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CIRRHOSIS

CIRRHOSIS. DEFINITION END STAGE CHRONIC LIVER DISEASE CHARACTERISED BY 1 . BRIDGING FIBROUS SEPTA 2. PARENCHYMAL NODULES 3 .DISRUPTION OF THE ARCHITECTURE OF THE ENTIRE LIVER. CIRRHOSIS. 1. DEFINITION 2. MORPHOLOGIC CLASSIFICATION 3. ETIOLOGIC CLASSIFICATION

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CIRRHOSIS

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  1. CIRRHOSIS DEFINITION END STAGE CHRONIC LIVER DISEASE CHARACTERISED BY 1. BRIDGING FIBROUS SEPTA 2. PARENCHYMAL NODULES 3 .DISRUPTION OF THE ARCHITECTURE OF THE ENTIRE LIVER

  2. CIRRHOSIS 1.DEFINITION 2.MORPHOLOGIC CLASSIFICATION 3.ETIOLOGIC CLASSIFICATION 4.PATHOGENESIS-MAJOR PATHOLOGIC MECHANISM 5.ALCOHOLIC LIVER DISEASES- PATHOGENESIS, ALCOHOLIC STEATOSIS,ALCOHOLIC HEPATITIS,ALCOHOLIC CIRRHOSIS-MORPHOLOGY, 6.OTHER TYPES OF CIRRHOSIS - PATHOGENESIS,MORPHOLOGY,PROGNOSIS 7.CLINICAL FEATURES,PORTAL HYPERTENSION

  3. MORPHOLOGIC CLASSIFICATION OF CIRRHOSIS 1 .MICRONODULAR- NODULES EQUAL TO OR LESS THAN 3 mm 2. MACRONODULAR – NODULES MORE THAN 3 mm 3. MIXED TYPE

  4. ETIOLOGIC CLASSIFICATION OF CIRRHOSIS ALCOHOLIC LIVER DESEASE 60 –70 % VIRAL HEPATITIS (POSTNECROTIC CIRRHOSIS) 10% BILIARY DESEASES 5 – 10% HEREDITARY HEMOCHROMATOSIS- 5%

  5. ETIOLOGIC CLASSIFICATION OF CIRRHOSIS WILSON DESEASE ALFA –I ANTITRYPSIN DEFICIENCY CRYPTOGENIC CIRRHOSIS -10 – 15%

  6. OTHER INFREQUENT CAUSES IN INFANTS & CHILDREN GALACTOSEMIA OR TYROSINOSIS INDIAN CHILDHOOD CIRRHOSIS DRUG INDUSED CIRRHOSIS SYPHILIS CARDIAC CIRRHOSIS CRYPTOGENIC CIRRHOSIS

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

  8. ALCOHOLIC LIVER DISEASE 1. HEPATIC STEATOSIS(FATTY CHANGE) 2. ALCOHOLIC HEPATITIS 3. ALCOHOLIC CIRRHOSIS

  9. ALCOHOLIC LIVER DISEASES

  10. PATHOGENESIS OF ALCOHOLIC LIVER DISEASE DETRIMENTAL EFFECTS OF ALCOHOL & ITS PRODUCTS. HEPATOCELLULAR STEATOSIS.RESULTS FROM SHUNTING OF NORMAL SUBSTRATE AWAY FROM CATABOLISM TOWARDS- LIPID BIOSYNTHESIS

  11. PATHOGENESIS OF ALCOHOLIC LIVER DISEASE DETRIMENTAL EFFECTS OF ALCOHOL & ITS PRODUCTS. HEPATOCELLULAR STEATOSIS.RESULTS FROM SHUNTING OF NORMAL SUBSTRATE AWAY FROM CATABOLISM TOWARDS- LIPID BIOSYNTHESIS

  12. PATHOGENESIS OF ALCOHOLIC LIVER DISEASE 1 . INCREASED PERIPHERAL CATABOLISM OF FAT. 2. LIPID BIOSYNTHESIS BY THE ACTION OF ALCOHOL DEHYDROGENASE & ACETALDEHYDE DEHYDROGENASE. 3. DECREASED LIPOPROTEIN SECRETION

  13. PATHOGENESIS CONTINEUD 4.FREE RADICAL GENERATED DURING OXIDATION OF ETHANOL BY MICROSOMAL ENZYMES INJURE THE HEPATOCYTE. 5.ALCOHOL DIRECTLY AFFECTS MICROTUBULAR & MITOCHONDRIAL FUNCTION - CAUSE INJURY TO HEPATOCYTE

  14. PATHOGENESIS CONTINEUD 6.ACETALDEHYDE – LIPID PEROXIDATION – DISRUPTS CYTOSKELETAL & MEMBRANE FUNCTION. 7.OTHER FACTORS CAUSING INJURY TO HEPATOCYTES ARE-TOXIC OXYGEN METABOLITES FROM ACTIVATED NEUTROPHILS

  15. OTHER FACTORS ACCELERATING ALCOHOLIC LIVER DISEASE MALNUTRITION & VITAMIN DEFICIENCY- SPECIALLY THIAMINE & VITAMINE B12 DUE TO IMPAIRED DIGESTIVE FUNCTION DUE TO DAMAGE TO GASTRIC & INTESTINAL MUCOSA & PANCREATITIS.

  16. GROSS APPEARANCE OF LIVER IN HEPATIC STEATOSIS FATTY LIVER OF CHRONIC ALCOHOLISM- LARGE UP TO 4 - 6 Kg SOFT , YELLOW ,GREASY

  17. HEPATIC STEATOSIS

  18. HEPATIC STEATOSISREVERSIBLE- MICROSCOPIC FEATURES MICROVASICULAR MACROVASICULAR- CENTRILOBULAR INITIALLY CONTINUED INTAKE OF ALCOHOL- FIBROSIS AROUND THE CENTRAL VEIN EXTENDING IN TO SINUSOIDS.

  19. HEPATIC STEATOSIS

  20. HEPATIC STEATOSIS

  21. HEPATIC STEATOSIS

  22. ALCOHOLIC HEPATITIS-GROSS LIVER – NORMAL OR INCREASED IN SIZE. MOTTLED RED GREENISH BILE STAINED AREAS. OFTEN – VISIBLE NODULES & FIBROSIS - INDICATIVE OF EVOLUTION OF CIRRHOSIS.

  23. ALCOHOLIC HEPATITIS - MICROSCOPY HEPATOCYTE SWELLING (BALLOONING –FAT & WATER ACCUMULATION) & SCATTERED FOCI OF NECROSIS. MALLORY BODIES(ACCUMULATION OF CYTOKERATIN INTERMEDIATE FILAMENTS)- EOSINOPHILIC INCLUSIONS IN THE CYTOPLASM OF DEGENERATING CELLS.

  24. MALLORY'S HYALIN AN EOSINOPHILIC CYTOPLASMIC INCLUSION, ALCOHOLIC HYALIN, FOUND IN THE LIVER CELLS. IT IS TYPICALLY, BUT NOT ALWAYS, ASSOCIATED WITH ACUTE ALCOHOLIC LIVER INJURY.

  25. MALLORY'S HYALIN THE GLOBULES ARE AGGREGATES OF INTERMEDIATE FILAMENTS IN THE CYTOPLASM RESULTING FROM HEPATOCYTE INJURY.

  26. MALLORY'S HYALIN

  27. MALLORY'S HYALIN • THEY ARE MOST COMMON IN ALCOHOLIC HEPATITIS (PREVALENCE OF 65%) AND ALCOHOLIC CIRRHOSIS (PREVALENCE OF 51%) • THEY ARE A RECOGNIZED FEATURE OF WILSON'S DISEASE (25%), PRIMARY BILIARY CIRRHOSIS (24%), HEPATOCELLULAR CARCINOMA (23%) AND MORBID OBESITY (8%)

  28. ALCOHOLIC HEPATITIS MORPHOLOGY CONTINEUD NEUTROPHILIC REACTION , LYMPHOCYTES MACROPHAGES FIBROSIS – SINUSOIDAL PERIVENULAR FIBROSIS.CHOLESTASIS MILD HEMOSIDERIN DEPOSITION IN HEPATOCYTES & KUPFFER CELLS

  29. ALCOHOLIC LIVER DISEASE-ALCOHOLIC HEPATITIS

  30. ALCOHOLIC CIRRHOSIS(FINAL & IRREVERSIBLE FORM) EVOLVES SLOWLY & INSIDIOUSLY GROSSLY- ENLARGED YELLOW TAN - OVER 2 Kg . MICRONODULAR(LESS THAN 0.3cm).

  31. ALCOHOLIC CIRRHOSIS(FINAL & IRREVERSIBLE FORM) WITH TIME LARGER NODULES - HOBNAIL APPEARANCE ON THE SURFACE. OVER THE SPAN OF YEARS –BROWN SHRUNKEN NONFATTY ORGAN LESS THAN 1Kg (NORMAL -1.5Kg) – END-STAGE ALCOHOLIC CIRRHOSIS

  32. ALCOHOLIC CIRRHOSIS

  33. CIRRHOSIS– GROSS FEATURES,MICROSCOPY SCANNER VIEW

  34. MACRONODULAR CIRRHOSIS

  35. NORMAL LIVER HISTOLOGY

  36. NORMAL LIVER HISTOLOGY

  37. CIRRHOSIS- MICROSCOPY

  38. CLINICAL FEATURES HEPATIC STEATOSIS – MILD INCREASED BILIRUBIN & ALKALINE PHOSPHATASE

  39. ALCOHOLIC HEPATITIS ACUTE ONSET AFTER A BOUT OF HEAVY DRINKING,MAY BE SEVERE-FULMINANT HEPATIC FAILURE .

  40. ALCOHOLIC HEPATITIS LABORATORY INVESTIGATIONS 1.HYPERBILIRUBINEMIA 2.ELEVATED ALKALINE PHOSPHATASE 3.NEUTROPHILIC LEUKOCYTOSIS.

  41. ALCOHOLIC HEPATITIS 4. ELEVATED ALENINE AMINOTRANSFERASE (ALT,ALSO KNOWN AS SGPT) & ASPERTATATE AMINOTRANSFERASE(AST ,ALSO KNOWN ASSGOT)

  42. CLINICAL FEATURES MALAISE ,ANOREXIA , WEIGHT LOSS UPPER ABDOMINAL DISCOMFORT, TENDERNESS HEPATOMEGALY - FEVER

  43. PROGNOSIS OF ALCOHOLIC HEPATITIS UNPREDICTABLE EACH BOUT CARRIES-10% -20 % RISK OF DEATH CAN SUPERIMPOSED ON CIRRHOSIS PROPER NUTRITION & CESSATION OF ALCOHOL CONSUMPTION ALCOHOLIC HEPATITIS MAY CLEAR SLOWLY

  44. CLINICAL FEATURES OF ALCOHOLIC CIRRHOSIS FIRST SIGN IS RELATED TO PORTAL HYPERTENTION – ASCITIS, WASTED EXTREMITIES,CAPUT MEDOSE OR FIRST PRESENTATION MAY BE LIFE THREATENING VARICEAL HEMORRHAGE DEATH

  45. HEPATIC ENCEPHALOPATHY HEPATIC ENCEPHALOPATHY IS A DISORDER OF MENTAL ACTIVITY, NEUROMUSCULAR FUNCTION AND CONSCIOUSNESS THAT OCCURS AS A RESULT OF EITHER CHRONIC OR ACUTE LIVER FAILUR EVENTUALLY LEAD TO COMA DUE TO FAILURE OF DETOXICATING FUNCTION OF LIVER(MAINLY INCREASE IN BLOOD AMMONIA)

  46. CAPUT MEDUSAE CAPUT MEDUSAE IS THE APPEARANCE OF DISTENDED AND ENGORGED PARAUMBILICAL VEINS, WHICH ARE SEEN RADIATING FROM THE UMBILICUS ACROSS THE ABDOMEN TO JOIN SYSTEMIC VEINS. THE NAME CAPUT MEDUSAE ORIGINATES FROM THE APPARENT SIMILARITY TO MEDUSA'S HAIR(GREEK MYTHOLOGY FIGURE)

  47. CAPUT MEDUSAE

  48. LABORATORY FINDINGS IN ALCOHOLIC CIRRHOSIS 1. ELEVATED AMINOTRANSFERASE 2. HYPERBILIRUBINEMIA 3. VARIABLE ELEVATION OF ALKALINE PHOSPHATASE 4. HYPOPROTEINEMIA 5. ANEMIA

  49. CAUSES OF DEATH 1.MASSIVE GIT HEMORRHAGE –FROM ESOPHAGEAL VARICES 2.HEPATIC FAILURE 3.INTERCURRENT INFECTION 4.HEPATORENAL SYNDROME AFTER A BOUT OF ALCOHOLIC HEPATITIS 5.HEPATOCELLULAR CARCINOMA – 3%-6% OF CASES

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