Lecture on Bilirubin and Congenital Hyperbilirubinemia

Overview

• Key Topics:
  • Bilirubin physiology
  • Differences between unconjugated and conjugated bilirubin
  • Diseases: Gilbert Syndrome, Crigler-Najjar Syndrome (type 1 and 2), Dubin-Johnson Syndrome, Rotor Syndrome

Bilirubin Physiology

• Heme to Bilirubin Conversion:
  • Heme converted to biliverdin by Heme Oxygenase
  • Biliverdin converted to bilirubin by Biliverdin Reductase
• Unconjugated Bilirubin:
  • Produced in reticuloendothelial system
  • Travels bound to albumin
• Conjugated Bilirubin:
  • Occurs in liver via UDP-Glucuronosyltransferase
  • Enables secretion into biliary system

Difference Between Unconjugated and Conjugated Bilirubin

• Unconjugated:
  • No glucuronic acid attached
  • Circulates bound to albumin
• Conjugated:
  • Has glucuronic acid attached
  • Can be excreted into bile and intestines

Bilirubin Metabolism

• In Intestines:
  • Bacteria convert bilirubin to urobilinogen
  • Urobilinogen Pathways:
    • Reabsorbed into cycle
    • Converted to urobilin in kidneys (yellow pigment in urine)
    • Converted to stercobilin in colon (brown pigment in stool)

Congenital Hyperbilirubinemia

• Unconjugated Hyperbilirubinemia Diseases:

  • Gilbert Syndrome:
    • UGT1A1 gene knockout
    • Decreased UDP-glucuronosyltransferase activity
  • Crigler-Najjar Syndrome Type 1:
    • Complete lack of UDP-glucuronosyltransferase
    • Kernicterus Risk
    • No response to phenobarbital
  • Crigler-Najjar Syndrome Type 2:
    • Partial deficiency of UDP-glucuronosyltransferase
    • Responds to phenobarbital (mnemonic: phenobarbi2)

• Conjugated Hyperbilirubinemia Diseases:

  • Dubin-Johnson Syndrome:
    • Dysfunctional MRP2 protein
    • Black liver appearance
    • Contraindicated with oral contraception
  • Rotor Syndrome:
    • Defective OATP1B1 and OATP1B3
    • No black liver
    • Contraindicated with oral contraception (mnemonic: RoOATP)

Mnemonics and Key Points

• Gilbert Syndrome: UGT (Unconjugated Gilbert Transferase)
• Dubin-Johnson Syndrome: Dwayne "The Rock" Johnson (black liver)
• Rotor Syndrome: RoOATP for impacted proteins
• Remember: Keep track of liver pigmentation and enzyme deficiencies for differentiating diseases.

Conclusion

• Understanding physiology helps in comprehending disease mechanisms.
• Focus on enzyme function, bilirubin transport, and clinical symptoms to diagnose and differentiate between hyperbilirubinemias.
• Use mnemonics to recall key characteristics of each syndrome.

These notes summarize the physiology of bilirubin, differences between types, metabolism processes, and congenital hyperbilirubinemia diseases, providing a robust study aid for understanding the lecture content.