1. Pathophysiology of the liver. Jaundice.
The State Education Institution of Higher Professional Training
The First Sechenov Moscow State Medical University
under Ministry of Health of the Russian Federation
 Department of Pathophysiology
Pathophysiology of the liver. Jaundice.
Lecture presentation
Professor Pirozhkov S.V.
education year

2. Liver insufficiency is a decrease of one or many functions of the liver below the level required to maintain normal homeostasis

3. Etiology of liver insufficiency
Damage to the liver parenchyma or bile ducts
- hepatitis (viral, bacterial, toxic, autoimmune)
- dystrophy
- cirrhosis
- tumors
- parasites
- gall bladder stones, inflammation of the bile ducts with cholestasis
2. Extrahepatic factors
- heart failure, shock
- general hypoxia
- renal failure
- protein malnutrition
- metastases in the liver

4. Manifestations of liver failure
I. Disorders of carbohydrate metabolism
Manifestations Their mechanisms
* Decrease in glucose Increased insulin
tolerance resistance of hepatocytes
* Increased plasma Decreased capacity to
lactate level utilize lactic acid in gluconeogenesis
* Hypoglycemia Depletion of glycogen stores
- Decreased capacity to
synthesize glycogen
- Decreased glucagon resposiveness of hepatocytes

5. Manifestations of liver failure
II. Disorders of amino acids and ammonia metabolism
Manifestations Mechanisms/explanations
* Elevated levels of plasma Decreased metabolism of
aromatic amino acids and amino acids in the liver
methionine
* Normal or depressed plasma Branched-chain amino
levels of the branched-chain acids are largely utilized
amino acids by skeletal muscles
(Leu, Iso-Leu, Val)
* Reduction in blood Decreased urea synthesis
urea nitrogen in the ornitine cycle
* Accumulation of ammonia Decreased utilization of
in the blood ammonia for urea synthesis

6. Manifestations of liver failure
III. Disorders of protein synthesis and degradation
Manifestations Mechanisms/explanations
* Hypoprothrombinemia Reduced synthesis of
prothrombin; reduced absorption of vitamin K due to
cholestasis
* Hypoalbuminemia Decrease in the number and function of hepatocytes; loss of albumin into the ascitic fluid
* Decreased plasma Decreased rate of its
level of factor V synthesis
* Increased production of A response stimulated by
fibrinogen (possibly abnormal) IL-1 and IL-6
and other acute phase reactants
(C-reactive protein etc.)
* Decreased plasma activity Impairment of its synthesis
of choline esterase in the liver cells

7. Manifestations of liver failure IV. Disorders of lipid metabolism
Manifestations Their mechanisms
* Accumulation of lipids Decreased apoprotein
in hepatocytes (lipidosis) synthesis
* Decrease in total plasma Decreased synthesis of
cholesterol level (free and cholesterol; decrease in esterified) lecithine-cholesterol acyl
transferase activity (severe
liver injury)
* Increase in total plasma Abnormal bile evacuation
cholesterol (cholestasis)

8. Manifestations of liver failure
V. Disorders of detoxification and neutralization of biologically active substances
■ Decreased capacity to neutralize toxic products of amino acids metabolism (phenol, indol, cadaverin etc.)
■ Decreased capacity to neutralize hormones:
- insulin, glucagon - (proteolysis, deamination)
- thyroxine, triiodothyronine (deiodination)
- estrogens, including estradiol (conversion to estriol and estrone, and further conjugation with glucuronic acid)
- adrenalin (О-methylation, deamination)
■ Decreased capacity to metabolize drugs

9. Manifestations of liver insufficiency
Coma
Fetor hepaticus
Esophageal
varices
Spider angiomas
Gastropathy
Gynecomastia
Melena
Jaundice
Splenomegaly
Ascitis
«Caput medusae»
Loss of pubic hair
Testicular atrophy
Ascitis
Liver «flap» (asterixis)
Rectal varices (hemorrhoids)
Hemorrhagic diathesis
Anemia
Ankle edema
Manifestations of liver insufficiency

10. TYPES OF HEPATIC COMA
● Porto-systemic shunting
● Hepatocellular

11. NH3 Bilirubin Indol Scatol Intestinal flora
Main factors of neurotoxicity in hepatic encephalopathy
Bilirubin
Inhibition of dopamine and norepinephrine synthesis; increased production of serotonin
NH3
Toxins
False neuromediators
Indol Scatol
Intestinal flora
Tryptophan Thyrosine Phenylalanine
Thyramine Octopamine

12. Manifestations of liver failure
VI. Disorders of bilirubin pigments metabolism
Manifestations Mechanisms
* Accumulation of Decreased activity of
unconjugated bilirubin UDP-glucuronosyl
in blood plasma transferase in hepatocytes
* Accumulation of Cytolysis of hepatocytes,
conjugated bilirubin cholestasis
in blood plasma
J A U N D I C E

13. METABOLISM OF BILIRUBIN IN THE LIVER
ALB – albumin; GSTr – glutathione-S transferase
UCB – unconjugated bilirubin; GLT-glucuronosyl transferase
BM(D)G – bilirubin mono(di)glucuronide
АLB
Transporter-protein
UCB
GLT
BMG
GSTr-UCB
UCB
BDG
UCB
АLB-UCB
GSTr
GLT
Sinusoid
Disse space

14. TYPES OF THE SECONDARY (ACQUIRED) JAUNDICE
● Hemolytic
● Hepatocellular
● Obstructive

15. Types and mechanisms of hereditary jaundice
Bilirubin glucuronide
Watersoluble bilirubin glucuronide
Dubin-Johnson and Rotor syndromes 3
Glucuronyltransferase
Crigler-Nadjjar syndrome and neonatal jaundice 2
Watersoluble bilirubin
Gilbert syndrome 1
Bilirubin formed in other parts of the mononuclear phagocyte system
Hemoglobin
Kupffer cell