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" With ordinary talent and

extraordinary perseverance, all

things are attainable."- Thomas E. Buxton

" Achievement is connected

with action, not in genes..!- Conrad Hilton


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Pathology ofHepatitis & Cirrhosis

Venkatesh Murthy ShashidharAssociate Professor of Pathology

Fiji School of Medicine

A Commitment to Excellence


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Normal Liver


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Autopsy

1.5 kg, wedge shape

4 lobes, Right, left,

Caudate, Quadrate.

Double blood supply

Hepatic arteries

PortalVenous blood

Acini / Portal triad.

Lobulescentral. V


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Normal Liver - Infant


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CT Upper abdomen - Normal


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VHP- Upper abdomen


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Normal Liver - Microscopy


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Liver Functions:

MetabolismCarbohydrate, Fat & Protein

Secretorybile, Bile acids, salts & pigments

ExcretoryBilirubin, drugs, toxins

SynthesisAlbumin, coagulation factors

StorageVitamins, carbohydrates etc.

Detoxificationtoxins, ammonia, etc.


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Jaundice

Yellow discoloration of skin & sclera due toexcess serum bilirubin. >40umol/l, (3mg/dl)

Conjugated & Unconjugated types

Obstructive & Non Obstructive (clinical)

Pre-Hepatic, Hepatic & Post Hepatic types

Jaundice - Not necessarily liver disease *


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Pathology of

Hepatitis


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Hepatitis:

Hepatitis: Inflammation of Liver

Viral, Alcohol, immune, Drugs & Toxins

Biliary obstructiongall stones.

Acute, Chronic & Fulminant - types

Viral Hepatitis

SpecificHeptitis A, B, C, D,E, & other

Systemic - CMV, EBV, other.


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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


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Acute - Hepatitis- Chronic


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Acute Hepatitis:

Swelling and Apoptosis

Piecemeal or Bridging, panacinar necrosis

Inflammationlymphocytes, Macrophages

Ground glass hepatocytesHBV

Mild fatty changeHCV

Portal inflammation and Cholestasis


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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 inflammationtime

More than a weekregenerative activity

-


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Chronic Hepatitis:

Persistent & Active types. CPH/CAH

Lymphoid aggregates

Periportal fibrosis

Necrosis with fibrosisbridging fibrosis.

Cirrhosisregenerating nodules.


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Acute viral Hepatitis:


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Acute viral Hepatitis C:


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Liver BiopsyCPH:


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Liver BiopsyCirrhosis


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Viral Hepatitis: Microbiology

Virus Hep-A Hep-B Hep-C

agent ssRNA dsDNA ssRNA

Transm. Feco-oral Parenteral Parenteral

Carrierstate None 0.1-1.0% 0.2-1.0%

Chronic

Hepatitis

None 5-10% >50%


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Alcoholic Liver Injury: Pathogenesis

Acetaldehydemetabolitehepatotoxic

Diversion of metabolismfat storage.

Oxidation of ethanol NAD to NADH. NAD isrequired for the oxidation of fat..

Increased peripheral release of fatty acids.

Inflammation, Portal bridging fibrosisStimulates collagen synthesisfibrosis.

Micronodular cirrhosis.


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Alcoholic Liver Damage


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Alcoholic Fatty Liver


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Steatosis in Alcoholism


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Cirrhosis in Alcoholism
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Alcoholic Cirrhosis


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BilirubinMetabolism

BloodConjugated &

Conjugated

UrineUrobilinogen

StoolStercobilin


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Common Causes of Jaundice

Pre Hepatic (Acholuric) - Hemolytic

Unconjugated/Indirect Bil, pale urine

HepaticViral, alcohol, toxins, drugs

Liver damage - unconjugated

Swelling, canalicular obstruction - Conjugated

Post Hepatic (Obstructive)Stone, tumor

Conjugated/Direct Bil, High colored urine,


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Jaundice


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Time is the best kept

secret of the rich..!

Jim Rohn


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Pathology of

AlcoholicLiver Disease


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Definition:

1. Diffusedisorder of liver characterised by;

2. Complete loss of normal architecture,

3. Replaced by extensive fibrosis with,

4. Regeneratingparenchymalnodules.


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Introduction

Cirrhosis is common end result of manychronic liver disorders.

Diffuse scarring of liverfollows

hepatocellular necrosis of hepatitis.

Inflammtionhealing with fibrosis -

Regeneration of remaining hepatocytes form

regenerating nodules.

Loss of normal architecture & function.


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Normal Liver


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Cirrhosis


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Normal Liver Histology

CV

PT


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Cirrhosis

Fibrosis

Regenerating Nodule

Eti l f Ci h i


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Etiology of Cirrhosis

Alcoholic liver disease 60-70%

Viral hepatitis 10%

Biliary disease 5-10%

Primary hemochromatosis 5%

Cryptogenic cirrhosis 10-15%

Wilsons, 1AT def rare


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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.


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Cirrhosis Features:

Liver Failure

Parenchymal regeneration but why ..??.

Portal obstruction, Porta systemic shunts

Portal hypertension, Splenomegaly

Jaundice, Coagulopathy, hypoproteinemia,

toxemia, Encephalopathy,


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BRAIN

LIVER

Toxic N2 metabolites

From Intestines

Porta systemic

shunts

Pathogenesis of Hepatic Encephalopathy


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Micronodular cirrhosis

A iti i Ci h i


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Ascitis in Cirrhosis

A iti i Ci h i


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Ascitis in Cirrhosis


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Micronodular cirrhosis:


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Micronodular cirrhosis:

Al h li H titi


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Alcoholic Hepatitis


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Macronodular Cirrhosis

Liver Biopsy Cirrhosis


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Liver BiopsyCirrhosis


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Nutmeg Liver-Cardiac Sclerosis

Clinical Features


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Clinical Features

Hepatocellular failure. Malnutrition, low albumin & clotting factors,

bleeding.

Hepatic encephalopathy.

Portal hypertension.

Ascites, Porta systemic shunts, varices,

splenomegaly.

Bleeding in Liver disease:


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Bleeding in Liver disease:

vitamin Kin liver gamma-carboxyglutamicacidfor coagulation factors II, VII, IX, and X.

Liver disease factor VII is the first to go

so the defect will appear initially in theextrinsic pathway, i.e., abnormal PT. When

severe it affects both pathways.


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Gynaecomastia in cirrhosis


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Gynaecomastia in cirrhosis

Porta-systemic anastomosis:


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yProminent abdominal veins.


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MRI Cirrhosis

Complications:


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Complications:

Congestive splenomegaly.

Bleeding varices.

Hepatocellular failure.

Hepatic encephalitis / hepatic coma.

Hepatocellular carcinoma.



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Conclusions:


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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 distortand abstruct blood flow. (inefficient function)

Hepatocellular insufficiency & portal

hypertension.Shrunken, scarred liver, ascitis,

spleenomegaly, liver failure, CNS toxicity.

Conclusions: Hepatitis


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Conclusions: Hepatitis.

HepatitisAlcohol, Virus (ABCD), Drugs

Hepatocyte damageinflammation

Acute / Chronic (Active / Persistent)

Fever, Jaundice, Malaise, Fat intolerance.

Complications.

AlcoholNAD, Acetaldehydemetabolism

Fatty liver Necrosis Cirrhosis.


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Learn from the

mistakes of others.You can't live long

enough to make them

all yourself!

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