Cirrhosis

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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 of Hepatitis Cirrhosis

• Venkatesh Murthy Shashidhar
• Associate 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
• Portal Venous blood
• Acini / Portal triad.
• Lobules central. 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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(No Transcript)
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Normal Liver - Microscopy
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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.

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Jaundice

• Yellow discoloration of skin sclera due to
  excess serum bilirubin. gt40umol/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 obstruction gall stones.
• Acute, Chronic Fulminant - types
• Viral Hepatitis
• Specific Heptitis 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
• Inflammation lymphocytes, Macrophages
• Ground glass hepatocytes HBV
• Mild fatty change HCV
• 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 inflammation time
• More than a week regenerative activity
• Complete recovery or - cirrhosis.

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Chronic Hepatitis

• Persistent Active types. CPH/CAH
• Lymphoid aggregates
• Periportal fibrosis
• Necrosis with fibrosis bridging fibrosis.
• Cirrhosis regenerating nodules.

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Acute viral Hepatitis
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Acute viral Hepatitis
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Acute viral Hepatitis
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Acute viral Hepatitis C
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Liver Biopsy CPH
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Liver Biopsy Cirrhosis
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Viral Hepatitis Microbiology
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Pathology of Alcoholic Liver Disease
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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.

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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.

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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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Alcoholic Fatty Liver
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Alcoholic Fatty Liver
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Cirrhosis in Alcoholism
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Alcoholic Cirrhosis
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Bilirubin Metabolism

• Blood
• Conjugated Conjugated
• Urine Urobilinogen
• Stool Stercobilin

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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,

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Jaundice
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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 Alcoholic Liver Disease
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Definition

• Diffuse disorder of liver characterised by
• Complete loss of normal architecture,
• Replaced by extensive fibrosis with,
• Regenerating parenchymal nodules.

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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.

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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
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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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Pathogenesis of Hepatic Encephalopathy
BRAIN LIVER Toxic N2 metabolites From
Intestines
Porta systemic shunts
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Micronodular cirrhosis
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Ascitis in Cirrhosis
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Ascitis in Cirrhosis
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Micronodular cirrhosis
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Micronodular cirrhosis
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Alcoholic Hepatitis
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Macronodular Cirrhosis
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Liver Biopsy Cirrhosis
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Liver Biopsy Cirrhosis
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Nutmeg Liver-Cardiac Sclerosis
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Clinical Features

• Hepatocellular failure.
• Malnutrition, low albumin clotting factors,
  bleeding.
• Hepatic encephalopathy.
• Portal hypertension.
• Ascites, Porta systemic shunts, varices,
  splenomegaly.

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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.

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CirrhosisClinical Features
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Gynaecomastia in cirrhosis
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Porta-systemic anastomosis Prominent abdominal
veins.
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MRI Cirrhosis
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Complications

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

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Hepatocellular Carcinoma
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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 distort and
  abstruct blood flow. (inefficient function)
• Hepatocellular insufficiency portal
  hypertension.
• Shrunken, scarred liver, ascitis, spleenomegaly,
  liver failure, CNS toxicity.

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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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