In our #AMreport today at @WCHospital, we reviewed a case of jaundice secondary to cholestatic liver injury and but focused our discussion a basic approach to isolated hyperbilirubinemia. A common misconception is that isolated bilirubinemia is automatically a hemolytic picture. It is true that hemolytic processes would be a more common cause of hyperbilirubinemia but a step-wise approach as outlined below would not overlook other causes. The figure below underscores the four major steps of how bilirubin is handled from being a senescent red blood cell to being excreted into the bile ducts.
Take home points on isolated hyperbilirubinemia
- Determine the fractionated bilirubin levels.
- Direct bilirubin >15% suggests a process in “conjugative & excretory” phases such as Dubin-Johnson Syndrome or Rotor syndrome, the former being due to mutations in MRP2
- Direct bilirubin <15% suggests a problem in the “pre-conjugative” phase. If hemolytic workup is negative then the possibilities the would be Gilbert’s syndrome or Crigler-Najjar type I or II but the latter are extremely rare and associated with profound unconjugated hyperbilirubinemia due to deficiencies in UDP-glucuronosyltransferase activity
- Processes happening in the “pre-conjugative” phase or impairments in step 3 as is the case in Crigler-Najjar & Gilbert will give rise to unconjugated hyperbilirubinemia.
- Direct bilirubin can also overestimate conjugated bilirubin as it also takes into account bilirubin bound to albumin