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1. "With ordinary talent and extraordinary perseverance, all things are attainable." - Thomas E. Buxton "Achievement is connected with action…..!” - Conrad Hilton

2. Pathophysiology of LiverGuo xiaosunShandong University

3. Liver anatomy: • Four Lobes

4. Anatomy • Lungs • Heart • Liver • Omentum • Diaphragm • Gall bladder

5. Structure of Liver Lobule

6. Structure of Liver Lobule

7. Normal Liver Histology

8. Liver Functions: • Metabolism– Carbohydrate, Fat & Protein • Secretory– bile, Bile acids, salts & pigments • Excretory– Bilirubin, drugs, toxins • Synthesis– Albumin, coagulation factors • Storage– Vitamins, carbohydrates etc. • Detoxification– toxins, ammonia, etc.

9. Causes and mechanisms of Liver Disease • Biological Factors: virus(HBV) • Physical and Chemic Factors(Alcohol， Tetrachloride) • Genetic Factors（Hemochromatosis） • Immunity Factors: （chronic hepatitis --activated T cell） • Nutritional Factors: (nutritional deficiency –worsen the condition)

10. Alcoholic Fatty Liver

11. Jaundice • A yellowing of the skin, sclerae, and other tissues caused by excess circulating bilirubin.

12. Jaundice

13. Jaundice

14. Bilirubin Metabolism • Formation • Plasma transport • Liver uptake • Conjugation • Biliary excretion

16. CHOLESTASIS • A clinical and biochemical syndrome that results when bile flow is impaired.

17. Etiology • intrahepatic causes • hepatitis, drug toxicity, and alcoholic liver disease. • intrahepatic and extrahepatic causes • duct stone and pancreatic cancer

18. Contributing factors • interference with microsomal hydroxylating enzymes • impaired activity of Na+,K+-ATPase • altered membrane lipid composition and fluidity • interference with the function of microfilaments • enhanced ductular reabsorption of bile constituents

19. The pathophysiologic effects • mixed hyperbilirubinemia • pruritus • steatorrhea and hypoprothrombinemia • osteoporosis or osteomalacia • hyperlipidemia

20. Portal Hypertension • Increased pressure in the portal venous system.

23. Mechanism • vascular compression and distortion by the fibrosis and regenerating nodules enhance resistance in the sinusoids and terminal portal venules. • contractility of sinusoidal lining cells, production of vasoactive substances (eg, endothelins, nitric oxide), various systemic neurohumoral factors that affect splanchnic arterioles, and Swelling of hepatocytes.

24. Cirrhosis

25. Cirrhosis Fibrosis Regenerating Nodule

26. Complications • portal-systemic venous collaterals develop (caput medusae , rectal varices , esophageal varices ) • hepaticencephalopathy • ascites • hypersplenism

27. The principal consequences of portal hypertension are the result of reduced blood flow though the liver and the effects of elevated pressure in the hepatic portal system.

28. With less blood flowing through the cirrhotic liver,its remaining functional cells have reduced access to the blood, compromising their detoxification activities. It's as if the blood is by-passing the liver (shunting) . As a result,toxins are more concentrated in the blood and are more likely to produce damaging effects.

29. Massive ascites in an elderly woman.

33. Ascites • Free fluid in the peritoneal cavity

34. Etiology • cirrhosis • chronic hepatitis, severe alcoholic hepatitis without cirrhosis, and hepatic vein obstruction

35. review:Pathogenesis of edema • 1. imbalance of exchange between intra- and extra-vascular fluid • increased capillary blood presure • decreased plasma colloid osmotic presure • increased capillary permeability • obstruction of lymphatic flow; • 2. imbalance of exchange between intra- and extra- body fluid: • decreased filtration rate of glomeruli • increased water and sodium reabsorption in renal.

36. Pathophysiology • Low serum osmotic pressure Synthesized by the liver, albumin is the major contributor to oncotic pressure in the serum. Decreased levels usually develop only in severe hepatic dysfunction. osmotic pressure tends to retain fluid in capillaries (2) High portal venous pressure

37. (3) Hepatic lymphatic obstruction may also be involved. plasma proteins leaking into interstitial space rely on the lymphatics for movement back into the circulatory system with the interstitial fluid. If lymph flow is obstructed, not only is backflow of interstitial fluid blocked but also colloid pressure in interstitial fluid increases.

38. (4) Na retention • In cirrhosis, arterial vasodilation leads to a decrease in splanchnic and systemic vascular resistance with pooling of blood in the splanchnic circulation, leading to a reduction in the effective arterial blood volume. This in turn leads to stimulation of the sympathetic nervous and renin-angiotensin-aldosterone systems, promoting renal sodium and water retention in an attempt to restore the effective arterial blood volume and maintain blood pressure.

39. patient with alcoholic cirrhosis and portal hypertension. Note the parotid hypertrophy, distended abdomen from ascites, and scrotal and pedal edema.

42. SYSTEMIC ABNORMALITIES • Depression of the liver’s chemical and drug detoxification function • Skin and endocrine changes • Spider nevi, palmar erythema • Complex derangements in the metabolism of sex hormones • Other endocrine derangements

43. Hematologic abnormalities • Renal and electrolyte abnormalities • Hypokalemia • Hyponatremia • Renal failure

44. Close-up view of a spider angioma of the skin in a patient with liver disease. Note the central, punctate filling vessel and the "spider-like" vessels emanating from it.

45. Liver palms: thenar and hypothenar erythema in a patient with chronic liver disease.

47. Hepatic Encephalopathy • A neuropsychiatric syndrome caused by liver disease and usually associated with portal-systemic shunting of venous blood.

48. Etiology • fulminant hepatitis ( viruses, drugs, or toxins) • cirrhosis or other chronic disorders

49. Grade 0 - Clinically normal mental status but minimal changes in memory, concentration, intellectual function, and coordination , Asterixis absent • Grade 1 - Mild confusion, euphoria, or depression; decreased attention; slowing of ability to perform mental tasks; irritability; and disordered sleep pattern, such as inverted sleep cycle, Asterixis can be detected

50. Grade 2 - Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, usually regarding time, Obvious asterixis • Grade 3 - Somnolent but can be aroused, unable to perform mental tasks, disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech, Asterixis generally absent • Grade 4 - Coma with or without response to painful stimuli