| Feature | Unconjugated (Indirect) Hyperbilirubinemia | Conjugated (Direct) Hyperbilirubinemia |
|---|---|---|
| Bilirubin Type | Lipid-soluble, not water-soluble. Bound to albumin. | Water-soluble. |
| Urine Bilirubin | Absent. Cannot be excreted in urine. | Present. Causes dark, tea-colored urine. |
| Stool Color | Normal colored. | Pale/Acholic (if due to biliary obstruction). |
| Pathophysiology | 1. Overproduction: ↑ bilirubin (e.g., hemolysis) 2. Impaired Conjugation: ↓ UGT enzyme activity | 1. Hepatocellular Dysfunction: ↓ excretion from liver (e.g., hepatitis) 2. Biliary Obstruction: ↓ drainage (obstructive) |
| Key Causes | - Hemolytic anemias - Gilbert syndrome (mild ↓ UGT) - Crigler-Najjar syndrome (absent UGT) - Physiologic jaundice of newborn | - Gallstones, Pancreatic cancer - Hepatitis, Cirrhosis - Dubin-Johnson syndrome - Rotor syndrome - Primary Biliary Cholangitis / Sclerosing Cholangitis |
| Neurotoxicity | Risk of Kernicterus in neonates (bilirubin crosses BBB). | No risk of kernicterus (cannot cross BBB). |
Diagnostics
- Initial Labs:
- Total and fractionated (direct/indirect) bilirubin.
- Liver chemistry panel (AST, ALT, ALP, GGT).
- CBC, reticulocyte count, peripheral blood smear, and Direct Coombs Test (if hemolytic origin suspected).
- Workup for Unconjugated Hyperbilirubinemia:
- If hemolytic markers positive (↑ retic, ↓ haptoglobin, ↑ LDH) -> work up hemolysis.
- If hemolytic markers negative -> evaluate for Gilbert, Crigler-Najjar, or thyroid dysfunction (hypothyroidism).
- Workup for Conjugated Hyperbilirubinemia (Direct >20% of Total):
- Initial Imaging: RUQ Ultrasound to assess for biliary dilation. c
- Dilation present: Suggests extrahepatic obstruction (choledocholithiasis, malignancy). Proceed to MRCP (diagnostic) or ERCP (diagnostic and therapeutic).
- No dilation: Suggests intrahepatic cholestasis or hepatocellular injury. Work up hepatitis (viral/autoimmune), drug-induced liver injury, or genetic causes.
- Initial Imaging: RUQ Ultrasound to assess for biliary dilation. c