Isolated Hyperbilirubinemia

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

  1.  Determine the fractionated bilirubin levels.
  2.  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
  3. 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
  4. 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.
  5. Direct bilirubin can also overestimate conjugated bilirubin as it also takes into account bilirubin bound to albumin
Screen Shot 2015-11-03 at 11.43.31 AM
The 4 main steps of processing bilirubin from blood to bile. Isolated hyperbilirubinemia can be explained by defects in these steps. Abnormalities before or at step 3 such as ineffective erythropoeisis, hemolysis, Gilbert’s syndrome and Crigler-Najjer will give you an isolated unconjugated hyperbilirubinemia. Abnormalities in export and transport particularly as mediated by MRP2 (step 4) will result in an isolated conjugated hyperbilirubinemia.

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