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2. EpidemiologyEpidemiology40% cases asymptomaticIt is the 12thleading cause of death inUnited States.Approximately 30,000 to 50,000 deathsper yearAdditional 10,000 deaths due to livercancer secondary to cirrhosis 3. CirrhosisCirrhosisDefinition: It is the end stage of liverdisease characterized byBridging fibrous septa in the form ofdelicate bands or broad scar linkingportal tracts with one another and portaltracts with terminal hepatic veinParenchymal nodules containinghepatocytes encircled by fibrosisDisruption of architecture entire of liver 4. Normal LiverNormal Liver 5. Normal Liver HistologyNormal Liver HistologyCVPT 6. Histological classificationHistological classificationMicronodular Cirrhosis :Thickregular septa and regenerating smallnodules varying little in size andinvolvement of every lobule, mainlyseen in alcoholic cirrhosis.Size of the nodule is less than 1cm 7. Histological classificationHistological classificationMicronodular Cirrhosis 8. Micronodular cirrhosis:Micronodular cirrhosis: 9. Histological classificationHistological classificationMacronodular Cirrhosis :Septaand nodules of variable size andnormal lobules in larger nodules,mainly seen in post necroticcirrhosis.Size of the nodule is more than 1cm 10. Histological classificationHistological classificationMacronodular Cirrhosis 11. Histological classificationHistological classificationMacronodular Cirrhosis 12. Aetiological classificationAetiological classificationViral: Chronic Hepatitis B, Hepatitis Cinfection.AlcoholNon alcoholic fatty liverMetabolic disorder:Haemochromatosis, Wilsonsdisease,Alpha-1 antripsin deficiency.Autoimmune HepatitisPrimary biliary cirrhosis 13. Aetiological classificationAetiological classificationProlong cholestasisHepatic venous outflow obstruction:Constrictive pericarditis, Veno occlusivedisease, Budd chairi syndrome.Drugs: Methotraxate, Amioderone.Cryptogenic: Unknown origin. 14. Etiology of CirrhosisEtiology of CirrhosisAlcoholic liver disease 60-70%Viral hepatitis 10%Biliary disease 5-10%Primary hemochromatosis 5%Cryptogenic cirrhosis 10-15%Wilsons, 1AT def rare 15. Pathogenesis of cirrhosisPathogenesis of cirrhosisHepatocellular deathRegenerationProgressive fibrosisNormal liver consists of I, III , IV Collagenin portal tracts and around central veins.A delicate reticulin network of IV collagenin the space of disse ( b/w sinusoidalendothelial cell and hepatocyte.) Incirrhosis there is deposition of type I, IIIand other components of ECM aredeposited in all portion of lobule . 16. Pathogenesis of cirrhosisPathogenesis of cirrhosisThe induction of fibrosis occurs withactivation of hepatic stellate cells,resulting in formation of increasedamounts of collagen & othercomponents of extracellular matrix.Stimuli :o1.Chr.inflammation cytokines like TNF,Lymphotoxin, IL-1o 2.Cytokine production by injuredKupffer cells, endothelial cells,hepatocytes, bile duct epithelial cells 17. Pathogenesis of cirrhosisPathogenesis of cirrhosiso 3.Disruption of ECMo 4.Direct stimulation of stellate cells bytoxinsOn the other hand portal hypertensiondeveloped in following way 18. Pathogenesis of cirrhosisPathogenesis of cirrhosisNecrosis of hepatic parenchyma due to some injuryCollapse of hepatic lobuleFormation of diffuse fibrous septaNodular regrowth of liver cellsAltered hepatic vasculaturePortal blood flow is impairedDevelopment of portal hypertensionCirrhosis of liver 19. CirrhosisCirrhosisFibrosisRegenerating Nodule 20. Liver Biopsy CirrhosisLiver Biopsy Cirrhosis 21. Liver Biopsy Cirrhosis:Liver Biopsy Cirrhosis: 22. Alcoholic cirrhosisAlcoholic cirrhosisEthyal alcohol is a common cause ofacute/chronic liver disease.Paterns of alcoholic liver disease:1. Fatty change2. Acute Hepatitis3. Chronic hepatitis with fibrosis4. Cirrhosis, Chronic liver failureAll are reversible except cirrhosisstage 23. Pathogenesis of Alcoholic cirrhosisPathogenesis of Alcoholic cirrhosisAcetaldehyde metabolite hepatotoxicDiversion of metabolism fat storageOxidation of ethanol NAD to NADH. NAD isrequired for the oxidation of fat..Increased peripheral release of fatty acidsInflammation, Portal bridging fibrosisStimulates collagen synthesis fibrosisMicronodular cirrhosis 24. Alcoholic Liver DamageAlcoholic Liver Damage 25. Alcoholic Fatty LiverAlcoholic Fatty Liver 26. Alcoholic Fatty LiverAlcoholic Fatty Liver 27. Alcoholic Fatty LiverAlcoholic Fatty Liver 28. Clinical Feature of cirrhosisClinical Feature of cirrhosisSymptoms: Non specific symptoms:weakness, fatigue, anorexia JaundiceAbdominal distensionSwelling if legsLoss of libido in males and amenorrhoeain females.Low grade feverLess commonly symptoms of complicationsuch as epistaxis, heamatemesis,melaena, menorrhagia. 29. Clinical Feature of cirrhosisClinical Feature of cirrhosis 30. Clinical Feature of cirrhosisClinical Feature of cirrhosisSigns: Jaundice Fetor hepaticus Pedal oedema Generalized wasting Hands: Leuconychia, clubbing, Jaundice,Flapping tremor, palmar erythema, dupuytrenscontructure 31. Clinical Feature of cirrhosisClinical Feature of cirrhosisParotid enlargement in alcoholiccirrhosisLoss of secondary sexual hair, axillaryand pubicGynaecomastia in males and breastatrophy in females.Testicular atrophy in spider naevi in the upper limbsand chest, generalized pigmentation,purpura, bruising 32. Clinical Feature of cirrhosisClinical Feature of cirrhosisAbdomen :Dilated abdominal vessels, caput medusa AscitisSplenomegalyHepatomegalyHaemorrhoid 33. Palmar erythemaPalmar erythema 34. Clinical Feature of cirrhosisClinical Feature of cirrhosis 35. Ascitis in CirrhosisAscitis in Cirrhosis 36. Porta-systemic anastomosis:Porta-systemic anastomosis:Prominent abdominal veins.Prominent abdominal veins. 37. Gynaecomastia in cirrhosisGynaecomastia in cirrhosis 38. Splenomegaly in cirrhosisSplenomegaly in cirrhosis 39. Submucosal veins in the esophagus become dilated. TheseSubmucosal veins in the esophagus become dilated. Theseare known as esophageal varices. Varices are seen here inare known as esophageal varices. Varices are seen here inthe lower esophagus as linear blue dilated veins. There isthe lower esophagus as linear blue dilated veins. There ishemorrhage around one of them. Such varices are easilyhemorrhage around one of them. Such varices are easilyeroded, leading to massive gastrointestinal hemorrhageeroded, leading to massive gastrointestinal hemorrhage 40. Lab investigationsLab investigationsLiver function: serum albumin andprothrombin are the best indicator of liverfunctions.o Albumin is less than 28 g/loProthrombin time increase according to theseverity of the diseaseoSerum bilirubin is elevatedLiver biochemistry: this can be normaldepending on the severity of the cirrhosisoALP is elevatedoALT is elevated 41. Lab investigationsLab investigationsSerum electrolytes: A low sodium indicatesevere disease due to defect in the freewater clearance or excess diuretictherapy. Serum Creatinine: An elevationconcentration of more than 130micromol/lindicate worse prognosisIn addition Alpha feto protein more than200ng/ml strongly suggest that hepatocellular carcinoma 42. Lab investigationsLab investigations Other test to identify the causeViral marker : HBsAg,Anti HCVAlpha-1 antitripsinSerum copper, CaeruloplasminSerum immunoglobulinAuto antibodyIron indices,ferritin 43. ImagingImagingUltrasonogram examinition: Liver may show coarse ecotexture Dilated portal veins Splenomegaly AscitisCT scan may show hepatosplenomegalyand dilated collaterals are seen in chronicliver diseaseUpper GI endoscopy: Oesophageal varicesmay seen LIVER BIOPSY IS CONFIRMATORY 44. Prognosis of CirrhosisPrognosis of CirrhosisPoor prognostic indicator of cirrhosis:Blood tests low Serum albumin is( 130micromol/l)ClinicalPersistent jaundiceAscitisFailure of response to therapyHemorrhage from the varices,particolarly withpoor liver function 45. Prognosis of CirrhosisPrognosis of CirrhosisNeuropsychiatric complications developingwith progressive liver failurePersistent hypertensionSmall liverAetiology eg.alcoholic cirrhosis if thepatient continue to drink alcohol 46. Prognosis of CirrhosisPrognosis of CirrhosisPrognosis can be assessed by usingCHILD-PUGH CLASSIFICATIONPrameterAscitis None Mild Moderate/SevereEnchaphalopathyNone Mild MarkedBilirubin 3mg/dlAlbumin >3.5g/dl 2.8-3.5g/dl