Cholestasis

Overview
  • Regardless of the etiology, stasis of bile results in certain common morphological, laboratory, and clinical features which are discussed here and referred to as "Cholestasis".
Laboratory Features
  • Hypercholesterolemia
    • Because cholesterol can no longer be hepatically excreted in the bile, its levels can build up manifesting as hypercholesterolemia and can manifest as clinically as xanthomas
  • Conjugated Hyperbilirubinemia
    • In addition to cholesterol, conjugated bilirubin generated by hepatocytes cannot be excreted into the bile and can result in jaundice
  • Serum Alkaline Phosphatase elevation:
    • Alkaline Phosphatase is an enzyme that is present on the luminal membranes of biliary epithelial cells and thus in bile ducts and ductules as well as on the canalicular membrane of hepatocytes
    • Prolonged contact of bile acids with these membranes, due to stasis, results in the detergent action of bile acids releasing membrane-bound alkaline phosphatase which subsequently leaks into the plasma
Clinical Features
  • Intense pruritis is a classic symptom of cholestasis as high levels of bile acids are released into the circulation and can deposit in the skin. Xanthomas may develop due to hypercholesterolemia discussed above. Jaundice frequently arises due to an inability to excrete bilirubin in the bile.
  • Malabsorption Syndromes also often arise as a consequence of cholestasis as GI Lipid Absorption requires bile acids. Consequently, cholestatic conditions can cause lipid malabsorption, leading to steatorrhea. Furthermore, because GI Vitamin Absorption of fat soluble vitamins A, D, E, and K is dependent on proper lipid absorption, deficiencies of these vitamins can also occur if cholestasis persists over a long timescale
Morphological Features
  • Overview
    • Regardless of where the stasis occurs, hepatocytes and the biliary tree upstream of the stasis respond to the progressive buildup of bile in a characteristic way. Importantly, the chronic presence of bile acids can be highly injurious to membranes due to their fairly strong detergent properties, which are normally designed for assisting in GI Lipid Absorption.
  • Gross Appearance
    • When severe, retained bile can turn the liver grossly green.
  • Histological Appearance
    • Bile ducts upstream of the point of stasis initially respond by proliferating, increase their total volume in order to confine the accumulating bile. However, the strong detergent action of retained bile acids frequently leads to rupture of the bile ducts and severe damage to surrounding tissue which may cause infiltration of neutrophils into the portal tracts. Additionally, because they can no longer excrete synthesized bile, degenerating hepatocytes begin to retain droplets of bile which gives them a foamy appearance termed "Feathery Degeneration".
    • Over time, areas around portal tracts undergo progressive fibrosis (i.e. Periportal Fibrosis) which septates the hepatic parenchyma. In the absence of treatment, a picture of frank cirrhosis emerges. It should be noted that when a cirrhotic picture emerges due to an extra-hepatic source of cholestasis it is termed "Secondary Biliary Cirrhosis" since the hepatic pathology is secondary to a biliary obstruction outside of the actual liver.