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Pathology of Pathology of Hepatitis & CirrhosisHepatitis & Cirrhosis
Venkatesh Murthy ShashidharVenkatesh Murthy ShashidharAssociate Professor of Pathology
Fiji School of Medicine
A Commitment to Excellence… A Commitment to Excellence…
Normal Liver
Autopsy
1.5 kg, wedge shape
4 lobes, Right, left, Caudate, Quadrate.
Double blood supply
Hepatic arteries
Portal – Venous blood
Acini / Portal triad.
Lobules – central. V
Normal Liver - Infant
CT Upper abdomen - Normal
VHP- Upper abdomen
Normal Liver - Microscopy
Liver Functions:
Metabolism – Carbohydrate, Fat & Protein
Secretory – bile, Bile acids, salts & pigments
Excretory – Bilirubin, drugs, toxins
Synthesis – Albumin, coagulation factors
Storage – Vitamins, carbohydrates etc.
Detoxification – toxins, ammonia, etc.
Jaundice
Yellow 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 types
Jaundice - Not necessarily liver disease *
Pathology of Pathology of HepatitisHepatitis
Hepatitis:
Hepatitis: Inflammation of Liver
Viral, Alcohol, immune, Drugs & Toxins
Biliary obstruction – gall stones.
Acute, Chronic & Fulminant - types
Viral Hepatitis – Specific – Heptitis A, B, C, D, E, & other
Systemic - CMV, EBV, other.
Pattern of Viral Hepatitis:
Carrier state / Asymptomatic phase
Acute hepatitis
Chronic Hepatitis Chronic Persistent Hepatitis (CPH)
Chronic Active Hepatitis (CAH)
Fulminant hepatitis
Cirrhosis
Hepatocellular Carcinoma
Acute - Hepatitis - Chronic
Acute Hepatitis:
Swelling and Apoptosis
Piecemeal or Bridging, panacinar necrosis
Inflammation – lymphocytes, Macrophages
Ground glass hepatocytes – HBV
Mild fatty change – HCV
Portal inflammation and Cholestasis
Fulminant Hepatitis:
Hepatic failure with in 2-3 weeks.
Reactivation of chronic or acute hepatitis
Massive necrosis, shrinkage, wrinkled
Collapsed reticulin network
Only portal tracts visible
Little or massive inflammation – time
More than a week – regenerative activity
Complete recovery – or - cirrhosis.
Chronic Hepatitis:
Persistent & Active types. CPH/CAH
Lymphoid aggregates
Periportal fibrosis
Necrosis 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: Microbiology
Virus Hep-A Hep-B Hep-C
agent ssRNA dsDNA ssRNA
Transm. Feco-oral Parenteral Parenteral
Carrier state
None 0.1-1.0% 0.2-1.0%
Chronic Hepatitis
None 5-10% >50%
Pathology of Pathology of Alcoholic Alcoholic
Liver DiseaseLiver Disease
Alcoholic Liver Injury:
Ethyl alcohol : Common cause of acute/Chronic liver disease
Alcoholic Liver disease - Patterns Fatty change,
Acute hepatitis (Mallory Hyalin)
Chronic hepatitis with Portal fibrosis
Cirrhosis, Chronic Liver failure
All reversible except cirrhosis stage.
Alcoholic Liver Injury: Pathogenesis
Acetaldehyde – metabolite – hepatotoxic
Diversion 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 fibrosis
Stimulates collagen synthesis – fibrosis.
Micronodular cirrhosis.
Alcoholic Liver Damage
Alcoholic Fatty Liver
Steatosis in Alcoholism
Alcoholic Fatty Liver
Alcoholic Fatty Liver
Cirrhosis in Alcoholism
Alcoholic Cirrhosis
Bilirubin Metabolism
•Blood
•Conjugated & Conjugated
•Urine – Urobilinogen
•Stool – Stercobilin
Common Causes of Jaundice
Pre Hepatic (Acholuric) - Hemolytic Unconjugated/Indirect Bil, pale urine
Hepatic – Viral, alcohol, toxins, drugs Liver damage - unconjugated Swelling, canalicular obstruction - Conjugated
Post Hepatic (Obstructive) – Stone, tumor Conjugated/Direct Bil, High colored urine,
Jaundice
Jaundice
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Pathology of Pathology of Alcoholic Alcoholic
Liver DiseaseLiver Disease
Definition:
1. Diffuse disorder of liver characterised by;
2. Complete loss of normal architecture,
3. Replaced by extensive fibrosis with,
4. Regenerating parenchymal nodules.
Introduction
Cirrhosis 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
CV
PT
Cirrhosis
Fibrosis
Regenerating Nodule
Etiology of Cirrhosis
Alcoholic liver disease 60-70%
Viral hepatitis 10%
Biliary disease 5-10%
Primary hemochromatosis 5%
Cryptogenic cirrhosis 10-15%
Wilson’s, 1AT def rare
Pathogenesis: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 shunts…
Portal hypertension, Splenomegaly
Jaundice, Coagulopathy, hypoproteinemia, toxemia, Encephalopathy,
BRAIN
LIVER
Toxic N2 metabolitesFrom Intestines
Porta systemic shunts
Pathogenesis of Hepatic Encephalopathy
Micronodular 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 Features
Hepatocellular 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), Drugs…
Hepatocyte damage – inflammation
Acute / Chronic (Active / Persistent)
Fever, Jaundice, Malaise, Fat intolerance.
Complications.
Alcohol – NAD, Acetaldehyde – metabolism
Fatty liver Necrosis Cirrhosis.
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