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Richard Thompson



These include health benefits of high normal levels of bilirubin, and discussion of the genetic basis of Gilbert’s syndrome.

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date: 19 September 2021

All haem molecules are degraded in macrophages by haem oxygenase to biliverdin, and thence by biliverdin reductase to bilirubin, which is selectively removed by hepatocytes from sinusoidal blood and then conjugated, mainly by one of the two specific isoforms of the microsomal enzyme UDP-glucuronyl (glucuronate-glucuronosyl) transferase, chiefly with two glucuronic acid moieties. Conjugated bilirubin is excreted into the bile by the anionic conjugate transporter protein (MRP2), but in many liver diseases it refluxes back into blood and—since it is water soluble and less firmly bound to albumin than unconjugated bilirubin—about 1% is filtered across the glomerular membrane and darkens the urine (choluria). In the distal intestine conjugated bilirubin is deconjugated and reduced to a series of uro- and stercobilinogens that give the normal colour to faeces. Some colourless urobilinogen is normally absorbed from the colon and undergoes an enterohepatic circulation, with a small amount being excreted in urine. If this biliary excretion is impaired in liver disease, or increased in haemolysis, then excess urobilinogen is excreted in urine, where it is easily detected by routine clinical ‘stix’....

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