Bilirubin Metabolism and Jaundice

Bilirubin Metabolism and Jaundice

• Jaundice becomes clinically apparent when the plasma bilirubin concentration reaches about 50 μmol/L (hyperbilirubinaemia).

Causes of Jaundice

• Jaundice occurs when bilirubin production exceeds the hepatic capacity to excrete it.
• Possible causes of jaundice include:
  • Increased rate of bilirubin production exceeding normal excretory capacity of the liver (prehepatic jaundice).
  • Damaged liver cells unable to conjugate and/or excrete bilirubin (hepatic jaundice).
  • Obstruction of biliary flow, resulting in conjugated bilirubin being regurgitated into the systemic circulation (post-hepatic jaundice).

Unconjugated Hyperbilirubinemia

• Occurs when there is a marked increase in bilirubin load due to:
  • Haemolysis or breakdown of large amounts of blood after haemorrhage.
  • Impaired binding of bilirubin to ligandin or impaired conjugation with glucuronate in the liver.
• Unbound, unconjugated bilirubin can damage brain cells (kernicterus).

Conjugated Bilirubinemia

• One of the earliest signs of impaired hepatic excretion.
• Conjugated bilirubin is water-soluble and less strongly protein-bound than unconjugated bilirubin.
• Can be excreted in the urine, causing bilirubinuria.

Enzymes and Metabolism

• Bilirubin is conjugated with glucuronate in the liver.
• Stercobilinogen is formed from conjugated bilirubin in the gut lumen.
• Some stercobilinogen is absorbed into the portal circulation and re-excreted in bile (enterohepatic circulation).
• A small amount enters the systemic circulation and is excreted in the urine as urobilinogen.