Which disorder is characterized by inability to transport bilirubin from the sinusoidal membrane into the hepatocyte?

Which disorder is characterized by inability to transport bilirubin from the sinusoidal membrane into the hepatocyte?

• A. Carcinoma of the common bile duct
• B. Crigler-Najjar syndrome
• C. Dubin-Johnson syndrome
• D. Gilbert syndrome

Answer: (D)

This question hinges on how bilirubin is handled by the liver, specifically the uptake into hepatocytes. Bilirubin in the blood is taken up by hepatocytes across the sinusoidal membrane, then it’s conjugated inside the cell and finally excreted into bile. If the uptake into the hepatocyte is impaired, unconjugated bilirubin remains in the blood, causing mild hyperbilirubinemia that is often brought out by fasting or stress. Gilbert syndrome is exactly this scenario: reduced hepatic uptake (and a mild defect in conjugation) leads to predominantly unconjugated hyperbilirubinemia. That uptake defect at the sinusoidal membrane explains the question’s description. By comparison, Dubin-Johnson syndrome involves a problem with excreting conjugated bilirubin into bile, leading to conjugated hyperbilirubinemia. Crigler-Najjar involves a severe inability to conjugate bilirubin due to deficient UDP-glucuronosyltransferase. Carcinoma of the common bile duct typically causes obstructive, conjugated hyperbilirubinemia from cholestasis.

This question hinges on how bilirubin is handled by the liver, specifically the uptake into hepatocytes. Bilirubin in the blood is taken up by hepatocytes across the sinusoidal membrane, then it’s conjugated inside the cell and finally excreted into bile. If the uptake into the hepatocyte is impaired, unconjugated bilirubin remains in the blood, causing mild hyperbilirubinemia that is often brought out by fasting or stress.

Gilbert syndrome is exactly this scenario: reduced hepatic uptake (and a mild defect in conjugation) leads to predominantly unconjugated hyperbilirubinemia. That uptake defect at the sinusoidal membrane explains the question’s description.

By comparison, Dubin-Johnson syndrome involves a problem with excreting conjugated bilirubin into bile, leading to conjugated hyperbilirubinemia. Crigler-Najjar involves a severe inability to conjugate bilirubin due to deficient UDP-glucuronosyltransferase. Carcinoma of the common bile duct typically causes obstructive, conjugated hyperbilirubinemia from cholestasis.