Practice Session 8.

1. Liver Function;
2. Hepatitis
3. Cirrhosis;

Diagnostic and Therapy of Internal Diseases

For Faculty of Physical Medicine and Rehabilitation
 1. Liver Functions;

Diagnostic and Therapy of Internal Diseases

For Faculty of Physical Medicine and Rehabilitation
• Metabolic Active – receives approx. 28%
of whole body blood flow;
• Highly aerobic – extracts approx. 20% of
O2 used by body;
• Directs Synthesis and Degradation of:
– Carbohydrates;
– Proteins;
– Fats
• Blood Supply from Hepatic Arteries;
– Supplying of liver tissues
• Portal and Hepatic Veins create main web of
intrahepatic circulation:
– Portal veins collect blood from intestinal
system and deliver it to hepatic cells;
– Hepatic veins derive blood hepatic cells to
the Vein Cava Inferior, toward the right
ventricle
Blood Flow and Liver Circulation
Liver Circulation

• Lobule – functional unit of the liver;

• Hepatic veins – takes of blood from hepatic

cells into the systemic circulation with its
branches;

• Portal Triad – Branches of hepatic artery,

portal vein and bile ducts;

• Space of Disse – extracellular gap;

• Hepatic Cells – Hepatocytes, main structural

unit of lobules
Basic Structure of Liver Lobule
• Hepatocytes (yellow) occupy 80% of the
parenchymal volume;
• Form one cell thick epithelium that forms a
functional barrier between two fluid containing
compartments with distinct ionic compositions:
– Tine canalicular lumen - bile flow;
– Sinusoidal blood space – portal blood flow
• Hepatocytes alter the composition of these
fluid spaces by vectorial transport of solutes
across their membranes;
• Apical and basolateral hepatocyte membranes
have many distinct characteristics
Hepatocyte
• Space of Disse: perisinusoidal space = an extracellular
“gap” between endothelial cells that line the sinusoids
and the basolateral membranes of the Hepatocytes;
• Hepatocytes have microvilli on basolateral side (in
the Space of Disse) that project into space. This
facilitates contact with solutes transported in the
sinusoidal blood;
• Single cell thickness of hepatocyte – tight junctions
and desmosomes between cells:
– Apical membrane faces canalicular lumen;
– Basolateral membrane faces Space Disse;
• Bile canaliculi – two adjacent hepatocytes juxtapose
their groove-like apical membranes along their
common face forming 1μm diameter tiny canaliculus;
 Other Cell Type in the Liver
• Comprise 6% of cells;
• Endothelial cells – lining the vascular sinusoids
forming fenestrated structures allowing movement
of plasma solutes (not RBC) into the Space of Disse;
• Kupffer cells – fixed macrophages in sinusoidal
vascular space – remove particulates from
circulation;
• Stellate cells – located in the Space of Disse; contain
large fat droplets in their cytoplasm may be involved
in pathogenesis of cirrhosis; have central role in
Vitamin A storage; May be capable of transforming
proliferative, fibrogenic and contractile myo-
fibroblasts
 Liver Functions
• Liver cells are most versatile cell in the human body with different functions in
sustaining of body homeostasis
– Carbohydrate and Lipid metabolism
• Maintaining of blood glucose and lipids level:
– Under the control of insulin blood glucose is transformed in glycogen and
stored in muscles and liver;
– Glycogen can be mobilized from deposits and under the control of glucagon
and converted in glucose;
– When the liver cells are saturated with glycogen carbohydrates are
transformed in triglycerides and stored in the form of body fat;
» In turn, stored lipids and amino acids can be backward transformed into
glucose;
– The liver produces cholesterol which plays an important role in the structure
of normal cell membranes and synthesis of hormones
 Liver Functions – cont’

• Liver cells are most versatile cell in the human body with different functions in
sustaining of body homeostasis
– Protein Metabolism;
• Principal location for synthesis and formation of amino acids and proteins
– Enzymes and Hormones;
– Albumins, globulins and other fractions of proteins;
– Protein complexes;
– Clotting factors (clotting proteins);
– The ammonia, the main product of protein metabolism processes, transforms into
urea, which is excreted by kidney from the systemic circulation in the urine.
 Liver Functions – cont’

• Liver cells are most versatile cell in the human body with different functions in
sustaining of body homeostasis
– Inactivation and Detoxification;
• The liver deactivates almost all substances that could not been excreted from
kidney and existence of those are not expedient for sustaining of homeostasis at
the particular time period;
– Toxins (endogenous, exogenous);
– Substances absorbed from gastrointestinal tract but are alien for
homeostasis;
– Alcohol;
– Pharmaceuticals;
– Enzymes and hormones (e.g. Steroid hormones)
 Liver Functions – cont’
• Liver cells are most versatile cell in the human
body with different functions in sustaining of body
homeostasis
– Bile Production
• Liver cells produce bile, a substance consisting
largely:
• Water;
• Bile acids;
– The important product for digestion of fats
• Bilirubin;
• Cholesterol
• Products of biotransformation in the Liver
– First Bile excreted in the intrahepatic ducts, than
is collected by extrahepatic bile ducts, through
which bile comes to Gallbladder and
Duodenum;
• Gallbladder serves to store bile
 2. Viral Hepatitis;

Diagnostic and Therapy of Internal Diseases

For Faculty of Physical Medicine and Rehabilitation
 Definition
• Acute or Chronic Inflammation of Liver lobules;
• Caused by Infection or non-infection agents;
– Non-infection
• Alcohol
• Toxic agents, incl. pharmaceuticals;
• Auto-immune;
– Viral Infection
• Resulted in irreversible damage liver structures
 Etiology
• Virus A-E
• Rarely other virus such as Epstein-Bar Virus
Comparisons of Hepatitis A, B and C
Hepatitis A Hepatitis B Hepatitis C
Transmission Smear infection Blood and Blood Products Blood and Blood Products
Contaminated water Sexual Intercourse Sexual Intercourse
Contaminated Food Birth Birth
Incubation 2-6 weeks 1-6 months 0.5-6 months
Danger of As long as virus is detectable in the
As long as viral DNA can be As long as viral DNA can be
stool, i.e. 2 weeks before and 2
infection weeks after start of illness identified in the blood identified in the blood

Spontaneous About 90% cure; About 15% cure;

About 10% chronic course with: About 85% chronic course
course About 100% cure;
Liver cirrhosis; with:
About 0.2% fulminating course with
Liver cell Cancer Liver cirrhosis;
acute liver failure About 1% fulminating course with Liver cell Cancer
acute liver failure Rarely fulminating course
Immunization Indicated vaccination, e.g. before
Standard immunization No Vaccine available
traveling certain countries
 Clinical Signs
• Symptoms mostly appeared in acuity phases;
• All forms can exhibit the same clinical sighs and symptoms at different intensities
– Cardinal :
• “Jaundice” – icterus;
• Feelings of pain, pressure, or distension at right upper abdomen
– General:
• Fatigue, tiredness, fever
• Nausea;
• Pain in muscles and joints
• Asymptomatic course is also possible;
– History with hints of:
• Etiology;
• Transmission
• Incubation
 Symptoms
• Inspection
– Jaundice – “icterus”;
– Some hoove abdomen;
• Percussion
– Enlargement of percussion borders of liver;
• Auscultation
– No specific sighs
• Palpation
– Hepatosplenomegaly
 Labs
• Elevated Levels of liver enzymes
– ALT, AST, γ-GT, ALP
– A consequence of liver cell damage;
• Signs of reduced synthetic activity of the liver
– Increased blood Glucose Levels;
– Decreased levels of blood proteins
• Total Protein, Albumin;
• Clotting proteins: Prothrombin, Fibrinogen
– Decreased level of Lipids;
• CBC
– Leucopenia, Neitropenia, Lymphocytosis
– If appears, it’s the result of viral infection
• Viral antibodies and Viral Antigens
– Proofing of relations with causal factors
– Diagnosis
 Treatment Approach

• Limitation of physical exertion

• Avoidance of substances toxic to the liver
• Symptomatic treatment
• Antiviral agents if Hepatitis B or C
– Sofosbuvir or combination with Valpataspavir or Daclastavir;
– Interferons;
– Ribavirine
 3. Cirrhosis;

Diagnostic and Therapy of Internal Diseases

For Faculty of Physical Medicine and Rehabilitation
 Definition

• Chronic progressive degenerative disease

that destroy the structure of hepatic lobes
and vessels;
• Replacement of hepatic lobes with
nonfunctional connective tissue – fibrosis
(scar tissue);
• Transformation in scar tissue is irreversible
 Prevalence and Etiology
• 250/100000 new cases per year;
• Men are affected twice as frequently as women;
• 50% of cases can be traced to chronic alcoholism
– Man who regularly drink more than 40gr pure alcohol (Ethanol) a day;
– Women who regularly drink more than 20gr pure alcohol (Ethanol) day;
• 30% of cases originate with chronic hepatitis B or C;
• 10% of cases are result of non-alcoholic steatohepatitis (NASH) - fatty liver in diabetes
or metabolic syndrome;
• 10% of cases are related with so called less frequent causes
– Long-term cholestasis (blockage of bile ducts);
– Long-term right heart failure – congestion cirrhosis; Alcoholic
Hepatitis
– Wilson Disease – excess accumulation of cooper in the tissues; NASH
– Hemochromatosis – excess accumulation of iron in the tissue; Less fequent
– causes
Hepatotoxic medications, e.g. methotrexate, amyodarone
– Autoimmune disease
 General Clinical Signs

• Unspecific for the liver disease

– Fatigue and decreasing in physical capacity;
– Feeling of pressure, pain or fullness in the upper abdomen;
– Meteorism;
– Nausea;
– Loss of weight
 Cardinal Skin Manifestation - Inspection
• Specific, Diagnostically
significant
– Jaundice – “Icterus”;
– Itching – skin excoriations;
– Spider hemangioma, navi;
– Palmar and plantar erythema;
– Atrophic tongue;
– White nails;
– Rhagedes in the corner of the
mouth;
– Dupuytren contracture –
contracture of palmar
aponeurosis
 Cardinal Signs of Estrogen Activity - Inspection
• Only partial inactivation of estrogens in
damaged liver provides imbalance between
estrogen and testosterone
– Disturbances or cessation of menstrual
cycle (in women);
– Gynecomastia (enlarged breast in men);
– Loss of secondary hear (in men);
– Atrophy of testicles;
– Loss of libido and potency
 Clinical Manifestation of Disrupted Protein Biosynthesis

• Tendency to bleed and to clot caused by disorders of clotting factors

and inhibitors synthesis
– Prothrombin , Fibrinogen , Vitamin K  (LABs)
• Susceptibility to infection caused by oppression of WBC generation
– Leucopenia, Neitropenia, Limphopenia, Thrombocytopenia – Hypersplenism
(LABs)
• Decreased oncotic pressure caused by hypoproteinemia
– Edema; (Inspection)
– Gaining in Ascitis (inspection)
 Clinical Manifestation of Portal Hypertension
• Increased portal vein pressure (>12mmHg) due
destroying of vessel structures in the liver lobules;
• Blood seeks for bypassing that offers the least resistance
– Caput medusae – appearance of extremally distended
and engorged paraumbilical, abdominal, thoracic and
esophageal veins and hemorrhoids
– Bleeding of esophageal varices are associated with
30% of lethality
• Increased pressure in abdominal veins causes pressing of
plasma from the lumen towards the abdominal cavity;
• Plasma is discharging the vessel. Decreased oncotic
pressure promotes the process.
– Ascitis;
– Spleenomegaly (Enlarged spleen);
• Capturing of thrombocytes increases risk for
bleeding
 Other Clinical Manifestation
Stages of Hepatic Encephalopathy
• Decreasing of detoxification function Stage Symptoms Survival (%)
causes increasing in circulation amounts I Beginning of sleepiness;
Confusion;
70

of ammonia that results neurological and Mood swings;

Blurred speech
psychiatric manifestations - hepatic II More intense sleepiness; 60
Apathy;
encephalopathy; Changed Handwriting;
Flapping tremor;
• Excessive release and circulation of III Somnolence; 40
Agitation;
different vasoactive substances, Aggressiveness;
Alterations on EEG
hypovolemia due vein congestions and IV Coma; 20
discharging of excessive amounts of No reaction to pain;
Extinguished corneal reflex;
plasma from vessels leads to hepatorenal Fetor Hepaticus
syndrome
 Labs/Instrumentals
• Elevated or Normal values of liver enzymes
indicate active or inactive damaging of lobules’
structure
– ALT, AST, γ-GT, ALP
• Bilirubin metabolism disorder
– Direct Bilirubin, Total Bilirubin Levels
• Signs of reduced synthesis in liver
– Albumin, Total Protein, Total Cholesterol,
Glucose levels,
– Clotting disorders – Prothrombin, Fibrinogen
levels
• Imaging
– Sonography
– CT/MRI
• Liver Biophsy
 Treatment Approach
• Prophylaxis or treatment of:
– deficiencies with balanced increase in calories, nutrients and vitamins;
– complications
• Diet rich in calories and protein, if compensation;
• Reduction of proteins solely in decompensated hepatic encephalopathy;
– Proteins are usually transformed in excessive amounts of ammonia
• Fluid and sodium restrictions and spironolactone (as aldosterone antagonist ) and
diuretics in cases of ascites and paracentesis, if necessary
• Β-blockers to decrease portal vein pressure and avoid consequences;
• Treatment of bleeding esophageal varices with endoscopic hemostasis