Notes on Jaundice and Hyperbilirubinemia

Definition of Jaundice

• Jaundice (J) is the yellow discoloration of skin, mucous membranes, and sclera due to elevated bilirubin levels.
• Important terms:
  • Hyperbilirubinemia: Increase in bilirubin levels in the blood.
  • Cholestasis: Impaired bile flow.

Bilirubin Production

• Bilirubin is produced from the breakdown of hemoglobin (Hb) and hemoproteins (e.g., cytochromes).
• Normal bilirubin production is about 2-3 grams per day.
• Normal bilirubin levels in the blood: 2-1.2 mg/dL.

Types of Jaundice

1. Prehepatic Jaundice (excessive bilirubin production):
   • Due to hemolysis (e.g., hemolytic anemia).
   • Characterized by high unconjugated bilirubin and normal conjugated bilirubin.
2. Hepatic Jaundice (impaired conjugation):
   • Due to liver disease (e.g., hepatitis, cirrhosis).
   • Elevated total bilirubin with varying levels of conjugated and unconjugated bilirubin.
3. Posthepatic Jaundice (cholestasis):
   • Caused by obstruction of bile flow (gallstones, tumors, etc.).
   • Characterized by high conjugated bilirubin and normal or low unconjugated bilirubin.

Mechanisms of Jaundice

• Hyperbilirubinemia can be due to:
  • Excessive production of unconjugated bilirubin.
  • Impaired uptake or conjugation of bilirubin in the liver.
  • Obstruction of bile flow leading to cholestasis.

Pathophysiology

• Bilirubin is produced from the breakdown of RBCs and normally conjugated in the liver.
• Unconjugated bilirubin is lipid-soluble and not water-soluble, hence not excreted in urine.
• Conjugated bilirubin is water-soluble and excreted in urine and bile.

Clinical Features of Jaundice

• Physical Examination: Yellowing of skin, mucous membranes, and sclera.
• Urine Tests:
  • Absence of urobilinogen suggests obstructive jaundice.
  • Presence of bilirubin in urine indicates conjugated bilirubin.
• Stool Color: Pale stools indicate lack of bilirubin in bile (obstructive jaundice).

Differential Diagnosis

1. Hemolytic Anemia:
   • Low hemoglobin, high reticulocyte count, high unconjugated bilirubin.
2. Liver Disease:
   • High AST/ALT, alkaline phosphatase, and bilirubin.
3. Obstruction:
   • Dark urine, pale stool, high alkaline phosphatase, and conjugated bilirubin.

Investigations

• Liver Function Tests (LFTs):
  • AST and ALT levels for hepatic injury.
  • Alkaline phosphatase and GGT for cholestasis.
• Ultrasound/ERCP: To evaluate bile duct obstruction.
• Liver Biopsy: If liver disease is suspected.

Management

• Treat underlying cause (e.g., hemolysis, liver disease, obstruction).
• Monitor bilirubin levels and liver function tests.

Conclusion

• Understanding the pathophysiology and causes of jaundice is essential for diagnosis and treatment. Different types of jaundice require different management strategies.