pathology of cholestasis

8/6/2019 Pathology of Cholestasis

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a o ogy o o es as s

Cholestasis

Bile formation

Bile flow

Definition

Histopathologic Clinical

Bile within elements of liver

Associated with secondary cell injury

Substances normally excreted into

bile are retained

Causes of Cholestasis

Hepatocellular Type Obstructive Type

Hepatocellular dysfunction Intra-hepatic obstruction

(small bile duct)Extra-hepatic obstruction

(large bile duct)

Hepatitis

Alcoholic liver disease

Primary biliary cirrhosis

-1 antitrypsin deficiency

Inborn errors of bile acid synthesis

Drug induced cholestasis

Progressive familial intrahepatic

cholestasis

Stones in common bile duct

Pancreatic tumour

Biliary atresia

Choledocal cyst

Cholelithiasis

Primary sclerosing choleangitis

Alagille syndrome

Pregnancy

Sensitivity of bile ducts to estrogen

Cholestasis

y Often develops during 2nd

, 3rd

trimesters of pregnancy

y 2nd

most common cause of jaundice during pregnancy

y Generalized itching (pruritus gravidarum) (only symptom experienced)

y Run in families

y Symptoms disappear within 2-4 weeks after babys birth

May reappear if pregnant again

y Birth control pills (symptoms disappear after women stop using)

Neonatal Jaundice

Physiological Pathological

Phase 1

Term infants

y Jaundice lasts for 5 days

y Bilirubin

Perterm infants

y Jaundice lasts for a week

y Bilirubin

Phase 2

Bilirubin decline for 2 weeksPreterm infants

y Last more than 1 month

Babies who receive exclusive breast

feeding

y Last more than 1 month

Clinical jaundice appearing in 1st

24h

Bilirubin

Hyperbilirubinemia

Bile Duct

Normal Biliary Obstruction

Bile Secretion

Normal

Abnormal

Cholestasis

Retention of bile salts

Results in injury to biological membranes throughout body

Liver (most affected)

Retention of hydrophobic bile salts

(results in their incorporation into membranes)

Alter membrane fluidity, function

Bile salt injure hepatocyte membranes

(important amplifier of cholestasis)

Retention of secondary cholestatic bile acids (eg. l ithocholic acid)

Results in further membrane injury

Retention of cholesterol

Cholesterol content of membranes

Fluidity

Impair function of integral membrane proteins

Further retention of damaging substances

Accelerated membrane injury, dysfunction

Generalized failure of excretory mechanism for bile



Clinical Features

Jaundice

y Absent in partial obstruction

y Yellowish discoloration of skin

y Excess bilirubin

y > 2.0 2.5 mg/dl

y Disturbance in bilirubin production, clearance

Pruritus (bile acids)

Cholesterol deposits on skin

Laboratory Features

Dark urine

Conjugated bilirubin

Bile acids

Cholesterol

Serum Alkaline phosphatase

Transaminases

Morphology

Normal

Bile pigments within hepatocytes, canaliculi

Hepatocytes larger

Apoptosis

Mild Bile Duct Proliferation

Portal fibrosis



Specific Cholestatic Disorders

Large Bile Ducts Small Bile Ducts Hepato-cellular

Acute Acute biliary

obstruction

Acute cholangit is Pure cholestasis

Drug injury Drug injury

Compound

cholestasis

Chronic Chronic biliary

obstruction

Primary biliary

cirrhosis

Drug injury

Progressive familia l

cholestasisPrimary sclerosing

cholangitis

Primary sclerosing

cholangitis

Biliary Obstruction

Mechanical blockage of

y Large intrahepatic bile ducty Extra hepatic duct

Can lead to bacterial cholangitis, sepsis

Causes

Morphology

Extrahepatic biliary atresia

Inflammation with stricture of hepatic, common bile ducts

Cholestasis with intrahepatic bile duct proliferation, fibrosis, cirrhosis

Extrahepatic biliary atresia

Brown-green bile plugs

Bile duct proliferation

Extensive fibrosis

Morphology (cont.)

Primary Biliary Cirrhosis(Rare autoimmune disease)

Destruction of bile ductules (within triads of liver)

Cholestasis

Acute Chronic

Hepatocyte injury

Degeneration

Inflammatory cell infiltration

(acute inflammation)

Repair

Restoration of normal architecture

Foamy changes of hepatocytes

Focal destruction of parenchyma

Unrelieved obstruction

y Portal tract fibrosis

y End stage cirrhosis

Cirrhosis

End stage of liver disease

Bridging fibrous septae

Disruption of entire architecture of liverParenchymal nodules

y Micronodular (nodules < 3mm) Alcoholic

y Macronodular (nodules > 3mm) Hepatitis C infection

Macronodular Cirrhosis

Morphology

Regenerative nodules of hepatocytes

Surrounded by fibrous connective tissue (bridges between portal tracts)

Bile plugs

Diagnosis

Biliary Obstruction Intrahepatic Cholestasis

Clinical

Radiological

Clinical

Radiological

Liver biopsy

pathology of cholestasis

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