Jaundice Types and Bilirubin Metabolism
The three types of jaundice (prehepatic, hepatic, and posthepatic) have distinct laboratory profiles and associated disorders that reflect different pathophysiological mechanisms in bilirubin metabolism. 1
Comprehensive Jaundice Classification Table
| Type of Jaundice | Conjugated and/or Unconjugated Bilirubin Levels (plasma) | Urine Bilirubin Level | Urine Urobilinogen Level | Associated Disorders |
|---|---|---|---|---|
| Prehepatic | Predominantly unconjugated (conjugated bilirubin <20-30% of total) | Absent | Increased | Hemolytic disorders (hemolytic anemias, spherocytosis, thalassemia), ineffective erythropoiesis, hematoma resorption [1] |
| Hepatic | Mixed (both conjugated and unconjugated) | Present | Variable (normal to increased) | Viral hepatitis, alcoholic hepatitis, drug-induced liver injury, cirrhosis, Gilbert syndrome, Crigler-Najjar syndrome [1,2] |
| Posthepatic | Predominantly conjugated (conjugated bilirubin >35% of total) | Present | Decreased or absent | Biliary obstruction (gallstones, strictures, tumors), Dubin-Johnson syndrome, Rotor syndrome [1,2] |
Pathophysiology of Different Jaundice Types
Prehepatic Jaundice
- Results from excessive bilirubin production that exceeds the liver's conjugation capacity
- Characterized by increased breakdown of red blood cells (hemolysis)
- Unconjugated bilirubin is not water-soluble, so it cannot be excreted in urine
- Increased production of urobilinogen occurs as more unconjugated bilirubin reaches the intestine 1
Hepatic Jaundice
- Caused by impaired uptake, conjugation, or excretion of bilirubin by damaged hepatocytes
- Both conjugated and unconjugated bilirubin levels rise in plasma
- Conjugated bilirubin appears in urine as it is water-soluble and can be filtered by the kidneys
- Urobilinogen levels vary depending on the severity of hepatocellular damage 1, 3
Posthepatic Jaundice
- Results from obstruction to bile flow after bilirubin has been conjugated in the liver
- Conjugated bilirubin refluxes back into the bloodstream
- High levels of conjugated bilirubin appear in urine
- Urobilinogen is decreased or absent in urine because conjugated bilirubin cannot reach the intestine to be converted to urobilinogen 1, 4
Clinical Pearls and Pitfalls
- Important pitfall: Failing to recognize mixed hyperbilirubinemia in advanced liver disease, which can present with features of both hepatic and posthepatic jaundice 1
- Common mistake: Overlooking medication-induced jaundice, which can present with either conjugated or unconjugated hyperbilirubinemia patterns 1
- Key consideration: In cirrhosis, portal blood flow distortion decreases hepatic clearance of bilirubin, while portosystemic shunting and splenomegaly increase hemolysis and bilirubin production 3
- Diagnostic approach: Measuring fractionated bilirubin (conjugated vs. unconjugated) is essential for determining the type of hyperbilirubinemia and narrowing the differential diagnosis 5
- Monitoring recommendation: The frequency of bilirubin monitoring should be adjusted based on the severity of elevation - every 6-12 months for stable conditions, every 2-5 days for moderate to severe elevations 1
Understanding these distinct patterns of bilirubin metabolism is crucial for accurate diagnosis and appropriate management of jaundice across its various etiologies.