Lecture Notes on Jaundice and Bilirubin Metabolism

Introduction to Jaundice

• Origin of Terms:
  • "Jaundice" comes from the French "jaunice," meaning yellowing.
  • "Icterus" originates from the belief that jaundice could be cured by looking at a yellow bird.
• Description: Involves yellow pigmentation of skin and eyes due to bilirubin.

Bilirubin Metabolism

• Bilirubin:
  • Component of bile.
  • Responsible for yellowing in bruises, yellow urine, and brown feces after metabolism.
• Source:
  • Red blood cells (RBCs) live ~120 days.
  • Phagocytosed by macrophages in the reticuloendothelial system, primarily in the spleen and lymph nodes.

Breakdown Process

1. RBCs Breakdown:
   • Hemoglobin split into heme and globin.
   • Globin → Amino acids.
   • Heme → Iron + Protoporphyrin.
   • Protoporphyrin → Unconjugated bilirubin (UCB).
2. Unconjugated Bilirubin (UCB):
   • Lipid-soluble, also known as indirect bilirubin.
   • Binds to albumin and transported to the liver.
3. Conjugation in the Liver:
   • UCB is converted to water-soluble conjugated bilirubin (CB) by uridine glucuronyl transferase (UGT).
   • CB secreted into bile canaliculi, stored in the gallbladder.
4. Conversion in Intestines:
   • CB → Urobilinogen (UBG) by intestinal microbes.
   • UBG → Stercobilin (excreted, brown feces) or reabsorbed as urobilin (yellow urine).

Causes of Jaundice

• Disruption in Process:
  • Damage to liver cells could lead to increased bilirubin in the blood.
  • Jaundice visible when serum bilirubin > 2.5 mg/dL.
  • Early sign: Yellow sclera due to high elastin affinity for bilirubin.

Disorders Related to Jaundice

• Increased Unconjugated Bilirubin (UCB):

  1. Extravascular Hemolytic Anemias: Premature breakdown of RBCs.
  2. Ineffective Hematopoiesis: Malformed blood cells broken by macrophages.
  3. Newborn Jaundice:
     • Lower UGT activity in newborns.
     • High UCB can lead to kernicterus (brain damage).
     • Treated with phototherapy to increase solubility of bilirubin.
  4. Genetic Disorders:
     • Gilbert’s Syndrome: Low UGT activity.
     • Crigler-Najjar Syndrome: Near absence of UGT, high fatality risk.

• Increased Conjugated Bilirubin (CB):

  1. Dubin-Johnson Syndrome:
     • Deficiency in MRP2 transporter.
     • Leads to dark liver and increased CB in blood.
  2. Obstructive Jaundice:
     • Bile flow obstruction (gallstones, tumors, etc.).
     • Can lead to itchiness, hypercholesterolemia, dark urine, steatorrhea, and vitamin deficiency.
  3. Viral Hepatitis:
     • Hepatocyte damage leads to increased UCB and CB in blood.
     • Results in darker urine.

Conclusion

• Understanding the bilirubin process helps identify potential causes and treatments for jaundice.
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