Cirrhosis

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Pathology of Hepatitis & CirrhosisVenkatesh Murthy ShashidharAssociate Professor of PathologyFiji School of Medicine

A Commitment to Excellence Normal Liver

Autopsy1.5 kg, wedge shape4 lobes, Right, left, Caudate, Quadrate.Double blood supplyHepatic arteriesPortal Venous bloodAcini / Portal triad.Lobules central. V

Normal Liver - Infant

CT Upper abdomen - Normal

VHP- Upper abdomen

Normal Liver - MicroscopyLiver Functions:Metabolism Carbohydrate, Fat & ProteinSecretory bile, Bile acids, salts & pigmentsExcretory Bilirubin, drugs, toxinsSynthesis Albumin, coagulation factorsStorage Vitamins, carbohydrates etc.Detoxification toxins, ammonia, etc.JaundiceYellow discoloration of skin & sclera due to excess serum bilirubin. >40umol/l, (3mg/dl)Conjugated & Unconjugated types Obstructive & Non Obstructive (clinical)Pre-Hepatic, Hepatic & Post Hepatic typesJaundice - Not necessarily liver disease *

Pathology of HepatitisHepatitis:Hepatitis: Inflammation of LiverViral, Alcohol, immune, Drugs & ToxinsBiliary obstruction gall stones.Acute, Chronic & Fulminant - typesViral Hepatitis Specific Heptitis A, B, C, D, E, & other Systemic - CMV, EBV, other.Pattern of Viral Hepatitis:Carrier state / Asymptomatic phaseAcute hepatitisChronic HepatitisChronic Persistent Hepatitis (CPH)Chronic Active Hepatitis (CAH)Fulminant hepatitisCirrhosisHepatocellular Carcinoma

Acute - Hepatitis - Chronic

Acute Hepatitis:Swelling and ApoptosisPiecemeal or Bridging, panacinar necrosisInflammation lymphocytes, MacrophagesGround glass hepatocytes HBVMild fatty change HCVPortal inflammation and CholestasisFulminant Hepatitis:Hepatic failure with in 2-3 weeks.Reactivation of chronic or acute hepatitisMassive necrosis, shrinkage, wrinkledCollapsed reticulin networkOnly portal tracts visibleLittle or massive inflammation timeMore than a week regenerative activityComplete recovery or - cirrhosis.Chronic Hepatitis:Persistent & Active types. CPH/CAHLymphoid aggregatesPeriportal fibrosisNecrosis with fibrosis bridging fibrosis.Cirrhosis regenerating nodules.

Acute viral Hepatitis:

Acute viral Hepatitis:

Acute viral Hepatitis:

Acute viral Hepatitis C:

Liver Biopsy CPH:

Liver Biopsy Cirrhosis

Viral Hepatitis: MicrobiologyVirusHep-A

Hep-B

Hep-CagentssRNAdsDNAssRNATransm.Feco-oralParenteralParenteralCarrier stateNone0.1-1.0%0.2-1.0%Chronic HepatitisNone5-10%>50%Pathology of Alcoholic Liver DiseaseAlcoholic Liver Injury:Ethyl alcohol : Common cause of acute/Chronic liver diseaseAlcoholic Liver disease - PatternsFatty change, Acute hepatitis (Mallory Hyalin)Chronic hepatitis with Portal fibrosis Cirrhosis, Chronic Liver failureAll reversible except cirrhosis stage.Alcoholic Liver Injury: PathogenesisAcetaldehyde metabolite hepatotoxicDiversion of metabolism fat storage.Oxidation of ethanol NAD to NADH. NAD is required for the oxidation of fat..Increased peripheral release of fatty acids.Inflammation, Portal bridging fibrosisStimulates collagen synthesis fibrosis.Micronodular cirrhosis.Alcoholic Liver Damage

Alcoholic Fatty Liver

Steatosis in AlcoholismAlcoholic Fatty Liver

Alcoholic Fatty Liver

Cirrhosis in Alcoholism

Alcoholic Cirrhosis

Bilirubin MetabolismBloodConjugated & ConjugatedUrine Urobilinogen Stool StercobilinCommon Causes of JaundicePre Hepatic (Acholuric) - HemolyticUnconjugated/Indirect Bil, pale urineHepatic Viral, alcohol, toxins, drugsLiver damage - unconjugatedSwelling, canalicular obstruction - ConjugatedPost Hepatic (Obstructive) Stone, tumorConjugated/Direct Bil, High colored urine, Jaundice

Jaundice

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Pathology of Alcoholic Liver DiseaseDefinition:Diffuse disorder of liver characterised by;Complete loss of normal architecture,Replaced by extensive fibrosis with, Regenerating parenchymal nodules.IntroductionCirrhosis is common end result of many chronic liver disorders.Diffuse scarring of liver follows hepatocellular necrosis of hepatitis.Inflammtion healing with fibrosis - Regeneration of remaining hepatocytes form regenerating nodules.Loss of normal architecture & function.Normal Liver

Cirrhosis

Normal Liver Histology

CVPTCirrhosis

Fibrosis

Regenerating NoduleEtiology of CirrhosisAlcoholic liver disease60-70%Viral hepatitis10%Biliary disease5-10%Primary hemochromatosis5%Cryptogenic cirrhosis10-15%Wilsons, 1AT defrarePathogenesis:Hepatocyte injury leading to necrosis.Alcohol, virus, drugs, toxins, genetic etc..Chronic inflammation - (hepatitis).Bridging fibrosis.Regeneration of remaining hepatocytes Proliferate as round nodules.Loss of vascular arrangement results in regenerating hepatocytes ineffective.Cirrhosis Features:Liver Failure Parenchymal regeneration but why ..??.Portal obstruction, Porta systemic shuntsPortal hypertension, SplenomegalyJaundice, Coagulopathy, hypoproteinemia, toxemia, Encephalopathy, BRAIN

LIVER

Toxic N2 metabolitesFrom IntestinesPorta systemic shuntsPathogenesis of Hepatic EncephalopathyMicronodular cirrhosis

Ascitis in Cirrhosis

Ascitis in Cirrhosis

Micronodular cirrhosis:

Micronodular cirrhosis:

Alcoholic Hepatitis

Macronodular Cirrhosis

Liver Biopsy Cirrhosis

Liver Biopsy Cirrhosis:

Nutmeg Liver-Cardiac Sclerosis

Clinical FeaturesHepatocellular failure.Malnutrition, low albumin & clotting factors, bleeding.Hepatic encephalopathy.Portal hypertension.Ascites, Porta systemic shunts, varices, splenomegaly.Bleeding in Liver disease:vitamin K in liver gamma-carboxyglutamic acid for coagulation factors II, VII, IX, and X. Liver disease factor VII is the first to go so the defect will appear initially in the extrinsic pathway, i.e., abnormal PT. When severe it affects both pathways.

CirrhosisClinical Features

Gynaecomastia in cirrhosis

Porta-systemic anastomosis: Prominent abdominal veins.

MRI Cirrhosis

Complications:Congestive splenomegaly.Bleeding varices.Hepatocellular failure.Hepatic encephalitis / hepatic coma.Hepatocellular carcinoma.

Hepatocellular Carcinoma

Conclusions:Common end result of diffuse liver damage. (Viral hepatitis, Alcohol, congenital, drugs, toxins & Idiopathic)Characterised by diffuse loss of architecture.Fibrous bands & regenerating nodules distort and abstruct blood flow. (inefficient function)Hepatocellular insufficiency & portal hypertension.Shrunken, scarred liver, ascitis, spleenomegaly, liver failure, CNS toxicity.Conclusions: Hepatitis.Hepatitis Alcohol, Virus (ABCD), DrugsHepatocyte damage inflammation Acute / Chronic (Active / Persistent)Fever, Jaundice, Malaise, Fat intolerance.Complications.Alcohol NAD, Acetaldehyde metabolismFatty liver Necrosis Cirrhosis.

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