 66% and 45%, respectively. See Chapter 58 for a discussion of treatment issues.
44. How should infertile queens be evaluated?
In addition to the tests listed in question 39, infertile queens should be tested for toxoplas-
mosis.
Ultrasound does not detect the normal uterus or ovaries, but fetal resorption with thicken-
ing of the uterine horns, endometritis, follicular cysts, and neoplasia may be detected.
Infusion of saline into the uterine horns with a small-gauge needle can determine patency
of uterine horns and oviducts. Both horns should fill uniformly, and saline should leak
through the oviducts. The uterotubular junction is tight (closed) in proestrus.
45. Any rmal comments about infertility in cats?
The cause of most breeding disorders is inappropriate breeding management. Proper hous-
ing, nutrition, and preventative care, including vaccinations, and parasite and disease control,
need to be discussed with the breeder. Timing of mating is also crucial and requires careful ob-
servation. It is important to work with the breeder through one or more estrous cycles. The high-
est fertility rate is seen in l-o-year-old queens. Diagnostic evaluation of older females may not
be warranted.
BIBLIOGRAPHY
I. Baldwin Cl, Peter AT: Use of ELISA test kit for estimation of serum progesterone concentrations in cats.
Feline Pract 24:27-31,1996.
2. Brockus CW: Endogenous estrogen myelotoxicosis associated with functional cystic ovaries in a dog.
Vet Clin Pathol 27: 55-56, 1998.
3. Cain JL: Disorders of feline reproduction. In Morgan R (ed): Handbook of Small Animal Practice, 3rd
ed. Philadelphia, WB. Saunders, 1997, pp 645-648.
4. Feldman EC, Nelson RW: Feline reproduction. In Feldman EC, Nelson RW (eds): Canine and Feline
Endocrinology and Reproduction. Philadelphia, WB.Saunders, 1996. pp 741-768.
5. Grooters AM: Diseases of the ovaries and uterus. In Birchard SJ, Sherding RG (eds): Saunders Manual
of Small Animal Practice, 2nd ed. Philadelphia, W.B. Saunders, 2000. pp 1016-1028.
6. Johnson CA: Disorders of the estrus cycle. In Nelson RW, Couto CG (eds): Small Animal Internal
Medicine. Mosby, St. Louis, 1998. pp 842-844, 846-892.
7. Johnston SO, Root MV: Managing infertility in purebred catteries. In August JR (ed): Consultations in
Feline Internal Medicine, 3rd ed. Philadelphia, WB. Saunders, 1997, pp 581-586.
8. Millis DL, Hauptman JG, Johnson CA: Cryptorchidism and monorchism in cats: 25 cases {I 980-(989).
J Am Vet Med Assoc 200: 1128-1130, 1992.
9. Purswell Bl: Diseases of pregnancy and puerperium. In Leib MS, Monroe WE (eds): Practical Small
Animal Internal Medicine. Philadelphia, W.B. Saunders, 1997, pp 463-464.
10. Root M, Johnston S, Olson P: Estrous length, pregnancy rate, gestation and parturition lengths, litter
size, and juvenile mortality in the domestic cat. JAm Anim Hosp Assoc 31:429-432, 1995.
II. Root Kustritz MY: Reproductive abnormalities of the queen, infertility in the queen and tom cat, and
anatomy and normal reproductive physiology of the queen and tom cat. A series of lectures presented
at the American Association of Feline Practitioners' Winter Meeting in Park City, Utah, February 6
and 7,2000.
12. Schwartz S: Stereotypic pacing associated with ovarian and uterine anomalies in a Siamese cat. Feline
Pract 24:29-32, 1996.
\3. Soderberg SF: Infertility and disorders of breeding. In Birchard SJ, Sherding RG (eds): Saunders Manual
of Small Animal Practice, 2nd ed. Philadelphia, WB. Saunders, 2000, pp \ 050--\ 059.
14. Von Reitzenstein M, Archbald LF: Theriogenology question of the month. J Am Vet Med Assoc
216:1221-1223,2000.
60. PREGNANCY LOSS
Sara Stephens, D.V.M.
1. What is the length of gestation in queens?
The duration of pregnancy in queens is 56-69 days. In one cat colony, the average gestation
was 66 days. The onset of pregnancy is defined as the first day on which plasma progesterone is
> 2.5 ng/ml. If progesterone rise is used as a starting point, the length of gestation in the queen is
63-66 days.
2. How is pregnancy diagnosed in queens?
After ovulation, the egg is in the oviduct for 5-6 days. Fertilization is presumed to occur
within the oviducts. The blastocysts become localized and recognized as spherical enlargements
within the uterus by day 13-14 of gestation. Trophoblastic attachment occurs near day 15 after
coitus. The fetal stage occurs when the thoracic cavity of the embryo closes at about 4 weeks
when the fetuses have a crown-to-rump length of 2.4 em, Progesterone concentrations during the
first 20 days of pregnancy are similar to those in pseudopregnant cats. After day 20, the plasma
progesterone is increased in pregnant cats. The placenta begins to synthesize and secrete proges-
terone after day 30 of gestation.
In one study, a serum progesterone concentration> 5 nglml at 6 or more days after breeding
was indicative of pregnancy with 81% accuracy. Pregnancy diagnosis in the cat is easily accom-
plished by ultrasonography 16-30 days after breeding, by abdominal palpation 21 days after
breeding, and by radiography 37 days after breeding. If a single radiograph is not definitive for
pregnancy, a second radiograph taken 5 days later should show progressive mineralization from
proximal to distal. Fetal viability is best accessed by ultrasonography, which may demonstrate the
fetal heart as early as day 16. Fetal numbers and gestational age are best assessed by radiography.
3. In what ways can pregnancy loss occur?
Embryonic death Retention of mummified or macerated fetuses
Resorption of the fetus Stillbirths
Abortion of the fetus
4. What causes pregnancy loss in queens?
There are maternal, fetal, and environmental causes of pregnancy loss in the queen. Often
the outcome depends on the stage of gestation when the queen is affected; gestational age of the
fetus determines whether a nonviable fetus will be resorbed or aborted. Pregnancy resorption
with no vulvar discharge occurs before day 30 of gestation. Abortion occurs in the second half of
pregnancy. Any fetus delivered before 60 days of gestation will be stillborn.
5. Define abortion.
Abortion results in fetal loss and occurs after mid-gestation in cats. Abortion usually is ac-
companied by discharge of fluid or fetal tissue. Any hemorrhagic vaginal discharge is abnormal
during the second-to-eighth week of pregnancy. The queen may remain clinically healthy despite
resorbing fetuses or aborting a litter. Queens may abort part of litter and carry the rest to term.
Sometimes it is difficult to tell an aborting cat from one with an open cervix pyometra.
6. What maternal factors may cause abortion?
Any serious systemic disease can result in resorption or abortion of fetuses. Uterine diseases
that can cause abortion include chronic endometritis, cystic endometrial hyperplasia, and uterine
adhesions.
306
Pregnancy Loss 307
7. How is abortion diagnosed?
Definitive diagnosis of abortion is hard to make unless a fetus is expelled. Habitually abort-
ing queens with multifocal placental necrosis and subsequent fetal autolysis during the third or
fourth week of gestation have been reported.
8. What are some environmental causes of pregnancy loss in queens?
Poor nutrition, trauma, and stress, such as shipping or bringing the cat to a new home, can
cause pregnancy loss in a queen. Taurine deficiency causes a postimplantation defect that is asso-
ciated with a decline in progesterone.
9. How is early embryonic death differentiated from failure to conceive?
Pregnancy loss in the first 3 weeks of gestation is also called early embryonic death and
cannot be distinguished from failure to conceive. Until an early pregnancy test becomes available
for cats, early embryonic death is unlikely to be diagnosed or treated effectively.
10. Can low plasma progesterone cause pregnancy loss?
Yes. Low progesterone makes the endometrium a poor substrate for implantation of the blas-
tocyst. This clinical scenario appears as an infertile cycle. Resorption or abortion can also occur
when the plasma progesterone is < I ng/ml; serum progesterone concentrations must be > 2
ng/mI to support pregnancy.
11. What is the source of gestational progesterone in cats?
The source of gestational progesterone in cats is debated. Studies have shown that cats have
a normal pregnancy despite ovariectomy at 45-50 days' gestation, indicating a placental source
of progesterone in late gestation. However, other recent studies have indicated that cats ovariec-
tomized at day 45 of gestation abort; thus, the maintenance of the corpus luteum may be crucial
for a normal pregnancy in the queen. To diagnose hypoluteoidism, both progesterone drop and
early pregnancy have to be confirmed with ultrasound. Hypoluteoidism is probably an uncom-
mon cause of pregnancy loss in the queen.
12. How is progesterone measured in cats?
Progesterone is measured by radioimmunoassay (RIA) and enzyme-linked immunosorbent
assay (ELISA). The structure of progesterone does not vary among species; any progesterone assay
may be used to determine progesterone levels in queens. Hemolysis and lipemia may affect results.
13. What may cause early embryonic death?
Possible causes of early embryonic death include taurine deficiency, abnormalities of follic-
ular or luteal function, abnormalities of the genital tract, cystic endometrial hyperplasia, genetic
fetal defects, and subclinical uterine infection.
14. What is the most common infectious cause of abortion in queens?
Viral agents are the most commonly reported infectious cause of abortion in queens.
Examples include feline herpes virus I (FHV-I, rhinotracheitis), panleukopenia, feline infectious
peritonitis (FlP), feline immunodeficiency virus (FlV), feline calicivirus, and feline leukemia
virus (FeLV).
15. When does abortion due to FHV-1 occur?
Abortion secondary to FHV-I usually occurs at 5-6 weeks of gestation and is probably sec-
ondary to upper respiratory infection in the queen. FRV-I infection can result in abortion, mum-
mification, and stillborns.
16. How does panleukopenia affect pregnancy in queens?
Panleukopenia virus attacks tissue with a high mitotic rate. The queen may have adequate
neutralizing antibodies for self-protection but insufficient immunity for the developing fetuses.
308 Pregnancy Loss
Panleukopenia can cause early embryonic loss, abortion of mummified or macerated fetuses, and
stillbirths. Kittens also may be born blind, with hydrancephaly, and/or ataxia due to retinal. cere-
bral, and/or cerebellar degeneration. Prenatally infected kittens may have retinal dysplasia.
Antemortem definitive diagnosis can be difficult, because many cats have antibodies against pan-
leukopenia but titers only rise during acute viremia.
17. Discuss the role of feline coronaviruses in pregnancy loss.
Feline coronaviruses have been suggested as a cause of failure to conceive, abortion, stillbirth,
and congenital defects as well as the fading kitten syndrome (kitten mortality complex). Abortion
due to infection with FIP is thought to occur late in gestation and is associated with prolonged
vaginal bleeding. However, an epidemiologic study failed to link feline coronavirus with repro-
ductive failure or neonatal kitten mortality; thus its causative role in abortion is controversial.
18. How does FIV affect pregnancy in queens?
In utero transmission of FlV leads to several pathogenic consequences, including arrested
fetal development, abortion, stillbirth, subnormal birth weights, and birth of viable, virus-in-
fected, and asymptomatic but T-cell--deficient kittens.
19. Discuss the role of FeLVin pregnany loss.
FeLV has been reported to cause abortion from 3 weeks to term. FeLV can result in infertil-
ity, early embryonic death, resorption of fetuses, and abortion of normal-appearing fetuses. In
late pregnancy, fetuses may acquire lymphocyte-associated virus transplacentally, or the neonate
may be infected from the queen's milk or saliva. Such kittens may fail to thrive. The queen also
may develop pyometra and endometritis due to immunosuppression and then become infertile.
Seronegative healthy carriers have been identified. Positive cats should be removed from the cat-
tery with retesting at 90-day intervals until no positive cats are identified on two consecutive
tests. FeLV is a fragile virus. Routine cleanliness interrupts spread of disease in the environment.
Vaccination of negative cats is also helpful.
20. What is the risk of abortion due to calicivirus?
To date, only 2 cats have had calicivirus isolated from the genital tract after abortion. Thus
the true risk is unknown.
21. What are the bacterial causes of abortion in queens?
Bacterial infection of the uterus and subsequent pregnancy loss is uncommon in healthy cats
housed in a clean environment. Cats aborting due to Escherichia coli, staphylococcal. or strepto-
coccal uterine infection usually present with anorexia, depression, fever, straining, and a fetid,
yellow-brown vaginal discharge. The discharge should be cultured, and amoxicillin therapy (22
mg/kg orally every 12 hr) should be instituted pending culture results. Bacterial abortion may
occur in cats infected with FeLV secondary to virus-induced immunosuppression. The bacterial
pathogens causing abortion are usually present in normal vaginal flora.
22. What are the rickettsial causes of abortion in queens?
Coxiella burnetii is a rickettsial agent that can cause abortion. Cats may acquire the infection
by tick bites or ingestion or inhalation of organisms while feeding on infected body tissues or
milk. Although the true incidence of this infection in cats in unknown, C. burnetii has been grown
from the vagina of normal cats in Japan. There have been frequent reports of people becoming in-
fected with Q fever after exposure to aerosols from a contaminated environment or fomites from
feline parturient or aborted tissues (see Chapter 88).
23. Can protozoal agents cause abortion?
Toxoplasmosis is a common tissue protozoan that occasionally causes abortion. Most queens in-
fected with toxoplasmosis are asymptomatic carriers, but systemically ill queens may abort because
of placentitis. Toxoplasmic abortion usually occurs if the first exposure occurs early in gestation.
Pregnancy Loss
309
24. What drugs are associated with abortion or birth defects in cats?
Drugs associated with abortion include hormones (androgens, bromocriptine, estrogens, glu-
cocorticoids), anticancer drugs, anesthetics (barbiturates, halothane, methoxyflurane), and chlo-
ramphenicol. Misoprostol causes abortions due to the effect of prostaglandin on the reproductive
tract. Teratogenic drugs include primidone, griseofulvin, ketoconazole, amphotericin-B,
ciprofloxacin, and enrofloxacin, nonsteroidal anti-inflammatory drugs, tetracycline, aminoglyco-
sides, metronidazole. aspirin, propranolol, dimethylsulfoxide (DMSO), glucocorticoids, diethyl-
stilbestrol (DES), estradiol cypionate (ECP), testosterone, mibolerone, progesterone, diazepam,
midazolam, vitamin A, and vitamin D. Teratogens present during the first 26 days often cause
cephalic, ocular, otic, and/or cardiac abnormalities, whereas those present in the next 26 days are
more likely to cause palate, cerebellar, and/or urogenital defects.
25. What other factors may cause abortion?
Fetal causes of abortions include genetic fetal defects, such as X-monosomy, autosomal tri-
somy, and mosaicism. Uterine torsion, ectopic pregnancy and, possibly, hypocalcemia are rare
causes of abortion. Females older than 7-8 years tend to cycle irregularly, to have smaller litters,
and to have more problems with abortions and kittens with congenital defects.
26. Are all causes of stillbirths known?
The average rate of stillbirths is 12.9%with a range of 4.7-22.1%. Anatomic abnormalities
are found in 20%of kittens that are stillborn or die within the first 3 days of life, and most con-
genital abnormalities have no identifiable cause. Most birth defects have no identifiable cause,
and subsequent breedings are often uneventful.
27. What can be done to determine the cause of pregnancy loss?
Pregnancy can be confirmed by day 20 of gestation with ultrasound, and fetal viability can be
monitored. Ultrasound also may be used to confirm pregnancy loss before day 20. Breeding records
should be scrutinized to identify inherited problems. After an observed abortion, the queen should
receive a thorough physical examination and ophthalmic examination. Routine tests in most cases
include complete blood cell count, serum biochemical panel, FeLV antigen test, FlV antibody test,
panleukopenia antibody test, T. gondii antibody test, urinalysis, and progesterone concentration.
Hysterotomy can be done to obtain tissue for histology, microbial isolation, and karyotyping of
fetal tissue. Necropsy and histopathology should be performed on aborted or stillborn fetuses.
28. What can be done to decrease pregnancy losses?
Vaccinations should be up to date, and queens should be given antihelmintics before breeding.
All cats should be housed indoors in a clean environment. If the cats are gang-housed, multiple
litter boxes should be provided and kept clean to lessen coronavirus exposure. The food should be
of high quality; raw meat should not be fed during gestation to lessen the risk for toxoplasmosis.
All breeding females should test negative for FeLV and FlY. No drugs causing abortion or birth
defects should be given during pregnancy. Vaccines should not be given during pregnancy.
29. What contraceptives are available for cats?
Progestogens can prevent pregnancy in cats. Megestrol acetate (Ovaban; Schering-Ptough,
Kenilworth, NJ) is given at 2.5 mg orally every 24hr for up to 2 months or 5 mg/day for 3 days, fol-
lowed by 2.5mg/week for up to 18months. Side effects of progestogens in cats may be severe and
include mammary carcinoma, mammary hypertrophylfibroadenoma complex, uterine disease, dia-
betes mellitus, and suppression of the adrenal cortex. Progestogens are not approved for use as con-
traceptives in cats in the U.S. Preliminary studies in cats have shown that the slow-release
subdermal implant levonorgestral (Norplant) is effective in suppressing estrus for 12months with
no adverse effects except the development of cystic endometrial hyperplasia.
Mibolerone (Checque; Pharmacia & Upjohn, Kalamazoo, MI), an androgen approved for use
as a contraceptive in dogs, cannot be used safely in cats because the side effects include thyroid
dysfunction, hepatocellular lesions with increased systemic arterial pressure and cholesterol,
310
Pregnancy Loss
thickening of the cervical dennis, and clitoral hypertrophy. The mortality rate is significant with
doses as low as twice the estrus suppression dose. Contraceptive vaccines that immunize against
the zona pellucida surrounding the feline ova also may be used for contraception, but this method
is not currently available.
30. Howshould an unwanted pregnancy be terminated?
No drugs are approved for feline pregnancy termination in the United States, but several protocols
have been used. Mating should be confirmed with a vaginal smear to look for clearing (absence of
noncellular debris) and sperm. Estrogen is not recommended immediately after mating, but megestrol
acetate in a single oral dose of 2.0 mg during estrus has been reported to prevent implantation.
Pregnancy termination in cats can beeffected surgically (ovariohysterectomy) or medically. Medical
methods include prostaglandin F
2a
(PGF
2a
; Lutalyse, Pharmacia & Upjohn) at 500-1000 /!g/kg for 2
days at mid-gestation; c1oprostenol (Estrumate; Bayer, Shawnee Mission, KS) at 5 f.lg/kg subcuta-
neously for 2 days; and the prolactin inhibitor/dopamine agonist, cabergoline (Dostinex; Pharmacia &
Upjohn), at 5 f.lg/kg orally for 10-12 days at mid-gestation. A combination of daily oral administration
of cabergoline (5 f.lg/kg) and c1oprostenol injections (5 f.lg/kgsubcutaneously) every 2 days appears to
bea reliable, safe, and practical method for terminating pregnancy at day 30 of pregnancy, when a di-
agnosis of pregnancy by palpation or ultrasonography can easily be made. All five queens treated in
one study aborted in 9 1 day without side effects except a mild hemorrhagic vulvar discharge.
Progesterone concentrations were < 1 ng ml by day 38.
A PGF
2a
abortifacient protocol, administered near day 45 of gestation, was effective in 3 of
4 cats in one study. On the first day, 0.2 mglkg/day was given, followed by 0.5 mglkg/day. The
cats were treated subcutaneously twice daily until abortion occurred or for up to 5 days. All cats
receiving PGF
2a
had decreasing concentrations of progesterone during treatment. Cats that
aborted had < I ng/ml, whereas cats that did not abort had> 1 ng/ml of progesterone. Cats should
be hospitalized during the administration of prostaglandins. Nesting behavior may be observed
1-2 days before the abortion, and a temperature drop similar to the one observed with normal
parturition may be seen within 24 hours of abortion.
BIBLIOGRAPHY
1. Baldwin C, Evans LE: Evaluation of natural prostaglandin therapy for pregnancy termination in the do-
mestic cat. Feline Pract 28:16-21, 2000.
2. Baldwin CJ, Peter AT: Use of ELISA test kit for estimation of serum progesterone concentrations in cats.
Feline Pract 24:27-31, 1996.
3. Cain JL: Disorders of feline reproduction. In Morgan R (ed): Handbook of Small Animal Practice. 3rd
ed. Philadelphia, WB. Saunders, 1997, pp 645--{)47.
4. Fascetti AJ: Preparturient hypocalcemia in four cats. J Am Yet Med Assoc 215:1127-1129, 1999.
5. Grooters AM: Diseases of the ovaries and uterus. In Birchard SJ, Sherding RG (eds): Saunders Manual
of Small Animal Practice, 2nd ed. Philadelphia, WB. Saunders, 2000, pp 1022-1026.
6. Johnson CA: False pregnancy, disorders of pregnancy, parturition, and the postpartum period. In Nelson
RW,Couto CG (eds): Small Animal Internal Medicine. St. Louis, Mosby, 1998, pp 889-892.
7. Johnston SD, Root MY: Managing infertility in purebred catteries. In August JR (ed): Consultations in
Feline Internal Medicine, 3rd ed. Philadelphia, WB. Saunders, 1997, pp 581-586.
8. Nagaoka H, Sugieda M, Akiyama M, et al: Isolation of Coxiella bumetii from the vagina of feline clients
at veterinary clinics. J Vet Med Sci 60:251-252, 1998.
9. Onclin K, Verstegen J: Termination of pregnancy in cats using a combination of cabergoline, a new
dopamine agonist, and a synthetic PGF2 alpha, c1oprostenol. J Reprod Fertil Suppl 51:259-263.
1997.
10. Purswell BJ: Diseases of pregnancy and puerperium. In Leib MS, Monroe WE (eds): Practical Small
Animal Internal Medicine. Philadelphia, W.B. Saunders, 1997, pp 465--466.
II. Root Kustritz MV: Reproductive abnormalities of the queen, and anatomy and normal reproductive phys-
iology of the queen and tom cat. A series of lectures presented at the American Association of Feline
Practitioners' Winter Meeting in Park City, Utah, February 6 and 7,2000.
12. Smith KC: Herpesviral abortion in domestic animals. VetJ 153:239-244.253-268,1997.
13. VanVuuren M, Geissler K, Gerber D, et al: Characterization of a potentially abortigenic strain of feline
calicivirus isolated from a domestic cat. Vet Rec 144:636-638, 1999.
VI. Polysystemic Problems
Section Editor: Michael R. Lappin, D.V.M., Ph.D.
61. OBESITY ANDPOLYPHAGIA
Heather E. Connally, D.v.M., M.S.
1. Define obesity.
Obesity is defined as a body weight 20% above the ideal weight for breed, sex, and species.
Obesity is the most common nutritional disorder in cats (prevalence between 20% and 40%).
2. What are the primary differential diagnoses for an apparently obese cat?
Before a definitive diagnosis of obesity is made, a thorough physical examination should be
performed to rule out other conditions resulting in a large patient. such as pregnancy, peripheral
edema, subcutaneous emphysema, intraabdominal organomegaly (especially hepatic or splenic
enlargement), abdominal masses, or ascites (see Chapter 37).
3. How do you determine whether a patient is obese?
Body condition scoring scales range from 1 to 5 or 1 to 9. In both scales, I is an emaciated
animal. Depending on the scale used, 3 or 5 is an ideal weight and 5 or 9 is grossly obese. The as-
sessment is based in part on ability to palpate the outline of the ribs. Ribs obscured by subcutaneous
fat suggest obesity, whereas ribs that are readily visible without palpation indicate emaciation.
4. What are the risk factors for obesity in cats?
Risk factors associated with obesity in cats include apartment dwelling, inactivity, middle
age, male gender. neutering, type of food, and mixed breeding. Overweight cats are more likely
to be fed prescription diets rather than grocery store brands. In addition, purebred cats, such as
Siamese and Abyssinians, are generally leaner than cats of mixed breed.
5. Can neutering lead to obesity?
Studies have demonstrated that ovariohysterectomy and castration result in a decrease in
maintenance energy requirements in adult cats. Castrated males gain more weight as fat than
intact males. In other studies, cats that were neutered at 7 weeks or 7 months of age had an in-
crease in falciform ligament fat and body weight compared with intact controls. In addition, food
intake increases significantly after neutering.
6. Which metabolic conditions are associated with weight gain and obesity?
Metabolic conditions that lead to obesity, such as hypothyroidism in dogs, are rare in cats.
However, they may include hyperadrenocorticism (see Chapter 54), acromegaly (see Chapter
56), and hypothyroidism. In most instances, hypothyroidism and hyperadrenocorticism are iatro-
genic, caused by treating hyperthyroidism (see Chapter 53) and overuse of glucocorticoids, re-
spectively. Only one case of spontaneous adult-onset hypothyroidism has been documented in
cats. Congenital hypothyroidism generally causes failure to thrive rather than obesity in affected
kittens. If the abdomen of a kitten with congenital hypothyroidism appears distended, it is most
likely secondary to constipation or obstipation, which can be confirmed radiographically. In cats
with hyperadrenocorticism and acromegaly, it must be determined whether the enlarged abdomen
is due to organomegaly or true obesity.
311
312
Obesity and Polyphagia
7. What are the potential negative sequelae of obesity?
Risks that have been associated with obesity in the cat include a higher likelihood for the de-
velopment of hepatic lipidosis (see Chapter 30), diabetes mellitus (see Chapter 56), lower urinary
tract disease, constipation (see Chapter 27), lameness (secondary to osteoarthritis and soft tissue
injuries), nonallergic skin conditions, and possibly cardiac disease and exacerbation of chronic
respiratory conditions. Risks associated with anesthesia and surgery also are increased in obese
patients. Hepatic lipidosis generally is associated with a recent history of anorexia. Diabetes mel-
litus may be associated with a history of polyuria, polydipsia, polyphagia, and weight loss. Lower
urinary tract disease generally accompanies a history of straining to urinate, frequent urination,
or inappropriate urination. Constipated cats generally spend an excessive amount of time in the
litter box, vocalize, strain to defecate, and may produce small amounts of watery feces. The most
common skin problems associated with obesity include dry, flaky skin and feline acne. These ab-
normalities may reflect difficulties in grooming.
8. What are the most important historical findings in cats with obesity?
It is important to question the owner carefully about the eating habits of the obese cat, in-
cluding diet type (both meals and snacks), amount, and frequency of feedings. This information
allows calculation of daily caloric intake, which helps to determine whether caloric overcon-
sumption contributes to obesity. In addition, it is important to gain insight into the energy expen-
diture of the cat. Factors to consider include whether the cat is housed primarily indoors or
allowed indoors and outdoors, whether other animals live in the home, lifestyle and body appear-
ance of the owner, and age-associated decrease in activity. Other historical habits of the cat, such
as polyuria and polydipsia (see Chapter 39), can aid in the diagnosis of concurrent disease.
Determine whether prescription drugs are administered; glucocorticoids, phenobarbital, cypro-
heptadine, benzodiazepines, and megestrol acetate increase appetite.
9. What must be done before implementing a weight-less program?
First and foremost, it is essential that the owner recognizes the need for weight reduction in
the cat and is willing to participate vigilantly in a weight-reduction program. During the initial
examination, it is important to completely screen the patient's medical record and history for
medical conditions that may be exacerbated by a change in diet (e.g., lower urinary tract disease,
constipation, food sensitivity). In addition, a thorough physical examination should be performed
as well as a minimal database of screening tests, including complete blood count (CRC), serum
biochemical profile, and urinalysis. These laboratory data can be assessed for alterations in blood
glucose, liver enzymes, and evidence of urinary tract disease. In addition, if problems arise
during the program, the baseline laboratory data are available for reference.
10. What is the best diet to use for weight reduction?
Maintenance diets should not be used for a weight-loss program because the time taken to
achieve the optimal weight is prolonged (over months) and owner frustration caused by the eat's con-
stant attempts to obtain extra food may bring a premature end to the program. In addition, nutritional
deficiencies may develop as important essential nutrients and micronutrients are underfed with re-
striction of maintenance-type diets. At this point the best diet for weight reduction is unknown.
Published studies have demonstrated the efficacy of a high-fiber, low-fat diet in safely promoting
weight loss in obese cats. High-fiber, low-fat diets also significantly improve insulin sensitivity in
cats with subclinical or clinical carbohydrate intolerance. Low-fiber, low-fat diets also may be effec-
tive for weight loss as well as more palatable to cats. In addition, a recent study demonstrated that a
high-fat diet in cats, unlike in people and dogs, may promote increased fat oxidation. This finding
may mean that a high-fat, high-protein diet in cats can promote weight loss. At this time, however, no
studies have been completed to determine the long-term efficacy and safety of either diet type.
11. How is a weight-loss program developed for an obese cat?
The diet must be palatable to the patient, and acclimation to the new diet must occur over 7
days. This approach helps to ensure that the new diet is tolerated. If it is not, a new diet must be
313
chosen until an acceptable formulation is found. The amount of the specified diet that the cat
should receive daily can be calculated from the formula and table below.
Divide the total daily food quantity into 2 or 3 meals per day. On recheck visits for weight de-
termination every 2 weeks, be sure to use a single calibrated pediatric scale. The goal is to lose
1.0-2.0% of initial body weight per week over at least 16-18 weeks. This rate is safe and does not
induce hepatic lipidosis. If the cat is not losing weight or if the body weight stabilizes before the
goal weight is achieved, restrict caloric intake by 10%. If the weight loss is > 2.5% per week, in-
crease caloric intake by 15%. Once the goal weight is achieved, the food dose can be recalculated
based on maintenance energy requirement using a maintenance diet.
ideal
MER(kcal/day)
BER(kcallday)
1.2 Cats
Animals less than 2 kg body weight:
1. Calculate Balal Energy Requirement (BER) baled on ideal body _'ght
70075 OJ
bodyweight (kg) =0
Animals more than 2 kg body weight: 30 0 + 70 BER(kcaVday)
bodyweight (kg)
2. Calculate Maintenance Energy Requirement (MER) based on Ideal weight
OxO=IOI
factor
chosen
3. Calculate energy Intake for moderate caloric reltrlctlon
Cats 70% OxO=
factor ideal
chosen MER(kcallday)
4. Calculate food dOle balled on caloric density of dIet
101
adjusted
MER(kcaVday)
Nameof diet chosen adjusted
MER(kcallday)
for weightloss
caloricdensity
(kcaVcup dry)
or (kcallean)
=[0]
food dose/day
(cupsof dry)
or (eans)
Composition of Commercial Diets *
FATCONTENT PROTEIN CONTENT
CALORICCONTENT(ASFEDBASIS) (GMlIOO GMDM) (GM/l00 GMDM)
PRODUCT KCALlGM' KCAUCUP-DRyl KCAUCANI CAN DRY CAN DRY
Hill's feline products
Maintenance 4.1 503 447 25.5 23.0 45.3 33.8
Maint light 3.2 243 346 12.1 9.0 45.0 40.8
Growth 4.6 555 661 34.0 26.8 49.0 37.1
Wid 3.2 244 377 16.8 9.3 41.5 38.8
Rid 3.0 226 296 9.1 9.1 36.0 37.1
Purina feline products
CNMUR 3.9 366 493 36.5 11.6 41.4 35.4
CNMNF 3.9 398 12.9 30.8
CNMOM 2.8 283 7.7 37.0
lams feline products
Lamb and rice 4.5 461 248 29.6 23.3 45.5 35.6
Less actlve" 3.9 348 205 15.9 15.6 45.5 31.1
Rest'd cal 3.9 298 8.9 35.6
* Weight reduction diets in boldface.
~ Dry form only as example; can form differs slightly.
j Volume reference: 8-oz. measuring cup.
Hill's products: 14.25 oz per can; Purina products: 12.5 oz per can; lams products: 6.0 oz per can
# Canned chicken and rice formula.
Hills Nutrition, Inc., Topeka, KS; Ralston Purina Company, St. Louis, MO; lams Company, Dayton, OH.
314
12. Define polyphagia.
Polyphagia is food consumptionin excess of caloric need. Becauseregions within the cen-
tral nervous system (CNS) control hunger, satiety, and eating behaviors, polyphagia is classified
as either primary (CNSproblem), or secondary(systemicproblemaffectingthe CNS).
13. What are the primary dift'erential diagnoses for polyphagia?
Primarycauses of polyphagiainclude psychogenicfactors (e.g., stress, introduction of more
palatablediet); destructive lesionsof the satietycenter,suchas traumaand space-occupying lesions
(neoplasia, abscess); and infection. Drugs suchas glucocorticoids, anticonvulsants, antihistamines,
progestins, benzodiazepines, and amitrazcan inducepolyphagia. The manypotentialcausesof sec-
ondarypolyphagiaincludeincreasedmetabolicrate (physiologic or pathologic), decreasedenergy
supply, and disease states for whichthe mechanismis unknown. A physiologicincrease in meta-
bolic rate induced by cold temperature, lactation, pregnancy, growth, and increasedexercisecan
cause an increase in feed consumption. Hyperthyroidism(see Chapter 53) and acromegaly (see
Chapter 56) can cause pathologicincreasesin metabolicrate. Diabetesmellitus (see Chapter 56),
hypoglycemia, decreased intakebecauseof a low-calorie diet, andmalassimilation syndromes (e.g.,
pancreatic exocrineinsufficiency, infiltrative bowel disease,parasites [seeChapter 19], lymphang-
iectasia) can cause a decrease in energy supply that may lead to an increase in consumption.
Diseasesfor whichthe causeof polyphagiais unknown includehyperadrenocorticism (seeChapter
54) and portosystemic shunt (see Chapter 35). In addition, diseasesnot commonlyassociated with
polyphagiabut for whichit has been documented includefeline infectious peritonitis (see Chapter
38), lymphocytic cholangitis (seeChapter29), and spongiform encephalopathy.
14. How can the history aid in diagnosis of polyphagia?
The most important initial diagnostic tool is the history. On the basis of a thorough history
many conditions can be ruled out, and possibly a diagnosis can be made. First, one must deter-
mine whether the increase in food consumption is accompanied by maintained weight, weight
loss or weight gain. There may be no weight change early in the disease process. However, if the
cat has gained weight, the cause is most likely primary or drug-induced. Physiologicpolyphagia
can lead to weight gain (e.g., pregnancy or growth) or maintenance of weight (e.g., lactation,
living in a cold environment, increasedexercise). Polyphagiasecondaryto pathologicconditions
generally results in weight loss because the nutrient demand is not met. Exceptions include
acromegaly and hyperadrenocorticism, which usually are associated with weight gain. History
can reveal trauma, signs of CNS disease, newstress in the household(e.g., introductionof a new
animal), current diet (more palatable or low-calorie), drug administration, pregnancy, lactation,
exposureto a cold environment,or increasedexercise. Many metabolicdiseases are accompanied
by a history of polyuria and polydipsia. There may be a recent behavior change or an increase in
activity, as with hyperthyroidism. Abnormal feces characterized as soft, voluminous, and mal-
odorous can be seen with malassimilationdiseases. Neurologic signs such as depression, weak-
ness, ataxia, disorientation, and seizures can be seen with hypoglycemiaor portosystemicshunt.
15. How should one approach the polyphagic cat diagnostically?
The physical examination is the next diagnostic step. A careful neurologic examination,
good abdominal palpation, and palpationof the neck for a thyroid"slip" may aid in rankingCNS
disease, pregnancy, infiltrativebowel disease, hyperadrenocorticism, and hyperthyroidism on the
differential list. Distinct changes in conformation may suggest acromegalyor hyperadrenocorti-
cism. A minimal database includingCBC, serumchemistryprofile, and urinalysis should be per-
formed. Results of these screening tests, in addition to the history, may suggest the need for
further diagnosticwork-up, suchas thyroidfunction tests, liver functiontests, or adrenal function
tests. Fecal examination for parasites and evaluation for other causes of malabsorption or
maldigestion may be warrantedin some cats. Radiographyor ultrasonography also may be con-
sidered, especiallyif pregnancyis suspected. Endoscopyor exploratorysurgeryand biopsyof the
gastrointestinal systemmay be required to rule out other malassimilation syndromes.
Anorexia and Weight Loss
315
Analysis of cerebrospinal fluid or more advanced diagnostic imaging such as computed to-
mography or magnetic resonance imaging may be necessary to rule out CNS disease.
BIBLIOGRAPHY
1. Behrend EN: Polyphagia. In Ettinger SM (ed): Textbook of Veterinary Internal Medicine. 5th ed.
2. Bouchard GO, Sunvold GO: Dietary modification of feline obesity with a low fat, low fiber diet. In
Reinhart GA, Carey DP (eds): Recent Advances in Canine and Feline Nutrition, vol II. Wilmington,
DE, Orange Frazer Press, 1998, pp 183-192.
3. Burkholder WJ, Toll PW: Obesity. In Hand MS, Thatcher CD, Remillard RL, Roudebush P (eds): Small
Animal Clinical Nutrition, 4th ed. Marceline, MO, Walsworth Publishing, 2000, pp 401-430.
4. Center S: Safe weight loss incats. In Reinhart GA, Carey DP (eds): Recent Advances in Canine and Feline
Nutrition, vol II, Wilmington, DE, Orange Frazer Press, 1998, pp 165-181.
5. Fellman MJ, Stanton CA, Banks LL, et al: Effects of neutering on body weight, metabolic rate and glu-
cose tolerance of domestic cats. Res Vet Sci 62:131-136,1997.
6. Fellman MJ, Stanton CA, Banks LL, et al: Effects of weight gain and loss on metabolic rate, glucose tol-
erance, and serum lipids in domestic cats. Res Vet Sci 64:11-16,1998.
7. Lester T, Czarnecki-Maulden G, Lewis 0: Cats increase fatty acid oxidation when isocalorically fed meat-
based diets with increasing fat content. Am J PhysioI277:R878-R886, 1999.
8. Scarlell, JM, Donoghue S: Associations between body condition and disease in cats. J Am Vet Med Assoc
212:1725-1731,1998.
9. Wolfsheimer KJ: Obesity. In Ellinger SM (ed): Textbook of Veterinary Internal Medicine. 5th ed.
62. ANOREXIA ANDWEIGHT LOSS
Cynthia L. Bowlin, D.V.M.
1. Define anorexia.
Anorexia is defined as the lack or loss of appetite for food. Food intake less than daily caloric
requirement over time results in weight loss.
2. What causes anorexia?
Anorexia is a clinical sign of an underlying problem. Some authorities classify anorexia into
primary causes, secondary causes, and pseudoanorexia. Primary anorexia is caused by diseases
that affect the areas of the brain housing the appetite and satiety centers. Secondary anorexia
has many pathologic and nonpathologic causes. Pathologic causes of secondary anorexia include
pain, loss of smell, inflammation, fever, infection, toxins, neoplasia, and gastrointestinal, meta-
bolic, or neurologic disorders. Nonpathologic conditions that may cause secondary anorexia in-
clude lack of diet palatability, strong dietary preferences, and environmental stress. Cats with
pseudoanorexia have diseases that affect the mechanics of prehension and swallowing or painful
diseases of the mouth or pharynx. An example is lymphocytic plasmocytic stomatitis; affected
cats have an appetite but often do not eat.
3. What causes weight loss?
Weight loss results from decreased caloric intake or increased caloric requirement. Decreased
caloric intake results from decreased consumption, absorption, or utilization. Examples of de-
creased consumption include decreased desire for food caused by disease, inability, or reluctance
to eat and insufficient availability of food. Examples of decreased absorption include diseases of
the gastrointestinal tract, liver. biliary system, and pancreas that cause maldigestion or malab-
sorption. Diabetes mellitus is an example of the lack of utilization of ingested food. Weight loss
316 Anorexia and Weight Loss
as a result of increased caloric requirement occurs with increased metabolism and utilization.
Examples include pathologic conditions such as hyperthyroidism, neoplasia, or fever and non-
pathologic conditions such as lactation or exercise.
Causes ofAnorexia and Weight Loss
DECREASED CALORIC INTAKE INCREASED CALORIC REQUIREMENT
Appetite with reduced food intake
Starvation
Food preference
Pain
Inability to prehend, chew, or swallow
Environmental factors
Appetite with adequate food intake
Malabsorption/maldigestion
Poor food caloric density/digestibility
Anorexia or inappetance
Neurologicdisease
Pain
Loss of smell
Fever
Inflammation/infection
Toxins
Neoplasia
Metabolic disorders
Systemic disease
Gastrointestinal disorders
Increased nutrient loss
Vomiting/diarrhea
Bums/wounds
Increased nutrient need
Surgery/trauma
Infection
Fever
Bums
Growth
Lactation
Increasedexercise
Decreased nutrient utilization
Diabetes mellitus
Portosystemic shunt
4. What are the pathophysiologic consequences of anorexia and weight loss in cats?
Cats are obligate carnivores that require a regular intake of certain nutrients to maintain
health. During periods of reduced caloric intake, malabsorption/maldigestion, or increased
caloric utilization, cats mobilize stores to meet metabolic needs. However, cats do not have the
ability to store and/or synthesize certain amino acids and soon show signs of nutritional deficien-
cies. For example, cats are unable to synthesize the amino acid arginine, an important part of the
urea cycle. During periods of reduced protein intake, the highly active protein catabolic hepatic
enzymes of cats produce ammonia from the deamination of protein for energy. But without argi-
nine to complete the conversion of ammonia to urea, hyperammonemia and its toxic affects
quickly result. Cats require 8 times more vitamin B than dogs. Deficiency in B vitamins alone
can precipitate or perpetuate an anorexic episode. Idiopathic hepatic lipidosis occurs most fre-
quently in previously obese cats when calorie intake is restricted for any reason (see Chapter 30).
5. How long can cats survive without eating?
Inadequate food intake may be more detrimental to the patient than the underlying disorder.
Even short-term fasting of a few days has been shown to have a negative effect on the immune
system, gastrointestinal system, heart muscle, kidneys, liver, and endocrine systems. Healing is
significantly hampered by lack of adequate nutrition. Early resumption of eating after an anes-
thetic, dental, or surgical procedure greatly enhances recovery, especially in debilitated. very
young, and aged patients. Unless there is a medical indication for fasting (e.g., preoperative fast-
ing, vomiting, acute gastritis, pancreatitis), adequate nutritional support should begin immedi-
ately. If inappetence or anorexia is predictable, as after surgery or dental work, provision for
nutritional support should be part of the original treatment plan.
6. How can the history aid in determining the cause of anorexia and weight loss?
Identifying the cause of anorexia and/or weight loss starts with a complete and thorough
history:
317
o Does the cat show an interest in foods that are offered?
o Is the cat attempting but failing to prehend the food? (The cat has an appetite but is unable
or unwilling to eat.)
o What and how much is the cat eating? More or less than usual? Often in multi-cat house-
holds it is difficult to access how much an individual cat is consuming, but this crucial in-
formation affects the diagnostic plan. Recommend that the affected cat be isolated to
measure food intake and appetite.
o Has there been a diet change? Cats are relatively insensitive to the caloric content of food
and ingest relatively constant volumes of dry matter volumes. Changing to a lower calorie
food usualIy results in weight loss.
o Has there been a change in the environment (e.g., move or new baby)?
Where is the cat fed? Is food always accessible?
o Is there something or someone that would make the cat reluctant to approach the food or
eat (e.g., dog, dominant cat, children)?
o Have other foods been offered? To what effect?
This information will help to differentiate pathologic from nonpathologic causes of anorexia
and weight loss. If acceptable (to the cat) and adequate food is provided and polyphagia accom-
panies weight loss, the cat most likely has a disease that causes malabsorption/maldigestion, in-
creased requirement of calories (e.g, hyperthyroidism), or decreased utilization of calories (e.g.,
diabetes mellitus). All of these diseases and the metabolic derangements that accompany their
progression can result in a state of true anorexia.
7. How does the physical examination aid in the assessment of anorexia and weight loss?
If anorexia or inappetence is suggested by the history, the physical examination should pro-
vide additional direction in identifying the cause. If possible, weight loss should be verified objec-
tively by serial weight comparisons. Significant weight loss can occur in an obese cat before it
becomes subjectively apparent. Conversely, loss of a few ounces can be significant in a small or
geriatric cat. A thorough examination of the oral cavity is necessary to rule out acute or chronic
dental disease, neoplasia, stomatitis, or diseases that affect prehension, swallowing, or smell. A
CNS evaluation should be done to rule out diseases that may cause primary anorexia. Fever in cats
commonly suppresses the appetite; for the classical diagnostic plan, see Chapter 64. The chest
should be auscultated thoroughly for cardiac murmurs, gallops, or arrhythmias to rule out cardiac
disease. Visual observation of respiration, percussion, and auscultation should be done to evaluate
the patient for upper or lower airway disease. Most animals that cannot breathe do not eat, and in
cats respiratory disease can be subtle until well advanced. Complete digital palpation of the ab-
domen often identifies masses, organomegaly, pain, abnormal kidney size or shape, constipation,
intestinal abnormalities, or urogenital disease. Examination of the eyes, including the fundus, may
suggest infectious disease (feline infectious peritonitis, toxoplasmosis) or CNS disease. The ears
should be evaluated for disease or polyps that may cause pain or affect smell and/or swallowing.
Thorough examination of the coat and skin completes the physical evaluation and may suggest
parasites, dehydration, toxins, or chronicity evident by poor coat quality or lack of self-grooming.
8. Describe the initial diagnostic plan.
If the cause of anorexia and/or weight loss is not found after evaluation of the signalment,
history, and physical examination, then a complete blood count, serum biochemical profile, uri-
nalysis, feline leukemia virus antigen test, feline immunodeficiency virus antibody test, and total
T4 concentration (in cats> 5 years of age) usually are performed. Radiographs, ultrasound exam-
ination, or more advanced imaging such as magnetic resonance or computed tomography is war-
ranted if a cause is not confirmed with the initial data.
9. What is the best diet for the cat?
The one the cat will eat! It is far more important that the cat eats than that the cat eats a spe-
cific diet. Although many nutrient-controlled diet formulations have been developed over the past
318
20 years for nutritional treatment and support of specific diseases, the diet will do no good and
may actually do more harm if the cat refuses or is reluctant to eat it. Cats have such strong taste
preferences and such a propensity to develop malnutritional disease quickly that, whenever the
diet is changed, every cat should be monitored closely, even on a daily basis, to ensure consump-
tion of an adequate volume of food. If consumption is not adequate, the diet must be changed to
one that is acceptable to the cat. When cats with chronic renal failure are forced to eat renal diets,
many succumb more to inadequate nutrition than to renal disease. Even novel protein diets used
in diagnosis and treatment of food allergy need to be monitored closely for intake volume. I have
seen cats lose 50%of body weight because they were offered only a specific diet that they did not
accept. Foods should be measured and serial body weights checked regularly until stable. A cat
will die before it will eat something that it does not like.
10. What are the treatments for anorexia?
No method of nutritional support substitutes for proper identification and treatment of the
underlying cause of anorexia, which should be the primary goaL In the interim. various methods
of nutritional support and appetite stimulation should be provided.
11. What dietary manipulation can I try?
Taste, odor. and texture of food playa large role in acceptability. Cats may develop a learned
aversion to foods previously associated with nausea, vomiting, or cramping and subsequently
reject them, even if previously preferred. Trying various types of foods (moist vs, dry ki bble),
strained baby formula meats, semimoist textures, fruits. vegetables, or others may entice the
anorexic cat to resume eating. Feeding of liquefied or strained meat diets by hand or syringe
often stimulates the cat to begin eating. Any medication given orally to a cat can cause gastroin-
testinal upsets, even if no vomiting or diarrhea is apparent. Always be sure that the cat has re-
sumed eating before starting oral medications, and if a cat that has been eating reduces its food
intake, loses weight, or stops eating, consider that oral medication may be at fault.
12. Should I try appetite stimulants?
Appetite stimulating drugs can beused in the short term to encourage food intake in recover-
ing cats or cats for which a cause has been identified but cannot be eliminated. Too often these
drugs are used instead of exhausting the search for a cause of the anorexia and weight loss. That
temptation must be avoided. Measurement of food intake and serial weight monitoring must be
done to assess the effectiveness of the drugs and the success of meeting caloric needs. If the re-
sponse to drugs is inadequate or if long-term nutritional support is expected, other means of par-
enteral or enteral nutritional support should be instituted as soon as possible.
Appetite-stimulating Drugs
DRUG
Cyproheptadine (Periactin)
Merial Limited, Iselin NJ
Megestrol acetate (Ovaban)
Schering-Plough, Madison, NJ
Prednisolone
Stanozolol (Winstrol)
Sanofi, NewYork
VitaminB complex
Diazepam(Valium)
Roche, Basel
Oxazepam(Serax)
Wyeth-Ayerst, Philadelphia
DOSE
1-2 mg PO every 8-24 hr
0.5 mglkg124 hr PO for 3-5 days,
then once every5 days
0.25-0.5 mglkg/24hr PO
2 mlILfluids in IV
0.2 mg/kg IV every 2 hr
1.25-2.5 mg/cat PO every
18-24 hr
POTENTIAL SIDEEFFECTS
Extreme excitability and
aggression
Diabetes, mammary hyper-
plasia/neoplasia, pyometra
Immune suppression, hyper-
glycemia
Hepatotoxicity(rare)
Sedation, short effectiveness
Sedation potentially less than
diazepam
Anorexia and Weight Loss 319
13. Should enteral or parenteral nutritional support be used in anorexic cats?
Compared with the parenteral route. enteral nutrition has fewer complications and is more
physiologic. less expensive, and technically easier. Hyperalimentation is the administration of
adequate nutrients to malnourished patients or patients at risk. Enteral hyperalimentation pro-
vides nutrients to a functional gastrointestinal tract-for example. through a nasoesophageal,
esophagostomy, gastrostomy. or enterostomy tube. Parenteral hyperalimentation provides nutri-
ents intravenously. Enteral nutritional support also maintains gastrointestinal integrity: "If the gut
works. use it." The parenteral route may be used when the gastrointestinal tract cannot adequately
maintain and absorb nutrients (vomiting. severe diarrhea. intestinal resection or obstruction),
when stimulation of the pancreas is to be avoided because of pancreatitis, or when additional
support is indicated in severely malnourished cats. Factors that make total parenteral nutrition
(TPN) more difficult include catheter placement and management (maintaining sterility and
avoiding sepsis from formula or catheter site), need for specialized equipment (infusion pump),
constant patient monitoring. and diet preparation and storage.
14. What methods are used for enteral feeding of cats?
Generally oral administration of food is most efficient, easier. and safer; it also stimulates
hormonal and neural centers to enhance digestion and absorption of nutrients. The further aboral
the materials are placed. the more complicated delivery and composition of the formulas
become. Other available techniques include nasoesophageal, nasogastric, pharyngostomy,
esophagostomy, gastrostomy, and jejunostomy tubes.
15. Are nasoesophageal and nasogastric tubes effective?
Although nasoesophageal and nasogastric tubes are quick and easy to place in cats, the type of
nutritional support that can be provided is limited because of their small size. Soft polyvinyl and red
rubber feeding tubes from 3-5 French (Jorvet Specialty Products. Loveland. CO; Sherwood Medical.
St. Louis. MO) are easy to insert with little or no local anesthesia or sedation. Nutritionally complete.
commercially available liquid diet preparations are available for use with tubes of this size:
Jevity (Abbott Labs. Columbus. OH: 1.06 kcal/ml; 4.20 gml100 kcal of protein, 3.48
gmllOO kcal of fat; 310 mOsmlkg)
Osmolite HN (Abbott Labs, Columbus, OH: 1.06 kcal/ml; 4.44 gml100 kcal of protein,
3.68 gmllOO kcal of fat; 310 mOsmlkg)
Clinicare Feline (Abbott Labs. North Chicago. IL: 0.92 kcaUml; 4.60 gmI100 kcal of pro-
tein, 3.68 gmllOOkcal of fat; 310 mOsmlkg)
An Elizabethan collar is usually required to prevent the patient from rubbing or dislodging
the tube, although many cats resent the presence of the collar. To provide adequate quantities of
nutrients, a feeding pump and constant infusion are necessary. thus restricting the use of this
feeding method to hospitalized cats requiring minimal. short-term nutritional support.
16. Why have esophagostomy tubes become increasingly popular?
Esophagostomy tubes have become increasingly popular in recent years because of ease of
placement and lack of required special instrumentation. This technique has largely replaced the
pharyngostomy tube.
17. Howare esophagostomy tubes placed?
The cat is anesthetized and intubated. and a mouth gag is applied to keep the mouth open.
With the cat in right lateral recumbency. the area on the left side of the neck from the wing of the
atlas to the scapula is clipped and surgically prepared. With the curved tip pointed upward toward
the skin. a 6-8-inch curved Carmalt forcep is inserted into the throat and down the esophagus to
the mid-neck area. Upward pressure is applied. and a scalpel blade is used to incise through the
skin. subcutaneous tissues. and esophagus just over the tip of the forcep. The end of the tube is
cut just above the side fenestration to allow better flow of formula. The tube is laid along the out-
side of the cat. measured from the tenth rib to the forcep tip, and marked. The mark places the
distal end of the tube in the preferred lower esophagus, not into the stomach. The forcep tip is
320 Anorexia and Weight Loss
opened, and the distal end of the tube is grasped and withdrawn from the mouth with the forcep.
The distal end of the tube is then turned back on itself and directed down the esophagus. The
forcep can aid in directing and advancing the tube into the esophagus. Light traction on the tube
at its exit point from the neck as the tip passes helps to relieve the bend in the tube and assists fur-
ther advancement down the esophagus to the point previously marked. The tube is secured to the
skin of the neck with a Chinese finger-trap suture or by gluing the tube to an adhesive tape wing
and suturing to the skin of the neck. The tube is laid up over the neck and secured again dorsally.
with one skin suture, to keep the tube accessible. A gauze pad with antibiotic ointment is applied
over the incision, and the neck is wrapped lightly with a gauze bandage and secured. Systemic
antibiotics are required for 5-7 days until the stoma forms and the incision heals. The bandage
should be changed every other day until healing is complete. A light neck wrap after healing
helps to keep the cat from dislodging the tube.
18. How is the esophagostomy tube used for feeding?
The esophagostomy tube is well tolerated by cats and can be as large as 10-16 French, allow-
ing adequate size for feeding of blenderized canned food. Feedings should begin with frequent
(every 2-3 hours) small servings (5-15 ml). If vomiting is nota problem, feeding volume can be in-
creased and frequency decreased until the total daily caloric requirement is met. Most cats tolerate
50-60 ml per feeding. The tube should be kept plugged. Clogged tubes often can be relieved by
pressure or injection of cola to dissolve the clog. Cats can and will eat with the esophagostomy tube
in place. Once the cat is eating sufficiently on its own, the tube can beremoved without sedation.
19. When should gastrostomy tubes be used?
Gastrostomy tube placement frequently is used if other diagnostic procedures are performed,
such as exploratory laparotomy or endoscopy for procurement of biopsies. Another indication for
gastrostomy tube placement is disease above the stomach that precludes use of the oral or
esophageal route; for example, a cat that has undergone rnandibulectomy for neoplasia and/or is
no longer able to prehend, chew, or swallow food properly.
Various methods of gastrostomy tube placement have been described. Gastrostomy tubes are
well tolerated in cats and can be used for months or years. Once the stoma has formed, the gas-
trostomy tube can be removed and cleaned or replaced with mild or little sedation. Gastrostomy
tubes are indicated if longer-term nutritional support is anticipated (months or years) because
their larger diameter allows more variety in diet and tube formula selection. The new "button"
gastrostomy tubes lie close to the body wall, thus decreasing the chance of dislodgement.
20. When are jejunostomy tubes used?
The jejunostomy feeding tube is indicated in any cat that is undergoing oral, esophageal, gas-
tric, pancreatic, duodenal, or biliary tract surgery in which the intestinal tract distal to the surgical
site is functional. Patients with preexisting protein-calorie malnutrition that must undergo major
abdominal surgery are candidates for early feeding via a jejunostomy tube. Celiotomy is required
for placement, but the cat can begin a liquid diet into the jejunostomy tube immediately after
surgery. Complications include premature removal, tube-induced jejunal perforation, and subcuta-
neous leakage; however, proper technique minimizes these complications. Frequently, gastros-
tomy tubes are placed at the same time for use when jejunostomy feedings are no longer required.
21. What unique facts about cats should be kept in mind?
A cat will die before it will eat something that it does not like. Cats never get "hungry
enough" to eat whatever is available.
Weigh feline patients regularly. An 8-ounce weight loss can be far more significant than a
5-pound weight gain.
Oral medications can cause anorexia.
Cats develop learned aversions to foods previously associated with a negative experience,
such as pain, nausea, vomiting, cramping, bad flavor, or hidden medications. Try some-
thing different.
Systemic Hypertension 321
Start at an early age to feed the cat a variety of foods with different textures and smells.
Diet variety should be the rule for the cat.
Treat the cat, not the lab test. If lab values improve but the patient deteriorates, think of
food intake.
We do not know the nutritional requirements of cats.
BIBLIOGRAPHY
I. Crisp MS: Nutritional management of the critical patient. In Birchard S1, Sherding RG (eds): Saunders
Manual of Small Animal Practice. Philadelphia, W.B. Saunders, 1994, pp 29-37.
2. Hill, R: Feline enteral and parenteral nutrition. In Gumbs MW, Sokolowski JH (eds): Proceedings of the
Waltham Feline Medicine Symposium in Association with The North American Veterinary
Conference. Waltham, MA, 1999, pp 42-50.
3. Macy, OW, Ralston, SL: Cause and control of decreased appetite. In Kirk RW (ed): Current Veterinary
Therapy X. Philadelphia, W.B. Saunders, 1989, pp 30-36.
4. Norsworthy GO: Tube feeding anorexic cats. From Instructions for Tube Feeding Anorexic Cats.
Bloomington, IN, Cook Veterinary Products, 1998.
5. Seim HB, Willard M: Postoperative care of the surgical patient. In Fossum TW (ed): Small Animal
Surgery. St Louis, Mosby, 1997, pp 65-85.
6. Seim, HB: Feeding tube placement. In Gumbs MW, Sokolowski JH (eds): Proceedings of the Waltham
Feline Medicine Symposium in Association with The North American Veterinary Conference.
Waltham, MA, 1999, pp 6-14.
63. SYSTEMIC HYPERTENSION
Drew Weigner, D.v.M.
1. Define systemic hypertension.
Systemic hypertension is a consistently elevated systolic or diastolic arterial blood pressure
(BP). Systolic pressure is generated by contraction of the ventricles. Normal systolic pressure
varies greatly from 118 to 170 mmHg. One report suggests normal systolic pressure may be
somewhat higher in cats older than II years. Many clinicians use a value of 150 mmHg for
normal systolic pressure in a clinical setting (i.e., by indirect methods). Diastolic pressure is the
arterial BP during relaxation of the ventricles. Diastolic pressure is clinically difficult to measure
but should be approximately 100 mrnHg. Variations in reported data probably are due to differ-
ences in technique and equipment as well as method of restraint or anesthesia. Accordingly, each
practice should establish its own normal parameters.
2. What are the other types of hypertension1
1. Pulmonary arterial hypertension describes elevation of BP in the pulmonary arteries. It
is associated most commonly with chronic obstructive pulmonary diseases and dirofilariasis.
2. Pulmonary venous hypertension denotes increased BP in the pulmonary veins and
occurs most frequently with congestive heart failure.
3. Portal hypertension is elevation of BP in the portal system of the liver. It can result from
systemic hypertension but is more relevant clinically as a component of portosystemic shunts or
chronic endstage liver diseases.
3. What are the major causes of systemic hypertension?
Systemic hypertension in cats is most commonly due to underlying diseases. Approximately
50% of cats with chronic renal failure have systemic hypertension. The incidence may be higher
with hyperthyroidism. Occasionally, diabetes mellitus is associated with systemic hypertension.
Uncommon causes include pheochromocytoma, hyperaldosteronism, and kidney transplantation.
322
Systemic Hypertension
Hypertension also may be a rare sequela of erythropoietin administration. Although suspected,
hypertension from primary vascular disease (known as essential hypertension) has not been doc-
umented in cats. Furthermore, although hypertension can lead to secondary cardiac hypertrophy
and resultant heart failure, no evidence suggests that heart disease causes hypertension.
4. What methods are available to determine arterial BP?
The gold standard for blood pressure measurement is direct arterial cannulation, usually of
the carotid or femoral artery. Because special equipment and often anesthesia are required, indi-
rect measurement is more common. However, indirect measurement typically understates blood
pressure obtained by direct methods. Accordingly, a "correction factor" is sometimes added to
indirect blood pressure readings.
5. How is indirect BP determined?
As in humans, a cuff is used to occlude a peripheral artery. The cuff pressure is decreased
gradually until blood flow resumes. The cuff pressure at that point is the systolic pressure. The
pressure remaining when blood flow temporarily ceases between heartbeats is the diastolic pres-
sure. Accurate determination of diastolic pressure may not be possible via indirect measurement.
6. What is the preferred method for measuring systolic BP in cats?
Doppler ultrasonography is used most commonly to detect arterial blood flow. Doppler flow
detection is less expensive and generally more accurate than other methods, particularly at higher
pressures. Unfortunately, diastolic pressure cannot be measured with this technique. A correction
factor of 14 mmHg has been suggested when systolic pressure is measured via Doppler: actual
BP = Doppler BP + 14 mmHg, where actual BP is the value obtained by direct measurement.
7. Where is BP usually measured in cats?
Blood flow usually is measured at the plantar or palmar common digital arteries (proximal to
the metatarsal or metacarpal pads, respectively) or the coccygeal artery with the cuff placed prox-
imally. Ideally, pressures are determined with the patient in lateral recumbency so that the limb is
at the same level as the heart, although it is not known how much this position affects blood pres-
sure results.
8. What cuff size is appropriate for use in cats?
Use of an appropriate cuff size is important to obtain accurate determinations. Ideally, the
width of the cuff should be 40% of the limb circumference. For most patients, a 2.5-cm cuff is
appropriate. Cats that weigh over 7 kg or are obese or heavily muscled may require a 3.0-cm cuff.
For practical purposes, it is easier to use a sphygmomanometer with an integral bulb/dial and a
single tube that can be operated with one hand (Propper Manufacturing, Long Island City, NY).
9. What other indirect techniques of BP measurement are used in cats?
J. Oscillometric methods detect oscillations in cuff pressure to determine systolic, dias-
tolic. and mean blood pressure. Although reasonably accurate at normal or low pressures, accu-
racy decreases markedly as the pressure increases.
2. Plethysmography, a newer method, uses infrared radiation to determine blood pressure.
Although one report equates its accuracy with that of the Doppler technique, its use has yet to be
critically evaluated in cats.
10. What is the "white coat effect"?
The "white coat effect" described in human medicine is a spurious elevation of blood pres-
sure from stress during measurement in a clinical setting. It has been described in cats as increas-
ing systolic pressure by 18 mmHg. Allowing patients 15 minutes to acclimate to the clinical
environment before measurement of BP minimizes this effect. To increase accuracy and repro-
ducibility, multiple determinations are recommended. One method is to obtain five readings, dis-
card the highest and lowest, and average the remaining three.
11. What are the common signalment findings of systemic hypertension?
Systemic hypertension is more common in geriatric cats but may occur in patients of any age
with predisposing conditions. Although systemic hypertension has no breed or sex predilection,
it should be suspected in all cats with renal disease, such as Abyssinian cats with amyloidosis
(see Chapter 40).
12. What are the common historical fmdings of systemic hypertension?
Systemic hypertension is called "the silent killer" because signs of early-to-moderate hyper-
tension are vague or absent. Most cats do not exhibit overt clinical signs of systemic hypertension
until systolic pressure exceeds 200 rnmHg. Most cats with systemic hypertension have a history
of weight loss, including obese diabetics. Appetite increases frequently in cats with hyperthy-
roidism and occasionally in cats with diabetes mellitus but may be normal or decreased in cats
with renal disease. Astute owners may observe increased thirst or urination. Overt clinical signs
are often acute and severe, including blindness from detached retinas, dyspnea from heart failure,
and seizures or other neurologic signs of cerebral vascular hemorrhage. Anecdotally, excessive
nocturnal vocalization has been reported in many hypertensive patients.
13. Describe the common physical examination findings of systemic hypertension.
Physical examination abnormalities are usually those of the primary disease process.
Examples include small, irregularly marginated kidneys in cats with chronic renal failure and en-
larged thyroid glands in cats with hyperthyroidism. Other findings relate to the effects of hyper-
tension. Bounding pulses, increased intensity of heart sounds, and/or a gallop rhythm may be
noted, usually in relation to secondary ventricular hypertrophy. Retinal artery tortuosity, retinal
hemorrhage, and retinal detachment may be detected on ophthalmic examination. Seizures or
other neurologic signs of cerebral vascular hemorrhage also may be present.
14. What is the initial diagnostic plan for systemic hypertension?
Indirect measurement of systolic blood pressure is essential to diagnose systemic hyperten-
sion. Because systemic hypertension is usually secondary to underlying diseases, complete blood
count, serum biochemical profile, total T4 concentration, and urinalysis also should be performed.
15. What other tests are useful in determining the cause of systemic hypertension?
Direct or indirect ophthalmoscopy detects hyphema, retinal hemorrhage, or retinal detach-
ment. Chest radiographs are useful for evaluating dyspnea associated with pleural effusion or
pulmonary edema. Ultrasound techniques can be used to assess the degree of cardiac changes
and primary causes of renal disease. Magnetic resonance imaging or computerized tomogra-
phy with angiography to detect intracranial hemorrhage is ideal when neurologic symptoms
are present.
16. Why are cats with systemic hypertension sometimes presented as emergencies?
Dyspnea from pleural effusion or pulmonary edema is the most common cause of emer-
gency presentation of systemic hypertension. Although rare, intractable seizures or unilateral
neurologic signs from intracranial hemorrhage also present as emergencies. Blindness is an un-
common emergency presentation. Indeed, some owners are unaware that the cat is blind until it is
diagnosed during a thorough physical examination.
17. What is the initial treatment for systemic hypertension?
Although it is appropriate to decrease BP in patients with systemic hypertension, initial
management may be directed toward treatment of acute symptoms such as dyspnea or seizures.
Nitroglycerine may be particularly useful in fulminant cardiac failure secondary to systemic hy-
pertension. Amlodipine, a calcium channel blocker, is reported to decrease blood pressure
within 8-9 hours of oral administration in humans, but feline pharmacokinetics have not been
determined.
324
Systemic Hypertension
Products Commonly Usedfor the Control of Feline Systemic Hypertension *
V4 inch cutaneously every 6-8 hr
1-2 mg/kg orally every 12 hr
1-2 mglkg orally every 12 hr
2.5-5.0 mg orally every 8-12 hr
2 mglkg or 6.25-12.5 mg/cat orally every 24 hr
0.18 mglkg or 0.625-1.25 mg/cat orally every 24 hr
0.5-2.5 mglkg orally every 8hr
Sodium-restricted diets (several renal diets are commercially available)
Angiotensin-converting enzyme inhibitors
Enalapril 0.25--0.5mg/kg orally every 12-24 hr
Lisinopril 0.5 mglkg orally every 24 hr
Beta blockers
Propranolol
Atenolol
Calcium channel blockers
Amlodipine
Diltiazem
Emergency vasodilators
Nitroglycerine ointment 2%
Diruretics
Furosemide
Spironolactone
*Whendrugs are usedfor the treatmentof systemichypertension, start at the lowend of the dose rangeand
monitorarterial bloodpressureandrenal functionparametersevery3-4 days until theyare stabilized.
18. What should I use for long-term control of systemic hypertension?
In otherwise clinically normal cats with moderate hypertension, BP control may be at-
tempted initially with low-salt diets (Dry Hills Prescription Diet and canned Waltham Low
Protein are palatable to most cats). Symptomatic patients or patients with systolic pressures>
200 mmHg before or 170 mmHg after sodium restriction also should be medicated. The most ef-
fective medications for systemic hypertension are amlodipine and atenolo!. Amlodipine is more
reliably effective, but atenolol is the treatment of choice for patients with severe tachycardia, par-
ticularly with suspected hyperthyroidism. Angiotensin-converting enzyme inhibitors (enalapril,
captopril, lisinopril), and diuretics (furosemide, spironolactone) are less effective in most cats
and should be used with caution if concurrent renal failure is present. (See figure.)
Medical management of feline hypertension. RAAS =renin-angiotensin-aldosterone system. NaCI-x =
sodiumrestriction. (Courtesy of ClarkeAtkins. D.Y.M., withpermission.)
19. What is thelong-term prognosis for catswithsystemic hypertension?
The prognosis for cats with manageable systemic hypertension depends on the underlying
disease. Early detection and control of hypertension may slow the progression of renal disease
and improve prognosis. Hyperthyroidism generally has a good prognosis when diagnosed before
the onset of heart failure. Control of hyperthyroidism may resolve systemic hypertension in some
cases. The prognosis of diabetic patients depends on the degree of glycemic control, but most pa-
tients do well on diet and insulin therapy. Acute blindness, if detected and treated within hours,
may reverse if the retinas reattach. Uncontrollable systemic hypertension has a poor prognosis,
regardless of the underlying cause.
BIBLIOGRAPHY
I. Belew AM, Bartlett T, Brown SA: Evaluation of the white-coat effect in cats. J Yet Intern Med
13:134-142, 1999.
2. Binn SH, Sisson DO, Buoscio DA, et al: Doppler ultrasonographic, oscillometric sphygmomanometric,
and photoplethysmographic techniques for noninvasive blood pressure measurement in anesthetized
cats. J Yet Intern Med 9:405-414, 1995.
3. Bodey AR, Sansom J: Epidemiological study of blood pressure in domestic cats. J Small Anim Pract
39:567-573, 1998.
4. Bonagura J, Stepien RL: Vascular diseases. In Birchard SJ and Sherding RG (eds): Small Animal
Practice. Philadelphia, W.B. Saunders, 1994, pp 496-497.
5. Caulkett NA, Cantwell SL, Houston OM: A comparison of indirect blood pressure monitoring tech-
niques in the anesthetized cat. Vet Surg 27:370--377,1998.
6. Goodwin J-K: Systemic hypertension. In Norsworthy GO, Crystal MA, Fooshee SK, Tilley LP (eds):
The Feline Patient. Baltimore, Williams & Wilkins, 1998, pp 413-416.
7. Grandy JL, Dunlop CI, Hodgson OS, et al: Evaluation of the Doppler ultrasonic method of measuring
systolic arterial blood pressure in cats. Am J Vet Res 53: 1166-1169,1992.
8. Grosenbaugh DA, Muir WW: Blood pressure monitoring. Vet Med 93:48-59, 1998.
9. Henik RE, Snyder PS, VolkLM: Efficacy of amlodipine in the treatment of systemic hypertension in cats
with chronic renal failure. J Am Anim Hosp Assoc 33:226-234, 1997.
10. Plotnick AN, Greco DS: Endocrine hypertension. In August JR (ed): Consultations in Feline Internal
Medicine, 3rd ed. Philadelphia, W.B. Saunders, 1997, pp 163-168.
II. Polzin OJ, Osborne CA, James KM: Medical management of chronic renal failure in cats. In August JR
(ed): Consultations in Feline Internal Medicine, 3rd ed. Philadelphia, W.B. Saunders, 1997, pp
331-332.
12. Snyder PS: Amlodipine: A randomized blinded clinical trial in cats with systemic hypertension. j Vet
Intern Med 12:157-162, 1998.
13. Sparkes AH, Caney SM, King Me, et al: Inter- and intraindividual variation in Doppler ultrasonic indi-
rect blood pressure measurements in healthy cats. J Vet Intern Med 13:314-318, 1999.
14. Thornhill JA: Hypertension, systemic. In Tilley LP, Smith FWK (eds): The Five Minute Veterinary
Consult. Baltimore, Williams & Wilkins, 1997, pp 706-707.
64. ELEVATED BODY TEMPERATURE
Kristy L. Dowers. D.V.M.
1. What is considered an elevated temperature in cats?
A rectal temperature> 39.2 C (102.5 F) in cats should be investigated. Rectal temperature
is the most accurate reflection of core body temperature. Human ear thermometers may be useful
to estimate core body temperature in cats that are stressed and/or difficult to handle but are less
accurate because of the shape of a eat's ear canal. When ear thermometers are used, the rectal set-
ting should be used, and 1 F should be added to the temperature reading.
2. Does an elevated temperature mean that the cat has a fever?
The two main rule-outs for elevated temperature are true fever and hyperthermia. Hyper-
thermia can be caused by stress, excitement, exercise, elevated ambient temperature, or heat
stress/stroke. If a cat appears normal except for the elevated temperature, the rectal temperature
should be confirmed a second time after the cat has been allowed to remain calm with the owner
in a quiet area for 15-20 minutes.
3. Describe the mechanism for elevated temperature due to hyperthermia.
Body temperature regulation occurs in the hypothalamus, which attempts to maintain core
temperature at 38.3-38.8 C (101-102.0" F). This normal range is known as the thermoregulatory
set point. With hyperthermia, the thermoregulatory set point remains unchanged, but increased
muscle activity, metabolic activity, or ambient temperature causes an increase in core body tem-
perature. The body responds by attempting to return the body temperature to the set point range,
primarily by panting. Sweating is not as important because cats have few sweat glands and their
skin is fur-covered.
4. Describe the mechanism for elevated body temperature due to fever.
In contrast to hyperthermia, the thermoregulatory set point is adjusted upward with fever.
Exogenous pyrogens (e.g., bacteria, viruses, fungal agents, parasites, tissue necrosis, immune-
mediated disease) activate mononuclear cells and neutrophils. These activated leukocytes release
endogenous pyrogens such as interleukin-l, tumor necrosis factor, and interferons. Endogenous
pyrogens, unlike exogenous pyrogens, can cross the blood-brain barrier and directly alter the
thermoregulatory set point. Alternatively, endogenous pyrogens can stimulate the production of
prostaglandins or cyclic adenosine monophosphate (cAMP) and therefore indirectly affect the set
point. The body then attempts to raise the core temperature to the new set point by conserving
(vasoconstriction) or generating heat (shivering).
5. What is the advantage of fever for the body?
I. Fever enhances the body's immune response:
Leukocyte mobility, phagocytic activity, and lymphocyte transformation increase.
Lysosomes break down more easily, releasing more proteolytic enzymes.
Interferon production rises.
Leukocytes have enhanced bactericidal capabilities.
2. Fever is thought to be detrimental to microorganisms by inhibiting their growth, reducing
the availability of iron nutrients for bacteria, and interfering with bacterial iron chelation.
6. At what point is fever detrimental?
Fevers> 41.1 C (106.0 F) may be harmful to cellular metabolism. Permanent brain and
organ damage can occur with fevers> 41.4 C (106.5 F). Cats with core body temperatures in
these ranges should be treated immediately.
326
Elevated Body Temperature 327
7. What physical examination findings accompany fever?
Most of the clinical signs of fever are nonspecific. Examples include anorexia, depression,
reluctance to move, hyperpnea, and muscle or joint pain. Specific clinical signs are attributable to
the inciting cause and organ system involved. For example, a cat with hemobartonellosis also
may have anemia and icterus in addition to the nonspecific signs of fever.
8. What are the primary causes of fever in cats?
There are five major groups of differentials to consider in the febrile cat: (I) infectious (bac-
terial, rickettsial, viral, fungal, parasitic), (2) inflammatory (e.g., pancreatitis), (3) primary
immune-mediated, (4) neoplasia, and (5) drug-induced. A fever that has lasted for 2 weeks and
does not have an apparent cause is defined as a fever of unknown origin.
9. What are the most common causes of infectious fever in cats?
DIAGNOSTIC
ORGANISM TESTS TREATMENT
Viral
Feline leukemia Any age; intermittent fever; chronic FeLVantigen test Supportivetherapy; treat
virus (FeLV) infections; weight loss; anemia; infections; manage
thrombocytopenia weight loss/anorexia
Feline immuno- Oldercats; intermittent fever;chronic FlV antibody test Supportivetherapy; treat
deficiency infections, weight loss; gingivitis/ infections; manage
virus (FlV) stomatitis weight loss/anorexia
Feline infectious Cats < 2 yr or > 10yr old. Effusive Tissue diagnosis No known therapy; fatal
peritonitis form; peritoneal/pleuraleffusion. (biopsy) disease
(FIP) Noneffusiveform: neurologicl
ocularsigns; signsof specificorgan
involvement; persistent fever
Panleukopenia Young, unvaccinated cats; vomiting, Parvoviralantigen Supportivetherapy:
diarrhea, dehydration,fever, leuko- test of feces; fluids, nutrition, anti-
penia electronmicros- biotics (broadspec-
copy trum)
Feline herpes- Any age; sneezing; oculonasal dis- Clinical signs; IFA, Supportivetherapy:anti-
virus I charge; conjunctivitis;ocular ulce- virus isolation, or biotics with secondary
rations; variablefever PCRof nasal/con- bacterial infection
junctivalscrapings
Feline calcivirus Anyage; serous oculonasal discharge; Clinical signs; viral Supportivetherapy: anti-
mildconjunctivitis; oral ulceration; isolation biotics with secondary
biphasicfever bacterial infection
Bacterial
Bite wound Outdoor cats; pain, heat, swellingat Aspirate; hetero- Drainabscess;antibiotics
abscesses abscesssite;anorexia; fever genouspopulation (penicillin)
of bacteria
Felineplaque Anyage; historyof huntingin endemic Cytology; bipolar Zoonosis! Isolation; anti-
(Yersinia areas;fleaexposure; fever;anorexia; staining for cocco- biotics(doxycycline
pestis) submandibular lymphadenopathy bacilli;IFA or enrofloxacin)
Tularemia Youngercats; exposureto rabbits; IFAor culture from Zoonosis! Isolation;anti-
(Francisella fever; icterus; lethargy; depression; lymph nodes,blood, biotics (doxycycline
tularensis) oral ulcers, septicemia urine,bone marrow or enrofloxacin)
Ehrlichiosis Any age; intermittentfever;hyper- E. canis andE. risticii Supportivetherapy;anti-
(Ehrlichia esthesia;joint pain; Iymphadenop- serumantibody rickettsialdrugs
risticil/canis) athy; variableappetite titers; PCR (doxycycline)
Songbirdfever Any age; indoor/outdoorwith history Blood and fecal Antibioticsif septicemic
(Salmonella of huntingbirds; vomiting; diarrhea; cultures (broad spectrum)
spp.) fever; septicemia
328
Elevated Body Temperature
DIAGNOSTIC
ORGANISM CLINICALDESCRIPTION TESTS TREATMENT
Bacterial(continued)
Haemobartonellosis Any age; pale mucous membranes; Marginatedblood Supportivetherapy
(Haemobartonella icterus; anorexia; depression; smear;PCR (transfusions); anti-
felis) severe regenerativehemolytic
biotics (doxycycline,
anemia
enrofloxacin)
Chlamydiosis Any age; purulent oculonasal dis- Conjunctival scrap- Supportivetherapy;anti-
(Chlamydia charge; conjunctivitis; fever ing cytology; in- biotics (doxycycline
psittaci)
elusion bodies in or chloramphenicol
epithelial cells topically)
Protozoal
Toxoplasmosis Any age; fever; dyspnea; icterus; Tissue diagnosis Supportivetherapy;anti-
(Toxoplasma abdominalpain; uveitis;chorio- (biopsy);IgM biotics(clindamycin)
gondii) retinitis;neurologicsigns; inter- and IgGserum
mittentfever;lethargy; depression aqueoushumor or
CSF titers
Cytauxzoonosis Any age; highfever; dyspnea; Blood cytology: Supportivetherapy;anti-
(Cytauxzoonfelis) anemia; thrombocytopenia; "signet ring" protozoals(irnidocarb
splenomegaly organismswithin or dirninazene)
erythrocytes
Fungal
Histoplasmosis Younger cats 4 yr); peripheral Cytology:intracellu- Itraconazole; flucona-
(Histoplasma and viscerallymphadenopathy; lar (macrophages) zole; amphotericinB
capsulatum) dyspnea;fever; weight loss thincapsule;serol-
ogy inaccurate
Blastomycosis Anyage (morecommonin dogs); Cytology:extra- Itraconazole; flucona-
(Blastomyces respiratorysigns; ocular signs; cellular,broad- zole; amphotericinB
dermatitidis] fever; weight loss based budding
yeast; serology:
antibodytests
Coccidioidomycosis Any age (rarein cats); skinlesions; Ctyology:extra- Itraconazole; flucona-
(Coccidioides fever cellular double- zole; amphotericinB
immitis) walled; serology:
antibodytests
Cryptococcosis Any age; sneezing; stertorous Cytology:extra- Itraconazole; flucona-
(Cryptococcus breathing;chronicnasal dis- cellular, thick zole; amphotericinB
neoformans) charge; skinlesions; low-grade capsule; serology:
fever antigentests
IFA =immunofluorescent assay, PCR =polymerase chain reaction, IgM = immunoglobulin M, IgG =im-
munoglobulinG, CSF = cerebrospinal fluid.
10. What are thecommon causes of inflammatory feverincats?
DISEASE
Pancreatitis
Cholangio-
hepatitis
Meningoen-
cephalitis
CLINICALDESCRIPTION
Any age; chronic, intermittent form;
anorexia; lethargy; variableabdomi-
nalpain; icterus
Anyage; icterus; vomiting; anorexia;
feverin suppurative form
Any age; recurrent seizures; multifocal
neurologic signs; vomiting; diarrhea;
fever
DIAGNOSTIC
TESTS
SerumTLI; ultrasound;
biopsy; lipase activity
of peritonealeffusion
Abdominal ultrasound;
liverbiopsywithculture
andsensitivity testing
None. CSF analysis to
rule out other causes
of seizures
TREATMENT
Supportivetherapy:
fluids,nutrition; anti-
biotics; glucocor-
ticoids
Antibiotics if suppura-
tive;glucocorticoids
if nonsuppurative
No known therapy;
possible viraletiology
Tablecontinuedonfollowingpage
Elevated Body Temperature 329
DISEASE
Myocarditis!
diaphragrnitis
CLINICAL DESCRIPTION
Any age; biphasic fever at 10 days
and 3-4 weeks; hyperesthesia;
lymphadenopathy; cardiac signs
DIAGNOSTIC
TESTS
None. Rule out other
causes of fever, car-
diac disease
TREATMENT
No known therapy;
multifactorial
etiology
CSF = cerebrospinal fluid.
11. What are the most common causes of immune-mediated fever in cats?
DIAGNOSTIC
DISEASE CLINICAL DESCRIPTION TESTS TREATMENT
Systemic lupus Rare in cats; multiple systemic ANA titers; skin Immunosuppression
erythematosus signs; fever; weight loss; biopsies
cutaneous lesions
Primary hemolytic Anemia; icterus; fever, anorexia Work-up for Haemo- Treat underlying cause;
anemia bartonellafelis; immunosuppression
FeLVIFIV tests
Idiopathic throm- Rare in cats; fever; lethargy; FeLVlFlV tests Treat underlying cause;
bocytopenia petechiae immunosuppression
Idiopathic poly- Uncommon in cats; stiff, painful Arthrocentesis Treat underlying cause;
arthritis joints; fever; lethargy immunosuppression
ANA =antinuclear antibody, FeLV =feline leukemia virus, Fl V =feline immunodeficiency virus.
12. What neoplasms most commonly cause fever in cats? What are the clinical signs and
symptoms?
Any neoplasm may cause fever, but the most common is lymphoma. Cats of any age may be
affected. Signs and symptoms are attributable to the organs involved; fever may be persistent or
intermittent.
13. How is fever related to neoplasms diagnosed and treated?
Diagnosis depends on blood work, imaging, titers of feline leukemia virus and feline im-
munodeficiency virus, bone marrow aspirates, and biopsies. Treatment depends on the specific
tumor.
14. What drugs may induce fever in cats?
The most common examples are tetracycline and amphotericin B. Cats of any age may be af-
fected. The fever is disproportionate to clinical signs in an otherwise healthy cat. Treatment is
discontinuance of the drug.
15. Howdo the history and signalment help rank the differential diagnoses?
Young cats, especially those with outdoor access, are more likely to have infectious causes
of fever. Examples include abscessed bite wounds, feline leukemia virus (FeLY), feline plague,
tularemia, and salmonellosis (song-bird fever). Fever of unknown origin in older cats is more
likely to be due to neoplasia or chronic infections such as FeLY and feline immunodeficiency
virus (FlY). Purebred cats may have a genetic predisposition for feline infectious peritonitis
(FlP). Travel history to fungal-endemic areas, current medications, and exposure to ticks and
fleas are important historical findings that help to prioritize the differential list.
16. What specific physical examination findings are helpful?
A good physical examination can direct your approach to febrile cats. An oral examination
may reveal dental disease, pale mucous membranes, petechiae, or icterus. Heart murmurs and de-
creased lung sounds are identified with auscultation of the chest. Muscles, joints, and bones should
330
Elevated Body Temperature
be palpated for evidence of pain. Abdominal palpation allows you to assess pain, organomegaly,
peritoneal effusion, and irregular kidneys. A fundic examination should be performed in every cat
because infectious diseases such as Cryptococcus neoformans, Toxoplasma gondii, and FIP can
cause ocular lesions. In some cats, however, the only presenting sign is fever.
17. What is the recommended diagnostic work-up for fever of unknown origin?
Complete blood count FeLV antigen test
Serum biochemistry panel FlY antibody test
Urinalysis with or without urine culture Serum T4 concentration (> 5 years old)
Fecal examination
Chest and abdominal radiographs are also recommended, especially if the physical examina-
tion and/or blood work do not reveal the cause of the fever. Abdominal ultrasound may be neces-
sary to evaluate organomegaly, suspected pancreatitis. mass effects, or peritoneal effusion. Blood
cultures, both aerobic and anaerobic, are indicated in many cats with fever because a cause may
not be apparent in the preliminary work-up.
18. What is the optimal technique for performing blood cultures?
Three separate blood cultures should be obtained over 2 hours, preferably during a period of
fever. Fresh venipuncture samples are preferred. At least 3-5 ml of blood should be collected for
each sample; care should be taken not to oversample cats with concurrent anemia. The skin over
the jugular vein should be shaved and prepared as for a surgical procedure. Sterile gloves should
be worn. After the sample is collected aseptically, a new needle should be used to introduce the
blood into the culture medium. Do not refrigerate the culture. It should be kept at room tempera-
ture if incubation at 37 C is not immediately available.
19. How should hyperthermia be treated?
As mentioned above, all cats with core body temperature> 41.1 C (106.0 F) should be
treated immediately. The goal in cats with hyperthermia or heat stroke is rapid cooling of the core
body temperature to 39.4C (103.0 F) within 30-60 minutes. Cooling can be accomplished by
soaking the eat's fur with cool water, using fans to promote evaporative cooling, and applying ice
packs to the inguinal, axillary, and jugular vein areas. Intravenous fluid therapy should be used
carefully; excessive fluids during initial cooling can lead to pulmonary edema. Once the target
temperature of 39.4 C is achieved, cooling measures should be stopped. Shivering and heat pro-
duction are induced at temperatures below this level. The cat should be monitored carefully after
initial cooling for complications of heat stroke, including renal failure, hepatic failure, cerebral
edema, and disseminated intravascular coagulation.
20. How should fever of unknown origin be treated?
Intravenous therapy with room temperature fluids can reduce a high fever and improve the
eat's sense of well-being. The underlying cause should be identified and treated primarily.
Examples include antibiotic therapy for infectious causes, glucocorticoids for immune-mediated
and inflammatory causes, and surgery or chemotherapy for neoplasia. As with hyperthermia.
fevers> 41.1 C (106.0 F) should be treated using the techniques described above. Most true
fevers, however, do not exceed 41.1 C (106.00 F).
21. Should drugs such as dipyrone or aspirin be used?
Dipyrone and other nonsteroidal anti-inflammatories such as aspirin and flunixin meglumine
are contraindicated for treatment of heat stroke. These drugs decrease the hypothalamic set point
(which is normal with heat stroke) and may exacerbate the gastrointestinal ulceration and renal
damage that can occur with heat stroke. For treatment of true fever, aspirin can be administered at
5 mglkg orally every 24 hr. Use of dipyrone is discouraged because dosages for cats are not well
established, and the side effects include bone marrow suppression and clotting abnormalities, es-
pecially with long-term use.
Joint Disease
BIBLIOGRAPHY
331
I. Dunn JK, Green CE: Fever. In Green CE (ed): Infectious Diseases of the Dog and Cat, 2nd ed.
Philadelphia, W.B.Saunders, 1990,pp 64-71.
2. JohnsonKE: Pathophysiology of heatstroke. Comp Cont Educ Pract Vet4:141-144, 1982.
3. Lappin MR: Fever, sepsis, and principles of antimicrobial therapy. In Leib MS, Monroe WE (eds):
Practical SmallAnimal Internal Medicine. Philadelphia, W.B.Saunders, 1997, pp 829-836.
4. Larson RL, Carithers RW: A review of heat stroke and its complications in the canine. N Z Vet J
33:202-206, 1985.
5. Lorenz MD: Pyrexia (fever). In Lorenz MD, Cornelius LM (eds): Small Animal Medical Diagnosis, 2nd
ed. Philadelphia, J.B. Lippincott, 1993,pp 15-22.
6. Lorenz MD: General (polysystemic) problems: Pyrexia, anorexia, weight loss, and obesity. In Lorenz
MD, Cornelius LM, Ferguson DC (eds): Small Animal Medical Therapeutics. Philadelphia, 1.B.
Lippincott, 1993,pp 25-26.
65. JOINT DISEASE
Catriona M. MacPhail, D.v.M.
1. How is joint disease typically classified?
Joint disease is initially categorized as either inflammatory or noninflammatory. Inflam-
matory arthritis may have an infectious or immune-mediated etiology. Immune-mediated
arthropathies can be further classified as erosive or nonerosive. The classic noninflammatory
joint disease is osteoarthritis, a low-grade inflammatory condition that results in destruction of
articular cartilage, typically secondary to injury or chronic abnormal wear.
Classification of Feline Joint Diseases
Noninflammatory
Degenerative: osteoarthritis
Congenital: Scottish fold arthropathy
Inflammatory
Infectious
Erosive
Sepsis
L-forms
Nonerosive
Mycoplasmal
Viral
Calcivirus
Noninfectious
Erosive
Feline chronic progressive polyarthritis
Rheumatoid arthritis
Nonerosive
Systemic lupus erythematosus
Drug-induced
Vaccine-associated
Chronic inflammatory response
Idiopathic
2. Define polyarthritis.
Polyarthritis is an inflammatory joint disease involving two or more joints, usually with a
specific etiology. It is less common in cats than in dogs. Typically systemic illness accompanies
inflammatory joint changes. Systemic signs include pyrexia, anorexia, malaise, and occasionally
lymphadenopathy.
3. What is the initial diagnostic plan for cats with suspected joint disease?
Thorough physical, orthopedic. and neurologic examinations help to differentiate among
bone, joint, muscle, or neurologic sources of pain and lameness. Multiple joint involvement also
332 Joint Disease
may be identified. Radiographs and synovial fluid analysis are the hallmark diagnostic tests
for joint disease. Other diagnostic tests vary based on the suspected disease. Radiographs
help to confirm suspicions of osteoarthritis, identify possible septic arthritis, and determine
whether a polyarthritis is erosive or nonerosive. MUltiple distal joints should be radiographed
if immune-mediated polyarthritis is suspected. Nonerosive inflammatory joint disease typi-
cally causes radiographic abnormalities other than soft tissue swelling and joint capsule dis-
tention. The overall cell count and predominant cell type in the synovial fluid can help
differentiate among the multiple causes of arthritis. Synovial fluid analysis also can be used
to monitor response to therapy.
4. How are joint taps performed and analyzed?
Mild-to-heavy sedation is often required to perform arthrocentesis. Select the joints with
obvious effusion for initial sampling. However, if polyarthritis is suspected, multiple joints
should be sampled, particularly the carpi and tarsi. Often only a small amount of synovial
fluid is obtained. Therefore, tests on the fluid should be prioritized. If only a drop or two of
fluid is retrieved, cytologic assessment helps to estimate differential cell counts, thus distin-
guishing between inflammatory and noninflammatory joint disease. Viscosity can be subjec-
tively assessed as joint fluid drips from the needle onto a slide or culturette. Other tests that
can be performed on synovial fluid include determination of total nucleated cell count and
total protein concentration, mucin clot test, and aerobic bacterial, anaerobic bacterial, and
mycoplasmal cultures.
5. What are the characteristics of normal joint fluid?
Normal joint fluid is clear, colorless, and highly viscous. Normal protein count is < 2.5 gmJdl
with a total nucleated cell count <3000 cells/ul (primarily mononuclear cells).
6. Why is osteoarthritis often not recognized in cats?
Osteoarthritis is a chronic, slowly progressive disorder that may be insidious in onset.
Because of a eat's small size and ability to redistribute weight to other limbs, subtle gait abnor-
malities often go unrecognized by owners. Other clinical signs associated with osteoarthritis in
cats include behavior or temperament changes, anorexia, dull hair coat, decreased jumping abil-
ity, and decreased activity level.
7. Where does osteoarthritis most often occur in cats?
Osteoarthritis is thought to occur most commonly in the shoulders and elbows of older cats.
Hip dysplasia is a common cause of coxofemoral osteoarthritis in dogs but has received relatively
little attention in cats. A recent feline population study found a 6.6% breed-dependent radi-
ographic incidence of hip dysplasia. Purebred cats, predominantly Maine coons and Himalayans,
are particularly overrepresented.
8. How can osteoarthritis be managed in cats?
As with canine osteoarthritis, areas to address for the management of osteoarthritis include:
Nutrition and weight management Drugs
Exercise modification Surgery
9. Discuss pain control in cats with osteoarthritis.
Pain control is difficult because many available drugs are not safe to use in cats. Newer
nonsteroidal anti-inflammatory drugs can be used in cats but only for short-term relief.
Potential choices for chronic administration include aspirin, piroxicam, butorphanol, or corti-
costeroids; however, owners must be educated about potential side effects. Glucosamine/chon-
droitin sulfate supplement administration has been described with anecdotal reports of
improved quality of life.
Joint Disease 333
10. List the drugs used to treat feline joint disease, their indications, and appropriate doses.
Drugs Used to Treat Feline Joint Disease
NAME INDICATION DOSE COMMENTS
Aspirin Analgesic, anti- 10-25 mg/kg PO every
inflammatory 2 ~ 8 h r
Auranofin Immunosuppressive 0.05-2 mg PO every 12 hr Not to exceed 9 mg/24 hr
Aurothioglucose Immunosuppressive I mg/cat 1Mevery 7 days, Can be tapered after 2--4
then I mg/kg 1Mevery wk to every 30 days
7 days
Azathioprine Immunosuppressive 1.1 mg/kg PO every 48 hr Use with caution
Butorphanol Analgesic I mg/cat PO every 12 hr
Carprofen Analgesic, anti- 4 mg/kg PO oncer Use with caution
inflammatory
Chlorambucil Immunosuppressive 0.25--0.5 mg/kg PO every
48-72 hr
Chloramphenicol Antimicrobial 25-50 mg/kg PO every 12 hr
Cosequin Disease-modifying I capsule PO every 24 hr Sprinkle on food
Cyclophospha- Immunosuppressive 2.5 mg/kg PO every 48 hr Use with caution
mide up to 3 wk
7 mg/kg IV every 7 days
In conjunction with- 2.5 mg/kgd PO every 24 hr
prednisone/pred- for 4 days, then off 3 days
nisolone
Doxycycline Antimicrobial 5-10 mg/kg PO every 12 hr
Ketoprofen Analgesic, anti- 1 mg/kg PO every 24 hr Limit 5 days
inflammatory
2 rng/kg SC every 24 hr Limit 3 days
Prednisone/pred- Immunosuppressive 2--4 mg/kg PO every 24 hr
nisolone divided
Piroxicam Anlagesic/anti- 0.3 mg/kg PO every 48-72 Use with caution
inflammatory hr
PO =orally, 1M=intramuscularly, IV =intravenously.
11. What environmental changes may benefit cats with osteoarthritis?
Easier accessibility to food, toys, and bedding allows the cat to avoid large leaps up and
down, thereby decreasing stress on affected joints. Weight loss for obese cats or improved nutri-
tion for thin cats also may be of some benefit.
12. What surgical options are available for treatment of cats with osteoarthritis?
Surgical options are limited to femoral head and neck excision for coxofemoral arthritis and
amputation. Arthrodesis can be performed in distal joints, such as the carpus or tarsus, but these
joints are affected more commonly by inflammatory arthritides.
13. Why are cats less likely to develop infectious arthritis than dogs?
Systemic infections commonly localize in joints because of the abundant blood supply of the
synovial tissue. Monoarticular disease is more likely than polyarticular disease, and previously
damaged joints are more likely to be infected. Typical infections include urinary tract or prostatic
infections, pyoderma, and bacterial endocarditis. These conditions are relatively rare in cats com-
pared with dogs. More commonly, bacterial arthritis occurs in neonates with omphalophlebitis or
neonates that nurse from queens with postparturient uterine or mammary gland infections.
334
loint Disease
14. Infection by what cellwall-deficient bacteriamaycauseerosivepolyarthritis?
L-fonns are mutant, wall-deficient bacteria derived from many different species. Infection is
characterized by distal asymmetric polyarthritis that causes articular cartilage destruction, meta-
physeallysis, and periosteal proliferation. Cats may become nonambulatory with elevated body
temperature. Distal joints are markedly swollen with occasional development of fistulating tracts
erupting from the distended joint capsule. Subcutaneous draining abscesses are another manifes-
tation of the infection. The thick brown exudate is pyogranulomatous inflammation.
15. Howis Lfonn bacterial infection diagnosed?
Diagnosis is based on consistent clinical signs, cytologic and radiographic findings, elimina-
tion of other possible causes of erosive polyarthritis, and response to treatment. The L-fonn bac-
terium is difficult to isolate and identify. However, affected cats respond quickly to oral tetracycline.
Joint changes are irreversible; if marked instability is present, arthrodesis may be a consideration.
16. Infection by whatcell wall-deficient bacteria maycausenonerosive polyarthritis?
Mycoplasma spp. are normal flora in certain organ systems in the body. However, they are
opportunistic secondary pathogens that may cause problems in immunocompromised animals or
animals receiving penicillins or cephalosporins. Several cases of mycoplasmal arthritis in cats
have been reported. Clinical signs are similar to those of other nonerosive arthritides. Myco-
plasmal organisms can be isolated from the joint fluid by culture. Recently, M. felis was isolated
from the joints of a cat with polyarthritis, and DNA was detected in joint fluid by polymerase
chain reaction. Mycoplasmal infections are generally responsive to tetracyclines, chlorampheni-
col, fluoroquinolones, and aminoglycosides.
17. Whatare the otherinfectious causesof polyarthritis in cats?
Feline calicivirus (FCV) infection causes a short-lived limping syndrome in kittens infected
naturally or experimentally. Other clinical signs include elevated temperature, hyperesthe-
sia, and ulceration of the tongue or palate. This syndrome also may occur after immuniza-
tion of kittens with vaccines containing live FCV. Signs typically last 48-72 hours.
Mild-to-severe synovitis has been reported in cats with the effusive form of feline infectious
peritonitis (see Chapter 38). Affected cats typically show no signs of lameness or discomfort.
An epidemiologic association between polyarthritis in cats and the presence of Ehrlichia
spp. antibodies (see Chapter 78) was recently reported.
Although cats develop Borrelia burgdorferi antibodies, polyarthritis due to infection by
this bacterium has not been well documented.
18. Asidefromsepticarthritisand bacterialL-formpolyarthritis, what otherdifferential
diagnoses mustyou consider in cats witherosivepolyarthritis?
Several cats have been reported to have positive rheumatoid factor titers concurrent with ero-
sive polyarthritis. However, rheumatoid arthritis is not well characterized in cats. A criterion for
diagnosis has not been established for cats, as it has for humans and dogs. Feline chronic pro-
gressive polyarthritis (FCPP) is a rare condition that occurs in male cats. Although the etiology is
probably immune-mediated, an association with feline leukemia virus (FeLV) and feline syncy-
tia-forming virus (FeSFV) is suspected.
19. Whatare the twoformsof FCPP?
The periosteal proliferative fonn occurs only in young male cats. Typical clinical signs in-
clude elevated temperature, marked joint pain, distal limb stiffness and lameness, and regional
lymphadenopathy. The carpi and tarsi are the most commonly affected joints, and usually the dis-
ease is symmetrical. Radiographic changes lag behind clinical signs; however, typical abnormal-
ities include periosteal proliferation, osteophytosis, subchondral bone lysis, and joint space
collapse. Fibrous ankylosis may be present in advanced cases. Diagnosis of FFCP is usually by ex-
clusion of infectious causes of erosive arthritis. Immunosuppressive drug therapy is the treatment
Joint Disease 335
of choice; corticosteroids alone lessen the severity of clinical signs but do not slow the progression
of the disease. Combination therapy with corticosteroids and cyclophosphamide or azathioprine
has been more successful, achieving remission in approximately 50% of treated cats.
The erosive or deforming form of FFCP is less common and occurs mostly in older cats.
The disease is slowly progressive, and clinical signs develop gradually. Joint deformities occur in
the carpal, metacarpophalangeal, metatarsophalangeal, and interphalangeal joints. Radiographic
changes include severe subchondral bone erosion, relatively mild periosteal proliferation, and
joint subluxation or luxations. Information about treatment and prognosis of this form of FFCP is
limited, although immunosuppressive therapy probably is indicated.
20. Describe the association between FFCP and FeSFV.
FeSFV is a retrovirus of the subfamily Spumarininae. The incidence of FeSFV infection is
high among both normal and diseased cats. The prevalence in a cat population varies between 4%
and 50%. Vertical transmission is possible: at least 50% of kittens born to infected queens are in-
fected at birth. FeSFV has not been associated with any disease, although in one study the virus
was present in 100% of cats affected with FFCP. However, polyarthritis cannot be reproduced
with FeSFV isolated from diseased cats. Concurrent FeLV infection was found in 70% of these
cats, and concurrent infection with feline immunodeficiency virus (FlV) is also common. It is
postulated that FeLV and FIV alter the host immune system to potentiate the ability of FeSFV to
produce disease, manifesting primarily as an arthropathy through immune complex deposition in
the synovium. However, this theory has yet to be verified.
21. Discuss specific causes of immune-mediated nonerosive polyarthritis.
Systemic lupus erythematosus (SLE) is a chronic, immune-mediated polysystemic disease
that is not as well characterized in cats as in dogs. Polyarthritis is only one manifestation of the
disease. Other clinical signs include dermatitis, lymphadenopathy, conjunctivitis, glomeru-
lonephritis, and fever. Lameness and joint pain are often overlooked, and polyarthritis is typically
diagnosed from arthrocentesis that shows an increased cell count primarily consisting of nonde-
generate neutrophils. The presence of antinuclear antibodies (ANA) in the blood is a potentially
diagnostic feature of SLE. However, a positive ANA titer alone does not diagnose SLE. If other
causes of nonerosive polyarthritis have been ruled out, a cat with consistent clinical signs and a
positive ANA titer is likely to have SLE.
A chronic inflammatory process or antigenic source can cause secondary polyarthritis.
Immune complexes become trapped in the synovial membrane, initiating a marked inflammatory
response. Sources of immune complexes include chronic bacterial or parasitic infection, neopla-
sia, and recent drug or vaccine administration. When the cause of immune-mediated nonerosive
joint disease is undetermined, it is referred to as idiopathic polyarthritis.
22. How are immune-mediated nonerosive polyarthritides diagnosed and differentiated?
The clinical history of immune-mediated polyarthritides is fairly similar. Often the disease is
cyclic and associated with periods of fever, mala.ise, and anorexia. The joints can be grossly
swollen and are painful on manipulation. The smaller distal joints are more often affected, and
radiographic changes are minimal to nonexistent.
Synovial fluid analysis retrieves a nontoxic neutrophilic inflammation and cultures are nega-
tive. Serologic tests include ANA titer, LE-cell preparation, and rheumatoid titer. Results of these
tests must be considered in relation to history, clinical signs, and results of other diagnostic tests
to distinguish among various etiologies.
23. What drugs are used to treat immune-mediated polyarthritis?
Immunosuppressive doses of corticosteroids are the cornerstone of therapy for immune-me-
diated disease. However, some patients may require combination therapy with cyclophos-
phamide, chlorambucil, or gold salts. Supportive care such as rest, dietary management, and
exercise modification, should not be overlooked.
336
Muscle Diseases
24. What type of arthropathy is associated with Scottish fold cats?
The folded ears of Scottish fold cats are due to an abnormality in the ear cartilage caused by
a simple autosomal dominant gene. Cats that are homozygous for the gene develop generalized
cartilage abnormalities. This condition is manifested by a shortening and thickening of axial
and appendicular bones, resulting in a short, crouched appearance. Clinical signs include pro-
gressive lameness and stiffness as joint involvement advances. The joints of the distal hindlimbs
are usually affected most severely. Medical management of pain and lameness is the only avail-
able therapy.
BIBLIOGRAPHY
I. Bennet D: Treatment of the immune-based inflammatory arthropathies of the dog and cat. In Kirk RW
(00): Kirk's Current VeterinaryTherapy XII. Philadelphia, WB, Saunders, 1995, pp 1188-1204.
2. Bennet D, Nash AS: Feline immune-based polyarthritis: A study of thirty-one cases. J Small Anim Pract
29:501-523, 1988.
3. Carro T: Polyarthritis in cats. Compend Cont Educ Pract Vet 16:57-67,1994.
4. Carro T: L-Forms and mycoplasmal infections. In August JR (ed): Consultations in Feline Internal
Medicine, 2nd ed. Philadelphia. W.B. Saunders, 1994, pp 13-20.
5. Hardie EM: Management of osteoarthritis in cats. Vet Clin North Am 27:945-953, 1997.
6. Keller GG, Reed AL, Lattimer JC, et al: Hip dysplasia: A feline population study. Vet Radiol Ultrasound
40:460-464, 1999.
7. Pederson NC, Morgan JP, Vassuer PB: Joint diseases of dogs and cats. In Ettinger SJ (ed): Textbook of
VeterinaryInternal Medicine. 5th ed. Philadelphia, W.B. Saunders, 2000, pp 1862-1885.
8. Stubbs CJ, Holland CJ, Reif JS, et al: Feline ehrlichiosis: Literature reviewand serologic survey. Comp
Cont Educ Pract Vet 22:307-317,2000.
66. MUSCLE DISEASES
Catnona M. MacPhail, D.V.M.
1. What are the most common muscle diseases (myopathies) of cats? How are they clas-
sified?
Although most are rare, there are multiple causes of myopathy in cats. Some myopathies
can be diagnosed indirectly using history and routine blood tests (hypokalemic myopathy).
Others are classified by histologic appearance of tissue collected by biopsy. Myopathies can be
inflammatory or degenerative, depending on the cause. Inflammatory myopathies are further
classified into immune-mediated or infectious causes. Degenerative myopathies are congenital
or acquired.
Feline Myopathies
Degenerative
Congenital
Muscular dystrophy
Myotonia
Nemaline rod myopathy
Myasthenia gravis
Acquired
Myasthenia gravis
Myositis ossificans
Metabolic
Hypokalemia
Endocrine
Hyperthyroidism
Inflammatory
Immune-mediated (idiopathic)
Infectious
Bacterial
Protozoal
Parasitic
Vascular
Ischemic neuromyopathy
Muscle Diseases 337
2. What are the most common clinical signs associated with myopathies?
Generalized weakness is the predominant sign associated with skeletal muscle disorders.
Other clinical signs include tremors, stilted gait, abnormal posturing, muscle pain, palmigrade or
plantigrade stance, and variable lameness. Muscle atrophy, fibrosis, and contracture may be ap-
parent in advanced myopathies. Cats with generalized weakness are more likely to present with
cervical ventroflexion than dogs because cats lack the nuchal ligament that helps to maintain
normal neck posture.
3. What are the other possible differential diagnoses for generalized weakness in cats?
Toxicities, neuropathies, nutritional deficiencies, cardiopulmonary disease (including
anemia), and hypoglycemia can present with generalized weakness. The most common toxins as-
sociated with weakness include pyrethroid insecticides and organophosphates. Thiamine defi-
ciency has been reported to cause a responsive generalized weakness, because thiamine is
essential for aerobic metabolism. Cats with mild-to-moderate hypoglycemia, most commonly as-
sociated with insulin overdose, may present with acute generalized weakness before showing any
neurologic abnormalities. Cats with polyneuropathy associated with diabetes mellitus typically
present with hindlimb weakness and plantigrade stance.
4. What is the initial diagnostic plan for cats with suspected myopathy?
A thorough history, physical examination, and neurologic examination should help to differ-
entiate between musculoskeletal, neurologic, and cardiopulmonary causes of generalized weak-
ness. Complete blood cell count, serum biochemical panel, and urinalysis may further characterize
metabolic and endocrine causes. Complete blood count helps to rule out anemia as a cause of
weakness, and leukocyte counts may reflect a systemic inflammatory response. Hypokalemia is
one of the most common causes of myopathy in cats. Serum potassium concentrations usually
must be < 3.0 mEqlL to produce clinical signs. Renal azotemia mayor may not be detected con-
currently. Activities of creatine kinase (CK) and aspartate aminotransferase (AST) may be ele-
vated, although some muscular diseases may cause few enzymatic changes. Therefore, normal
CK and AST activities should not be used to rule out muscle disease. Urinalysis is crucial to
identify renal disease, urinary tract infections, or glucosuria. Serum total T4 concentration should
be measured in cats with suspected myopathy that are > 5 years of age.
5. What are the most important clinical aspects of hypokalemic myopathy?
Hypokalemia caused by decreased intake or increased excretion is frequently recognized in
cats, especially those with chronic renal disease (see Chapter 40). Generalized weakness and cer-
vical ventroflexion are common clinical abnormalities, A heritable form of hypokalemic myopa-
thy has been detected in Burmese kittens that demonstrate intermittent muscle weakness and
cervical ventroflexion, beginning at 2-6 months of age. Hypokalemia causes muscle weakness
by increasing resting membrane potential, which makes skeletal muscle more refractory to stim-
uli. Clinical signs usually resolve after potassium supplementation.
6. How is potassium supplementation achieved?
Mildly affected cats are given potassium gluconate at 2 mEq per 4.5 kg body weight orally
every 12 hr (Tumil-K; Daniels, St. Petersburg, FL). Periodic evaluation of potassium levels dic-
tates the need for chronic administration.
Severely affected cats 2.5 mEqlL) require parenteral administration of potassium-sup-
plemented fluids. Potassium should be administered cautiously via the intravenous route (0.5-
1.0 mEqlkg/hr), diluted in a balanced electrolyte solution. Serum potassium concentrations
should be monitored periodically during the infusion, and treatment should be discontinued once
serum levels have reached 3.5 mEqlL. Electrocardiographic monitoring is also critical to observe
for dysrrhythmias associated with hyperkalemia. Rapid administration of intravenous fluids may
worsen hypokalemia by expanding venous vascular volume, which dilutes serum potassium con-
centrations. Critically low serum potassium values 2.0 mEqlL) may lead to respiratory arrest
338
Muscle Diseases
due to profound muscle weakness. Dopamine administration (0.5 mcglkglmin, IV) is an alterna-
tive; dopamine causes translocation of potassium from the intracellular to extracellular fluid.
7. What is the diagnostic plan for cats with suspected myopathy when routine testing is
inconclusive?
Electromyography (EMG) and muscle biopsy are commonly used. EMG helps to differenti-
ate among neuropathies, neuromuscular junction disorders, and myopathies. EMG changes are
fairly similar, regardless of the etiology of the myopathy. Muscle biopsy is used for definitive di-
agnosis. However, EMG findings help to characterize the distribution of the disease. EMG abnor-
malities consistent with muscle disease include polyphasic decreased motor unit action
potentials, single sharp wave or trains of positive sharp waves, bizarre high-frequency waves, and
myotonic discharges. Fibrillation potentials classically indicate denervation but can be seen in
polymyositis and muscular dystrophy. Nerve conduction velocity studies should be normal.
8. How is the site for muscle biopsy chosen?
The pathologist should be consulted for preferred methods of sample acquisition and han-
dling to obtain reliable results. The biopsy site should be based on history and clinical findings,
although ideally multiple muscles should be sampled. EMG may be used to identify affected
muscles, but needle insertion sites should be avoided during sample collection. For diffuse dis-
eases, easily accessible superficial muscles such as the biceps femoris (distal third), long head of
triceps (distal third), forelimb superficial digital flexor (proximal third), and lateral gastrocne-
mius (proximal third) usually are chosen.
9. How is the muscle biopsy collected?
Biopsies usually are collected under general anesthesia, but heavy sedation and local analge-
sia may be used as an alternative. Muscle samples should be handled as atraumatically as possi-
ble. Stay sutures can be used to help manipulate the tissue. A muscle sample is obtained (without
any overlying fascia) by using a scalpel blade or fine, sharp scissors and incising parallel to the
long direction of the muscle fibers. Take care to avoid significant neurovascular structures. A typ-
ical biopsy sample measures I x 2 x 1 em, After sampling, the biopsy is wrapped in saline-
damped sponge, placed in a watertight container, and forwarded to the pathology laboratory as
soon as possible. Processing can be delayed up to 30 hours as long as the sample is kept moist
and cool (0-4C). If a preservative is to be used, glutaraldehyde is preferred, because formalin
fixation causes marked contraction artifacts. Electron microscopy evaluation requires the muscle
to be stretched without excessive tension to prevent contraction or damage to the myofibers.
Ideally special biopsy clamps are used to keep the muscle slightly stretched. Alternatively, stay
sutures or small pins can keep a muscle slightly stretched across a tongue depressor.
10. What is idiopathic polymyositis? How is it managed?
Feline idiopathic polymyositis is an acquired inflammatory myopathy. Affected cats have an
acute onset of weakness with marked cervical ventroflexion. Diagnosis is made by exclusion of
other causes of myopathy with supportive EMG and muscle biopsy abnormalities. Histopatho-
logic findings include severe myofiber necrosis and phagocytosis, lymphocytic inflammation,
and fibrosis. Spontaneous recovery occurs in 30% of cats. Prednisone therapy may alleviate
signs, but recurrence is common.
11. What are the common infectious causes of polymyositis? How are they managed?
Bacterial polymyositis is uncommon in companion animals, but when it occurs in cats, it
typically is associated with Pasteurella multocida, although anaerobic infections must be consid-
ered. Localized myositis results from external trauma, such as bite wounds, whereas polymyosi-
tis typically is a manifestation of an overall disease process in which infection is spread
hematogenously from a distant site. Clinical signs include muscle pain and swelling, pyrexia, and
occasionally fistulation. Empirical antimicrobial therapy is based on the most likely contaminant.
In general, an antibiotic with a broad gram-positive and anaerobic spectrum is a good first choice.
Muscle Diseases 339
Toxoplasma gondii is associated more commonly with respiratory, ocular, or gastrointestinal
signs in cats, although the organism may be found in the musculoskeletal and nervous systems.
Typical musculoskeletal signs include abnormal gait, shifting leg lameness, mild-to-moderate
hyperesthesia on muscle palpation, and muscle atrophy. Diagnosis is based on serologic evidence
of active infection (high IgM and IgG titers), exclusion of other causes of muscle disease, and
clinical response to treatment. The drug of choice is clindamycin, 10-12 mglkg orally every 12
hr (Antirobe; Upjohn, Kalamazoo, MI). Systemic signs usually begin to subside within 24-48
hours of initiation of treatment, but muscle atrophy may take several weeks to resolve.
Trichinella spiralis seldom causes musculoskeletal signs, although cats are thought to be
more susceptible to infection than dogs. Sarcocystis cysts have been found in the muscle of cats,
but they are thought to be incidental and nonpathogenic.
12. What endocrine disorders are commonly associated with myopathy?
Muscle tremors and generalized weakness have been reported in cats with hyperthyroidism.
Thyroid hormone excess is thought to affect mitochondrial oxidative phosphorylation. Total body
water loss and hypokalemia associated with hyperthyroidism also may contribute to generalized
weakness (see Chapter 53). Although rare in cats, hyperadrenocorticism has been associated with
muscle weakness. Glucocorticoid excess increases muscle protein catabolism and inhibits synthe-
sis of myofibrillar proteins, resulting in progressive loss of skeletal muscle mass (see Chapter 54).
13. Define muscular dystrophy.
Muscular dystrophy refers to a group of inherited muscle disorders characterized by progres-
sive degeneration of skeletal muscles. X-linked disorders have been described in both dogs and
cats. The disease in cats is characterized by generalized skeletal muscle hypertrophy, whereas in
dogs marked muscle atrophy is typically present. Other clinical signs in cats include generalized
muscle stiffness and decreased agility. Because of muscle stiffness, affected cats characteristi-
cally have to fall to one side in order to lie down. Dysphagia, vomiting, and regurgitation result
from tongue protrusion, megaesophagus, and diaphragmatic hypertrophy, which frequently lead
to fatal complications. Serum activity of CK is dramatically increased. Muscle biopsies reveal
myofiber degeneration, necrosis, and multifocal mineralization. Immunohistochemical staining
definitively diagnoses muscular dystrophy by demonstrating lack of the gene dystrophin in skele-
tal and cardiac muscle.
14. What other causes of feline myopathies may be diagnosed by muscle biopsy?
Nemaline myopathy has been described in a small number of cats and is characterized by
a generalized weakness that progresses to tremors, hypermetric gait, and muscle atrophy.
Muscle biopsy reveals marked fiber size variation with severe atrophy of type IIa fibers and
scant type I fibers. Nemaline rods, which arise from the Z bands of myofibers, are seen
throughout.
Myositis ossificaus has been reported in isolated dogs and cats in both localized and gener-
alized forms. Clinical signs include weakness, muscle pain and swelling, and firm, palpable en-
largements in affected muscles. Muscle biopsy demonstrates excessive connective tissue between
muscle fibers with inflammation that can progress to replacement of muscle by fibrous tissue and
heterotropic bone in severe cases.
A rare inherited myopathy has been reported in Devon Rex kittens between I and 6 months
of age. Neurologic examination is normal as well as CK activities. Muscle biopsy demonstrates
marked dystrophic changes, although the mechanism responsible is unknown at this time.
15. What are myotonic myopathies?
Myotonia is a condition in which active muscle contraction continues after voluntary effort
or stimulation has ceased. Congenital myotonia has been reported in several kittens. Typical clin-
ical signs include stiff, stilted gait that improves with activity and nonpainful hypertrophy of ap-
pendicular muscles. Myotonia is best diagnosed by EMG, which reveals classic myotonic
340
Muscle Diseases
discharges. Muscle biopsies demonstrate mild nonspecific changes but are helpful in ruling out
other causes of myopathies.
16. What are themuscular manifestations of feline aorticthromboembolismlischemic neu-
romyopathy?
Thrombolic occlusion of the caudal aorta secondary to underlying cardiomyopathy results in
acute motor dysfunction in the hindlimbs (see Chapter 17). Physical examination reveals weak-
to-absent femoral pulses, cool hindpaws, and hard, swollen, painful muscles. Concurrent multi-
systemic signs may result from embolization of renal, gastrointestinal, and pulmonary
vasculature. Histologically, affected muscles have areas of focal necrosis. marked architectural
change, and hypertrophic fibers. If vital organ systems are not affected, most cats show slow clin-
ical improvement over time with the reestablishment of collateral circulation.
17. Describe theclinical aspects of myasthenia gravis.
Myasthenia gravis is suspected in cats with progressive generalized weakness that is exac-
erbated by exercise. Additional clinical signs may include megaesophagus, dysphagia, and the
presence of a cranial mediastinal mass (thymoma). The disease can be either congenital or ac-
quired. The acquired form is an immune-mediated disease with antibodies directed at the acetyl-
choline receptors. Acquired immune-mediated myasthenia gravis is confirmed by
demonstration of increased serum acetylcholine receptor autoantibodies. The congenital form of
myasthenia gravis is rare in cats, and the diagnosis can be difficult, because affected cats do not
have receptor autoantibodies. The diagnosis is based on characteristic clinical signs, EMG. and
response to therapy. EMG demonstrates a decremental response of evoked action potentials
with repetitive nerve stimulation. Intravenous administration of edrophonium chloride tran-
siently improves clinical signs and EMG results. Edrophonium should be administered to cats
with caution because a potentially life-threatening cholinergic crisis may develop. This risk can
be minimized by pretreatment with atropine or immediate intravenous administration of at-
ropine if problems develop. Successful treatment of feline myasthenia gravis has been reported
with pyridostigmine bromide.
BIBLIOGRAPHY
1. Amann JF: Techniques of skeletal muscle biopsy. In Bojrab MJ (ed): Current Techniques in Small
Animal Surgery, 4th ed. Baltimore,Williams& Wilkins, 1998,pp 91-94.
2. Blot S: Disordersof skeletal muscles. In Ettinger SJ (ed): Textbookof Veterinary Internal Medicine,4th
ed. Philadelphia, W.B.Saunders, 1999,pp 684-690.
3. BraundKG: Skeletal musclebiopsy. SeminVetMed Surg4:108-115,1989.
4. CuddonP: Feline neuromuscular disease. In KirkRW(ed): Current Veterinary TherapyXI. Philadelphia,
W.B. Saunders, 1992,pp 1024-1030.
5. DowSW, LeCouteurRA, FeltmanMJ, et al: Potassiumdepletionin cats: Hypokalemiapolymyopathy. J
Am VetMedAssoc 191:1563-1567, 1987.
6. Ducote JM, DeweyCW, Coates JR, et al: Clinical forms of acquired myasthenia gravis in cats. Comp
Cont Educ Pract Yet21:440-447, 1999.
7. Hickford FH, Jones BR: Congenital myotonia in the cat. In Kirk RW(ed): Current Veterinary Therapy
XIII. Philadelphia, W.B.Saunders, 2000, pp 987-989.
8. Jones BR: Hypokalemic myopathy in cats. In Kirk RW (ed): Current Veterinary Therapy XIII.
9. KornegayIN: Lower motor neuron tetraparesis: neuromuscular disease. Probl Yet Med 3:378-390,
1991.
10. Shelton GD: Diseases of the muscle and the neuromuscular junction. In Sherding RG (ed): The Cat:
Diseases and Clinical Management, 2nd ed. NewYork, Churchill Livingstone, 1994. pp 1569-
1576.
II. TaylorSM: Selecteddisordersof muscleand the neuromuscular junction. VetClin NorthAmr 20:59-75.
2000.
67. UVEITIS
Tammy L. Miller, DYM., M.S., and Cynthia C. Powell, D.V.M., M.S.
1. What is uveitis?
Uveitis is any condition that involves inflammation of the uveal tract. It is one of the most
important ocular diseases in cats.
2. Describe the structure of the uvea.
The uvea constitutes the vascular portion of the eye and consists of three main components:
1. The iris forms the most anterior portion and is the boundary between anterior and poste-
rior chambers. Inflammation of the iris is termed iritis.
2. The ciliary body is the middle portion of the uvea that is responsible for formation of
aqueous humor and accommodation. Inflammation of the ciliary body is termed cyclitis.
Together the iris and ciliary body are considered the anterior uvea.
3. The choroid, located between the sclera and retina, supplies oxygen and nutrients to the
outer layer of the retina and the optic nerve. It is considered the posterior uvea. Inflammation of
the choroid is termed choroiditis. Inflammation of the choroid typically also affects the retina, in
which case it is termed chorioretinitis.
3. Define endophthalmitis and panophthalmitis.
Inflammation of the entire uveal tract is termed endophthalmitis. When endophthalmitis is
coupled with scleral and corneal inflammatory changes, it is termed panophthalmitis.
4. How is uveitis classified?
Location (anterior, posterior)
Duration (acute, chronic, recurrent)
Pathology (e.g., granulomatous, suppurative)
Cause (trauma, infection, neoplasia, immune-mediated)
5. What determines the clinical manifestations of uveitis?
The clinical appearance of uveitis depends on location, duration, and severity. Clinical signs
of uveitis in cats are generally subtle and divided into those that affect either the anterior (iris and
ciliary body) or posterior (choroid) segment.
6. Describe the clinical signs of anterior uveitis.
1. Photophobia, blepharospasm, enophthalmos, elevation of the third eyelid, and epiphora man-
ifest as ocular pain. Pain is common with acute uveitis but may be absent with mild or chronic cases.
2. Injection of conjunctival and episcleral vessels results in a "red eye."
3. Low intraocular pressure (lOP) occurs when aqueous humor formation is impaired by in-
flammation of the ciliary body. A difference> 5 mmHg between eyes is considered significant. If
uveitis is complicated by secondary glaucoma, lOP can be elevated or in the normal range if the
decrease in lOP caused by uveitis is counterbalanced by the impairment of aqueous humor out-
flow associated with secondary glaucoma.
3. Aqueous flare is cloudy aqueous humor that results from influx of cells and protein when
the blood-ocular barrier is disrupted as a result of uveal inflammation.
4. Corneal edema can result from effects of inflammation on the corneal endothelium and
ranges from perilimbal to generalized.
5. Keratic precipitates are inflammatory cells in the aqueous humor that are deposited on the
corneal endothelium. Normal convection currents of the aqueous humor cause the precipitates to
be located primarily on the ventral half of the cornea.
341
342 Uveitis
6. Miosis results from direct effects on the iris sphincter of inflammatory mediators such as
prostaglandins. Its absence does not rule out uveitis because mild miosis is difficult to detect.
7. Iritis is manifested by vasodilatation and increased vessel permeability that can produce a
subtle-to-pronounced change in iris color. The iris may appear swollen and have a thin coat of
fibrin and cells, giving it a velvety appearance. Rubeosis iridis is the proliferation of small ves-
sels on the iris surface.
8. Hyphema.
9. Hypopyon.
7. What clinical signs indicate chronic or previous inflammation in the anterior segment?
I. Posterior synechia are adhesions to the anterior lens capsule that may cause the pupil to
be irregularly shaped and impair its ability to respond to light or dilating agents.
2. Iris bombe forms when posterior synechia involve the entire pupil margin and prevent
aqueous humor from moving from the posterior chamber to the anterior chamber and exiting
through the filtration angle. The accumulation of aqueous humor behind the iris causes it to
billow forward and is associated with increasing lOP and glaucoma.
3. Peripheral anterior synechia are adhesions of the peripheral iris to the corneal endothe-
lium secondary to iris swelling or iris bombe,
4. Glaucoma.
8. Describe the clinical manifestations of posterior uveitis.
Clinical signs of posterior uveitis are often difficult to observe. Focal or diffuse hyporeflec-
tivity of the retina indicates active fluid accumulation. This inflammatory subretinal transuda-
tion or exudation may result in retinal hemorrhage and retinal detachment. Chronic
inflammation may result in loss of the normal tapetal color and loss of retinal pigment epithelial
cells and choroidal pigmentation. Posterior uveitis almost always extends to involve the retina.
Chronic chorioretinitis results in degeneration of the involved retina. Inactive chorioretinitis le-
sions appear hyperreflective.
9. What are the differential diagnoses of uveitis in cats?
Causes of uveitis in cats can be endogenous or exogenous and are listed in the tables below.
In contrast to dogs, systemic infectious disease is more commonly found to be the cause of
uveitis in cats. Appropriate treatment of uveitis, therefore, requires proper diagnosis, because the
uveitis may be the first indication of a serious or life-threatening illness. Clinical or serologic ev-
idence of systemic disease is detected in 25-90% of cats with uveitis.
Primary Endogenous Differential Diagnoses for Uveitis in Cats
Infectious
Bacterial
Bartonella henselae
Ehrlichia spp.
Mycobacterium spp.
Mycotic
Candida albicans
Parasitic
Cuterebra spp.
Metastrongylidae
Protozoal
Toxoplasma gondii
Infectious (continued)
Viral
Feline immunodeficiencyvirus (FlV)
Feline leukemia virus (FeLV)
Feline infectious peritonitis (FlP)
Neoplastic
Metastatic
Lymphosarcoma
Others
Primary
Ciliary body adenoma
Ciliary body adenocarcinoma
Diffuse iris melanoma
Immune-mediated
Lens-induced
Idiopathic
Uveitis
Primary Exogenous Differential Diagnoses for Uveitis in Cats
343
Trauma
Secondary bacterial infection
Sterile inflammation
Ocular surgery
Secondarybacterial infection
Sterile inflammation
Keratitis
Ulcer
Infection
Drug or toxin
Pilocarpine
Latanoprost
10. How do you determine the cause of uveitis in cats?
A good history, physical examination, and a minimal database of complete blood chemistry,
serum biochemical profile, and urinalysis are essential. Thoracic and abdominal radiographs as
well as abdominal ultrasonography may be indicated if a neoplastic or infectious process is sus-
pected. Outdoor cats should be routinely tested for Toxoplasma gondii, feline leukemia virus
(FeLV) and feline immunodeficiency virus (FIV). Cats raised in a cattery or < 2 years of age
should be routinely screened for coronaviruses. Ocular fluids can be used for cytology, culture
and sensitivity, polymerase chain reaction (PCR), and determination of antibody content.
11. What are the four most common causes of systemic endogenous uveitis in cats?
I. T. gondii
2. Feline infectious peritonitis (FIP)
3. FlV
4. Lymphoma with or without serologic evidence of FeLV
12. What are the ocular signs of T. gondii infection?
Ocular toxoplasmosis can result in anterior or posterior uveitis and may be unilateral or bi-
lateral.
13. Do all field strains of T. gondii induce ophthalmic disease?
The disease-inducing potential of T. gondii probably varies, because relatively few of the
many seropositive cats have ophthalmic disease. The actual prevalence of ocular toxoplasmosis
in naturally exposed cats is unknown because it is difficult to confirm the diagnosis. Recent work
suggests that ocular toxoplasmosis may occur in kittens infected transplacentally or in the post-
natal period.
14. How do you diagnose ocular toxoplasmosis?
Serologic evaluation for T. gondii infection should include assays that detect IgG and IgM.
T. gondii-specific IgM is detected for days to weeks in subclinically infected cats but may be of
high magnitude in cats with clinical toxoplasmosis. Serum IgG antibodies develop approximately
2 weeks after infection and remain elevated in cats for years after exposure. A 4-fold increase in
IgG titer over 2-3 weeks or an IgM titer> I :256 indicates recent or active infection. Cats with
ocular toxoplasmosis may be seropositive for IgM and seronegative for IgG, particularly if they
are FIV-seropositive. Detection of local antibody production or T. gondii DNA in aqueous humor
may aid in the diagnosis of ocular toxoplasmosis (Veterinary Diagnostic Laboratory, College of
Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins. CO).
15. What are the ocular signs of FIP?
Bilateral granulomatous anterior uveitis may be present. Clinical findings range from iritis,
large keratic precipitates, clots of fibrin and blood in the anterior chamber, pyogranulomatous
cuffing of the retinal vasculature, and chorioretinitis to retinal hemorrhage and retinal detachment.
16. Are ocular lesions most often seen with the effusive or noneffusive form of FIP?
Ocular lesions are most often seen with the noneffusive, or dry form of FIP.
344
Uveitis
17. How do you diagnose FIP?
Diagnosis of FIP-associated ocular disease is difficult because of the nonspecific nature of
available coronavirus serum antibody tests. Positive coronavirus serum antibodies document only
exposure to coronavirus and do not correlate with FlP. In addition, results of blood reverse tran-
scriptase polymerase chain reaction (RT-PCR) do not correlate with FIP. Characteristic ocular le-
sions in the presence of rising serum antibody titers suggest the diagnosis particularly, if the
appropriate signalment and history are also present (see Chapter 38). If effusions are present,
characteristic findings aid in the diagnosis of FIP (see Chapter 38).
18. What are the ocular signs of FIV?
Anterior uveitis and pars planitis are the most common ocular findings in cats with FlY. The
uveitis is typically chronic and mild. A higher incidence of glaucoma has been associated with or
without uveitis in FlY-positive cats.
19. Inwhat two ways can FIV produce uveitis?
Directly: through the local production of FIV antibodies and antigens.
Indirectly: immunodeficiency associated with FIV can result in opportunistic infections
such as T. gondii and C. neoformans.
20. How is ocular disease due to FIV diagnosed?
It is difficult to prove that ocular inflammation is due to FlY. Presence of serum antibodies
against FlY usually correlates with current infection but cannot be used to prove illness due to in-
fection. Currently, the only way to document FlV-associated uveitis is to exclude all other known
causes in a seropositive cat.
21. Can feline herpesvirus 1 (FHVl) cause intraocular disease?
FHV-l DNA and local FHV-l antibody production were detected in the aqueous humor of
cats with suspected idiopathic uveitis. These results show that FHV-l can enter the eyes of cats
and, in addition to keratoconjunctivitis, may be associated with uveitis. Serum antibody detection
is of no benefit in the diagnosis of FHV-l uveitis because most cats are vaccinated or previously
exposed to FHV-I. Aqueous humor can be tested for FHV-l by PCR commercially (Veterinary
Diagnostic Laboratory, College of Veterinary Medicine and Biomedical Sciences, Colorado State
University, Fort Collins, CO).
22. Is Bartonella henselae associated with uveitis in cats?
Cats are the apparent reservoir host for B. henselae. Although clinical disease is rare, 55-
81% of cats are seropositive. B. henselae is one of the causes of cat-scratch disease in humans,
and uveal tract inflammation has been reported in association with infection. Bartonella spp. was
suggested as a likely cause of anterior uveitis in one cat based on the presence of antibody pro-
duction in aqueous humor and response to doxycycline. Bartonella spp., therefore, may be able
to invade the eyes of cats and result in uveitis.
23. How does FeLV cause ocular disease?
FeLV has not been shown to cause primary ocular disease. Ocular disease associated with
FeLV is manifested in two ways:
Metastatic lymphosarcoma of the anterior uvea and neurologic tissue
Opportunistic infections secondary to immunosuppression
24. How is FeLV-associated ocular disease diagnosed?
The clinical presentation of neoplastic infiltration of the uveal tract and resultant uveitis may
vary widely. Nodular or diffuse infiltration of the posterior or anterior uveal tract is possible.
Although isolated ocular lymphosarcoma is rare, many cats present primarily for ocular signs. A
search for neoplastic involvement of other organs should be made. Cats with lymphosarcoma
should be staged (I-V) and FeLVstatus should be determined because both are related to treatment
Uveitis 345
response and prognosis (see Chapter 68). Ocular involvement is by definition stage V lymphosar-
coma. Aqueous humor cytology may be diagnostic in cases in which obvious lymphosarcoma cannot
be identified in other organs. Testing for FeLV is always indicated in cats with uveitis whether or
not lymphosarcoma is suspected, because opportunistic infection may be present. The enzyme-
linked immunosorbent assay (ELISA) for detection of the p27 antigen in the blood (serum) is a
useful screening tool for FeLV, but a positive immunofluorescent assay (lFA) correlates better
with persistent viremia (see Chapter 76). A positive FeLV test does not prove ocular disease due to
the virus, nor does a negative test rule out lymphosarcoma. Most FeLV-positive cats do not have
lymphosarcoma, and 20-70% of cats with confirmed lymphosarcoma are FeLV-negative.
25. What is idiopathic uveitis? How is it diagnosed?
Idiopathic uveitis is any uveitis in which a cause cannot be identified. Unfortunately, a cause
is not identified in 10-70% of cats with uveitis. The lymphocytic-plasmocytic infiltration of the
anterior uvea found on histopathology in eyes lacking an etiologic diagnosis suggests that it may
be immune-mediated. Whether this immune-mediated reaction is a true autoimmune disease or
triggered by other antigenic stimulation remains to be determined in cats.
26. What are the goals of treating uveitis in cats?
Nonspecific
1. Stop or decrease the inflammation.
2. Prevent or control the complications caused by inflammation.
3. Relieve pain
Specific
1. Address etiologic agents (e.g., virus, bacteria, fungi).
2. Address specific causes of inflammation (e.g., foreign body, corneal ulcer, luxated lens).
27. How should you treat uveitis in cats?
Specific therapies for treating infectious agents are addressed in other chapters. In general,
clindamycin hydrochloride is used for toxoplasmosis (see Chapter 11), doxycycline is used for B.
henselae (see Chapter 85) and feline ehrlichiosis (see Chapter 78), and itraconazole or fluconazole
is used for C. neoformans (see Chapter 4). Nonspecific therapies are listed in the table below.
Drugs Commonly Used to Treat Uveitis in Cats
Glucocorticoids
Topical (every 1-12 hr)
Dexamethasone sodium phosphate 0.1% (solution), 0.5% (ointment)
Prednisolone acetate I % (suspension)
Oral (0.5-2.2 mg/kg every 12-24 hr)
Prednisolone (5-mg tablet)
Prednisone (5- or 20-mg tablet)
Subconjunctival agents
Betamethasone (0.75 mg/eye)
Methylprednisolone acetate (4 mg/eye)
Triamcinolone (4 mg/eye)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Topical (every 6-12 hr)
Diclofenac 0.1% (solution)
F1urbiprofen0.03% (solution)
Ketorolac 0.5% (solution)
Suprofen 1% (solution)
Oral
Acetylsalisylic acid (80-mg tablet every 48-72 h)r
Ketoprofen (12.5 mg tablet; 2mglkg initially; lrng/kg/day maintenance)
346 Uveitis
Drugs Commonly Used to Treat Uveitis in Cats (Continued)
Mydriatic/cycloplegic (parasympatholytic) agents
Topical
Atropine sulfate (0.5% and I% solution and ointment every 8-24 hr)
Tropicamide (0.5% and 1% [solution] every 6--12hr)
Lens luxation
Retinal degeneration
Retinal detachment
28. What is the main difference in treatment of anterior and posterior uveitis?
Systemic therapy is the treatment of choice for posterior uveitis. Systemic glucocorticoid
administration must be used with caution if an infectious process is suspected.
Topical therapy is the treatment of choice for anterior uveitis. If inflammation is not well
controlled, addition of subconjunctival or systemic medication may be necessary.
29. For what two reasons are topical and subconjunctival glucocorticoids contraindicated
in the treatment of uveitis in the presence of corneal ulceration?
I. Inhibition of wound healing
2. Augmentation of collagenase activity in the cornea
30. When should you use subconjunctival glucocorticoids?
This form of treatment should be used only in cases of severe intraocular inflammation as an
adjunct to topical or systemic steroids or in cases in which frequent topical therapy is not possi-
ble. A serious disadvantage to this method is inability to withdraw the medication if complica-
tions arise.
31. When should topical and systemic NSAIDs be used in cats?
There is little information about their use in cats. NSAIDs should be considered only when
glucocorticoids are contraindicated. Topical NSAIDs may complicate bacterial corneal infections
and are not recommended. Systemic NSAIDs should be used with caution in cats because they
have been associated with potentially severe side effects, such as vomiting, diarrhea, gastroin-
testinal ulceration and hemorrhage, and bone marrow suppression.
32. How do you relieve the ocular pain associated with uveitis?
Mydriatics/cycloplegics relieve pain by relaxation of ciliary body and iris spasm. The dura-
tion and frequency of use depend on the severity of the inflammation.
33. What are the potential sight-threatening complications of failure to control intraocular
inflammation?
Posterior synechiae
Glaucoma
Cataracts
BIBLIOGRAPHY
I. Brightman AH, OgilvieGK, Tompkins M: Oculardiseasein FeLV-positive cats: 11cases (1981-1986).J
AmVetMedAssoc 198:1049-1051. 1991.
2. ChavkinMJ. LappinMR. Powell CC. et al: Seroepidemiologic and clinical observations of93 cases of
uveitisin cats. ProgVetCompOphthaJmoI2:29-36. 1992.
3. Chavkin MJ. LappinMR. PowellCC. et al: Toxoplasma gondii-specific antibodies in the aqueoushumor
of cats withtoxoplasmosis. AmJ VetRes 55:1244-1249, 1994.
4. DavidsonMG. Nasisse MP. EnglishRV. et aJ: Feline anterior uveitis: A study of 53 cases. J AmAnim
HospAssoc27:77-83. 1991.
5. English RV. DavidsonMG. Nasisse MP.et al: Intraocular disease associatedwith feline immunodefi-
ciencyvirusinfection in cats. J AmVetMedAssoc 196:1116--1119, 1990.
6. LappinMR: Opportunistic infectionsassociatedwith rettoviral infectionsin cats. SeminVet Med Surg
(SmaJl Anim) 104:244-250, 1995.
Uveitis 347
7. Lappin MR, Black lC: Bartonella spp. infection as a possible cause of uveitis in a cat. 1 Am Vet Med
Assoc 214:1205-1207,1999.
8. Lappin MR, Kordick DL, Breitschwerdt EB: Bartonella spp, antibodies and DNA in aqueous humor of
cats. 1 Fel Med Surg 2:61--{j8, 2000.
9. Lappin MR, Marks A, Greene CE, et a1: Serologic prevalence of selected infectious diseases in cats with
uveitis. 1Am Vet Med Assoc 201:1005-1009,1992.
10. Maggs OJ, Lappin MR, Reif IS, et al: Evaluation of feline herpes-specific antibodies and DNA in aque-
ous humor from cats with or without uveitis. Am 1 Vet Res 60:932-936, 1999.
II. Martin CL, Stiles 1: Ocular infections. In Greene CE (ed): Infectious Diseases of the Dog and Cat, 2nd
12. Peiffer RL Jr, Wilcock BP: Histopathologic study of uveitis in cats: 139 cases (1978-1988). 1 Am Vet
MedAssoc 198:135-138,1991.
13. Powell CC, Lappin MR: Uveitis in cats. Part I: Definitions and causes. Comp Cont Educ Pract Vet [in
press].
14. Powell CC, Lappin MR: Uveitis in cats. Part 2: Diagnostic and treatment plans. Comp Cont Educ Pract
Vet [in press].
15. Stiles 1: The cat. In Gelatt KN (ed): Veterinary Ophthalmology. Philadelphia, Lippincott Williams &
Wilkins, 1999, pp 1448-1473.
VII. Hemolymphatic Problems
Section Editor: Christine S. Olver, D.v.M., ph.D.
68. LYMPHADENOPATHYAND LYMPHOMA
Elizabeth A. McNiel, D.V.M., M.S., Ph.D.
1. How is lymphadenopathy recognized?
On physical examination, determination oflymphadenopathy may be quite subjective. "Normal"
lymph node size varies among individuals and as a function of lymph node location, age of the
animal, body condition, and conformation. Variation in lymph node size can even be based on en-
vironmental factors such as geographical location. Although pronounced lymphadenopathy is
usually obvious to both the pet owner and the veterinarian, mild lymph node enlargement may be
difficult to appreciate and may go unrecognized. The potential difficulty in identifying this prob-
lem underscores the importance of a thorough physical examination, including palpation of pe-
ripherallymph nodes and regular reassessment of lymph nodes. As a disease progresses, the
lymphadenopathy may become more evident.
2. What causes lymphadenopathy in cats?
The primary differential diagnoses for generalized lymphadenopathy in cats are infectious
diseases; immune-mediated, inflammatory. and neoplastic diseases are less common. The reverse
may well be true for dogs, depending on geographical location. Generalized lymphadenopathy in
dogs is commonly caused by multicentric lymphoma. In cats, multicentric lymphoma is diag-
nosed relatively infrequently.
Causes ofLymphadenopathy in Cats
Infections
Bacterial
Bartonella henselae
Mycobacterium spp
Yersinia pestis
Norcardia spp.
Actinomyces spp.
Ehrlichia spp.
Viral
Feline leukemia virus (FeLV)
Panleukopenia
Parasitic
Toxoplasma gondii
Fungal
Inflammatory/immune-mediated disorders
Hypereosinophilic syndrome (cause is unknown
but may be a neoplastic process)
Polyarthritis
Polymyositis
Neoplastic processes
Lymphoma
Leukemia
Metastatic neoplasia
Benign lymphadenopathy
Benign hyperplasia resembling Iymphoma-
with or without FeLVinfection
Plexiform vascularization
349
350 Lymphadenopathy and Lymphoma
3. How should lymphadenopathy be approached diagnostically?
If lymphadenopathy is clearly secondary to some other process, specific diagnostic tests may
be unnecessary. Unexplained lymphadenopathy should be approached systematically, regardless
of species and underlying etiology (see algorithm below).
In cases of chronic lymphadenopathy without obvious cause, advanced diagnostics should
be considered. Flow cytometry is now available at a number of veterinary institutions for evalua-
tion of peripheral blood, bone marrow, and single cell suspensions of lymphoid tissue to detect
cell surface antigens and measure relative DNA content. Flow cytometric detection of cell sur-
face antigens is helpful in differentiating a homogenous, clonal population of lymphoid cells
consistent with lymphoid neoplasia from a mixed population consistent with an immunologic
process. Altered DNA content also can be evaluated when neoplasia is suspected, as many tumors
are not diploid.
Recently, polymerase chain reaction (PCR) of lymphoid tissue, blood, or bone marrow, de-
tecting clonal expansions of lymphoid cells with unique antigen receptor gene rearrangements,
has been added to the armamentarium of diagnostic tests for lymphoma in dogs. The test is
under evaluation for use in cats. PCR is used to detect a clonal population of lymphocytes in
blood or tissue sample and also the immunophenotype (B or T cell) of that population. This in-
formation provides support for a diagnosis of lymphoma and potentially provides prognostic in-
sight. PCR may be useful for cases of unexplained lymphadenopathy, lymphocytosis, and
hypercalcemia. For information on the status of PCR, contact the Colorado State University
Diagnostic Laboratory at (970) 491-1281.
In an apparentlyhealthy
animal, reassess thelymph
nodesat a laterdate.
(Note:Doingnothingis
not an option!)
Isthere evidenceof
diseaseinthearea
drained by the lymph
node?
~ I NotSure????
-------'
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systemicdiaease: L---..
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profile,FeLVondFIV
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Diagnostic( eg,
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infectiousagent)
2. Considerlymphnode
biospyfor unexplained, L......
pronounced,cbronic ,......
lymphadenopathy.
In the sickanimal,
identifyotherprohlems
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Treat according
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&genlS.
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cytometty or Polymerase
chain reactionto examine
clonalityof poIJU1ation.
(see text for availabilityof
PCR.)
Diagnostic approachto lymphadenopathy in cats.
Lymphadenopathy and Lymphoma 351
4. Describe the clinical presentation of feline lymphoma.
Cats with lymphoma are usually "sick." The clinical signs depend on the organ system af-
fected. For example, spinal lymphoma may be associated with hind limb paralysis, alimentary
lymphoma is often characterized by vomiting, and nasal lymphoma results in signs of upper res-
piratory disease. Generalized lymphadenopathy is a relatively uncommon presentation for cats
with lymphoma and, like mediastinal lymphoma, may become increasingly infrequent. The
changing prevalence of FeLV antigenemia in cats with lymphoma may account for this decrease.
Cats with multicentric and mediastinal lymphoma are frequently FeLV-positive. Over the past 15
years, the number of cats with lymphoma that test positive for FeLV has decreased from about
70% to 20-30%. The change in FeLVprevalence accompanies a shift in the anatomic site of lym-
phomas (alimentary lymphoma seems to be most common) and in the age of cats affected (cats
with lymphoma that are FeLV-negative are older than cats that are FeLV-positive).
5. What laboratory abnormalities are associated with lymphoma?
Laboratory findings are usually nonspecific. Anemia is common and may result from any
combination of chronic illness, bone barrow infiltration by neoplastic cells, or immune-mediated
or infectious disease (e.g., FeLV). Lymphocytosis is probable with lymphoid leukemia.
Hypercalcemia of malignancy has been reported but is much less common than in dogs.
Azotemia may result from hypercalcemia or nephric lymphoma. Hyperglobulinemia occurs in
some cats and may be polyclonal or monoclonal.
6. Howis lymphoma diagnosed?
Histologic evaluation of tissue is the most definitive diagnostic technique for lymphoma,
particularly with the use of immunohistochemical stains for B- and T-cell surface markers.
Cytology also may be diagnostic. A diagnosis of lymphoma based on lymph node cytology
should be viewed cautiously, however, because benign lymphoid hyperplasia has been described
in cats. Cytology in such cases may be difficult to distinguish from lymphoma. If other lymph
nodes are enlarged, mandibular lymph nodes should be avoided when samples are collected for
cytologic evaluation because hyperplasia is particularly common at this site. As mentioned for
the work-up of lymphadenopathy, flow cytometry and PCR can be valuable diagnostic tools.
7. Why do cats get lymphoma?
FeLV is known to cause lymphoma in cats (see Chapter 76). The prevalence of FeLV-posi-
tive lymphomas appears to have declined in recent years. It is not known whether this decrease is
a result of management changes, such as testing and vaccination, or a change in the typical virus.
Feline immunodeficiency virus may indirectly result in lymphoma (see Chapter 77). Many lym-
phomas do not have an obvious retroviral etiology; their cause is unknown. Because cancer is a
genetic disease, it is assumed that induced and inherited mutations in cancer-associated genes
playa role in lymphoma development in cats.
8. What treatments are available for cats with lymphoma?
Chemotherapy and radiation therapy are the most effective modalities for treating lymphoma
in any species. Chemotherapy is indicated in most cases because of the disseminated, systemic
nature of many feline lymphomas and may be used as the sole treatment modality for alimentary,
renal, and multicentric disease. Prednisone used as a single agent results in a short remission and
improvement in clinical signs in about one-half of treated cats. Multiagent chemotherapy regi-
mens are the mainstay of therapy. The addition of doxorubicin to the standard combination ther-
apy with cyclophosphamide, vincristine, and prednisone appears to improve prognosis.
Unfortunately, few prospective studies compare various chemotherapeutic combinations for effi-
cacy and toxicity in cats with a single type of lymphoma. The available information is insuffi-
cient to select the "optimal" protocol for all situations (see table on following page).
Appealing attributes of radiation therapy in the treatment of lymphoma include the exquisite
sensitivity of lymphoid cells to radiation and the ability to localize the dose. Radiation therapy
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354
Lymphadenopathy and Lymphoma
should be considered for localized lymphomas, drug-resistant lymphomas, and cases in which a
primary mass results in severe dysfunction. Excellent results are reported for irradiation of cats
with nasal lymphoma. As radiation therapy becomes increasingly available to veterinarians, its
role in the treatment of lymphoma is likely to expand.
9. How much toxicity is expected with treatment?
Quality of life is a primary concern in the treatment of any veterinary problem, including
cancer. The most commonly used chemotherapeutic protocols are designed to cause minimal tox-
icity. Gastrointestinal (GI) toxicity (anorexia, vomiting, and diarrhea) is the most common side
effect, but it is dose-dependent and usually self-limiting. It is possible to achieve acceptable
levels of GI toxicity in most cases through the use of supportive measures and individually de-
signed dose and administration schedules. Bone marrow suppression and most drug-specific tox-
icities are uncommon in cats. Cats on long-term chemotherapy lose their whiskers!
Toxicity due to radiation is classified as acute (concurrent with or shortly after treatment) or
late (> 6 months after treatment). Late effects are extremely unlikely in the treatment of lym-
phoma with standard-dose protocols. Acute effects depend on the site. In nasal irradiation, mu-
cositis of the nasal and oral cavity is probable. For superficial treatments, there is the possibility
of moist or dry skin desquamation. These effects can be minimized with appropriate treatment
planning and are of limited duration (a few weeks).
10. What is the prognosis for feline lymphoma?
Without treatment, cats with lymphoma do not live very long (see questions I I and 12), par-
ticularly because most cats are sick at the time of diagnosis. For treated cats, the prognosis is
quite variable and usually unpredictable in individual patients. Site, clinical stage, and FeLV
status have an effect on outcome.
11. How does FeLV status influence outcome?
Cats that are FeLV-positive may respond well to chemotherapy initially but have median sur-
vival periods of just a few months. Mediastinal and multicentric lymphoma is commonly associ-
ated with FeLV infection.
12. How do anatomic site and clinical stage affect outcome?
The table below provides the staging scheme recommended by the World Health Organization
for feline lymphoma. For the various anatomic sites and clinical stages, the response of individual
cats may vary a lot. Overall, 50-70% of cats treated for lymphoma achieve complete remission
with median remission times of 2--4 months and median survival times of about 4-6 months. Cats
surviving for years after treatment are frequently reported, particularly with solitary nasal lym-
phoma (and perhaps other stage I lymphomas) and with some alimentary lymphomas. Cats that
achieve complete remission initially respond better than those cats that do not. The heterogeneity
in the response of feline lymphomas probably reflects diversity in the disease. Subclassifications
based on immunologic markers, genetic mutations, and chromosome rearrangements may be of
considerable value as prognostic factors. Research in these areas is ongoing.
Clinical Stages of Feline Lymphoma
Stage I
Stage II
Stage III
Stage IV
Stage V
Substage A
Substage B
Single node or solitary extranodal site, including mediastinum
Regional lymph node involvement; resectable gastrointestinal mass
Generalized lymph node involvement; unresectable abdominal disease; epidural tumor
Stages I-III with liver or spleen involvement
Stages I-IV with bone marrow involvement
No systemic signs
Systemic signs
Neutrophilia and Neutropenia
BIBLIOGRAPHY
355
1. Elmslie RE, Ogilvie GK, Gillette EL, et al: Radiotherapy with and without chemotherapy for localized
lymphoma in 10 cats. Vet RadioI32:277-280, 1991.
2. Jeglum KA, Whereat A, Young K: Chemotherapy of lymphoma in 75 cats. J Am Vet Med Assoc
190:174-178, 1987.
3. Meleo KA: The role of radiotherapy in the treatment of lymphoma and thymoma. Vet Clin North Am
Small Anim Pract 27:115-129,1997.
4. Mooney SC, Hayes AA, MacEwen EG, et al: Treatment and prognostic factors in lymphoma in cats: 103
cases (1977-1981). J AmVet MedAssoc 194:696-702, 1989.
5. Moore AS, Cotter SM, Frimberger AE, et al: A comparison of doxorubicin and COP for maintenance of
remission in cats with lymphoma. J Vet Intern Med 10:372-375, 1996.
6. Moore AS, Ruslander D, Cotter SM, et al: Efficacy of, and toxicoses associated with, oral idarubicin ad-
ministration in cats with neoplasia. J AmVet Med Assoc 206: 155D--1554, 1995.
7. Moore FM, Emerson WE, Cotter SM, et al: Distinctive peripheral lymph node hyperplasia of young cats.
Vet PathoI23:386-391, 1986.
8. Rassnick KM, Mauldin GN, Moroff SD, et al: Prognostic value of argyrophilic nucleolar organizer
region (AgNOR) staining in feline intestinal lymphoma. J Vet Intern Med 13:187-190, 1999.
9. Vail DM, Moore AS, Ogilvie GK, et al: Feline lymphoma (145 cases): Proliferation indices, cluster of dif-
ferentiation 3 immunoreactivity, and their association with prognosis in 90 cats. J Vet Intern Med 12:
349-354, 1998.
10. Zwahlen CH, Lucroy MD, Kraegel SA, et al: Results of chemotherapy for cats with alimentary malig-
nant lymphoma: 21 cases (1993-1997) [see comments]. J Am Vet Med Assoc 213:1144-1149.
1998.
69. NEUTROPHILIA AND NEUTROPENIA
Armando R. [rizarry-Rovira, D.v.M.
1. Define neutrophilia and neutropenia.
Neutrophilia is an absolute increase in the number of neutrophils circulating in the periph-
eral blood (circulating neutrophil pool). Neutropenia is an absolute decrease in the number of
neutrophils circulating in the peripheral blood. The number of circulating neutrophils, as mea-
sured in a complete blood count (CRC), is a one-time snapshot, the result of the balance among
production, distribution, utilization, and destruction of neutrophils.
2. What causes neutrophilia?
In general, neutrophilia can be caused by four main conditions, acting singly or in combi-
nation:
I. Epinephrine release/administration. Epinephrine is released during excitement, fear,
and/or exercise. The leukogram changes associated with epinephrine are also referred to as phys-
iologic leukocytosis.
2. Corticosteroid release/administration. Endogenous corticosteroids are released during
injury, pain, prolonged emotional stress, abnormal body temperature, and hyperadrenocorticism.
The leukogram picture of neutrophilia and accompanying lymphopenia associated with corticos-
teroids is commonly referred to as stress leukogram. Epinephrine- and corticosteroid-mediated
neutrophilias are commonly seen in veterinary patients.
3. Inflammation. This important cause of neutrophilia is elicited by both infectious and non-
infectious causes.
4. Myeloproliferative disease (MPD). Although rarely seen, feline patients with acute myel-
ogenous leukemia with differentiation (AML-M2) and chronic myelogenous leukemia (CML)
may present with neutrophilia.
356 Neutrophilia and Neutropenia
Primary Differential Diagnoses for Neutrophilia in Cats
Epinephrine release/administration
Fear
Excitement
Exercise
Corticosteroid release/administration
Trauma or injury
Pain
Prolonged emotional stress
Abnormal body temperature
Exogenous administration (length of effect depends on short- vs. long-acting formulation)
Metabolic imbalance (diabetic ketoacidosis, hyperthyroidism, ethylene glycol toxicosis)
Inflammation
Infectious
Bacterial infections (various)
Systemic fungal infections
Viral infections (feline infectious peritonitis virus, feline herpesvirus I)
Rickettsial infections (Haemobartonellajelis, ehrlichiosis)
Immune-mediated
Autoimmune hemolytic anem.ia
Immune-mediated arthritis
Necrosis
Infarctions, gangrene
Tumor necrosis
Trauma
Surgery
Gunshots
Other trauma
Foreign bodies (intestinal, oropharyngeal, m.igrating grass awns, iatrogenic)
Neoplasms
Myeloproliferative disease
Lymphosarcoma
Adenocarcinoma
Tumor necrosis
Neoplasms in general may cause inflammation, pain, and "stress" (neutrophilia is common in small
animals with neoplastic diseases)
Paraneoplastic syndrome (production of cytokines by neoplastic cells)
3. By what mechanisms do the causes listed above lead to neutrophilia?
Neutrophilia is elicited by three general mechanisms, acting singly or in combination with
each other: (I) neutrophil redistribution, (2) increased bone marrow production, and (3) de-
creased egress from the peripheral blood to the tissues.
4. Explain the mechanism of neutrophil redistribution.
Neutrophils may be redistributed from the marginal neutrophil pool (MNP) to the circulating
neutrophil pool (CNP). The MNP is not sampled during routine blood collection; it consists of
neutrophils that are found rolling along arteriolar and venular endothelial surfaces or have tran-
siently ceased moving within capillaries. Redistribution of neutrophils from the MNP to CNP
can be caused by corticosteroids (endogenous or exogenous) and/or epinephrine (endogenous or
exogenous). Generally, in cats the MNP-to-CNP ratio is 3: I; therefore, dramatic increases in cir-
culating neutrophils may result from redistribution into the CNP. Neutrophils also may be redis-
tributed from the bone marrow mature neutrophil storage pool to the total blood neutrophil pool
by corticosteroids and inflammation.
357
S. When does bone marrow increase production of neutrophil precursors?
Increased bone marrow production of neutrophil precursors occurs when there is demand for
neutrophils in the peripheral tissues. Trauma, infections, immune-mediated cell injury, and cer-
tain neoplasms cause neutrophilia by eliciting the release of chemical mediators (cytokines,
growth factors) that stimulate neutrophil precursors to proliferate and differentiate. Certain
tumors (carcinomas) may be the direct source of these chemical mediators. Increased neutrophil
production also occurs in certain rare types of MPD (e.g. AML-M2, CML). In 80% of human
cases of CML, a reciprocal translocation between chromosomes 9 and 22 in the leukemic cells
results in the formation of the Philadelphia chromosome. The protein product of this oncogene
has tyrosine kinase activity that results in the marked proliferation of granulocytic precursors.
Although chromosomal abnormalities are seen in feline leukemia virus (Fel.Vj-positive cats in
general and FeLV-positive cats with leukemia, characteristic chromosomal abnormalities specifi-
cally associated with the development of MPD in cats are not documented.
6. What causes decreased egress of nentrophils from peripheral blood into tissues?
Decreased egress of neutrophils from peripheral blood into tissues occurs in combination with
the other mechanisms mentioned above but is due primarily to the effects of corticosteroids.
Although not currently recognized in cats, neutrophilia also may result from congenital defects in
leukocyte adhesion, such as leukocyte adhesion molecule ( ~ 2 integrin) deficiency in dogs and cattle.
7. Howcan the signalment help in ranking the differential list for neutrophilia?
Neutrophilia due to endogenous epinephrine release (physiologic leukocytosis) is frequently
seen in young cats; however, it may be seen in cats of any age. Neutrophilia due to endogenous
corticosteroid release or inflammatory diseases may be seen in cats of any age. Neutrophilia due
to MPD is seen in FeLV-infected cats. Cats with MPD are generally younger ( 5.5 years old).
8. How can the history help in ranking the differential list?
Neutrophilia due to endogenous epinephrine release (physiologic leukocytosis) is frequently
seen in healthy cats that are excited or frightened during the visit to the veterinarian. It is also
seen in cats that vigorously struggle during restraint or blood collection. Neutrophilia due to en-
dogenous corticosteroid release is seen in cats affected by stressful conditions such as severe,
painful injuries or, less commonly, diseases that cause endogenous corticosteroid release, such as
primary or secondary hyperadrenocorticism (polyuria/polydipsia associated with diabetes melli-
tus, poor haircoat, skin infections, skin bruising). Patients with neutrophilia due to inflammatory
diseases present with a variety of clinical histories. For example, the patient may have a history
of lethargy, anorexia, being hit by a car (trauma), recent surgery (sterile foreign body. dehis-
cence), or diabetes (diabetic ketoacidosis). Inflammation in diabetic ketoacidotic patients may
develop from the combined effects of immunosuppression and hyperglycemia (which predispose
to bacterial infections) or in association with pancreatitis. Patients affected with MPD may have a
history supportive of FeLV (multiple cat household, outdoor cat, previous positive FeLV test).
hemorrhages (thrombocytopenia, coagulation factor deficiency due to liver involvement).
lethargy, anorexia, or masses (lymphadenomegaly).
9. Howcan the physical examination help in ranking the differential list?
Neutrophilia due to endogenous epinephrine release in healthy cats may be characterized by
increases in heart and respiratory rate, blood pressure, and muscular activity. Neutrophilia due to
endogenous corticosteroid release in cats with primary or secondary hyperadrenocorticism may
be associated with potbelly appearance, rough hair coat, and thin fragile skin. Patients with neu-
trophilia due to inflammatory diseases may present with a multitude of physical examination ab-
normalities. including fever, depression, elevated heart and respiratory rates. distended and/or
painful abdomen (pyometra, peritonitis, hemoabdomen, surgical dehiscence, foreign bodies).
dyspnea (pyothorax. pneumonia), nasal discharge (feline viral rhinotracheitis, foreign bodies.
neoplasia). space-occupying masses (neoplasia, abscesses), pale mucus membranes (anemia due
358
to H. felis), and splenomegaly and/or hepatomegaly (neoplasia, diffuse fungal or bacterial infec-
tion). Cats affected with MPD may present with organomegaly, elevated heart and respiratory
rates, fever, hemorrhages, pallor, icterus, and lymphadenopathy.
10. What are the typical eBe findings in cats with epinephrine-induced neutrophilia?
Epinephrine-induced neutrophilia is mild-to-moderate (12,500-25,000 cells/ul) and transient
(usually 20-30 minutes in duration). It may be accompanied by lymphocytosis or a normallym-
phocyte count. An elevated packed cell volume (PCV) may be seen due to splenic contraction sec-
ondary to the effects of epinephrine. A second blood sample collected a few hours later when the
cat is calmer helps to confirm the diagnosis (i.e., the leukogram will be within reference ranges).
11. Describe the typical eBe findings in cats with corticosteroid-induced neutrophilia.
Corticosteroid-induced neutrophilia is mild-to-moderate (12,500-25,000 cells/ul), not asso-
ciated with a left shift, and frequently accompanied by lymphopenia and eosinopenia. Mono-
cytosis secondary to corticosteroids is an inconsistent finding in cats. Corticosteroid-induced
leukogram changes, specifically lymphopenia, also may be seen with inflammatory disease.
12. What are the typical eBe rmdingsin cats with neutrophilia of mild inflammatory disease?
Neutrophilia may be the only leukocyte abnormality associated with mild inflammatory
changes. Neutrophil counts of 12,500-25,000 cells/ul with no other significant leukogram
change may be difficult to differentiate from neutrophil counts seen with corticosteroids and epi-
nephrine. Although not specifically studied in cats, fibrinogen levels may increase with inflam-
mation and help to differentiate neutrophilia of inflammation from neutrophilia induced by
epinephrine or corticosteroids. Fibrinogen levels should be within normal reference values in pa-
tients with corticosteroid or epinephrine-induced neutrophilia that do not have inflammatory,
neoplastic or hemostatic abnormalities. Hyperfibrinogenemia also is seen in neoplastic condi-
tions (due to inflammation, increased synthesis from tumor cells or secondary to cytokine pro-
duction by the tumor cells) and in certain species with compensated intravascular coagulation.
13. Describe the eBe findings that suggest more severe inflammatory disease.
Neutrophil toxicity (cytoplasmic basophilia, foaminess, increased numbers of Dohle bodies)
and circulating immature neutrophils (bands, metamyelocytes, and myelocytes) indicate inflam-
mation of increased severity. Circulating immature neutrophils are referred to as a left shift and
indicate that the bone marrow is not able to meet the demand for mature neutrophils. The more
pronounced the left shift and the toxic change, the more severe the inflammatory insult. Moderate
to severe neutrophilia (>30,000 cells/ul) is seen with localized, long-standing infections such as
pyothorax, pyometra, and peritonitis. Severely elevated neutrophil counts (50,000-75,000
cells/ul) with a prominent left shift are also referred to as a leukemoid reaction and can be diffi-
cult to differentiate from certain forms of MPD (e.g., AML-M2, CML). The neutrophilia associ-
ated with MPD may be mild-to-severe and accompanied by significant numbers of immature
neutrophils (e.g., AML-M2 and CML with blast crisis [not described in cats]). Select cytopenias
(e.g., nonregenerative anemia) may accompany the leukemic changes. Caution is warranted in
cats suspected of feline panleukopenia virus (FPLV) infection because dramatic left shifts during
the recovery phase may be reminiscent of myelogenous leukemia. Repeating the CBC on subse-
quent days should help to clarify this distinction. Neutrophilic series mature in cats recovering
from FPLV but not in cats with leukemia.
14. What is the diagnostic plan for cats with neutrophilia after an epinephrine or corticos-
teroid response is ruled out?
The plan usually includes a serum biochemical panel and urinalysis. Patients with epineph-
rine-induced neutrophilia may exhibit mild-to-marked, transient hyperglycemia with resulting
glucosuria. Patients with corticosteroid-induced neutrophilia may exhibit mild and potentially
persistent hyperglycemia. The hyperglycemia induced by corticosteroids should not exceed the
renal threshold for glucose.
Neutrophilia and Neutropenia 359
Metastatic neoplasia
Systemic mast cell tumor
Serum FeLV antigen test and feline immunodeficiency virus antibody test should be per-
formed. Other diagnostic procedures (e.g., diagnostic imaging, cytology, histopathology, micro-
biology) may be necessary to characterize the process eliciting neutrophilia (see questions 15 and
16). Bone marrow evaluation should be pursued in unexplained, persistent neutrophilia or when
leukocyte morphology or the magnitude of neutrophilia raises suspicion of leukemia. Bone
marrow aspirates are useful for detecting the presence of morphologically bizarre neoplastic/dys-
plastic hematopoietic precursors or abnormal distribution of hematopoietic precursors in the
marrow (i.e., too many immature cells).
15. How do imaging techniques aid in the ranking of differential diagnoses?
Radiographs, ultrasound, computed tomography scan, or magnetic resonance imaging may
be used in some cases to aid in detecting organomegaly, effusion, space-occupying masses, and
localizing lesions. Abnormalities are expected in patients with some inflammatory conditions
and some patients with leukemic disease.
16. When are aspirates or biopsies indicated?
Aspirates or biopsies are indicated when space-occupying lesions, effusions, organomegaly,
or abnormal organ shape and appearance are present. Exploratory surgery may be required to
obtain diagnostic samples. Aspirates are generally easier to perform and less expensive and can
be examined almost immediately. Tissue biopsies are necessary to examine tissue architecture
and determine the extent of involvement of a particular organ or location. Bone marrow aspirates
and biopsies are indicated in suspected cases of leukemia. A coagulation profile should be per-
formed before sampling procedures are done in bleeding patients and patients suspected of
having liver disease or coagulation abnormalities.
17. What are the predominant causes of neutropenia?
In general, neutropenia can be caused by five main conditions, acting singly or in combination:
(I) severe, sudden tissue demand; (2) neutrophil redistribution; (3) abnormalities in bone marrow
neutrophil production; (4) ineffective granulopoiesis; and (5) peripheral neutrophil destruction.
Primary Differential Diagnoses for Neutropenia in Cats
Severe, sudden tissue demand for neutrophils
Infection (various bacteria causing diseases such as peritonitis, pyothorax, and pneumonia)
Redistribution of neutrophils from CNP to MNP
Infection (gram-negative endotoxemia)
Abnormalities in bone marrow neutrophil production
Drugs
Azathioprine
Griseofulvin
Chloramphenicol
Sulfa-trimethoprim combinations
Human G-CSF (cats initially respond with neutrophilia but later develop antihuman G-CSF
antibodies that cross-react with feline G-CSF)
Radiation therapy
Neoplastic disease
Myeloproliferative disease
Myelodysplastic syndrome
Lymphoproliferative disease
Infections
Feline leuekmia virus (FeLV)
Feline infectious peritonitis virus (particularly in cats coinfected with FeLV)
Feline panleukopenia virus
Histoplasmosis
Idiopathic abnormalities
Primary Differential Diagnoses for Neutropenia in Cats (Continued)
Ineffective granulopoiesis
Drug-related (anticancer drugs, griseofulvin, chloramphenicol, azathioprine, others)
Peripheral neutrophil destruction
Corticosteroid-responsive (suggests an immune-mediated mechanism), "hypersplenism"
Paraneoplastic syndrome (immune-mediated mechanism may be involved): dermal squamous cell
carcinoma
G-CSF =granulocyte colony-stimulatingfactor, CNP =circulating neutrophil pool, MNP =marginal neu-
trophil pool.
18. What is the most common cause of a severe, sudden tissue demand for neutrophils?
Severe, sudden tissue demand, which is probably the most common cause of neutropenia in
cats, is due primarily to inflammation (infectious or noninfectious) and results from the release of
potent chemical signals that attract neutrophils to the inflammatory site.
19. When does neutrophil redistribution occur?
During endotoxemia due to gram-negative infections, neutrophils shift from the CNP to the
MNP as a result of the release of various cytokines that increase neutrophil adhesion to endothe-
lial surfaces.
20. What may cause abnormalities in bone marrow neutrophil production?
Various infectious agents (FeLV, feline immunodeficiency virus [FlY], feline panleukopenia
virus [FPLVJ, histoplasmosis), chemicals (anticancer drugs, griseofulvin, chloramphenicol),
toxins (mycotoxins), neoplastic diseases (lymphoproliferative disease, myeloproliferative dis-
ease, metastatic neoplasm), myelodysplastic syndromes, and idiopathic disease can lead to a de-
crease in the proliferating pool of neutrophil precursors.
21. Explain ineffective granulopoiesis.
In cats with ineffective granulopoiesis. neutropenia is present concurrently with bone
marrow hyperplasia or normal bone marrow cellularity. This condition may be due to an
immune-mediated destructive process directed at a single type or multiple types of neutrophil
precursors. Many causes of abnormalities in bone marrow neutrophil production also may cause
ineffective granulopoiesis. Ineffective granulopoiesis is seen in cats with FeLV and/or FlY infec-
tion and cats with myelodysplastic syndromes. It may be seen after administration of certain
drugs (sulfa-trimethoprim, anticancer drugs, griseofulvin, chloramphenicol). FeLV-associated
neutropenia is more common than FeLV-associated myeloproliferative disease. The marrow is
frequently hypercellular in FeLV-associated neutropenic patients.
22. What causes peripheral neutrophil destruction?
Immune-mediated destruction, "hypersplenism" (sequestration in the spleen or removal of
neutrophils by splenic macrophages), administration of certain drugs, and paraneoplastic syn-
drome associated with cutaneous squamous cell carcinoma (an immune-mediated mechanism
may be involved).
23. How can the signalment help in ranking the differential list?
The specific signalment can vary with the particular cause of the neutropenia. Some diseases
affect cats of any age (endotoxemia, toxins, intestinal foreign bodies), whereas others affect spe-
cific age groups:
FIV is more commonly seen in older (> 5 years of age), outdoor, male cats.
FeLV-affected cats are generally younger 5 years of age).
Cats < I year of age are at increased risk for disseminated histoplasmosis.
Cats infected with FPLV are generally < I year of age.
Neutrophilia and Neutropenia 361
Cats most susceptible to FIPV tend to be young (6 months to 2 years of age) or geriatric
(14-15 years of age) .
The mean age of cats with MPD is 3-5.5 years old.
24. How can the history help in ranking the ditTerentiallist?
The history varies with the specific cause and may not be suggestive of neutropenia. For in-
stance, fever, anorexia, and lethargy may be reported by the owner but are clearly not specific for
neutropenia. The history is important in determining whether the cat is at increased risk for viral
disease (e.g., outdoor cats and cats that live in multiple-cat households are at increased risk for
FIV and FeLV). Cats affected with FlPV have histories reflecting multisystemic disease. Neutro-
penic patients often present with a clinical history of specific organ system involvement. For ex-
ample, diarrhea may be seen with FPLV and FeLV and intestinal foreign bodies with perforation,
neoplasia involving the intestines, or septicemia. Dyspnea may be seen in patients with acute
pneumonia. Patients with abnormalities in bone marrow neutrophil production may have a his-
tory of administration of marrow-suppressive drugs, FeLV-positive status, or multiple "lumps"
(lymphadenomegaly associated with systemic neoplasia). Patients with peripheral neutrophil de-
struction or ineffective granulopoiesis may have a history of recent drug administration.
25. How can physical examination findings help in ranking the differential list?
Physical examination findings may be nonspecific or vary with the specific cause of neu-
tropenia. Patients with neutropenia due to severe, sudden demand for neutrophils may present
with a multitude of abnormalities, including fever, depression, elevated heart and respiratory
rates, distended and/or painful abdomen (pyometra, peritonitis, ruptured intestine), or dyspnea
(pyothorax). Cats with abnormalities in bone marrow neutrophil production may have evidence
of systemic neoplasia or infection (organomegaly, space-occupying masses, icterus) and pancy-
topenia (pale mucous membranes due to anemia, petechiae due to thrombocytopenia).
26. How can the CBC help to determine the cause of neutropenia?
Cats with inflammatory disease, endotoxemia, or septicemia have inflammatory leukograms
(left shift, neutrophil toxicity). Leukemic patients may have atypical cells in the circulation.
Pancytopenias may be present in patients with abnormalities in bone marrow neutrophil produc-
tion and ineffective granulopoiesis. Patients with peripheral neutrophil destruction may have neu-
tropenia as the only hematologic abnormality (immune-mediated neutropenia, cyclic neutropenia).
Leukoerythroblastic (immature white and red blood cells) reactions may be seen in patients with
bone marrow infiltration by massive numbers of neoplastic or inflammatory cells.
27. Describe the initial diagnostic plan for cats with neutropenia.
If the neutropenia is an incidental finding (i.e., the cat is not ill), a repeat CBC may be used to
confirm neutropenia. CBC, peripheral blood smear evaluation, serum biochemical analysis, FeLY
and FlY testing, and bone marrow aspirate and biopsy should be obtained in persistently or ill neu-
tropenic cats. CBC and peripheral blood smear evaluation are necessary to identify other hemato-
logic and bone marrow production abnormalities (pancytopenia, leukemia). Additional diagnostic
tests may be necessary. including imaging examinations (radiography, ultrasonography), micro-
scopic examination of cytologic preparations, tissue biopsies and effusions, microbiologic culture,
and serology. Patients must be examined carefully for the presence of an inflammatory focus (ab-
scess), systemic neoplasia, or systemic infection.
28. Can routine biochemical testing aid in the ranking of differential diagnoses?
Biochemical testing and urinalysis may be helpful in localizing a particular disease process
or documenting the extent of the disease. Coagulation profiles are recommended in patients with
hemorrhage or liver involvement and patients suspected of having coagulation abnormalities.
Cats affected with FlPY often have hyperglobulinemia (polyclonal or monoclonal gammopathy).
Serum protein electrophoresis is recommended to characterize the hyperglobulinemia.
29. How do imaging techniques aid in the ranking of differential diagnoses?
Imaging techniques (radiography, ultrasonography) help to detect organomegaly, fluid in
body cavities, and space-occupying masses; to localize lesions; and to direct biopsies (ultra-
sonography). Abnormalities are expected in patients with some inflammatory conditions and
some patients with leukemic and neoplastic disease.
30. When are aspirates or biopsies indicated?
Aspirates or biopsies are indicated in patients with space-occupying lesions, effusions,
organomegaly, or abnormal organ shape and appearance. Exploratory surgery may be required to
obtain diagnostic samples. Bone marrow aspirates and biopsies are indicated in suspected cases
of MPD and pancytopenia. In cases of bone marrow hypoplasia, aspirates may produce low num-
bers of cells. Bone marrow core biopsies may help to differentiate a poor aspirate sample from
true hypoplastic bone marrow and hypoplasia associated with myelofibrosis from hypoplasia
seen with other conditions (e.g., FPLV). Tissue biopsies are necessary to examine tissue architec-
ture and determine the extent of involvement of a particular organ or location. A coagulation pro-
file should be performed before sampling procedures in bleeding patients and patients suspected
of having liver disease or coagulation abnormalities.
31. Describe the initial treatment plan for cats with neutrophilia and neutropenia.
Intravenous fluids are indicated in most sick patients, particularly those that are dehydrated.
Patients with infectious diseases (bacterial, fungal) should be treated with appropriate antimicro-
bial therapy. Patients with immune-mediated diseases frequently benefit from immunosuppressive
therapy. Patients with neoplastic disease, depending on the stage of the disease, may benefit from
anticancer chemotherapy or surgery. Other treatments depend on the primary disease process.
BIBLIOGRAPHY
I. Baldwin CJ, Ledet AE: Pancytopenia. In August JR (ed): Consultations in Feline Internal Medicine. 2nd
ed. Philadelphia, WB. Saunders, 1994, pp 495-502.
2. Bjoersdorff A, Svendenius L, Owens JH, et al: Feline granulocytic ehrlichiosis: A report of a new clini-
cal entity and characterization of the infectious agent. J Small Anim Pract 40:20-24, 1999.
3. Duncan JR, Prasse KW, Mahaffey EA: Leukocytes. In Veterinary Laboratory Medicine: Clinical
Pathology. Ames, lA, Iowa State University Press, 1994, pp 37--62.
4. Hall RL: Interpreting the leukogram. In August JR (ed): Consultations in Feline Internal Medicine, 2nd
5. Hawkins Ee: Investigation and management of neutropenia. In August JR (ed): Consultations in Feline
Internal Medicine. Philadelphia, W.B. Saunders, 1990, pp 343-348.
6. Kidd R: Interpreting neutrophil numbers. Vet Med 86:975-978,1991.
7. Linenberger ML, Shelton GH, Persik MT, Abkowitz JL: Hematopoiesis in asymptomatic cats infected
with feline immunodeficiency virus. Blood 78:1963-1968, 1991.
8. Meyer DJ, Harvey JW: Evaluation of leukocytic disorders. In Veterinary Laboratory Medicine: Interpre-
tation and Diagnosis. Philadelphia, WB. Saunders, 1998, pp 83-109.
9. Raskin RE: Myelopoiesis and myeloproliferative disorders. Vet Clin North Am 26:1023-1042, 1996.
10. Rojko JL, Hardy WD Jr: Feline leukemia virus and other retroviruses. In Sherding RG (ed): The Cat:
Diseases and Clinical Management. New York, Churchill Livingstone, 1994, pp 263-432.
I I. Thoday KL, Mooney CT: Historical and laboratory features of 126 hyperthyroid cats. Vet Rec 131:257-
264,1992.
12. Thrall MA, Grauer GF, Mero KN: Clinicopathologic findings in cats with ethylene glycol intoxication. J
Am Vet Med Assoc 184:37-41, 1984.
13. Tyler RD, Cowell RL, Meador V: Bone marrow evaluation. In August JR (ed): Consultations in Feline
Internal Medicine, 2nd ed. Philadelphia, WB. Saunders, 1994, pp 515-523.
14. Ward H, Couto CG: Myeloid leukemias. In August JR (ed): Consultations in Feline Internal Medicine,
3rd ed. Philadelphia, W.B. Saunders, 1997, pp 509-513.
15. Wellman ML, Hammer AS, DiBartola SP, et al: Lymphoma involving large granular lymphocytes in cats:
II cases (1982-1991). J Am Vet Med Assoc 201:1265-1269,1992.
70. EOSINOPHILIA AND EOSINOPENIA
Robin W. Allison, D.V.M.
1. Define eosinophilia and eosinopenia.
Eosinophilia refers to increased numbers of circulating eosinophils (depending on the labo-
ratory reference range, usually> 1,200-1,500 cells/ill). Eosinopenia is rarely recognized be-
cause the low normal value for eosinophils in cats is zero.
2. In what tissues are eosinophils most abundant?
After production in the bone marrow and release into peripheral blood, eosinophils migrate
after only a few hours in circulation into various tissues, where they can survive for several days.
Eosinophils generally are most abundant in submucosal and mucocutaneous areas (skin, respira-
tory tract, gastrointestinal tract, and genitourinary tract).
3. What are the normal functions of eosinophils?
The characteristic pinkish-red cytoplasmic granules of eosinophils (rod-shaped in cats) con-
tain a wide variety of chemical constituents with different functional roles. In general, eosinophils
are important in controlling tissue parasites and regulating allergic and acute inflammatory re-
sponses. Specifically, eosinophils migrate into tissues in response to local chemoattractants, in-
cluding antigen-antibody complexes involving IgE, mast cell products such as histamine,
activated complement components, and cytokines such as interleukin-2 and eotaxin. Once in tis-
sues, eosinophils interact through surface receptors, eventually releasing potent granule contents
(e.g., major basic protein, histaminase, phospholipase D) and lipid mediators (e.g., leukotrienes,
platelet -activating factor). These reactive substances have a diverse array of local effects, includ-
ing antibody-mediated parasite killing, inhibition and inactivation of mast cell products such as
histamine and serotonin, amplification of the inflammatory cascade via cytokine release, tissue
injury through collagen degradation, and alterations in vascular permeability.
4. How does eosinophilia occur?
Blood eosinophilia may result from:
Increased production
Increased release from bone marrow
Redistribution from the marginal pool
Prolonged intravascular survival
The first two mechanisms are probably responsible for most instances of eosinophilia and
occur in response to cytokines produced by activated T lymphocytes (primarily interleukin 5).
Redistribution may occur in association with neutrophilia and lymphocytosis during the epineph-
rine-induced excitement response. Prolonged survival may be important in some hypere-
osinophilic syndromes.
5. What causes eosinopenia?
Although of limited significance, eosinopenia may result from stress associated with illness
and exogenous corticosteroid administration. Concurrent lymphopenia supports a diagnosis of
true eosinopenia due to stress.
6. What are the primary causes of eosinophilia?
Inflammatory disorders, frequently parasitic or allergic in origin. involving the skin, respira-
tory tract, or gastrointestinal tract (GI) are common causes of eosinophilia. Flea allergy,
363
364
Eosinophilia and Eosinopenia
bronchial asthma, eosinophilic granuloma complex, and eosinophilic gastroenteritis are the most
common underlying diseases in cats. Less frequent causes include neoplasia (e.g., mast cell
tumor, lymphoma, eosinophilic leukemia), fungal, viral, or bacterial infections, and hypere-
osinophilic syndrome (RES). RES is characterized by blood eosinophilia, bone marrow hyper-
plasia of eosinophil precursors, and multiple organ infiltration by eosinophils; it may be difficult
to distinguish from eosinophilic leukemia.
Diseases Associated with Eosinophilia in Cats
Gastrointestinal diseases
Coccidiosis
Eosinophilic enteritis*
Giardia spp.
Hookworrns*
Inflammatory bowel disease (chronic)
Roundworrns*
Tapeworrns*
Toxoplasma gondii
Infectiousdiseases
Feline panleukopenia
Viral upper respiratory disease
Neoplasia
Lymphoma
Mast cell disease (systemic, cutaneous)
Myeoloproliferative disorders
Solid tumors (uncommon)
Myxosarcoma
Basal cell tumor
Salivary adenocarcinoma
Sweat gland adenocarcinoma
Transitional cell carcinoma
* Most commoncauses.
Respiratory disease
Aleurostrongylus abstrusus
Dirofilaria immitis
Feline bronchial asthma"
Paragonimus kellikotti
Pneumonia (bacterial, viral)
Pneumothorax
Rhinitis/sinusitis (chronic)
Upper respiratory infection (chronic)
Skin diseases
Atopy
Ctenocephalides felis*
Eosinophilic granuloma complex*
Flea allergy derrnatitis*
Food hypersensitivity
Notoedres cati
Otodectes cyanosis
Pemphigus foliaceous
Miscellaneous
Cardiomyopathy
Feline urologic syndrome
Focal inflammatory disorders
Hyperthyroidism
Renal failure
Soft tissue trauma
Suppurative processes
7. Describe the initial diagnostic plan for cats with eosinophilia.
Initial evaluation should be aimed at excluding parasitic and allergic disorders and can be di-
rected by the clinical signs.
8. What tests are appropriate for cats with respiratory signs?
For cats exhibiting respiratory signs such as dyspnea, tachypnea, or wheezing, appropriate
diagnostic tests include thoracic radiographs, Dirofiliaria immitis antibody and antigen testing,
fecal flotation, and Baermann examination (see Chapter 8). If bronchial or alveolar lung disease
are present, eosinophilic inflammation may be evident in a tracheal wash, indicating a hypersen-
sitivity reaction that could be allergic or parasitic. Occasionally parasite larvae or ova also may
be present in the wash, but often multiple fecal examinations are necessary to identify parasites
that have been coughed up and swallowed.
9. What tests are useful in cats with skin disease?
Cats with skin disease should be examined for fleas, have skin scrapings or cultures to iden-
tify ectoparasites or other microorganisms, and may require skin biopsies, food trials. or allergy
testing. Fine-needle aspiration or surgical biopsy can be used to evaluate masses.
Bleeding Problems
365
10. Describe the elements of GI tract evaluation.
GI evaluation should include an oral examination for eosinophilic granuloma, fecal flotation,
fecal wet mount examination, and abdominal radiographs (see Chapter 18). Endoscopy or ex-
ploratory laparotomy may be indicated with cytology or biopsy of any identified lesions used to
prove eosinophilic inflammation. Hypoadrenocorticism is another cause of eosinophilia and GJ
signs (see Chapter 55).
11. What additional diagnostic tests may be needed?
Once the more common parasitic and allergic disorders have been ruled out, other causes
such as hematopoietic or nonhematopoietic neoplasia and various infectious and inflammatory
diseases should be pursued. Bone marrow aspirates; ultrasound-guided aspirates of enlarged ab-
dominal organs such as liver, spleen, or lymph nodes; and cytologic evaluation of any thoracic or
abdominal effusion may be helpful.
12. How is eosinophilia treated?
The underlying disease must be identified and treated to resolve the eosinophilia. HES and
eosinophilic leukemia in cats have been treated with corticosteroids with some short-term im-
provement, but long-term results have been poor.
BIBLIOGRAPHY
I. Center SA, RandolphJF, Erb HN, et al: Eosinophiliain the cat: A retrospective study of 312 cases (1975
to 1986). J AmAnimHospAssoc26:349-358, 1990.
2. Center SA, Randolph JF: Eosinophilia. In August JR (ed): Consultations in Feline Internal Medicine.
3. CorcoranBM, Foster DJ, FuentesVL: Feline asthma syndrome:A retrospective study of the clinical pre-
sentationin cats. J SmallAnimPract. 36:481, 1995.
4. CoutoCG, Wellman M: Disordersof leukocytes and leukopoiesis. In SherdingRG(ed):The Cat: Diseases
and Clinical Management. NewYork, Churchill Livingstone, 1994, pp 721-737.
5. HuibregtseBA, Turner JL: Hypereosinophilic syndromeand eosinophilicleukemia: A comparisonof 22
hypereosinophilic cats. J AmAnimHospAssoc30:591-599, 1994.
6. Jain NC: The eosinophils. In Essentialsof Veterinary Hematology. Philadelphia, Lea & Febiger, 1993, pp
247-257.
7. Power HT, Ihrke PJ: Selected feline eosinophilic skin diseases. Vet Clin North Am Small Anim Pract
25:833-850, 1995.
71. BLEEDING PROBLEMS
Michael R. Lappin, D.V.M., ph.D., and Christine Olver, D.V.M., Ph.D.
1. What are the primary differential diagnoses for cats with evidence of bleeding?
Cats presented for evaluation of clinical findings consistent with hemorrhage usually have
one of the four following conditions:
I. Local vascular disease
2. Disorders of hemostasis
3. Hypertension
4. Generalized vascular disease (vasculitis)
Local diseases of blood vessels (e.g., trauma, tumors, chronic inflammation) are the most
common conditions resulting in bleeding in cats. Widespread vasculitis is rare in cats.
Hypertension usually results only in retinal hemorrhage, but epistaxis and bleeding into the cen-
tral nervous system occur in some cats (see Chapter 63). Although apparently less common than
366
Bleeding Problems
in dogs, disorders of hemostasis do occur in cats. One study found abnormalities in 38 of 85 clin-
ically ill cats assessed for coagulopathies.
2. How can disorders of hemostasis be classified?
Primary hemostasis is basically the primary platelet plug that develops at the site of a
defect in a vessel wall. As the primary platelet plug is forming, fibrin is deposited in the dis-
eased area (secondary hemostasis) via activation of soluble and cell-associated coagulation
pathways.
3. Describe the mechanisms of primary hemostasis.
Platelets bind to adhesive glycoproteins in the exposed subendothelium of damaged blood
vessels, forming the primary platelet plug that continues to grow as platelets aggregate.
Primary hemostasis helps to control local hemorrhage for seconds to minutes. Primary hemo-
stasis disorders can be divided into disorders resulting in platelet function deficits or disorders
resulting in thrombocytopenia. Platelet function deficits in cats are apparently rare; von
Willebrand's disease has been reported in several cats. Mechanisms leading to thrombocytope-
nia include decreased production, increased destruction, or increased consumption of platelets.
4. Describe the disorders associated with secondary hemostasis.
Defects in secondary hemostasis can be grouped into disorders leading to factor decrease or
absence or factor inhibition. Examples of factor decrease or absence include decreased produc-
tion due to hepatic insufficiency; congenital lack; failure to convert procoagulants to coagulants
(factors Il, VII, IX, and X) due to vitamin K absence (cholestatic liver disease or malabsorption
syndromes) or vitamin K antagonism (some rodenticides); and consumption due to disseminated
intravascular coagulation (DIC).
5. Where are clotting factors produced?
With the exception of von Willebrand's factor and factor VIII, circulating polypetide clotting
factors are produced exclusively by the liver.
6. Which clotting factors are vitamin K-dependent?
Factors II, VII, IX, and X.
7. Which factor is the most significant component measured by the one-stage prothrom-
bin time (OSPT)?
Factor VII.
8. How is a balance maintained between clot formation and clot dissolution?
When secondary hemostasis is activated, fibrinolysis also occurs.
Tissue activators of plasminogen include urokinase and tissue plasminogen activator.
Activation of plasminogen generates plasmin, which degrades fibrinogen and fibrin to fib-
rinogen degradation products (FOPs).
Physiologic anticoagulants include antithrombin III (ATIIl), which inhibits thrombin
(factor II), activated factors X, IX, XI, and XII, and kallikrein, and the vitamin K-depen-
dent proteins S and C, which inhibit factors V and VIII. ATIII is produced by the liver and
potentiated by heparin.
9. Describe the clinical findings of hemostatic disorders.
Petechiae and ecchymoses are most common with primary hemostatic disorders. Mucous
membranes and the retina are the areas with the highest sensitivity for detection of petechiae.
Cats with secondary hemostatic disorders can be clinically normal. Factor abnormalities often
result in deep-tissue and body-cavity bleeding. Bleeding tendencies may not be evident until
Bleeding Disorders 367
vessels are traumatized (e.g., at surgery). Other clinical findings depend on the primary disease
and the site of hemorrhage. For example, cats with warfarin toxicity resulting in hemothorax usu-
ally present with lethargy, dyspnea, and restrictive breathing pattern.
10. What tests are used to help classify hemostatic disorders?
The tests used most commonly include platelet count, activated clotting time (ACT), and
bleeding time (BT) because each can be performed easily in the feline hospital in an emergency
situation without expensive equipment. Machines (SC2000 Coagulation Analyzer; Synbiotics,
San Diego, CA) available for in-clinic use can perform the OSPT and activated partial thrombo-
plastin time (APTT). These tests also can be performed accurately in commercial laboratories if
the samples are handled appropriately. Fibrinogen degradation products (FOP), thrombin time
(IT), proteins induced by vitamin K absence or antagonism (PIVKAs), von Willebrand's factor,
ATIII, and other specific factor assessments are sometimes needed. With the exception of FOP,
platelet count, and ACT, coagulation tests are performed on citrated plasma. After collection, cit-
rated blood should be centrifuged immediately and the plasma frozen until assayed. When col-
lecting samples for assessment of hemostasis, make a clean venipuncture to avoid liberating
procoagulant tissue factors.
11. Summarize the test results associated with hemostatic disorders in cats.
PLATELET ACTIVATED BLEEDING
DISEASE COUNT CLOITING TIME TIME DIAGNOSIS
Primary hemostasis
Thrombocytopenia Decreased Slight prolongation Prolonged Varies withprimarydisease
vonWillebrand's disease Normal Normalor prolonged Prolonged Measurementof vonWille-
andother plateletdys- withconcurrentfactor brand's antigen
functiondiseases VIII hemophilia
Secondary hemostasis
Hemophilia Normal Prolongedunlessfactor Normal Specificfactor assessment
VII deficiency
Hepaticinsufficiency Normal Prolonged Normal Serumbiochemicalpanel, bile
acids, imaging,biopsy
Cholestaticliver disease Normal Prolonged Normal Serumbiochemicalpanel,
or malabsorption syn- imaging,biopsy
dromes
Vitamin K antagonist Normal Prolonged Normal Measurement of PIVKAor
rodenticides warfarinbyproducts
12. How are platelet count and morphology assessed?
Platelets can be counted or estimated by microscopic examination of a stained thin blood
smear. Under oil immersion, each platelet per field is equivalent to 15,OOO/J,lI; normal cats have
11-19 platelets per field. Whenever thrombocytopenia is detected, evaluate for evidence of
platelet clumps, which may signify falsely lowered numbers. Giant platelets may indicate the
release of immature platelets from an appropriately active bone marrow, making decreased
production of platelets less likely. Spontaneous hemorrhage from thrombocytopenia usually
does not occur unless the count is < 50,000/J.1l. The platelet count of normal cats should be >
200,OOO/J,l1.
13. How is ACT assessed?
Assessment of ACT requires only a special tube (Becton Dickinson Microbiology Systems,
Rutherford, NJ) and a 37C incubator. The test estimates decreases in factors in the intrinsic and
common pathways and thus is similar to the APTT. However, platelet phospholipid affects the
ACT but not the APIT. Thus, extreme thrombocytopenia 50,OOO/J.1l) may result in a slight pro-
longation of the ACT (l0-15 seconds). ACT does not detect decreases in factor VII (extrinsic
368
Bleeding Problems
pathway). However, factor VII hemophilia is either nonexistent or extremely rare in cats. Cats
with ACT < 165 seconds should be considered normal.
14. Describe the assessment of bleeding time.
Bleeding time evaluates platelet function and thus is not indicated in cats with thrombocy-
topenia. Platelet function abnormalities are rare in cats since von Willebrand's disease is uncom-
mon. If bleeding time is assessed, the lip should be gently rolled back and held in place lightly
with gauze under light sedation. A Simplate device (Organon Teknika Corp., Durham, NC) is ap-
plied gently to the mucosa, and the trigger is released to make a measured incision. Filter paper
or gauze is used to wick away excessive blood but should not touch the incision or risk dislodg-
ing the platelet plug. A normal mucosal bleeding time is < 2.5 minutes.
15. When are other tests indicated?
Results of the initial screening tests determine which other tests are needed:
OSPT detects abnormalities in the extrinsic and common pathways; APTT detects abnor-
malities in the intrinsic and common pathways.
VonWillebrand's factor can be measured to assess for von Willebrand's disease.
PIVKAs are procoagulants of the vitamin K-dependent factors II, VII, IX, and X and in-
crease in plasma if vitamin K is absent or antagonized (see questions 19-23).
FDPs are products of fibrinolysis and are increased in cats with DIe.
ATIII is consumed in DIC, resulting in decreased activity; thus, ATII activity can be used to
aid in the diagnosis (see questions 26-28).
16. What causes decreased production of platelets in cats?
Decreased production of platelets can be caused by a number of different syndromes. Throm-
bocytopenia is often extreme, and other cell lines (neutrophils and erythrocytes) are decreased
with some diseases. Bone marrow aspiration or biopsy may be needed to diagnose the specific
syndrome. Diseases likely to be encountered include:
Myelophthisis due to infiltrative lymphoma, leukemias, or multiple myeloma
Feline leukemia virus-associated myelosuppression (see Chapter 76)
Immune-mediated disease directed at megakaryocytes
Drug induced bone marrow suppression
In a study of 41 cats with thrombocytopenia, FeLV and myeloproliferative neoplasia ac-
counted for 44% of the cases. Primary immune-mediated thrombocytopenia was suspected in
only [ cat.
17. What causes increased platelet utilization, consumption, or destruction in cats?
Increased platelet utilization, consumption, or destruction occurs rarely in cats. The degree
of thrombocytopenia is mild to moderate. Diseases that may be encountered include:
Idiopathic immune-mediated thrombocytopenia (rare compared with dogs)
Systemic lupus erythrematosus (extremely rare compared with dogs).
Disseminated intravascular coagulation (see questions 26-28).
Modified live vaccines, which may cause transient thrombocytopenia that usually is inap-
parent clinically (see Chapter 82).
Platelet utilization at sites of hemorrhage due to trauma or secondary hemostatic problems
(e.g., rodenticide toxicity), which may cause mild thrombocytopenia
Feline ehrlichiosis (see Chapter 78).
Any disease resulting in vasculitis (e.g., sepsis) can result in thrombocytopenia due to local
consumption of platelets.
18. Summarize the approach to management of platelet problems.
The primary disease should be identified and treated. Whole blood transfusion may be indi-
cated if extreme anemia is occurring. Fresh whole blood transfusion does not provide many
Bleeding Problems 369
platelets but may be indicated if active bleeding is occurring. Suspected primary immune-medi-
ated thrombocytopenia is managed like immune-mediated hemolytic anemia (see Chapter 72).
19. Does von WiUebrand's disease occur in cats?
Compared with dogs, this disease is extremely rare in cats. Expected findings include a pro-
longed bleeding time due to platelet dysfunction (decreased von Willebrand's antigen) and a
normal platelet count, with or without a prolongation in ACT or APTT (depending on the pres-
ence of concurrent factor VIII deficiency) (see question 9).
20. What are other inherited coagulation abnormalities?
Factor XII deficiency is an autosomal recessive trait that appears to be the most common in-
herited secondary hemostatic disorder in cats. Most cats are subclinically affected, but increased
hemorrhage may be noted after surgical procedures. Factor VIII deficiency, factor IX deficiency,
combined factor VIII and XII deficiency, combined factor IX and XII deficiency, and vitamin K-
dependent multifactor coagulopathy of Devon Rex cats are reported sporadically.
21. With what disorders is vitamin K absence associated?
o Hepatic lipidosis and cholangiohepatitis. Bile salts are required for the absorption of vita-
min K because it is a fat-soluble vitamin.
o Malabsorption syndromes. Fats and vitamin K must be absorbed from the gastrointestinal
(GI) tract.
o Anorexia and administration of antimicrobials that decrease anaerobic bacterial flora in the
GI tract. Vitamin K comes from the diet as well as GI bacterial flora.
22. With what disorder is vitamin K antagonism usually associated?
Anticoagulant rodenticides.
23. What test results are associated with vitamin K absence or antagonism?
o ACT, OSPT, and APTT are usually increased by the time active hemorrhage occurrs.
o Because factor VII has the shortest half-life, OSPT is the most sensitive test for detection of
toxicity in cats that are not bleeding.
o PIVKAs increase. In one study, the PIVKA test was more sensitive than other coagulation
tests.
o Mild thrombocytopenia may occur, probably from utilization of platelets at sites of hemor-
rhage.
24. How do cats become intoxicated with rodenticides?
Cat are thought to be intoxicated by rodenticides from direct ingestion of the bait or ingest-
ing rodents that have ingested the rodenticide.
25. Describe the management of cats with suspected vitamin K absence or antagonism.
I. Collect samples needed for further diagnostic tests.
2. Administer vitamin K, subcutaneously at a loading dose of 2.5-5.0 mg/kg; it should not
be given intravenously because of the risk of an anaphylactoid reaction.
3. Give vitamin K] orally at 1.0-5.0 mg/kg every 12 hours, depending on the form of roden-
ticide ingested. Lower doses given for 7-10 days are usually effective for first-generation drugs
such as warfarin. Diphacinonone, chlorphacinone, brodifacoum, and bromadiolone (second-gen-
eration drugs) usually require the high end of the dose for up to 6 weeks.
4. When given orally, vitamin K, should be given with a fatty meal to increase absorption.
5. Give whole blood transfusion if needed for anemia or uncontrollable hemorrhage.
6. Coagulation tests generally start improving within 12 hours because procoagulants are
rapidly converted to active coagulants in the presence of vitamin K.
370
Bleeding Problems
7. Treat with oral vitamin K for a minimum of 2 weeks
8. Stop treatment and assess ACT or OSPT 2 days later. If the results are normal, further
treatment is not needed. If the results are prolonged, repeat the treatment cycle.
26. Describe the signs and symptoms of hemostatic abnormalities associated with liver in-
sufficiency.
Because most coagulation factors are produced at least in part by the liver, hepatic insuffi-
ciency can ultimately result in factor deficiencies. Factor deficiencies typically occur only in late-
stage liver disease when other clinical abnormalities are usually present, including cachexia, Gl
signs, ascites, and low concentrations of blood urea nitrogen, albumin, cholesterol, and glucose
(see hepatic disease chapters). ACT, OSPT, and APTT are expected to be prolonged as hepatic
function worsens. Thrombocytopenia may be present in cats with concurrent DIC or severe in-
flammation. Because clotting factors are not produced, there is no dramatic response to vitamin
K as seen with cholestasis.
27. Describe the management of hemostatic abnormalities associated with liver insufficiency.
There is no specific treatment except to attempt to remove the primary disease process so
that hepatic function improves.
28. What is DIC?
DIC is the result of a primary disease process that activates widespread intravascular coagula-
tion as a result of endothelial damage, massive platelet activation, or release of tissue procoagulants.
One example is feline infectious peritonitis; in one study, all 6 experimentally inoculated cats devel-
oped coagulation test results consistent with DIe. After a brief period of hypercoagulability that is
difficult to document, platelets and factors are consumed, ultimately resulting in bleeding.
29. How common is DIC in cats?
Although DIC in cats is thought to be rare, 21% of cats at the Ohio State University with he-
mostatic screening procedures had findings consistent with DIe. The authors considered cats to
have evidence of DIC if four of the following were present.
Thrombocytopenia Low ATllI concentration
Prolonged APTT Positive FDPs
Prolonged OSPT Schistocytes
Low fibrinogen concentration
In another study of thrombocytopenic cats, 5 of 41 were considered to have DIC.
30. How is DIC treated?
Treatment of DIC in cats has not been objectively assessed. General recommendations based
on treatment of people and dogs include:
1. Remove the primary cause if possible.
2. Give low-dose heparin in an attempt to lessen disseminated coagulation (90-200 U/kg-
subcutaneously every 8 hours).
3. Give blood components to replenish ATIII and clotting factors.
BIBLIOGRAPHY
I. Bay JD, Scott MA, Hans JE: Reference values for activated coagulation time in cats. Am J Vet Res
2000.
2. Boudreaux MK. Weiss RC, Cox N, et al: Evaluation of antithrombin-III activity as a coindicator of dis-
seminated intravascular coagulation in cats with induced feline infectious peritonitis virus infection.
Am J Vet Res 1989.
3. Center SA, Warner K, Corbett J et al: Proteins invoked by vitamin K absence and clotting times in clini-
cally ill cats. J Vet Intern Med 14:292-297,2000.
4. Couto CG, Hammer AS: Disorders of hemostasis. In Scherding RG (ed): The Cat: Diseases and Clinical
Management, 2nd ed. NewYork, Churchill Livingstone, 1994, pp 739-753.
Immune-mediated Hemolytic Anemia
371
5. Hart SW, Nolte I: Hemostatic disorders in feline immunodeficiency virus-seropositive cats. J Vet Intern
Med 8:355-362,1994.
6. Jordan HL, Grindem CB, Breitschwerdt EB: Thrombocytopenia in cats: A retrospective study of 41
cases. J Vet Intern Med 7:261-265, 1993.
7. Maddison JE, Watson AD, Eade IG, et al: Vitamin K-dependent multifactor coagulopathy in Devon Rex
cats. J Am Vet Med Assoc 197:1495--1497, 1990.
8. Randolph JF, DeMarco J, Center SA, et al: Prothrombin, activated partial thromboplastin, and proteins
induced by vitamin K absence or antagonists clotting times in 20 hyperthyroid cats before and after
methimazole treatment. J Vet Intern Med 14:56-59,2000.
9. Rivera-Ramirez PA, Deniz A, WIrth W, et al: Antithrombin III activity in healthy cats and its changes in
selected diseases. Berliner-und-Munchener-Tierarztliche-Wochenschrift llO:44D-444, 1997.
10. Thomas JS, Green RA: Clotting times and antithrombin III activity in cats with naturally developing dis-
eases: 85 cases (1984-1994). J Am Vet Med Assoc 213:1290-1295,1998.
II. Weiss OJ: Uniform evaluation and semiquantitative reporting of hematologic data in veterinary laborato-
ries. Vet Clin Patho113:27, 1988.
72. IMMUNE.. MEDIATED HEMOLYTIC ANEMIA
1. What are the primary differential diagnoses for pale mucous membranes in cats?
Pale mucous membranes are usually the result of anemia or hypoperfusion (shock). These
two problems are differentiated by packed cell volume (PCY). In cats, anemia is defined as PCY
<27.
2. Describe the two types of anemia.
Anemia is classified as regenerative or nonregenerative. By definition, regenerative anemia
is characterized by reticulocyte counts> 50,OOD/lll; nonregenerative anemia has < 50,OOO/1l1 (see
Chapter 79). Because it takes 3-5 days after acute development of anemia for maximal reticulo-
cytosis to appear, acute anemia initially may appear as nonregenerative.
3. How are regenerative anemias initially classified?
The two primary differential diagnoses for regenerative anemia are hemolysis and blood
loss. Hemolytic regenerative anemia can be intravascular or extravascular. Intravascular he-
molysis can lead to hemoglobinuria and pink plasma. Extravascular hemolysis usually has icteric
serum or plasma. Blood can be lost into body spaces (e.g., hemothorax, hemoabdomen) or out of
the body (e.g., epistaxis, gastrointestinal hemorrhage). If blood is lost out of the body, total pro-
tein concentrations are usually decreased, whereas total protein concentrations usually are
normal with blood loss into a body cavity and hemolytic anemias.
4. What forms of hemolytic anemia occur in the cat?
Immune-mediated Drug- or toxin-related
Infectious Metabolic
Microangiopathic Congenital
5. Describe the two basic types of immune-mediated hemolytic anemia.
Immune reactions can result in destruction of erythrocytes. With primary immune-mediated
hemolytic anemia, the immune reaction is directed specifically against erythrocyte antigens.
Sytemic lupus erythematosus (SLE) can be associated with primary immune-mediated hemolytic
anemia. Primary immune-mediated hemolytic anemia appears to be more common in dogs than
372
in cats. With secondary immune-mediated hemolytic anemia, the immune reaction is induced by
other causes; erythrocyte damage occurs secondarily. In cats, most immune-mediated hemolytic
anemias are secondary to drugs or infectious agents.
6. Describe the basic mechanism of infectious hemolytic anemia.
In cats, the most common causes of hemolytic anemia are infectious. The primary infection
starts a specific immune response that damages erythrocytes secondarily. In dogs, secondary
immune-mediated hemolytic anemia is thought to be associated with modified live vaccines.
This mechanism is suspected in cats as well but has not been well documented.
7. How is infectious hemolytic anemia diagnosed and treated?
Diagnosis is based on cytologic demonstration of the organism (e.g., Haemobartonella spp.,
Cytauxzoonfelis), serologic testing (e.g., feline leukemia virus [FeLV], feline infectious peritonitis
[FIP] virus), or polymerase chain reaction (e.g., Haemobartonella spp.). Treatment is based pri-
marily on removal of the primary agent. Occasionally, glucocorticoids are required to lessen the
secondary immune reaction as the primary cause is removed. For example, doxycycline and glu-
cocorticoids are commonly given concurrently to cats with severe agglutination due to hemo-
bartonellosis (see Chapter 74).
8. Describe the mechanism of microangiopathic hemolytic anemia.
Erythrocytes can be damaged when passing through abnormal vessels, resulting in schisto-
cytes or fragments. Disseminated intravascular coagulation (fibrin strands), dirofilariasis, and
splenic tumors or hematomas can damage red blood cells.
9. How do drugs and toxins cause hemolytic anemia?
Some drugs or toxins (e.g., acetaminophen, benzocaines) result in Heinz body anemia,
which is usually regenerative (see Chapter 73). Other drugs and toxins induce nonregenerative
anemia (see Chapter 79). Secondary immune-mediated hemolytic anemia can be induced by
propothiouracil, a drug previously used to treat hyperthyroidism. Secondary immune-mediated
hemolytic anemia is thought to occur in some dogs with repeated exposure to beta-lactam antibi-
otics. This mechanism is suspected in cats as well but has not been documented.
10. What is the most common metabolic cause of hemolytic anemia in cats?
Extreme hypophosphatemia during treatment of ketoacidotic cats results in increased red
blood cell fragility and resultant lysis.
11. What are the congenital causes of hemolytic anemia in cats?
Congenital defects can result in erythrocyte fragility and hemolytic anemia. Pyruvate kinase
deficiency in Abyssinian cats is one example. Neonatal isoerythrolysis also occurs in some cats
(see questions 20 and 21).
12. Why does primary immune-mediated hemolytic anemia occur?
The initiating cause is unknown. Antibodies are developed that attach to erythrocytes, and
the cells are removed by the reticuloendothelial system (extravascular hemolysis) or lysed after
complement fixation (intravascular hemolysis). IgM or IgG antibodies can be involved. IgM is
commonly associated with agglutination. Cold agglutinin disease is a rare manifestation of pri-
mary immune-mediated hemolytic anemia in cats. IgM antibodies interact with the surface of
the erythrocyte only at temperatures < 37C. Agglutination in peripheral vessels results in is-
chemic necrosis of the ear tips, tail tip, and, rarely, distal extremities. The immune reaction can
be directed at erythrocyte precursors (pure red cell aplasia). In this syndrome, the anemia is
nonregenerative (see question 16). Disease sometimes occurs in Iitterrnates, suggesting a ge-
netic predisposition.
Immune-mediated Hemolytic Anemia 373
13. Describe the signalment of immune-mediated hemolytic anemia in cats.
The signalment varies with the primary disease. Examples include:
Neonatal isoerythrolysis occurs in 1-2-day-old kittens.
FeLV infection is most common in young cats.
Drug reactions can occur at any age.
Because of the small number of reported cases of primary immune-mediated hemolytic
anemia in cats, it is impossible to specify an association with age or sex.
14. What are the historical clues to immune-mediated hemolytic anemia in cats?
Cats with secondary immune-mediated hemolytic anemia often have historical evidence of
the primary cause. Examples include:
Cats with haemobartonellosis may be infested with Ctenocephalides fells,
Cats with cytauxzoonosis come from specific regions of the United States and may have
history of exposure to Dermacenter variabilis.
The mating of a blood type Atom with a blood type B queen predicts neonatal isoerythrolysis.
The cat may be from an FeLV-infected cattery.
Drugs or vaccines may have been given recently.
15. Describe the clinical presentation of cats with immune-mediated hemolytic anemia.
Nonspecific presenting complaints usually include weakness or lethargy, depression, inappe-
tence, elevated respiratory rate, polyuria, and polydipsia. On rare occasions, the owner notices
pale mucous membranes, icterus, or necrosis of ear or tail tips (cold-agglutinin disease).
Nonspecific physical examination abnormalities may include pale mucous membranes, elevated
heart and respiratory rates, heart murmur, icterus, splenomegaly, low-grade fever, lymphadenopa-
thy, depression, necrosis of ear or tail tips, and weakness.
16. What is pure red cell aplasia?
Pure red cell aplasia develops when erythrocyte precursors are damaged by a primary
immune-mediated reaction. The anemia is usually severe and poorly regenerative, or reticulo-
cytes are absent but platelet and neutrophil numbers are normal. Cytologic examination of bone
marrow cells reveals a decrease in erythroblasts and an increase in small lymphocytes. In a report
of 9 cases, cats were between 8 months and 3 years of age and were seronegative for FeLV anti-
gen. Pale mucous membranes, heart murmur, lethargy, and anorexia were the most common clin-
ical findings. Each cat responded to immunsuppressive therapy with glucocorticoids and
cyclophosphamide or cyclosporine (see question 23).
Microscopic agglutination in a cat with H. felis infection. Note the clumps of red blood cells.
374 immune-mediated Hemolytic Anemia
17. What is the diagnostic plan for cats with suspected hemolytic anemia?
Complete blood cell count, reticulocyte count, platelet count, and total serum protein con-
centration are the minimal diagnostic tests for evaluation of anemia. If a regenerative anemia is
present, the total serum protein concentration is normal; if there is no evidence of body cavity he-
morrhage, hemolytic anemia is most likely. Careful examination of the blood smear is imperative
for evaluation for hemoparasites, spherocytes, schistocytes, microscopic agglutination, or Heinz
bodies, which further direct the diagnostic plan. It is difficult to detect spherocytes cytologically
in cats because normal erythrocytes are small and dense. If agglutination is present, rule out mas-
sive rouleaux formation by mixing I drop of EDTA blood with I drop of saline and repeating the
cytologic examination. Agglutination is not dispersed by saline.
18. What is the only way to prove primary immune-mediated hemolytic anemia?
Exclude all known secondary causes. Use the history to exclude drug- or vaccine-associ-
ated disease. FeLV antigen testing and cytologic evaluation for H. felis are imperative. If H.felis
is not detected cytologically in EDTA blood smears or fresh blood smears, polymerase chain re-
action should be performed (HESKA Diagnostic Laboratory, Fort Collins, CO). Direct Coombs'
testing can detect antibodies on the surface of erythrocytes in cats with no evidence of micro-
scopic agglutination or spherocytes. However, positive results occur with most secondary causes
of immune-mediated hemolytic anemia and have been detected in normal cats. If hyperbiliru-
binemia is present, hemolysis is probably extravascular. If the plasma is pink, intravascular he-
molysis is likely.
19. How is pure red blood cell aplasia diagnosed?
The anemia is usually nonregenerative, but platelet and neutrophil numbers are normal.
Bone marrow aspiration for cytologic evaluation is required to provide evidence of disease.
Erythroblasts are absent or reduced in number, and increased proportions of small lymphocytes
are noted.
20. Why does neonatal isoerythrolysis occur in some kittens?
Toms with blood type A always produce kittens with blood type A, regardless of the blood
type of the queen. Blood type A kittens born to blood type B queens can develop neonatal isoery-
throlysis. Passive transfer of anti-A antibodies from the queen to the kittens in milk results in he-
molytic anemia.
21. How is neonatal isoerythrolysis diagnosed and treated?
Weakness, depression, pale mucous membranes, and pigmenturia are the most common
findings. Diagnosis can be conftrmed by blood-typing the tom and queen. Kittens should be re-
moved from the queen when clinical signs are noted and hand-reared. After 2-3 days, they can be
returned to the queen because at that time passive transfer of antibodies no longer occurs.
Treatment is supportive.
22. Is SLE a common cause of hemolytic anemia in cats?
SLE has rarely been documented in cats. It is primarily an immune complex disease, but cy-
tophilic antibodies directed at circulating erythrocytes or erythrocyte precursors occur in some
cases, resulting in immune-mediated hemolytic anemia. Other common clinical ftndings include
leukocytosis, leukopenia, neutropenia, lymphopenia, fever, neurologic abnormalities, lym-
phadenopathy, polyarthritis, myopathy, dermatitis, oral ulceration, and progessive renal failure.
In Pedersen's study, the cats were positive for antinuclear antibodies in serum, and most re-
sponded to immune suppressive therapy.
23. How is primary immune-mediated hemolytic anemia treated?
There is no consensus for the most appropriate protocol because the disease is so rare in cats.
The following table lists the dosages of drugs that may be considered for treatment.
Drugs Used in the Management ofPrimary immune-mediated Hemolytic Anemia
DRUG DOSE
375
Dexamethasone
Chlorambucil (Leukoran)
Cyclophosphamide(Cytoxan)
Cyclosporine (Sandimmune)
Methylprednisoloneacetate
(Depo-Medrol)
Prednisolone
0.25-1 mg/kg IV once acutely
0.2-0.4 mg/kg POevery 24-48 hr for maintenance
2 mg/cat PO every 24-48 hr for maintenance
50 mg/m'' PO 4 days weekly or every 48 hr acutely
5-10 mg/kg PO every 12-24 hr acutely or for maintenance in
resistant cases
2--4mg/kg 1Mevery 3--4wk for maintenance
2--4mg/kg POevery 12-24 hr for inductionacutely
0.5-2 mg/kg PO every 24-48 hr for maintenance
IV= intravenously, PO= orally, 1M= intramuscularly.
24. How is dexamethasone used?
Many clinicians give rapid-acting dexamethasone intravenously when the diagnosis is made
in an attempt to suppress as quickly as possible macrophage removal of antibody-coated erythro-
cytes. Oral dexamethasone typically is used only if the cat fails to respond to prednisolone or be-
comes resistant.
25. Discuss the role of prednisone or prednisolone.
On day 2 of therapy, one of these drugs is usually started orally as long-term maintenance
therapy. Some clinicians believe that cats respond more consistently to prednisolone. Once
anemia is resolved, the dose is generally decreased by no more than 25% every 2 weeks.
Complete blood count should be performed at each recheck examination. Cats are relatively re-
sistant to the adverse effects of glucocorticoids. However, a reasonable dose for long-term pred-
nisone or prednisolone is 0.5 mglkg orally every 24-48 hours. Most cats do not have evidence of
glucocorticoid-induced illness with this protocol. In cats that are difficult to treat with oral med-
ications, methlyprednisolone acetate (DepoMedrol) may be given intermittently by intramuscular
injection in an attempt to control the disease.
26. When is cyclophosphamide used?
Cyclophosphamide (Cytoxan) is an alkylating agent used with prednisone or prednisolone
for acute management of primary immune-mediated hemolytic anemia and SLE. It should be
considered for use in cats with severe autoagglutination or intravascular hemolysis. Because
vomiting, diarrhea, and bone marrow suppression may occur in cats, cyclophosphamide is not
used for chronic management.
27. Describe the role of chlorambucil.
If an alkylating agent is needed chronically, chlorambucil (Leucoran) should be used. It
should be considered in cats with refractory hemolytic anemia or severe side effects associated
with glucocorticoids.
28. When is cyclosporine used?
Cyclosporine (Sandimmune) typically is used in conjunction with glucocorticoids for acute
management of primary immune diseases, as a rescue drug when other drugs fail, or when the
syndrome is resistant to other treatments.
29. What other agents may be considered?
Danazol and human gammaglobulin have been used to treat immune-mediated hemolytic
anemia in dogs, but little is known about their use in cats. Blood transfusion or hemoglobin
376
replacement products should be administered if clinically indicated. Oxyglobin administration in
cats has been associated with pulmonary edema.
30. What is the prognosis for primary immune-mediated hemolytic anemia?
Generally guarded, particularly if intravascular hemolysis, autoagglutination, or pulmonary
thromboembolic disease is present. In one study of 9 cats with pure red cell aplasia, all responded
to therapy, but most required chronic administration of immunosuppressive drugs. Pulmonary
thromboembolic disease is a common cause of death in dogs with primary immune-mediated he-
molytic anemia; whether this complication is common in cats is unknown.
31. What is the prognosis for secondary immune-mediated hemolytic anemia?
Some causes have a good prognosis. For example, H. felis, vaccines, and drug induction of
secondary immune-mediated hemolytic anemia theoretically should resolve when the inciting
cause is removed and appropriate treatment administered. The prognosis of FeLV-associated he-
molytic anemia is more guarded.
BIBLIOGRAPHY
I. Adams LG, Hardy RM, Weiss DJ, et al: Hypophosphatemia and hemolytic anemia associated with dia-
betes mellitus and hepatic lipidosis in cats. J Vet Intern Med 7:266-271,1993.
2. Bridle KH, Littlewood JD: Tail tip necrosis in two litters of Birman kittens. J Small Anim Pract 39:88-89,
1998.
3. Dunn JK, Searcy GP, Hirsch VM: The diagnostic significance of a positive direct agglutination test in
anemic cats. Can J Comp Med 48:349-353,1984.
4. Faircloth JC, Montgomery JK: Systemic lupus erythematosus in a cat presenting with autoimmune he-
molytic anemia. Fel Pract 11:24-26,1981.
5. Ford S, Giger U, Duesberg C, et al: Inherited erythrocyte pyruvate kinase (PK) deficiency causing he-
molytic anemia in an Abyssinian cat. J Vet Intern Med 6:123,1992.
6. Gunn Moore DA, Day MJ, Graham MEA, et al: Immune-mediated haemolytic anaemia in two sibling
cats associated with multicentric lymphoblastic infiltration. J Fel Med Surg 1:209-214,1999.
7. Heise SC, Smith RS, Schalm OW: Lupus erythematosus with hemolytic anemia in a cat. Feline Pract
3:14-19,1973.
8. Hitt ME, McCaw DL: FeLV infection, hemolytic anemia and hypocellular bone marrow in a cat: Treat-
ment with protein A and prednisone. Can Vet J 29:737-739, 1988.
9. Lusson D, Billiernaz B, Chabanne JL: Circulating lupus anticoagulant and probable systemic lupus ery-
thematosus in a cat. J Fel Med Surg I: 193-196, 1999.
10. Pedersen NC, Barlough JE: Systemic lupus erythematosus in the cat. Feline Pract 19:5-13, 1991.
II. Person JM, Sicard M, Pellerin JL: Autoimmune haemolytic anaemia in the cat: A clinical and im-
munopathological study of five cases. Rev Med Veterin 148:107-114, 1997.
12. Scott DW, Schultz RD, Post JE, et al: Autoimmune hemolytic anemia in the cat. J Am Anim Hosp Assoc
9:53(}-539, 1973.
13. Stokol T, Blue IT: Pure red cell aplasia in cats: 9 cases (1989-1997). J Am Vet Med Assoc 214:75-79,
1999.
14. Utroska B: Autoimmune hemolytic anemia in sibling cats. Vet Med Small Anim Clin 75: 1699-1701,
1980.
73. HEINZ BODIES
Stacy B. Smith, D.V.M., Rick L. Cowell, D.V.M., M.S.,
and Karen E. Dorsey, DV.M.
1. What is a Heinz body?
A Heinz body, also known as a Schumach body or erythrocyte refractile body, is a precipi-
tate or clump of denatured hemoglobin.
2. How are Heinz bodies formed?
Heinz bodies are formed during oxidative injury to erythrocytes. Any chemical, endogenous
or exogenous, that inhibits glutathione reduction within the erythrocyte can lead to denaturation
of hemoglobin.
3. Can Heinz bodies be detected on a routine blood smear?
Heinz bodies sometimes can be seen on blood smears, but generally they do not stain well
with routine hematologic stains. On blood smears they appear as faint or unstained areas near the
edge of, or protruding from, the surface of the red blood cell (RBC).
4. If Heinz bodies are suspected from a blood smear, how can their presence be confimed?
New methylene blue stain can be used to stain another blood smear. Heinz bodies are easily
recognized as dark staining structures near the periphery of the erythrocytes.
Scattered RBCs containing
dark-staining Heinz bodies.
one aggregate reticulocyte.
and one neutrophil (new
methylene blue stain; origi-
nal magnification 250 x).
5. What makes cats more susceptible to Heinz body formation than other species?
The feline hemoglobin molecule contains 8-10 sulfhydryl groups that are readily oxidized,
whereas the hemoglobin of most other species contains 4 or fewer sulfhydryl groups.
6. When Heinz bodies are formed, why do higher numbers continue to circulate in the pe-
ripheral blood of cats compared with other domestic species?
Most species have a sinusoidal spleen, which is efficient at removing RBCs that contain
Heinz bodies. Cats have a nonsinusoidal spleen, which is ineffective at removing such RBCs.
7. When Heinz bodies are seen on a feline blood smear, are they diagnostic of disease?
Heinz bodies can be seen in apparently healthy and nonanemic cats. In normal cats they tend
to be small (0.5- I mm).
377
378
Heinz Bodies
8. How do Heinz bodies contribute to clinical disease?
Heinz bodies are formed during oxidative injury to the erythrocyte. Some cells with Heinz bodies
lyse, whereas others remain in the circulation. Cells that remain in the circulation have a shortened life
span and fragile cell membrane. These characteristics can lead to mild-to-severeanemias.
9. What are the most common pharmacologic agents known to cause Heinz body forma-
tion in cats?
Although numerous agents can lead to Heinz body formation, the most commonly adminis-
tered are acetaminophen, Dl.-methionine, methylene blue, and benzocaine-containing products.
Consecutive-day use of propofol also may induce increased Heinz body formation in cats.
10. Besides drugs, what other mechanisms cause increased Heinz body formation?
Increased numbers of Heinz bodies can occur in association with certain systemic diseases,
including diabetes mellitus, hyperthyroidism, and lymphoma. Specific food additives, including
onion products and propylene glycol, also induce formation of Heinz bodies.
11. What clinical signs are seen with Heinz body-associated problems?
Signs associated with anemia such as pale mucous membranes, weakness, tachycardia,
tachypnea, lethargy, and icterus may occur with Heinz body-associated anemia. The severity of
these signs depends on the acuteness of the developing anemia.
12. How should Heinz body anemias be treated?
The inciting cause needs to be identified. In the case of toxic causes, the involved agent
needs to be discontinued. In systemic illness, the underlying process needs to be definitively di-
agnosed and treated to stop Heinz body formation and associated anemia. Other supportive mea-
sures may be necessary, such as intravenous fluids and possibly blood transfusion.
13. In cats with acetaminophen toxicosis, what other process is affected by oxidative insult?
Iron is converted from the ferrous to the ferric state, thus causing methemoglobinemia.
14. What other clinical signs are seen with acetaminophen-associated methemoglobine-
mia?
Cyanosis, dark brown blood, dyspnea, and facial edema.
15. What additional treatments are necessary in such cases?
Induce vomiting if ingestion occurred less than 2 hours previously, and administer N-acetyl-
cysteine (140 mg/kg intravenously or orally once, followed by 70 mglkg intravenously or orally
every 4 hr for 7 doses) and ascorbic acid (30 mglkg subcutaneously or orally every 6 hr for 7
doses). Oxygen therapy may be necessary in some cases. Sometimes a single intravenous dose of
methylene blue may be indicated.
BIBLIOGRAPHY
I. Andress JL, et al: The effects of consecutive day propofol anesthesia on feline red blood cells. Vel Surg
24:277-282, 1995.
2. Christopher MM: Relation of endogenous Heinz bodies to disease and anemia in cats: 120 cases
(1978-1987). J Am Vel Med Assoc 194:1089-1095, 1989.
3. Christopher MM, et al: Erythrocyte pathology and mechanisms of Heinz body-mediated hemolysis in
cats. Vet PathoI27:299-31O, 1990.
4. Christopher MM, et al: Heinz body formation associated with ketoacidosis in diabetic cats. J Vel Intern
Med 9:24--31, 1995.
5. Ewing PJ. et al: Heinz bodies. In August JR (ed): Consultations in Feline Internal Medicine, 3rd ed.
6. Maede Y. et al: Methionine toxicosis in cats. Am J Vet Res 48:289-292. 1987.
7. Robertson JE, et al: Heinz body formation in cats fed baby food containing onion powder. J Am Vet Med
Assoc 212:1260-1266,1998.
74. HEMOBARTONELLA FELIS
Severine Tasker, B.Sc., B.V.Sc.
1. What type of organism is Hemobartonellafelis?
Hemobartonellafelis is a bacterium currently classified as a rickettsial organism. However,
recent data about DNA sequences have revealed that they are more closely related to the myco-
plasmal organisms, and reclassification has been recommended. In polychrome-stained blood
smears, H. felis is pleomorphic and appears as coccoid, rod, or ring forms. The thickness of a
blood smear and position of the parasite on the erythrocyte may influence the morphology of the
organism, but the coccoid form is most commonly recognized. The coccoid forms range from
0.2-0.8 um in diameter. H. felis appears on the surface of the erythrocyte and around the periph-
ery of the cell; it may be found singly, in pairs, or in chains with severe infestation. Occasionally
organisms may detach and lie free of the erythrocytes.
Wright-Giemsa-stained blood
smear showing epicellular H.
felis organisms attached to ery-
throcytes.
2. How many different strains of H.Jelis have been recognized? Discuss the differences.
Currently two strains of H. felis have been recognized. They vary genetically, in pathogenic-
ity, and in morphologic appearance. The large strain (Ohio strain) is approximately twice the di-
ameter of the small strain; experimental inoculation of cats usually results in severe anemia. With
the small strains studied to date, experimental inoculation of cats results in minimal clinical
signs, and anemia is not usually induced. In addition, dual infection has been documented in nat-
urally infected cats, and experimental infection of cats with both strains results in more severe
clinical disease than either strain alone.
3. What disease is associated with H. felis infection?
H. felis causes feline infectious anemia, a common hemolytic anemia in cats. In recent in situ
hybridization studies, H. felis DNA sequences were physically linked to areas of known cellular
pathology on feline erythrocytes. In addition, the appearance of H. felis DNA in blood coincides
with clinical evidence of experimental infection, and the amount of DNA correlates with the
number of organisms in the blood.
4. Describe the clinical findings of H. felis infection.
Clinical signs are often vague and nonspecific, reflecting the presence of anemia rather than
H. felis infection per se. Anorexia, lethargy, pallor, weight loss, and depression are common.
379
380 Hemobartonella feUs
Intermittent pyrexia is common, particularly in the acute stages of the disease. Splenomegaly and
lymphadenopathy may result from extramedullary hematopoiesis and stimulation of immune re-
sponses. Icterus is rare. Organisms appear in the blood on average about 7-8 days (range = 2-20
days) after experimental inoculation of cats with H. felis. Cycles of parasitemia then occur. One
study reported that males and cats younger than 3 years are more likely to be infected. Other risk
factors include lack of vaccinations, feline leukemia virus (FeLV)-positivestatus, and presence of
anemia. Up to 47.2% of H.jelis-infected cats are FeLV-positive. Cats with Hi felis infection may
be more susceptible to FeLVinfection, FeLVinfection may activate latent H. felis infection, or
the two organisms may be acquired under the same circumstances. An association with feline im-
munodeficiency virus (FlV) infection also was proposed when it was found that 40% of anemic
FlY-positive cats were infected with H. felis. All cats infected with H. felis should be tested for
FeLVand FlV. Cats that are retrovirus-positive may show more severe clinical disease.
5. Describe the pathogenesis of H. felis-associated anemia.
Hemolysis, erythrophagocytosis, andsequestration of red bloodcellsare thethreecommonmech-
anisms.The attachmentof H. felis to erythrocytes results in direct damageto the erythrocyticmem-
brane, causing an increase in erythrocytic osmotic fragility and shortened erythrocyte lifespan.
Erythrocyte damagealsomay exposehiddenerythrocytic antigens or result in an alteration in erythro-
cyticantigens, inducing theproduction of antierythrocytic antibodies. Antibodies alsomay be directed
against the organismitself, resulting in erythrocytic damage as an "innocent bystander." Positive
Coombs' tests and autoagglutinationhave been reported in acute hemobartonellosis, indicatingthe
presence of erythrocyte-bound antibodies. Although someintravascular hemolysis mayoccur bydirect
damage to the erythrocytes, the majority of hemolysis induced by H. felis is extravascular.
Erythrophagocytosis occursin the spleen, liver, lungs, and bone marrow. In addition, erythrocytes are
sequestered in the spleen,wheremacrophages removeH. felis organisms fromtheirsurface("pitting"),
retumingunparasitized cellsintothecirculation. Releaseof sequestered erythrocytes explains therapid
increase inpackedcell volume(PCV)in somecatsafterclearance of H. felis fromthecirculation.
6. Is the parasitemia associated with H. fells infection continuous or intermittent?
After infection with H. felis, cycles of parasitemia occur with an average duration of 6 days
between episodes, which usually last 1-2 days. PCV tends to fall in association with the appear-
ance of H. felis. The clearance of parasites from the blood can be rapid, with reports of a high
level of parasitemia falling to undetectable levels within hours. No relationship has been found
between degree of parasitemia and severity of anemia.
7. How does splenectomy affect hemobartoneUosis in cats?
In animals other than cats, splenectomy usually is required before Hemobartonella spp. pro-
duce clinical disease. In cats, splenectomy has little effect on incubation period or severity of dis-
ease induced by H. felis, although the parasitemia may last longer than in intact cats.
8. How is H.felis transmitted?
Experimental transmission has been demonstrated via the intravenous, intraperitoneal. and
oral routes using blood from infected cats. Vertical transmission from dam to offspring has been
implicated but not proven. Uninfected and infected cats housed together for several months often
show no evidence of horizontal spread of infection. Many believe that infection can be spread by
blood-sucking arthropods, although this theory has not yet been proved.
9. Describe the hematologic abnormalities induced by H. fells,
Infection by H. felis typically causes regenerativeanemia. The severityof anemia depends on
the stage of infection, but PCV usually falls to < 20%, with average values of 15-18%. Aniso-
cytosis, macrocytosis, and polychromasia are common hemopathologic findings. Reticulocytosis
occurs when anemia has been present for 3-5 days. Anemia associated with H. felis infection is
usually categorized as a macrocytic, normochromic regenerative anemia. One study found that
macrocytosis usuallyreflectedconinfectionwith FeLV. In one review, 44% of H. felis-infected cats
Hemobartonella felis 381
had nonregenerative anemia.Whetherthis findingwas due to acuteanemiaor concurrent diseases is
unknown.Alternatively, it is possible that H. felis causes anemia of chronic inflammatorydisease.
Platelet countsare usuallynormal. Changesin the whitebloodcell countsduringhemobartonellosis
are variable. Moderateneutropenia maybe seenafter the onset of anemia,followed by neutrophilia.
10. What are the other major differential diagnoses for regenerative anemias in cats?
Regenerative anemias result from hemorrhage and blood loss or hemolysis. The most
common cause of hemorrhage in cats is trauma, but neoplasia and amyloidosis also may cause
organ or blood vessel rupture. Bleedingdisorders such as coagulopathies are rare in cats. Causes
of hemolysis include hemobartonellosis, oxidative injury to erythrocytes (e.g., acetaminophen,
methylene blue, onions), hypophosphataemia (which can develop during the treatment of dia-
betic ketoacidosis), and immune-mediatedhemolysis secondary to infections (including H. felis
and FeLV) or vaccinations. Hemolytic anemias in cats also result fromdrugs (e.g., trimethoprirn-
sulphonamides, methimazole), neonatal isoerythrolysis, and microangiopathies (e.g., dissemi-
nated intravascular coagulopathy).
11. How is H. felis infection diagnosed?
Because the organismcannot be cultured, diagnosis has been based on demonstrating the or-
ganism cytologicallyon blood smear or DNAin blood by polymerase chain reaction (PCR).
12. Which method best demonstrates the organism in blood films?
Romanowskystains such as Giemsa, Wright, Wright's-Giemsa, and May-Grunwald-Giemsa
and acridine orange (AD) stain can be used (see figure in question I). ADstaining is more sensi-
tive than standardRomanowskystains for Hi felis. but its use is limitedby the need for a fluores-
cent microscope.False-positivediagnoses may result fromartifact generationby improper drying,
improper fixation, or stain precipitation. Only fresh filtered stain solutions should be used. Stain
precipitate usually is found above the plane of focus of the erythrocytes and is more dense and
larger than H. felis organisms.Refractileartifacts, which occur when moisture adheres to the cells
on the film, tend to haveirregularborders and appear colorless when the erythrocytesare in focus.
Other cytologic findings may be confused with H. felis. Because cyclical parasitemia occurs, the
absence of H. felis organismson blood smears does not rule out a diagnosisof hemobartonellosis.
Examinationof multiplefresh blood smears duringthe course of a day or over a fewdays may in-
crease the chances of obtaining a positive diagnosis. It has been shown that ethylenediaminete-
traacetic acid (EDTA) anticoagulant dislodges the organism from the erythrocyte cell surface
within hours, making identificationon blood smears extremelydifficult. It is important, therefore,
to prepare blood smears immediatelyafter collectionof nonanticoagulated blood.
Differentiation of H. felisjrom Other Inclusions and Artifacts on Blood Smear
STRUCTURE SIZE APPEARANCE POSITION
H. felis 0.2-O.8/lm Coccoid, rod-or ring-shaped Onsurface of erythrocyte,
oftenon periphery
Cytauxzoon felis (see 1-4/lm Signetring-shaped, bipolar Within erythrocyte, usually
Chapter75) oneorganism percell
Babesia felis 2.5-3.0/lm Signetring-shaped, round, Usually intracellular
by 4-5/lm pear-shaped. or Maltese
cross-shaped
Stainprecipitate Variable Round Anywhere on bloodsmear
Howell-Jolly body 1-2/lm Round Within erythrocyte
Heinzbody(see 1-2/lm Roundor irregular Within erythrocyte but at
Chapter 73) periphery; mayprotrude
Refractile artifact Variable Variable andclear Appear to be within erythro-
cyteandrefractile asplane
of focus ischanged
382
Hemobartonella /elis
13. How does PCR aid in the diagnosis of hemobartonellosis?
PCR is a technique used to amplify specific fragments of H. felis DNA to detectable
amounts. It is, therefore, an extremely sensitive test. One study claimed that as few as 52 H. felis
organisms can be detected by PeR from blood samples.
14. How does PCR compare with cytologic examination of blood smears?
PCR has been adapted to detect both strains of H. felis and is more sensitive than examina-
tion of blood smears for the detection of H. felis. PCR has been used to identify chronically in-
fected asymptomatic cats, indicating that a positive PCR result does not correlate with the
presence of clinical disease. PCR studies have shown that anemic cats are more likely to be in-
fected with the large strain of H. felis or dually infected with both strains than nonanemic cats.
15. What percentage of cats become chronically infected with H. felis? How can they be
identified?
It is believed that all cats that recover from infection remain chronically infected with H.
felis for an undetermined period, potentially for life. Parasitemia generally is not visible on blood
smears during this period, and chronically infected cats appear clinically normal. Such cats
appear to be in a balanced state in which replication of organisms is balanced by phagocytosis
and removal, although reactivation of infection may occur, resulting in clinical disease. Demon-
stration of the presence of H. felis in the blood is possible by PCR.
16. Which antibiotics are routinely used for the treatment of hemobartonellosis?
Currently the tetracycline group is commonly used. The preferred tetracycline derivative is
doxycycline because of fewer side effects and less frequent dosing than oxytetracycline. The rec-
ommended doxycycline dose is 5-10 mg/kg orally every 24 hours, and therapy should be contin-
ued for 14-21 days, depending on response to treatment. PCR has shown that, despite being
effective for the treatment of anemia, doxycyline does not eliminate the causal organism; treated
cats still become chronic carriers. Enrofloxacin also has been recommended for the treatment of
hemobartonellosis (10 mg/kg/day orally for at least 14 days). Azithromycin is effective against
many Mycoplasma spp., but a one-dose regimen (15 mg/kg orally every 12 hr) was ineffective in
one group of H. felis-infected cats.
17. What other therapies may be of benefit in the treatment of hemobartonellosis?
Supportive care, including whole-blood transfusion, and glucocorticoid therapy for treat-
ment of the immune-mediated component of hemolytic disease have been used in many infected
cats. However, concurrent diseases (e.g., respiratory infections, toxoplasmosis) that may be exac-
erbated by the use of glucocorticoids should be ruled out first. Positive retroviral status does not
preclude the use of glucocorticoids. Some clinicians advocate the use of glucocorticoids only if
the anemia is pronounced or acute in onset and/or accompanied by autoagglutination. The rec-
ommended dose of prednisolone is 2 mg/kg/day orally, with a tapering of dosage toward the end
of therapy. The value of glucocorticoids in the treatment of H. felis is not proven at present.
18. What is the prognosis for cats infected with H. felis?
The long-term prognosis for cats after recovery from uncomplicated hemobartonellosis ap-
pears to be good if a definitive diagnosis is made and therapy is instituted promptly. Recovered
cats become chronic carriers and are believed to be prone to relapse of clinical disease after peri-
ods of illness or stress, although relapse is rare.
19. What is the prevalence of H.felis infection in the cat population?
Reports of the prevalence of H. felis in different cat populations vary greatly from 3.6%
to 28%. This wide range may be due, in part, to the different methods of diagnosis used by
different studies. The cytopathologic diagnosis of H. felis infection by the examination of
blood smears may have both false-positive (stain precipitate, other erythrocytic inclusions)
and false-negative (intermittent parasitemias, collection of blood into EDTA) diagnoses. A
Cytauxwon teUs 383
recent prevalence study using PCR reported that 28.0% of cats with suspected hemobartonel-
losis were found to be infected compared with 14.5% of control cats. The latter group of cats
showed no clinical signs of hemobartonellosis, emphasizing that a positive PCR result does not
equate with clinical disease.
BIBLIOGRAPHY
I. Alleman AR, Pate MG, Harvey IW, et al: Western immunoblot analysis of Haemobartonellafelis with
sera from experimentally infected cats. J Clin Microbiol 37: 1474-1479, 1999.
2. Berent LM, Messick JB, Cooper SK: Detection of Hemobartonella felis in cats with experimentally in-
duced acute and chronic infections, using a polymerase chain reaction assay. Am J Vet Res 59: 1215-
1220, 1998.
3. Berent LM, Messick JB, Cooper SK, et aI: Specific in situ hybridisation of Hemobartonellafelis with a
DNA probe and tyramide signal amplification. Vet Pathol 37:47-53, 2000.
4. Bobade PA, Nash AS, Rogerson P: Feline hemobartonellosis: clinical, haematological and pathological
studies in natural infections and the relationship to infection with feline leukaemia virus. Vet Rec
122:32-36, 1988.
5. Cooper SK, Berent LM, Messick JB: Competitive, quantitative PeR analysis of Hemobartonella felis in
the blood of experimentally infected cats. J Microbiol Methods 34:235-243, 1999.
6. Cotter SM, Hardy WD Jr, Essex M: Association of feline leukemia virus with lymphosarcoma and other
disorders in the cat. J AmVet Med Assoc 166:449-454, 1975.
7. Foley IE, Harms S, Poland A, et aI:Molecular, clinical, and pathologic comparison of two distinct strains
of Hemohartonellafelis in domestic cats. Am J Vet Res 59:1581-1588,1998.
8. Hopper CD, Sparkes AH, Gruffydd-Jones 'I'I, et al: Clinical and laboratory findings in cats infected with
feline immunodeficiency virus. Vet Rec 125:341-346, 1989.
9. Jensen WA, Lappin MR, Kamkar Set aI: Prevalence of Hemobartonellafelis infection in cats. Am J Vet
Res [in press).
10. Rikihisa Y, Kawahara M, Wen B, et al: Western immunoblot analysis of Hemobartonella muris and com-
parison of 16S rRNA gene sequences of H. muris, H.felis, and Eperythrozoon suis. J Clin Microbiol
35:823-829, 1997.
II. VanSteenhouse JL, Millard JR,Taboada J: Feline hemobartonellosis. Comp Cont Educ Pract Vet 15:535-
545, 1993.
12. Westfall OS, Jensen WA, Reagan WJ, et aI: Experimental infection of cats with two Hemobartonella felis
genotypes (California and Ohio variants) and response to treatment with azithromycin. Am J Vet Res
[in press].
75. CYTAUXZOON FELIS
James H. Meinkoth. D.V.M., Ph.D.
1. What type of organism is Cytauxzoon felis?
c. fells is a protozoan parasite somewhat similar to Babesia spp. Unlike Babesia spp., which
typically are limited to erythrocytes in mammalian hosts, organisms of the genus Cytauxzoon
have two tissue phases: piroplasms (found in red blood cells) and schizonts (found in macro-
phages in various organs throughout the body).
2. How do cats become infected with C.felis?
C. felis is a tick-transmitted parasite. Dermacentor variabilis is highly effective at transmit-
ting the organism under experimental conditions and is probably the major vector for natural dis-
ease. Many wild cats, most notably bobcats, have a high prevalence of C. felis infection. Unlike
domestic cats, infection in wild cats is typically subclinical. Tick transmission of the organism
from subclinically infected bobcats to domestic cats produces fatal clinical disease in recipient
domestic cats.
384
Cytauxzoon fells
3. How common is cytauxzoonosis?
The incidence of cytauxzoonosis varies tremendously by geographic location and type of
clientele. Cytauxzoonosis occurs in the southcentral to southeastern United States. In certain
areas of Oklahoma, Missouri, and Arkansas it is not unusual for a practitioner to see 3-4 cases
per week during early summer months. Conversations with practitioners indicate that the geo-
graphic distribution of C. felis may be expanding. As a tick-transmitted disease, cytauxzoonosis
is seen in cats exposed to outdoor, particularly wooded, environments. Even in endemic areas of
the country, veterinarians who work in clinics in urban environments or whose clients maintain
strictly indoor cats are less likely to see the disease.
4. What clinical presentation should cause suspicion of cytauxzoonosis?
Historically, owners report an acute onset of profound depression and anorexia. Cats often
are found outside after failing to return home and are reluctant to move. Prominent findings on
physical examination are marked fever (commonly ~ 106P), dehydration, and icterus. Some
cats appear to be in pain when touched and may have abnormal vocalizations. Severe mental de-
pression and abnormal vocalizations have led some practitioners to consider rabies as the initial
diagnosis. An outdoor cat from an endemic area, particularly in a rural environment, is at risk.
The disease is most prevalent in the early (May-June) and late (September) summer months,
when the tick host is active.
5. What causes the clinical manifestations of cytauxzoonosis?
Most clinical signs are not the result of infected red cells. Cats that are experimentally in-
fected with only the red cell phase of the organism become parasitemic but usually do not show
clinical illness, nor are they immune to subsequent challenge. The widespread infiltration of schi-
zont-infected macrophages in various body tissues produces the profound clinical illness.
Development of schizonts occurs before piroplasms are seen in peripheral blood.
6. Describe the clinicopathologic changes seen in cytauxzoonosis.
Anemia, leukopenia, and thrombocytopenia, alone or in combination, may be detected on
complete blood count. Nonregenerative anemia of variable severity is the most common find-
ing. Profound leukopenia is present in many cats and is more common later in the course of
disease. Thrombocytopenia is often present, more commonly in cats that show severe clinical
signs. Serum biochemical findings are variable. The most common abnormality is hyper-
bilirubinemia.
7. What tests are available to confirm a diagnosis?
Cytauxzoonosis is diagnosed by examining a blood smear and finding the characteristic piro-
plasms in red cells (see figures on following page). Serologic tests and DNA-based tests (e.g.,
polymerase chain reaction) have been used in research settings but are not widely available for
diagnostic use, nor are they usually needed.
8. Does a lack of organisms on blood smear effectively rule out cytauxzoonosis?
Although organisms are frequently found, some cats test negative on initial evaluation of
blood smears. Negative results may be due to various factors:
I. Laboratory personnel must be familiar with identifying C.[elis.
2. The organism is easily overlooked because it is extremely small and can be present in low
numbers. It is best to alert the diagnostic laboratory that cytauxzoonosis is suspected and to re-
quest specifically that the sample be examined for piroplasms. Many practitioners in endemic
areas examine blood smears themselves to get a quick diagnosis.
3. Many cats simply do not have organisms in their blood at the time of initial presentation.
The magnitude of parasitemia typically increases as the disease progresses, and organisms are
common late in the disease course.
CytauxZOOI1 relis 385
Differentiation of C. felis piroplasms from other red
cell inclusions in feline peripheral blood. A. Two
signet ring-shaped C. fells piroplasms (arrows) and
two Howell-Jolly bodies (arrowheads) seen in ery-
throcytes. B, Hemobartonella felis organisms are
seen as distinct chains (arrows) and as less distinct
dots and rings (arrow heads). Hifelis is an extracel-
lular organism, as can be seen from the position of
the chains at the periphery of the cell. Organisms on
the top and bottom of the cell are out of the plane of
focus and appear less distinct. C. Stain precipitate is
seen between red cells as well as on red cells. Stain
precipitate superimposed on top of red cells
(arrows) can mimic red cell parasites (Wright stain,
original magnification x 330)
9. Howcan cytauxzoonosis be diagnosed whenno organismsare evidentonthe blood smear?
The first option is to collect an additional blood sample at a later time since the magnitude of
parasitemia increases as the disease progresses. It is not uncommon for animals to show signifi-
cant parasitemia as few as 24 hours after having been negative on initial blood smear examination.
The second option is to look for the schizont phase of the organism. They occur in macrophages in
many organs of the body, but are most common in the spleen, lung and liver (bone marrow and
lymph nodes are also often affected), Fine needle aspirates (or impression smears in animals that
have died) of these organs often reveal numerous large schizont-laden macrophages.
Impression smear of the spleen
from a cat with cytauxzoonosis.
Twoenlarged macrophages con-
tain C.[elis schizonts. The mac-
rophagic nuclei contain large,
prominent nucleoli (arrows).
The schizonts (outlined by ar-
rowheads) are ill-defined, gran-
ular structures that completely
fill and distend the cell cyto-
plasm (Wright stain, original
magnification x 165).
386 CytauxzOOI1 feUs
10. What is needed to look for C.felis on a blood smear in the clinic?
A reasonably good microscope with an oil immersion objective (100 x) is needed because
the organisms are small. They stain well with routine hematologic stains, such as Diff-Quik. The
other essential ingredient is a well-made blood smear. The smears need to be thin so that a large
area contains red cells that are well spread out and not crowded together. It is nearly impossible
to see the organisms in thick areas of a blood smear where red cells are piled on top of each other.
The smear also must be dried well before staining. One of the biggest problems in examining
for small red cell parasites is the presence of water artifact in the red cells. Water retained in red
cells during the staining process appears as refractile areas that can easily be confused with para-
sites and also obscure identification of anything that may be within the cell. To avoid water arti-
fact, let the smears sit for several minutes (even after they appear to have dried) before
staining-or better yet, dry the smears for 15-20 seconds with a hair dryer. If you still get refrac-
tile areas, replace the fixative portion (the clear solution in Diff-Quik) of the stain set.
Besides water artifact, C. felts organisms must be differentiated from Howell-Jolly bodies,
stain precipitate, and Hemobartonellafelts (see figures with question 8). Howell-Jolly bodies are
larger, round, dark dots that do not have the ring fonn typical of C. felis. Stain precipitate is usu-
ally abundant and seen between the cells as well as overlying the cells. H. felts organisms are
smaller and usually form dots and chains. They can be small rings, but they do not have the nu-
clear area (thick "dot" on the ring) that is typical of C.felis.
11. How is cytauxzoonosis treated?
Recently two drugs have been advocated for treating C.felts infections: diminazine aceturate and
irnidocarb dipropionate. One recent study reported the successful treatment of 5 cats with diminazine
aceturate (2.0 mglkg/wk intramuscularly for 2 doses), a drug used to treat babesiosis and other proto-
zoal diseases. The cats also were treated with heparin and supportive fluid therapy to prevent dissemi-
nated intravascular coagulation. Unfortunately, diminazine is not marketed in the United States.
Based on anecdotal reports and 1 case report, imidocarb dipropionate (5.0 mglkg intramus-
cularly every 2 weeks for 2 doses) has been recommended as a potential therapy. Imidocarb
(lmizol, Schering-Plough Animal Health, Union, NJ) is available in the United States for the
treatment of canine babesiosis. Limited experience with imidocarb in Oklahoma and Arkansas
has not been as promising; further studies are needed to determine efficacy.
12. Describe the prognosis for cats with cytauxzoonosis.
The prognosis for a cat infected with C. felis is grave. Historically, the case fatality rate has
been nearly 100%, regardless of therapeutic attempts. There have been sporadic reports of cats
surviving experimental or natural infection, but they are rare. Recently, some cats that had clini-
cal signs compatible with cytauxzoonosis and C.fells organisms within erythrocytes at presenta-
tion recovered with supportive care in the absence of specific antiprotozoal therapy. Currently,
such cases have been limited to an area of western Arkansas and eastern Oklahoma, prompting
suspicion of the emergence of a less virulent strain. Infected cats are persistently parasitemic but,
once recovered, have not shown recurrence of clinical signs.
13. What are the implications for other cats in the household?
It is not unusual for an owner to lose several cats to cytauxzoonosis in a short period.
However, infection is not spread directly from cat to cat, even when they are housed in close con-
tact. When multiple cats in the household are infected, it is most likely from exposure to the same
population of ticks. Clinical signs in other family cats usually occur within approximately 2-3
weeks of exposure to infected ticks. The only method to determine whether other cats in the
family were infected is to monitor blood smears for organisms. However, this approach has an
extremely low sensitivity early in the course of infection.
14. How can cytauxzoonosis be avoided?
Limiting (or eliminating) exposure to outdoors and good external parasite control are the
best methods of preventing infection with C.felis.
Feline Leukemia Virus 387
15. What public health risks are associated with C. felis?
The organism does not infect people. However. cats can bring ticks that may carry other
zoonotic agents into the human environment.
BIBLIOGRAPHY
1. Greene CE, Latimer K, Hopper E, et al: Administration of diminazeneaceturateor imidocarbdipropi-
onatefor treatment of cytauxzoonosis in cats. J AmVetMedAssoc215:497-500, 1999.
2. KierAB,GreeneCE: Cytauxzoonosis. In GreeneCE(00):Infectious Diseasesof the DogandCat. 2nded.
Philadelphia, WB.Saunders, 1998,pp 470-473.
3. Meinkoth JH, Kocan AA, Whitworth L, et al: Cats survivingnatural infectionwithCytauxzoonfelis: 18
cases (1997-1998). J VetInternMed 14:521-525,2000.
76. FELINE LEUKEMIA VIRUS
Margo L. Men!. D.v.M.
1. What is feline leukemia virus (FeLV)?
FeLV is a pancytotropic virus horizontally transmitted and capable of inducing lyrnphopro-
liferative and myeloproliferative diseases. FeLV belongs to the subfamily Oncovirinae of the
family Retroviridae. Like other retroviruses, FeLV has a single-stranded RNA genome and with
reverse transcriptase infects a host cell and makes a DNA copy of its genome (provirus), which is
inserted into the host genome.
2. How is FeLV transmitted?
The most likely route of transmission of FeLV is continued intimate moist contact, such as
mutual grooming and sharing food and water bowls. The virus can be transmitted to neonates in
utero and through the milk of infected queens. Feline leukemia virus also has been transmitted
via blood transfusions; therefore, FeLV-positive cats should not be used as blood donors.
3. Is FeLVstable in the environment?
FeLV is relatively fragile in the environment. It can be inactivated by ordinary hospital and
household detergents, alcohol, bleach, heating, and drying.
4. Describe the typical signalment of FeLV-lnfected cats.
Cats with FeLV infection tend to be young (1-5 years old) at the time of diagnosis. Kittens
younger than 4 months have an increased susceptibility to developing persistent viremia com-
pared with adult cats.
5. Do all FeLV-infected cats succumb to disease?
The outcome of infection depends on many factors, including host immune response, viru-
lence of the viral strain, dose and duration of exposure, presence of concurrent diseases, and age
of the cat at time of infection. In one study, approximately 30% of virus-infected cats actually de-
veloped disease. Healthy and persistently positive cats had a median survival time of 2 years;
20% were still alive after 3 years. Disease in infected cats usually results from bone marrow or
lymphoid suppression with life-threatening secondary infections or neoplastic manifestations.
6. What are the outcomes of FeLV exposure?
(I) The cat may mount an immune response, clear the virus, and become resistant to future
infection; (2) some cats fail to mount an effective immune response, become persistently viremic,
and succumb to FeLV-associated diseases; or (3) the virus is cleared from the plasma or serum
but persists in a latent form in the bone marrow or lymphatic tissue.
388
Feline Leukemia Virus
7. Describe the six stages of FeLV infection.
The first stage occurs after oronasal exposure and replication of FeLV in tonsillar and
pharygeal lymphoid tissues. In the second stage, the virus infects circulating small lymphocytes
and monocytes. The virus is then amplified in the spleen, gastrointestinal tract, and lymph nodes
which is considered the third stage of infection. The fourth stage involves bone marrow replica-
tion and infection of platelets and neutrophils. Once bone marrow cell lines are infected, periph-
eral viremia occurs (fifth stage). The sixth stage of infection begins with epithelial infection,
which results in excretion of FeLV in saliva and urine. In the sixth stage the cat is contagious.
Stages of Feline Leukemia Virus Infection with Corresponding Test Results
!FA EUSA
STAGE ORGANISMLOCAUZATION TIMING RESULT RESULT
Replication in local lymphoid tissues (tonsil- 2-12 days Negative Negative
lar and pharyngeal with oronasal exposure)
II Dissemination in circulating lymphocytes and 2-12 days Negative Positive
monocytes
III Replication in the spleen, distant lymph nodes 2-12 days Negative Positive
and gut-associated lymphoid tissue
IV Replication in bone marrow cells and intestinal 2-6wk Negative Positive
epithelial crypts
V Peripheral viremia, dissemination via infected 4-6wk Positive Positive
bone marrow derived neutrophils and platelets
VI Disseminated epithelial cell infection with 4-6wk Positive Positive
virus secretion in saliva and tears
IFA= immunofluorescent assay, ELISA= enzyme-linked immunosorbentassay.
AdaptedfromRojkoJL, HardyWD: Feline leukemiavirus and other retroviruses. In SherdingRG(ed): The
Cat: DiseasesandClinical Management, 2nd ed. NewYork, Churchill Livingstone, 1994,pp 263-432.
8. What are the clinical findings of FeLV infection?
FeLV infection results in a wide variety of clinical findings, which result either from the
virus itself or from secondary infections. Clinical manifestations of FeLV result from secondary
infections due to immunosuppression, cytopenias due to retrogression of bone marrow precursor
cells, or myeloid or lymphoid neoplasia. Cytopenias include nonregenerative anemia, thrombo-
cytopenia, neutropenia, and lymphopenia. Secondary infections that appear to be worsened by
concurrent FeLV infection include hemobartonellosis, toxoplasmosis, chronic stomatitis, and res-
piratory tract infections. Lymphosarcoma, fibrosarcoma, and myeloproliferative diseases are
common FeLV-associated neoplasms.
Clinical Findings of Feline Leukemia Virus Infection
Neoplasia
Myeloproliferative
Megakaryocytic leukemia
Myelomonocytic leukemia
Erythroid leukemia
Lymphoproliferative
Lymphosarcoma
Lymphocytic leukemia
Myelosuppression/myelodysplasia
Anemia
Neutropenia
Thrombocytopenia
Immunosuppression and secondary syndromes
Chronic bacterial infections
Calicivirus
Dermatophytosis
Haemobartonella felis
Stomatitis
Toxoplasma gondii
Other related syndromes
Glomerulonephritis
Lymphadenopathy
Osteochondromas
Reproductive failure and abortion
Feline Leukemia Virus 389
9. How is FeLV infection detected?
The most commonly used tests to detect FeLV infection are enzyme-linked immunosorbent
assay (ELISA) and immunofluorescent assay (IFA); both are based on the detection of viral p27
antigen (see table in question 7). ELISA is the recognized screening test for FeLV infection.
Serum is the preferred media for testing individual animals because it gives fewer false-positive
and false-negative results than plasma, blood, tears, or saliva. IFA detects the p27 antigen after
bone marrow infection has occurred and the p27 antigen has been incorporated into leukocytes
and platelets; it is used primarily as a confimatory test.
10. How are ELISA and IFA results interpreted?
There are three major reasons for negative ELISA results: (I) the cat is not infected due to
lack of exposure or development of neutralizing antibodies and elimination of infection; (2) the
cat is undergoing peracute infection; or (3) the cat has cleared the serum but is latently infected.
ELISA-positive cats are undergoing transient infection (stages 1-4; see table in question 8)
or are persistently infected. Thirty percent of ELISA-positive cats may convert to a negative
status, which is believed to be due to transient infection or development of a latent infection.
ELISA-positive cats without clinical signs of FeLV-related disease should be quarantined
from other cats and immediately tested by IFA or retested by ELISA in 4-8 weeks to determine
whether transient or persistent viremia is present. If results of both ELISA and IFA are positive,
the cat probably will be viremic for life. If ELISA results are positive but IFA results are nega-
tive, the cat should be retested by ELISA and IFAevery 4-8 weeks for up to 90 days to determine
whether the ELISA becomes negative or the IFA becomes positive. If false-positive FeLV results
are suspected, you should test serum from the cat with a different FeLV test.
11. What cats should be tested for FeLV infection?
All cats that go outdoors or come from unknown backgrounds should be tested for FeLV in-
fection when first examined by the veterinarian. Cats with clinical disease consistent with FeLV
infection should be tested as part of the diagnostic work-up. Cats vaccinated for FeLV infection
but allowed outdoors should be tested yearly because vaccines do not give complete protection
(see Chapter 81). If a cat has had a presumed exposure, it should be tested 4-8 weeks later and
again 12 weeks later.
12. Can kittens be tested for FeLV infection?
Kittens can and should be tested for FeLV infection. Because ELISA is an antigen test and
not affected by maternal antibodies, kittens should be tested immediately when first evaluated by
the veterinarian-preferably before allowing contact with other household cats.
13. How is latent FeLV infection documented?
Latent infection occasionally is associated with clinical disease, particularly immunosup-
pression and cytopenias. It can be documented by IFA, virus isolation, or polymerase chain reac-
tion on bone marrow cells.
14. What other tests are available for FeLV?
Feline oncornavirus-associated cell membrane antigen (FOCMA) and neutralizing antibod-
ies can be detected in some laboratories but usually are not used clinically for individual cats.
15. Describe the approach to treatment of clinically ill FeLV-positive cats.
First a diagnostic work-up is performed to characterize the clinical illness and to determine
whether the clinical syndrome is related directly to FeLV or to secondary invaders, for which spe-
cific treatment is administered (if available). For example, hemolytic anemia in FeLV-positive
cats may be due to the virus or H. felis, which responds well to doxycycline. Cats with leukemia
or myeloproliferative diseases generally do not respond well to available therapy and have a poor
prognosis. Cats with lymphosarcoma may respond well to chemotherapy protocols, but survival
times vary based on the location of lymphosarcoma and individual responses (see Chapter 68).
390 Feline Leukemia Virus
Bone marrow suppression from FeLV infection often results in nonregenerative anemia or pan-
leukopenia syndrome, which may respond to whole-blood transfusions. Administration of human
granulocytic colony-stimulating factor causes only transient increases in neutrophil count.
16. What other therapies have been used?
Many other therapies have been used in the management of FeLV-related diseases, including
antivirals and immunomodulators. Immunomodulators used most frequently include interferon
alpha, Proprionibacterium acnes (Immunoregulin), acemannan, diethylcarbamazine, and staphy-
lococcal protein A. To date, well-designed studies assessing these therapies are not available, but
beneficial effects have been suggested by some veterinarians. Use of interferon alpha (30 U
orally every 24 hr) has resulted in perceived improvement in clinical well-being in some cats
treated by the author. The antiviral drugs zidovudine (AZT) and 9-(2-phosphonyl-methoxyethyl)
adenine (PMEA) have been assessed for the treatment of FeLV in several studies. Cats with stom-
atitis showed improved clinical status. AZT (5 mglkg orally every 12 hr) may be indicated in
some cats and has minimal side effects.
17. What recommendations can be made for management of FeLV-positive cats?
A single positive FeLV test in a healthy cat should be confirmed by a second test. Once a
healthy cat is found to be persistently Fel.V-positive, the following topics should be addressed
with the owner:
o Prognosis: the median survival for an FeLV-infected healthy cat is 2 years.
o Risk to other cats: the cat should be housed indoors to lessen odds of infecting other cats.
o Secondary invaders: the cat should be housed indoors to lessen the potential for acquiring
secondary infection.
o Public health risk: the risk to humans from contact with FeLV-positive cats appears to be
minimal (see question 19).
o Therapeutic options
o Avoidance of stressful environments (e.g., travel, elective surgery, introduction of a new cat)
o Avoidance of glucocorticoid use, if possible
o Vaccines: if the cat is housed indoors, there is little need for vaccines. If vaccines are indi-
cated, inactivated products should be used.
CONTROVERSIES
18. Should FeLV vaccines be used?
Vaccination for FeLV should be considered for seronegative cats with a high risk of expo-
sure; examples include outdoor cats, indoor-outdoor cats, stray or feral cats, cats in multiple or
open cat households, and cats in households of unknown FeLV status or with FeLV-positive cats
(see Chapter 81). Immunity from FeLV vaccination is reported as fair-to-good and varies with
different vaccines. The FeLV vaccine is considered to be a noncore vaccine by the Advisory
Panel on Feline Vaccines of the American Association of Feline Practitioners. The panel recom-
mends that cats at risk be given a series of boosters as kittens and annual boosters in the left hind-
leg as distal as practical, according to the manufacturer's instructions. The vaccination site
recommendations are aimed at understanding the potential causal link between vaccination and
tumor development. To date, approximately 1-3 in 10,000 cats have developed vaccine-associ-
ated sarcomas after receiving adjuvanted products.
19. What public health concerns are related to FeLV?
FeLV grows in some human cell cultures. However, no study to date has shown human in-
fection with FeLY. In separate studies, people with chronic fatigue syndrome, people with
leukemia, and normal veterinarians had no evidence of FeLV infection. It is possible that a cat
immunosuppressed by FeLV may shed other zoonotic agents in higher numbers than normal cats,
but this theory has not been well documented. FeLV-seropositive cats with clinical signs of dis-
ease should be assessed for potentially zoonotic agents.
Feline Immunodeficiency Virus
BIBIOGRAPHY
391
1. Butera ST, Brown J, Callahan ME, et al: Survey of veterinary conference attendees for evidence of
zoonotic infection by feline retroviruses. JAm Vet MedAssoc 217:1475-1479, 2000.
2. Cotter SM: Management of healthy feline leukemia virus-positive cats. J Am Vet Med Assoc 199: 1470-
1473, 1991.
3. Cotter SM: Feline viral neoplasia. In Greene CE (ed): Infectious Diseases of the Dog and Cat, 2nd ed.
4. Elston T, Rodan I, Flemming DF, et al: AAFP/AFM Vaccination Guidelines. J Am Vet Med Assoc
212:228-241, 1998.
5. Hartmann K, Donath A, Beer B, et al: Use of two virustatica (AZT, PMEA) in the treatment of FIV and
FeLV seropositive cats with clinical symptoms. Vet Immunol ImmunopathoI35:167-175, 1992.
6. Hartmann K, Donath A, Kraft W: AZT in the treatment of feline immunodeficiency virus infection. Part
1. Feline Pract 23:16-21, 1995.
7. Hartmann K, Donath A, Kraft W: AZT in the treatment of feline immunodeficiency virus infection. Part
2. Feline Pract 23: 13-20, 1995.
8. Rojko JL, Hardy WD: Feline leukemia virus and other retroviruses. In Sherding RG (ed): The Cat:
Diseases and Clinical Management, 2nd ed. NewYork, Churchill Livingstone, 1994, pp 263-432.
9. Tizard I: Use of immunomodulators as an aid to clinical management of feline leukemia virus-infected
cats. J Am Vet Moo Assoc 199:1482-1484, 1991.
10. Weiss RC, Cummins JM, Richards AB: Low-dose orally administered alpha interferon treatment for
feline leukemia virus infection. J Am Vet Med Assoc 199:1477-1481, 1991.
II. Wolf AM: CVT update: Feline leukemia virus. Bonagura J (ed): Kirk's Current Veterinary Therapy XIII.
77. FELINE IMMUNODEFICIENCY VIRUS
Paul R. Avery, V.M.D.
1. What is the feline immunodeficiency virus (FIV)?
FIV, first described in 1987in Petaluma, California, is a retrovirus of the subfamilyLentiviridae.
Like all retroviruses, FIV uses the enzyme reverse transcriptase to make a DNA copy from the viral
RNAonce inside an infectedcell. The viral DNAis then integratedinto the host genome, where it per-
sists as proviral DNA. FIV has been the focus of much research because of its importance as a feline
pathogen and also because it serves as a model of human immunodeficiencyvirus (HIV) infection.
2. How common is FIV infection?
FlV occurs worldwide. The seroprevalence of infection within the United States is approxi-
mately 1-4% in clinically healthy cats and increases up to 14%when clinically ill cats are surveyed.
These general incidence rates are relativelyconsistent worldwide, although higher rates of infection
have been reported in regions of Japan and Australia. FIV is more prevalent in free-ranging, intact
male cats. This finding is consistent with the proposed major mode of transmission: bite wounds.
3. Can FlV be transmitted by routes other than biting?
Epidemiologic evidence suggests that bite wounds are the most common means of transmis-
sion. The virus can be isolated from the saliva of infected cats and transmitted experimentally via
biting. FIV also can be isolated from the semen of infected cats, and, in the laboratory setting,
semen and cell culture supernatants can be used to transmit FlY. The significance of venereal trans-
mission in the natural setting is unknown. Like mv, FIV crosses the rectal mucosa when inoculated
experimentally. In utero transmission has been demonstrated in queens chronically infected with
three of the major subtypes of FlY despite the fact that peripheral blood viral loads were quite low
at the time of pregnancy. Lactating queens also have been shown to transmit FIV via milk, and
foster-raising kittens of FlV-infected queens can decrease the transmission rate.
392 Feline Immunodeficiency Virus
The question of whether close, daily contact with an FlV-infected cat in the absence of ag-
gression poses a significant risk of transmission has been addressed in several studies of multi-
cat households. The transmission rate has ranged from 0-100%. A recent well-controlled study
of a closed, 26-cat household over a lO-year period showed a 35%transmission rate of FlY de-
spite a lack of any subjective or objective evidence of aggressive behavior.
4. Describe the progression of disease in FIV-infected cats.
Many investigators have recognized broad phases of FlV infection that are quite similar to
those seen with HIV infection. The duration of each stage varies considerably in infected cats,
but the general phases of progression are consistent. Some feline practitioners have combined
stages 3 and 4, because the two stages are often difficult to distinguish clinically.
STAGE CLINICALSIGNS HEMATOLOGY DURATION DETECTION COMMENTS
J. Acute phase With or without Neutropenia Several days Maybe Signs mild,
fever, lethargy, to weeks ELISA, generally
diarrhea Lymphade- WB,IFA overlooked by
Lymphadenopathy nopathy negative owner
can persist upt080r Youngercats tend
for months morewk to have more
PositivePCR severesigns
1-3 wk after
infection
2. Asympto- Generally none CBC Quite variable; Generally Outwardly
matic carrier generally generally positiveon healthy despite
normal several yr up ELISA, demonstrable
CD4/CD8 to 100yr WB,IFA, immune system
T-cell ratio PCR defects
decreased
3. Persistent Vague signs: with With or without 6 months to Generally Approximately
generalized or without an- leukopenia several yr positiveon one-third of
lymphade- orexia, weight Anemia ELISA, infected cats
nopathy loss, fever of CD4/CD8ratio WB,IFA, present during
unknown origin, decreased PCR this stage
lymphadenopathy FlVmay be
overlooked
4. AIDS-related Secondary bacte- Anemia, leu- 6 month to Generally Approximately
complex rial infections: kopenia, or 1-2 yr positiveon one-half of
oral cavity, upper leukocytosis ELISA, infected cats
respiratory tract, CD4/CD8ratio WB,IFA, present during
Gl tract, skin decreased PCR this stage
Neurologic signs Opportunistic
and neoplasia infections not
less common present
5. AIDS Opportunistic Leukopenia Cats seldom Some par- Only approxi-
infections: herpes Anemia survive more ticularly mately 10%of
and calicivirus CD4/CD8ratio than a few debilitated FlV-infected
Toxoplasma spp. decreased weeks to cats may be cats reach this
Cryptosporidium spp. months at negative on stage
Candidaspp. this stage ELISA,
Mycobacterium spp. WB,IFA,
Demodex spp. but most are
Neurologic disease positive
(- 5% of cats) PositivePCR
Neoplasia
ELISA =enzyme-linked irnmunosorbent assay, WB =Western blot test, IFA =immunofluorescent assay,
PCR =polymerase chain reaction, CBC =complete blood count.
Feline Immunodeficiency Virus 393
5. How is the diagnosis of FIV infection made?
There are four major types of assays to detect FlV infection: antibody enzyme-linked im-
munosorbent assay (ELISA), immunofluorescent antibody assay (lFA), western blot assay (WB)
and polymerase chain reaction (PCR).
6. Which test is used most commonly?
The ELISA, which detects antibodies to FIV, is the most commonly used test and the pre-
ferred screening method. Because virtually all cats that mount an antibody response to FlV
become persistently infected, the presence of antibodies can be used as a surrogate marker to
detect ongoing FlV infection. ELISA tests consist of microwell formats used by diagnostic labo-
ratories and in-house kits generally marketed to the practitioner.
7. Why are WBs used for confirmation?
Western blots also detect antibodies to FIV but are more specific than the ELISA. The speci-
ficity of this assay lies in the fact that the test sera are allowed to react with particular FIV anti-
gens that have been separated on a gel based on size. Antibodies to FIV specifically bind to
antigens in the gel, producing an identifiable band pattern. Depending on which antigens are
used, some FlV-specific antibodies may go undetected. Because this assay is more laborious and
expensive than an ELISA, it is generally reserved as a confirmatory test for a positive ELISA.
8. How accurate are IFAs?
IFAs also detect antibodies to FIV. FIV-infected cells are fixed to a slide as the source of
viral antigen, and any antibodies in the test sample are allowed to bind to these cells. Bound FIV
antibodies are then detected with a fluorescent secondary antibody to feline IgG. Some laborato-
ries report that IFA performs as well as WB and is more reliable than ELISA. Despite this fact,
occasional nonspecific fluorescence has been reported, obscuring both positive and negative re-
sults and requiring interpretation by an experienced operator.
9. Discuss the role of peR.
PCR is an extremely sensitive tool for amplifying and detecting small amounts of viral RNA
or DNA, but its use thus far has generally been restricted to the research setting. The detection of
viral DNA by PCR indicates that the virus has entered the cell and integrated into the host
genome. Viral RNA levels indicate ongoing virus production. RNA measured with PCR has been
used to monitor progression of disease in patients with HIV and FlV (experimental) infections.
RNA levels also have been shown to correlate with disease stage. It is likely that laboratories per-
forming FIV PCR will become more prevalent in the future.
10. What causes false-negative results on the ELISA?
I. Some cats may take 8 weeks or more from the time of infection to produce detectable an-
tibodies. During this window of time, a recently infected cat can be ELISA-negative (no antibod-
ies), yet infectious to other cats. Because of this potential, the American Association of Feline
Practitioners and the Academy of Feline Medicine have issued a recommendation that animals
with known or potential exposure to an FlV-infected animal be retested at least 120 days after the
exposure before being declared FIV negative.
2. User error or test failure is always a potential source of a false-negative result. The test
should be repeated. preferably at a reference laboratory, when the clinical index of suspicion for
FlV infection is high.
3. Some FIV-positive cats can become antibody-negative late in the disease. The proposed
mechanism involves severe debilitation of the immune system.
11. What causes false-positive results on the ELISA?
1. Any screening test, even one with a relatively high specificity, has the potential to pro-
duce false-positive results when used to detect a disease with a low incidence. The positive pre-
dictive value (the percent of positive results that are true positives) of a test decreases as the
394
incidence of the disease decreases. This point is dramatically demonstrated in the case of FlY,
which may have an incidence of 1-4% in healthy cats. One study in Germany comparing the re-
sults of the PetCheck microwell ELISA (IDEXX, Portland, ME) with Western blots for screening
clinically normal cats showed that more than half (59%) of the positive results were false-de-
spite the fact that previous reports had shown that the PetCheck test had a specificity of
98.0-99.6%. This finding clearly demonstrates the importance of confirming a positive ELISA
result, particularly in healthy cats.
2. A false-positive result may be seen in young kittens that received maternal antibodies in
the colostrum. Maternal antibodies are transmitted to the kitten more readily than the virus itself.
These passively acquired antibodies may persist for 4 months or longer and produce a positive
ELISA result that may not reflect the true infection status of the kitten. For this reason, it is rec-
ommended that kittens with a positive ELISA result be retested after 6 months of age.
3. There are reports that infection with feline leukemia virus, feline infectious peritonitis, or
Toxoplasma gondii can result in a false-positive microwell ELISA (PetChek) reading.
12. When should tests other than ELISA be used to aid in the diagnosis of FIV infection?
1. Ideally, any positive ELISA result should be confirmed with a WB, particularly in an oth-
erwise healthy cat, because of the relatively high chance of a false-positive result.
2. In any cat with a high clinical index of suspicion for flY and a negative ELISA test, the
ELISA should berepeated at a diagnostic laboratory or PCR should be performed. In the case of
user error, a repeat ELISA at a reference laboratory may result in a positive result. In the case of
a severely debilitated FlY-infected cat with little or no antibody production, PCR detects the inte-
grated provirus.
3. In kittens that may have passively received colostral antibodies, there are no advantages
to a WB or IFA because they both detect antibodies. The general recommendation in such cases
is to retest the kitten after 6 months of age. PCR may be helpful in young kittens because FlY
DNA should be absent (PCR-negative) if the ELISA test is positive because of the passive acqui-
sition of antibodies.
4. PCR also can shorten the retest interval in cats with an unknown recent history or known
recent contact with an FlY-infected animal. A negative ELISA in this instance may misdiagnose an
infected cat in which antibodies have not yet developed. The general recommendation is to retest
such cats with an ELISA in 12-16 weeks. Because most cats become PCR-positive in the peripheral
blood within 1-3 weeks after infection, the detection of viral DNA via PCR may allow an owner to
decide whether to introduce the cat into a multicat household without having to wait 3-4 months.
13. Which parameters can be monitored over time to predict when a particular FIV-in-
fected cat is likely to progress to AIDS?
Despite intensive monitoring of both naturally occurring and experimental infections, bio-
chemical or hematologic prediction of impending disease progression has proved difficult. None
of the routinely measured parameters in complete blood counts or biochemical panels have been
shown to correlate specifically with disease stage. Cats can have intermittent cytopenias for many
years before developing overt FlY-induced disease. The development of hyperglobulinemia has
been documented in some FlY-infected cats, but this, too, can precede actual disease by years.
The monitoring of CD4+ 'I-cell counts and CD4/CD8 ratios has been quite useful in follow-
ing the progression of HIV infection. Unfortunately, Flv-infected cats demonstrate a relatively
early decrease in CD4+ T-cell counts that can remain low for many years before development of
AIDS. Limited studies to date have not shown an apparent correlation between the CD4/CD8
ratio and clinical stage of infection.
Peripheral plasma viral RNA levels measured via PCR are routinely used to monitor HIY
progression. Evidence in FlY-infected cats suggests that the magnitude of the initial virus levels
can predict the rapidity with which they progress to AIDS-like illnesses. Peripheral viralloads
decrease as cats move from the acute phase to the asymptomatic stage, where they remain rela-
tively stable. Some experimentally infected cats have shown a rise in peripheral viral loads as
Feline Immunodeficiency Virus 395
they begin to progress to the terminal stages of infection. Further work is needed to establish the
utility and practicality of monitoring viral loads over time in naturally infected cats.
14. What are the accepted treatment options for FIV-infected cats?
Clearly. general supportive care and treatment of clinical signs is as important in Flv-posi-
tive cats as in any ill animal. The judicious use of antimicrobials to treat any specific infectious
agent is also critical in these often immunosuppressed animals.
Targeted treatment of the virus itself has been attempted with some of the same antiviral
compounds shown to be effective against HIY. The nucleoside analogs 9-(2-phospho-
nomethoxyethyl) adenine (PMEA) and (S)-9-(3-fluoro-2-phosphonylmethyoxypropyl) adenine
(PMPA) and 3'azido-2',3'-deoxythymidine (AZT; Retrovir, Glaxo-Wellcome, Middlesex, UK)
have been shown to inhibit FlY replication. Protease inhibitors dramatically reduce HIY levels in
humans with AIDS, but, despite the structural similarities between the proteases of HIV and FlY,
none of the currently identified drugs is effective against FlY.
15. Discuss the use of PMEA and PMPA for the treatment of FIV infection.
In one study, 5 of 6 naturally infected cats suffering from a variety of clinical signs (diarrhea,
stomatitis, gingivitis, weight loss) showed moderate-to-marked improvement when treated with
PMEA at 2-20 mg/kg intramuscularly (lM) every 12 hours for 3 weeks. The improvement in oral
lesions may be related to the effect of PMEA on concurrent herpes or calicivirus replication. All
cats had recrudescence of clinical signs weeks to months after discontinuation of treatment, but a
3-week retreatment period induced an even longer clinical remission in some cats. Nine months
after the termination of treatment, 4 of the 5 responding cats were clinically healthy. Side effects
were limited to slight anemia at the highest dose (20 mg/kg lM every 12 hr). In another double-
blind study, Flv-positive cats were treated with either PMEA (10 mg!kg), PMPA (25 mg/kg) or
placebo lM twice weekly for 6 weeks. Both drugs caused significant improvement in stomatitis
and conjunctivitis. PMEA had a greater effect on increasing CD4+ T-cell numbers and improving
the eat's quality of life (based on a modified Karnofsky's score, which is used in humans with
cancer) than PMPA, although PMPA had a more potent effect on decreasing the levels of circu-
lating virus. Side effects were tolerable and consisted of mild anemia, which was more pro-
nounced in PMEA-treated cats. Unfortunately, neither drug is readily available to the practitioner.
16. How effective and safe is AZT in FIV-infected cats?
AZT has been shown to improve general clinical status, increase CD4/CD8 ratios, and im-
prove stomatitis in FlY-positive cats. It is equally effective when given orally or subcutaneously
at a dose of 5 mg/kg twice daily. AZT is administered orally in a gelatin capsule or subcuta-
neously diluted in 5 rnI of isotonic sodium chloride. Cats must be monitored for development of
anemia, which can be associated with Heinz bodies, although the drug is generally well tolerated.
Cats have been maintained on symptomatic therapy for as long as 9 months without significant
side effects. AZT appears to be somewhat less efficacious in controlling FlY-induced symptoms
and viral levels than PMEA and PMPA, but it is currently the only commercially available drug
with demonstrated utility against FlY.
17. Is the development of resistant strains a problem in FIVinfected cats?
Strains of FlY resistant to some or all of the above drugs have been generated in experimen-
tal settings. Thus, as has proved true for HIV, long-term use in cats probably will generate viruses
that are no longer susceptible to nucleoside analog drugs.
18. Discuss the connection between FIV infection and lymphoma.
Most feline lymphomas occur in cats infected with the feline leukemia virus, which, as an on-
covirus, plays a direct role in causing tumors. Lentiviruses such as FlY generally are not considered
direct tumor-inducing viruses, but several studies have identified an increased risk of developing
lymphoma in FlY-infected cats. One epidemiologic study showed that Flv-infected cats had a five-
fold increased risk for the development of lymphoid malignancies compared with FlY-negative cats
396
(FeLY-infected cats had a 60-fold increased risk). In addition, the lymphomas described in FIY-
infected cats share many features. They tend to be high-grade immunoblastic or centroblastic B-
cell tumors, the same type of lymphomas associated with HIV infection. Many theories for an in-
direct role of Flv in tumorigenesis have been proposed, including long-term polyclonal stimula-
tion of B cells, which eventually may result in malignant transformation and decreased tumor
surveillance due to immunodeficiency. A recent study has identified a B-cell tumor in which FlY
virus was integrated at a single site, indicating that the virus had integrated prior to malignant
transformation. This study raises the possibility that, in some flY-associated lymphomas, the
virus may playa more direct role in the induction of neoplastic transformation.
19. What are the prospects for the development of a commercially available FIV vaccine?
The search for a means to protect cats from FlY infection has been ongoing since the initial de-
scription of the virus in the late 1980s. Three basic approaches to vaccination have been studied:
whole inactivated virus, viral subunits, and viral DNA. Despite some of the promising results shown
in the experimental setting, the challenge of developing a universally effective Flv vaccine is great.
Much still needs to be learned about the natural immune response to the virus, but each vaccine
construct sheds more light on the subject and brings protection from FlY infection closer to reality.
20. What are the limitations of whole inactivated virus vaccines?
Whole inactivated virus preparations have induced protective immunity against the particu-
lar virus used in the vaccine but, in general, have shown little or no protection to heterologous
viral isolates. Because of the high degree of variability among FlY viral strains and subtypes. this
technique may not be able to afford a broad enough range of protection against natural infection.
There is also concern that an inactivated whole virus preparation may have the potential to reac-
quire virulence once inside the cat.
21. What is the major problem with viral subunit vaccines?
Because of concerns about whole inactivated virus vaccines. subunit vaccines using portions
of the viral envelope protein have been investigated. Like whole inactivated viruses, the viral sub-
units were capable of inducing high levels of antibodies to FlY, and some have shown partial pro-
tection against FIV infection. However, it appears that some of these subunit vaccines induced
antibodies to FIV that actually enhanced subsequent infection rather than protecting cats. It is
thought that the affinity of the antibodies and the identity of the particular epitopes to which they
bind influences whether they result in protection or enhancement of infection. Clearly this ambi-
guity is a significant obstacle in the development of viral subunit vaccines.
22. What are the potential advantages of viral DNA vaccines?
The third approach that has been studied is the relatively new technique of using viral DNA
as a vaccine. Molecular clones of FlY in which specific regions have been deleted to make them
replication-defective have been used to vaccinate cats. There was evidence of significant protec-
tion when the cats were challenged with the same virus used as the vaccine, and in cats that were
not completely protected, the severity of clinical signs was reduced. DNA vaccination holds par-
ticular promise because it can be manipulated to stimulate cellular and humoral arms of the
immune system, both of which are important in controlling retrovirus replication.
BIBLIOGRAPHY
I. Addie DO, Dennis JM, Toth S, et al: Long-term impact on a closed household of pet cats of natural in-
fection with feline corona virus, feline leukaemia virus and feline immunodeficiency virus. Vet Rec
146:419-424,2000.
2. Barr MC: FIV, FeLV, and FIP: Interpretation and misinterpretation of serological test results. Semin Vet
Med Surg II: 144-153, 1996.
3. Beatty JA, Callanan 11, Terry A, et aI: Molecular and immunophenotypical characterization of a feline
immunodeficiency virus (FIV)-associated lymphoma: A direct role for FlV in B-Iymphocyte transfor-
mation? J Virol72:767-77 I. 1998.
Ehrlichiosis 397
4. Egberink H, Borst M, Niphuis H, et al: Suppression of feline immunodeficiency virus infection in vivo
by 9-(2-phosphonomethoxyethyl) adenine. Proc NatlAcad Sci 87:3087-3091, 1990.
5. Elder JH, Dean GA, Hoover EA, et al: Lessons form the cat: Feline immunodeficiency virus as a tool to
develop intervention strategies against human immunodeficiency virus type I. AIDS Res Human
Retrovir 14:797-801,1998.
6. Hartmann K, Kuffer M, Balzarini J, et al: Efficacy of the acyclic nucleoside phosphonates FPMPA and
PMEA against feline immunodeficiency virus. J AIDS Human Retrovirol 17:120-128, 1997.
7. Hartmann K: Feline immunodeficiency virus infection: an overview. Vet J 155:123-137, 1998.
8. Hartmann K, Donath A, Kraft W: AZT in the treatmant of feline immunodeficiency virus infection.
Feline Pract 23:13-21,1995.
9. Hosie MJ, Jarrett 0: Analysis of the protective immunity induced by feline immunodeficiency virus vac-
cination. Adv Vet Med 41:325-333,1999.
10. Hosie MJ, Flynn IN, Rigby MA, et al: DNA vaccination affords significant protection against feline im-
munodeficiency virus infection without inducing detectable antiviral antibodies. J Virol 2:7310-7319,
1998.
11. Novotney C, English RV, Houseman J, et al: Lymphocyte population changes in cats naturally infected
with feline immunodeficiency virus. AIDS 4:1213-1218,1990.
12. O'Neil LL, Burkhard MJ, Diehl U, et a1: Vertical transmission of feline immunodeficiency virus. AIDS
Res Human Retrovir 1:171-182,1995,
13. Pedersen NC, Barlough JE: Clinical overview of feline immunodeficiency virus. J Am Vet Med Assoc
199: 1298-1305, 1991.
14. Shelton GH, Grant CK, Cotter SM, et a1: Feline immunodeficiency virus and feline leukemia virus infec-
tions and their relationships to lymphoid malignancies in the cat: A retrospective study (1968-1988).
J AIDS 3:623-630, 1990.
15. Torten M, Franchini M, Barlough JE, et al: Progressive immune dysfunction in cats experimentally in-
fected with feline immunodeficiency virus. J Viro165:2225-2230, 1991.
78. EHRLICHIOSIS
Cynthia J. Stubbs, D.V.M., M.S.
1. What are Ehrlichia spp.?
Ehrlichia spp, members of the family Rickettsiaceae, are pleomorphic, gram-negative, ob-
ligate intracellular microorganisms. Morulae, which are intracytoplasmic inclusions formed by
clusters of the rickettsia, can be found transiently in mononucler cells, neutrophils, eosinophils,
or platelets during acute illness. Animals known to be naturally infected by Ehrlichia spp. in-
clude cats, dogs, horses, ruminants, mice, and humans.
Mononuclear cell of an Ehrlichia
canis and E. risticii seropositive cat
containing a cluster of organisms
morphologically consistent with
Ehrlichia spp.
398 Ehrlichiosis
2. What evidence indicates that cats become infected with Ehrlichia spp.?
In 1986, the first naturally occurring case of feline ehrlichiosis was documented in a cat in
France by Charpentier and Groulade. Intracytoplasmic inclusion bodies in neutrophils,
eosinophils, and mononulcear cells that resemble Ehrlichia spp. morulae have been detected in
naturally exposed cats in several countries, including France, Kenya, Sweden, Brazil, Thailand,
and the United States. In one study, electron microscopic assessment of these Ehrlichia-like
boides revealed organisms from 0.54-1.3 urn, intermediate in size between E. canis and E. sen-
netsu morulae. In other studies, morphologic descriptions of morulae were not available. To date,
the only sequenced isolate from a domestic cat was genetically identical to the Ehrlichia spp. that
causes human, canine, and equine granulocytic ehrlichiosis.
Cats have been infected experimentally with E. risticii, the causative agent of Potomac horse
fever, and E. equi, which causes equine ehrlichiosis. Experimental infections of cats with E. canis
or other ehrlichial species have not been attempted. Based on the reports of morulae in different
cell types, genetic sequencing, and results of experimental infection studies, it appears that cats
may be infected by more than one ehrlichial species.
3. How common is feline ehrlichiosis?
Internationally, antibodies that react with Ehrlichia antigens have been detected in serum of
cats from Sweden, Africa, France, and the United States. In separate reports, seropositive cats
were detected in Maryland, Colorado, Virgina, and California. In a national seroprevalence study
of 599 cats, antibodies to E. canis and/or E. risticii were detected in 29.2%; positive cats were
identified throughout the United States. Of these cats, 4.4% were seropositive for E. canis alone,
28.5% for E. risticii alone, and 3% for both species.
4. What are the most common clinical signs of feline ehrlichiosis?
A wide variety of clinical signs has been reported. The most common is fever. Other clinical
signs include anorexia, weight loss, attitude changes (lethargy, depression, general malaise, irri-
table disposition), gastrointestinal signs (vomiting or diarrhea), pain (generalized hyperesthesia,
lameness, or arthralgia), ocular discharge, pale mucous membranes, dyspnea. splenomegaly, and
lymphadenopathy. Less commonly reported clinical signs include dehydration, gingivitis,
polyuria, polydipsia, and tachypnea.
S. How is ehrlichiosis definitively diagnosed in cats?
Demonstration of intracytoplasmic inclusion bodies typical of Ehrlichia spp. within blood
leukocytes makes a definitive diagnosis of feline ehrlichiosis. However, in most ehrlichial
infections of other species, morulae usually occur in detectable numbers only transiently in
the acute phase of illness. In addition, detection of morulae cannot be used to determine
which species of Ehrlichia is involved.
Polymerase chain reaction (PCR) has been used to document ehrlichial DNA in the blood
of cats. Currently PCR for Ehrlichia spp. is commercially available in at least two labora-
tories (HESKA Diagnostic Laboratory, Fort Collins, CO; North Carolina State University,
Raleigh, NC). As more cats are assessed by PCR, it will be easier to determine which
Ehrlichia spp. infect cats.
6. On what evidence is a presumptive diagnosis of ehrlichiosis based?
Presumptive diagnoses have been based on the combination of serum Ehrlihcia antibody de-
tection (Prototek Reference Laboratory, Chandler, AZ), appropriate clinical signs, exclusion of
other causes of disease, and response to treatment with antirickettsial drugs. However, because
positive serologic results are seen in healthy cats as well as clinically ill cats, a diagnosis of ehrli-
chiosis should not be based on serologic results alone. A fourfold rise in the acute and convales-
cent titers also may correlate with recent or active infection. To date, no consistent pattern of titer
duration has been noted in cats with ehrlichiosis. As in dogs, it appears that clearance of serum
antibodies to Ehrlichia spp. is prolonged in some cats.
Ehrlichiosis 399
7. What laboratory abnormalities are most commonly associated with feline ehrlichiosis?
The most frequent hematologic change is nonregenerative anemia. Several cats with feline
ehrlichiosis have had regenerative anemia, but they also were infected with Hemobartonella felis.
Thrombocytopenia, neutrophilic leukocytosis, general leukocytosis, lymphocytosis, monocyto-
sis, leukopenia, neutropenia, and lymphopenia also have been reported in some cats,
Hyperglobulinemia is a common biochemical profile abnormality in cats with feline ehrli-
chiosis. The increased globulin level has not been well described in the literature, but both mono-
clonal and polyclonal gammopathies have been reported. Other reported changes in the
biochemical profile include elevated blood urea nitrogen, elevated creatinine, hyperbilirubinemia,
hypoalbuminemia, hyperglycemia, hypokalemia, and elevated creatine phosphokinase activity.
8. Describe the pathogenesis of feline ehrlichiosis.
The pathogenesis is unknown, but based on clinical and laboratory findings, it is probably
similar to acute E. canis infection in dogs.
9. How are Ehrlichia spp, transmitted?
The route of transmission to cats is currently unknown. Most ehrlichial species are tick-
borne; cats in Kenya and the cat from Sweden were infested with Haemaphysalis leachi and
Ixodes ricinus. respectively. Whether other arthropods or transport hosts are involved is not
known. It is plausible that feline ehrlichiosis can be transmitted by blood transfusions, as re-
ported in dogs. Because ehrlichial infection of cats appears to be common on the basis of sero-
logic studies, it may be prudent to screen blood donor cats for antibodies or DNA by PCR.
Further studies are needed to determine the mode of transmission to cats.
10. How is feline ehrlichiosis treated?
Antirickettsial drugs, including tetracycline, doxycycline, chloramphenicol, and imidocarb
dipropionate, can be used to treat feline ehrlichiosis. Doxycycline at 5 mglkg every 12 hours for
21 days is a commonly used protocol. Some cats require a longer course of treatment (4-6
weeks) because of recurring laboratory abnormalities. Two intramuscular doses of imidocarb
dipropionate (5 mglkg) 14 days apart appear to be safe and effective.
11. When should I do a trial of tetracycline therapy?
When a presumptive diagnosis of ehrlichiosis is based on the combination of serum antibody
detection, appropriate clinical signs, and exclusion of other causes of disease, a trial of tetracy-
cline is indicated. In dogs, clinical signs of ehrlichiosis develop before antibodies can be de-
tected. Thus, treatment should be considered if the cat is acutely ill with appropriate clinical
signs even if seronegative. It is possible that acutely infected seronegative cats are PCR-positive.
12. What public health concerns are associated with feline ehrlichiosis?
Both cats and people can be infected with a granulocytic strain of Ehrlichia spp. Dogs can
harbor E. chaffeensis, the causative agent of human monocytic ehrlichiosis that cross-reacts sero-
logically with E. canis. Cats are not known to be infected by E. canis but commonly have E.
canis antibodies; thus, cats also may be infected with E. chaffeensis. Further work is required to
determine whether cats are a reservoir for Ehrlichia spp. Cats may serve to bring infected vectors
into the human environment (see Chapter 90).
BIBLIOGRAPHY
I. Almosny NRP, de Almeida LE, Moreira NS, et al: Ehrlichiose clinica em gato (Felis canis). R Bras Ci
Vet 5:82-83, 1998.
2. Artursson K, Malmqvist M, Olsson E, et al: Diagnosis of borreliosis and granulocytic ehrlichiosis of
horses, dogs, and cats in Sweden. Svensk Veterinartidning 45:331-336, 1994.
3. Beaufils JP, Marin-Granel J, Jumelle P: Ehrlichia infection in cats: A review of three cases. Pratique
Medicale Chirurgicate de l' Animale de Compagnie 30:397--402, 1995.
400 Nonregenerative Anemia
4. Bjoersdorff A, Svendenius L, Owens 1, et al: Feline granulocytic ehrlichiosis: A report of a new clinical
entity and characterisation of the infectious agent. 1 Small Anim Pract 40:20-24, 1999.
5. Bouloy RP, Lappin MR, Holland Cl, et al: Clinical ehrlichiosis in a cat. 1 Am Vet Med Assoc 204:
1475-1478,1994.
6. Buoro 181, Atwell RB, Kipoon lC, et al: Feline anaemia associated with Ehrlichia-Iike bodies in three
domestic short-haired cats. Vet Rec 125:434--436, 1989.
7. Buoro 181, Nyamwange SB, Kiptoon lC: Presence of Ehrlichia-Iike bodies in monocytes of an adult Ii-
oness. Feline Pract 22:36-37, 1994.
8. Charpentier F, Groulade P: Probable case of ehrlichiosis in a cat. Bull Acad Vet France 59:287-290, 1986.
9. Dawson JE, Abeygunawardena I, Holland Cl, et al: Susceptibility of cats to infection with Ehrlichiaris-
ticii, causative agent of equine monocytic ehrlichiosis. Am 1 Vet Res 49:2096-2100, 1988.
10. Jittapalapong S, lansawan W: Preliminary surve on blood parasites of cats in Bangkhen District Area.
Kasetsart 1 Nat! Sci 27:330-335, 1993.
I I. Lewis GE, Huxsoll DL, Ristic M, et al: Experimentally induced infection of dogs, cats, and nonhuman pri-
mates with Ehrlichia equi, etiologic agent of equine ehrlichiosis. J Am Vet Med Assoc 36:85-88, 1975.
12. Matthewman LA, Kelley PI, Wray K, et al: Antibodies in cat sera from southern Africa react with anti-
gens of Ehrlichiacanis. Vet Rec 138:364-365, 1996.
13. Peavy GM, Holland Cl, Dulta SK, et al: Suspected ehrlichial infection in five cats from a household. 1
Am Vet MedAssoc 210:231-234,1997.
14. Stubbs CJ, Holland Cl, Reif IS, et al: Feline ehrlichiosis. Compend Contin Educ Pract Vet 22:307-318.
2000.
79. NONREGENERATIVE ANEMIA
DinaA. Andrews, D.V.M., ph.D.
1. Define nonregenerative anemia.
Nonregenerative anemia is defined by a decrease in red cell mass with an inadequate release of
normal immature red blood cells into the peripheral circulation by the bone marrow. In recognizing
nonregenerative anemia, it is important to know the duration of the anemia because the bone
marrow requires approximately 5 days to respond adequately to a decrease in red cell density.
2. Howis nonregenerative anemia identified on a peripheral blood smear?
Nonregenerative anemia is identified on a peripheral blood smear by a decrease in red cell
density that is not accompanied by polychromasia in the monolayer portion of the smear. Poly-
chromatophils correlate with aggregate reticulocytes, the most accurate marker of recent bone
marrow regeneration in cats. Anisocytosis, nucleated red blood cells, and Howell-Jolly bodies
without concurrent polychromasia are not specific indicators of regeneration.
3. What abnormal red cell morphologies provide information about the pathogenesis of
nonregenerative anemia?
Nonpolychromatophilic macrocytes (large red cells) are associated with feline leukemia virus
(FeLV) infection. Macrocytes also are identified in normal kittens less than 5 weeks of age.
Nucleated erythroid precursors in circulation without accompanying polychromasia can be seen
with myeloproliferative disease, often secondary to FeLY. Microcytes (small red cells) can indi-
cate an early iron deficiency anemia. Poikilocytosis (cells of different shapes) are often present in
iron deficiency anemia because of oxidative damage to the red cell membrane. Although not
pathognomonic, dacryocytes (teardrop-shaped red cells) have been associated with myelofibrosis.
4. Howis nonregenerative anemia identified by a complete blood count (CBC)?
Red cell parameters indicate a decreased hematocrit or packed cell volume. The red cell in-
dices are most commonly normocytic and normochromic. An inflammatory leukogram can provide
Nonregenerative Anemia 401
support for anemia due to a wide variety of infectious, noninfectious, and neoplastic conditions.
Because iron sequestration and altered iron kinetics are common to these anemias, the possibility
that microcytic anemia may develop in long-standing disease processes must be considered but is
not a common finding.
5. Can red cell indices help to narrow the ditTerentiailist?
Macrocytic/normochromic anemias are characteristic of FeLV infection. Minimal-to-mild
macrocytic/normochromic anemias also may be seen in young kittens < 5 weeks old. Microcytic/
normochromic and microcyticlhypochromic anemias are characteristic of iron deficiency.
Normocytic/normochromic anemias are nonspecific and can be seen with a variety of hypoprolif-
erative anemias due to inflammation and chronic disease processes. A microcytic/normochromic
anemia can be found in humans with long-standing disease processes, although this finding has
not been documented in cats.
6. What laboratory tests confirm the presence of nonregenerative anemia?
A highly sensitive and cost-effective way to detect nonregenerative anemia is microscopic
evaluation of the monolayer portion of a peripheral blood smear (see above). If polychromasia is
questionable on the peripheral blood smear, an absolute reticulocyte count (using a vital stain,
such as new methylene blue) should be performed by a laboratory familiar with the identification
of feline reticulocytes. Cats have both aggregate and punctate reticulocytes. The aggregate reticu-
locytes mature into punctate reticulocytes within 12 hours, whereas punctate reticulocytes mature
slowly over 10-14 days. Aggregate reticulocytes are the most accurate indicator of recent bone
marrow response in cats, and their absolute numbers should be reported for categorizing an
anemia as regenerative or nonregenerative. Although punctate reticulocyte numbers may be re-
ported, they represent a cumulative indicator of bone marrow response because of their lengthy
maturation time in the circulation and should not be used to evaluate recent bone marrow response.
Aggregate (A) and punctate (B) reticulocytes in a cat with regenerative anemia.
7. What reticulocyte count is considered nonregenerative?
Cats do not respond as vigorously to anemias as humans and dogs, and their bone marrow re-
serves are small. Feline aggregate reticulocytes in health range from 0.0-0.4% of circulating ery-
throcytes when several reported ranges are averaged. Any increase in this percentage is considered
indicative of regeneration. Caution must be used in interpreting the reticulocyte percentage as in-
dicative of a regenerative reponse because this value does not correct for the degree of anemia. An
absolute reticulocyte number is the most accurate means to evaluate regeneration. An absolute
reticulocyte count of 0-50,000/111 is normal in cats, and an absolute reticulocyte count> 50.000/111
402
Nonregenerative Anemia
is considered indicative of regeneration. In interpreting both reticulocyte percentage and absolute
reticulocyte count, the duration of the anemia and appropriateness of the regenerative response
relative to the degree of anemia must be taken into consideration. For example, in an anemia of
undetermined origin that has persisted for several weeks, a mild increase in aggregate reticulo-
cyte numbers would not be considered an appropriate regenerative response. Bone marrow aspi-
ration should be done to evaluate production of the erythroid series.
8. When can nonregenerative anemia bediagnosed confidently in a newly presenting patient?
If the underlying pathology of the disease process can support the finding of nonregenerative
anemia (e.g., chronic renal failure), the diagnosis can beconfidently made on initial presentation.
If the patient presents with no obvious disease process on physical examination and no CBC or
chemistry abnormalities that support nonregenerative anemia, the CBC should berepeated to con-
firmthe presence of the anemia for longer than 4-5 days with no evidence of regeneration. If the
nonregenerative anemia is deemed persistent, a bone marrow aspirate is warranted. Establishing a
baseline aggregate reticulocyte count in patients with nonregenerative anemia is recommended so
that any small increase in reticulocyte numbers due to treatment can be recognized on serial CBCs.
9. How long does nonregenerative anemia take to develop?
The time frame depends on the cause of the anemia. If the nonregenerative anemia is due to
an acute inflammatory process (e.g., abscess), a decrease in red cell mass can develop within 4
days because of an increased rate of red cell destruction without an appropriate bone marrow re-
sponse. Conversely, if the anemia is due to a long-standing disease process such as chronic renal
failure, failure of the bone marrow to replace normally senescent red cells during their 80-day
life span results in a more slowly evolving anemia.
10. What general categories of disease can cause nonregenerative anemia?
Distinguishing whether nonregenerative anemia is a singular abnormality in the CBC or ac-
companied by other cytopenias is extremely helpful in determining the cause of the anemia. This
distinction generally differentiates anemia due to secondary or extramarrow causes from anemia
due to intramarrow disease, respectively. As always, there are exceptions and overlap with the
manifestations of certain disease processes, particularly FeLV and feline immunodeficiency virus
(FlV) infections. Recognition of abnormal red cell morphologies, classification of the severity of
anemia, and description of red cell indices are also helpful criteria.
11. What diseases result in selective nonregenerative anemia without cytopenias?
Important differential diagnoses include FeLV-induced selective red cell aplasia, iron defi-
ciency anemia, acute inflammation, and chronic disease processes, including renal disease, en-
docrine disorders, immune-mediated disease, and neoplasia. If the anemia is severe, congenital
or acquired pure red cell aplasia also should be considered.
Secondary Bone Marrow Failures: Nonregenerative Anemia without Cytopenias
SEVERITY OF RBC
CAUSE ANEMIA RED CELL INDICES MORPHOLOGY BONE MARROW
FeLV-induced Mild to severe
selectiveRBC
aplasia
Anemia of acute Mild
intlanunation
Anemia of chronic Mild
disease
Normocytic-
normochromic
or
Macrocytic-
normochromic
Normocytic-
normochromic
Normocytic-
normochromic
Normal:
macrocytes
Normal
Normal
Variable: ineffective
erythropoiesis,
erythroid hypo-
plasia, absence of
RBC precursors
Erythroid hypoplasia
Secondary Bone Marrow Failures: Nonregenerative Anemia without Cytopenias (Continued)
SEVERITY OF RBC
Renal disease
Iron deficiency
anemia
Red cell aplasia
Acute hemorrhage
(first 4 days)
Mild to mode-
rate
Mild (early)
Mild to mode-
rate (late)
Usually severe
Variable
Normocytic-
normochromic
Normocytic-
normochromic
(early)
Microcytic-
normochromic
(late)
Normocytic-
normochromic
Normocytic-
normochromic
Normal; with
or without
Burr cells
Microcytes
Poikilocytosis
(red cell frag-
mentation)
Normal
None
Left-shiftederythroid
series, ineffective
erythropoiesis
Absence of RBC
precursors, other
marrowelements
normal
Normal
RBC=red bloodcell, FeLV =felineleukemia virus.
12. What diseases cause nonregenerative anemia with leukopenia and/or thrombocy-
topenia?
The presence of multiple cytopenias indicates injury or destruction to the stem cell popula-
tion in the bone marrow. The general category of myelophthisic disorders encompasses bone
marrow failure or dysfunction due to abnormal proliferation of any or multiple cell lines, includ-
ing bone marrow-occupying metastatic disease. Myeloproliferative disorders involve the clonal
proliferation of one or more nonlymphoid precursors (erythroid, granulocytic, monocytic, mega-
karyocytic, or fibroblastic series) and are more common in cats than in dogs. An underlying FeLV
infection is suspect in most cases. Circulating atypical or neoplastic cells mayor may not be pre-
sent. Infiltration of the marrow due to lymphosarcoma or primary lymphoid leukemias (acute or
chronic) can cause similar marrow suppression. Myelofibrosis also serves as a space-occupying
lesion in the bone marrow, effectively crowding out proliferating stem cells.
Myelodysplastic syndromes are characterized by multiple peripheral cytopenias in the face
of a hypercellular marrow and are considered a preleukemic condition of the bone marrow,
probably caused by FeLV. Abnormal morphology of the red cell, white cell, and/or megakary-
ocytic lineage is found in the bone marrow, and the functional result is ineffective hemato-
poiesis. Direct injury to the stem cell population due to administration of toxic drugs (e.g.,
chloramphenicol, griseofulvin, azathioprine) or idiopathic immune-mediated destruction of
stem cells (aplastic anemia) also can cause primary bone marrow failure. Certain infections
(e.g., cytauxzoonosis, ehrlichiosis) are also documented to cause nonregenerative anemias in
addition to other cytopenias in cats.
Primary Bone Marrow Failure: Nonregenerative Anemia with Other Cytopenias
SEVERlTYOF RBC
FeLV-related: stem Moderate Normocytic- Normal Hypocellular
cell damage to severe normochromic macrocytes
Macrocytic-
normochromic
Other viral diseases Mild to mode- Normocytic- Normal Hypocellular
(e.g., FIP, FlV) rate normochromic
Table continued on/allowing page
Primary Bone Marrow Failure: Nonregenerative Anemia with Other Cytopenias (Continued)
SEVERITY OF RBC
CAUSE ANEMIA REDCELLINDICES MORPHOLOGY BONEMARROW
Myelophthisic Usually severe Normocytic- Variable: normal, Hyperplastic mega-
disorders (myelo- normochromic atypical/blasts, lobiastic changes
proliferative dis- Macrocytic- normal RBCs > 30% blasts in bone
ease, lymphoid normochromic with no poly- marrow
leukemia, Iym- chromasia
phosarcoma)
Myelodysplastic Mild to severe Normocytic- Normal Normal to hyper-
syndrome normochromic cellular
Macrocytic- Ineffective erythro-
normochromic poiesis
Dyserythropoiesis,
dysgranulopoiesis,
andlor dysthrom-
bopoiesis
Myelofibrosis Severe Normocytic- Normal Hypocellular
normochromic dacryocytes
Aplastic anemia Severe Normocytic- Normal Hypocellular
normochromic
Feline ehrlichiosis Mild to mode- Normocytic- Morulae in mono- Not examined
rate normochromic nuclear cells
Cytauxzoonosis Mild to mode- Normocytic- Piroplasms of Not examined
rate normochromic C.feUs in
erythrocytes,
toxic neutrophils
Drugs/chemicals Severe Normocytic- Normal Hypocellular
normochromic
RBC=red blood cell, FeLY=feline leukemia virus, FlP =feline infectious peritonitis, Flv =feline immuno-
deficiency virus.
13. What is the most common cause of nonregenerative anemias in cats?
There is a high incidence of nonregenerative anemias in cats with FeLV and FlV infections.
Any cat with anemia should be tested for these viruses. Anemias caused by chronic disorders
(e.g., inflammation, renal disease, neoplasia, immune-mediated diseases, endocrine disease, liver
disease) are also common causes ofnonregenerative anemia in cats.
14. Describe the classic profile of anemia due to chronic inflammation or chronic disease?
Such anemias are commonly described as mild (packed cell volume [peV] > 20%), normo-
cytic, and normochromic, with no evidence of regeneration (0-50,000/fll reticulocytes) and no
erythrocytic morphologic abnormalities.
15. Describe the pathogenesis of anemia of chronic disease.
Anemias resulting from chronic disease are not well understood but are believed to share a
common pathogenesis. Sequestration of iron in bone marrow macrophages, decreased response
to erythropoietin by bone marrow, and decreased red cell life span are significant contributors.
Altered iron handling is also involved based on common findings of decreased iron absorption by
the gut, decreased serum iron, decreased serum iron-binding capacity, and increased tissue iron
stores. Although some of these features are similar to those associated with true iron deficiency,
classic hematologic features of iron deficiency anemia, such as microcytosis and hypochromasia,
do not usually develop.
16. How do I treat anemia due to chronic disease?
Anemias due to chronic disease are secondary disorders. Resolution of the underlying dis-
ease process is necessary to restore normal red cell mass. Although the pathogenesis in part de-
scribes an iron-deficient state, body stores of iron are adequate, and patients do not respond to
oral or injectable iron administration.
17. Describe the classic profile of anemia due to renal failure.
Anemias due to renal failure are classically mild (PCV > 20%), normocytic, normochromic,
and nonregenerative. If the renal disease has been present for several months or other factors as-
sociated with renal disease have contributed to increased red cell destruction (e.g., uremia), the
hematocrit may be moderately decreased (PCV::: 15-19%).
18. Describe the pathogenesis of anemia due to renal failure.
The cause of the anemia is believed to be a combination of failure of the injured kidney to re-
lease adequate erythropoietin, impaired hematopoietic cell response to erythropoietin, and short-
ening of erythrocyte survival, probably related to metabolic injury associated with uremia.
19. Can nonregenerative anemia associated with renal failure be treated?
Although erythropoietin levels in cats with chronic renal failure are often within the normal
range, a relative erythropoietin deficiency (inappropriate erythropoietin response for the degree
of anemia) is believed to be present. Patients respond to recombinant human erythropoietin
(rHuEpo) therapy (see Chapter 40), but its administration poses risks of anemia due to rHuEpo
antibody production, seizures, systemic hypertension, and iron deficiency. The production of
rHuEpo antibodies interferes with the erythropoietic effects of rHuEpo and endogeneous erythro-
poietin. These effects are reversible on withdrawal of rHuEpo.
20. Describe the classic profile of nonregenerative anemia due to FeLV infection.
The hematologic findings are extremely varied. Anemias range from mild to severe, depend-
ing on the manifestation of the viral infection. Mild, normocytic, normochromic to macrocytic
normochromic anemias (mean corpuscular volume [MCV] > 50 fl) can be present with normal
leukocyte and platelet counts when viral infection results in selective depression of erythroid ele-
ments. Alternatively, infection can result in primary bone marrow disease, manifesting as pure
red cell aplasia, aplastic anemia, myeloproliferative disorder, or myelodysplastic syndrome. In
such instances, PCV can be dramatically decreased 10%) and associated with concurrent
leukopenia and thrombocytopenia. Atypical erythroid (megaloblasts) or neoplastic cells may be
present in the peripheral circulation and bone marrow aspirates.
21. What is the classic profile of nonregenerative anemia due to FIV infection?
The anemia is usually mild to moderate, normocytic and normochromic in subclinically in-
fected cats. Multiple cytopenias are reported in cats with clinical evidence of disease.
22. Describe the classic profile of iron deficiency anemia.
Iron deficiency anemias are recognized infrequently in older cats as a result of chronic blood
loss and malnutrition. Transient iron deficiency anemia is also recognized in kittens at approxi-
mately 5 weeks of age due to rapid growth and an all-milk diet. The classic profile for cats is a
microcytic, normochromic nonregenerative anemia with prominent erythrocyte fragmentation
(schistocytes, poikilocytes). However, this profile often evolves over a period of months after
typically beginning as regenerative anemia. The key factor in the pathogenesis of the classic pro-
file is insufficient hemoglobinization of red cell precursors. Normally precursor cells continue di-
viding until they reach a critical cytoplasmic hemoglobin concentration. At this point, cell
division ceases and maturation proceeds. With iron deficiency, inadequate hemoglobinization
causes precursors to undergo extra cell divisions, resulting in smaller cells. This process is first
seen on the blood smear as anisocytosis due to the presence of microcytosis. Eventually, enough
microcytes reach the circulation to reduce the population mean size and result in low MCV.
Hypochromasia, a hallmark feature of iron deficiency in humans and dogs, is not commonly rec-
ognized in cats.
23. When is a bone marrow aspirate appropriate?
Clinical and laboratory findings often reveal the cause of nonregenerative anemia as bone
marrow failure. In such cases, a bone marrow aspirate is usually not necessary. If the anemia re-
mains unexplained or is accompanied by other cytopenias, a bone marrow aspirate is essential to
determine the cause of the primary marrow failure.
24. When is it appropriate to submit a bone marrow core biopsy specimen?
A bone marrow core biopsy is most helpful when bone marrow aspirates are hypocellular.
The core biopsy provides important information about cellularity of the bone marrow and recog-
nizes fibrosis or local lesions in the bone marrow.
BIBLIOGRAPHY
I. Cook SM, Lothrop CD: Serum erythropoietin concentrations measured by radioimmunoassay in normal,
polycythemic, and anemic dogs and cats. J Vet Intern Med 8:18-25, 1994.
2. Cowgill LD, James KM, Levy JK, et a1: Use of recombinant human erythropoietin for management of
anemia in dogs and cats with renal failure. J Am Vet MedAssoc 212:521-528, 1998.
3. Hoover JP, Walker DB, Hedges 10: Cytauxzoonosis in cats: Eight cases (1985-1992). J Am Vet Med
Assoc 205:455-460, 1994.
4. Hoover EA, Mullins Jl: Feline leukemia virus infection and diseases. J Am Vet Med Assoc 199:1287-
1297, 1991.
5. Loar AS: Anemia: Diagnosis and treatment. In August JR (ed): Consultations in Feline Internal
Medicine. Philadelphia, w.B. Saunders, 1994, pp 469-487.
6. Perkins PC, Grindem CB, Cullins LD: Flow cytometric analysis of punctate and aggregate reticulocyte
responses in phlebotomized cats. Am J Vet Res 56: 1564-1569, 1995.
7. Raskin RE: Myelopoiesis and myeloproliferative disorders. Vet Clin North Am 26: 1023-1042, 1996.
8. Shelton GH, Linenberger ML, Abkowitz JL: Hematologic abnormalities in cats seropositive for feline
immunodeficiency virus. J Am Vet MedAssoc 199:1353-1357, 1991.
9. Stokol T, Blue JT: Pure red cell aplasia in cats: 9 cases (1989-1997). J Am Vet Med Assoc 214:75-79,
1999.
10. Tvedten H, Weiss D: Erythrocyte disorders. In Willard MD, Tvedten H, Turnwald GH (eds): Small
Animal Clinical Diagnosis by Laboratory Methods, 3rd ed. Philadelphia, W.B. Saunders, 1999, pp
31-37, 45--49.
II. Weiser MG: Disorders of erythrocytes and erythropoiesis. In Sherding, RG (ed): The Cat: Diseases and
Clinical Management, 2nd ed. NewYork, Churchill Livingstone, 1994, pp 691-720.
VIII. Prevention ofDiseases
Section Editor: Michael R. Lappin, D.V.M., Ph.D.
80. HOSPITAL BIOSECURITY
1. Why is hospital biosecurity important?
Transmission of an infectious disease in the veterinary clinic (nosocomial infection) usually can
beprevented, and it is always preferable to prevent rather than treat infections. Acquisition of an in-
fectious disease in the hospital can be devastating for the infected cat because many hospitalized an-
imals are extremely ill. In addition, if an infectious disease is acquired in the hospital, many clients
may lose faith in their veterinary health care provider and seek veterinary care elsewhere. Some in-
fectious agents infect cats and humans (see Chapter 83). It is extremely important to avoid zoonotic
transfer of infectious agents, because many zoonotic diseases, such as plague and rabies, are life-
threatening. Veterinarians should strive to understand the biology of each infectious agent so that
they can counsel clients and staff about the best strategies for prevention. Vaccines available for some
infectious agents can prevent infection or lessen clinical illness when infection occurs (see Chapter
81). However, vaccines are not uniformly effective and are not available for alI pathogens; thus, it is
paramount to develop sound biosecurity procedures to avoid exposure to infectious agents.
2. How are infectious diseases transmitted in the hospital?
Most infectious agents of cats are transmitted in fecal material, respiratory secretions, repro-
ductive tract secretions, or urine; by bites or scratches; or by contact with vectors or reservoirs.
Some infectious agents, such as Bordetella bronchiseptica and feline herpesvirus I, can be trans-
mitted by direct contact with subclinically infected cats. Thus, appropriate housing (individual
cages) is extremely important. Many infectious agents are environmentally resistant and can be
transmitted by contact with a contaminated environment (fomites). In addition, fleas or ticks
from infested cats can contaminate the hospital and transmit infectious diseases. Thus, appropri-
ate cleaning and disinfecting of the premises are imperative.
3. What are the common general biosecurity guidelines?
I. Recognition of risk factors associated with infectious agents is the initial step in preven-
tion of infectious diseases.
2. Contaminated hands are the most common source of infectious disease transmission in
the hospital environment.
o Fingernails of personnel having patient contact should be cut short.
o Personnel should not touch patients, clients, food, doorknobs, drawer or cabinet handles
or contents, equipment, or medical records with soiled hands or gloves.
3. Hands should be washed before and after attending to each individual animal. Hands
should be washed as follows;
o Collect clean paper towels, and use them to tum on water faucets.
o Wash hands for 30 seconds with antiseptic soap, taking care to clean under fingernails.
o Rinse hands thoroughly.
o Use paper towels to dry hands.
o Use paper towels to tum off the water faucets.
407
408
Hospital Biosecurity
4. All employees should wear an outer garment such as a smock or scrub suit when attend-
ing to patients. A minimum of 2 sets of outer garments should always be available, and garments
should be changed immediately after contamination with feces, secretions, or exudates.
5. Footwear should be protective, clean, and cleanable.
6. Equipment such as stethoscopes, pen lights, thermometers, bandage scissors, cat carriers,
percussion hammers, and clipper blades can be fomites and should be cleaned and disinfected
with 0.5% chlorhexidine solution after each use if infectious disease is suspected. Disposable
thermometer covers should be used.
7. To avoid zoonotic transfer of infectious diseases, food or drink should not be consumed
in areas where cat care is provided.
8. All areas where cats are examined or treated should be cleaned and disinfected immedi-
ately after use, regardless of infectious disease status of the individual animal.
9. Litter boxes and dishes should be cleaned and disinfected after each use.
4. Can front-desk personnel aid in lessening transmission of infectious diseases in the
clinic?
Prevention of infectious diseases starts with front-desk personnel:
1. Staff should be trained to recognize the presenting complaints for infectious agents within
the geographic area of the hospital.
2. Cats with gastrointestinal or respiratory diseases are the most likely to be contagious.
Infectious gastrointestinal disease should be suspected in all cats with small or large
bowel diarrhea, whether the syndrome is acute or chronic.
Infectious respiratory disease should be suspected in all cats with sneezing (especially
with purulent oculonasal discharge) or coughing (especially if productive).
3. The index of suspicion for infectious diseases is increased for cats with acute disease and
fever, particularly if the cat is from a crowded environment such as a breeding facility, boarding
facility, or humane society.
4. Front-desk personnel should indicate clearly on the hospital record that gastrointestinal or
respiratory disease is present.
If the presenting complaint is known before admission into the hospital, it is optimal to
meet the client in the parking area to determine the risk of infectious disease before en-
tering the hospital.
If infectiousgastrointestinalor respiratorydisease is suspected, the cat should be transported
(i.e., not allowed to walk on the premises) to an examination room or isolation facility.
If a cat with acute gastrointestinal or respiratory disease is presented directly to the re-
ception desk, the receptionist should contact the receiving clinician or technician imme-
diately and coordinate placement of the animal in an examination room to minimize
hospital contamination.
5. How can patient management lessen nosocomial transmission of infections?
I. Cats with suspected infectious diseases should be treated as outpatients if possible.
2. If hospitalization is required, the cat should be transported to the appropriate housing area
by the shortest route possible, preferably by cat carrier to lessen hospital contamination.
3. The cat carrier and any hospital material contacted by potentially contaminated employ-
ees (including examination tables and door knobs) should be immediately cleaned and disin-
fected (see routine disinfection protocols).
4. If possible, all cats with suspected infectious diseases such as Salmonella spp.,
Campylobacter jejuni, parvovirus, feline upper respiratory disease syndrome, rabies, or plague
should be housed in an isolated area of the hospital.
Because feline leukemia virus and feline immunodeficiency virus are not contagious if
the infected cat is individually housed, seropositive cats should not be placed in the iso-
lation area to avoid exposing them to other infectious diseases. However, they should
not be allowed direct contact with other cats.
Hospital Biosecurity 409
The number of staff members entering the isolation area should be kept to a minimum.
On entry into the isolation area, outerwear should be left outside and surgical booties or
other disposable shoe covers should be placed over the shoes. Alternatively, a footbath
filled with disinfectant should be placed by the exit and used when leaving the area (see
question 6).
When the room is entered, a disposable gown (or smock designated for the patient) and
latex gloves should be put on. A surgical mask should be worn when attending cats with
plague. Separate equipment and disinfectant supplies should be used in the isolation
area.
Procedures requiring general hospital facilities, such as surgery and radiology, should
be postponed to the end of the day, if possible, and the contaminated areas disinfected
before use with other animals.
All biologic materials submitted to clinical pathology or diagnostic laboratories from
animals with suspected or proven infectious diseases should be clearly marked as such.
Fecal material should be placed in a plastic, screw-capped cup using a tongue depressor
or wearing gloves. Place the cup in a clean area, and place the lid with a clean, gloved
hand. Remove the used gloves, and place the cup in a second bag clearly marked with
the name of the infectious disease suspected. The outer surface of the bag should be dis-
infected before leaving the isolation area.
Disposable materials should be placed in plastic bags in the isolation area. The external
surfaces of the bags should be sprayed with a disinfectant before being removed from
the isolation area.
After attending to the patient, contaminated equipment and surfaces should be cleaned
and disinfected, and contaminated outer garments and shoe covers should be removed.
Hands should be washed after discarding the contaminated outerwear. Dishes and litter-
pans should be cleansed thoroughly with detergent before being returned to the central
supply area.
Optimally, materials to be returned to a central supply area, such as outerwear and equip-
ment, should be placed in plastic bags and sprayed with a disinfectant before transport.
Cats should be discharged from the isolation area using the shortest path possible to the
parking lot.
6. What basic disinfection protocols should be followed?
1. Cat beds, blankets, collar tags, and leash must go home with owner.
2. Cats should be housed individually.
3. Cats should never be moved from cage to cage.
4. Cage papers and litterpans soiled by feces, urine, blood. exudates, or respiratory secre-
tions should be removed and placed in trash receptacles. Bulk fecal material also should be
placed in trash receptacles.
5. Disinfectants do not penetrate deeply into contaminated materials such as feces; clean-
ing is as important or more important than disinfecting.
6. Many agents are resistant to disinfectants or require prolonged contact time to be inacti-
vated.
7. Contaminated surfaces, including the cage or run floor, walls, ceiling, door, and door
latch, should be wetted thoroughly with a disinfectant, which is then blotted with clean paper
towels or mops.
8. Surfaces should be in contact with the disinfectant for 10-15 minutes if possible, partic-
ularly if known infectious agents are present.
9. Soiled paper towels should be placed in trash receptacles. If infectious diseases are sus-
pected, the trash bags should be sealed, the surface of the bag sprayed with a disinfectant, and the
trash bags discarded.
10. Contaminated surfaces in examination rooms should be cleaned to remove hair, blood,
feces, and exudates.
410
Vaccine Recommendations
II. Examination tables, countertops, floors, canister lids, and water taps should be saturated
with disinfectant for 10 minutes, if possible.
12. Surfaces should be blotted with paper towels until dry, and the soiled towels should be
placed in a trash receptacle. Urine or feces on the floor should be contained with paper towels, blot-
ted, and placed in trash receptacles. The soiled area of the floor should be mopped with disinfectant.
13. Disinfectants are relatively effective for viral and bacterial agents but require high con-
centrations and long contact times to kill parasite ova, cysts, and oocysts. Cleanliness is the key
to lessening hospital-borne infection with these agents, most of which are inactivated with deter-
gent or steam cleaning. Litterpans and dishes should be cleaned thoroughly with detergent and
scalding water.
BIBLIOGRAPHY
Lappin MR: Prevention of infectious diseases. In Nelson RW, Couto GC (eds): Small Animal Internal
Medicine, 2nd ed. St Louis, Mosby, 1998. pp 1265-1272.
81, VACCINE RECOMMENDATIONS
Dennis W. Macy, D.V.M., and Micnael R. Lappin, D.V.M., pn.D.
1. Which vaccines should all cats receive?
The core vaccines that all cats should receive include:
Panleukopenia (feline parvovirus) Calicivirus
Rhinotracheitis (feline herpesvirus I) Rabies
2. Should other vaccines be considered?
Noncore vaccines that should be administered on the basis of medical risk include:
Feline leukemia virus (FeLV) Bordetella bronchiseptica
Feline infectious peritonitis (PIP) Giardia spp.
Chlamydia psittaci Microsporum canis
3. What types of vaccines are currently available?
Attenuated (modified-live) vaccines generally have low antigen mass and almost never
induce local reactions; they can be given locally (e.g., modified-live B. bronchiseptica intranasal
vaccine) or parenterally (e.g., modified-live panleukopenia). However,living vaccines must repli-
cate in the host to stimulate an effective immune response.
Noninfectious vaccines include killed virus, killed bacteria (bacterins), and subunit vac-
cines. In general, noninfectious vaccines require higher antigen mass than modified-live vaccines
to stimulate immune responses because they do not replicate in the host. Noninfectious vaccines
stimulate immune responses of lesser magnitude and shorter duration than attenuated vaccines,
unless adjuvants are added. Adjuvants improve immune responses by stimulating uptake of anti-
gens by macrophages, which present the antigens to lymphocytes. Adjuvants can cause or poten-
tiate adverse vaccine reactions; induction of vaccine-associated sarcomas in cats may be one
example (see Chapter 82). Most adjuvanted vaccines studied in cats have led to pyogranulorna-
tous reactions that may undergo malignant transformation to soft tissue sarcomas. Subunit vac-
cines may be superior to killed vaccines that use the entire organism because only the
immunogenic parts of the organism are used; thus the potential for vaccine reactions is decreased.
Vector vaccines combine the advantages of attenuated and subunit vaccines. The DNA that
codes for the immunogenic components of the infectious agent is inserted into the genome of a
nonpathogenic organism (vector) that replicates in the vaccinated species. As the vector repli-
Vaccine Recommendations 411
cates in the host, it expresses the immunogenic components of the infectious agent, resulting in
induction of specific immune responses. Because the vector vaccine is live and replicates in the
host, adjuvants and high-antigen mass are not required, and because only DNA from the infec-
tious agent is incorporated into the vaccine, there is no risk of reverting to the virulent parent
strain, as occasionally occurs with attenuated vaccines. Only vectors that do not induce disease in
the vaccinate are used.
4. Does the duration of immunity conferred by a vaccine vary?
In general, modified live virus vaccines and vector vaccines provide better cell-mediated im-
munity and longer duration of humoral immunity than killed or inactivated vaccines.
5. Should all adjuvanted vaccines be avoided in cats?
Because of the risk for vaccine-associated sarcomas (see Chapter 82), the nonadjuvanted
product should be used when both adjuvanted and nonadjuvanted products are available. Many
killed vaccines contain adjuvants, a fact that may not always be indicated on the label. Some
killed feline rhinotracheitis, calcivirus, and panleukopenia (FVRCP) vaccines contain adjuvants
and should not be used routinely. In addition, Microsporum canis and Giardia spp. vaccines con-
tain adjuvants and should be avoided unless medically necessary.
6. Does the level of protection vary among vaccines for various diseases?
Some vaccines provide sterilizing immunity; infection is totally prevented if the animal is ex-
posed (e.g., panleukopenia). Other vaccines, including those for upper respiratory disease, do not
prevent infection but limit clinical signs if vaccinated cats are exposed. In general, vaccination
should be expected to provide no better immunity than that conferred by recovery from the disease.
7. How often should core vaccines be given to pet cats?
Kittens presented for vaccination between 6 and 12 weeks of age should be given an inacti-
vated or modified live FVRCP vaccine every 3--4 weeks until 12 weeks of age.
Kittens presented at > 12 weeks of age should be given either 2 inactivated FVRCP. 3--4
weeks apart, or 1 modified live FVRCP.
Rabies vaccination should be based on local ordinances.
Core vaccines should be boosted in 1 year, then every 3 years thereafter unless a rabies vac-
cine approved only for 1 year is used (see question 9).
Titer and challenge studies indicate that core vaccines are effective for more than 6 years;
for some antigens, such as panleukopenia, duration of immunity is probably lifelong.
8. How should the core vaccines be administered?
1. Topical (intranasal) and injectable FVRCP vaccines are available.
Intranasal rhinotracheitis and calicivirus vaccines induce IgA antibodies more rapidly
and should be used if speed of response is important (e.g., during outbreaks).
Intranasal vaccines often are associated with sneezing.
Intranasal vaccines are not as likely as injectable vaccines to cause vaccine-associated
sarcomas.
2. Injectable FVRCP vaccines should be administered subcutaneously as low as possible
over the right shoulder.
3. Rabies vaccines should be given intramuscularly or subcutaneously as low as possible on
the right rear limb.
9. Which rabies vaccines should be used in cats?
One nonadjuvanted rabies vaccine (Merial, Athens, GA) is currently available; at this time,
it is the rabies vaccine of choice for cats. Chronic inflammation is thought to be necessary for
the development of vaccine sarcomas (see Chapter 82); this product induces no chronic reaction
at the injection site.
412
Vaccine Recommendations
10. How often should core vaccines be given in crowded environments such as catteries or
shelters?
If outbreaks occur, modified live intranasal vaccines containing feline herpesvirus I and cali-
civirus have been given to kittens as young as 2 weeks of age. In this scenario, one vaccine is
usually divided among several kittens.
H, Why not use an interval longer than 3 years?
Memory T-lymphocytes probably exist for a lifetime after the administration of a modified
live virus vaccine; thus vaccination intervals for some antigens probably could be longer. If re-
covery from the natural disease results in lifelong immunity, prolonged immunity may be ex-
pected from vaccination. Evolutionary concepts suggest that cats that are susceptible to acutely
fatal diseases twice would be purged from the gene pool. For example, panleukopenia has never
been reported in a cat that has received the initial set of vaccines, regardless of whether they re-
ceived additional booster vaccines.
12. Can serum antibody titers be used to determine need for boosting individual cats?
Serum antibody titers are an indirect measure of protection that may be used for some dis-
eases, but they have limitations:
1. Reproducibility from laboratory to laboratory is sometimes poor; only laboratories that
have correlated titer magnitude to protection should be used (NewYork State Diagnostic Labora-
tory, Ithaca, NY; HESKA Diagnostic Laboratory, Fort Collins, CO).
2. For some diseases, mucosal and cell-mediated immunity is more important than humoral
immunity for protection.
3. The presence of antibodies against panleukopenia, herpesvirus I, and calicivirus usually
predicts protection, but the absence of antibodies does not accurately predict susceptibility.
13. When should FeLV vaccination be used?
Cats that benefit the most from FeLVvaccines are young cats with a high risk of contact with
FeLV carriers. For example, when exposed to an FeLV-infectedcat, l2-week-old kittens and adult
cats have an 85% and 15% chance, respectively, of becoming persistently infected. This age-ac-
quired immunity limits the protection that can be attributed to the FeLV vaccine in adult cats.
Naive cats should receive 2 vaccinations initially.
Adjuvanted products should be administered subcutaneously or intramuscularly in the
distal left rear limb because of the risk for development of soft tissue sarcomas.
Because duration of immunity is unknown, annual boosters are currently recommended.
The vaccine is not effective in persistently viremic cats and so is not indicated. However.
administration of the vaccine to viremic or latent cats is not associated with an increased
risk of vaccine reaction.
FeLV testing should be performed before vaccination because the retrovirus serologic
status of all cats should be known to maintain appropriate husbandry.
14. When should FIP vaccine be used?
The incidence of FIP is only I in 5000 cat households. The vaccine has been shown to be ef-
fective only in cats that do not harbor the coronavirus. Given that 20-40% of cats already harbor
the coronavirus, that the maximal protection of the vaccines is 60-80%, and that the duration of
protection is limited to secretory IgA, the value of the FIP vaccine in any situation is question-
able. The vaccine may be indicated for seronegative cats entering a household or cattery known
to be FlP-infected.
15. Should cats be vaccinated agaiust chlamydiosis?
In the United States, Chlamydia psittaci infection in cats generally results only in mild con-
junctivitis; therefore, whether vaccination is ever required is controversial. Use of this vaccine
should be reserved for cats with a high risk of exposure to other cats and in catteries with endemic
VaccineRisks 413
Cytopenias
Prenatal infections (modified live
vaccines)
Chronic stomatitis
Renal disease
disease. Duration of immunity for chlamydial vaccines may be short-lived; thus, high-risk cats
should be immunized before a potential exposure.
16. Should cats be vaccinated against bordeteUosis?
Many cats have antibodies against B. bronchiseptica, and there are sporadic reports of severe
lower respiratory disease due to bordetellosis in young kittens from crowded, stressful environ-
ments. Clinical infection in pet cats, however, is extremely rare. B. bronchiseptica vaccination
should be considered primarily for cats at high risk for exposure. Because the disease is appar-
ently not life-threatening in adult cats, is uncommon in pet cats, and responds to various antibi-
otics, routine use of the vaccine in client-owned cats seems unnecessary.
17. Should cats be vaccinated against giardiasis?
A Giardia spp. vaccine has been introduced for use in cats. When given twice, the vaccine
lessens numbers of cysts shed and clinical disease on challenge with one heterologous strain. The
vaccine is adjuvanted and given subcutaneously and ultimately may be associated with fibrosar-
comas. Because the disease is usually not life-threatening and at least 90% of cases respond to
therapy, routine use in client-owned cats seems unnecessary. The vaccine may have therapeutic
utility in cats with recurrent or persistent infection, as was recently documented in dogs.
BIBLIOGRAPHY
I. 2000 Report of the American Association of Feline Practitioners and Academy of Feline Medicine
Advisory Panel on Feline Vaccines. Nashville, TN, AAFPlAFM, 2000.
2. Burton G, Mason KV: Do postvaccinal sarcomas occur in Australian cats? Aust Vet J 75: 102-106,
1997.
3. Coutts AJ, Dawson S, Binns SH, et al: Studies on the natural transmission of Bordetella bronchisep-
tica in cats. Vet MicrobioI48:19-27, 1996.
4. Lappin MR. Jensen W, Andrews J: Prediction of resistance to panleukopenia, herpesvirus I, and cali-
civirus utilizing serology. J Vet Intern Med 14:364.2000.
5. Macy DW: Are we vaccinating too much? J Am Vet Med Assoc 207:421-425, 1995.
6. Macy DW, Bergman P: Vaccine associated sarcomas in cats. Fel Pract 23:24-27, 1995.
7. Macy DW, Hendrick MW: The potential role of inflammation in the development of post-vaccinal sarco-
mas in cats. Vet Clin North Am 26: 103-109, 1996.
8. Olson ME, Morch DW, Ceri H: The efficacy of a Giardia lamblia vaccine in kittens. Can J Vet Res
60:249-256, 1996.
9. Scott FW: Duration of immunity in cats vaccinated with an inactivated feline panleukopenia, her-
pesvirus, and calicivirus vaccine. Fel Pract 25:12-22,1997.
10. Schultz RD: Current and future canine and feline vaccination programs. Vet Med 3:233-254,1998.
82. VACCINE RISKS
Dennis W. Mac!l, D.V.M.
1. What are the most common vaccine reactions?
Vaccines are suspected to cause a number of reactions, some of which are better documented
than others:
Vaccine associated sarcomas
Acute anaphylaxis
Polyarthritis from modified live calicivirus vaccines
Sneezing and nasal discharge from topical vaccines
Fever
414
VaccineRisks
2. How common are vaccine-associated sarcomas?
Studies indicate an incidence of 111,000to 1/10,000 in cats receiving either FeLV or rabies
vaccines. Most experts believe that the incidence is 112,000and 114,000in cats receiving either
FeLV or rabies vaccination.
3. Which vaccines are most often associated with vaccine-associated sarcomas? Why?
Adjuvanted feline vaccines, particularly FeLV and rabies vaccines, are associated most fre-
quently with sarcoma development at injection sites. Adjuvanted vaccines produce inflammation,
stimulate fibroblasts to divide, and are responsible for free radical formation, which results in ox-
idative damage to DNA.
4. Why do the same rabies vaccines not produce tumors in dogs?
Apparently cats are unique in terms of their susceptibility to sarcoma development. It is be-
lieved that the eat's unique species susceptibility to oxidative injury (acetominophen-associated
Heinz body anemia, steatitis) is one reason for the high vaccine-associated tumor rate.
5. If granulomas and inflammation occur in all cats receiving certain adjuvanted vac-
cines, why do only 1-5 in 10,000develop sarcoma?
It may depend on individual susceptibility to oxidative stress (reduced glutamine levels have
been demonstrated in some cats with vaccine-associated sarcoma). Individual cats may have de-
fects in the tumor suppressor gene, P53. Aberrations in P53 have been reported in some cats with
vaccine-associated sarcomas.
6. Have sarcomas been reported after administration of products other than vaccines?
Virtually anything that results in chronic inflammation can result in sarcoma formation (e.g.,
sutures, polyethylene glycol tubes, parenteral antibiotics, injectable lufenuron). However, adju-
vanted vaccines are the only substances that are injected repeatedly in large numbers of cats.
7. What is the time from vaccine administration to subsequent tumor formation?
Reports indicate that tumors may develop 3 months to 11 years after vaccine administration.
Tumors that occur sooner than 3 months are probably due to previous vaccination or tissue injury.
8. What can be done to prevent vaccine-associated sarcomas?
I. Do not overvaccinate.
2. Limit the use of adjuvanted vaccines.
3. Avoid using any medication that produces chronic inflanunation.
9. How long do postvaccinallumps remain?
Adjuvanted vaccines produce granulomas that reach their maximal size 3 weeks after vacci-
nation but disappear within 3 months after vaccination.
10. When should a postvaccinal lump be removed?
The Vaccine-Associated Sarcoma Task Force recommends that any lump at a vaccination
site be biopsied and removed if it meets anyone of the following three criteria:
1. Still present 3 months after vaccination
2. > 2 em in size at any time after vaccination
3. Growing in size 4 weeks after vaccination.
11. What biopsy techniques should be used?
A wedge or Tru-Cut biopsy technique should be used. Fine-needle aspiration is unreliable.
12. Should granulomas be removed?
If a biopsy determines the postvaccinallump to be a granuloma, simple marginal resection
of the granuloma should be performed.
Vaccine Risks 415
13. How should a vaccine site sarcoma be managed?
The following should be done before treatment of a vaccine-associated sarcoma:
1. Computed tomography examination should be done to determine the extent of the lesion.
2. A chest radiograph should be done to determine whether metastatic disease is present
(usually 5% or less at the time of first diagnosis, but the incidence may increase to 25% in pa-
tients with prior treatment).
3. FeLV test should be performed to eliminate the possibility of a feline sarcoma virus-in-
duced tumor. Sarcomas caused by the feline sarcoma virus do not benefit from surgery.
14. What treatment is best?
A combination of surgery, radiation therapy, and chemotherapy gives the best results.
15. Which treatment regimen should be used first?
Surgery followed by radiation therapy or radiation therapy followed by surgery have been
recommended; chemotherapy usually follows radiation and surgery regimens.
16. How large a margin should be used in surgery?
Large. Margins of 2-5 cm are recommended.
17. Should I refer the surgery?
Significant improvement in disease-free interval has been shown if a referral institution does
either the initial or second surgery. No difference in disease-free interval is found if multiple
surgeries have been done before referral.
18. What is the prognosis?
Surgery alone: 60% recurrence rate (86% recur within 6 months); average survival is 1-1.5
years.
Radiation and surgery: 3Q-40% recurrence rate; average survival 700-800 days.
Some chemotherapeutic agents are active against vaccine-associated sarcomas but are mar-
ginally effective in increasing patient survival, perhaps adding 10% to survival time. Although a
wide variety of drugs have been evaluated (including doxorubicin, carboplatin, mitoxantrone, cy-
clophosphamide, and vincristine), doxorubicin appears to be the most effective.
BIBLIOGRAPHY
l. Burton G, Mason KV: 00 postvaccinal sarcomas occur in Australian cats? Aust Vet J 75:102-106, 1997.
2. Hendrick MJ, Brooks 11: Postvaccinal sarcomas in the cat: Histology and immunohistochemistry. Vet
PathoI31:126--129,1994.
3. Hendrick MJ, Goldschmidt MH: 00 injection site reactions induce fibrosarcomas in cats? J Am Vet Med
Assoc 199:968, 1991.
4. Hendrick MJ, Kass PH, McGill LO, et al: Commentary: Postvaccinal sarcomas in cats. J Natl Cancer
Inst 86:5, 1994.
5. Hendrick MJ,Shoter FS, Goldschmidt MH, et a1: Comparison of fibrosarcomas developed at vaccination sites
and at nonvaccination sites in cats: 239 cases (1991-1992). JAm Vet Med Assoc 205:1425-1429, 1994.
6. Hendrick MJ, Goldschmidt MH, Shoter FS, et al: Postvaccinal sarcomas in the cats: Epidemiology and
electron probe microanalytical identification of aluminum. Cancer Res 52:5391-5394,1992.
7. Kass PH, Barnes WG, Spangler WL, et al: Epidemiologic evidence for a causal relationship between
vaccination and fibrosarcoma tumorigenesis in cats. J Am Vet Med Assoc 203:396--405, 1993.
8. Macy OW, Bergman PJ: Vaccine associated sarcomas in cats. Fel Pract 23:24-27, 1995.
9. Macy OW, Hendrick MJ: The potential role of inflammation in the development of post-vaccinal sarco-
mas in cats. Vet Clin North Am 26:103-109,1996.
10. Macy OW: The potential role and mechanisms of FeLV vaccine-induced neoplasms. Semin Vet Med
Surg 10:234-238, 1995.
I I. Macy DW, Bergman JP: Postvaccinal reactions associated with three rabies and three leukemia virus
vaccines in cats. Proceedings of the 14th Annual Veterinary Cancer Society Conference, Townsend.
TN, Veterinary Cancer Society, 1994, pp 90-91.
12. Smith CA: Current concepts: Are we vaccinating too much? J Am Vet Med Assoc 207:421-425, 1995.
IX. Public Health Risks
Section Editor: Michael R. Lappin, DYM., Ph.D.
83. ZOONOSES: OVERVIEW
1. Define zoonotic disease.
Zoonotic diseases are common to, shared by, or naturally transmitted between humans and
other vertebrate animals.
2. What are the most likely ways to become exposed to an infectious agent with zoonotic
potential?
Transmission of zoonotic agents can occur by direct contact with the cat; indirect contact with
secretions from the cat; contact with contaminated vehicles such as water, food, or fomites; or
shared vectors. Some of the most common zoonoses are associated with the gastrointestinal tract
(see Chapter 84) and bites and scratches (see Chapter 85). The respiratory tract (see Chapter 86),
exudates (see Chapter 87), and urogenital tract (see Chapter 88) also harbor infectious agents ca-
pable of infecting humans. With some agents, infection of humans and cats occurs from a shared
environment (see Chapter 89) or shared vector (see Chapter 90), but the organism is not directly
transmitted from cats. Overall, the most likely ways of contracting a cat-associated infectious dis-
ease are fecal-oral contact, bites or scratches, or infected fleas or ticks in the human environment.
3. Do you have to be immunocompromised to be infected by a zoonotic agent?
Immunosuppression is common in people. The acquired immunodeficiency syndrome
(AIDS) is discussed frequently, but there are many other common immunosuppressive syndromes:
People on chemotherapy for organ transplantation, inflammatory diseases, immune medi-
ated diseases, or neoplasia
Older people with decrimental decreases in immune function
Young people with poorly developed immune systems, such as the fetus
Splenectomized people
Most zoonotic infectious agents will infect anyone regardless of immune status, but the mag-
nitude of clinical illness is often much more severe in immunosuppressed people. For example,
giardial infection of an immunocompetent person usually is associated only with transient diar-
rhea, whereas an immunosuppressed person may develop life-threatening disease.
4. Should immunosuppressed people own cats?
Because many agents infect both cats and human beings, it is sometimes assumed that direct
contact zoonoses are common. In actuality, healthy, adult, parasite-free, indoor cats are unlikely
to transmit infectious agents to people.
Families with a proven or suspected immunodeficient member are commonly told to avoid
cat ownership because of potential health risks. Often these recommendations are based on inac-
curate information. For example, pregnant women and immunosuppressed people are commonly
told to avoid cats because of the risk of acquiring toxoplasmosis. However, it is extremely rare to
acquire Toxoplasma gondii from touching cats; the organism is transmitted most commonly from
contact with sporulated oocysts in a contaminated environment or from ingesting undercooked
meats (see Chapter 84).
417
418
Zoonoses: Overview
Cat ownership provides many health benefits; it is well recognized that pet ownership results
in increased happiness and decreased depression. Thus, any decision about cat ownership should
consider both potential risks and potential benefits. Veterinarians should familiarize themselves
with zoonotic issues and take an active role in discussion of the health risks and benefits of pet
ownership with clients so that logical decisions about ownership and management of individual
animals can be made.
5. What overall recommendations can be made to an immunosuppressed person for
avoidance of feline zoonoses?
As discussed previously and in Chapters 84-90, the risk of acquiring an infection from a cat
is minimal. The following recommendations may further decrease the risk:
o The common enteric zoonoses occur most frequently in young cats with diarrhea from
crowded environments. Thus, the cat least likely to be a zoonotic risk is a clinically normal,
indoor adult from a private family.
o If possible, someone other than the immunosuppressed individual should remove fecal ma-
terial produced in the home environment daily.
The cat should be housed indoors.
o The cat should be fed only commercially processed pet food.
o The owner should not allow the cat to share utensils and should avoid licking.
o Kittens or cats with external parasites should be avoided or treated because of increased
risk of Bartonella henselae infection and other shared vector zoonoses.
Kittens or cats with respiratory disease, ocular disease, or skin disease should be avoided or
treated.
Physical examination and fecal examination should be performed at least once or twice
yearly.
o If a new cat is desired, the immunosuppressed person should avoid direct contact while it is
evaluated for zoonotic agents.
o Once the cat to be adopted is identified, a thorough physical examination should be per-
formed.
o Fecal flotation for giardial cysts and helminth eggs, wet mount for protozoal trophozoite
identification, special stains or antigen testing for Cryptosporidium parvum, and fecal cul-
ture for enteric bacteria can be performed to screen for enteric zoonoses.
o Blood should be collected aseptically from cats and placed in an EDTA tube for Bartonella
culture or polymerase chain reaction; serum should be submitted at the same time for
Bartonella antibody testing.
o Because direct contact with individual cats rarely results in toxoplasmosis, there is no indi-
cation for serologic evaluation of healthy cats.
o The cat should be routinely dewormed with a drug that kills hookworms, roundworms, and
tapeworms.
Flea and tick control should be instituted.
o Previously owned cats with clinical signs of disease associated with the gastrointestinal
tract, eyes, respiratory tract, genital tract, urinary system, or skin should be evaluated for
zoonotic agents by the veterinarian.
BIBLIOGRAPHY
1. Angulo FJ, Glaser CA, Juranek DD, et al: Caring for pets of imrnunocompromised persons. J Am Vet
Moo Assoc 205:1711-1718,1994.
2. Burton B: Pets and PWAs: Claims of health risk exaggerated. AIDS Patient Care Feb:34-37, 1989.
3. Carmack B: The role of companion animals for persons with AIDSIHIV. HoI Nurs Pract 5:24-31, 1991.
4. Evans RH: Public health and important zoonoses in feline populations. In August JR(ed): Consultations
in Feline Internal Medicine, 3rd ed. Philadelphia, w.B. Saunders, 1997, pp 611-629.
5. Greene CE: Imrnunocompromised people and pets. In, Greene CE (ed): Infectious Diseases of the Dog
and Cat, 2nd ed. Philadelphia, W.B. Saunders, 1998, pp 710-717.
Enteric Zoonoses 419
6. Glaser CA, Angulo FJ, Rooney JA: Animal associated opportunistic infections among persons infected
with the human immunodeficiency virus. Clin Infect Dis 18:14-24, 1994.
7. Lappin MR: Feline zoonoses. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI Small
Animal Practice. Philadelphia, WB. Saunders, 1992, pp 284-291.
8. Olsen CW: Vaccination of cats against emerging and reemerging zoonotic pathogens. Adv Vet Med
41:333-346,1999.
9. Patronek G: Free-roaming and feral cats: Their impact on wildlife and human beings. J Am Vet Med
Assoc 212:218-226, 1998.
10. Spencer L: Study explores health risks and the human animal bond. J Am VetMed Assoc 201:1669, 1992.
II. TanJ: Human zoonotic infections transmitted by dogs and cats. Arch Intern Med 157:1933-1943, 1997.
84. ENTERIC ZOONOSES
1. What are the major classes of enteric zoonotic agents?
Bacteria, protozoans, helminths, and cestodes.
Enteric Zoonoses Associated with Contact with Cats or Their Excrement
ORGANISM
Bacteria
Campylobacter spp.
Eschericia coli
Helicobacter spp. *
Salmonella spp.
Yersinia enterocolitica
Cestodes
Dipylidium caninum
Protozoan-cocddlaas
Toxoplasma gondii
Protezoan-flagellate
Giardia spp.
Helminths
Ancylostoma braziliense
Ancylostoma tubaeforme
Uncinaria stenocephala
Toxocara cati
* Zoonotic potential undetermined.
COMMENT
Immediately infectious
Ova are immediately infectious
Requires ingestion of flea
Oocysts are immediately infectious
Oocysts are infectious after 1-5 days of incubation; exposure
from environment
Cysts are immediately infectious
Larva infectious after> 3 days of incubation; skin penetration
from larva in environment
Larva immediately infectious
Larvated ova infectious after 3-4 weeks of incubation; exposure
from environment
2. What are the odds of acquiring a gastrointestinal disease from my cat?
Prevalence of enteric zoonotic agents varies by region, whether cats are housed indoors or
outdoors, and whether diarrhea occurs. Odds of being infected from contact with cats or cat
7. Lappin MR: Feline zoonoses. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI Small
Animal Practice. Philadelphia, WB. Saunders, 1992, pp 284-291.
8. Olsen CW: Vaccination of cats against emerging and reemerging zoonotic pathogens. Adv Vet Med
41:333-346,1999.
9. Patronek G: Free-roaming and feral cats: Their impact on wildlife and human beings. J Am Vet Med
Assoc 212:218-226, 1998.
10. Spencer L: Study explores health risks and the human animal bond. J Am VetMed Assoc 201:1669, 1992.
II. TanJ: Human zoonotic infections transmitted by dogs and cats. Arch Intern Med 157:1933-1943, 1997.
84. ENTERIC ZOONOSES
1. What are the major classes of enteric zoonotic agents?
Bacteria, protozoans, helminths, and cestodes.
Enteric Zoonoses Associated with Contact with Cats or Their Excrement
ORGANISM
Bacteria
Campylobacter spp.
Eschericia coli
Helicobacter spp. *
Salmonella spp.
Yersinia enterocolitica
Cestodes
Dipylidium caninum
Protozoan-cocddlaas
Toxoplasma gondii
Protezoan-flagellate
Giardia spp.
Helminths
Ancylostoma braziliense
Ancylostoma tubaeforme
Uncinaria stenocephala
Toxocara cati
* Zoonotic potential undetermined.
COMMENT
Ova are immediately infectious
Requires ingestion of flea
Oocysts are immediately infectious
Oocysts are infectious after 1-5 days of incubation; exposure
from environment
Cysts are immediately infectious
Larva immediately infectious
Larvated ova infectious after 3-4 weeks of incubation; exposure
from environment
2. What are the odds of acquiring a gastrointestinal disease from my cat?
Prevalence of enteric zoonotic agents varies by region, whether cats are housed indoors or
outdoors, and whether diarrhea occurs. Odds of being infected from contact with cats or cat
420
Enteric Zoonoses
excrement also vary with the organism (see discussions that follow). In a recent study, enteric
zoonotic agents were detected in feces of 13.1%of 206 cats in north central Colorado. Although
enteric zoonotic agents are common, people are unlikely to acquire infections from direct contact
with cats. Most cats are fastidious and do not leave fecal material on the fur. Thus, contact with
enteric zoonotic agents is probably more common from environmental contamination. Because
cat fecal material is usually concentrated in one area and of small volume, extensive contamina-
tion of the home environment is probably uncommon.
Prevalence of enteric zoonotic agents in 206 cats of north central Colorado. (Data from Hill S, Lappin MR.
Cheney J. et al: Prevalence of enteric zoonotic agents in cats. J Am Vet Med Assoc 216:687--692. 2000.)
3. Which helminths are most commonly associated with infection of people?
Both cats and people can be infected with Toxocara cati, Ancylostoma brazlliense, A. tubae-
forme, Uncinaria stenocephala, and Strongyloides stercoralis.
4. What syndromes in humans are associated with T. catiinfection?
Visceral larva migrans and ocular larva migrans are the two most common syndromes asso-
ciated with human toxocariasis. Most cases are thought to be due to T. canis infection, but the
same syndromes can occur after infection with T. cati. Infected cats pass ova into the human en-
vironment. After 3--4 weeks, the ova larvate and then are infectious. Humans are infected by in-
gestion of larvated ova, which release infective larvae in the gastrointestinal tract. The larvae
penetrate the mucosa of the small intestine and migrate to the liver, lungs, and other organs (vis-
cerallarva migrans). The eosinophilic reaction against the larvae can result in clinical signs of
disease. Manifestations include eosinophilia, abdominal pain, anorexia, nausea, vomiting fever,
cough, hepatomegaly, myocarditis, and encephalitis. Asthma is more common in Toxocara-
seropositive people than Toxocara-seronegative people, suggesting that toxocariasis contributes
to asthma. If larvae migrate to the eye (ocular larva migrans), the eosinophilic reaction can result
in severe intraocular inflammation. Adult T. cat; worms have been detected in some infected chil-
dren. Humans with toxocariasis are generally treated symptomatically with antihistamines and
glucocorticoids; the use of antihelmintics is controversial.
5. Is human toxocariasis common?
Toxocaraova are environmentally resistant; when an area is contaminated, the potential for in-
fection persists for months. In the United States, the seroprevalence of antibodies against Toxocara
spp. is 2.8% in the general population and 4.6-7.3% in children 1-11 years of age. Thus, exposure
to infective roundworms is still common. Visceral larva migrans is most common in children < 6
years of age; ocular larva migrans is most common in older children and young adults.
6. What is cutaneous larva migrans?
Cats can be the definitive host for A. braziliense,A. tubaeforme, U. stenocephala, and S. ster-
coralis. Ova are passed into the environment, where they larvate after several days in warm, humid
conditions. Infective larva penetrate the skin of people in direct contact. Pruritic, serpiginous, ery-
thrematous tracts occur as the larva migrate in the epidermis. A. caninum has been linked with
eosinophilic enteritis in humans; the syndrome has not been described with hookworms that infect
cats. Topical or oral administration of thiabendazole lessens symptoms in infected humans.
7. Howcan the potential for human infection by feline helminths be lessened?
Prevention of hookworm and roundworm infections revolves around control of animal ex-
crement in human environments. The children's sandbox should becovered when not in use, and
fecal material should beremoved immediately. Geophagia and ingestion of water in the environ-
ment should be discouraged. For hookworms, direct skin contact with moist, potentially infected
soil should be avoided. Anthelmintics should be routinely administered to all kittens at least
twice, 14-21 days apart (see Chapter 19for drugs and doses). In high-risk kittens, anthelmintics
should be administered at 6, 8, and 10 weeks of age. Fecal flotation should be performed to
assess for other parasites once or twice yearly, particularly if the cat goes outdoors, even if it is
taking heartworm preventatives.
8. What human syndromes are associated with cestodes that infect cats?
Both cats and people can be infected with Dipylidiumcaninumand Echinococcusmultilocu-
laris. Transmission to humans occurs after ingestion of the intermediate host (flea, D. caninum)or
by the ingestion of eggs (E. multilocularis). Dipylidial infection is most common in children and
can lead to diarrhea and pruritus ani. Cats playa role in this infection only by bringing fleas into
the human environment (see Chapter 90). Cats become infected by E. multilocularis when they
ingest infected intermediate hosts (rodents). Cats are subclinically infected but pass infective ova
into the human environment. After a human ingests ova, E. multilocularisonchospheres enter the
portal circulation and spread throughout the liver and other tissues. Metacestodes then develop in
infected tissues as hydatid cysts. The liver, lung, and brain are most commonly infected. The hy-
datid cysts are multilocular and grow rapidly (alveolar echinococcosis). A combination of surgical
excision and drugs is used to treat the syndrome in people, but the disease has a poor prognosis. E.
multilocularisis most common in the northern and central parts of North America but seems to be
spreading with the fox population (the most common definitive host). Although the incidence of
the disease is rare in humans, cats should not be allowed to hunt in endemic areas. Praziquantel
has been shown to be effective for the treatment of echinococcosis (see Chapter 19).
9. Which enteric protozoans of cats also infect people?
Both cats and people can be infected with Entamoeba histolytica, Cryptosporidiumparvum,
C. felis, Toxoplasmagondii, and Giardia spp. E. histolytica has been described in cats only occa-
sionally and is not likely to be a significant zoonosis.
10. Can the Giardia spp. of cats infect people? .
Giardia spp. are flagellates with worldwide distribution; they cause significant gastrointesti-
nal disease in dogs, cats, and people. The organism is believed to have a wide host range; all
mammalian isolates are currently classified as G. lamblia. Studies of the cross-infection potential
of Giardia spp. isolates have had varying results. In one study, Giardia spp. from humans were
inoculated into cats; the cats were relatively resistant to infection. In another study, isoenzyme
422
Enteric Zoonoses
electrophoresis comparison of human and feline isolates suggested that cats may serve as a reser-
voir for human infections. There also appears to be a separate feline giardial genotype. Because it
is impossible to determine zoonotic strains of Giardia spp. by microscopic examination, it seems
prudent to assume that feces from all cats infected with Giardia spp. are a potential human health
risk. Giardia spp. are common enteric pathogens and can be detected in feces of cats with and
without diarrhea. These findings emphasize that fecal examination should be performed on all
cats at least yearly, and treatment with antigiardial drugs (see Chapter 19) should be administered
if indicated. Vaccination against Giardia spp. may be considered in cats with recurrent infection
and is under evaluation as a therapeutic strategy.
11. What is cryptosporidiosis?
Cryptosporidium parvum is a coccidian that can result in severe gastrointestinal tract disease
in infected people; infection of immunosuppressed people may be life-threatening. Infection is
common in humans; approximately 300,000 people in Milwaukee developed cryptosporidiosis
when a water purification system malfunctioned; approximately 10-20% of patients with AIDS
are infected with C. parvum at some time during their life; and the organism commonly causes
diarrhea outbreaks in daycare centers. Many infected people require hospitalization for adminis-
tration of intravenous fluid therapy; people with AIDS may never be cured.
12. Do Cryptosporidium spp. infect cats?
C. parvum oocysts have been documented in feces of many domestic cats in the United
States, Japan, Scotland, Australia, and Spain. Presence of serum antibodies can be used to esti-
mate numbers of cats exposed to C. parvum. An enzyme-linked immunosorbent assay (ELISA)
for detection of C. parvum IgG placed the seroprevalence of C. parvum antibodies in cats in
Colorado and the United States at 15.3% and 8.3%, respectively. Oocysts or antigens of C.
parvum were detected in feces of 5.4% of cats tested in north central Colorado.
13. Do the Cryptosporidium spp, that infect cats infect people?
The source of C. parvum infection in humans usually is undetermined; contaminated water
is the most likely source. However, cryptosporidiosis has been documented in people and cats in
the same environment, suggesting the potential for zoonotic transfer. Limited cross-infection
studies have been performed with C. parvum isolates from cats. In one study, a feline isolate
failed to cross-infect mice, rats, guinea pigs, or dogs. In another study, a C. parvum isolate from a
cat cross-infected lambs. An alternative to cross-infection studies is genetic comparison of iso-
lates. A feline genotype that varies considerably from human and cattle genotypes has been iden-
tified. The feline genotype (C.jeUs) was documented in an infected human and an infected cow,
suggesting that the feline genotype can infect other mammals. A study of Hlv-infected people
with cryptosporidiosis found no statistical association with cat ownership, suggesting that cat
contact is an uncommon way to acquire cryptosporidiosis.
14. How should cats with cryptosporidiosis be managed?
As with Giardia spp., it is impossible to determine zoonotic strains of C. parvum by micro-
scopic examination. Thus, it seems prudent to assume that feces from all cats infected with C.
parvum are a potential human health risk. Techniques for the detection of C. parvum should be
included in the diagnostic evaluation of all cats with diarrhea and all cats in the homes of im-
munosuppressed people. Infected cats generally do not shed large numbers of cryptosporidial
oocysts, but acid-fast staining or immunofluorescent antibody staining of feces helps to identify
the parasite (approximately 5 microns). Alternatively, fecal antigen ELISAs are available. Drugs
for the treatment of cryptosporidiosis are discussed in Chapter 19. Because oocysts are immedi-
ately infectious, care should be taken in handling feces of infected cats.
15. Define toxoplasmosis.
Toxoplasma gondii is one of the most common small animal zoonoses; approximately
30-40% of adult humans in the world are seropositive, suggesting previous or current infection.
People are most commonly infected by T. gondii after ingestion of sporulated oocysts or
tissue cysts. Thus, prevention of toxoplasmosis in people can be achieved by avoiding these
two life stages. Clinical disease is generally mild after primary infection of immunocompe-
tent people. Self-limiting fever, malaise, and lymphadenopathy are the most common clinical
abnormalities, and most people do not know when their first T. gondii infection occurred. The
disease is potentially confused with infectious mononucleosis. Clinical disease can be much
more severe in immunosuppressed people, including fetuses, people with AIDS, and people
treated with immunosuppressive agents for cancer and prevention of organ transplant rejec-
tion. T. gondii is a common opportunistic infection of the central nervous system (CNS) in
people with AIDS; as T-helper cell counts decline, toxoplasmic encephalitis may result from
activation of bradyzoites in tissue cysts. If a mother has her first T. gondii infection during
gestation, stillbirth, CNS disease, and ocular disease are common clinical manifestations in
the fetus.
16. What role do cats play in human toxoplasmosis?
Cats are the only known definitive host for T. gondii and thus are responsible for passage of
oocysts into the environment. Once passed into the environment, sporulated oocysts survive for
months to years. It is likely that some people acquire toxoplasmosis when working with soil or
drinking contaminated water. Clinical toxoplasmosis developed in a group of people after a
cornmon exposure in a riding stable and in a group of soldiers drinking contaminated water in
Panama. Although it cannot be stated definitively that a person will not acquire toxoplasmosis
from a household cat, it is probably unlikely.
Cats shed oocysts for days to several weeks after primary inoculation. Thus, an individual cat
passes oocysts into the human environment for only a small fraction of its entire life span. T. gondii
oocysts are not infectious when passed by cats; sporulation requires 1-5 days in the environment.
Most cats are fastidious and do not leave feces on their fur for this time period. Bioassay failed to
detect oocysts on the fur of cats 7 days after they were shedding millions of oocysts in feces.
In general, veterinary health care providers are no more likely than the general population
to be seropositive for T. gondii infection. Because oocysts are passed in an unsporulated and
non-infectious form, working with fresh feline feces 1 day old) is not a risk for veterinary
health care personnel. People with HIV infection that owned cats were not more likely to ac-
quire toxoplasmosis during their illness than people with HIV infection that did not have con-
tact with cats.
17. Does oocyst shedding recur in previously infected cats?
After primary inoculation of cats, it is difficult to induce repeat oocyst shedding. Prednisolone
(10-80 mglkg orally) or methylprednisolone (10-80 mg/kg intramuscularly) induces repeat oocyst
shedding in some cats with toxoplasmosis. However, these doses are not routinely used in clinical
practice. Administration of methylprednisolone acetate at 5 mglkg weekly for 4-6 weeks to cats
infected with T. gondii for 14 weeks or 14 months failed to induce oocyst shedding.
In one unpublished study, cats infected with T. gondii were given feline immunodeficeincy
virus (FlV) followed by feline leukemia virus (FeLV). Although they developed immunodefi-
ciency-associated syndromes, repeat T. gondii oocyst shedding could not be demonstrated. Cats
with FlV or FeLV infections have been inoculated with T. gondii; oocyst shedding periods and
number of oocysts shed were similar to those for cats without FlY or FeLVinfections.
Gut immunity to T. gondii in cats is not permanent; 4 of 9 cats inoculated 6 years after pri-
mary inoculation shed oocysts, although each had high serum antibody titers. However, T. gondii-
infected cats with and without FlY infection failed to repeat oocyst shedding when reinfected with
T. gondii 16 months after primary inoculation. Thus, cats that are exposed to T. gondii frequently
probably do not shed large numbers of oocysts after the first infection.
18. What are other means of transmission of T. gondii to people?
Ingestion of T. gondii in tissues can result in human toxoplasmosis. Meats (particularly pork
in the United States) should be cooked to medium or well-done to inactivate tissue cysts. Gloves
424 Enteric Zoonoses
should be worn for handling raw meats (including field dressing) for cooking, or hands should be
cleansed thoroughly afterwards. Freezing meat at -12C for several days kills most tissue cysts.
Ingestion of raw goat's milk also can result in human toxoplasmosis.
19. Should healthy cats be evaluated serologically for toxoplasmosis?
No serologic assay accurately predicts when a cat shed T. gondii oocysts in the past, and
most cats that are currently shedding oocysts are seronegative. Most seropositive cats have com-
pleted the oocyst shedding period and are unlikely to repeat shedding; most seronegative cats will
shed the organism if infected. But since humans are probably not commonly infected with T.
gondii from contact with cats and since serologic test results cannot accurately predict the oocyst
shedding status of seropositive cats, testing healthy cats for toxoplasmosis is of little clinical use.
Fecal examination is an adequate procedure to determine when cats are actively shedding oocysts
but cannot predict when a cat has shed oocysts in the past. Owners who are concerned that they
may have toxoplasmosis should see their doctor for testing.
20. How can people avoid developing toxoplasmosis?
All water collected from the environment should be boiled or filtered before drinking.
Care should be taken to wash hands carefully after working with soil; alternatively, gloves
should be worn.
Produce from the garden should be washed carefully before ingestion. The children's sand-
box should be covered when not in use.
A litterbox liner should be used, and the litterbox should be cleaned daily. Oocysts require
1-5 days to sporulate.
lmmunosuppressed or pregnant cat owners should not clean the litterbox.
Sporulated oocysts are extremely resistant to most disinfectants. Thus, cleaning with scald-
ing water or steam is most practical.
Oocysts measuring 10 x 12 I! in a cat fecal sample may be T. gondii. Hammondia hammondi
and Besnoitia darlingi are morphologically similar coccidians passed by cats but are not
human pathogens. The feces should be collected daily until the oocyst shedding period is com-
plete; administration of clindamycin (25-50 mglkglday orally), sulfonamides (100 mg/kg/day
orally), or pyrimethamine (2.0 mglkglday orally) can reduce levels of oocyst shedding.
Cats should not be allowed to hunt and should be fed only processed or cooked foods.
Potential transport hosts such as flies and cockroaches should be controlled.
Meat should be cooked to medium well-done.
Gloves should be worn or hands washed after handling meat.
21. What are the common bacterial zoonotic agents?
Salmonella spp., Campylobaeterjejuni, E. coli. and Yersinia enteroeolitieainfect cats and
can cause disease in humans. Gastroenteritis may occur in both species after infection. Y. entero-
eolitieais probably a commensal agent in cats but induces fever, abdominal pain, and bacteremia
in humans. Helieobaeterpylori causes ulcers in people and has been isolated from a colony of
cats; the zoonotic risks are currently undetermined but appear to be minimal. Infected cats and
people in the same family have been found to be infected with Helieobaeter spp. Three other
studies, including one of veterinarians, found no epidemiologic association of cat contact with
human helicobacteriosis. Salmonellaspp. infection in cats is often subclinical, but in one study
the incidence was only I % in client-owned and shelter cats with and without diarrhea.
Approximately 50% of clinically affected cats have gastroenteritis; many are presented with
abortion, stillbirth, neonatal death, or signs of bacteremia. Some cats with salmonellosis have a
history of ingesting a songbird (songbird fever). If neutrophils are noted on rectal cytology, cul-
ture for Salmonellaand Campylobaeter spp. is indicated. Human infection with Campylobacter
spp. has been associated with cat contact. Infection occurs after fecal-oral or fomite exposure,
and prevention is based on sanitation and control of exposure to feces. See Chapter 20 for a dis-
cussion of the clinical management of these infections.
22. What is the recommended diagnostic evaluation for enteric zoonotic agents?
If enteric zoonotic agents are of concern, procedures that should be performed include fecal
flotation for giardial cysts and helminth eggs, fecal wet mount for protozoal trophozoite identifi-
cation, acid-fast monoclonal antibody staining of fecal smears or fecal antigen testing for C.
parvum, and fecal culture for enteric bacteria.
BIBLIOGRAPHY
I. Angulo FJ, Glaser CA, Juranek DD, et al: Caring for pets of immunocompromised persons. J Am Vet
Med Assoc 205:171 1-1718, 1994.
2. Blagburn BL, Conboy G, Jutras P, et al: Strategic control of intestinal parasites: Diminishing the risk of
zoonotic disease. Comp Cont Educ Pract Vet 19S:4-20, 1997.
3. Deming MS, Tauxe RV, Blake PA, et al: Campylobacter enteritis at a university: Transmission from
eating chickens and from cats. Am J Epidemiol 126:526-534, 1987.
4. Dubey JP, Lappin MR: Toxoplasmosis and neosporosis. In Greene CE (ed): Infectious Diseases of the
Dog and Cat, 2nd ed. Philadelphia, W.B .Saunders, 1998, pp 493-503.
5. Eberhard ML, Alfano E: Adult Toxocara cati infections in U.S. children: Report offour cases. Am J Med
Hyg 59:404-406, 1998.
7. Glaser CA, Safrin S, Reingold A, et al: Association between Cryptosporidium infection and animal ex-
posure in HIV-infected individuals. J AIDS 17:79-82, 1998.
8. Hill S, Lappin MR, Cheney J, et al: Prevalence of enteric zoonotic agents in cats. J Am Vet Med Assoc
216:687-692,2000.
9. Homan WL, Gilsing M, Bentala H, et al: Characterization of Giardia duodenal is by polymerase-chain-
reaction fingerprinting. Parasitol Res 84:707-714, 1998.
10. Hopkins RM, Meoni BP, Groth DM, et al: Ribosomal RNA sequencing reveals differences between the
genotypes of Giardia isolates recovered from humans and dogs living in the same locality. J Parasitol
83:44-51,1997.
II. Juranek DD: Cryptosporidiosis: Sources of infection and guidelines for prevention. Clin Infect Dis
21:S57-S6I,1995.
12. Jutras P: Important zoonotic helminth infections. Comp Cont Educ Pract Vet IOS:4-9, 1997.
13. Kirkpatrick CE and Green GA: Susceptibility of domestic cats to infections with Giardia lamblia cysts
and trophozoites from human sources. J Clin Microbiol 21:678-680, 1985.
14. Lu SQ, Baruch AC, Adam RD: Molecular comparison of Giardia Lamblia isolates. Int J Parasitol
28:1341-1345,1998.
15. Meloni BP, Lymbery AJ, Thompson RCA: Isoenzyme electrophoresis of 30 isolates of Giardia from
humans and felines. Am J Trop Med Hyg 38:65-73,1988.
16. McReynolds C, Lappin MR, McReynolds L, et al: Regional seroprevalence of Cryptosporidium parvum
IgG specific antibodies of cats in the United States. Vet Parasitol 80: 187-195, 1998.
17. Neiger R, Simpson KW: Helicobacter infection in dogs and cats: Facts and fiction. J Vet Intern Med
14:125-133,2000.
18. Sargent KD, Morgan UM, Elliot A, et al: Morphological and genetic characterisation of Cryptosporidium
oocysts from domestic cats. Vet Parasitol 77:221-227, 1998.
19. Tan JS: Human zoonotic infections transmitted by dogs and cats. Arch Intern Med 157:1933-1943, 1997.
20. Thompson RCA, Hopkins RM, Homan WL: Nomenclature and genetic groupings of Giardia infecting
mammals. Parsitol Today 16:210-213,2000.
21. Wallace MR, Rossetti RJ, Olson PE: Cats and toxoplasmosis risk in HIV-infected adults. J Am Med
Assoc 269:76-77, 1993.
85. BITE.. ORSCRATCH..ASSOCIATED ZOONOSES
Alice J. Johns, D.V.M.
1. What infectious agents are transmitted by scratches or bites?
Multiple bacteria can induce infection of people after bites and scratches. Bartonella hense-
lae (cat scratch disease [CSDD and oral flora such as Pasteurella spp. are most common. Rabies
is the only significant viral disease transmitted by this means. Although Blastomyces dermatitidis
has been transmitted by dog bites, systemic fungal diseases usually are not transmitted directly
from animals to humans.
Common Feline Bite- and Scratch-associated Zoonoses
ORGANISM
Bacteria
Bartonella spp.
Capnocytophaga canimorsus
Francisella tularensis
Yersinia pestis
Fungus
Sporothrix schenkii
Virus
Rabies
eNS =central nervous system.
CLINICAL SYNDROME
Cats: subclinical; rarely uveitis, fever
Humans: lymphadenopathy, fever, malaise,
bacillary angiomatosis, bacillary peliosis
Cats: subclinical
Humans: bacteremia
Cats: septicemia, pneumonia
Humans: ulceroglandular, glandular, oculo-
glandular, pneumonic, or typhoidal
(depending on route of infection)
Cats: bubonic, bacteremic, or pneumonic
Humans: bubonic, bacteremic, or pneumonic
Cats: chronic draining cutaneous tracts
Humans: chronic draining cutaneous tracts
Cats: progressive CNS disease
Humans: progressive CNS disease
RELATIVE RISK
FROM CATS TO
HUMANS
Common
Rare
Extremely rare
Rare; regional
Extremely rare
Rare
2. Are bites and scratches common?
Animal bites result in approximately 300,000 emergency department visits per year in the
United States. The majority of the aerobic and anaerobic bacteria associated with bite or scratch
wounds lead only to local infection in immunocompetent people. However, 28-80% of cat bites
become infected, and uncommon severe sequelae, including meningitis, endocarditis, septic
arthritis, and septic shock, can occur. Most bite wounds are located on the hands, arms, or face.
Bite wounds are contaminated with aerobic and anaerobic flora from the eat's mouth and aerobic
bacteria from the skin. Cat bites may be at higher risk of infection than dog bites because they
create small, deep puncture wounds that are difficult to irrigate and debride.
3. What bacteria are usually involved with bites or scratches?
Bite wounds typically have multiple bacterial isolates. Pasteurella multocida is responsible for
90% of infections resulting from cat bite wounds. Also commonly isolated are alpha-hemolytic
Streptococcus spp., Staphylococcus spp., Bacteriodes spp., and Fusobacterium spp. Irnmuno-
compromised people or those exposed to Pasteurella spp. or Capnocytophaga canimorsus (DF-2)
426
Bite- or Scratch-associated Zoonoses 427
more consistently develop systemic clinical illness after bites or scratches. Local cellulitis is
noted initially, followed by evidence of deeper tissue infection. Bacteremia and the associated
clinical signs of fever, malaise, and weakness are common. Death can occur from either genus,
particularly in splenectomized individuals. At least two cases of mycoplasmal infection associ-
ated with cat bites have been reported in humans.
4. How should cat bites and scratches be treated?
Wounds should be irrigated voluminously with sterile saline and scrubbed. Refer to a physi-
cian any client or staff member who is bitten. Delay in seeking treatment may result in a more se-
rious infection, requiring hospitalization for intravenous antibiotics. Diagnosis of bacterial
infections is confirmed by culture. Treatment includes local wound drainage and systemic antibi-
otic therapy. Penicillin derivatives are highly effective against most Pasteurella infections.
Penicillins and cephalosporins are effective against Capnocytophaga spp. in vitro.
5. How can cat bites and scratches be prevented?
Cats should not be teased, and appropriate restraint techniques should be used at all times to
attempt to avoid being bitten or scratched.
6. What causes CSD?
CSD is most commonly associated with infection by Bartonella henselae (formerly
Rochalimaea henselae). The organism is a small (0.3-3 um), highly pleomorphic, gram-negative
bacillus. It is facultatively intracellular and hemotropic and stains with Warthin-Starry silver
stain. B. henselae also causes bacillary angiomatosis and bacillary peliosis in immunocompro-
mised people. Cats also carry B. clarridgeiae and B. koehlerae.
7. Describe the epidemiology of B. henselae infection in cats.
Subclinical bacteremia is common in the feline population; as many as 54.6--81% of cats in
some geographical areas of the United States are seropositive for Bartonella spp. and presumably
were infected at one time. B. henselae has been cultured from the blood of many naturally ex-
posed cats; cats infected with the organism by inoculation intradermally, subcutaneously, intra-
venously, or intramuscularly; and cats infected by Ctenocephalidies felis. Bacteremia occurs in
cats within 2 weeks of exposure to infected fleas. Once infected, cats are intermittently bac-
teremic for months. B. henselae can be cultivated from 9-day-old flea feces, and it is likely that
contact with fleas or their feces can transmit the organism to humans. The organism is present in
feline red blood cells and may reside in or be excreted into the oral cavity. The organism proba-
bly is transferred to the claws during grooming or by bite wounds or licking open sores.
8. Do infected cats develop clinical illness?
Most cats have subclinical B. henselae infections. However, intravenous, intramuscular, and
intradermal inoculation has resulted in fever, lymphadenopathy, and neurologic diseases in some
cats. Uveal tract inflammation and other clinical signs of disease, including gingivitis and lym-
phadenopathy, have been reported in some naturally infected cats..
9. Describe the clinical signs of CSD.
CSD is the most common cause of chronic, benign lymphadenopathy in children and young
adults. Typically, a nonpruritic, erythematous papule or pustule develops at the inoculation site
3-10 days after exposure. Regional lymphadenitis without lymphangitis follows within several
weeks and may persist for weeks or months. Affected lymph nodes may abscess and drain sponta-
neously. Systemic signs may include fever, malaise, headache, anorexia, and myalgia. Weight loss,
sore throat, splenomegaly, nausea, and vomiting occur in some patients. The syndrome is usually
self-limiting. Imrnunocompromised or immunosuppressed people can develop hypotension, septic
shock, metabolic acidosis, pulmonary infiltrates, and persistent fever. In unusual cases, ocular dis-
ease (Parinaud's oculoglandular disease), neurologic signs (convulsions or delirium), osteolytic
428
Bite- or Scratch-associated Zoonoses
lesions, or cutaneous eruptions may develop. In rare cases, splenic abscesses, hemolytic anemia.
granulomatous hepatitis, pulmonary granuloma or atypical pneumonia may develop.
10. How is CSD diagnosed?
In people. a diagnosis is made if three of the four following criteria are met:
I. History of traumatic cat contact (scratch or bite)
2. Regional lymphadenopathy with characteristic nodal lesions
3. Negative laboratory investigation for unexplained lymphadenopathy
4. Detection of antibodies to B. henselae or detection of B. henselae DNA using polymerase
chain reaction (PCR) analysis of tissue samples or lymph node aspirates.
11. How is B. henselae infection diagnosed in cats?
Several tests available can be used to assess the B. henselae infection status of individual
cats. Cats should be screened for antibodies as well as by an organism demonstration technique
(culture or PCR).
Antibodies against B. henselae can be detected in serum. Positive test results suggest cur-
rent or previous infection. Negative test results suggest peracute exposure 3 weeks) or
absence of infection.
Detection of local production of antibodies in aqueous humor was used to document ocular
bartonellosis in I cat.
The organism can be grown from the blood (EDTA anticoagulant). Positive test results
prove current infection. Negative results suggest peracute exposure 2 weeks) or absence
of infection. However, intermittent bacteremia commonly occurs and may lead to false-
negative results on a single test.
B. henselae DNA can be detected in blood or aqueous humor by PCR. Positive test results
suggest current infection. Negative test results suggest peracute exposure 2 weeks) or
absence of infection. However, intermittent bacteremia commonly occurs and may lead to
false-negative results on a single test.
An antibody-negative, PCR/culture-negative cat is probably not infected.
12. Should infected cats be treated?
Whether to treat bacteremic cats is controversial. To date, administration of antimicrobials
has led to rapid resolution of bacteremia, but some treated cats become bacteremic again after
treatment is discontinued. The following drugs, used singly, have been reported:
Doxycycline (25-50 mg/cat orally every 12 hr for 30 days)
Enrofloxacin (22.7 mg/cat orally every 12 hr for 4 weeks)
AmoxiciIIin (100-200 mg/cat orally every 12 hr for 1--4weeks)
13. Describe the clinical course of CSD.
Most cases resolve spontaneously in a few weeks or months. Antibiotics (rifampin,
ciprofloxacin, trimethoprim-sulfa, or gentamycin) are used by some clinicians. Treatment is con-
tinued for 2 weeks in severe cases in immunocompetent patients and for 6 weeks in immunocom-
promised patients.
14. What is the prognosis of CSD?
The prognosis is excellent for immunocompetent people. Primary infection is likely to result
in life-long protection. Life-threatening or relapsing infections can occur in immunocompro-
mised people.
15. How can CSD be prevented?
I. Avoid traumatic contact with cats or avoid behaviors that may lead to a bite or scratch.
2. Do not kiss cats or allow them to lick open wounds.
3. Wash hands thoroughly after handling cats.
4. Wash bites, scratches, and cuts promptly with antiseptic soap.
5. Contact a physician for any bite wound.
6. Maintain good flea and tick control and prevention programs.
429
16. Can Yersinia pestis be transmitted by the bite of an infected cat?
Plague is considered endemic in the southwestern United States (see Chapter 86). Because
many cats are infected by ingesting bacteremic rodents and have Y. pestis replication in the
oropharynx, infection of humans may occur after bites or scratches. The organism also can be
transmitted to humans by respiratory secretions and is a shared vector zoonosis.
17. What causes tularemia?
Tularemia is a syndrome caused by Francisella tularensis, a gram-negative bacillus found
throughout the continental United States.
18. How is tularemia acquired?
The disease is vector-borne by Dermacenter variabilis, D. andersoni, and Amblyomma
americanum. Human tularemia results most commonly from tick exposure and less commonly
from contact with infected animals, including cats. Cats are infected most frequently by tick bites
or by ingesting infected rabbits or rodents. Cat-associated tularemia in humans has occurred most
frequently via bites.
19. How is F. tularensis managed clinically?
Ulceroglandular, oculoglandular, glandular, oropharyngeal, pneumonic, and typhoidal forms
have been described in humans. The specific form depends on the route of exposure. Infected
cats exhibit generalized lymphadenopathy and abscess formation in organs such as the liver and
spleen, which leads to fever, anorexia, icterus, and death. Cultures and documentation of increas-
ing antibody titers can be used to confirm the diagnosis in cats and humans. Ectoparasite control
should be maintained, and cats should not be allowed to hunt to lessen risk of exposure.
20. What causes rabies?
Rabies is caused by a single-stranded RNA virus in the genus Lyssavirus, family
Rhabdoviridae. There are 10 genetically distinct rabies variants in the United States.
21. Describe the pathogenesis of rabies.
The rabies virus enters the body through a wound, usually a bite, or the mucous membranes.
After replicating in monocytes, it spreads to neuromuscular junctions and neurotendinal spindles.
The virus travels to the central nervous system (CNS) via intraaxonal fluid within peripheral
nerves, then spreads throughout the CNS. From the CNS it spreads to the peripheral sensory and
motor neurons. Large quantities of virus are present in saliva.
22. What are the clinical signs of rabies?
Atypical presentations of rabies are common. Rabies must be included on the differential list
for any cat showing unusual mood or behavior changes or exhibiting any unaccountable neuro-
logic signs. Handle cases with extreme caution to prevent exposure of personnel. The three stages
of rabies are prodromal, furious, and paralytic. Rabies should be suspected in animals with the
following symptoms:
Change in attitude (apprehension, nervousness, anxiety, unusual aggressiveness or shyness)
Anxious, staring, wild, spooky, or blank look in the eyes
Erratic behavior (biting, snapping, licking, or chewing at a wound site, biting at cage, wan-
dering or roaming)
Excitability, irritability, or viciousness
Muscular incoordination, abnormal gait (especially involving the rear limbs), disorienta-
tion, seizures, or paralysis
430
Change in sound or pitch of voice or increased frequency of vocalization
Excessive salivation or frothing
Physical examination may reveal mandibular and laryngeal paralysis with dropped jaw, in-
ability to swallow, and hypersalivation. Fever may be present.
23. What are the dift'erential diagnoses for rabies?
Other neurologic disease (brain tumor, viral encephalitis)
Head wound or trauma
Laryngeal paralysis
Choking
Pseudorabies
24. Howis rabies diagnosed?
Complete blood count and serum biochemical panel reveal no characteristic abnormalities.
Cerebrospinal fluid may show a slight increase in protein or leukocyte counts. Direct im-
munofluroescent antibody testing must be done on nervous tissue (brain) or dermal tissue (skin
biopsy of sensory vibrissae of maxillary area, including deeper subcutaneous hair follicles).
25. Howis rabies treated?
Nearly 100%of cats die within 7-10 days of the onset of symptoms. There is no treatment.
Once the diagnosis is certain, the cat should be humanely euthanized.
26. Howcan rabies be prevented?
Cats should be vaccinated according to local ordinances with an inactivated vaccine (see
Chapter 81). Previously vaccinated cats should be given a booster vaccine if treated for wounds
that may be bite-related. Quarantine procedures should be used for any rabies suspect, and the
case should be reported to the authorities. The virus can be inactivated by disinfection with a 1:32
dilution of bleach. Personnel at risk should be immunized.
27. Can people be infected by feline retroviruses?
Feline leukemia virus (FeLV) and feline foamy virus (syncycia-forming virus) grow in
human cell cultures; feline immunodeficiency virus (FIV) does not. Studies of people with
chronic fatigue syndrome (FeLV), leukemia (FeLV and FlV), and veterinarians (FeLV, FlV, feline
foamy virus) have failed to find evidence that these viruses infect people in vivo.
BIBLIOGRAPHY
I. Bonilla HF, Chenoworth CE, Tully JG, et al: Mycoplasmafelis septic arthritis in a patient with hypogam-
maglobulinemia. Clin Infect Dis 24: 222-225,1997.
2. Butera ST, Brown J, Callahan ME, et al: Survey of veterinary conference attendees for evidence of
zoonotic infection by feline retroviruses. J Am Vet Med Assoc 217:1475-1479,2000.
3. Carpenter PD, Heppner BT, Gnann JW: DF-2 bacteremia following cat bites: Report of two cases. Am J
Med 82:621,1987.
4. Chomel BB, Kasten RW, floyd-Hawkins K, et al: Experimental transmission of Bartonella henselae by
the cat flea. J Clin MicrobioI34:1952-1956, 1996.
5. Clark KA: Rabies. JAm Vet MedAssoc 192:1404-1406, 1998.
6. Fogelman V, Fischman HR, Horman IT, et al: Epidemiologic and clinical characteristics of rabies in cats.
J Am Vet Med Assoc 202:1829-1833, 1993.
7. Gasper PW: Plague. In August JR (ed): Consultations in Feline Internal Medicine, vol. 3. Philadelphia,
W.B.Saunders, 1997, pp 12-22.
8. Guptill L, Slater L, Ching-Ching W, et al: Experimental infection of young specific pathogen-free cats
with Bartonella henselae. J Inf Dis 176:206--216, 1997.
9. Kordick DL, Breitschwerdt EB: Bartonella infections in domestic cats. In Bonagura JD (ed): Current
Veterinary Therapy XIII-Small Animal Practice. Philadelphia, W.B. Saunders, 2000, pp 302-307.
10. Lappin MR, Black JC: Bartonella spp. associated uveitis in a cat. J Am Vet Med Assoc 214;1205-1207,
1999.
Respiratory Zoonoses 431
II. Lappin MR, Jensen W, KordickDL, et al: Bartonella spp. antibodies and DNAin aqueous humor of cats.
Feline Med Surg 2:61--68, 2000.
12. Rohrbach BW: Tularemia. J AmVet MedAssoc 193:428-432, 1988.
13. Talan DA, Citron DM, Abrahamian FM, et al: Bacteriologic analysis of infected dog and cat bites. N
Engl J Med 340:85-92, 1999.
14. Trevejo RT: Rabies preexposure vaccinationamong veterinarians and at risk staff. J Am Vet Med Assoc
217:1647-1650,2000.
15. ValtonenM, LauhioA, Carlson P,et al: Capnocytophaga canimorsus septicemia: Fifth report of a cat-as-
sociated infection and five other cases. Eur J Clin Microbiol Infect Dis 14:520-523, 1995.
86. RESPIRATORYZOONOSES
Michael R. Lappin, D.v.M., Ph.D., and Alice J. Johns, D.V.M.
1. Howoftendo cats andpeople sharerespiratory tractinfections?
Although infectious causes of respiratory disease are extremely common in cats (see Section I),
most causes are not transmissible to humans (feline herpesvirus I, calicivirus). Humans are po-
tentially exposed to Bordetella bronchiseptica and Chlamydia psitacci but rarely develop clinical
infection. Yersinia pestis is a notable exception; both cats and people can develop pneumonic
plague, which is a life-threatening disease. Group A streptococcal infections are a reverse zoono-
sis: humans are the primary reservoir, and cats are infected by contact with humans. Pasteurella
multocida from a cat was cultured from the lungs of a man with AIDS who had had only passive
contact with the cat.
Common Zoonoses Associated with Direct Contact with Respiratory
or Ocular Secretions of Cats
ORGANISM
Bordetellabronchiseptica
Chlamydia psittacii
Coxiellabumetii
Pasteurellamultocida
Streptococcus group A
Yersinia pestis
CLINICAL SIGNS
Cats: upper respiratory, rarely, pneumonia
Humans: pneumonia in immunosuppressed
patients
Cats: conjunctivitis, mild upper respiratory
disease
Humans: conjunctivitis, bacteremia
Cats: subclinical, abortion, or stillbirth
Humans: fever, pneumonitis, lymphadenopathy,
myalgia, arthritis
Humans: ulceroglandular, oculoglandular,
glandular, pneumonic, or typhoidal (depend-
ing on route of inoculation)
Cats: normal flora
Humans: one case of pneumonia from passive
contact with a cat has been reported
Cats: subclinical, transient carrier
Humans: strep throat, septicemia
Humans: bubonic, bacteremic, or pneumonic
RELATIVE RISK
FROMCATS TO
HUMANS
Extremely rare
Extremely rare
Unknown:
probably rare
Extremely rare
Extremely rare
Extremely rare
Extremely rare
and regional
432
Respiratory Zoonoses
2. How common is bordetellosis in cats?
B. bronchiseptica commonly causes infectious tracheobronchitis in dogs. Many cats from
crowded environments have serologic evidence of exposure or are culture-positive, but most in-
fected cats are clinically normal (see Chapters 2 and 12).
3. Do people develop bordetellosis from contact with cats?
Bordetella pertussis commonly infects and causes disease in people but is not a disease of
cats. By 1998, 39 cases of B. bronchiseptica infection in people had been reported; most patients
were immunodeficient. One person who was coinfected with B. bronchiseptica and HIV owned a
cat. Because cats are commonly exposed but people are rarely infected, B. bronchiseptica infec-
tion of people from contact with cats appears to be unlikely. However, a diagnostic work-up and
antimicrobial therapy should be considered for cats with suspected bacterial respiratory disease if
the household has an immunosuppressed member. Definitive diagnosis is based on culture.
Tetracycline derivatives, axomicillin-clavulanate, and quinolones are effective in controlling clin-
ical signs of disease, but treated cats can be culture-positive for months.
4. Describe the clinical fmdings of chlamydiosis in cats.
Chlamydia psittaci infection of cats commonly causes conjunctivitis (see Chapter 2). If res-
piratory disease occurs, it is a mild rhinitis; lower respiratory tract disease is uncommon.
5. Are cats and people commonly exposed to C.psittaci?
In a recent study from Japan, antibodies against a feline strain of C.psittaci were detected in
45.5% of stray cats, 17.3% of pet cats, 1.7% of the general human population, and 8.8% of small
animal veterinarians, suggesting that exposure is common.
6. Do feline strains of C. psittacicause disease in people?
Although exposure to C. psittaci seems common, it has been associated with disease only in
rare cases. Conjunctivitis in humans after direct contact with ocular discharges has been sus-
pected. A chlamydial species isolated from an infected person was inoculated into cats, resulting
in conjunctivitis and persistent infection. This experiment suggests that the isolate was from a cat.
Feline Chlamydia spp. were indirectly associated with atypical pneumonia in an apparently im-
munocompetent 48-year-old man; with malaise and cough in an immunosuppressed woman; and
with endocarditis and glomerulonephritis in a 40-year-old woman. Care should be taken to avoid
direct conjunctival contact with discharges from the respiratory or ocular secretions of cats, espe-
cially by immunosuppressed persons. Topical or oral tetracycline derivatives are effective for the
treatment of infected cats.
7. Do cats harbor group Astreptococci?
It has been proposed that cats can be infected with group A streptococci and transmit the
infection to children, ultimately causing strep tho at. Humans are the principal natural hosts
for group A streptococci, but cats may develop a transient (about 2 weeks), subclinical infec-
tion from contact with an infected human. Because cats are occasionally infected, it is plausi-
ble that cat contact can lead to infection of people. However, this scenario is poorly
documented and believed to be unlikely. Culture of a group A streptococcal organism from
the tonsillar crypts can document a feline infection. Administration of penicillin derivatives is
generally effective. However, if the cats are treated in an attempt to stop a strep throat prob-
lem in humans, all family members should be treated because humans can have a prolonged
subclinical carrier phase.
8. What is feline plague?
Yersenia pestis is a gram-negative, bipolar staining coccobacillus in the family Entero-
bacteriaceae. It is endemic in rodent populations worldwide, including the western United States,
where prairie dogs, rock squirrels, and ground squirrels are the commonly involved rodents.
Respiratory Zoonoses 433
9. Describe the pathogenesis of plague.
Fleas ingest a blood meal from an infected animal. The blood clots and blocks the gut of the
flea. When the flea bites the next victim, it regurgitates Y. pestis onto or into the skin. Cats also
are infected by ingestion of infected rodents when the organism enters via the mouth or esopha-
gus. The bacteria migrate from the skin lymphatics to the regional lymph nodes. The organism is
transmitted to humans by the bite of infected rodent fleas, aerosalization, bites and scratches
from infected animals (including cats), or direct contact with infected people. The organism has a
capsular glycoprotein with antiphagocytic properties and potent endotoxins. It proliferates
rapidly and massively in susceptible hosts.
10. What are the three fonns of plague in cats and people?
I. Bubonic (from a flea bite or ingestion of an infected transport host)
2. Pneumonic (via droplets or hematogenous spread)
3. Septicemic (via direct blood injection or extension of the bubonic or pneumonic form)
11. Describe the clinical signs of plague in cats and people.
In cats, the symptoms include lethargy, anorexia, fever (103-105P), and lymphadenopathy
(typically the submandibular, anterior cervical and medial retropharyngeal lymph nodes).
Dyspnea and cough also can occur. The incubation period is 2-7 days after a flea bite or inges-
tion of an infected rodent.
In people, the symptoms are fever, lymphadenopathy, intense local inflammation, depression,
vomiting and diarrhea, dehydration, enlarged tonsils, ocular discharge, weight loss, ataxia, coma,
and oral ulcers. The lymph nodes become hemorrhagic, necrotic, and edematous. The lymph
nodes may abscess, rupture, and drain through fistulous tracts to the skin. Septicemia may occur.
12. How is plague diaguosed?
History and physical examination findings can be used to place the disease high on the dif-
ferential list. Most cases of feline plague are diagnosed between April and October when rodent
fleas are most active. Any outdoor cat from an endemic area with fever and submandibular lym-
phadenopathy or fever and signs of pneumonia should be considered a plague suspect and imme-
diately placed in isolation. The following steps should be taken:
I. Sedate the cat to avoid bites and scratches while collecting tissue aspirates.
2. Place a small amount of material on a swab for bacterial culture and label as plague sus-
pect.
3. Make more than I thin smear of material so that routine cytology as well as fluorescent
antibody staining can be performed.
4. The diagnosis is confirmed by culture of exudates, tonsillar area, and saliva, fluorescent
antibody staining of exudates, and documentation of increasing antibody titers.
5. Contact county and state public health officials as well as the Centers for Disease Control
if plague is suspected.
13. How is feline plague treated?
Infected cats should be treated with enrofloxacin (5 mglkg/day intramuscularly) or amino-
glycosides for the first 4 days of treatment. Doxycycline (5-10 mglkg/day orally) then is pre-
scribed for at least 14 days. Oral antibiotics should not be used while the cat is hospitalized to
avoid placing your hands in the eat's mouth, where large numbers of the organism are present.
Most treated cats survive. Cats are not considered infectious after 3-4 days of antibiotic therapy
and can be discharged.
14. How is plague prevented?
Hospitalized cats are maintained in isolation and handled by as few people as possible.
Handlers should wear a barrier gown, safety goggles, and surgical mask. Some recommend that
cats with pneumonic plague be humanely euthanized because of the high zoonotic potential.
434
Respiratory Zoonoses
People in contact with the infected cat should seek medical advice about prophylactic antibiotic
treatment. Untreated pneumonic plague is 100%fatal in people. The mortality rate is 5-20% with
appropriate antibiotic treatment but much higher if antibiotics are started later than 24 hours after
the onset of pneumonic or septicemic forms of the disease. Flea control should be initiated im-
mediately for the affected cat and other client pets. Cats should be housed indoors and not be al-
lowed to hunt.
IS. Howcanrespiratory zoonoses be prevented?
House cats indoors to avoid contracting respiratory diseases.
Have a veterinarian evaluate cats with clinical evidence of respiratory disease.
Have someone other than an immunosuppressed person treat cats with suspected infectious
respiratory diseases.
BIBLIOGRAPHY
1. Bart M, Guscetti F, Zurbriggen A, et al: Feline infectious pneumonia: A short literature review and a ret-
rospective immunohistological study on the involvement of Chlamydia spp. and distemper virus. Vet J
159:220-230,2000.
2. Binns SH, Dawson S, Speakman AJ, et al: Prevalence and risk factors for feline Bordetella bronchisep-
tica infection. Vet Rec 144:575-580, 1999.
3. Cotton MM, Partridge MR: Infection with feline Chlamydia psittaci. Thorax 53:75-76, 1998.
4. Eidson M, Thilsted JP, Rollag OJ: Clinical, clinicopathologic and pathologic features of plague in cats:
119 cases (1977-1988). J Am Vet Med Assoc 199:1191-1197, 1991.
5. Dworkin MS, Sullivan PS, Buskin SE, et al: Bordetella bronchiseptica infection in human immunodefi-
ciency virus-infected patients. Clin Infect Dis 28:1095-1099,1999.
6. Drabick n, Gasser RA, Saunders NB, et al: Pasteurella multocida pneumonia in a man with AIDS and
nontraumatic feline exposure. Chest 103:7-11, 1993.
7. Greene CE, Prescott JF: Streptococcal and other gram-positive bacterial infections. In Greene CE
(ed): Infectious Diseases of the Dog and Cat, 2nd ed. Philadelphia, W.B.Saunders, 1998, pp 205-
2[4.
8. Griffins PD, Lechler RI, Treharne JD: Unusual chlamydial infection in a human renal allograft recipient.
BMJ 277: [264-1265. 1978.
9. Hoskins JD, Williams J, Roy AF, et al: Isolation and characterization of Bordetella bronchiseptica from
cats in southern Louisiana. Vet Immunol Immunopathol 65:173-176.1998.
10. Macy DW: Plague. In Greene CE (ed): Infectious Diseases of the Dog and Cat, 2nd ed. Philadelphia,
W.B. Saunders, 1998, pp 295-300.
11. Ostler HB. Schacter J, Dawson R: Acute follicular conjunctivitis of epizootic origin. Arch Ophthalmol
82:587-591, 1%9.
12. Regan RJ, Dathan JRE, Treharne JD: Infective endocarditis with glomerulonephritis assocated with cat
chlamydia (c. psittaci) infection. Br Heart J 42:349-352, 1979.
13. Stefanelli P, Mastrantonio P, Hausman SZ. et al: Molecular characterization of two Bordetella
bronchiseptica strains isolated from children with coughs. J Clin Microbiol 35:1550-1555,
1997.
[4. Yan C, Fukushi H, Matsudate H, et al: Seroepidemiological investigation of feline chlamydiosis in
cats and humans in Japan. Microbiol Immunol44: 155-160,2000.
87. EXUDATE ANDCUTANEOUS ZOONOSES
Michael R. Lappin, D.V.M., Ph.D., and Tammy P. Sadek, D.V.M.
1. What infectious agents can be transmitted to people directly from contact with tbe skin
or exudates of cats?
Several bacterial agents, fungal agents, and ectoparasites that cause skin or exudative dis-
eases of cats are transmittable to people. Dermatophytes and fleas are most common.
Common Feline Cutaneous and Exudate-associated Zoonoses
ORGANISM
Bacteria
L-formbacteria
Yersinia pestis
Eetoparasites
Cheyletiella spp.
Ctenocephalides felis
Noteodres cati
Sarcoptes scabei
Ticks
Fungi
Dermatophytes
Sporothrix schenkii
CLINICAL SYNDROME
Humans: ulceroglandular, glandularoculoglandular,
pneumonic, or typhoidal (depending on routeof
infection)
Cats: chronicdrainingtracts, polyarthritis
Humans: chronicdrainingtracts, polyarthritis
Humans: bubonic,bacteremic, or pneumonic
Cats: superficial dermatologic disease
Humans: superficial dermatologic disease
Cats: superficial dermatologic disease; anemia;
transmission of vector-borne diseases
Humans: superficial dermatologic disease;
Cats: superficial dermatologic disease;anemia;
Humans: superficial dermatologic disease;
Cats: chronicdrainingcutaneoustracts
Humans: chronicdrainingcutaneoustracts
RELATIVE RISK'
TO HUMANS
Extremely rare
Extremely rare
Rare; regional
Common
Common
Rare
Rare
Common
Common
Extremely rare
* Frequency of infection from direct contact with infected cats.
2. Wbat is the most common dermatopbyte of cats?
Microsporum canis is the most common dermatophyte of cats; it is also the organism most
commonly associated with zoonotic transfer to people.
3. How common is buman infection with feline dermatopbytes?
Approximately 50% of people exposed to dermatophytes become infected; most people that
live in a household with infected cats become infected.
435
436
Exudate and Cutaneous Zoonoses
4. Describe the range of clinical symptoms in cats and humans.
Cats can be subclinical carriers or develop superficial dermatologic disease characterized by
broken haired alopecia, crusts, and scale.
Humans develop characteristic red, raised, circular, pruritic lesions at infection sites; inva-
sive infection may occur in immunocompromised people.
Ringworm lesionon a human. (Courtesy of Rodney Rosychuk, M.D., ColoradoStateUniversity.)
5. What are the most common risk factors for dermatophytosis?
Kittens from shelters with known history of infection
Exposure to pet cats housed with large numbers of other animals
Age of both human and cat (children and kittens are most likely to be infected)
6. How is dermatophytosis diagnosed?
Microconidia are noted within hair shafts on cytologic examination after KOH clearance;
definitive diagnosis is made by culture of hair.
7. How can zoonotic transfer be prevented?
To lessen potential for zoonotic transfer of infection from infected cats, the body should be
shaved, and both topical and systemic treatment should be instituted.
The vaccine is not recommended by most authorities as a preventive measure. Some believe
that the vaccine can be used beneficially in cats that are difficult to handle or treat, but vaccina-
tion may increase the rate of subclinical carriers.
8. Do fungi associated with systemic infections cause human disease from direct contact
with infected cats?
Cats are rarely infected by Blastomyces dermatitidis, Coccidioides immitis, Histoplasma
capsulatum, Cryptococcus neoformans, and Sporothrix schenkii. Each of these fungi can cause
exudative skin disease, but only S. schenkii has a high rate of transmission from infected cats to
people. The others are acquired from environmental exposure.
9. Howdoes S. schenkii infect the host?
S. schenkii is a soil saprophyte that usually infects the host through wound contamination or
penetrating foreign objects; there is no known geographical distribution. Infection of cats and
humans usually occurs after the organism contaminates broken skin. Cats are thought to be in-
fected by scratches from contaminated claws of other cats. Multiple cases have been reported in
cats; infection is most common in outdoor males. Exudates from infected lesions of cats usually
contain numerous organisms and are another source of human infection.
Exudate and Cutaneous Zoonoses 437
10. What are the clinical manifestations of S. schenkii infection in cats and humans?
Cats usually develop a Iymphocutaneous form of disease. Dermal and subcutaneous nodules
spread from the inoculation site along lymphatics. This process causes tissue cording and ulcera-
tion and eventual pyrexia and depression. The cat may inoculate itself at sites distal to the pri-
mary lesion via grooming. If the immune response is strong, the lesion usually remains localized
and appears ulcerated or acne-like. In rare cases, the organism disseminates throughout the body
and infects multiple organs.
In humans, infections are commonly associated with rosebushes, sphagnum moss, and ar-
madillo hunting. Most human infections are localized cutaneous lesions, although disseminated
disease in immunocompromised people has been reported.
11. How is S. schenkii infection diagnosed?
Presumptive diagnosis is based on cytology of exudates or histopathology; the organism is
round, oval, or cigar-shaped and may be extracellular or intracellular after being engulfed by
macrophages. Definitive diagnosis is based on culture.
12. Describe the treatment for S. schenkii infection.
Potassium iodide is used to treat cats and people. The usual regimen in cats consists of 20
mglkg orally every 12-24 hours for at least 3 weeks after resolution of signs. Alternative therapy
includes itraconazole (5 mg/kg orally every 24 hr) or ketoconazole (5-15 mglkg orally every
12-24 hr).
13. What bacterial diseases of cats can be transmitted to people by contact with exudates?
Theoretically, any bacterial disease of cats can infect a person if the organism is inoculated
by biting or into an open wound. Yersinia pestis (see Chapter 86) and Fransicella tularensis (see
Chapter 85) are of most concern because they are associated with life-threatening bacteremia in
people.
14. Do ectoparasites of cats infest people?
In addition to being the vector or reservoir of some zoonotic agents (see Chapter 90), ec-
toparasites also can induce cutaneous disease in people. Ctenocephalides [elis, Cheyletiella spp.,
Sarcoptes scabei, Notoedres cati, and various ticks parasitize both cats and people. Multiple
species of Cheyletiella exist, and cross-infection to dogs and rabbits may occur.
15. Describe the clinical manifestations of Cheyletiella blakei mite infestations in cats and
humans.
Cats with C. blakei may be subclinically infected or have scales of variable severity, primar-
ily over the dorsum. Pruritus is also variable. Long-haired cats such as Persians are common sub-
clinical carriers.
In humans, infestation causes a self-limited but intensely pruritic dermatitis with papules
progressing to pustules and then to erythemic areas with areas of central necrosis.
16. How is C. blakei infestation diagnosed?
Diagnosis is made by demonstrating the mites after taking skin scrapings or acetate tape
preparations of affected areas. Occasionally, a presumptive diagnosis is made by response to
treatment in difficult-to-diagnose cats.
17. How is C. blakei infestation treated and controlled?
Once a diagnosis is made, all pets in the household must be treated. Lime sulfur 2% dips have
been successful if applied weekly for 6-8 weeks. 1\\'0 or three treatments with ivermectin (0.2--0.3
mglkg subcutaneously every 2-3 weeks) is generally effective but not approved for use in cats.
Environmental control with an effective flea spray of the premises, disinfection of grooming
brushes, and thorough vacuuming is essential to eradicate C. blakei, which can live off the body
for a number of days.
438 Exudate and Cutaneous Zoonoses
18. How common are Notoedres cati infections of cats and humans?
Notoedric mange has a worldwide distribution but is relatively uncommon in the U.S.
19. Describe the presentation of N. cati infections in cats and humans.
Cats present with intense pruritus of the head and neck, with marked crusting, scaling, ery-
thema, and hair loss in affected areas. Kittens may show a severe moist dermatitis of the ventrum,
perineum, and legs, which may befatal if left untreated.
Humans occasionally develop transient notoedric infestation and may experience intensely
pruritic urticarial lesions on the arms, legs, and chest.
20. How is N. coo infection diagnosed and treated?
The mites usually are found easily on microscopic examination of skin scrapings.
Treatment with ivermectin (0.25 mglkg subcuatneously every 2 weeks for 3 treatments) is
usually successful. Lime sulfur dips and pyrethrin dips also have been used successfully; lime
sulfur may bepreferred in debilitated cats.
21. How is N. cati infection controlled?
As for cheyletielliosis, all animals in the household must be treated, and the premises must
bedisinfected with an effective flea spray.
22. What are the clinical manifestations of Sarcoptes scabeiinfections in cats and humans?
Cats are rarely infested by S. scabei but occasionally present with a miliary type of dermati-
tis similar to flea allergy dermatitis. More severe cases may show allergic sensitization with in-
tense pruritus, crusting, alopecia, and lichenification spreading from the head and ears to
encompass the entire body. Hyperkeratosis of the ears has been reported in cats that test positive
for feline immunodeficiency virus.
Human infestations from contact with cats are transient and result in intensely pruritic,
small, linear grooves, papules, and vesicles with possibly purulent secondary infections.
23. How is S. scabeiinfection treated?
Treatment is the same as for notoedric mange.
24. How can cutaneous and exudate-associated zoonoses be avoided?
All cats with exudative or cutaneous diseases should betaken to the veterinarian for appro-
priate diagnostic tests and appropriate treatment. Tick, flea, and mite control should be main-
tained. Kittens from crowded environments are most likely to carry cutaneous zoonoses.
BIBLIOGRAPHY
I. Chakrabarti A: Human notoedric scabies from contact with cats infested with Notoedres cati. Int 1
DermatoI25:646-648, 1986.
2. DaviesC, TroyGC: Deepmycoticinfectionsin cats. 1AmAnim HospAssoc32:380-391,1996.
3. DunstonRW, LanghamRF, ReimannDA, et al: Feline sporotrichosis: A report of five cases with trans-
missionto humans.1AmAcadDermatoI15:37, 1986.
4. Foil CS: Dermatophytosis. In' Greene CE (ed): Infectious Diseases of the Dog and Cat. 2nd ed.
Philadelphia, W.B.Saunders, 1998,pp 362-370.
5. King D, Cheever LW, Hood A, et al: Primary invasivecutaneous Microsporum canis infections in im-
munocompromised patients.1Clin MicrobioI34:46G-462, 1996.
6. Merchant SR: Zoonotic diseases with cutaneous manifestations. Part I. CompendCont Educ Pract Vet
12:371-377, 1990.
7. Merchant SR: Zoonoticdiseases with cutaneous manifestations. Part II. CompendCont Educ Pract Vet
12:515-521, 1990.
8. MorrielloKA, DeBoer D1: Felinedermatophytosis: Recent advancesand recommendations for therapy.
VetClin NorthAmSmall Animal Pract 25:901-921, 1995.
9. Romano R, Valenti L, Barbara R: Dermatophytes isolated from asymptomatic stray cats. Mycoses
40:471-472,1997.
10. RosserEJ, DunstanRW: Sporotrichosis. In GreeneCE (ed): InfectiousDiseasesof the Dogand Cat, 2nd
ed. Philadelphia, W.B.Saunders, 1998,pp 399-402.
88. UROGENITAL TRACT ZOONOSES
1. What infectious agents of the urogenital system of cats are capable of infecting people?
Coxiella bumetii and Leptospira spp. potentially infect both people and cats and are considered
zoonotic.
Feline Urinaryand Genital Tract Zoonoses
ORGANISM
Bacteria
Leptospira spp.
Rickettsia
Coxiella bumetii
CLINICALDISEASE
Cats: usually subclinical infection
Humans: fever, malaise, inflammatory urinary tract or
hepatic disease, uveitis, central nervous system disease
Cats: subclinical disease, abortion, or stillbirth
Humans: fever, pneumonitis, lymphadenopathy, myalgia,
arthritis
RELATIVE RISK
FROMCATS TO
HUMANS
Extremely rare
Unknown;
probably rare
2. Define Qfever.
Qfever in people is a clinical syndrome caused by C. bumetii, a rickettsial agent found
throughout the world, including North America. Ticks and other arthropods are natural hosts for
the organism, which is maintained in a sylvan cycle with reservoir hosts. Cats, cattle, sheep, and
goats are commonly infected subclinically and pass the organism into the environment in urine,
feces, milk, and parturient discharges. Acute clinical signs in people include fever, malaise,
headache, interstitial pneumonitis, myalgia, and arthralgia. In cat-associated infections, clinical
signs develop 4-30 days after contact. In approximately I %, chronic Q fever can develop years
after primary infection and may manifest as hepatic inflammation or valvular endocarditis.
3. How are cats and humans infected?
Infection of cats most commonly results from tick exposure, ingestion of contaminated car-
casses, or aerosolization from a contaminated environment.
Humans usually are infected by ingesting the organism in raw milk or meat from infected
food animals or by inhaling the organism in parturient secretions. Thus, people associated with
livestock are particularly susceptible to infection. Human infection has been associated with
aborting cats and normal parturient cats. Tick-borne infection also may occur. Because the organ-
ism is present in body secretions, person-to-person infection may occur in rare cases.
4. How common is C. burnetti infection of cats?
The true incidence of disease in cats has not been determined. In two studies, 20% of cats
from a humane society in southern California and 20% of cats in maritime Canada were seropos-
itive, suggesting that exposure is common. The organism was grown from the vagina of normal
cats in Japan. Although the organism has been associated with aborting cats, infection is consid-
ered subclinical in most cases.
5. How is Qfever managed clinically?
Diagnosis in people can be based on organism isolation, polymerase chain reaction, or sero-
logic test results. Tetracyclines, chloramphenicol, and quinolones are usually effective therapeu-
tic agents in people.
439
440 Urogenital Tract Zoonoses
6. Howcan infection with C. burnetii be prevented?
Gloves and masks should be worn while attending to parturient or aborting cats. Arthropod
control should be maintained. The organism is extremely resistant to environmental extremes and
disinfectants once it has sporulated.
7. Define leptospirosis.
Various bacteria are included in the Leptospira interrogans sensu lato group. Leptospires
are maintained in nature in subclinically infected reservoir hosts; infection of incidental hosts
results in clinical disease. People are incidental hosts to multiple serovars and develop fever
as well as manifestations of liver, and kidney disease. Leptospires are passed by reservoir
host in large numbers in infected urine and can enter the body through abraded skin and
mucous membranes.
8. What are the clinical manifestations of leptospirosis in cats?
In one study, cats were experimentally inoculated with a L. interrogans serovars icterohaem-
orrhagiae and canicola. Although most cats seroconverted and L. canicola was shed in the urine,
clinical abnormalities were not detected. Several other serovars have been isolated from cats, but
reports of naturally occurring disease are rare. Ascites due to infection may have occurred in one
cat; pleuritis, pericarditis, hepatitis, and uveitis occurred in another. Seropositive cats are
common; exposure may be from contact with dogs or rodents.
9. Are cats a likely reservoir host for leptospires that infect humans?
Cats appear to be an unlikely source for human leptospirosis. In fact, two studies found that
cat owners were less likely to be seropositive than people who did not own cats.
BIBLIOGRAPHY
I. Agunloye CA, Nash AS: Investigation of possible leptospiral infection in cats in Scotland. J Small Anim
Pract 37:126-129,1996.
2. Bryson DO, Ellis WA: Leptospirosis in a British domestic cat. J Small Anim Pract 17:459.-465, 1976.
3. Childs JE, Schwartz BS, Ksiazek TO, et al: Risk factors associated with antibodies to leptospires in
inner-city residents of Baltimore: A protective role for cats. Am J Public Health 82:597-599,
1992.
4. Oreene CE, Miller MA, Brown CA: Leptospirosis. In Greene CE (ed): Infectious Diseases of the Dog
and Cat, 2nd ed. Philadelphia, W.B, Saunders, 1998, pp 272-281.
5. Higgins D, Marrie TJ: Seroepidemiology of Q fever among cats in New Brunswick and Prince Edward
Island. Ann NY Acad Sci 590:271-274, 1990.
6. Larsson CE, Santa Rosa CA, Larsson MH, et al: Laboratory and clinical features of experimental feline
leptospirosis. Int J Zoonoses 12:2 111-119, 1985.
7. Levesque B, Serres de G, Higgins R, et al: Seroepidemiologic study of three zoonoses (leptospirosis, Q
fever, and tularemia) among trappers in Quebec, Canada. Clin Diagnos Lab Immunol 2:496-498,
1995.
8. Nagaoka H, Sugieda M, Akiyama M, et a1: Isolation of Coxiella bumetii from the vagina of feline clients
at veterinary clinics. J Vet Med Sci 60:251-252,1998.
9. Marrie TJ: Coxiella burnetii (Q Fever) pneumonia. Clin Infect Dis 21:S253-S264, 1995.
10. Marrie TJ, Durant H, Williams JC, et a1: Exposure to parturient cats: A risk factor for acquisition of Q
fever in maritime Canada. J Infect Dis 158:101-108, 1988.
II. Marrie TJ, Langille D, Papukna V, et al: Truckin' pneumonia: An outbreak of Q fever in a truck repair
plant probably due to aerosols from clothing contaminated by contact with newborn kittens. Epidemiol
Infect 102:119-127, 1989.
12. Marrie TJ, MacDonald A, Durant H, et al: An outbreak of Q fever probably due to contact with a parturi-
ent cat. Chest 93:98-103, 1988.
13. Pinsky RL, Fishbein DB, Greene CR, et a1: An outbreak of cat-associated Q fever in the United States. J
Infect Dis 164:202-204, 1991.
14. Randhawa AS, Dieterich WH, Jolley WB, et al: CoxieUosis in pound cats. Feline Pract 4:37-38, 1974.
89. ENVIRONMENTAL ZOONOSES
Tammy P. Sadek, D.v.M.
1. What environmental agents commonly infect both cats and humans?
Various infectious agents are acquired by cats and people from environmental sources. For
some agents, soil and other environmental materials are the primary reservoir:
Blastomyces dermatitidis Mucor spp.
Coccidioides immitis Sporothrix schenkii
Histoplasma capsulatum Mycobacterium spp.
Cryptococcus neoformans Rhodococcus equi
Aspergillus spp.
For other infectious agents, people or other animals are the primary host and reservoir. They
contaminate the environment with infected secretions or excrement, allowing infection of others.
Common examples include the enteric zoonoses, such as Toxoplasma gondii, Cryptosporidium
parvum, Toxacara cati, Ancylostoma tubaeforme, and Giardia spp. (see Chapter 84). However,
any infectious agent that survives outside the host may be acquired from contact with infected
fomites in the environment.
2. Are systemic fungal infections acquired from direct contact with infected cats?
With the exception of Sporothrix schenkii, human infection by any of the systemic fungal
agents is unlikely from contact with an infected cat. If both a cat and human in the same house-
hold are infected with a fungal agent, the likely source is a shared environmental exposure.
3. How does infection with Blastomyces dermatitidis occur?
B. dermatitidis survives in soil in a mycelial stage. Spores are released from the mycelium
and result in infection by inhalation. The mycelial phase develops in culture and on bandages and
is contagious to people.
The yeast form of the organism that occurs in the body does not spread by aerosal transmis-
sion between infected animals or from animals to people. It is possible to induce infection by
contamination of wounds with the yeast phase.
4. How common is blastomycosis?
B. dermatitidis has highest concentrations in the regions of the Ohio, Missouri, and
Mississippi Rivers and mid-Atlantic states. It seems to be confined to small areas within endemic
regions; exposure is generally uncommon. Blastomycosis is uncommon in cats but has been as-
sociated with dyspnea, panopthalmitis, anorexia, weight loss, and granulomatous skin lesions
(see Chapter 12).
5. How does infection with Coccidiomyces immitisoccur?
The organism grows as a mycelium in the environment. Multinucleate arthroconidia are
formed, dispersed by the wind, and inhaled by susceptible hosts to induce infection. The
spherules and endospores found in tissues of infected individuals are not considered contagious.
As for H. capsulatum and B. dermatitidis, the mycelial phase that develops in cultures or ban-
dages used on draining tracts is infectious to people.
6. How common is C. immitisinfection?
C. immitis is limited geographically to the desert Southwest. In endemic areas, most people
and dogs have serologic evidence of exposure. The same is probably true for cats. Clinical illness
occurs in approximately 40% of exposed humans; most develop transient respiratory disease.
441
442 Environmental Zoonoses
Increased incidence of infection occurs in dry periods following periods of rain because more
arthroconidia are produced and dispersed.
7. Describe the mechanisms by which Cryptococcus neotormans is transmitted.
C. neoformans lives in the soil as a saphrocytic yeast-like stage. Cats and people are thought to
beinfected by inhalation. There are no reports of animal-to-animal or animal-to-human infections.
Risk of infection increases with the presence of pigeon droppings (c. neoformans var neoformans)
and eucalyptus trees (c. neoformans var gatti).
8. Where is C. neotormans infection most common?
C. neoformans is considered to have worldwide distribution, but larger numbers of infections
are reported in Australia and southern California.
9, How does infection with C. neotormans manifest in cats?
In cats, infection usually localizes in the upper respiratory tract, but disseminated infections
can occur (see Chapter 4).
10. Describe the mechanisms by which Histoplasma capsulatum infection is spread.
The organism is a dimorphic fungus; macroconidia and microcondia of the myelial environ-
mental stage probably are inhaled or ingested by cats and people to initiate infection. The yeast
form that occurs in the body of infected mammals is not contagious from cat to cat or from cats
to people. The mycelial phase that develops in cultures or bandages used on draining tracts is in-
fectious to people.
11. Howcommon is infection with H. capsulatum?
H. capsulatum is a common systemic mycosis in cats of some regions (see Chapter 22). The
agent is ubiquitous in the soil, particularly soil contaminated with bird or bat droppings. The re-
gions of the Ohio, Missouri, and Mississippi Rivers have the highest numbers of cases.
12. How does infection with Sporothrix schenkii occur?
S. schenkii is a dimorphic soil saprophyte. The organism exists as a mycelium in soil and as
a yeast in infected people or animals. Infection usually occurs through wound contamination or
penetrating foreign objects. Human infections are commonly associated with rosebushes, sphag-
num moss, and armadillo hunting. Exudates from infected lesions of cats may contain numerous
organisms and are another source of human infection (see Chapter 87). There is no known geo-
graphical distribution.
13. By what mechanisms does infection with Rhodococcus equi occur?
R. equi is a gram-positive soil bacillus. The primary route of infection appears to be
aerosolized soil, but local wound contamination also occurs.
14. Describe the clinical manifestations of R. equi infection.
R. equi most frequently causes suppurative bronchopneumonia in foals. In cats, local infec-
tions may appear as caseating pyogranulomatous abcesses that ulcerate and drain. Occasionally,
spread via the lymphatic system leads to pyothorax and visceral organ infection. HIV-positive
people are most at risk and may develop cavitary pneumonia and pleural effusion.
15. How are Mycobacterium tuberculosis and M. bovistransmitted?
M. tuberulosis and M. bovis do not survive well outside the host and are not environmental
zoonoses. Although cats can be infected, they are not considered a primary host. When infection
occurs, it is the result of reverse zoonosis: the cat was infected by the owner. Cats can be infected
with an M. tuberculosis-M. bovis variant by ingestion of infected prey species. However, this
variant is not known to infect people.
Environmental Zoonoses 443
16. Describe the mechanisms by which the Mycobacterium aviumcomplex is transmitted.
The M. avium complex is a group of organisms, passed by birds, that survive well in soil.
Infection probably occurs by ingestion of the organism from a contaminated environment-not
from direct contact with cats.
17. What are clinical manifestations of M. avium infection?
Infection results in skin granulomas in immunocompetent cats and disseminated infections
in immunosuppressed cats. Infection with M. avium is common in immunocompromised people.
18. What causes feline leprosy? Can it be transmitted to humans?
M. leprae and M. lepraemurium, which cause multiple cutaneous nodules that are often ul-
cerated and draining. There are no known cases of transfer of infection from cats to people.
19. Summarize the significance of atypical mycobacterial infections in cats and humans.
Agents associated with atypical mycobacterial infections include M. fortuitum, M. chelonae,
M. phlei, and M. smegmatis. These free-living, saprophytic organisms usually do not cause dis-
ease in immunocompetent animals. Cats seem to be more susceptible than other species and de-
velop cutaneous nodules and draining tracts. Humans are rarely infected, and the agents are not
considered direct zoonoses from infected cats.
20. How can infection by zoonotic agents in the environment be avoided?
Housing cats indoors is the best way to reduce the potential for infection by organisms that
colonize the environment.
Control of transport hosts, such as flies, cockroaches, and rodents, may decrease environ-
mental contamination by enteric zoonoses.
BIBLIOGRAPHY
I. Evans RH: Public health and important zoonoses in feline populations. InAugust JH (ed): Consultations
in Feline Internal Medicine. Philadelphia,W.B.Saunders, 1997, pp 611-629.
2. Greene CE, Gunn-Moore DA: Tuberculous mycobacterial infections. In Greene CE (ed): Infectious
Diseases of the Dog and Cat, 2nd ed, Philadelphia,WB. Saunders, 1998, pp 313-321.
3. Hill SL, Cheney1M, Taton-AllenGF et al: Prevalence of enteric zoonotic organisms in cats. J AmVet
Med Assoc 216:687-692, 2000.
4. LappinMR: Feline zoonoticdiseases. Vet Clin NorthAm Small An Pract23:57-78. 1993.
5. Legendre AM: Systemic mycotic infections. In Sherding RG (ed): The Cat: Diseases and Clinical
Management. NewYork, Churchill Livingstone, 1994, pp 553-564.
6. Lewis DT, KunkleGA: Feline Leprosy. In Greene CE (ed): Infectious Diseasesof the Dog and Cat, 2nd
ed. Philadelphia,WB. Saunders, 1998, pp 321-322.
7. Lewis DT, Kunkle GA: Opportunistic rapid-growing mycobacterial infections. In, Greene CE (ed):
Infectious Diseases of the Dog and Cat, 2nd ed. Philadelphia. W.B. Saunders, 1998, pp 322-
325.
8. Malik R, Wigney DI, Dawson D et al: Infection of the subcutis and skin of cats with rapidly growing
mycobacteria: A review of microbiological and clinical findings. J Feline Med Surg 2:35-48,
2000.
9. Stevenson K, Howie FE, Cameron ME et a1: Feline skin granuloma associated with Mycobacterium
avium. Vet Rec 143:109-110,1998.
10. Werner AH, Werner BE: Feline sporotrichosis. Compend Cont Educ Small Anim Prac 15:1189-1197,
1993.
90. VECTOR..ASSOCIATED ZOONOSES
Tammy P. Sadek, D.V.M.
1. Define vector-bornediseases.
A vector is a carrier that transfers an infective agent from one host to another. Fleas, ticks,
reduviid bugs (Trypanosoma cruzi), mosquitoes (Dirofilaria repens), and sandflies (Leishmania
spp.) may transmit agents that infect cats and people. For some agents, cats serve only to bring
infected vectors into the human environment (e.g., Borrelia burgdorferi and Rickettsia rickettsii).
For others, the cat is also an effective reservoir and maintains the infectious agent (e.g.,
Bartonella henselae and Rickettsiafelis). Disease in people can be induced by the parasitism
itself or by the organism transmitted by the vector.
Vector-associated Zoonoses in Cats
ORGANISM VECTOR
Bartonella spp. Ctenocephalides
felis
Borrelia Ixodes ticks
burgdorferi
Coxiella Many ticks
burnetti
Diplyidium Ctenocephalides
caninum felis
Dirofilaria Mosquitoes
immitis
Erlichia spp. (Ticks; un-
(granulocytic) determined)
Fransicella Ticks
tularensis
Leishmania spp.
Rickettsia felis
Rickettsia
rickettsii
444
Sand flies
c.nu,
Dermacenter spp.
Ambylomma
americanum
Rhipicephalus
sanguineus
CLINICAL SYNDROMES
Cats: subclinical, fever, uveitis
Humans: lymphadenopathy, fever,
malaise, bacillary angiomatosis,
bacillary peliosis
Cats: subclinical
Humans: polyarthritis, cardiac
disease, neurologic disease
Cats: subclincal, abortion, stillbirth
Humans: fever, pneumonitis, lym-
phadenopathy, myalgia, arthritis
Cats: subclinical, failure to thrive
Humans: pruritus ani
Cats: cough, dyspnea, vomiting, death
Humans: asymptomatic
Cats: fever, polyarthritis
Humans: fever, polyarthritis, death
Humans: ulceroglandular, glandular,
oculoglandular, pneumonic, or
typhoidal (depending on route of
transmission)
Cats: both visceral and cutaneous
forms are rare; extremely rare
in North America
Humans: visceral and cutaneous
Cats: subclinical
Humans: fever, malaise
Cats: subclinical
Humans: fever, malaise, petechiae,
death
ROLE OFCATIN
HUMAN SYNDROME
Reservoir; transmitted
by bites and
scratches
Transport host for ticks
Direct transmission to
humans by aerosol;
transport host for
ticks
Transport host for
fleas
None
Unknown reservoir
potential; trans-
port host for ticks
Direct transmission
to humans by
bites; transport
host for ticks
Minimal reservoir
potential
Reservoir likely: trans-
host for fleas
Reservoir unlikely:
transport host for
ticks
Vector-associated Zoonoses
Vector-associated Zoonoses in Cats (Continued)
445
ORGANISM VECTOR CLINICALSYNDROMES
ROLEOF CATIN
HUMANSYNDROME
Rickettsia typhus C. felis Cats: subclincal
Humans: fever, malaise
Reservoir likely;
transport host
for fleas
Trypanosoma
cruzi
Yersinia pestis
Reduviid bugs
Rodent fleas
Cats: subclinical
Humans: cardiac disease, megaesophagus
Humans: bubonic, bacteremic, or pneu-
monic
None; reservoir
unlikely
Direct transmission
by exudates or
aerosol; transport
host for fleas
2. Which infectious agents are carried by fleas?
The significant infectious agents that are transmitted by fleas and involve cats include:
Bartonella spp. (cat scratch disease, bacillary angiomatosus, bacillary peliosis)
Yersiniapestis (plague)
Rickettsia typhus (murine typhus)
Rickettsiafelis
Dipylidiumcaninum
3. Are Bartonella spp. infections important vector-borne diseases in humans?
Cats and people can be infected with B. henselae and B. clarridgeiae;cats are infected by B.
koehlerae (see Chapter 85). Ctencephalidiesfelis can transmit B. henselae between cats. Cats are
a chronic reservoir host for B. henselae and B. clarridgeiae, both of which cause cat scratch dis-
ease. Epidemiologically, cat scratch disease has been linked most often with cat contact, but flea
transmission also may be important. Bacillary angiomatosis and bacillary peliosis in immuno-
suppressed people are also caused by B. henselae.
4. Are cats important in the vector-borne pathogenesis of plague?
Both cats and people have the potential to develop bubonic, pneumonic, or septicemic plague
when infected by Y. pestis (see Chapter 86). Approximately 35% of reported human cases of plague
in the United States have occurred in veterinarians or their assistants. The organism is maintained in
a cycle between rodent fleas and infected rodents. Y. pestis infects over 230 species of rodents and
over 1500 species of fleas, but C. felis is thought to be a poor vector. It is plausible that cats preying
on rodents may be infested by rodent fleas and bring the Y. pestis-infectedfleas into the human en-
vironment. However, it appears more likely that feline-associated plague in humans results most
commonly from contact with exudates or respiratory secretions of infected cats.
5. Which rickettsial agents are transmitted by fleas?
Murine typhus (endemic typhus) is caused by Rickettisia typhi. Infection is usually through a
flea bite or by contaminating flea bite wounds with flea feces. Opossums are the reservoir host in
Texas and California. In a study in Los Angeles County, most cats tested were seropositive, sug-
gesting that they may playa role infection of people. However. it is unknown whether the cats
were infected with R. typhi or the related organism, R. felis. At the very least, cats serve to bring
the infected flea vector into contact with the susceptible human host.
Using polymerase chain reaction and restriction fragment length polymorphism, R.felis was
discovered in a person with clinical signs similar to typhus. Subsequently, it was shown that C.
felis could be infected by Rifelis; infected fleas have been found in many states. Cats infected ex-
perimentally seroconvert, but the infection appears to be subclinical. Whether cats are a reservoir.
whether infection can result from direct contact, and the prevalence of naturally occurring dis-
ease are as yet unknown. Both R. felis and R. typhi can exist in the same flea.
446
Vector-associated Zoonoses
6. Describe the clinical signs of murine typhus in humans.
Clinical signs in humans are similar to those of Rocky Mountain spotted fever: fever,
headache, generalized pain, weakness, and rash.
7. What problems do D. caninum infections cause in people?
D. caninum is spread to people through ingestion of infected fleas. Young children are most
likely to beaffected. Clinical signs include mild abdominal discomfort, diarrhea, and anal pruri-
tus. The infection is usually self-limiting.
8. Do ticks infest cats?
In many areas of the country, tick infestation is rarely noted by owners or veterinarians. Cats
may beinfested with the nymphal stages of ticks, which are so tiny that they are easily missed on
physical examination. In addition, the meticulous grooming habits of cats may remove attached
ticks after spread of disease but before examination. Because ticks that infect cats can transmit
some tick-borne diseases to humans, tick control should always bemaintained.
9. What are the common tick-borne infections in humans and cats?
B. burgdorferi is transmitted by Ixodes spp. ticks and causes Lyme disease in people. Most
cats exposed to B. burgdorferi are subclinically infected (see Chapter 65). People are un-
likely to develop Lyme disease from direct contact with cats or their secretions, but cats can
transport B. burgdoiferi-infected ticks into human households.
Francisella tularensis can infect both cats and humans (see Chapter 85). Contact with in-
fected cats has resulted in human infection most commonly via bites and scratches, but it is
also possible that cats could transport F. tularensis-infected ticks into human households.
Coxiella burnetti, the cause of Q fever, infects over 40 species of ticks. Both cats and
people can become infected via tick bite, and cats may bring ticks into the human environ-
ment. People, however, are more likely to be infected through inhalation of aerosolized ma-
terial from parturient cats than via tick exposure (see Chapter 86).
Cats seem to be very resistant to infection by R. rickettsii, the cause of Rocky Mountain
spotted fever in people. People are unlikely to develop Rocky Mountain spotted fever from
direct contact with cats or their secretions, but cats may transport R. rickettsia-infected
ticks into human households.
Several Ehrlichia spp. have been documented in cats (see Chapter 78). An isolate from a
cat in Sweden was shown to be genetically identical to the agent causing human granulo-
cytic ehrlichiosis. To date, no information suggests that direct contact with cats results in
human ehrlichiosis, but cats may bring infected vectors into the human environment.
10. Do cats playa role in human dirofilariasis?
Although cats can be infected with Dirofilaria immitis, first-stage larvae (microfilaria) are
rarely produced because of an intense immune response against the organism (see Chapter 10).
Thus, it is unlikely that infected cats function as a reservoir for heartworm disease in humans. In
the tropics, however, D. repens is a subcutaneous parasite in dogs and cats that uses mosquitos as
a vector and has been implicated as a cause of abscesses and tumors in humans.
11. Is Chagas disease important in cats?
American trypanosomiasis, or Chagas disease, is caused by Trypanosoma cruzi, which is
carried by the reduviid bug, Triatoma spp. It is common in South America and also has been
identified in the southern United States. Dogs are considered important hosts in South America.
Although infection in cats is not well documented, clinical disease in dogs appears to be similar
to that in humans. The acute symptoms of fever and palpebral edema are followed by he-
patomegaly, cardiac disease, and central nervous involvement. The chronic form generally causes
myocardial disease and megaesophagus. Transmission occurs when a reduviid bug infected with
Triatomaspp. deposits metacyclic trypanosomes on the host's skin after its blood meal. Treatment
Vector-associated Zoonoses 447
is relatively unrewarding in both humans and animals. Environmental control to eliminate contact
with the reduviid bug vector is required. In North America, cats are unimportant reservoirs.
12. Is leishmaniasis of cats an important zoonosis?
Leishmania spp. are protozoan parasites endemic in South and Central America and portions
of Africa, Europe, and the south central United States. Transmission occurs through the bite of
blood-sucking sandflies, especially those of the genera Phlebotomus and Lutzomyia. Although
common in dogs of endemic areas, infection is rare in cats, particularly in North America.
Cutaneous lesions of the ear pinna of cats appear nodular. Visceral forms of the disease are ex-
tremely rare in cats. Definitive diagnosis is based on demonstrating the organisms cytologically
or histologically. Treatment with pentavalent antimony compounds, allopurinol, and ampho-
tericin B have been used successfully in dogs but minimal information about cats is available.
Leishmaniasis appears to be an emerging opportunistic infection in humans and is seen regularly
in HIV-infected humans in endemic areas. Cats are unlikely reservoir hosts in North America.
Contact with exudates or open wounds of affected animals should be avoided.
13. What are the recommendations for control of vector-associated zoonosis?
Keep house cats indoors at all times.
Control potential transport hosts, such as rodents.
Use flea- and tick-control products.
BIBLIOGRAPHY
I. BjoersdoerffA, Svendenius L, Owens JH, et al: Feline granulocyticehrlichiosis: A report of a newclini-
cal entity and characterizationof the infectious agent. J Small Anim Pract 40:2(}"'24, 1999.
2. Chomel BB, Kasten RW, Floyd-Hawkins K, et al: Experimental transmission of Bartonella hense/ae by
the cat flea. J Clin Microbiol 34:1952- I956, 1996.
3. Couto CG: Rickettsial diseases. In Birchard SJ, Sherding RG (ed): Saunders' Manual of Small Animal
Practice. Philadelphia, W.B.Saunders, 1994, pp 124--127.
4. Davenport DJ: Bacterial and rickettsial diseases. In Sherding RG (ed): The Cat: Diseases and Clinical
Management. NewYork, Churchill Livingstone, 1994, pp 527-551.
5. Evans RH: Public health and important zoonoses in feline populations. In August JR (ed): Consultations
in Feline Internal Medicine, vol. 3. Philadelphia, W.B. Saunders, 1997, pp 611-629.
6. Hart CA, TreesAJ, Duerden BI: Zoonoses. J Med Microbiol 46:4--33,1997.
7. Kordick DL, Breitschwerdt EB: Bartonella infections in domestic cats. In Bonagura JD (ed): Current
VeterinaryTherapy Xlll-Small Animal Practice. Philadelphia, W.B. Saunders, 2000, pp 302-307.
8. Lappin MR: Feline zoonoses. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI.
Philadelphia, W.B. Saunders, 1992, pp 284--291.
9. Macy DW: Plague. In Greene CE (ed): Infectious Diseases of the Dog and Cat, 2nd ed. Philadelphia,
wn, Saunders, 1998, pp 295-300.
10. Noden BH, Radulovic S, Higgins JA, et al: Molecular identification of Rickettsia typhi and R.felis in
coinfected Ctenocepahlidesfelis (Siphonaptera: Pulicidae). J Med EntomoI34:4IMI4, 1998.
I I. Schreifer ME and Azad AF: Arthropod-borne diseases. In August JR (ed): Consultations in Feline
Internal Medicine, vol. 2. Philadelphia, W.B. Saunders, 1994, pp 47-51.
12. Stubbs CJ, Holland CJ, Reif JS, et al: Feline ehrlichiosis. Comp Cont Educ Prac Vet 22: 307-318,2000.
13. Walker DH, Barbour AG, Oliver JH, et al: Emerging bacterial zoonotic and vector-borne diseases:
Ecological and epidemiological factors.JAmMed Assoc 275:463-469, 1996.
14. Weber DJ, Rutala WA: Zoonotic infections. Occup Med State Art Rev 14:247-285, 1999.
APPENDIX
Drugs Commonly Usedin FelineInternalMedicine Practice
DRUG DOSEREGIMEN INDICATIONS CHAPTER(S)
Acarbose 12.5-25 mg/cat PO with Diabetes mellitus 56,23,21
meals
Acepromazine Up to OJ mglkg IVq 12-24 Smoothmuscle relaxant for functional 49
hr urethral obstruction; sedativefor
1.1-2.2 mg/kgPOq 12-24 hr restraint
N-Acetylcysteine 140mg/kgIV or PO, fol- Acetominophentoxicity 34, 73
(5%solution) lowedby 5-7 additional
treatments of 70 mg/kg
IVorPOq4hr
Acyclovir 10-50 mg/kgPOq 8-12 hr Feline herpesvirus 1 keratitis, conjuncti- 3
vitis, and possiblyrhinitis
Alprazolam O. I25--D.25 mg/cat PO Skeletal musclerelaxant for functional 49
urethral obstruction
Aluminum 30-120mg/kg/daydivided, Phosphatebinder 40
carbonate withmeals
Aluminum 3Q....loo mglkg/daydivided, Phosphatebinder 40
hydroxide with meals
Aminophylline 4-5 mg/kgPO, 1M, IVq 8- Acute small airway disease 9
12hr
Amitriptyline 2.5-12.5 mg/cat/dayPO Idiopathic lower urinarytract disease 47
syndrome
Amlodipine 0.625-1.25 mg/cat/dayPO Antihypertensive 40
AmoxiciIlin 11-22 mg/kgPOq 12 hr Susceptiblebacteria; gram-positive, 2
anaerobes includingClostridium
perfringens
Arnoxicillin- 11-22 mg/kgPOq 12 hr Susceptiblebacteria; gram-positive, 2
c1avulanate anaerobes,and select gram-negative;
B. bronchiseptica
AmphotericinB 0.25 mg/kgIV 3 times/wk Systemicfungal infections 4,12,22
(regular) 0.5--D.8 mg/kg SQ 2 times/
wk diluted in 400 ml of
2.5%dextroseand 2.5%
saline
AmphotericinB 0.5 mg/kg IVas test dose, Systemicfungal infections 4,12,22
(lipid or then 1.0mg/kgIV 3-5
liposomal) times/wk
Ampicillin lQ....20 mg/kgPOq 8 hr Clostridium perfringens 20
10-20 mg/kgIVor SQq 8 hr Anaerobicor gram-positivesepsis 20
Amprolium 6D-- 100mg/dayPOfor 5 days Cystoisospora spp. 19
Arginine I gm/cat/dayPO Supplement for cats withhepaticlipidosis 30
Ascorbicacid 30 mg/kg SQor POq 6 hr Acetominophentoxicity 34, 73
for 7 doses
Aspirin 12-25 mg/cat PO q 48-72 hr Platelet functioninhibitionto lessen risk 17,64,65,
of thrombosis; fever control; arthritis; 67
uveitis
Atenolol 6.25-12.5 mg/cat POq 12- Cardiomyopathy; systemichypertension 17,63
24hr
449
450 Appendix
Drugs Commonly Used in Feline Internal Medicine Practice (Continued)
DRUG DOSE REGIMEN INDICATIONS CHAPTER(S)
19.84
30
65
23,65.72
2
3,65
27
3
14
17
67
49
Usedin cats withhepaticencephalopathy
Analgesic.anti-inflammatory, polyarthritis
Susceptiblebacteria; gram-positiveand
anaerobes
Susceptiblebacteria; gram-positive and
anaerobes
Susceptiblebacteria; gram-positiveand
anaerobes
Inappropriateurination 51
Analgesic 36
Polyarthritis 65
Chronic renal failure 40
Hypocalcemia 57
Phosphatebinder 40
Phosphatebinder 40
Hypocalcemia 40
Hypophosphatemia 40
Control of hyperthyroidism 53
Inflammatory boweldisease;polyarthritis;
primaryimmunediseases
Susceptible bacteria;B. bronchiseptica,
Mycoplasma spp., C. psittaci,gram-
negativeand anaerobes
Cardiomyopathy
Uveitis
Increase bladder contractility
Stimulant laxativefor USe with megacolon
Lymphocytic-plasmacytic stomatitis
Local anestheticfor chest tube placement
and other simple procedures
Topical anestheticfor pleural space pain
22-50 mglkg POevery8-12
hr
7-15 mglkgPOq 12hr for
5-7 days
0.25--{).5 mglkgldayPO
0.75 mg/eye, subconjunctival
1.25-7.5 mg/cat POq 8-12
hr
5 rug/cat/day PO
350 mg/catlday
2 mglkg maximal dose SQ
or 1M
0.75 mglkg in chest tube
q 8 hr
2.5-5.0 mglcat POq 12-24
hr
0.1--{).8 mglkgq 4 hr IV,1M,
SQ
I mg/cat POq 12 hr
2.5-3.5 nglkg/day PO; pulse
dose at 20 nglkgPO
2 times/wk
0.03--{).06 J.lglkgl24 hr PO
20--30 mglkgq 8-12 hr PO
with meals
30--50 mglkgq 8-12 hr PO
with meals
0.5-1.0 mglkgIV over 10--
15min
0.5-2.0 mmol/kgldayPO
2.5-5 mglcat POq 8-12 hr
for 7-10 days, then as
needed q 12-24 hr
250--500 mglcatlday
4 mglkgPO once
22 mglkg POq 12-24 hr
22 mglkg IV,1M,SQq 8 hr
0.5%and I% solutionand Uveitis 67
ointment, I drop or IAl
inch q 8-24 hr
I mg/cat 1Mq 7 days, then Polyarthritis;lymphocytic-plasmacytic
I mglkg1Mq 7 days until stomatitis
remission, then monthly
0.3 mglkg POq 48 hr indefi-
nitely
5-10 mglkgldayPOfor 3
days, then q 72hr
Benazepril
Betarnethasone
Bethanechol
Buspirone
Bisacodyl
Bovinelactoferrin
Bupivicaine
Cephalexin
Azathioprine
Azithromycin
Cefoxitin
Atropine sulfate
Aurothioglucose
Carnitine
Carprofen
Cefadroxil
Calciumcarbonate
Calcitriol
Butorphanol
Calciumgluconate
(10%)
Calciumphosphate
Carbimazole
Calciumacetate
Appendix
Drugs Commonly Usedin FelineInternalMedicine Practice (Continued)
451
Cephalothin 22-44 mglkg IVor 1M q 8 hr Susceptiblebacteria; anaerobicor gram- 20
positivesepsis
Chloramphenicol 25-50 mgfcat POq 12hr Susceptiblebacteria; B. bronchiseptica, 2
Mycoplasma spp., C. psittaci, anaerobes,
gram-positive
10-15mgfkg POor SQq 12hr Campylobacter spp. 20
Chlorambucil 2 mgfcat POq 48 hr Inflammatorybowel disease; other pri- 23, 72
mary immune-mediateddiseases
Chlorpheniramine 2-4 mgfcat POq 12hr Decongestant and antihistamine
Chlorpromazine 0.25-D.5mglkgq 8 hr 1M. Antiemetic 25,36
IV,SQ
Cimetidine 4-5 mg/kgq 6-8 hr PO, 1M, H
2
receptor blocker antacid
IV
Cisapride 0.1-D.5 mglkgPOq 8 hr Esophagitis, increasecolonic motilityin 26
megacolon
Clarithromycin 7.5 mglkgPOq 12-24 hr Helicobacterspp. 20
Clindamycin 11-24mglkg POq 24 hr Susceptiblebacteria; gram-positive and
anaerobes, good tissue penetration
10-12 mglkg POq 12hr Toxoplasma gondii II
for4wk
Clomipramine 1-5 mgfcatPOevery 12-24 Behavioralabnormalitiesincludinginap- 51
hr propriate urination
Cobalamine 125-250 JlgfwkSQor 1M Supplement for inflammatorybowel 23
for 6-8 wk disease
Cyclophosphamide 50 mg/m?PO4 timesfwk Inflammatory boweldisease,otherprimary 23, 72
When in remission, use immune mediateddiseases
chlorambucil
Cyclosporine 5-8.5 mglkgPOq 12-24 Inflammatory boweldisease, other primary 23, 72
hr indefinitely immunediseases
Cyproheptadine 2 mgfcat POq 12 hr SmaIlairwayinflammatory disease; appe- 9,62
tite stimulant
Dantrolene 0.5-2.0 mglkgPOq 8 hr Skeletal muscle relaxant for functional 49
1.0mglkg IV urethral obstruction
Desoxycorticoste- 10-12.5 mgfcatfmonth 1M Hypoadrenocorticism 55
rone pivalate
Dexamethasone 0.1%solutionor 0.5%oint- Uveitis 67
sodium ment 1drop or 1/
8
inchfeye
phosphate q 6-8 hr
Diazepam 0.2--D.3 mglkg q 12 hr SQ, Appetitestimulant 40
IV
0.2--D.5 mg/kg IV Skeletal muscle relaxant for functional 49
2.5-5.0 mgfcatPOq 8 hr or urethralobstruction
as needed
Diclofenac 0.1%solution, I dropfeye Uveitis 67
q 6-12 hr
Digoxin Cats < 3.0 kg: 0.031 mg PO Dilatedcardiomyopathy 17
q48-72hr
Cats 3.0-6.0 kg: 0.031 mg PO
q 24hr
Cats> 6.0 kg, 0.031 mg PO
q 12-24 hr
452 Appendix
Diltiazem(ex- 30 mg/cat POq 12hr Cardiomyopathy;systemichypertension 17.63
tended release)
Dimethylglycine 5 ~ 2 5 0 mg/catPOindefi- Supplement for inflammatory boweldisease 23
nitely
Dimenhydrinate 8.0 mglkg POq 8 hr Antihistamine.antiemetic 36
Diminazine 2.0 mglkg/wk1Mfor 2 doses Cytauxzoon felis 75
aceturate
Dioctyl calcium 50 mg/cat POq 12-24 hr Emollientlaxativefor use withmegacolon 27
sulfosuccinate as needed
Dioctyl sodium 50 mg/cat/dayPOas needed Emollientlaxativefor use withmegacolon 27
sulfosuccinate
Diphenhydramine 2.0-4.0 mg/kg POq 8 hr Antihistamine,antiemetic 36
2.0 mglkg1Mq 8 hr
Dopamine 3 Ilglkg/min Possiblyimprovespancreaticblood flow 36
in cats with pancreatitis 36
Doxycycline 5-10 mg/kg POq 12-24 hr B. bronchiseptica, Mycoplasma spp. 2, 74
C. psittaci, H. felis; possibly anti-
inflammatory
Enalapril 0.25-5.0 mg/kg POq 12-24 Cardiomyopathy;systemichypertension 17,63
hr
Enrofloxacin 5 mglkg POq 12-24 hr Susceptiblebacteria; gram-negative, 2,20
select gram-positive,Mycoplasma spp.
Campylobacter spp, Salmonella spp.,
Clostridium difficile
Ephedrine 2-4 mg/cat POq 8-12 hr Increase smooth muscleurethral tone 52
Epsiprantel 2.75 rug/kgPOonce Cestodes 19
Erythromycin 10 mglkgPOq 8 hr
Susceptiblebacteria; gram-positiveand 20
Campylobacter spp.
Erythropoietin 5 ~ I O O Ulkg SQ 3 times/wk Anemiaof chronic renal disease 40
Famotidine 0.5-1.0 rug/kg/dayPO Helicobacter spp. 20
Feline facial Spray area daily Urine marking 51
phermone
Fenbendazole 25-50 mg/kgPO q 12hr for Aelurostrongylus abstrusus, Capillaria 11
1 ~ 1 4 days aerophilia, Paragonimus kellicotti
50 mglkg/day POfor 3-5 days Giardia spp. Taenia spp., helminths 19
Fentanyl I ug/kgIV bolus Sedationfor short-termprocedures 14
(e.g.chest tube placement)
Ferrous sulfate 5 ~ 1 0 0 mg/cat/dayPO Iron deficiencyanemia 40
Flurbiprofen 0.03%solution, 1drop/eye, Uveitis 67
q 6-12hr
Fluconazole 50 mg POq 12-24 hr Systemicfungal infections 4.12,22
Flucytosine 50 mg/kg POq 8 hr Cryptococcus neoformans CNSinfections 4, 12
Fludrocortisone 0.1 mg/cat/dayPO Hypoadrenocorticism 55
Folate 0.5 mg/dayPOfor 1 month Supplement for inflammatory boweldisease 23
Furazolidone 8-20 mg/kg POq 12-24 hr Cystoisospora spp. 19
for 5 days
4 mg/kgPOq 12hr for 7 days Giardia spp. 19
Furosemide 6.25 mg/cat POq 24-48 hr Diureticfor pulmonarycongestion 17
up to 12.5mg/cat PO
q8 hr Table continued on following page
Appendix 453
27
23
36
40
56
23
10,19
17
4,12.22
II
20
75. 76
56
3, 76, 77
4,12,22
65
65
67
Anuric or oliguric renal failure
Factor inhibition to lessen risk of throm-
bosis
Analgesic
Gram-negative sepsis (including E. coli
and Salmonella spp.)
Diabetes mellitus
Supplement for inflammatory bowel disease
Cytauxzoon felis, Ehrlichia spp.
Diabetes mellitus
Chronic viral infections, FeLV, FIV,
feline herpesvirus I, FIP
Acute viral infections; FeLV, FIV, feline
herpesvirus I, calicivirus
Polyarthritis
Polyarthritis
Uveitis
Heartworm preventative; control of hook-
worms
Aelurostrongylus abstrusus, Capillaria
aerophila, ear mites
Sedation; short-term anesthesia
2-6 mglkg IV q 6-8 hr; in-
crementally increase dose
q 1 hr up to 6 mglkg if urine
output remains poor
2.2 mglk IV or SQ q 8 hr
2.5-5.0 mg/cat/day PO
25D-500 mg/cat PO
indefinitely
100-200 Ulkg IV once, then
100-300 Ulkg SQ q 8 hr
0.08--0.2 mglkg IV, 1M,SQ
q 4hr
5.0 mglkg/wk 1Mfor 2 doses
Multiple types and regimens
30 U1dayPO
lO,ooD-20,ooo Ulkg/day
SQ
5 mglkg PO q 12 hr for 4 days
and then 5 mglkg/day PO
24 ug/kgPO monthly
300-400 ug/kg/day PO for
1-3 days
0.05--0.1 mglkg IV with
diazepam
5-10 mglkg/day PO
I mglkg/day PO for 5 days
2 mglkg/day SQ for 3 days
0.5% solution, 1 drop/eye,
q 6-12 hr
5D-500x 10
6
organisms/cat Supplement for inflammatory bowel disease
until stool returns to normal
0.25-0.5 mlIkg PO q 8-12 hr Osmotic laxative for use with megacolon
as needed
Heparin
Itraconazole
Ivermectin
Hydromorphone
Furosemide
(cont.)
Gentamicin
Imidocarb
Insulin
Interferon alpha
Glipizide
Glutamine
Ketoconazole
Ketoprofen
Ketamine
Ketorolac
Lactobacillus
acidophilus
Lactulose
Osmotic diuresis for anuric or oliguric 40
renal failure
25
Table continued on jollowing page
Levothyroxine
Lidocaine (2%)
Lisinopril
L-Lysine
Magnesium
chloride
Mannitol (20%)
Meclizine
0.1mg/cat/day PO
0.75 mglkg SQ or 1M
0.25-0.75, IV or 5 min
0.25--0.5 mglkg/day PO
250 mg PO q 12 hr
0.75-1.0 mEqlkg/day IV for
3-5 days, mixed with 5%
dextrose in water
0.25-1.0 glkg; give as slow
IV bolus over 15-20 min;
can repeat q 4-6 hr
6.25-12.5 mg/cat PO q 12-
24 hr
Hypothyroidism
Local anesthetic for chest tube placement
and other simple procedures
Ventricular arrhythmias
Systemic hypertension
Feline herpesvirus I keratitis, conjuncti-
vitis, and possibly rhinitis
Hypomagnesemia
Antiemetic
53
14
63
3
40
454 Appendix
DrugsCommonly Usedin Feline Internal Medicine Practice (Continued)
17
19.23
27
22
20
25,36
40
52
36
10, 19
53
17
2
27
36
35
23
9
62
67
62
Uterine inertia
Uterine inertia
Acute congestiveheart failure
Cryptosporidium parvum 19, 84
Appetitestimulant
Decrease bladder contractility
Analgesic
Pulmonaryedema
Prokineticagent for use withmegacolon
Candidiasis
Helicobacter spp.; antacid
Antiemetic
Aggression;urine marking; eosinophilic
granulomacomplex
Used with hepaticencephalopathy
Supplement for inflammatory boweldisease
Eosinophilic and Iymphocytic-plasmacytic
inflammatorydiseases
GI motilitydisorders; esophagitis
Cardiomyopathy
Tissue infections; anaerobes; possibly
anti-inflammatory
Giardia spp, Pentatrichomonas hominis,
Clostridium perfringens, Helicobacter
spp., inflammatorybowel disease
Heartwormpreventative; control of hook-
wormsand roundworms
Lubricantlaxativefor use withmegacolon
Analgesic
Uveitis
GI motilitydisorders; esophagitis
Analgesia
Control of hyperthyroidism
1(}'-25 mglkg PO q 12hr
for 8 days
0.5--0.99 mglkg PO monthly
I(}'-25 mlIcatldayPO
0.05-0.4 mglkg, IV,1M,SQ
q 4hr
0.05--0.1 mglkg, 1M,SQ
q 6-8hr
1(}.-20 mglkg PO q 8-12 hr
25(}.-15oo mg/cat PO
indefinitely
1/
4
- Y2inchcutaneouslyto
pinna, q 6-8 hr for first
24-48 hr
2.5-5.0 mglkg/dayPO
100,000Vlcat PO q 6 hr
0.7-1.0 mglkg/dayPO
0.1-0.15 mglkgslowpushIV
q 6-12 hr as needed
0.2-0.4 mglkgPOq 12 hr
0.5 mg/cat POq 12 hr
0.025--0.1 mglkgq 4 hr IV,
IM,SQ
0.5-3 U IV infusion
0.5-3U 1Mq 20 min for
2 doses
150mglkgPOq 12-24 hr
for 5 days
Paromomycin
Oxytocin
Metronidazole
Milbemycin
Oxazepam
Oxybutynin
Oxymorphone
Metoprolol
Metronidizole
Nizatidine
Nystatin
Omeprazole
Ondansetron
Neomycin
N-acetyl glucosa-
mine
Nitroglycerine
(2%)
Meperidine
Methimazole
25-50 mg/cat SQq 3-6 Eosinophilicgranulomacomplex; miliary
months dermatitis; endocrinealopecia
0.5 mglkg/dayPO for 3-5 Appetite stimulation
days, then once q 5 days
2.2-4.4 mglkg/dayPO for
1 wk and then 1.1-1.2
mglkg q 1-2 wk
1-5 mglkg IV,1Mto effect
2.5-5 mg/cat PO q 12hr for
7-10 days, as needed
q 12-24 hr
Methylprednisolone 1(}.-20 mg/cat 1Mq 2 wk
acetate until controlled, then
as needed
4 mg/eye, subconjunctival
Metoclopramide 0.25--0.5 mglkg PO, SQ
q 8-12 hr
1-2 mglkg/dayIV CRI
2-15 mg/cat PO q 8 hr
7.5-10 mglkg PO q 8-12 hr
Mineral oil
Morphine
Medroxyproges-
terone acetate
Megestrol acetate
Appendix 455
DrugsCommonly Usedin FelineInternalMedicine Practice (Continued)
Potassiumgluco- 2-6 mEq/catJday PO
conate
21
47
27
49
19
7,46,65
52
40
Idiopathic lower urinarytract disease
Passiveimmunotherapyfor feline pan-
leukopenia
Hookwormsand roundworms
Lubricantlaxativefor use withmegacolon
Smooth muscle relaxant for functional
Increase urethral smoothmuscletone
Nasal adenocarcinoma,transitionalcell
carcinoma, polyarthritis
Hypokalemia;chronicrenal failure
2-10 mglkgPOq 12hr
1-5 mlfcatJday PO
1.25-7.5 mg/cat POq 8-12
hr
1.1-2.2 mglkg POq 8-12 hr Phenylpropanola-
mine
Plasma I mlIkgSQ, IV, IP
Pentosanpoly-
sulfate
Petrolatum
Phenoxybenzarrrine
Piperazine I 10mglkg POonce, repeat
in 2 weeks
Piroxicam 1 mglcat POq 24-48 hr
Prazosin 0.2S....().5 mglcatPOq 12-24 hr Smooth musclerelaxant for functional 49
Prednisolone
Prednisolone
acetate
Praziquantel
Proanthocyanidin
Prochlorperazine
0.03 mglkg IV
I mglkgPOq 12hrfor 10--
14days, then taperedto
2.5 mglkgPO q 48 hr
I% suspension, I drop/eye
q 6--12hr
5 mglkgldayfor 2-3 days PO
23 mglcatPOor56.8 mglml
SQorIM once
25mglkgPO q 8 hr for 2 days
10--200 mglcat POindefi-
nitely
0.1 mg/kg q 6 hr 1M
Eosinophilic and Iymphocytic-plasmacytic
inflammatorydiseases
Uveitis
Alaria marcianae
Cestodes
Paragonimus kellicotti
Supplement for inflammatory boweldisease
Antiemetic
9
67
19
19
II
23
25,36
27
15
10. \9
Prochlorperazine
+ isopropramide
Propanolol
Propantheline
Propofol
Pumpkin (canned)
Pyrantel pamoate
Pyrantel +prazi-
quantel
PsylIium
Ranitidine
Rutin
Selamectin
0.5-0.8 mglkgq 12hr IM,
SQ
2.5-5 mglcat POq 8-12 hr
5.0--7.5 mglcatPOq 24--72 hr
2-4 mglkgIV to effect
1-4 tbsp/daymixedwithfood
20 mglkg POonce; repeat in
2-3 wk
72.6mg pyranteland 18.2mg
praziquantel, I tab/cat PO
1-4 tsp mixedwith food
q 12-24hr
2.5 mglkg IV q 12 hr
3.5 mglkg POq 12hr
1.0--2.0 mglkg POq 8-12 hr
250--500 mg/cat POq 8 hr
6 mglkgtopicallyonce/month
Antiemetic 36
Systemichypertension 63
Decrease bladder contractility 52
Sedationfor short-termprocedures 14
(e.g., chest tube placement,TIW)
Bulk laxativefor use with megacolon 27
Hookwormsand roundworms 19
Hookworms, roundworms, and cestodes 19
Bulk laxativefor use withmegacolon 27
H
2
H
2
Prokineticagent for use with megacolon
Chylothorax
Heartwormpreventative;control of hook-
worms,roundworms, fleas,and ear mites
456 Appendix
Drugs Commonly Used in Feline Internal Medicine Practice (Continued)
23
23
23
40
29
19,84
23
63
62
26
19
29
23
71
17
27
9
77
23
67
17
9
9
30
67
19
67
Diuretic used for systemic hypertension
Appetite stimulation
Esophagitis and gastrointestinal ulcers
Uveitis
Inflammatory colitis
Cystoisosporaspp.
Supplement for inflammatory bowel disease;
hepatic diseases
Cholestatic liver disease
Cardiomyopathy
Small airway inflammatory disease
Used in cats with hepatic encephalopathy
Uveitis
Susceptible bacteria, Cystoisospora spp.,
T. gondii
Uveitis
Cryptosporidiumparvum, Clostridium
perfringens
Choleretic agent for biliary or gallbladder
disease
Vitamin K antagonism
Factor inhibition to lessen risk of thrombosis
Bulk laxative for use with megacolon
Clinical FlV infections
Suprofen
Sulfasalazine
15 ~ g / c a t / d a y PO indefinitely Supplement for inflammatory bowel disease
0.5-2.0 mEqlkg IV over 20- Extreme acidosis; extreme hyperkalemia
30 min; 5-10 mglkg PO
q8-I2hr
1-2 mglkg PO q 12 hr
1-2 mg/cat PO q 12hr
\4 gm crushed and mixed with
6 ml of water PO q 8 hr or
1.0-2.5 ml of 100 mg/ml
commercially available sus-
pension PO q 12hr
Sulfadimethoxine 50-60 mglkg/day PO for
5-20 days
10-20 mglkg/day PO for
7-10 days
1% solution, 1 drop/eye
q 6-12 hr
250-500 mg/cat PO q 12 hr
0.625 mg/cat PO q 12hr
50-100 mg/cat/day PO
50-100 mg/cat/day
4 mg/eye, subconjunctival
15 mglkg PO q 12hr for
5 days
0.5% and 1% solution q 6-
12 hr
10-15 mglkg PO q 8-12 hr
for 21 days
10-15 mglkg/day PO
1000-5000 ill/day PO as
beta carotine, indefinitely
250-300 mg/cat PO, indefi-
nitely
200 ill/cat/day PO as alpha
tocopherol, indefinitely
0.5-1.0 mglkg/day SQ for
3-4 days, then once weekly
0.3-0.8 mglkg PO q 12hr
Warfarin 0.25-0.5 mg/cat/day PO
Wheat bran (coarse) 1-2 tbsp/day mixed with food
Zafirlukast 5 mg/cat PO q 12hr
Zidovudine 5 mglkg PO, SQ q 12hr
Zinc 7.5 mg/cat/day PO, indefi-
nitely
Selenium
Sodium bicarbo-
nate
Vitamin K
1
Spironolactone
Stanozolol
Sucralfate
VitaminC
Vitamin E
Taurine
Terbutaline
Theophylline
Thiamine
Triamcinolone
Trimethoprim-
sulfonamide
Tropicamide
Tylosin
Ursodeoxycholic
acid
Vitamin A
Drugs for the treatment of lymphoma are described in chapter 68; drugs for use with reproductive disorders
are described in chapters 29 and 60.
Most doses listed are starting doses. Duration of treatment varies with the use. Please see individual chapters
for complete descriptions for the use of these drugs and a description of toxicities.
IV := intravenously, 1M:= intramuscularly, SQ := subcutaneously, PO := orally, CRl := constant-rate infusion.
INDEX
Page numbers in boldface typeindicate complete chapters.
Abdomen
distentionof, 172-175
hypercortisolisrn-related, 266
pancreatitis-related, 168
urinarytract neoplasia-related, 220
intestinal obstruction-relatedmass in, 114
pain in
hypoadrenocorticism-related, 273
inflammatorybowel disease-related,108
pancreatitis-related, 168, 169
palpationof, in fever evaluation, 330
Abdominal effusion, 154, 157
Abortifacients,310
Abortion, 306-309
Coxiella bumetii infection-related,439, 440
feline panleukopeniavirus-related, 101
salmonellosis-related, 97
therapeutic, 310
Abscess
bite wound-related,327, 329
pancreatic, 167
pulmonary,pyothorax-related, 55, 57, 60
Abyssiniancats
amyloidosisin, 181
pyruvatekinase deficiencyin, 372
renal amyloidosisin, 213
renal failure in, 185
Academyof Feline Medicine, vaccination
recommendationsof, 7
Acepromazine
contraindicationin portosystemicshunt patients, 166
as renal failure treatment, 192
as urethral relaxant,234
Acetaminophen
hepatotoxicityof, 160, 161
as methemoglobinemia cause, 378
N-Acetyicysteine
contraindicationas asthma treatment,42
as drug-inducedhepatic disease treatment, 161
N-Acetylglucosaminesupplementation,in inflammatory
bowel disease, III
Acid-baseabnormalities,chronic renal failure-related, 241
Acidosis, metabolic
as contraindicationto acidifyingdiets, 228
functional urinaryobstruction-related,233
renal failure-related, 187-188, 191, 196,201,241
uremicanorexia-related,239
Aciduria, induced, 243-244
Acinetobacter infections,40
Acquiredimmunodeficiencysyndrome(AIDS). See also
Feline immunodeficiency virus infection;
Immunocompromised humans
feline, 392, 394-395
human, 417-418
Acromegaly, 287, 311
Activatedclottingtime (ACT), 367-368
Activatedpartial thromboplastintime (APTT)
in bleedingdisorders, 367, 368, 369, 370
in hepatic lipidosis, 143, 144
Addison's disease, 272
Adenocarcinoma
adrenal, 270
gastrointestinal, 114, 115, 116-117, 118
Adenocarcinoma(cont.)
hepatocellular,147, 149
nasal, 23
pancreatic, 167, 171
pulmonary,71
of urinarytract, 220
Adenoma
of biliaryduct, 147
hepatocellular, 149
pituitary,265
Adrenalectomy, 270, 272
Adrenal tumors, 265, 271
Adrenocorticotropic hormone
decreasedsecretionof. See Hypoadrenocorticism
excessivesecretionof. See Hyperadrenocorticism
Adrenocorticotropic hormonestimulationtest, 183,267,
268-269, 274
Aelurostrongylus abstrusus infections, 33,47,48--49, 52
Agglutination,373, 374
Agranulocytosis, methimazole-related, 264
Airwayfluid, in asthma, 39-40
Airwaysecretions, collectionof, 35
Airwaywashing, 34-35, 44, 48, 53
Alanine aminotransferaseelevation
in biliary disease, 154
in cholangiohepatitis/cholangitis syndrome, 136, 138
in drug-inducedhepatopathy, 160, 162
in hepatobiliaryneoplasia, 148
in hyperthyroidism,260
in portosystemicshunt, 164
Alaria marcianae, 88, 91
Albumin,calcium-bindingaction of, 288-289
Aldosterone-secreting adrenal tumors, 271-272
Alkalinephosphataseelevation
in cholangitisicholangiohepatitis complex, 138
in hepatic lipidosis, 136, 143
in hepatobiliaryneoplasia, 148
in hyperthyroidism, 260
Alkalosis, respiratory,drug-inducedhepatopathy-related,
16(}-161
Alkaluria, induced, 243, 244
Alpha-glucosidase inhibitors, 282, 283
Alprazolam,as urethral relaxant, 234
Aluminumcarbonate, asrenal failure treatment, 192
Aluminumhydroxide, as renal failure treatment, 192
Alveolar-arterial gradient (A-a), 53
Alveolar lung disease, thoracicradiographicabnormalities
in, 34
AmericanAssociationof Feline Practitioners,vaccination
recommendations of, 7
Amitriptyline,as lower urinary tract diseasetreatment,
226-227
Amlopidine,as renal failure treatment, 192
Ammoniagenesis, effect of proteinrestrictionon, 242
Amoebicinfections, 82, 83
Amoxicillin-clavulanate, as bacterial rhinitis treatment,6
Amphimerus pseudofelineus, 170
AmphotericinB
as fever cause, 329
liposome-encapsulated microsomal, 54, 106, 107
Amylase, pancreatitis-relatedincrease in, 168
Amyloidosis, 181,210,213,243
457
458 Index
Anabolic steroids, contraindicationin chronic renal failure,
201
Analgesia
in aortic thromboembolism,77-78
in pancreatitis, 169
after pleural lavage,59
during thoracocentesis,6I
Anaphylaxis,vaccine-related,413
Ancylostoma infections, 85, 86, 419, 420, 421
Anemia
chronic disease-related,404-405
cytauxzoonosis-related, 384
feline infectious, 372, 379, 380
as generalizedweaknesscause, 337
Heinz bodies associatedwith, 378
hemobartonellosis-related, 327, 379, 380-381
hemolytic
clinical featuresof, 329
feline leukemiavirus infection-related,389
immune-mediated,371-376
infectious, 372
lidocaine-related, 63
microangiopathic, 372
histoplasmosis-related, 106
intestinal obstruction-related,115
iron-deficiency, 197, 242, 402, 403, 405-406
microcytic. 109. 164
mucousmembranepallor in, 371
nonregenerative, 371, 400-406
without cytopenias,402-403
ehrlichiosis-related,399
feline leukemiavirus infection-related.390
hernobartonellosis-related, 380-381
nasal fungal disease-related, 13
pneumonia-related, 53
regenerative,371, 380
renal failure-related, 189, 197, 242
uremicanorexia-related,239
Anesthesia
in hyperthyroidpatients, 263
in portosystemicshunt patients, 166
prolonged, as kidneyfailurecause, 184
Anestrus, 301-302
Angiornatosus, bacillary,444, 445
Angiotensin-converting enzyme inhibitors, 78, 79, 212, 324
Anisocoria, 256
Anisocytosis.lung cancer-related,71
Anisokaryosis,lungcancer-related,71
Anorexia, 315-321
biliarydisorders-related, 154
cholangitislcholangiobepatitis complex-related. 138
chylothorax-related,66
definitionof, 315
diabetic ketoacidosis-related, 122
drug-inducedhepatopathy-related, 160
feline infectious peritonitis-related,175
feline panleukopeniavirus-related, 10I
fever-related, 327
heart disease-related,75
hepatic lipidosis-related,142. 143
inflammatorybowel disease-related, 108
intestinal obstruction-related, 114
laryngeal or tracheal cancer-related,69
megacolon-related, 129
nasal tumor-related,23
primary,315
Anorexia(com.)
primary lung tumor-related,70
pyothorax-related, 56, 59
renal failure-related, 190
secondary,315
uremic, 239--240
vitamin Kdeficiencyassociatedwith, 369
Antacids, magnesium-containing, contraindicationto, 201
Antibiotictherapy
for asthma, 38, 41-42
for bacterial gastrointestinaldiseases, %-97
for bacterial rhinitis, 6, 7
for campylobacteriosis, 98
for clostridial diarrhea, 99
contraindicationin lower urinarytract disease, 227
for diarrhea, 95
for feline infectiousperitonitis, 178, 179
for feline panleukopeniavirus infections, 103
for hemobartoncllosis, 382
as hemolyticanemia cause, 372
for pneumonia,54
for portosystemicshunt, 165
for pyelonephritis,205
for pyothorax,57
for salmonellosis,98
for urinarytract infections. 231
as vitamin Kdeficiencycause, 369
Anticoagulants,physiologic.366
Anticoagulanttherapy,78
Antiemetics, 122-123, 169
Antifungal agents, as fungal pneumoniatreatment. 54
Antihelminthics,88-89, 90, 94
Antihistamines
contraindicationas asthma treatment, 42
as motion sickness treatment, 123
Antihypertensive agents, 323-324
Anti-interleukin-5 antibody,as small airwaydisease
treatment, 41
Antinuclear antibodies, positive, methimazole-induced. 264
Antithrombinill, 366, 367, 368, 370
Anuria, 188
Anxiety,as inappropriateurinationcause, 245, 251, 252
Aorta, thromboticocclusionof, 75, 77-78, 340
Aorticthromboembolism/ischemic neuromyopathy, 340
Aplasia, pure red cell, 373, 374,402
Appetitestimulants, 240, 318
Aqueous flare, 341
Aqueoushumor
cryptococcal antigendetection in, 13
feline calcivirusdetectionin, 9
felineherpesvirus-I detectionin, 9
Argininesupplementation,in hepatic lipidosis, 146
Arrhythmia, hypercalcemia-related, 289
Arterial blood gas analysis, in pneumonia, 53
Arteritis, pulmonary,feline heartwormdisease-related,45
Arthritis, bacterial. in kittens, 333
Arthrocentesis,332
Arthrodesis, as osteoarthritistreatment. 333
Artificialinsemination, 300
Arythenoids,examinationof, 3
Ascarid infections(roundworms),86, 90. See also
Toxocariasis
Ascites, 172-173, 174
feline infectious peritonitis-related, J75, 177
Aspartateaminotransferaseelevation
in aortic thromboembolism,75
Index 459
Aspartate aminotransferaseelevation(cont.)
in biliary disease, 154
in drug-induced hepatopathy, 160, 162
in myopathy, 337
Aspergillosis
gastrointestinal, 107
hepatic, 151, 153
nasal, 12, 13-14
respiratory, 11-I2
zoonotic, 441
Aspergillus,culture of, 14
Aspiration
manual, in pneumothorax, 64
as pneumonia cause, 21-22, 30, 50, 55, 131
Aspiration biopsy
for cholangitis/cholangiohepatitiscomplex evaluation,
138-139
hepatic, 136
of lung mass, 71
for neutrophiliaevaluation, 359
transthoracic, 35-36
of urinary tract tumors, 221
Aspirin
as aortic thromboembolismtreatment, 78
contraindication as heat stroke treatment, 330
as fever treatment, 330
as joint disease treatment, 333
safety of, 160
Asthma, 37-40
bronchial patterns in, 34
as respiratory distress cause, 77
respiratory rate in, 31
Ataxia, infectious feline peritonitis-related, 176
Atropine, contraindicationsto, 42, 263
Auranofin, as joint disease treatment, 333
Auscultation, thoracic, 32
Aversiontraining, for inappropriate urination management,
248-249
Azathioprine, I 12, 333
Azidodeoxythyrnidine (AZT), 395
Azithromycin, as bacterial rhinitis treatment, 6
Azotemia, 183
heart disease-related, 75
renal failure-related, 184, 186, 199, 228
urinary obstruction-related, 233
AZf (azidodeoxythymidine), 395
Bacteremia, 97, 98, 103, 437
Bacterial infections. See also specificbacteria
bite or scratch-related transmissionof, 426-429
cutaneous, 435
diarrhea associated with, 82
gastrointestinal, 82,95-100,419
hepatic, 151
lower urinary tract disease associated with, 224
lymphadenopathyassociated with, 349
nasal discharge associated with, I
respiratory,4-8, 29
sneezing associated with, I
uterine, as abortion cause, 308
vomiting associatedwith, 82
zoonotic, 419, 426-429, 435
Bacterial overgrowth, duodenal, 100
Bacteriuria, 182,215,231
Bacteroidesinfections, 57, 426
Baermann fecal examination, 33, 48, 166, 364
Barbiturates, contraindication in portosystemicshunt
patients, 166
Barotrauma, as pneumothoraxcause, 61
Bartonellahenselaeinfections, 344, 427, 428
Bartonellaspp. infections, 344, 426
Basophilia, 33,44, 115
Behavior modificationtherapy, for inappropriate urination,
247,250,251
Benzopyrine derivatives,as chylothorax treatment, 68
Besnoitia,91, 92
Beta, agonists, effect on airways, 41
Beta blockers, 42, 78, 324
Biguanides, 282, 283
Bile acids, in hyperbilirubinemiaor icterus, 136
Bile duct
adenoma of, 147, 148
carcinoma of, 147
fibrosis of, 152
obstruction of, 143, 148
extrahepatic, 156
rupture of, 154, 156
Biliary diseases, 154-157
Biliary tree, anatomy of, 137
Bilirubinemia, cholangitis/cholangiohepatitiscomplex-
related, 138
Biopsy.See alsoAspiration biopsy
bone marrowcore, 406
hepatic, 136, 138-139, 143, 148
for inflammatorybowel disease evaluation, 109-110
for lower urinarytract disease evaluation, 225
oflung mass, 71
of muscle, 338, 340
of nasal tumors, 25
for neutropenia evaluation, 359, 362
of postvaccinallump, 414
renal, 187,206-207,211-212
Biosecurity, 407410
Bisacodyl, 131. 132
Bite wounds
feline immunodeficiencyvirus transmissionby, 391
in humans
treatment of, 427
as zoonotic disease cause, 407, 417, 426-431, 437
infectious disease transmission by, 407
as pneumothoraxcause. 61
as pyothorax cause, 55
Bladder, rupture of. 172
Bladder neck reconstruction, 257
Bladder tumors, 220, 221
Blastomycesdermatitidis. See also Blastomycosis
as primaryfeline fungal pathogen, II
Blastomycosis, 52, 55, 436, 441
clinical features of, 328
nasal, 12
pneumonia associated with, 54
treatment of, 328
Bleeding disorders, 365-371
liver disease-related, 143
Bleeding time (BT), 367, 368
Blepharospasm, 341
Blindness, 44, 54
Blood, calcium transport in, 288
Blood cultures, optimal technique for, 330
Blood glucose curve, 280-281
Blood pressure
diastolic, 321, 322
measurement of, 322
systolic, 321, 322
Blood smear
of Cytauxzoon felis, 384-386
of Heinz bodies, 377
460
Blood smear (cont.)
of Hemobartonella felis, 381, 382
for nonregenerativeanemia diagnosis,400
Blood transfusion
in chronicrenal failure-relatedanemia, 197
of citrated blood, 291-292
in feline panleukopeniavirus infection, 102
in hernobartonellosis, 382
in immune-mediatedhemolyticanemia, 375-376
in vitaminKdeficiencyor antagonism,369
Blood urea nitrogen(BUN)
hyperthyroidism-related increase in, 260
portosystemicshunt-relateddecreasein, 164
prerenal azotemia-relatedincrease in, 184
renal failure-relatedincrease in, 186
Bodytemperature,elevated, 326. See also Fever
Bone marrow,core biopsyof, 406
Bordetella bronchiseptica infection. See Bordetellosis
Bordetella bronchiseptica vaccination,7, 410, 413
Bordetellosis
conformationalrespiratorydisease-associated, 22
nasal,13
pneumoniaassociatedwith, 51
rhinitis, 4-5, 7
small airway disease associatedwith, 40
transmissionof, 407
as zoonoticdisease, 431, 432
Borrelia burgdorferi infections, 334, 444, 445
Brachycephalic cats, respiratorytract conformational
deformitiesin, 19, 20
Braindamage, fever-related, 326
Breathingpatterns
open-mouthed
in asthma, 37
in bilateral nasal obstruction, 4
in caudal nasopharynx, 20
in pneumothorax, 61
in respiratorytract conformationaldisease, 20
restrictive, 34
Breath sounds, absent or muffled, 32, 33
Bronchial dysgenesis, 19,20,21
Bronchial patterns, 34
Bronchiectasis, 19,21,22,39
Bronchitis, 37, 40
Bronchoconstriction, mediatorsof, 38
Bronchodilators,as asthma treatment, 38, 41
Bronchogram,air, in alveolar lung disease, 34
Burmesecats, 185,337
Butorphanol, 169,333
Cachexia, intestinal obstruction-related, 114
Cages, cleaning of, 97
Calcitonin, 288, 291
Calcitrol supplementation,in renal failure, 192,201
Calcium
physiologicroles of, 288
serumconcentrationof, 288-289
Calciumacetate, as renal failure treatment, 192
Calciumcarbonate, as renal failure treatment, 192
Calciumchannel blockers, 78, 324
Calcivirus. See Feline calicivirusinfection
Calculi. See Urinarycalculi
Calicotomcats, infertilityin, 304
Campylobacteriosis
gastrointestinal, 95, 98, 419
zoonotic, 419, 424, 425
Campylobacter jejuni
fecal smear of, 83, 84
morphologiccharacteristicsof, 95
Index
Campylobacter jejuni infections.See Campylobacteriosis
Cancer. See also specific types of cancer
conditions associatedwith
chylothorax, 65
eosinophilia,364
feline leukemiavirus infection, 388
fever,329
hypercalcemia,290, 291
lymphadenopathy, 349
neutropenia,359
vomitingand diarrhea, 119
Candidiasis, gastrointestinal, 107
Canine distemper virus, 51
Capillaria aerophilia infections,47, 49, 52, 88
Capnocytophaga canimorsus infections,426, 427
Carbimazole, as hyperthyroidismtreatment, 264
Carboplatin, as squamouscell carcinoma treatment, 27
Carcinoid, gastrointestinal, 114
Carcinoma,neuroendocrine, 118
Carcinomatosis,intestinal obstruction-related, 114
Cardiomyopathy
definitionof, 73
dilated, 66, 74-75, 77
hyperthyroidism-associated,75-76
hypertrophic,32, 66, 67, 73-74, 77, 78-79
idiopathicor primary,73
restrictive,66, 74, 77, 78-79
secondary, 73
vomitingassociatedwith, 122
Cardiopulmonarydisease, as generalizedweaknesscause,
337
Cardiovasculardisease
commonclinical signs of, 75
hyperthyroidism-related, 260, 261
respiratorytract disease-related,31
thoracicauscultationfindingsin, 32
Cardiovascularemergencies, 77
Carnitinedeficiency, 143
Carnitinesupplementation, in hepatic lipidosis, 146
Caroprofen,as joint disease treatment, 333
Castration
of cryptorchidtomcats, 303
as obesity cause, 311
Cataracts, 346
Cat carriers, use in inappropriateurinationmanagement,
247
Catheterization,urethral, 228-229
in functional urinaryobstruction, 229, 233, 235
Catheters, tom-cat, use in nasopharynxexamination,21
Cat ownership,by immunocompromised persons, 417-418
Cat-scratchdisease, 426, 427-429, 445
Caval syndrome,43, 46
Central nervoussystemdisorders
cryptococcal, 12
portosystemicshunt-related, 163
Centrifugationfecal flotationtest. See Fecal flotationtest
Cephalexin,as bacterial rhinitis treatment, 6
Cervix, open versus closed, 296
Cestodeinfections
gastrointestinal,85
treatmentof, 88
zoonotic, 419, 421
Chagas' disease, 446-447
Chemoreceptortrigger zone, 120, 123
Chemotherapy
as emesis cause, 123
for hepatic cancer, 149
for lower urinarytract cancer, 222
Index 461
Chemotherapy (cont.)
for lymphoma, 351, 352-353
for nasal tumors, 26, 27
for squamous cell carcinoma, 27
toxicity of, 354
for vaccine-related sarcoma, 415
for visceral mastocytosis, 150
Chest, traumatic injuries to, as pneumothorax cause, 61
Chest tubes
as pneumothorax treatment, 63-64
as pyothorax treatment, 57-59, 60
Cheyletiella infections, zoonotic cutaneous, 435, 437
Chlamydia psittaci infections. See Chlamydiosis
Chlamydia psittaci vaccination, 7, 410, 412-413
Chlamydiosis
clinical features of, 4, 328
lower respiratory disease, 51
nasal, 13
respiratory, 4,7,51,431
treatment of, 328
as zoonotic disease, 431, 432
Chlorambucil
as feline infectious peritonitis treatment, 178, 179
as immune-mediated hemolytic anemia treatment, 375
as inflammatory bowel disease treatment, 112-113
Chloramphenicol, as bacterial rhinitis treatment, 6
Chloride, recommended daily intake of, 241
Chloride restriction, in chronic renal failure, 240-241
Chlorpromazine, 169, 192
Cholangiohepatitis, 124
definition of, 137
pancreatitis associated with, 121
treatment of, 328
Cholangiohepatitis/cholangitis complex, 134, 136,
137-141,143,154
cholelithiasis associated with. 155
definition of, 137
pancreatitis associated with, 168
secondary gastrointestinal disease associated with,
121
Cholecystitis, 154, 155, 156
Choledochitis, 154, 155
Cholelithiasis, 155-156
Cholestasis, 158, 367
Chondrosarcoma, 23. 25
Chorioretinitis, 2, 341
chronic, 342
cryptococcal, 12
feline infectious peritonitis-related, 176
Choroid, structure of, 341
Choroiditis, 341
Chronic disease, anemia of, 404-405
Chyloperitoneum, 172
Chylothorax, 6 5 ~ 9
Ciliary body, structure of, 341
Cimetidine, as renal failure treatment, 192
Cirrhosis, 135, 141
Cisapride, 131
Cisplatin, as squamous cell carcinoma treatment, 27
Cleft palate, 19, 20, 21, 22
Clindamycin, 6, 49-50
Clostridium perfringens
fecal smear of, 83
morphologic characteristics of, 95. 98, 99
Clostridium perfringens infections, gastrointestinal, 95,
98-99
Clotting factnr deficiencies, 366. See also Coagulation
disorders
Clotting factors, production of, 366
Coagulation disorders
feline panleukopenia virus-related, 102
as hemoabdomen cause, 172
inherited, 369
sneezing associated with, 1, 2
vitamin Kj-responsive, pancreatitis associated with, 168
Coagulation tests, 143, 367, 368, 369
Coagulation times, in biliary disease, 154
Cobalamine. See Vitamin B
I2
Coccidian infections, gastrointestinal, 82, 83, 85, 91-92,
419
Coccidioides immitis infections. See Coccidioidomycosis
Coccidioidomycosis, 12,54,328,419,436,441-442
Coccidiosis, enteric, 92
Cold-agglutinin disease, 373
Colectomy, 133, 134
Colitis, 110
Colonic cancer, 118
Colonoscopy, for intestinal obstruction evaluation, 116
Colostral antibodies, 103
Combination test, for hypercortisolemia diagnosis, 267,
268,269
Complete blood cell count (CBC)
in biliary tract disease, 154
in cough or dyspnea, 33
in diarrhea, 82
in feline panleukopenia virus infections, 102
in hemolytic anemia, 374
in hepatic lipidosis, 143
in hypercortisolism, 266, 267
in hypoadrenocorticism, 273-274
in inflammatory bowel disease, 109
in intestinal obstruction, 115
in lower urinary tract disease, 225
in neutropenia, 361
in neutrophilia, 358
in nonregenerative anemia, 400-40 I, 402
in pneumonia, 52-53
in pyelonephritis, 204
in renal failure, 186
in vomiting, 82
Computed tomography, of nasal tumors, 26
Conceive, failure to, 298-305
differentiated from early embryonic death, 307
Conception rate, 299
Confinement therapy, for inappropriate urination
management, 252, 253-254
Conformational diseases, of the respiratory tract, 19-23
Congenital abnormalities, panleukopenia-related, 308
Congestive heart failure, 75, 77-78. 172
Conjunctivitis, 4, 9
Conn's syndrome, 76
Constipation, 129, 130-131, 133, 134,312
chronic renal failure-related, 185
definition of, 128
Contraceptives, 309-310
Contractures, myopathy-related, 337
Contusions, myocardial or pulmonary, 62
Coomb's test, positive, in methimazole therapy, 264
Copulation, 300
failure of, 302-303
Core temperature, 326
Cornea
edema of, 341
uveitis-associated ulceration of. 346
462
Coronaviruses. See also Feline enteric coronavirus
infection
in callery-raised cats, 343
definition of, 104
as gastrointestinal disease cause, 100, 104
as pregnancyloss cause, 308
Corticosteroids. See also Glucocorticoids
as neutrophilia cause, 355, 356, 358
Corynebacterium infection, 5
Cosequin, as joint disease treatment, 333
Cough
Aelurostrongylus abstrusus infection-related,48
anterior, viral upper respiratorydisease-related, 9
asthma-related, 37
Capillaria aerophila infection-related,48
chylothorax-related, 66
definition of, 28
differential diagnoses of, 28
feline heartwormdisease-related, 43
infection-related,29-30
initial diagnostic plan for, 28-36
laryngeal or tracheal cancer-related, 69
mediastinal cancer-related, 72
nasal discharge-related, 4
Paragonimus infection-related, 47
primary lung tumor-related, 70
tracheal, 32
wet versus dry, 32
Coupage, as pneumoniatreatment, 54
Coxiella bumetti infections
as abortion cause, 308
vaginal, 295
zoonotic, 431, 439, 444, 445
Crackles
asthma-related, 38
cardiovascular emergency-related, 77
hypertrophiccardiomyopathy-related, 32
Crayfish, as Paragonimus vector, 47
Creatine kinase elevation
in muscular dystrophy, 339
in myopathy, 337
Creatine phosphokinase, aortic thromboembolism-related
elevationof, 75
Creatinine, renal failure-related elevationin, 202
Cryptococcal antigen, detection of, 13
Cryptococcosis
nasal, 2, 3, 5, 14-15
ocular lesions associated with, 330
respiratory, 11-12, 13, 14,52,54
treatment of, 14-15,328
as zoonotic disease, 436, 441,442
Cryptococcus neoformans. See also Cryptococcosis
culture of, 14
Cryptocotyle lingua, 91
Cryptorchidism, 246, 303
Cryptosporidiosis, 92-93, 422
fecal antigen assay for, 83
fecal smear of, 83
Cryptosporidum parvum infections, 88, 91, 419, 420, 422
Cryptosporidum spp., 92
Crystalluria. See also Urinarycalculi
dietary therapyfor, 227
as idiopathic lower urinary tract disease cause, 223
Ctenocephalides felis infections, 135,373,437,444,445
Index
Cushing's syndrome. See Hyperadrenocorticism
Cutaneous diseases
eosinophilia associated with, 364
zoonotic, 435-438
Cyanosis, 56, 66, 69
Cyclophosphamide
as feline infectious peritonitis treatment, 178, 179
as immune-mediatedhemolytic anemia treatment,
375
as inflammatory bowel disease treatment, 112-113
Cycloplegic agents, as uveitis treatment, 346
Cyclosporine, 113,375
Cyclosporine-A, as small airway disease treatment, 41
Cyproheptadine
appetite-stimulatingaction of, 240
as small airway disease treatment, 41
Cyst
hepatobiliary, 157
hydatid, 90, 421
renal. See Polycystic kidneydisease
Cystitis, 254
idiopathic, 214-215
interstitial. in humans, 224
Cystocentesis, 215, 225, 231, 297,300
Cystoisopora, 91, 92
Cystoscopy,215, 226
Cystotomy, 218,225
Cystourethrography,contrast. 222, 225, 226
Cytauxzoon felis, 383
Cytauxzoonosis, 383-387, 404
as anemia cause, 372, 373
as hepatic disease cause, 151-152
as hyperbilirubinemiaand icterus cause, 135
Cytology
of airway washings. 35
of nasal discharge, 2, 5
of nasal tumors, 25
rectal, for diarrhea evaluation. 83, 95
vaginal. 295, 296, 302
Cytopenia, vaccine-related,413
Dantrolene, as urethral relaxant, 234
Dehydration
diabetic ketoacidosis-related, 284-285
as drug-inducedhepatotoxicityrisk factor, 159-160
hepatic lipidosis-related, 142
hyperosmolar diabetes mellitus-related. 286
hypoadrenocorticism-related,273, 274
pyothorax-related, 57
renal failure-related, 185, 189,190,241
Dental infections/disease. I, 13
Depression
fever-related,327
heart disease-related. 75
hypoadrenocorticisrn-related,273
Dermacenter variabilis, 373, 383
Dermatologic diseases
eosinophilia associated with, 364
zoonotic, 435-438
Dermatophytes, 435-437
Detrusor atony, 233
DevonRex cats, 339, 369
Index 463
Dexamethasone, as immune-mediatedhemolytic anemia
treatment, 375
Dexamethasone suppression tests, 267, 268, 269
Dextrose, as renal failure treatment, 192
Diabetes insipidus, nephrogenic, 182, 183
Diabetes mellitus, 276-288
adrenalectomyin, 270
conditions associated with
hepatic lipidosis, 142
hepatomegaly, 182
hypercortisolism265, 267, 270-271
hypertension, 321
pancreatitis, 168
polyneuropathy, 337
polyphagia, 314
polyuria/polydipsia, 183
definition of, 276
hyperosmolar, 284, 285-286
insulin-dependent, 277
insulin therapy for, 278, 279-282
non-insulin-dependent, 277
obesity-related, 312
oral hypoglycemicagent therapy for, 279, 282-284
Dialysis, 199-200
Diaphragm, abnormalities of, 34, 329, 339
Diaphragmitis, 329
Diarrhea
bacterial infection-related, 95, 97, 98-99
Campylobacter-related, 98
cholangitislcholangiohepatitiscomplex-related, 138
clostridial, 98-99
differential diagnoses for, 81, 82
drug-induced hepatopathy-related, 160
exocrine pancreatic insufficiency-related, 121
feline enteric coronavirus-related, 175
fungal infection-related, 105, 107
hyperthyroidism-related, 121-122,259,260
hypoadrenocorticism-related, 122, 266
hypoalbuminemia-related, 173
inflammatory bowel disease-related, 108, 110
large bowel, 8I, 82
mixed bowel, 8I, 82
pancreatitis-related, 120, 168, 170
Platynosomum concinnuminfection-related, 152
secondary gastrointestinal disease-related, 119, 120
small bowel, 81, 82
Strongloidesstercoralis-related, 87
Trichomonas-related, 94
Diazepam
contraindication in portosystemicshunt patients, 166
hepatotoxicityof, 161-162
as urethral relaxant, 234
Diet, 236-244
acidifying, as lower urinary tract disease treatment,
227-228
in anorexia or weight loss, 317-318
in bacterial rhinitis, 7
in cholangiohepatitislcholangitiscomplex, 139
for diabetic cats, 278
dry kibble, as urinarycalculi cause, 216
enteric bland, 170
high-carbohydrate, low-protein, for portosystemicshunt
modification, 165
Diet (cont.)
"ideal," 219
in idiopathic feline lower urinary tract disease, 236, 244
low-fat, as chylothoraxtreatment, 68, 69
in renal disease, 195, 202, 236, 239-243, 318
in urinarycalculi, 217, 218, 219
in urinary tract disease, 236, 237-238, 243-244
for weight loss, 312-313
Digitalis, as cardiomyopathytreatment, 78
Digoxin, as cardiomyopathytreatment, 78, 79
1,25-Dihydroxycholecalciferol,288
Dimethylglycinesupplementation, in inflammatorybowel
disease, III
Diocyti sodiumsuccinate, 130-131, 132, 133
Diphenhydramine, as pancreatitis treatment, 169
Diphenylhydrarnine,as pancreatitis treatment, 169
Diphyllobothrium latum, 90
Dipylidiumcaninuminfections, 85, 86, 89, 90
zoonotic, 419, 421, 444, 446
Dipyrone, contraindication in heat stroke, 330
Dirofilariaimmitis.See also Dirofilariasis
surgical removal of, 46
Dirofilariasis, 31, 43-46
as anemia cause, 372
as chylothoraxcause, 66
as pneumothoraxcause, 61
respiratory tract involvementin, 43-44, 47
testing for, 33
as vomitingcause, 122
as zoonotic disease, 444, 446
Disinfection, basic protocols in, 409-410
Disseminatedintravascularcoagulation, 102, 103, 368, 370,
372
Diuresis, in renal failure, 189,190
Diuretics
as cardiomyopathytreatment, 78
as chylothorax treatment, 68
contraindication in asthma, 42
as systemic hypertensiontreatment, 324
Domestic shorthair cats, hypertrophiccardiomyopathy in,
74
Dopamine, contraindication in renal failure, 190
Doppler ultrasonography,use in blood pressure
measurement, 322
Doxycycline
as bacterial rhinitis treatment, 6
as esophageal stricture cause, 125, 126
as esophagitis cause, 52
as helicobacteriosis treatment, 389
Drug interactions, in renal failure, 198-199
Drugs. See also specificdrugs
adverse effects of
abortion, 309
Heinz bodies, 378
hemolytic anemia, 372, 373, 376
hepatoxicity, 158-162
neutropenia, 359
polyphagia, 314
pyogenicity,329
teratogenicity,309
vomiting and diarrhea, 119
Duodenum, bacterial overgrowthin, 100, 110
Dysautonomia, 119,257
Dyschezia, 128, 129
Dysphagia, 72, I !4, 124, 339
Dyspnea
464
Index
Dyspnea (cont.)
definitionof, 28
differential diagnoses of, 29
feline heartwormdisease-related,43
handling-relatedexacerbationof, 38
hypertrophiccardiomyopathy-related, 32
infection-related,29-30
initial diagnosticplan for, 28-36
inspiratory, laryngeal paralysis-related, 21
mediastinalcancer-related,72
primarylung tumor-related, 70
Dyssynergia, reflex, 214, 232
Dysuria, 214, 216, 223, 232
!Oar, necrosisof, 373
Earexamination
for nasal polypevaluation, 17
for sneezingand nasal dischargeevaluation, 2
Early embryonicdeath, 304, 307
Echinococcosis,85, 90, 419, 421
Echinococcus multilocularis, 85, 90
Echocardiography
for cardiomyopathyevaluation, 77
for feline heartwormdisease diagnosis, 44,
46
Ectoparasites.See also Fleas; Ticks
zoonotic,435, 437-438
Edema
corneal,341
pulmonary,77, 376
EHBDO.See Extrahepaticbile duct obstruction
Ehrlichia, 397
Ehrlichiosis,397-399
platelet disorders associatedwith, 368
as polyarthritiscause, 334
treatment of, 327, 399
zoonotic, 444, 446
Electrocardiography
in cardiomyopathy, 76-77
in hypoadrenocorticism, 274
Electrodiagnostictests, for urinaryincontinenceevaluation,
256
Electrolytetherapy, for diabetic ketoacidosis,285
Electromyography, 338, 339-340
Emaciation
chronic respiratorytract disease-related,31
hyperthyroidism-related, 259
Embryonicdeath, early, 304, 307
Empyema, 59
Enalapril, as renal failure treatment, 193
Encephalopathy
hepatic, 141, 144, 16G-161, 164, 166
uremic, 187
Endocrinedisorders
myopathy-associated, 339
as vomitingand diarrheacause, 119
Endophthalmitis, 341
Endoscopy
for gastrointestinaltract disease evaluation,84
for intestinal obstructionevaluation, 116
for pollakiuriaevaluation, 215
Endotoxemia,97, 98, 99
Enema, 13G-131, 132
phosphate-containing, 2 9 1 ~ 2 9 2
Enrofloxacin
as bacterial rhinitis treatment, 6
as blindesscause, 54
Entamoeba histolytica, direct fecal smear of, 83
Enteral nutritional support, 319
Enteritis
bacterial, 95, 108
Iymphocytic-plasmacytic, 109, 110
pancreatitis-associated, 168
Enterobacter infections,5, 40, 231
Enterocolitis, 110
Enteropathy, protein-losing,105, 109, 174
Enzyme-linkedimmunosorbentassay (ELISA)
for feline immunodeficiency virus diagnosis, 393-394
for feline leukemiavirus infectiondiagnosis, 389
Eosinopenia, 363
Eosinophilia, 363-365
methimazole-related,264
peripheral, dirofilariasis-related, 44
respiratorydisease-related,33
Eosinophils
in asthma, 40
functionsof, 363
Eosinophlicgranulomacomplex, 363-364
Epinephrine,as neutrophiliacause, 355, 356, 357,358
Epistaxis, 2, 4, 23
Equipment, cleaningand disinfectionof, 408
Erythrocyterefractilebodies, 377
Erythropoietin
as hypertensioncause, 322
as renal failure-relatedanemia treatment, 193, 242
Escherichia coli, morphologiccharacteristicsof, 95
Escherichia coli infections, 99
gastrointestinal,95, 419
pneumonia, 51
pyometra, 297
rhinitis, 5
urinary, 231
uterine, as pregnancyloss cause, 308
Esophageal strictures, 52, 124--126, 127
Esophagitis, 126
Esophagostomyfeeding tubes, 144, 145,240,319-320
Esophagus
peristalticactivityof, 126
regurgitationfrom, 124--127
Estradiol, in anestrus, 301-302
Estrogen, 302
Estrogentherapy,for urethral incompetence,257-258
Estrus, 298--299
inductionof, 301
persistent, nonovulatory, 302
Ethanol, as renal failure treatment, 193
Ethyleneglycol toxicity, 291-292
Eurytrema procyonis, 167, 170
Exerciseintolerance, 37, 56, 66
Exophthalmos,nasal tumor-related,23
Extracorporealshock-wavelithotripsy(ESWL), 218
Extrahepaticbile duct obstruction(EHBDO), J56
Exudate-associatedzoonoses, 435-438
Exudates, as abdominaldistentioncause, 172, 173, 174
Facial nerve paralysis, 16, 18
Factor function test, 139
Fading kitten syndrome,97, 308
Famotidine, as renal failure treatment, 193
Fasting, 316
Fatty acid supplements, as renal failure treatment, 202
Index 465
Fey. See Felinecalicivirusinfection
Fecal antigenassays, 84
Fecal flotationtest, 83-84
for Capillaria aerophilia detection,49
for cough or dyspneaevaluation,33
for diarrheaevaluation, 82, 95
for migratoryrespiratoryparasitedetection,48
for nematodeegg detection, 86
for vomitingevaluation,82
Fecal impaction,severe,protracted.See Obstipation
Fecal samples, preservation of, 84
Fecal sedimentationtest, for Paragonimus eggs, 47-48
Fecal smear
for diarrheaevaluation,95
direct, 83
Fecal wet mount examination,for diarrheaevaluation, 95
Feces, acholic, 154
Feedingplans, 236
Feedingschedule, for diabeticcats, 278-279
Felinecalicivirusinfection
as abortioncause, 307, 308
clinical descriptionof, 327
diagnostictests for, 2
as lower urinarytract diseasecause, 224
as pneumoniacause, 5I
seropositivity for, 9
treatmentand preventionof, 10, 327
as upper respiratorydiseasecause, 8-9
Felinecalicivirusinfectionvaccination,7, 410, 411, 412
Felinecalicivirusstrains, coinfectionwith, 8
Felineentericcoronavirusinfection, 104, 152, 175
Felinefoamy virus, 430
Feline heartwormdisease. See Dirofilariasis
Felineherpesvirus-I, diagnostictests for, 2
Feline herpesvirus-I infection,5I
as abortioncause, 307
as ocular disease cause, 344
pancreatic, 167
as pneumoniacause, 51
seropositivity for, 9
transmission of, 407
treatmentand preventionof, 9, 327
as upper respiratorydiseasecause, 8, 9
Feline herpesvirus-I vaccination, 7, 410, 411, 412
Felineimmunodeficiency virus antibodyassay
in mediastinallymphoma,72
in nasal discharge,2
in outdoor cats, 343
in pyothorax,57
in vomitingor diarrhea,82
Felineimmunodeficiency virus infection,391-397
as nonregenerative anemiacause, 404, 405
as pneumoniacause, 50
as respiratorydiseasecause, 8, 30, 33
as secondarybacterialrhinitis cause, 5
as uveitiscause, 343
Felineimmunodeficiency virus vaccination, 396, 412
Felineinfectiousperitonitis, 167,175-180
causal virus of, 104, 152,175
conditionsassociatedwith, 175-176, 327
abdominaldistention, 173, 174
abortion, 307, 308
ascites, 177
diarrhea, 107
effusion, 135, 152, 175. 176
Felineinfectiousperitonitis(cant.)
conditionsassociatedwith (cant.)
gastrointestinal tract obstruction, 114, 115
hepaticdisease, 151, 152-153
hyperbilirubinemia, 134
ocular disease, 330, 344
pleural effusions, 177
pygranulomatous pneumonia,51-52
renalfailure, 184
secondarygastrointestinal disease, 12I
synovitis,334
uveitis,343
definitionof, 175
diagnosisof, 177-178
noneffusive, 152, 175, 176. 177-178
preventionof, 179-180
in purebredcats, 329
transudates in, 172
treatmentof, 178-179,327
Felineinfectiousperitonitisvaccination, 180, 410
Felineleukemiavirus, humancell cultureof, 430
Felineleukemiavirus antigenassay,327
in mediastinallymphoma,72
in nasal discharge,2
in outdoorcats, 343
in pyothorax, 57
for vomitingand diarrheaevaluation, 82
Felineleukemiavirus infection
conditionsassociatedwith, 327
anemia,402, 404, 405
diarrhea, 107
fever, 327, 329
hepaticdisease, 15I, 153
lymphoma,351, 354
lymphosarcoma, 135
myelosuppression, 368
ocular disease, 344-345
pneumonia,50
polyarthritis,334, 335
polyganglionopathy, 256
pregnancyloss, 307, 308
respiratorydisease, 8, 30, 33
secondarybacterial rhinitis,5
urinaryincontinence, 257, 258
urinarytract tumor,220, 22I
relationshipwithfelineinfectiousperitonitis, 177
stagesof, 388
treatmentof, 327
Felineleukemiavirus vaccination, 389, 390, 410, 412, 414
Felinepanleukopeniavirusinfection, 100-104,360,361
as pregnancy losscause, 307-308
treatmentof, 327
Feline panleukopenia virus vaccination, 7, 103-104,410,
411
Feline retrovirusinfections,zoonotic,430
Felinesyncytial-forming virus. as polyarthritiscause, 334,
335
FeLV. See Felineleukemiavirus infection
Fentanyl, 63, 166,
Fentanyl patch, use in pleural lavagepatients,59
Ferrous sulfate, as renal failuretreatment, 193
Fever,326-331
abdominaldistention-related, 173
advantagesof, 326
bacterial hepaticdisease-related, 135
bronchoesophageal fistula-related, 21
466
Fever tcont.i
detrimentaleffectsof, 326
immune-mediated, 329
immune-mediated polyarthritis-related, 335
infectious,327-328
inflammatory, 328-329
of unknown origin, 329, 330
vaccine-related, 413
Fiber,dietary
as chronicrenal failuretreatment,242-243
for clostridialdiarrheaprevention, 99
for constipationmanagement, 131, 132, 133
as inflammatory boweldiseasetreatment, 110
Fibrinogendegradationproducts,367, 368, 370
Fibrinolytic agents, usein pleurallavage,59
Fihrosarcoma, 23, 114, 147,388
Fibrosis
hepatic, 135, 141
pancreatic,168
FlP. See Felineinfectiousperitonitis
Fishoil, as small airwaydiseasetreatment,41
Fistula
bronchoesophageal, 19,20,21-22
nasopharyngeal, 13
oronasal,2, 3
pleurocutaneous, 61
Flagellateinfections,82, 85
Flail chest, 41, 62, 63
Flavobacterium infections,40
Flea allergy, 363-364
Fleas
as Bartonellahenselaevector,427
as infectiousdiseasevector,407
as plaguevector,433, 434, 445
as rickettsialdiseasevector,445-446
as tapewormintermediatehost, 89
as zoonoticdiseasevector,444, 445-446
Flehmanresponse, 253
Fluconazole
failureto respondto, 15
as fungal pneumoniatreatment,54
Fluid replacementtherapy
in chronic renal failure, 195
in diabetic ketoacidosis. 285
in feline panleukopeniavirus infections, 102
in hypoadrenalcrisis, 275
in pneumonia,54
in renal failure. 190
Fluid requirements. See alsoWaterconsumption
in chronic renal failure, 241
Flukes
gastrointestinal. 85
liver, 151, 152, 167, 170
lung, 33, 47, 52
Flunixinmeglumine,contraindicationas heat stroke
treatment,330
Fluoro-2-phosphonylmethoxypropyl adenine(PMPA), 395
Flurazepam, appetite-stimulating actionof, 240
Follicle-stimulating hormone, 299, 301
Fomites,407
Foodadditives,as Heinzbodycause, 378
Foodallergy, 318
Foodaversion, 320
Foodintake, neutering-related increasein, 311
Foreignbodies
esophageal, 124, 126
Index
Foreignbodies (cant.)
intestinal, 116
nasal,I3
as pyothoraxcause, 55, 60
thoracic.62
tracheal, 32
Fracture,of the rib, 62, 63
Francisella tularensisinfections. See Tularemia
Fungal infections.See alsospecificfungi
diarrheaassociatedwith, 82
gastrointestinal, 82. 105-107
hepatic, 151, 153
lymphadenopathy associatedwith, 349
nasal dischargeassociatedwith, I
pneumoniaassociatedwith, 51, 52. 54
respiratory,u-is, 29
sneezingassociatedwith, I
urinary,243
zoonotic,426, 435, 436-437
Funguria, 243
Furosemide
as dilatedcardiomyopathy treatment,79
as left-sidedcongestiveheart failuretreatment,77
as renal failuretreatment, 190, 193
Fusobacterium infection,bite or scratch-related
transmission of, 426
Gait abnormalities,myopathy-related, 337
Gallbladder, ruptureof, 154, 156
Gallstones(cholelithiasis). 155-156
Gamma-glutamyl transferase, 138, 148, 160
Ganglioneuroma, gastrointestinal, 114
Gastricextramedullary plasmacytoma, I 14
Gastricfeedingtubes, use in pancreatitis, 169
Gastritis,%, 196
Gastroenteritis, eosinophilic, 363-364
Gastrointestinal disorders
bacterialinfections,95-100
diagnosticproceduresin, 81-85
eosinophiliaassociatedwith, 364, 365
feline panleukopenia virus-related, 100-104
fungal infections,105-107
infectious,408
parasiticinfections,8S-95
secondary, 119-123
viral infections,100-105
zoonotic,419-425
Gastrointestinal tract, obstructionof, 114-118
Gastrointestinal tumors, 114-118
Gastrostomyfeedingtubes, 144, 145-146,240,320
water administrationthrough,241
General anesthesia
in musclebiopsypatients, 338
in urinaryobstructionpatients,228
Giardia,88
direct fecal smear of, 83
fecal antigenassay for, 84
life cycleof, 93
small bowelcontent of, 110
Giardialamblia, 85, 91
Giardiasis,93-94, 419, 421-422
Giardiavaccination, 410, 411, 413
Glaucoma,342, 346
Glipizide,283-284
Globuleleukocytetumor,gastrointestinal, 114
Glocusetoxicity,280
Glomerulardiseases, 210-213
Glomerulonephritis, 184, 2W-212
Index 467
G1ucocorticoids
as asthmatreatment, 39
as cholangitislcholangiobepatitis complextreatment, 139
as chylothorax treatment.68
as felineinfectiousperitonitistreatment.178
as glomerulardiseasetreatment. 212
as hypoadrenocorticism treatment,275-276
as inflammatory bowel diseasetreatment, 112
as lowerurinarytract diseasetreatment,228
as pancreatitis treatment. 170
as uveitistreatment,345
contraindication to, 346
Glucosarninelchondroitin sulfate,as osteoarthritis
treatment.332
Glucose
hypertonic. 190
as renal failuretreatment. 193
toxicityof, 277
Glucosecurve. 280-281
Glucuronyltransferase deficiency, 160
Glutaminesupplementation. in inflammatory bowel
disease. III
Glycosarninoglycans, as lowerurinarytract disease
treatment, 227
Gnathostomaspinigerum, 87
Gonadectomy. as sprayingpreventive. 250
Gonadotropin-releasing hormone,299. 301. 302, 303
GOSHDARNIT mnemonic. for hypercalcemia diagnosis.
290
Granulated roundcell tumors.gastrointestinal, 114
Granuloma
cryptococcal, 12. 14
gastrointestinal. 114
postvaccinal, 414
Granulopoiesis, ineffective. 360. 361
Halitosis,chronicrenal failure-related. 185
Halothane. contraindication in portosystemic shunt
patients, 166
Hammondia,91. 92
Handwashing, by veterinary personnel, 407, 409
Heartworm. See Dirofilariasis
Heat stroke,330
Heimlichvalves.as pneumothorax treatment.64
Heinzbodies,377-378. 414
Helicobacter, morphologic characteristics of. 95
Helicobacterinfections.See Helicobacteriosis
Helicobacteriosis, 84. 95, 96, 419. 424
Helminthinfections, 82. 85. 86-91,419
treatmentof, 88-89
zoonotic.419, 420, 421
Hemangiosarcoma. hepatic, 147
Hematochezia, intestinalobstruction-related, 114
Hematoma, as anemiacause. 372
Hematuria
functional urinaryobstruction-related, 233
lowerurinarytract disease-related. 223, 225
pollakinria-relatedzlo
portosystemic shunt-related, 163
urinarycalculi-related, 216
urinarytract neoplasia-related, 220, 221, 222
Hemoabdomen, 172, 173, 174
Hemobartonella felis, differentiated fromCytauxzoon felis,
386
Hemobartonellosis, 327. 379-383, 388
as anemiacause. 328. 372, 373, 374, 376
clinicalfeaturesof, 328
Hemobartonellosis (conI.)
Ctenocephalides-related, 135
treatmentof. 328
Hemodialysis, 199-200
Hemoglobin replacement products.375--376
Hemoglobinuria, dirofilarial, 43
Hemophilia, diagnostictests for. 367
Hemoptysis, laryngeal or trachealcancer-related, 69
Hemorrhage
differential diagnoses of, 365--366
retinal. 365
Hemostasis, disordersof, 365-367
Hemothorax. warfarintoxicity-related. 367
Hepaticinsufficiency, 163. 164, 181, 182, 183.367,370
Hepatitis,lymphocytic-plasmacytic, 137
Hepatobiliary neoplasia,148
Hepatomegaly
biliarydisease-related, 154-155
hepaticcancer-related, 147-148
hepaticlipidosis-related. 142. 143
hypercortisolism-related,267
Hernia,diaphragmatic, 32, 62. 65
High-risesyndrome. 61
Himalayancats
calciumoxalateurolithiasis in, 216
portosysytemic shuntsin. 163
respiratory tract conformational deformities in, 19
stenoticnares in. 20
Hipdysplasia, 332
Histamine-receptorsantagonists, use as prokineticagents,
131.132
Histoplasma capsulatum,fecal smear of, 83
Histoplasmosis
clinicalfeaturesof, 328
gastrointestinal, 107-108
nasal, 12
pneumonia associated with.52. 54
upperrespiratory. II
zoonotic, 436, 441, 442
Hookworms, 86
Hormonetherapy, for urethralincompetence. 257-258
Homer's syndrome, 16, 18
Hospitalbiosecurity, 407-410
Howell-Jolly bodies. 386. 400
Humidification therapy. for bacterialrhinitis,7
Hydatidcysts, 90, 421
Hydromorphone, as pancreatitis-related paintreatment. J69
Hyperadrenocorticism, 265-272, 311, 314
myopathy associated with. 174
pituitary-dependent, 265, 267. 269, 270
Hyperaldosteronism, 271-272, 321
Hyperbilirubinemia, 134-135, 136, 154
cholangitislcholangiohepatitis complex-related, 138
Cytauxzoonfelis-related, 151-152
drug-induced hepatopathy-related. 160
felineleukemiavirusinfection-related, 153
hepatobiliary neoplasia-related, 148
toxoplasmosis-related, 151
Hypercalcemia, 289-291
as calciumoxalateurolithcause, 216, 289
as secondarygastrointestinal diseasecause, 119
Hypercalciuria, 289
Hypercholesterolemia, 154.266
Hypereosinophilic syndrome, 110,364
Hyperglobulinemia, 115.178,361
Hyperglycemia
diabetesmellitus-related. 276, 277. 278, 285-286
468 Index
Hyperglycemia (cant.)
diabeticketoacidosis-related, 284, 285
glycosylatedproteinsin, 281-282
in nondiabeticcats, 278
Somogyiphenomenonof, 281
Hyperkalemia
hypoadrenocorticism-related, 274, 275
renal failure-related, 189, 190-191, 195
Hypermagnesemia, renal failure-related, 201
Hyperparathyroidism, 289, 290
dietarytreatmentfor, 242
primary,290, 291
renal secondary, 188,242
Hyperphosphatemia
consequencesof, 188
renal failure-related, 189, 195, 196
Hyperplasia, cysticendometrial,304-305
Hyperpnea, 29
Hyperprogesteronemia, 271
"Hypersplenism," 360
Hypertension
chronic, treatmentof, 197-198
portal,321
postoperative, 166
primary, 76
pulmonary, 321
renal failure-related, 187, 189, 195, 197,201,242
as retinal hemorthagecause, 365
systemic,3Zl-325
nasal dischargeassociatedwith, I, 2
renal failure-related, 197,201,242
uremicanorexia-related, 239
Hyperthermia, 326, 330
Hyperthyroidism, 259-265
diagnosisof, 183, 260-261
diarrheaassociatedwith, 121-122
heart disease-associated, 75-76
historicalsignof, 121
hypertensionassociatedwith, 262
myopathyassociatedwith, 339
polyphagiaassociatedwith, 314
secondarygastroinstestinal diseaseassociatedwith, 119,
121
treatmentof, 262-264
Hyphema,342
Hypoadrenalcrisis, 275
Hypoadrenocorticism, 272-276
as eosinophiliacause, 365
as secondarygastrointestinal diseasecause, 119, 121
spontaneousprimary,273
Hypoalbuminemia, 106, 164, 172, 174
Hypocalcemia, 291-292
definitionof, 289
Hypocholesterolemia, portosystemic shunt-related,
164
Hypochromasia, 406
Hypoglycemia, 281
insulinoverdose-related, 286
portosystemic shunt-related, 164
Hypoglycemic agents, oral, 279, 282-284
Hypokalemia
chronicrenal failure-related, 195-196,240
hepaticlipidosis-related, 144
myopathy-related,337-338
as secondarygastrointestinal diseasecause, I t9
Hyponatremia, hypoadrenocorticism-related, 274
Hypoperfusion,mucousmembranepallor in, 371
Hypophosphatemia
drug-inducedhepatopathy-related, 160-161
as hemolyticanemiacause, 372
Hypopyon,342
Hypotension, pneumothorax-related, 64
Hypothalamic-pituitary-adrenal axis, 272
Hypothermia, hypoadrenocorticism-related, 273
Hypothyroidism. 311
Icterus, 134, 135-136, 137
felinepanleukopeniavirus-related, 101
hepatobiliary neoplasia-related, 148, 149
immune-mediated hemolyticanemia-related. 373
Idiopathicfelinelowerurinarytract disease, 222, 2 ~ 2 3 0 ,
236,244
Imagingtechniques. See also Computedtomography;
Magneticresonanceimaging;Ultrasound; X-rays
for gastrointestinal tract diseaseevaluation,84
Imidazole, as fungalinfection-related diarrltea treatment, 107
Immune-mediated disorders,lymphadenopathy associated
with,349
Immune-modulating therapy,for felineinfectious
peritonitis, 179
Immunocompromised humans
cat ownershipby, 417-418
zoonoticdiseasein, 417
dermatophytoses, 436, 437
Pasteurella multocidainfections,431
Immunofluorescent assay
for felineimmunodeficiency virus diagnosis,393
for feline leukemiavirus infectiondiagnosis,389
Immunosuppressive therapy,for felineinfectious
peritonitis, 178, 179
Immunotherapy
for feline leukemiavirus infection,390
for feline panleukopenia virus infection, 103
Incontinence,overflow, 232
Infection
as chylothoraxcause. 65
as fevercause, 327-328
hepatic, 151-153
as neutropeniacause. 359, 360
Infertility, 304
definitionof, 300-301
female. 305
male, 303, 304
Inflammatory bowel disease, 82, 107-113
definitionof. 107
dietarymanagementof, 110-111
differentialdiagnosesof, 108-109
drug therapyfor, 112-113
forms of, 110
hepaticlipidosisassociatedwith, 142
pancreatitisassociatedwith, 168
Index 469
Inflammatorydisorders, conditions associated with
anemia,404
fever, 328-329
lymphadenopathy,349
neutropenia, 360
neutrophilia, 355, 356, 357, 358
vomitingand diarrhea, 119
Insulin, intravenous administrationof, 285
Insulin-likegrowth factor, in acromegaly,287
Insulin resistance, 282
Insulin therapy
for diahetes mellitus, 277, 278, 279-282
for diabetic ketoacidosis, 285
overdosein, 284, 286
for renal failure, 194
Interferon-alpha, as viral upper respiratory tract infection
treatment, 10
Interstitial pulmonary patterns, 34
Intestinal obstruction, 114-118
Intraocular pressure, 341, 342
Iris, structure of, 341
Iris bombe, 342
Iritis, 176, 342
Iron, hepatotoxicityof, 161
Iron deficiency, 197,242,405-406
Iron supplementation, as renal failure-relatedanemia
treatment, 242
Isoerythrolysis, neonatal, 372, 373, 374
Isoflurane, use in portosystemicshunt patients, 166
Isolation facilities, 408
Isospora, 88, 91, 92
Isosthenuria, 204
Itraconazole
failure to respond to, 15
as fungal pneumonia treatment, 54
as intestinal histoplasmosis treatment, 106
Iverrnectin, as feline heartwormdisease preventive,46
Jejunostomy feeding tuhes, 169,320
Joint disease, 331-336
Joint fluid, characteristics of, 332
Joint pain, fever-related, 327
Joint tap, 332
Jugular vein, thrombosis of, 65
Kennels, cleaning of, 97
Ketoacidosis,diahetic, 122, 280, 284-285
as secondary gastroinstestinal disease cause, 119,
121
Ketoconazole
as fungal infection-relateddiarrhea treatment, 107
as fungal pneumonia treatment, 54
as hyperadrenocorticismtreatment, 269, 270
Ketonuria, diahetes mellitus-related, 277
Key-Gaskellsyndrome, 126
Kidneys, effect of hypercalcemiaon, 289
Kittenmortality complex. See Fadingkitten syndrome
Kittens
bacterial arthritis in, 333
Bordetella bronchiseptica pneumonia in, 4-5
chlamydiosis in, 4
colostral and maternal virus-neutralzingantibodies in,
103
feline panleukopenia virus infection in, 101, 103
gastrointestinal parasites in, 86
isoerythrolysisin, 373, 373, 374
pneumonia in, 50
Klebsiella infections, 51, 231
Kussmaul respiration, 285
Lactate dehydrogenase, aortic thromboembolism-related
elevationof, 75
Lactobacillus acidophilus, III
Lactoferrin, bovine, 10
Lactulose, 131, 132
as portosystemicshunt treatment, 165
Lameness
metastatic lung tumor-related, 70
myopathy-related, 337
polyarthritis-related, in feline calicivirus infection. 9
Laparoscopy
in portosystemicshunt, 164, 165
for renal tissue collection, 212
in urinary tract tumors, 221
Laparotomy,exploratory
in portosystemicshunt, 164
for renal tissue collection, 212
Larva migrans, 420, 421
Laryngoscopy,70
Larynx
cancer/tumors of, 31, 69-70
examinationof, 3, 21
paralysis of, 19-20, 21, 22
Latex cryptococcal antigen test, 13
Laxatives, 131, 132, 133
use after intestinal obstruction surgery, 116
Left ventricular hypertrophy,74, 76
Leiomyosarcoma, 114, 147
Leishmaniasis, 444, 447
Lens luxation, 346
Leprosy, feline, 443
Leptospirosis, 439, 440
Lethargy
asthma-related, 37
biliary disorders-related, 154
drug-induced hepatopathy-related, 160
hyperadrenocorticism-related, 265, 266, 273
inflammatory bowel disease-related, 108
intestinal obstruction-related, I 14
primary lung tumor-related, 70
salmonellosis-related,97
urinary tract neoplasia-related, 220
Leukemia, 389
myelogenous, 355, 357
Leukocyte dysfunction, renal failure-related, 187
Leukocytosis, 115,355
Leukopenia, 102, 264, 403
L-fonn bacterial infections, 334
Libido, of tom cats, 304
Lidocaine, adverse effects of, 63
Lipase, serum content of, in pancreatitis, 168
Lipemia, as secondary gastrointestinal disease cause, I 19
Lipidosis, hepatic, 134, 136,142-147, 158
hyperthyroidism-related,260
idiopathic, 135,316
ohesity-related.312
as secondary gastrointestinaldisease cause, 119, 121
vitamin Kabsence deficiencyassociated with, 369
Lipids, dietary, in chronic renal failure, 240
Lipoma, gastrointestinal, 114
470
Lithotripsy, 218
Liller box
cats' dislikefor, 249, 252-253
as lowerurinarytract diseaseriskfactor,226
ideal,248
inappropriate placementof, 251
maintaneoce of, 103-104, 179,248,408
in multiple-cat households, 248, 252
numberof, 248, 252
plastic, 103-104
Liver
clottingfactorsynthesisby, 366
congestionof, 173
Livercancer/tumors, 121, 135,147-150
Liverdisease
drug-induced, 158-162
infection-related, 151-153
Liverflukes, 151, 152, 167, 170
Liverfunctiontests, in abdominal distention, 174
"Lizardpoisoning," 152
Lobectomy, hepatic, 149
Loweresophageal sphincter, obstructionof, 126
Lowerurinarytract disease.See Idiopathiclowerurinary
tract disease
Lung, parasticinfectionsof, 47-50
Lungfluke.See Paragonimuskellicotti
Lunglobes
collapsed, 32
consolidated, 32
torsionof, 65
Lungmass, differential diagnosisof, 71
Lungtumors,primary, 7 ~ 7 1
Lungworms, 47,48-49, 52
Luteinizing hormone,299, 301, 303
Lymedisease,446
Lymphadenopathy, 31, 349-350
regional,nasal tumor-related, 23, 24
Lymphocytosis, methimazole-related, 264
Lymphoma, 349, 352-354
felineimmunodeficiency virus-related, 395-396
as fevercause, 329
differentiated fromcolonicimpaction, 129-130
hepatic, 134, 136
laryngealor tracheal,70
mediastinal, 71-72
nasal, 23, 24, 26, 27
uveitisassociated with, 343
Lymphopenia, 53, 115, 178
Lymphosarcoma, 31, 388, 389
hepatic, 147-148, 149
intestinal, 116, 117, 118
ocular, 344-345
pancreatic,167, 171
of urinarytract, 220, 221
Macrocytes, nonpolychromatephilic, 400
Macrocytosis, 380
Macrophages, Histoplasmacapsulatum-containing, 105,
106
Magnesiumchloride,as renal failuretreatment, 193
Magnesiumsulfate, as renal failuretreatment, 193
Magnesium supplementation, in renal failure,201
Magnetic resonance imaging,of nasal tumors,26
Mainecooncats
hypertrophic cardiomyopathy in, 74
renal failurein, 185
Maintenance energyrequirements (MERs),239
Index
Malabsorption syndromes, 291-292, 316
diagnostic tests for, 367
inflammatory boweldisease-related, 109, III
vitaminKdeficiency associated with, 369
Malnutrition
as drug-induced hepatotoxicity risk factor, 159
hypocalcemia associatedwith, 291-292
Mannitol, 190, 193
Manxcats
megacolon in, 128
pubertyin, 298
Mast cell tumors, 114, 167
Mastocytosis, 136
visceral, 147-148, 149-150
Maternalvirus-neutralizing antibodies, 103
Mediastinal tumors,71-72
Megacolon, 129-130, 134
definitionof, 128
idiopathic, 128, 130, 131
Megaesophagus, 31, 339
acquired, 126
familialcongenital, 126
primaryidiopathiccongenital, 126
Melarsarnine, as felineheartworm diseasetreatment, 45
Melena,hookworminfection-related, 86
Meningitis, infectiousfelineperitonitis-related, 176
Meningoencephalitis, 12,328
Mesenchymal tumors,nasal, 23
Mesocestoides lineatus, 85, 90
Metals,transition,as oral hypoglycemic agent, 282, 283
Metastases
oflung cancer,70, 71
of nasal tumors, 23
of urinarytract cancer, 2 2 ~ 2 2 1
Methemoglobinemia, acetaminophen-related, 378
Methimazole
adverseeffectsof, 264
as hyperthyroidism treatment, 263-264
Methimazole challengetest, 261
Methylprednisolone, as immune-mediated hemolytic
anemiatreatment,375
Metocloprarnide
antiemeticactionof, 122, 123
as pancreatitis treatment, 169
as renal failuretreatment,193
Metronidazole
as bacterialrhinitistreatment,6
as cholangitis/cholangiohepatitis complextreatment, 139
as inflammatory boweldiseasetreatment, 112
as pancreatitis treatment,170
Metyrapone, as hyperadrenocorticismtreatment,269, 270
Mice
as cats' foodsource,219
as tapeworms'intermediate host, 89
Microfilaria, 43, 44
Microsporum canis, 435
Microsporum canis vaccination, 410, 411
Middleear, nasopharyngeal polypsof, 16, 17, 18
Milbemycin, as felineheartwormdiseasepreventive, 46
Miosis, 342
Miteinfestations, in cats andhumans,437-438
Monoclonal gammopathy, 115
Monocytosis, 13, 115
Monorchidism, 303
Moraxellainfections,51
Mosquito
as dirofilariasisvector, 43
as zoonoticdiseasevector,444, 446
Motionsickness,antihistamine therapyfor, 123
Index 471
Mucocele,pharyngeal, 19
Mucor. See Mucormycosis
Mucormycosis, 107, 151, 153,441
Mucousmembranes
cyanotic,31
pale. 31. 135, 185,357-358,371,373,378
Multiple-cat households
anxietymanagement in, 252
as felineinfectiousperitonitisriskfactor, 175. 179
inappropriate urinationin, 245. 252. 253
litterboxesin. 248
Musclepain
fever-related. 327
Musculardystrophy, 339
Myasthemiagravis.72, 340
Mycobacterial infections, atypical,443
Mycobacterium, 441. 442, 443
Mycoplasma infections
conformational respiratory disease-associated, 22
nasal, 13
pneumonia, 51
polyarthritis, 334
rhinitis.4, 7
small airwaydisease.40. 41. 42
vaginal,295
Mydriaticagents,as uveitistreatment.346
Myectomy, ischiocavernous, 250
Myelodysplastic syndromes, 403, 404
Myelophthisis, 368
Myeloproliferative disease,355, 356, 357. 358. 359. 360.
388,389
Myelosuppression, felineleukemiavirus-related, 368
Myocardial diseases.73-79
Myocarditis, 329
Myopathies, 336-340
classification of. 336
hyperadrenocorticism-associated. 174
Myositisossificans,339
Myotonia, 339-340
Nanophyetus, 9I
Nares, stenotic, 19, 20, 21, 22
Nasalairflow,assessment of. 20. 24. 31
Nasaldischarge
bilateral.23-24
cough-related. 31
cryptococcosis-related, 14
diagnosticevaluationof. 1-3
hemorrhagic, I. 2
mucoid, 1,2
mucopurulent, I. 2. 4, 5. 9-10
nasal tumor-related, 23-24
nasopharyngeal polyps-related. 16
nasopharyngeal stenosis-related, 20
palateabnormalities-related, 20
serous. 1,2
vaccine-related. 413
Nasal septal deviation. nasal tumor-related, 24
Nasaltumors, 13,23-27
Nasal turbinates. in bacterialrhinitis.5
Nasoesophageal feedingtubes, 240. 319
wateradministration through,241
Nasogastric feedingtubes. 319
Nasopharyngeal stenosis, 19,20,21,22
Nasopharynx
caudal, obstructionof. 20
examination of, 21
Nebulization, as pneumoniatreatment,54
Neckextension, laryngealor trachealcancer-related, 69
Necropsy. dirofilariasis diagnosisduring,45
Necrosis
of ear or tail tips, 373
hepatic. 158, 161
Nematodeinfections,gastrointestinal, 85-89
Neorickettsia, 9I
Nephrectomy, 207, 217
Nephroblastoma, 220
Nephrocalcinosis. 289
Nephroliths. See Urinarycalculi
NEPHRONS mnemonic, for dietarytreatmentof chronic
renal failure, 236, 239
Nephropathy, protein-losing, 236, 243
Nephrotomy, 217, 218
Neurologic disorders
felinepanleukopenia virus-related, 101
hyperosmolar diabetesmellitus-related, 286
infectiousfelineperitonitis-related, 176
nasal tumor-related. 23, 24--25
as vomiting and diarrheacause, 119
Neurologic examination, infunctional urinary obstruction. 232
Neuropathy. as generalized weaknesscause, 337
Neutering, as obesitycause. 311
Neutropenia, 53, 355, 359-362
Neutrophilia, 355-359, 361
Nitroglycerine, as cardiomyopathy treatment.79
Nitroglycerine ointment,as left-sidedcongestiveheart
failuretreatment. 77
Nitroprusside. as renal failuretreatment,193
Nizatidine, 131. 132
Nonsteroidal anti-inflammatory drugs
as osteoarthritis treatment,332, 333
as uveitistreatment, 345. 346
Nose. bacterialovergrowth in, 5
Nosedrops. antibiotic. 7
Nosocomial infections, prevention of, 407-410
Notoedres cati infestations, incats and humans,437. 438
Nuclearscintigraphy
for biliarytract diseaseevaluation. 155
for portosystemic shunt evaluation, 164. 165
renal. 187
for urinarycalculi evaluation. 217
Nutritionalassessment. 236
Nutritionaldeficiencies
as generalized weaknesscause. 337
inflammatory boweldisease-related. III
Nutritionalmanagement. Seealso Diet
in hepaticlipidosis, 144, 145-147
of inflammatory boweldisease, II (}-II I
in osteoarthritis, 333
inrenal failure, 194, 195
Nutritionalsupport.Seealso Esophagostomy feedingtubes;
Gastricfeedingtubes;Gastrostomy feedingtubes;
Jejunostomy feedingtubes; Nasoesophageal feeding
tubes
in cholangitislcholangiohepatitis complex, 139
in pancreatitis, 169, 170
after pleurallavage,59
in pyothorax, 59
in renal failure.239
Nystagmus, infectiousfelineperitonitis-related, 176
Nystatin. as fungal infection-related diarrheatreatment, 107
Obesity, 311-315
breathsoundsin, 32
definitionof. 311
as idiopathiclipidosisriskfactor, 135
472
Obstipation, 128, 132
Obstructiveairwaydisease, 22, 31
Ocular disorders
cryptococcal, 12
felineherpesvirus-I-related,344
feline infectiousperitonitis-related, 176,344
felineleukemiavirus-related, 344-345
infectiousdisease-related, 330
toxoplasmic, 343
viral upperrespiratorydisease-related, 9
Oliguria, 188
Ollulanus tricuspis. 85, 87
Omega3/6 fattyacids, 139, 170
Ondansetron, 122, 123, 169
Ophthalmicexamination,for sneezingand nasal discharge
evaluation, 2
Oral examination
for nasopharyngeal polypevaluation, 17
for sneezingand nasal dischargeevaluation,2
Organfailure, pancreatitis-related, 167
Organomegaly, 172, 173
Orthopnea,28, 31
Osmolality, serum, in polyuria/polydipsia, 182
Osteoarthritis, 331, 332-333
Osteosarcoma, 23, 114
Osteotomy, ventralbulla, 18
Ovarianremnantsyndrome,302
Ovariohysterectomy, 297, 302, 311
Ovulation,298, 299-300
detectionof, 303
failureof, 303
Oxazepam
appetite-stimulating actionof, 240
as renal failuretreatment, 193
Oxygentherapy
oxygenratio in, 53
in pyothorax,57
Oxyglobin,as pulmonaryedemacause, 376
Oxymorphone, as pancreatitis-related paintreatment, 169
Packedcell volume(PCV), 371
Pain
abdominal
abdominaldistention-related, 173
inflammatory boweldisease-related, 108
as dyspneaor tachypneacause, 31
ocular, 341
in osteoarthritis,332, 333
during urination,254
uveitis-related, 341, 346
Palate
conformational deformitiesof, 19,20--21,22
soft, in nasopharyngeal polypexamination, 17
Pancreaticcancer, 171
metastatic, 147-148
Pancreaticdisease, 167-171
Pancreaticinsufficiency
diagnosisof, 82
exocrine, 120, 121, 167, 171
Pancreatitis, 135, 136
acute, 167, 170, 171
chronic, 167, 171
clinical featuresof, 120, 328
diagnosisof, 82, 120--121
nonsuppurative, 168, 169
Index
Pancreatitistcont.i
as pleuraleffusioncause, 168, 173
suppurative, 168, 169, 170
treatmentof, 328
Pancytopenia, histoplasmosis-related, 106
Panhypoproteinemia, intestinalobstruction-related, 115
Panleukopenia. See Feline panleukopenia virusinfection
Panophthalmitis, 341
Paragonimus kellicotti infections,33, 47, 52
Paragonimus westermani infections,47
Parasitemia, Hemobartonellafelis-related, 380
Parasiticinfections.See also specific parasites
gastrointestinal, 85-95
hepatic, 151
lymphadenopathy associatedwith, 349
respiratory, 47-50
cough and dyspneaassociatedwith, 30
Parathyroidhormone,288
Parenteralnutritionalsupport, 194,319
Parvovirus, fecal antigenassay for, 84
Parvovirus infections, 100, 167
Parvovirusvaccination, 410
Pasteurella multocida infections
bite or scratch-related transmission of, 426
pneumonia,51
polymyositis,338
respiratoryzoonotic,431
rhinitis,S
Patient management, for nosocomialinfectionprevention,
408-409
Peliosis, bacillary,444, 445
Pelviclimbparalysis, 77
Pelvic nerve injury,as megacolon cause, 128, 129
Penetratinginjuries, as pneumothorax cause, 61, 62
Penicillin, as pneumoniatherapy, 54
Penicilliuminfections, upperrespiratory, II
Pentatrichomonas hominis, direct fecal smear of, 83
Pentatrichomonas hominis infections,85, 89, 91, 94
Peptic ulcer disease, 96
Pericentesis,136, 173
Peritonealdialysis, 199
Peritonealeffusion, 136
exudative, 173
hepatobiliary neoplasia-related, 148
Peritonitis.See also Felineinfectiousperitonitis
bile, 156-157
Persiancats
calciumoxalate urolithiasis in, 216
hypertrophic cardiomyopathy in, 74
polycystickidneydiseasein, 181,208,210
portosystemicshunts in, 163
pubertyin, 298
respiratorytract conformational deformitiesin, 19
stenoticnaresin, 20
Pertechnerate scan, 261
Pharyngitis,4
Pharynx, nasal, examinationof, 3
Phenoliccompounds,hepatotoxicity of, 160, 161
Phenoxybenzamine, as urethralrelaxant,234
Phenylpropanolamine, contraindications to, 257
Pheochromocytoma, 76, 321
9-2-Phosphonomethylethyl adenine(PMEA),395
Phosphorus, serumconcentration of, 291
Phosphorus-binding agents, as renal failuretreatment, 196
Phosphorusrestriction,as hyperparathyroidism treatment,
242
Phosphorusretention, as chronic renal failurecause, 242
Photodynamictherapy,for cutaneoustumors,26
Index 473
Photophobia, 341
Physaloptera, 87
Piroxicam,222-223, 333
Pituitarytumors, 287
PIVKA(proteininducedby vitaminK absenceor
antagonism)test, 139,367,368,369
Plague, 50, 51, 431, 432--433, 435, 445
as fever cause, 327, 329
pneumonic,50, 51
treatmentof, 327
Plateletcount, 367
in hemolyticanemia, 374
Platelet disorders,368-369
Platynosomum concinnuminfections, 151, 152, 154
Play therapy,248
Plethysmography, 322
Pleural disease, restrictive breathingin, 34
Pleural effusion, 32, 34. See also Pyothorax
ahdominaldistention-related, 173
as cardiovascularemergency, 77
as dyspneacause, 33
feline infectiousperitonitis-related, 175. 177
lung cancer-related, 70, 71
mediastinalcancer-related, 72
pancreatitis-related. 168
thymoma-related, 72
Pleural lavage,59
Pleural spacedisease, 77
Pleuritis, fibrosing, chylothorax-related, 67
Pleurodesis,as chylothoraxtreatment,68
PMEA(phosphonomethylethyl adenine),395
PMPA(fluoro-2-phosphonylmethoxypropyl adenine),
395
Pneumonia,5 ~ 5 5
aspiration,50, 52, 55
bronchoesophageal fistula-related, 21-22
"lipid-aspiration," 131
bacterial,4--5,32, 48, 51, 53, 54, 55
definitionof, 50
diagnosisof, 52-53
fungal, 31, 51, 52, 53, 54, 55
in kittens, 8
parasitic, 51, 52, 55
pygranulomatous,51-52
respiratorytract conformational diseases-related, 21
sterile, 52
toxoplasmic, 54
treatmentof, 53-54
viral, 8, 51-52, 55
Pneumonitis
toxoplasmic, 55
uremic, 30, 31, 187
Pneumothorax, 32, 34, 61-65
as dyspneacause, 33
open, 61
simple, 61
tension,61, 62
thoracocentsis in, 61--62
Poikilocytosis, 400
PoUakiuria.214--215
lower urinarytract disease-related, 223
portosysternic shunt-related, 163
Polyarthritis, 332
chronicprogressive, 334--335
definitionof, 331
erosive,334
felinecalicivirus-related, 9
idiopathic,329, 335
immune-mediated nonerosive, 335
Polycystickidneydisease, 157, 181, 185,208-210
Polycythemia, renal tumor-related, 220
Polydipsia,181-183
diabetesmellitus-related, 277
hypercalcemia-related, 289
hypoadrenocorticism-related, 265, 266, 273
psychogenic, 183
Polyganglionopathy, feline leukemiavirus-related,256
Polymerasechainreactionassay
for felineimmunodeficiency virus diagnosis, 393. 394
for feline infectiousperitonitisdiagnosis, 178
for hemobartonellosis diagnosis,382-383
Polymyositis, 338-339
Polyneuropathy, peripheral, 187
Polyphagia, 182, 183,314--315
exocrinepancreaticinsufficiency-related, 121
hypercortisolism-related, 265, 266
Polypnea,29
Polyps, nasopharyngeal, 2. 5, 13, 16-18
Polyuria,181-183
chronicrenal failure-related, 185, 195
diabetes mellitus-related, 277
hypercalcemia-related, 289
hypoadrenocorticism-re1ated, 265, 266, 273
Potassiumcitrate, as renal failuretreatment,193, 194,241
Potassiumgluconate,as renal failuretreatment, 194
Potassiumphosphate,as renal failuretreatment, 194
Potassiumsupplementation, in chronicrenal failure, 195
Potassiumsupplementation, in hypokalemic myopathy,
337-338
Prazosin,as urethral relaxant,234
Prednisolone
as hypoadrenalcrisis treatment,275
as immune-mediated hemolyticanemiatreatment,375
asjoint diseasetreatment,333
as pancreatitistreatment, 170
as respiratoryparasiticinfectiontreatment,48
Prednisone
as hypercalcemia treatment,291
as joint diseasetreatment,333
Pregnancy
diagnosisof, 306
durationof, 299, 306
false, 301
feline panleukopenia virus infectionduring, 10I
unwanted,terminationof, 310
Pregnancyloss, 306-310. See also Abortion
as earlyembryonicdeath, 304
Priapism,304
Proanthocyanidin, III
Prochlorperazine, as renal failuretreatment, 194
Prochlorpromazine, as pancreatitistreatment, 169
Proestms, 299
Progesterone
in anestrus, 302
excessivesecretionof, 271
gestational, 299, 306. 307
measurement of, 307
474
Index
Progesterone-secreting adrenal tumors, 271
Proglottids, 89
Prokineticdrugs, 131, 132
use after intestinal obstructionsurgery, 116
Propothiouracil, as hemolyticanemiacause, 372
Propranolol, contraindicationas asthma treatment, 42
Protein
dietary, in inflammatorybowel disease, 110, III
glycosylated, in hyperglycemia,278, 281-282
serumconcentrationof, relationshipwith serumcalcium
concentration, 289
Proteindeficiency
as drug-inducedhepatotoxicityrisk factor, 159, 160
proteinrestriction-related, 242
Proteinrestriction, in renal failure, 202, 241-242
Proteinuria,34, 186, 220, 221
Proteusinfections, 51, 231
Prothrombintime
in hepaticlipidosis, 143, 144
one-stage, 366, 368, 370
Prototheca, fecal smear of, 83
Protothecosis, 107
Protozoal infections
gastrointestinal,85, 91
zoonotic, 419, 421
hepatic, 151-152
Pseudoanorexia.315
Pseudochylouseffusion, 67
Pseudohermaphrodites, 30I
Pseudomonas infections,51, 231
Puberty
in females, 298
in males, 298
Punishment,of cats, 249
Purebredcats. See also specificbreeds
feline infectiousperitonitis in, 329
Purine urinarycalculi, 244
Pyelocentesis, 206-207
Pyelolithotomy, 218
Pyelonephritis, 181, 182,184,203-207
Pyelotorny, 217
Pyometra, 181,295-298, 304, 305
"stump,"298
Pyothorax, S5-(i1
complicationsof, 60
signs of, 56
thoracocentesisin, 56-57
treatment of, 57--60
Pyrexia, primarylung tumor-related,70
Pyrogens, exogenous, 326
Pyruvatekinase deficiency,372
Pytalism, 69,160,163
Pythiosis, 107
Pyuria, 182
pollakiuria-reIated,215
urinary tract neoplasia-related, 220, 221
Q fever,439-440
Rabies, 426, 429-430
Rabies vaccination,7, 410, 411, 430
as sarcoma cause, 414
Radiationtherapy
for lymphoma, 72, 351, 354
for nasal tumors, 26, 27
toxicityof, 354
for vaccine-relatedsarcoma, 415
Radioiodine(1
' 31
) , as hyperthyroidismtreatment, 262, 264
Ranitidine, 131, 132
Rat, as cats' food source, 219
Recombinanthumanerythropoietin, 197
Rectal temperature,326
Red eye, 341
Reduviidbugs, as zoonoticdisease vectors, 444, 446-447
Regurgitation, 124-128
differentiatedfromvomiting, 81
esophageal, 124
Rehydration, in renal failure, 189, 190
Renal disease
hyperthyroidism-related, 261-262
as polydipsiacause, 181
as polyuriacause, 181
vaccine-related,413
Renal failure, 183-202
acute, 181
differentiatedfromchronicrenal failure, 184. 185

anemia associatedwith, 405
chronic, 181, 182, 187
dietary managementof, 236, 239-243, 318
differentiatedfromacute renal failure, 184, 185
hypercalcemiaassociatedwith, 290
treatment of, 195-200,201-202
ureteral obstruction-related,221
complicationsof, 187
definitionof, 183
drug interactionsin, 198-199
drug therapyfor, 192-194
hyperthyroidism-related, 261, 262
polycystickidneydisease-related,209
preventionof,200--201
prognosis in, 200
pyelonephritisassociatedwith, 205
ureteral obstruction-related, 221
Renal tissue, collectiontechniquesfor, 211-212
Renal transplantation,as renal failure treatment, 200
Renal tumors, 220
Respiratorydisorders
conformationaldiseases, 19-23
eosinophiliaassociatedwith, 364
feline heartwormdisease-related,43
infectious, 408
of lower respiratorytract
cancer of, 69-73
conformationallesions of, 21-22
parasitic infections,47-50
physical examinationin, 31
upper respiratoryinfections
bacterial,4-8
bronchopulmonarydisease-related,40
fungal, 11-16
nasopharyngealpolyps associatedwith, 16
viral,8-11
zoonotic infections, 431-434
Respiratorydistress
acute, differentialdiagnosesin, 4lJ.-4J
acute onset of, 77
Aelurostrongylus abstrususinfection-related,48
asthma-related,37
cardiovascularemergency-related, 77
physical examinationin, 38
pneumothorax-related, 61
pyothorax-related,56
Respiratoryrate
assessment of, 31
Index 475
Respiratory rate (cont.)
in prehepaticdisease, 135
Respiratory tract,auscultation of, 32
Retching,nasal discharge-related, 4
Reticulocyte count, 374
in nonregenerative anemia,401-402
Retina
degeneration or detachmentof, 346
hemorrhage from, 364
Rhinitis
bacterial, 4-8
chronic,3, 9, 19, 20, 22, 24
fungal, 13-14
Rhinoscopy, 3, 14, 24-25
Rhinotomy, 3
Rhinotracheitis, felineviral. See Felineherpesvirus-I
infection
Rhodococcusequi, 441, 442
Rib, fracturesof, 62, 63
Rickettsiafells, 444
Rickettsia rickettsii, 444, 446
Rickettsia typhus, 445
Right heartfailure,chylothorax-related, 65
Ringworm, in humans,435, 436
Rochalimaea henselae. See Bartonellahenselae
RockyMountainspottedfever, 446
Rodenticides, intoxication with, 369
Roundworms, 85, 86, 90
Russianblue cats, renal failurein, 185
Rutin, as chylothorax treatment,68, 69
Salmonella
fecal smearof, 83, 84
morphologic characteristics of, 95
Salmonellosis, 95, 97-98
zoonotic,419, 420, 424
Sandflies,as zoonoticdiseasevectors,444, 447
Sarcocystis, 91-92
Sarcoma,vaccine-related, 413, 414-415
Sarcoptes scabei infestations, in cats andhumans,435, 437,
438
Schistocytes, 370, 374
Schumachbodies, 377
Scottishfoldcats, cartilageabnormalities in, 336
"Scrambledeggtheoryof litter boxnumber," 248, 252
Scratches,infectiousdiseasetransmission by, 407
of zoonoticdiseases,417, 426-431, 437
Sedation
for arthrocentesis, 332
for chest tubeplacement, 63
for musclebiopsy, 338
for thoracocentesis, 61
in urinaryobstructionpatients,228
Seizures
acute renal failure-related, 185
felineheartworm disease-related, 44
infectiousfelineperitonitis-related, 176
lidocaine-related, 63
Selarnectin, as felineheartworm diseasepreventive, 46
Semen,qualityassessmentof, 300
Separationanxiety, 251, 252
Sepsis,felinepanleukopenia virus-related, 103
Septicemia, Escherichiacoli infection-related, 99
Serumbiochemistry profile
in biliarytract disease, 154
indiabeticketoacidosis, 122
in hepaticlipidosis, 143
in hypoadrenocorticism, 266, 267, 273-274
Serumbiochemistry profile(cont.)
in inflammatory boweldisease, 109
Sexglands,accessory, of tomcats, 300
Shivering, 326, 330
Shock,mucousmembranepallorin, 371
Shunt,portosystemic, 135, UI3-167,314
as ammonium urateurolithrisk factor, 244
as drug-induced hepatotoxicity risk factor, 159-160
intrahepatic differentiated fromextrahepatic, 163
Siamesecats
bronchialdiseasein, 37
familialcongenitalmegaesophagus in, 126
renal failurein, 185
Sinusitis,chronic, viralupperrespiratory disease-related, 9
Slugs, as Aelurostrongylusabstrusus host, 48
Smallairwaydisease,37-42
Smellaversion,to litter box, 248, 253
Snails,as Aelurostrongylusabstrusus host, 48
Sneezing
bacterialrhinitis-related, 5
bacterialupper respiratory disease-related, 4
definition of, I
nasal tumor-related, 23
nasopharyngeal polyps-related, 16
nasopharyngeal stenosis-related, 20
vaccine-related, 413
Sodium,recommended dailyintakeof, 241
Sodiumbicarbonate, as renal failuretreatment, 194
Sodiumrestriction
in chronicrenal failure, 240-24I
in hypertension, 197
Somogyiphenomenon, 281
Songbirdfever, 327, 329
Songbirds,as Salmonellahost, 97, 327, 329
Spermatogenesis, 303, 304
Spherocytes, 374
Spinalcord injury
as functional urinaryobstruction cause, 232, 233
as megacolon cause, 128, 129
Spirocercalupi, 85, 87
Spirometramansoniodes,90
Spleen
congestionof, 173
tumorsof, as anemiacause, 372
Splenectomy, effect on hemobartonellosis, 380
Sporothrixschenkii infections, zoonotic,426, 435, 436,
441,442
Spraying,246, 247, 249-251
chemotherapy for, 27
esophageal, 125, 126
of nasal planum,23, 26
Staphylococcal infections
biteor scratch-related transmission of, 426
pneumonia, 51
pyometra, 297
rhinitis,5
urinary, 231
uterine,as pregnancyloss cause, 308
Steatitis,414
Stertor,20-21, 31
cryptococcosis-related, 12
differentiated fromstridor,21
Stillbirth,308, 309
476
Stomachcarcinoma, Helicobacter-related, 96
Stomach worms, 87
Stomatitis, 10,413
Stranguria, 163,214,216,232
Streptococcal infections
bite or scratch-relatedtransmissionof, 426
groupA, zoonotic, 431, 432
pneumonia,51
pyometra,297
rhinitis, 5
small airwaydisease, 40
urinary,231
uterine, as pregnancyloss cause, 308
Stress
as eosinopeniacause, 363
as hyperglycemiacause, 278, 281
as lower urinarytract diseasecause, 226
Stridor, 20, 21, 31
differentiatedfrom stertor, 21
Strongyloides stercoralis infections, 47, 49, 85, 87
pneumonia,52
zoonotic, 419, 420, 421
Sucralfate,as renal failure treatment, 194
Sulfasalazine,as inflammatoryboweldisease treatment,
112
Sulfonylureas,282, 283-284
Sweating, 326
Synechiae
anterior, 342
posterior,342, 346
Synovitis, felineinfectiousperitonitis-related,334
Systemiclupus erythematosus
platelet disorders associatedwith, 368
primaryimmune-mediatedhemolytic anemiaassociated
with, 371, 374
treatment of, 329
Tachyarrhythmia, 75
Tachypnea
definitionof, 29
dirofilariasis-related, 43
pneumothorax-related, 61
Taenia, 85, 86
Taenia hydatigena, 90
Taenia pisiformis, 90
Taenia taeniaeformis, 89
Tail, necrosisof, 373
Tapeworms, 85, 86, 89-91
Taurine, role in cardiac function, 74
Taurinedeficiency,66
as early embryonicdeath cause, 307
Taurinesupplementation
in cardiomyopathy, 74-75, 79
coadministrationwith ursodeoxycholic acid, 141
Tenesmus, 114, 128
Teratogens,drugs as, 309
Testes, small, 304
Testosterone,exogenous, 303
Testosteronetherapy,for urethral incompetence,257-258
Tetracycline
as ehrlichiosistreatment, 399
as fever cause, 329
Index
Therapeutictrials, in sneezingand nasal discharge, 3
Thermometers,ear, 326
Thermoregulatoryset point, 326
effect of nonsteroidalanti-inflammatory drugs on, 330
Thiacetarsamide,as feline heartwormdisease treatment, 45
Thiamine supplementation,in hepatic lipidosis, 146
Thiazolidinediones,282, 283
Thoracic duct
ligationof, as chylothoraxtreatment, 68
noncompliant,in chylothorax,66
rupture of, 65
Thoracocentesis
in chylothorax,66--67
in dyspnea, 33
in pneumothorax,61-62
in pyothorax,56-57
Thoracostomysites, care of, 60
Thorax, auscultationof, 32
Thrombintime (TT), 367
Thrombocytopenia
cytauxzoonosis-related, 384
hemostaticabnormalitiesassociatedwith, 370
idiopathic, 329
immune-mediated, 368, 369
methimazole-related, 264
nonregenerativeanemia-related,403
in vitaminK deficiencyor antagonism.369
Thromboembolism
aortic, 75, 77-78, 340
arterial, 77
Thromboxanesynthetaseinhibitors, 212
Thymoma, 71-72
Thyroidcarcinoma, 259
Thyroidectomy, 262-263, 264
as hypoparathyroidismcause, 291
Thyroid glands, normal anatomyof, 259
Thyrotoxicosis,259
Thyroxine (T4), 259
hyperthyroidism-related increasein, 260, 261
in icterus, 135-136
radioiodinetherapy-relateddecrease in, 263
Thyroxine(T4) concentrationtest, for vomitingand
diarrhea evaluation,82
Ticks
as Cytauxzoon felis host, 135,383,384
as infectiousdisease vector,407
as Qfever vector,439
Tissue plasminogenactivator,366
Tomcats
infertilityin, 303, 304
pubertyin, 300
Tortoiseshelltomcats, infertilityin, 304
Total parenteral nutrition, 319
Toxascaris leonina, 85, 86
Toxins
as hemolytic anemiacause, 372
Toxocara cati, distinguishedfromPhysaloptera, 87
Toxocara cati infections. See Toxocariasis
Toxocariasis,47, 49
hepatic, 151, 152
as zoonotic infection, 419, 420, 421
Toxoplasma gondii infections. See Toxoplasmosis
Toxoplasmosis, 85, 89, 91, 92, 388
Index 477
Toxoplasmosis (cont.)
as alveolarlung diseasecause, 34
definitionof, 422-423
hepatic, 151
in huntingcats, 135
ocular, 330, 343
pancreatic, 167, 170
pneumonitis, 55
polymyositis,339
polysystemic,92
pulmonic, 30, 31, 49-50
treatmentof, 328
uveitis,343
as zoonoticdisease,417, 422-424
Trachea
cancer/tumorsof, 31, 69-70
foreign bodyin, 32
rupture of, as pneumothorax cause, 61
Tracheoscopy, 70
Tractotomy, olfactory,250
TransitionalceOcarcinoma,221, 222-223
Transudates,as ascites cause, 172, 174
Trauma
as chylothoraxcause, 65
as pneumothoraxcause, 61, 62
Trematodeinfections,gastrointestinal, 91
Tremors
Triaditis, 121, 137, 139, 168
Trichinella spiralis infections,339
Trichobezoars, 114, 116
Trichomonas, 94
Trichuris, 85
Trichuris campanula, 88
Trichuroidea, 47
Triiodothyronine (T3), 259
Triiodothyronine (T3) suppressiontest, 260-261
Troglotrematids, 47
Trypanosomiasis, 445, 446-447
Trypsin-like immunoreactivity assay, 120-121, 168, 171
Tularemia,327, 329, 426, 429, 431, 435, 444, 446
Tympanicmembrane,nasopharyngeal polyp-related
abnormalitiesof, 17
Typanum, bulgingor discolorationof, 2
Typhus,murine,445, 446
UCCR(urinecortisol:creatinine ratio), 267-268
Ulcers,oral, uremia-related, 191>--197
Ultrasound
abdominal
in biliarytract disease, 155, 156
in cholangitis/cholangiohepatitis complex, 138
for fever evaluation, 330
for urinaryincontinenceevaluation, 256
in gastrointestinal tract disease, 84
in intestinalobstruction, 116
in lower urinarytract disease, 225
in pancreatitis, 120, 168
in polyuria/polydipsia, 183
in portosystemic shunt, 164, 165
in pyometra, 296
in pyothorax, 57
renal, 181>--187
for tissue biopsy, 211-212
Ultraviolet light exposure,as squamouscell carcinoma
cause, 23
Uncinaria stenocephala infections,85, 86, 419, 420, 421
Urea, excretionof, in chronicrenal failure, 242-243
Urease, as helicobacteriosis marker,84, 96
Uremia, 119, 191>--197
Uremicsyndrome, 185
Ureter,ectopic, 256
Ureteralobstruction,221
Urethra, hypercontractile, 232-233
Urethralincompetence, 257-258
Urethralobstruction
idiopathicfelinelowerurinarytract disease-related, 244
lower urinarytract disease-related, 223, 224
portosystemicshunt-related, 163
Urethralplugs, 223, 224, 227, 228
Urethralrelaxant drugs, 234
Urethral resistance,assessmentof, 256
Urethrospasm, 232
Urethrostomy, 230
perineal, 214, 229
Urinalysis
in biliarydiseases, 154
in coughor dyspnea, 33-34
in icterus, 136
in lower urinarytract disease, 225, 226
in myopathy, 337
in neutropenia,361
in pollakiuria,215
in portosystemicshunt evaluation, 164
in pyelonephritis, 204
in renal failure, 186
in urinarycalculi, 217
in urinaryincontinence, 256
in urinarytract infections,230-231
Urinarycalculi, 211>--219
ammoniumurate, 244
calciumoxalate, 215, 216, 219, 236, 244, 289
cystine, 236, 244
hypercalcemia-associated, 290
as lowerurinarytract diseasecause, 223
as pollakiuriacause, 215
struvite, 215, 216, 219, 227, 236, 243-244
urate, 236
as urinarytract infectionrisk factor, 230
Urinaryincontinence,25S-2S8
congenital,256, 257
Urinarytract, obstructionof
azotemiaassociatedwith, 184
functional, 232-235
Urinarytract disease
idiopathicfelinelower, 222, 223-230, 236, 244
as pollakiuriacause, 214
Urinarytract infections,230-231
bacterial, 214, 222, 227, 230-231
dietarymodification preventionand treatmentof, 243
fungal,243
lower,differentiated fromkidneyinfection,204
recurrent,205-206
Urinarytract neoplasia,220-223
Urination
inappropriate, 245-254
definitionof, 245
lower urinarytract disease-related,223, 312
managementof, 248-249, 250-254
pollakiuria-related,214
polyuria/polydipsia-relaetd, 182
painduring, 254
478
Urine
acidification of. as urinarytract infectiontreatment.243
clean-uptechniquesfor. 247
dilute, hypoadrenocorticism-related, 274
pHof, 216, 219
Urinecortisol:creatinine ratio (UCCR),267-268
Urineculture,bacteriuriain. 231
Urineprotein:creatinine ratio(UPC). 211
Uroabdomen, 172, 173
Urogenital tract. zoonoticinfectionsof. 439-440
Urography, intravenous, 186
Urohydropropulsion.217
Urokinase. 366
Urolithiasis. See Urinarycalculi
Uroliths. See Urinarycalculi
Uropathy. obstructive. 182
Ursodeoxycholic acid. 141, 156
Uvea, structureof, 341
Uveitis,341-347
anterior, 2. 346
bilateralgranulomatous, 343
clinicalsigns of, 341-342
viral upper respiratory disease-related. 9
differential diagnosisof, 342-343
felineinfectiousperitonitis-related, 135. 176
idiopathic,345
pneumonia-associated, 51
posterior, 342. 346
toxoplasmosis-related, 135
Vaccines. 407. 410-413. See also specific vaccines
core, 410, 411, 412
risksassociatedwith, 368, 373. 376. 413-415
viral subunit,396
Vaginal discharge. 295. 296
Vascular ring anomalies, as regurgitation cause, 124. 127
Vasculitis, 1, 2, 176,368
Vasoconstriction, 326
Vasodilators, as systemichypertension treatment.324
Vector-borne zoonoses,444-447
Venacava, anterior, occlusionof, 66
Verylowdensitylipoproteins,142
Vestibular disease. 16. 119
Vlfa1 infections. See also specific viruses
gastrointestinal. 82. 100-105
hepatic. 151. 153
as lowerurinarytract diseasecause,224
lymphadenopathy associatedwith. 349
nasal dischargeassociatedwith. I
respiratory. 8-11, 29
vomitingassociated with, 82
VIrus-neutralizing antibodies.maternal, 103
VItamin Asupplementation. ininflammatory bowel
disease. 111
VItamin Bcomplexsupplementation. in
cholangitislchoiangiobepatitis complex,140
VItamin Bdeficiency, uremicanorexia-related, 239
VItamin B,z supplementation, in int1ammatory bowel
disease. II I
VItamin C supplementation, in infJarnmatory bowel
disease, I I I
VitaminDdeficiency. 291-292, 316
VItamin D toxicosis, 290. 291
Vitamin E supplementation
incholangitislcholangiobepatic complex. 141
in bepaticlipidosis, 147
in inflammatory boweldisease, II I
Index
VItamin Kantagonism, 369-370
VItamin Kantagonist rodenticides, 367. 369
VItamin Kdeficiency, 136, 143,369
VItamin K-dependent clottingfactors. 366
VItamin K-dependentmultifactor coagulopathy, 369
VItamin Ksupplementation, in inflammatory bowel
disease. III
VItamin KI supplementation
in cbolangitislcholangiohepatitis complex. 140, 141
in hepaticlipidosis. 146
Vocalization
hyperthyroidism-related. 259
nocturnal.323
Voice change
laryngealdisease-related. 20
laryngealor trachealcancer-related. 69
Volvulus, 114
Vomiting
acuterenal failure-related. 185
as aspirationpneumoniacause, 50, 52
bacterialinfection-related. 95
biliarydisorders-related. 154
cancer-related. 119
cholangitislcholangiohepatitis complex-related, 138
cough-related. 30, 3I
definitionof, 124
differential diagnosesfor, 8I. 82
differentiated fromregurgitation, 81
dirofilariasis-related, 4 ~ , 122
endocrinedisorders-related, 119
exocrinepancreatic insufficiency-related, 121
feedingtube-related. 146
felinepanleukopenia virus-related. 100, 101
heartdisease-related. 75
hypercalcemia-related. 289
hyperthyroidism-related, 122,259.260
hypoadrenocorncism-related, 122, 266, 273
hypoalbuminemia-related, 173
infection-related. 119
inflammatory boweldisease-related. 108, 110
intestinalobstruction-related. 114
megacolon-related, 129
metabolicdisorders-related. 119
musculardystrophy-related, 339
neurologicdisorders-related. I19
pancreatitis-related, 135, 168, 170
Platynosomum concinnum infection-related. 152
renal failure-related. 190, 191-192
salmonellosis-related. 97
secondarygastrointestinal disease-related, 119, 120.
122
uremicanorexia-related, 240
vonWillebrand'sdisease, 367, 369
vonWillebrand'sfactor,366, 367, 368
Vulvarstrictures.303
Warfarin, as hemothorax cause, 367
Waterbalance,in chronicrenal failure.241
Waterconsumption
increasein
polyuria/polydipsia-related. 182
for urinarycalculiprevention. 2I8
24-hourmeasurement of, 182
Waterdeprivation test. 183
Wealcness
generalized, 337
hyperthyrdoidsm-related, 339
myopathy-related. 337
Index 479
Weight gain. See also Obesity
as diabetesmellitustreatment, 278
hypercortisolism-related, 266
Weightloss, 315-317
cholangitis/cholangiohepatitis complex-related, 138
as diabetesmellitustreatment,278
exocrinepancreaticinsufficiency-related, 121, 171
hepaticlipidosis-related, 142
hypoadrenocorticism-related, 265, 266, 273
as idiopathic felinelowerurinarytract diseasetreatment,
244
intestinalobstruction-related, 114
as ostoearthritis treatment, 333
Platynosomumconcinnuminfection-related, 152
pneumonia-related, 50, 51
primarylungtumor-related, 70
Weight-loss programs,312-313
Wheezing
asthma-related, 37
Capillariaaerophilainfection-related, 48
Whipworm. See Trichuriscampanula
"Whitecoat effect," 322
White-haired cats, squamouscell carcinomain, 23
Xanthineuroliths, 244
X-rays
abdominal
in biliarytract disease, 154-155
in constipation andmegacolon, 129, 130
ingastrointestinal tract disease,84
inhyperadrenocorticism, 267
in hyperbilirubinemia or icterus, 136
in lowerurinarytract disease,225, 226
in portosystemic shunt, 164, 165
X-rays(cont.)
in bacterialrhinitis,5
chest
in Aelurostrongylusabstrusus infections, 48
in dirofilariasis, 44, 45
in Paragoniusinfections, 47
in pneumonia, 53
in chylothorax, 66
in fungalrhinitis, 14
in hypoadrenocorticism, 274
in intestinalobstruction, I 15
open-mouth, in nasal disease,24
in pneumothorax, 62
thoracic
in asthma,39, 40
in cardiomyopathy, 76
dorsoventral, 34
in dyspnea,33
lateral,34
in pyothorax, 56
Yersiniaenrerocolitica infections, 424
Yersiniapestis, 30, 52. See also Plague
biteor scratch-related transmission of, 426, 429, 437
as zoonoticrespiratory diseasecause,43I
Zafirlukast, as small airwaydiseasetreatment,41
Zincsulfatefecal flotation test, 48, 83, 86
Zinc supplementation
in hepaticlipidosis, 147
in inflammatory boweldisease, II I
Zoonoses,417-419
bite-or scratch-associated, 426-431
definition of, 417
ehrlichiosis as, 399
enteric,419-425, 441
environmental,441-443
respiratory, 431-434
urogenital, 439-440
vector-associated, 444-447

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