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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:
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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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Alcoholic Fatty Liver
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Alcoholic Fatty Liver
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Cirrhosis in Alcoholism
http://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=/websites/emedicine/med/images/Large/2268MED0101-01.jpg&template=izoom2 -
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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.
Hepatocellular Carcinoma
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Hepatocellular Carcinoma
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!