Lecture Notes: Bilirubin Metabolism

Importance of Bilirubin Metabolism

• Hyperbilirubinemia: High levels of bilirubin leading to jaundice (yellowing of skin and eyes).
  • Indicates possible underlying serious condition.

Formation of Bilirubin

• Source: Breakdown of heme from hemoglobin in old red blood cells.
• Process:
  • Red blood cells enter the reticular endothelial system (liver and spleen).
  • Engulfed by macrophages, broken down into heme and globin.
  • Heme is further broken down by enzymes:
    • Heme oxygenase
    • Biliverdin reductase: Forms bilirubin and iron.
• Iron and globin are recycled to produce new red blood cells.

Unconjugated Bilirubin

• Characteristics:
  • Lipid soluble.
  • Binds to transport proteins like albumin and high-density lipoproteins.
• Sources: Also from breakdown of myoglobin and cytochrome enzymes.

Liver Processing

• Albumin-bilirubin complex circulates and enters the liver.
• Facilitated diffusion: Unconjugated bilirubin enters hepatocytes.
• Glucuronidation:
  • Enzyme family: UDP-glucuronosyltransferases (UGT), specifically bilirubin UGT.
  • Converts unconjugated bilirubin to conjugated (water-soluble).
• Conjugated Bilirubin:
  • Excreted into the biliary system and contributes to bile.

Journey Through the Intestines

• Conjugated Bilirubin:
  • Travels through the bile duct to the duodenum.
  • Majority in the small intestine is conjugated (98%).
  • Not absorbed due to water solubility.
• Unconjugated Bilirubin:
  • Partially reabsorbed and enters enterohepatic circulation (intestinal to liver circulation).

Role of Bacteria in Large Intestine

• Conjugated Bilirubin:
  • Continues to the large intestine.
  • Reduced by bacterial enzymes to urobilins.
• Urobilinogen:
  • Partially absorbed and re-enters liver.
  • Remainder enters general circulation and excreted in urine (causes yellow color of urine).
  • Majority excreted in feces as oxidized urobilins (sterocobilin gives brown color to feces).

Summary

• Bilirubin: Breakdown product of hemoglobin.
  • Unconjugated bilirubin enters liver, becomes conjugated (water-soluble).
  • Further digestion in intestines with bacteria forms urobilinogen.
  • Urobilinogen can be reabsorbed or excreted.
• Clinical Importance:
  • High bilirubin levels (hyperbilirubinemia) can lead to jaundice.
  • Potential indicator of underlying disease.

Note: Further discussion on the implications of bilirubin levels will be covered in a separate video.