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Diseases Associated with Hyperbilirubinemia
Several diseases are associated with hyperbilirubinemia. Direct and indirect bilirubin values are used in the differential diagnosis of hyperbilirubinemia.

Hyperbilirubinemia could be caused by

  • increased bilirubin production
  • decreased uptake into the liver cells
  • impaired conjugation
  • interference with the secretion of conjugated bilirubin.

Here is a schematic diagram that represents normal bilirubin metabolism. Use this to compare with various abnormal states described below.

Here are some examples of diseases in which hyperbilirubinemia is observed.

Hemolytic jaundice

  • results in increased production of bilirubin.
  • Here more bilirubin is conjugated and excreted than normally, but the conjugation mechanism is overwhelmed, and an abnormally large amount of unconjugated bilirubin is found in the blood.

Gilbert's disease

  • may be caused by an inability of the hepatocytes to take up bilirubin from the blood.
  • As a result, unconjugated bilirubin accumulates.

Physiological jaundice
Crigler-Najjar syndrome

  • are conditions in which conjugation is impaired.
  • Unconjugated bilirubin is retained by the body.

Dubin-Johnson syndrome

  • is associated with inability of the hepatocytes to secrete conjugated bilirubin after it has been formed.
  • Conjugated bilirubin returns to the blood.

Biliary obstruction

  • by (for example) biliary calculi causes backup and reabsorption of conjugated bilirubin.
  • Blood levels of conjugated bilirubin increase.
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