CHRONIC DIARRHEA

PRESENTOR: Dr. SAQLAIN MOHAMED

MODERATOR: Dr. BHASKAR
 contents
 Definition
 Clinical Classification
 Causes
 Pathophysiology
 Evaluation
 Management
 DEFINITION

 Three or more bowel movements per day .

 Stool weight more than 200 g daily in western diet.

 Decrease in fecal consistency lasting for four or more weeks.

 CLINICAL CLASSIFICATION

 Time course: Acute vs Chronic.

 Volume: Large vs Small

 Pathophysiology: Secretory vs Osmotic

 Stool character: Watery vs Fatty vs Inflammatory

 Acute Diarrhea: Diarrhea less than 2 weeks.
Usually infectious Self
limited mostly.

 Chronic Diarrhea: Diarrhea for more than 4 weeks.

Usually non infectious.

 Large Volume Diarrhea:If the source of diarrhea is upstream in the right
colon or small bowel and if the rectosigmoid reservoir is intact ,bowel
movements are fewer ,but larger.

 Small Volume Diarrhea:When the reservoir capacity is compromised by

inflammatory or motility disorders involving the left colon ,frequent small
volume bowel movements ensue.
 Causes of secretory diarrhea
1. Exogenous secretagogues
eg:enterotoxin(cholera)

2. Endogenous secretagogues
eg:neuroendocrine tumors(carcinoid syndrome)

3. Absence of ion transporter

eg:congenital chloridorrhea

4. Loss of intestinal surface area

eg:intestinal resection,diffuse intestinal mucosal disease

5.Intestinal ischemia
eg:diffuse mesentric atherosclerosis

6.Rapid intestinal transit

eg:post vagotomy
 Causes of steatorrheal diarrhea

 Intraluminal maldigestion (pancreatic exocrine insufficiency, bacterial

overgrowth, bariatric surgery, liver disease)

 Mucosal malabsorption (celiac sprue, Whipple’s disease, infections,
abetalipoproteinemia, ischemia, drug-induced enteropathy)

 Postmucosal obstruction (1° or 2° lymphatic obstruction)

 Inflammatory Causes of diarrhea

 Idiopathic inflammatory bowel disease (Crohn’s, chronic ulcerative colitis)

 Lymphocytic and collagenous colitis Immune-related mucosal disease (1° or 2°

 immunodeficiencies, food allergy, eosinophilic gastroenteritis, graft-versus-host

disease)

 Infections (invasive bacteria, viruses, and parasites, Brainerd diarrhea)

 Radiation injury

 Gastrointestinal malignancies
 Dysmotile Causes of diarrhea

 Irritable bowel syndrome (including postinfectious IBS)

 Visceral neuromyopathies

 Hyperthyroidism Drugs (prokinetic agents)

 PostvagotomyFactitial Causes
 Factitial Causes of diarrhea

 Munchausen
 Eating disorders
 Iatrogenic Causes of diarrhea

 Cholecystectomy
 Ileal resection
 Bariatric surgery
 Vagotomy, fundoplication
 Secretory diarrhea-mechanisms

 Exogenous secretagogues-inhibit Na-H exchange in the small intestine and

colon there by blocking the most important driving forces for electrolytes
and fluid absorption.
ex:Enterotoxins.
 Endogenous secretagouges:Interact with intracellular regulators or
intracellular messengers of enterocytes-stimulation of secretion by
epithelial cells.
ex:Neuroendocrine tumors
 Absence or disruption of a specific absorptive pathway .

ex:Congenital chloridorrhea.

 Loss of intestinal surface area.

ex:Intestinal resection,diffuse intestinal mucosal disease.

 Intestinal ischemia:Mechanism of diarrhea not known

ex:Diffuse mesenteric atherosclerosis.

 Intestinal transit:
Rapid intestinal transit:Decreased time for absorption
ex:following vagotomy
Slow intestinal transit:promotes small intestinal bacterial overgrowth.
ex:Scleroderma.
 Characteristics of secretory diarrhea:

1) watery, large-volume fecal outputs that are typically

painless

2)doesn’t disappear with fasting.

3)Electrolyte absorption is impaired and so

electrolyte concentration in stool water is high.
 OSMOTIC DIARRHEA-MECHANISM

 Ingestion of poorly absorbed agents:Ions are transported actively by

mechanisms that are saturated at low intraluminal ion concentrations and
passively by mechanisms that are slow.

 Together ,these processes limit total absorption to a fraction of the amount

that can be ingested.

 The unabsorbed ions that remain in the intestinal lumen obligate

retention of water leading to diarrhea.
 Sugars and sugar alcohols are other subcategory of substances that cause
osmotic diarrhea.

 Monosaccharides are absorbed intact across the apical membrane of

intestine,where as disaccharides require disaccharidase for absorption.

 Absence of disaccharidase leads to osmotic diarrhea.

 Disaccharidase deficiency may be congenital or acquired.

ex: Congenital lactase deficiency. Congenital

sucrase deficiency. Congenital trehalase
deficiency.
 Characteristics of osmotic diarrhea:

1) Disappears with fasting or cessation of ingestion of the offending

substance.

2) Electrolyte absorption is not impaired in osmotic diarrhea ,and

electrolyte concentrations in stool water are usually low
 COMPLEX DIARRHEA

 Most clinically significant diarrheas are complex; rather than being

produced by a single pathophysiologic mechanism.

 These may include the effects of substances released by enteric endocrine

cells, cytokines released by local and remote immunologically reactive cells,
by the activity of the enteric nervous system, and by peripherally released
peptides and hormones (paracrine, immune, neural, and endocrine systems).
 Thus, multiple modulators and multiple effectors contribute to the final
clinical picture.

 A full appreciation of the pathophysiology of diarrhea requires

consideration of paracrine, Immune, neural, and endocrine modulators,
a regulatory system that can be abbreviated by
the acronym “PINES”.
 Dysregulation of PINES in CHOLERA:

1)Cholera toxin targets the epithelial cell ,increases the second messenger
cAMP, which opens apical chloride channel to stimulate chloride secretion
and results in diarrhea.

2)Cholera toxin stimulates endocrine cells and neural elements that reinforce
its direct secretory effect on enterocytes.

3)Toxin causes distinct changes in intestinal motility.

 Dysregulation of PINES in IBD:

1.Destruction of mucosa leads to exudation into lumen.

2.Down regulation of sodium channels and pumps.
3.Bacterial proteins stimulate production of cytokines that
enhance polymorphonuclear function and diarrhea.
 Dysregulation of PINES in IBS:
1)Altered motility.
2)Bile acid malabsorption .
3)Compromised rectal reservoir capacity
 HISTORY

 A careful history can provide clues to the cause of chronic diarrhea.

 The following 14 points should be assessed as part of a comprehensive

history in a patient with chronic diarrhea:

 The characteristics of the onset of diarrhea should be noted as precisely as

possible. Note should be made of whether it was congenital, abrupt, or
gradual in onset.
 The pattern of diarrhea should be recorded: Are loose stools
continuous or intermittent?

 The duration of symptoms should be identified clearly.

 Epidemiological factors, such as travel before the onset of illness,

exposure to potentially contaminated food or water, and illness in
other family members should be elicited.
 Stool characteristics should be investigated. Specifically, the patient should
be queried as to whether stools are watery, bloody, or fatty.

 The presence or absence of fecal incontinence should be determined.

Some individuals complain of diarrhea when their major difficulty is
disordered continence.

 The presence or absence of abdominal pain and its characteristics should be

evaluated. Pain often is present in patients with inflammatory bowel
disease, irritable bowel syndrome, and mesenteric ischemia
 The presence of weight loss should be determined if possible by reference to
objective measurement of body weight. Substantial weight loss is more likely
to be caused by nutrient malabsorption, neoplasm, or ischemia.

 Aggravating factors, such as diet and stress, should be recorded.

 Mitigating factors, such as alteration of diet and use of both prescription and
over-the-counter drugs, should be listed.

 Previous evaluations should be reviewed whenever possible. Objective

records may be inspected, and radiograms and biopsy specimens should be
reexamined before new studies are ordered.

 Iatrogenic causes of diarrhea should be investigated by obtaining a

detailed medication history and a history of radiation therapy or surgery.
 Factitious diarrhea caused by surreptitious laxative ingestion
should be considered in every patient with chronic diarrhea.

 Markers of factitious diarrhea, such as a history of eating disorders,

secondary gain, or a history of malingering, should be sought.

 A careful review of systems should be conducted to look for systemic

diseases, such as hyperthyroidism, diabetes mellitus, collagen-vascular
diseases and other immune
problems.
 PHYSICAL EXAMINATION

 Peripheral neuropathy and orthostatic hypotension may be the only clues

to a diagnosis of amyloidosis.

 A thyroid nodule with cervical lymphadenopathy may be the only

lead to the presence of medullary carcinoma of the thyroid.

 Tremor and other systemic signs should lead to consideration of

hyperthyroidism
 The perineal, anal, and rectal examinations are important. Signs of
incontinence include skin changes from chronic irritation, gaping anus,
and weak sphincter tone.

 Crohn's disease is associated with perianal skin tags, ulcers, fissures,

abscesses, fistulas, and stenoses.

 Fecal impaction or masses might be noted

 Other associated physical findings include
 exophthalmos (hyperthyroidism),
 aphthous ulcers (IBD and celiac disease),
 lymphadenopathy (malignancy, infection or
Whipple's disease),
 enlarged or tender thyroid (thyroiditis, medullary
carcinoma of the thyroid),
 arthritis (IBD, Whipple's disease),
 wheezing and right-sided heart murmurs (carcinoid syndrome) ,
 clubbing (liver disease, IBD, laxative abuse, malignancy),
 Dermatitis herpetiformis(coeliac disease),
 Abdominal bruit (chronic mesenteric ischemia),
 Migratory necrotizing erythema(glucagonoma).
 Routine laboratory tests

 Complete blood picture: Anemia

Leucocytosis

 Serum chemistry screening can provide important information about the

patient's fluid and electrolyte status, his or her nutritional status, liver
problems, and dysproteinemia.
 Stool analysis

 In most instances, a quantitative stool collection and analysis can yield

important objective information about the type of diarrhea and its severity.
 When this is impractical, a spot stool collection can yield almost as much
information.
 In addition to stool weight, six groups of studies should be obtained to
classify the diarrhea as watery diarrhea (either secretory or osmotic),
inflammatory diarrhea, or fatty diarrhea and to gain insight into specific
diagnoses:
 Sodium and potassium concentrations in stool water may be measured,
so that the fecal osmotic gap can be calculated.

The fecal osmotic gap is best calculated as 290 − 2([Na+] + [K+]).

Osmotic diarrheas are characterized by osmotic gap >125 mOsm/kg,
whereas secretory diarrheas typically have osmotic gaps <50 mOsm/kg
 Stool pH may be assessed. Values of <5.6 are consistent with
carbohydrate malabsorption.

 Fecal occult blood testing with any of the available agents should be
conducted.
A positive test result suggests the presence of inflammatory
bowel disease, neoplastic diseases, or celiac sprue or other spruelike
syndromes.
 The presence of white blood cells in the stool suggests an
inflammatory diarrhea.

 The presence of excess stool fat should be evaluated by means of a Sudan

stain or by direct measurement. The presence of excessively large and
numerous fat globules by stain or measured stool fat excretion >14 g/24 h
suggests malabsorption or maldigestion. Stool fat concentration of >7%
strongly suggests pancreatic exocrine insufficiency.

 Laxative screening should be done in any patient with chronic diarrhea

that has defied diagnosis
 Further evaluation of patients with chronic
secretory diarrhea

 Patients with chronic watery diarrhea who have little or no osmotic gap as
calculated from stool electrolytes should be evaluated with three sets of
investigations.

 Although bacterial infection rarely causes chronic diarrhea, it can be

excluded by stool culture, including culture on special media for
Aeromonas and Pleisiomonas.
 In addition, the stool should be examined microscopically for ova and
parasites, with special tests for Cryptosporidium, Microsporidium, and
Giardia. Giardia antigen, measured in stool by enzyme-linked
immunosorbent assay, is the most sensitive test for giardiasis.
 An aspirate of small bowel contents for quantitative culture or breath tests
with glucose or isotopically labeled xylose can be used to establish the
presence of small bowel bacterial overgrowth but is likely to be meaningful
only in patients with disorders predisposing them to bacterial overgrowth
 Structural disease should be excluded by radiography of the small bowel,
sigmoidoscopy, or colonoscopy with multiple biopsies of the colonic
mucosa, computerized tomography of the abdomen, and endoscopic biopsy
of the proximal small bowel mucosa.
 A small bowel follow-through examination is preferable to an
enteroclysis study for the radiographic evaluation of patients with
chronic diarrhea.
 Selective testing for plasma peptides such as gastrin, calcitonin, vasoactive
intestinal polypeptide, and somatostatin, as well as urine excretion of 5-
hydroxyindole acetic acid, metanephrine, or histamine and other tests of
endocrine function, such as measurement of thyroid-stimulating hormone
and serum thyroxine levels or an adrenocorticotropin- stimulation test for
adrenal insufficiency, can be valuable
 Further evaluation of patients with chronic
osmotic diarrhea

 A low stool pH suggests carbohydrate malabsorption, and a high stool

magnesium concentration or output suggests magnesium ingestion.
 If carbohydrate malabsorption is suspected, a careful dietary history and
judicious use of breath hydrogen testing with lactose as the test sugar or
measurement of lactase in a mucosal biopsy specimen can be diagnostic.
 Patients with high stool magnesium outputs should be evaluated for
inadvertent ingestion of magnesium in mineral supplements or antacids
and for surreptitious laxative abuse.
 Further evaluation of chronic
inflammatory diarrhea
 Patients with blood and pus in the stool should undergo radiographic
evaluation of the small bowel with barium (small bowel follow-through
examination) and sigmoidoscopy or colonoscopy with biopsies of the
colonic mucosa.

 Stool culture and analysis of stool for Clostridium difficile toxin may
identify infectious causes of inflammation.
 Evaluation of chronic fatty diarrhea

 Patients with evidence of steatorrhea should undergo small bowel follow-

through radiographic studies to exclude structural problems.
 Small bowel biopsy specimens and an aspirate of small bowel contents for
quantitative culture should be obtained.
 pancreatic exocrine insufficiency should be assessed by direct tests, such
as the secretin test, or by indirect tests, such as measurement of stool
chymotrypsin activity or a bentiromide test
 Factitious diarrhea

 Factitious diarrhea may be characterized by a true increase in stool

volume, which is self-induced, or the creation of an apparent increase in
stool volume by the addition of various substances to the stool.
 Surreptitious laxative abuse is the most frequent cause of factitious diarrhea.
 Laxative abuse often presents as watery diarrhea that is high in frequency
and volume.
 The diarrhea is often associated with crampy abdominal pain, lethargy and
generalized weakness, malnutrition, dehydration, and electrolyte
abnormalities may result.
 In addition to the history, evaluation of the patient with suspected
factitious diarrhea consists of stool analysis and attempted detection of
chemical laxatives.
 Stool analysis consists of measurement of stool osmolality, and
sodium, potassium, and magnesium concentrations.
 An osmolal gap indicates the presence of an unmeasured
solute which can be due to laxatives containing magnesium, sorbitol,
lactose, lactulose, or polyethylene glycol as the active ingredients.
 Colonoscopy may reveal melanosis coli and a cathartic colon may be seen
on barium enema
Evaluation of suspected laxative abuse
 IDIOPATHIC SECRETORY DIARRHEA

 When an exhaustive evaluation fails to reveal a cause of chronic diarrhea and

stool analysis suggests a secretory diarrhea,the diagnosis of idiopathic
secretory diarrhea should be made.
 It occurs in two forms:
1)Epidemic form:Brainerd 2)Sporadic
form.
 Self limited forms of diarrhea.
 IRRITABLE BOWEL SYNDROME

 Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by

abdominal pain or discomfort and altered bowel habits in the absence of
detectable structural abnormalities.

 No clear diagnostic markers exist for IBS; thus the diagnosis of the disorder is
based on clinical presentation.

 In 2016, the Rome III criteria for the diagnosis of IBS were updated to Rome
IV
Pathophysiology
Gut dysbiosis and IBS
 Treatment

Education
Reassurance
Dietary modification
Fiber
Symptomatic treatment
Psychological/behavioral options
 Currently available
Rx treatments for IBS

• Dicyclomine HCl
• Hyoscyamine sulfate
(± other anticholinergics/sedatives)
• Belladonna and phenobarbital1
• Clidinium bromide with chlordiazepoxide

• Tegaserod

• Alosetron
 Empirical therapy for chronic diarrhea

 Empirical therapy is used in three situations:

 as a temporizing or initial treatment before

diagnostic testing,
 after diagnostic testing has failed to confirm a diagnosis,

 and when a diagnosis has been made, but no specific treatment is

available or specific treatment fails to effect a cure

 Empirical trials of antimicrobial therapy may be justified if the
prevalence of bacterial or protozoal infection is high in a specific
community or situation.
 An empirical trial of bile acid–binding resins, such as
cholestyramine, may be the least expensive way to diagnose bile acid–
induced diarrhea.
 Opiates are the most effective nonspecific
antidiarrheal agents.
 Octreotide should be reserved as a secondary agent.

 Enkephalinase inhibitor (delta opiate receptor effect)-

Racecadotril .
 Adequate hydration is an essential part of the treatment of
diarrheal diseases, and oral rehydration solutions may be necessary in
some instances.
 Some patients, particularly those with postresection diarrhea, may
need long-term intravenous fluid administration.
 Parenteral nutrition should be reserved for patients who are
unable to maintain an adequate nutritional status because of the
diarrheal disease.
 FODMAP

 FODMAP is an acronym for Fermentable Oligosaccharides,

Disaccharides, Monosaccharides, and Polyols
 It is an elimination diet which attempts to improve symptoms
in functional gastrointestinal disorders.
 FODMAPs are osmotically active and ferment rapidly, thereby
causing gastrointestinal symptoms in some
individuals.
 Currently there are no official published guidelines recommending
specific dietary treatment of functional gastrointestinal disorders,
but multiple studies have looked into this topic and there is
increasing evidence suggesting that this diet benefits certain
patients.
 SUMMARY

 A myriad of disorders are associated with chronic diarrhea . The

prevalence of specific disorders varies based upon the practice
setting.
 In developed countries, common causes are irritable bowel
syndrome (IBS), inflammatory bowel disease, malabsorption
syndromes (such as lactose intolerance and celiac disease), and
chronic infections (particularly in patients who are
immunocompromised).
 Optimal strategies for the evaluation of patients with chronic
diarrhea have not been established.
 A thorough medical history can guide appropriate evaluation.
 The physical examination rarely provides a specific diagnosis. However, a
number of findings can provide clues.
 There is no firm rule as to what testing should be done.
 The history and physical examination may point toward a specific
diagnosis for which testing may be indicated.
 The minimum laboratory evaluation in most patients should include a
complete blood count and differential, thyroid function tests, serum
electrolytes, total protein and albumin, and stool occult blood.
 In addition, most patients require some form of endoscopic evaluation
(either sigmoidoscopy, colonoscopy, or sometimes upper endoscopy)
depending upon the clinical setting.
 Inflammatory bowel disease

 Definition
Inflammatory bowel disease (IBD) is an immune-mediated chronic
intestinal condition. Ulcerative colitis (UC) and Crohn’s disease (CD) are
the two major types of IBD.
• Crohn’s Disease (CD) : An inflammatory bowel disease can be affected
any where in the intestine from mouth to anus.

• Has a particular tendency to occur in terminal ileum and ascending

colon(40-55%)
• Jejunoileitis(30–40%)
Peri anal disease ( 33 % )
Gastroduodenal disease(5-15%)
• CD is a transmural process.

• Most common in second to foruth decades and seventh to ninth decades

of life.
• Incidence in india is about 3.6per 100000person per year
Mild disease : Aphthous or small superficial ulcerations.

Active disease: stellate ulcerations fuse longitudinally and transversely

to demarcate islands of mucosa that frequently are histologically
normal. ( “cobblestone” appearance)

Granulomas : pathognomonic feature of CD: can be seen in lymph nodes,

mesentery, peritoneum, liver, and pancreas.
SIGNS AND SYMPTOMS

Inflammatory process evolves towards one of the following

1.Fibrostenotic obstructing pattern

2. penetrating fistulous pattern

The site of the disease influences the clinical manifestations

Ileocolitis(40–55%)
·Most common site : terminal ileum.

Common presentation : recurrent episodes of right lower quadrant pain and

diarrhea.

Pain : usually colicky; it precedes and is relieved by defecation.

Weight loss : due to diarrhea, anorexia and fear of eating.

High spiking fever: suggests intraabdominal abscess formation.

Inflammatory mass: may be palpable in the right lower quadrant of the

abdomen ( inflamed bowel adherents, indurated mesentery, and enlarged
abdominal lymph nodes).

In early stage: bowel wall edema and spasm produce intermittent obstructive
manifestation .

persistent inflammation leads to fibrostenotic narrowing and stricture

leading to chronic bowel obstruction.

Severe inflammation of the ileocecal region lead to localised wall thinning -

micro perforation - fistula formation to the adjacent bowel.

Entero vesical fistulas

Enterocutaneous fistula

Entero vaginal fistula

Jejunoileitis(30–40%)

Malabsorption (anemia ,hypoalbuminemia hypocalcaemia

hypomagnesaemia ,hyperoxaluria. Vitamin and mineral deficiencies)

Diarrhea : characteristic of active disease, due to

Bacterial over growth in obstructive stasis or fistulisation,
Bile acid malabsorption
Intestinal inflammation with increased secretion of
electrolyte.
Peri anal disease ( 33 % )

Low grade fever, malaise, crampy abdominal pain, and

hematochezia,
incontinence, anal stricture(4-6%), ano rectal fistula, and peri rectal abscess.

Pain due to the passage of fecal material through narrow and

inflammed segment of the large bowel.

May fistulise in to stomach or duodenum.

10% women with crohn colitis develop recto vaginal fistula

Gastroduodenal disease

• Nausea, vomiting and epigastric pain.

• Have helicobactorpylori-negative gastritis.

• second portion of duodenum more commonly affected.

• Advanced gastroduodenal CD may develop chronic gastric outlet

obstruction.
 showing thickening
of the wall, with stenosis, linear serpiginous ulcers
Lab,endoscopy and radiographic features

Lab
Elevated ESR,CRP
low Hb ,low albumin,
leukocytosis

Endoscopy feature
Aphthous ulceration fistula and skip lesion

Colonoscopy
Examination and biopsy of mass lesion or stricture or biopsy of the terminal
ileum.
Upper GI endoscopy for gatroduodinal involvement.

Wireless capsule endoscopy(WCE)

visualisation of entire small bowel.
Cant be used in small bowel stricture: lead to capsule retention and
obstruction.
for this patient patency capsule is used it is made up of barium started to
dissolve after 30 hours.
Radiographic

string sign

CT Enterography(CTE) and MRI Enterography (MRIE) of the small bowel can be

performed by using oral or Iv contrast .

CTE,MRIE and small bowel follow through : Equally accurate in the

identification of small bowel inflammation .

CTE and MRIE have been shown to be superior to SBFT for the detection of
extraluminal complications including fistulas ,sinus tract and abscess.
Serological markers

• pANCA (Perinuclear antineutrophil cytoplasmic antibody) : positive in 5 to

10 %

• ASCA (AntiSaccharomyces cerevisiae antibody): in 60 to 70%

• OmpC(Antibodies to escherichia coli outer membrane porin protein C): in

55%

• Antibody to I2 ,(a homologue of the bacterial transcription factor families

from a pseudomonas fluorescens associated sequence):positive 50 to 54% .

• Anti flagellin antibody identified in 50% of CD patients.

• Exact cause of UC remains unclear
• Three characteristics that define the etiology

Genetic
susceptibility

Altered
Immune
response to gut
dysregulation
microorganisms
 Patholog
y
• The rectum is always involved, with inflammation extending
proximally in a confluent fashion.
• The disease typically is most severe distally and less severe
proximally.
• According to extent of proximal involvement it is classified
into
• Proctitis/ proctosigmoiditis
• Left sided colitis/ extensive colitis
• Pancolitis
Patholog
y
• Inflammation is limited to the mucosal layer of the colon.

• Except in fulminant disease where inflammation extend beyond the

mucosal layer and can develop a toxic megacolon.
Symptoms/ signs
• Predominant symptoms are Rectal bleeding, with frequent stools
and mucous discharge from the rectum
• Others
• Tenesmus
• Nausea and weight loss
• In severe cases, purulent rectal discharge causes lower abdominal
pain and severe dehydration.
• Constipation may be the main symptom when the inflammation is
limited to the rectum (proctitis).
• Although UC can present acutely , symptoms have usually been present
for weeks or months.
Signs
• Pallor may be evident.
• PR examination may disclose visible red blood.
• Signs of malnutrition.

• Severe abdominal tenderness, fever, or tachycardia suggests

fulminant disease.
Grading of disease

Mild • Bleeding per rectum and

• <4 bowel motions/day

Moderate • Bleeding per rectum with

• >4-6 bowel motions/day

• Bleeding per rectum,

Severe • >6 bowel motions/day, and a systemic illness with

hypoalbuminemia (<30g/l)
Extraintestinal manifestations
• UC (IBD) is not restricted to GI tract, can involve almost any organ
system
• Upto 50% of patients can experience at least one EIM
• UC is associated with various extracolonic manifestations
• Musculoskeletal conditions:- Peripheral or axial arthropathy
• Cutaneous conditions:- Erythema nodosum, pyoderma
gangrenosum
• Ocular conditions:- Scleritis, episcleritis, uveitis
• Hepatobiliary conditions:- PSC
 INVESTIGATIONS
• Leucocytosis
CBC
• Anaemia
CMP • Thrombocytosis

Inflammatory
markers

Stool assays

Serological
studies
 • Hypoalbuminemia (ie, albumin <3.5 g/dL)
CBC
• Hypokalemia (ie, potassium <3.5 mEq/L)
CMP • Hypomagnesemia (ie, magnesium <1.5 mg/dL)

Inflammatory • Elevated ALP: >125 U/L suggests PSC (usually >3

markers times the upper limit of the reference range).
Stool assays

Serological studies
Infammatory markers
• ESR and CRP correlates with disease activity.
CBC
• Other inflammatory markers
CMP • Fecal calprotectin
• Can also be used to determine mucosal healing 3-6 months
Inflammatory after treatment initiation.
markers • Fecal lactoferrin and alpha-1-antitrypsin studies are
Stool assays used to exclude intestinal inflammation

Serological studies
Stool assays

CBC • Used to exclude other causes and to rule out

infectious enterocolitis.
CMP • Tests include
• Evaluation of fecal blood or leukocytes
Inflammatory • Ova and parasite studies
markers
• Viral studies
Stool assays • Culture for bacterial pathogens
• Clostridium difficile titer
Serological studies
Serological studies
P-ANCA
CBC
• M/c associated serologic marker.
CMP • Positive in 60%-80% of patients
• Helpful in predicting disease activity.
Inflammatory
markers • Associated with an earlier need for
surgery
Stool assays

Serological studies
Colonoscopy/ Sigmoidoscopy
• Essential at initial presentation
• To establish diagnosis
• Exclude alternate diagnosis like ischemic and infectious colitis
• Determine the extent and severity of disease.
• It may also be useful at the time of subsequent attacks
• To determine recurrence
• For surveillance for dysplasia.
• Multiple biopsies could be taken
• Biopsy of the terminal ileum should be attempted to exclude the
presence of Crohn's disease
Gross findings include:
• Abnormal erythematous mucosa, with or without ulceration,
extending continuously from the rectum to a part or all of the colon
• Contact bleeding may also be observed, with mucus identified in the
lumen of the bowel
• Pseudopolyps in patients with long-standing disease.
 Histologic finding of
UC
• Surface ulceration

• Inflammation confined to the mucosa

with
• Excess inflammatory cells in the lamina
propria
• Loss of goblet cells
• Presence of crypt abscess
Imaging Studies
• Plain Abdominal X-ray:
• Useful predominantly in patients
with symptoms of severe or
fulminant colitis.
• Images may show
• colonic dilatation with loss of
haustral markings , suggesting
toxic megacolon
• Evidence of perforation;
obstruction; or ileus.
 CT
scan
• Loss of haustra, especially in the distal colon
• Pseudopolyps

• Chronic cases - a narrow ,

featureless , shortened ‘hosepipe’
colon
A) Medical Treatment
1) 5-Aminosalicytes
5ASA
• The mainstay of therapy for mild to moderate UC
Corticosteroids • Preparations
• Sulfasalazine
Thiopurine • Mesalamine
• Effective at inducing and maintaining remission
Cyclosporine • Topical mesalazine given by suppository is the
preferred therapy for disease confined to the
rectum
Biologics
• Left-sided colonic disease is best treated with a
combination of mesalazine suppository and an
oral aminosalicylate.
Corticosteroids
• Used in acute treatment of moderate to
5ASA severe colitis.
• Preparations:
Corticosteroids • Oral Prednisone
• Iv Methylprednisolone
Thiopurine • Iv Hydrocortisone
• Budesonide - A new glucocorticoid
Cyclosporine • Released entirely in the colon
• Has minimal to no systemic glucocorticoid side
Biologics effects.
• The dose is 9 mg/d for 8 weeks and no taper is
required
• Rectally administered steroid enemas
provide therapy for flares of distal UC.
Thiopurines
• Effective for the maintenance of remission
5ASA
• Not appropriate as solo induction agents for
Corticosteroids patients with severe disease due to their slow
onset of action
Thiopurines • Preparations
• Azathioprine 2 - 2.5 mg/kg/day.
• 6-mercaptopurine 1 - 1.5 mg/kg/day.
Cyclosporine

Biologics
Cyclosporine

5ASA • Used to treat hospitalized patients with severe

ulcerative colitis.
Corticosteroids • Dose:
• * 2-4 mg/kg/day given as a continuous infusion.
Thiopurines • Side effects:
• Nephrotoxicity.
Cyclosporine • Opportunistic infections.
• Seizures.
Biologics
Biologics - antiTNF

5ASA • Its an IgG monoclonal antibody directed

against TNF.
Corticosteroids
• It is a less toxic alternative to cyclosporine for
Thiopurines patients with severe ,steroid refractory
disease
Cyclosporine • Effective for both induction and maintenance of
remission.
Biologics
• Preparations - infliximab
• Induction of remission: 5 mg/kg IV at weeks 0, 2,
6.
• Maintenance: 5 mg/kg IV every 8 weeks.
 Typical Celiac Disease
• Age 2 to 10 yrs
• Recurrent / chronic Diarrhea
• Malabsorption
• Abdominal distension
• Anemia
• Failure to thrive
• Poor weight gain
• Short stature
 Atypical Celiac Disease
• Age more than 10 yrs
• Resistant anemia
• Short stature
• Delayed Puberty
• Osteopenia / Osteoporosis
• Aphthous stomatitis
• Dental Enamel Hypoplasia
• Dematitis Herpetiformis
• Subfertility in women
• Peripheral Neuropathy
 Diagnosis
• Symptoms
• Signs on Physical Examination

• Serological Antibody tests on Gluten diet

– Anti-transglutaminase Ig A - 10 X ULN

• HLA detection – DQ2 ,DQ8

• Small Bowel Biopsy – Villus atrophy

• Clinical Response to Gluten free diet

 Anti-transglutaminase - Ig A
• Most sensitive and specific test
• Child should be on Gluten containing diet
• Antibody titer correlates with Villus atrophy
• > 10 X ULN is taken as positive evidence
• Small bowel Histology needed if strong clinical suspicion and
Values < 10 X ULN
• Antibody titer decreases to normal after strict Gluten free diet
ENDOSCOPIC FINDINGS
(DUODENAL BULB)
 Histological Features
Marsh criteria

Normal 0 Infiltrative 1 Hyperplastic 2

Partial atrophy 3a Subtotal atrophy 3b Total atrophy 3c

Horvath K. Recent Advances in Pediatrics, 2002. 25

 Gluten free Foods
• Cereals - Rice, Corn, Millet
• Meat
• Egg
• Milk
• Lentils
• Fruits
• Vegetables
 Management of Celiac crisis
• Hypoglycemia - 10% D/W 5ml/ kg
• Dehydration - Ringer Lactate + KCL 4ml/100ml
• Ca-gluconate in infusion 1 – 2 ml/kg
• MgSO4 (IV/IM: 25-50 mg/kg q6hr for 1 day
• Antibiotics
• Blood packed cells transfusion if needed
• Salt free albumin or FFP (10ml/kg)
• Steroids: Hydrocortisone 5mg/kg/dose 6 hourly
• Micronutrients: Vit-K (5mg ), Vit-A (2 lac IU), Vit-D (2 lac IU),
Folic Acid (5mg OD) and Zinc (20mg OD)
• Gluten free diet
 Tissue Transglutaminase
• Enzyme in Intestinal Mucosa
• Catalyzes metobolism of Gluten peptides
• Cross linkage of gliadin peptide to tissue transglutaminase
enzyme during these reactions results in formation of new
epitopes (antigens)
• Stimulation of immune system by these antigens results in formation
of Anti-tissue transglutaminase antibodies
THANK YOU