DEFINITION CIRRHOSIS END STAGE CHRONIC LIVER DISEASE CHARACTERISED

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

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

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

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

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

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

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

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

ALCOHOLIC LIVER DISEASES 9

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

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 13

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

OTHER FACTORS ACCELERATING ALCOHOLIC LIVER DISEASE MALNUTRITION & VITAMIN DEFICIENCY - SPECIALLY THIAMINE & VITAMINE B 12 DUE TO IMPAIRED DIGESTIVE FUNCTION DUE TO DAMAGE TO GASTRIC & INTESTINAL MUCOSA & PANCREATITIS. 15

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

HEPATIC STEATOSIS 17

HEPATIC STEATOSIS REVERSIBLE- MICROSCOPIC FEATURES MICROVASICULAR MACROVASICULARCENTRILOBULAR INITIALLY CONTINUED INTAKE OF ALCOHOLFIBROSIS AROUND THE CENTRAL VEIN EXTENDING IN TO SINUSOIDS. 18

HEPATIC STEATOSIS 19

HEPATIC STEATOSIS 20

HEPATIC STEATOSIS 21

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

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. 23

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. 24

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

MALLORY'S HYALIN 26

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%) 27

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

ALCOHOLIC LIVER DISEASEALCOHOLIC HEPATITIS 29

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ALCOHOLIC CIRRHOSIS (FINAL & IRREVERSIBLE FORM) EVOLVES SLOWLY & INSIDIOUSLY GROSSLY- ENLARGED YELLOW TAN OVER 2 Kg. MICRONODULAR(LESS THAN 0. 3 cm). 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 1 Kg (NORMAL -1. 5 Kg) – ENDSTAGE 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 AS SGOT) 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 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 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 50