Intrahepatic and Extrahepatic Cholestasis

Liver Disease and Function

• Can cause greenish-brown liver discoloration
• Intrahepatic cholestasis can occur due to liver injury, hemolysis, and inherited abnormalities of bile synthesis
• Extrahepatic cholestasis can occur due to intraluminal obstruction or extraluminal constriction

Types of Cholestasis

• Acute Intrahepatic Cholestasis: Bile plugs in canaliculi
• Chronic Intrahepatic Cholestasis: Bile taken up by Kupffer cells
• Acute Extrahepatic Obstruction: Portal area edema, neutrophilic infiltrate, proliferative reaction
• Chronic Extrahepatic Obstruction: Fibrosis in portal areas

Icterus

• Caused by hepatic dysfunction or prehepatic causes such as intravascular hemolysis
• Common cause in ruminants
• Horses can manifest icterus with acute hepatic dysfunction or obstruction, but icterus may or may not occur in horses with chronic hepatic disease
• Physiologic icterus can occur in horses when feed-deprived for days due to decreased bilirubin uptake by hepatocytes

Biliary Hyperplasia and Ductular Reaction

• Ductular reaction: special cells at the edges of the portal tract grow and can become either bile ducts or liver cells
• Can develop in injuries, cholestasis, and regions of hypoxia
• Can occur in response to many different types of liver damage

Liver Regeneration

• Liver can quickly regrow lost tissue
• A healthy animal can lose 2/3 of its liver without showing liver problems because the liver regrows through compensatory hyperplasia

Fibrosis

• Chronic liver injury leads to fibrosis
• Severe hepatic fibrosis can be lethal
• In the normal liver, collagens I and III are present in connective tissue of the portal tracts and around the terminal hepatic venule
• Collagen IV is the most abundant collagen type in the sinusoids
• Hepatic fibrosis involves increased ECM and changes in collagen types and their locations
• A severely fibrotic liver can contain up to six times more collagen and proteoglycans than a healthy liver

End-Stage Liver or Cirrhosis

• Cirrhosis involves widespread fibrosis, transforming the liver's architecture into abnormal lobules
• Includes loss of liver parenchyma, condensation of the reticulin framework, and the development of fibrous tissue tracts
• Regeneration of liver tissue within these tracts forms variable-sized nodules

Hepatic Failure

• In healthy animals, > 2/3 of the hepatic parenchyma can be removed without significant impairment of hepatic function, and normal hepatic mass can be regenerated
• This process of tissue removal can be repeated several times in younger animals, and function is retained

Normal Liver Function

• Gallbladder stores and concentrates bile
• Bile emulsifies fats and assists their absorption
• Liver performs various functions, including:
  • Converting glucose to glycogen
  • Producing and degrading plasma lipids
  • Converting foreign substances to water-soluble forms
  • Synthesizing 15% of body proteins
  • Containing 10% adaptive immune system (T and B lymphocytes) or innate immune system (Kupffer cells)

Morphologic Classification of Hepatobiliary Disease

• Liver injury should be characterized by:
  • Pattern of involvement (multifocal random, zonal, or massive)
  • Type of inflammatory cells involved
  • Evidence of necrosis or fibrosis
  • Severity of these processes, evidence of regeneration, etc.

Acute Hepatitis

• Inflammation of the liver parenchyma
• Characterized by hepatocellular necrosis and apoptosis
• In bacterial and protozoal hepatitis, neutrophils accumulate in response to usual chemotactic stimuli
• Acute hepatitis produced by viral infections results in a random distribution of necrosis and apoptosis with minimal inflammation or infiltrations of lymphocytes

Chronic Hepatitis

• Results when there is continued inflammation
• Characterized by fibrosis
• Different types of chronic hepatitis:
  • Granulomatous hepatitis: granulomas of sufficient size (focal, multifocal, or diffuse)
  • Chronic suppurative hepatitis: manifested as multiple abscesses

Nonspecific Reactive Hepatitis

• Diffuse process distributed throughout the liver in response to some systemic illness (GI tract) or prior liver inflammation
• In acute cases, there is a minimal to mild infiltrate of neutrophils within the connective tissue of the portal tracts

This quiz covers the causes and characteristics of intrahepatic and extrahepatic cholestasis, including liver injury, hemolysis, and bile synthesis abnormalities. Learn about the differences between acute and chronic forms of cholestasis and their effects on the liver.