"With ordinary talent and "With ordinary talent and extraordinary perseverance, all extraordinary perseverance, all things are attainable."things are attainable."- Thomas E. Buxton

"Achievement is connected "Achievement is connected with action, with action, not in genes..…!”not in genes..…!”- Conrad Hilton

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

‘‘Time’ is the best kept Time’ is the best kept secret of the rich..!secret of the rich..!

– Jim Rohn

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.

Learn from the Learn from the mistakes of others. mistakes of others. You can't live long You can't live long enough to make them enough to make them all yourself…!all yourself…!