CIRRHOSIS

1. CIRRHOSIS DEFINITION END STAGE CHRONIC LIVERDISEASE CHARECTERISED BY 1. BRIDGING FIBROUS SEPTAE 2. PARENCHYMAL NODULES 3. DISRUPTION OF THE ARCHITECTURE OF THE ENTIRE LIVER

2. ETIOLOGIC FACTORS 1. ALCOHOLIC LIVER DISEASE -60-70% OF CASES 2. POSTNECROTIC CIRRHOSIS INCLUDING VIRAL HEPATITIS – 10% 3. BILIARY DISEASES- 5 – 10%

3. ETIOLOGIC FACTORS 4. HEREDITARY HAEMOCHROMATOSIS -5% 5. WILSON’S DISEASE 6. ALFA 1 ANTITRYPSIN DEFICIENCY 7. CRYPTOGENIC CIRRHOSIS- 10-15%

4. OTHER INFREQUENT CAUSES OF CIRRHOSIS IN INFANTS CHILDREN GALACTOSEMIA & TYROSINOSIS DRUG INDUCED CIRRHOSIS SYPHILIS CARDIAC CIRRHOSIS INDIAN CHILDHOOD CIRRHOSIS

5. PATHOGENESIS THREE MAJOR PATHOLOGIC MECHANISMS 1. HEPATOCELLULAR DEATH 2. REGENERATION 3. PROGRESSIVE FIBROSIS

6. POSTNECROTIC CIRRHOSIS(MACRONODULAR CIRRHOSIS) LARGE IRREGULAR NODULES WITH BROAD BANDS OF CONNECTIVE TISSUE.

7. ETIOLOGY OF POSTNECROTIC CIRRHOSIS 1. VIRAL HEPATITIS–HEPATITIS B HEPATITIS C –MOST COMMON CAUSE 2. DRUGS & CHEMICAL HEPATOTOXINS 3. IDIOPATHIC

8. MORPHOLOGY OF POSTNECROTIC CIRRHOSIS GROSS - SMALL LIVER < 1 Kg DISTORTED NODULES OF VARYING SIZES WITH IRREGULAR COARSE SCARS

9. POSTNECROTIC CIRRHOSIS

10. POSTNECROTIC CIRRHOSIS

11. MICROSCOPIC FEATURES OF POSTNECROTIC CIRRHOSIS 1. NORMAL LOBULAR ARCHITECTURE OF LIVER IS NOT COMPLETELY LOST 2. THICK FIBROUS SEPTA CONTAINING CHRONIC INFLAMMATORY CELLS & PROLIFERATING BILE DUCTULES.

12. MICROSCOPIC FEATURES OF POSTNECROTIC CIRRHOSIS ACTIVE LIVER CELL NECROSIS MAY BE SEEN REGENERATING NODULES WITH VARYING SIZED LIVER CELLS WITH LARGE NUCLEI.

13. MICROSCOPIC FEATURES OF CIRRHOSIS

14. POSTNECROTIC CIRRHOSIS

15. BILIARY CIRRHOSIS FOLLOW LONG CONTINUED CHOLESTASIS OF INTRAHEPATIC OR EXTRAHEPATIC ORIGIN TWO TYPES – 1. PRIMARY BILIARY CIRRHOSIS OBSTRUCTIVE PROCESS OF UNKNOWN ETIOLOGY AFFECTING INTRAHEPATIC BILE DUCTS 2.SECONDARY BILIARY CIRRHOSIS

16. PRIMARY BILIARY CIRRHOSIS MIDDLE AGED WOMEN FAMILIAL INCIDENCE HYPERCHOLESTEROLEMIA AUTOIMMUNE ORIGIN

17. SECONDARY BILIARY CIRRHOSIS PROLONGED OBSTRUCTION OF EXTRAHEPATIC BILIARY PASSAGES EXAMPLE- 1. CHOLELITHIASIS , 2. BILIARY ATRESIA,

18. BILIARY SECONDARY CIRRHOSIS 3. CANCER OF BILIARY TREE & HEAD OF PANCREAS 4. POSTOPERATIVE STRICTURES

19. MORPHOLOGY OF BILIARY CIRRHOSIS GROSS - (BOTH PRIMARY & SECONDARY) - INITIALLY ENLARGED GREENISH YELLOW LIVER, LATER SMALLER FIRMER MICRONODULAR

20. MICROSCOPY OF PRIMARY BILIARY CIRRHOSIS MICROSCOPY – PRIMARY BILIARY CIRRHOSIS STAGE 1. PORTAL TRACTS SHOW DESTRUCTION OF BILE DUCTS, INFLAMMATION ,GRANULOMAS STAGE2. BILE DUCTULAR PROLIFERATION

21. PRIMART BILIARY CIRRHOSIS

22. PRIMART BILIARY CIRRHOSIS

23. MICROSCOPY OF PRIMARY BILIARY CIRRHOSIS INFLAMMATION EXTENDING INTO THE PERIPORTAL HEPATIC PARENCHYMA WITH MELLORY BODIES. STAGE 3. FIBROUS SCARRING CONNECTING THE PORTAL AREAS

24. MICROSCOPY OF PRIMARY BILIARY CIRRHOSIS NUMBER OF BILE DUCTS REDUCED INFLAMMATORY INFILTRATE IS REDUCED.

25. MICROSCOPY OF PRIMARY BILIARY CIRRHOSIS STAGE 4. WELL FORMED MICRONODULAR CIRRHOSIS

26. MICROSCOPIC FEATURES OF CIRRHOSIS

27. MICROSCOPIC FEATURES OF PRIMARY BILIARY CIRRHOSIS LATE STAGE

28. SECONDARY BILIARY CIRRHOSIS-GROSS & MICROSCOPY GROSS 1. YELLOW GREEN PIGMENTATION 2. O/S –HARD FINELY GRANULAR MICROSCOPY – JIGSAW PATTERN OF COARSE FIBROUS SEPTAE

29. SECONDARY BILIARY CIRRHOSIS-GROSS & MICROSCOPY DISTENDED LARGE & SMALL BILE DUCTS CONTAINING BILE PLUGS EXTENSSIVE PROLIFERATION OF SMALL BILE DUCTS WITH ASCENDING CHOLANGITIS,PYLEPHLEBITIS, BILE LAKES

30. SECONDARY BILIARY CIRRHOSIS

31. SECONDARY BILIARY CIRRHOSIS-MICROSCOPY –DILATED PROLIFERATING BILE DUCTS WITH BILE PLUGS

32. CLINICAL FEATURES OF BILIARY CIRRHOSIS INCIDIOUS ONSET PRURITUS DARK URINE

33. CLINICAL FEATURES OF BILIARY CIRRHOSIS PALE STOOL JAUNDICE SKIN PIGMENTATION

34. PIGMENT CIRRHOSIS IN HAEMOCHROMATOSIS AN IRON STORAGE DISORDER EXCESSIVE ACCUMULATION OF IRON IN PARENCHYMAL CELLS WITH EVENTUAL TISSUE DAMAGE

35. PIGMENT CIRRHOSIS IN HAEMOCHROMATOSIS ORGANS MAINLY AFFECTED – LIVER, PANCREAS,HEART, PITUITARY BRONZE DIABETES

36. CLASSIFICATIONOF HAEMOCHROMATOSIS 1. IDIOPATHIC( PRIMARY)TYPE 2. SECONDARY(AQUIRED) TYPE

37. ETIOPATHOGENESIS OF IDIOPATHIC HAEMOCHROMATOSIS AUTOSOMAL RECESSIVE EXCESSIVE INTESTINAL ABSORPTION OF DIETARY IRON

38. ETIOPATHOGENESIS OF IDIOPATHIC(PRIMARY) HAEMOCHROMATOSIS HEREDITARY HEMOCHROMATOSIS GENE ON SHORT ARM OF CHROMOSOME 6 DISEASE MANIFESTS AFTER 20 g OF STORAGE IRON GETS ACCUMULATED

39. ETIOPATHOGENESIS OF IDIOPATHIC HAEMOCHROMATOSIS MECHANISM OF INJURY 1. LIPID PEROXIDATION

40. ETIOPATHOGENESIS OF IDIOPATHIC HAEMOCHROMATOSIS 2. STIMULATION OF COLLAGEN FORMATION 3. DIRECT INTERACTION WITH DNA – HEPATOCELLULAR CARCINOMA

41. ETIOPATHOGENESIS OF SECONDARY HAEMOCHROMATOSIS EXCESS IRON RESULTS FROM MULTIPLE TRANSFUSIONS IN SICKLE CELL ANEMIA,APLASTIC ANEMIA

42. ETIOPATHOGENESIS OF SECONDARY HAEMOCHROMATOSIS PARENCHYMAL INJURY OCCURS RARELY IN SUB SAHARAN AFRICA – ALCOHOLIC BEVERAGES - BANTU SIDEROSIS

43. MORPHOLOGY OF HAEMOCHROMATOSIS 1. DEPOSITION OF HEMOSIDERIN IN LIVER , PANCREAS , MYOCARDIUM PITUITARY,ADRENAL THYROID & PARATHYROID GLANDS,JOINTS & SKIN

44. MORPHOLOGY OF HAEMOCHROMATOSIS 2. CIRRHOSIS 3. PANCREATIC FIBROSIS

45. MORPHOLOGY OF LIVER IN HEMOCHROMATOSIS GROSS –ENLARGED ,FIRM , CHOCOLATE BROWN INTENSELY PIGMENTED LIVER WITH MICRONODULAR CIRRHOTIC PATTERN WITH FIBROUS BANDS

46. LIVER IN HAEMOCHROMATOSISMICROSCOPIC FEATURE INITIALLY GOLDEN YELLOW HEMOSIDERIN GRANULES IN THE PERIPORTAL HEPATOCYTES

47. LIVER IN HAEMOCHROMATOSISMICROSCOPIC FEATURE WITH PROGRESSIVE INVOLVEMENT OF REST OF THE LOBULE, BILE DUCT EPITHELIUM, KUPFFER CELLS. PRUSSIAN BLUE STAIN

48. LIVER IN HAEMOCHROMATOSISMICROSCOPIC FEATURE IRON HAS DIRECT HEPATOTOXICITY FIBROUS SEPTA DEVELOP SLOWLY INFLAMMATION-- IS ABSENT

49. LIVER IN HEMOCHROMATOSISPRUSSIAN BLUE STAIN

50. MORPHOLOGY OF PANCREAS IN HEMOCHROMATOSIS INTENSELY PIGMENTED WITH DIFFUSE INTERSTITIAL FIBROSIS PARENCHYMAL ATROPHY HEMOSIDERIN IN – ISLET CELLS ACINAR CELLS & FIBROUS STROMA