Unconjugated bilirubin and cholesterol gallstone formation.
Cholesterol gallstones usually have small amounts of pigment at their centers and often have diffuse pigmentation or pigmented layers alternating with cholesterol layers and/or pigmented rims associated with calcium carbonate (eggshell calcification). The pigments are primarily monomeric calcium salts of unconjugated bilirubin anions and/or an insoluble, black, network polymer of tetrapyrroles. Bilirubin presumably can precipitate only if bile is supersaturated with calcium bilirubinates. Among various in vitro model systems, the aqueous solubilities and pK'a values for unconjugated bilirubin differ greatly. It is therefore not known whether normal bile is saturated with unconjugated bilirubin. However, all systems indicate that unconjugated bilirubin is solubilized by binding to bile salt monomers and oligomers, as well as micelles; marked metastable supersaturation of unconjugated bilirubin can occur in the presence of bile salt micelles, and both pK'a values of unconjugated bilirubin are greater than 6.0, probably because of internal hydrogen-bonding of the--COOH groups. Lecithin decreases equilibrium solubilization of unconjugated bilirubin crystals but enhances metastable supersaturation of unconjugated bilirubin. Calcium ions form insoluble salts with unconjugated bilirubin monoanions and dianions but soluble complexes with bilirubin conjugates. The solubility products of the calcium bilirubinate salts suggest that normal hepatic bile is not saturated with CaB or Ca(HB)2 but that gallbladder bile may be supersaturated with Ca(HB)2.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Veterans Administration Lakeside Medical Center, Chicago, Illinois 60611.
J D
JD
Ostrow
D000818:Animals; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism*; D002769:Cholelithiasis / Q000209:etiology* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003460:Crystallization; D006801:Humans; D012995:Solubility; D014867:Water
D014867:Water; D002784:Cholesterol; D001663:Bilirubin