What is the role of bilirubin in the formation of gallstones?

Updated: Apr 01, 2019
  • Author: Douglas M Heuman, MD, FACP, FACG, AGAF; Chief Editor: BS Anand, MD  more...
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Bilirubin, a yellow pigment derived from the breakdown of heme, is actively secreted into bile by liver cells. Most of the bilirubin in bile is in the form of glucuronide conjugates, which are water soluble and stable, but a small proportion consists of unconjugated bilirubin. Unconjugated bilirubin, like fatty acids, phosphate, carbonate, and other anions, tends to form insoluble precipitates with calcium. Calcium enters bile passively along with other electrolytes.

In situations of high heme turnover, such as chronic hemolysis or cirrhosis, unconjugated bilirubin may be present in bile at higher than normal concentrations. Calcium bilirubinate may then crystallize from the solution and eventually form stones. Over time, various oxidations cause the bilirubin precipitates to take on a jet-black color, and stones formed in this manner are termed black pigment gallstones. Black pigment stones represent 10%-20% of gallstones in the United States.

Bile is normally sterile, but in some unusual circumstances (eg, above a biliary stricture), it may become colonized with bacteria. The bacteria hydrolyze conjugated bilirubin, and the resulting increase in unconjugated bilirubin may lead to precipitation of calcium bilirubinate crystals.

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