What is the pathophysiology of impaired conjugation of bilirubin in unconjugated hyperbilirubinemia?

Updated: May 21, 2019
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: BS Anand, MD  more...
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Answer

Deficiency of bilirubin-UGT leads to an ineffective esterification of bilirubin, which in turn results in an unconjugated hyperbilirubinemia. Reduced bilirubin conjugation as a result of decreased or absent UGT activity is found in several acquired conditions and inherited diseases, such as Crigler-Najjar syndrome (types I and II) and Gilbert syndrome. Bilirubin conjugating activity is also very low in the neonatal liver. An illustration of bilirubin conjugation is shown in the image below.

Conjugation of bilirubin. Conjugation of bilirubin.

UGT activity toward bilirubin is modulated by various hormones. Excess thyroid hormone and ethinyl estradiol, but not other oral contraceptives, inhibit bilirubin glucuronidation. In comparison, the combination of progestational and estrogenic steroids results in increased enzyme activity.

Bilirubin glucuronidation can also be inhibited by certain antibiotics (eg, novobiocin or gentamicin at serum concentrations exceeding therapeutic levels) and by chronic hepatitis, [19] advanced cirrhosis, and Wilson disease. [20]


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