Bilirubin conjugate changes in the bile of gallbladders containing gallstones

Abstract

Gallbladder bile was obtained at laparoscopic cholecystectomy from 31 patients with gallstones, and duodenal aspirates from 18 normal controls. Bile pigments (9 conjugates and unconjugated bilirubin) were analyzed by high-performance liquid chromatography. The average proportional composition of the bile pigments from the patients with gallstones was characteristically different from the controls. Whereas the average values for the principal conjugates in the controls were bilirubin diglucuronide 83.4%, bilirubin monoglucuronide 10.1%, bilirubin monoglucuronide monoglucoside 4.5%, and bilirubin monoglucuronide monoxyloside 1.0%, the corresponding values in the biles from the patients with gallstones were 66.3%, 20.6%, 6.5%, and 2.8%, respectively. Values from the more minor conjugates and unconjugated bilirubin were less than 2% in either data set. In samples obtained in 9 of the gallstone patients early and late in the procedure, no significant change was found. Over the spectrum of findings in the gallstone patients, as the proportion of bilirubin diglucuronide became smaller, that of bilirubin monoglucuronide increased substantially, whereas those of bilirubin monoglucuronide monoglucoside and bilirubin monoglucuronide monoxyloside increased to a small extent. The findings suggest that bilirubin diglucuronide hydrolysis occurs in the gallbladder bile of gallstone patients, with the production of bilirubin monoglucuronide, and that if further hydrolysis of bilirubin monoglucuronide occurs with the formation of unconjugated bilirubin, the latter does not ordinarily increase because it is being absorbed. Stasis with increased gallbladder residence time was likely present in some of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

New pathophysiological concepts underlying pathogenesis of pigment gallstones

“…Increased proportions of biliary monoglucuronosyl bilirubin to bisglucuronosyl bilirubin are the rule in biles of patients with black pigment gallstones [43,44]. Monoglucuronosyl bilirubin can more easily be deconjugated in bile by endogenous acidic β-glucuronidase that is secreted by hepatic parenchymal cells [45], or less frequently by biliary epithelial β-glucuronidase and non-enzymatic hydrolysis [46].…”

Gallstones in Chronic Liver Disease

“…4,10 Studies have shown that however efficient, the liver does not convert all the unconjugated bilirubin into bilirubin monoglucuronides and diglucuronides: a small fraction of the unconjugated moiety escapes conjugation and 'spills' into bile. 37 In CLD, the fraction of bilirubin escaping conjugation increases. The resultant excess unconjugated bilirubin in bile is vulnerable to polymerization and/ or to co-precipitation with free ionized calcium.…”

“…The resultant excess unconjugated bilirubin in bile is vulnerable to polymerization and/ or to co-precipitation with free ionized calcium. 37,38 Deconjugation may also be catalyzed by glucuronidases of bacterial or mucosal origin, 39 and bilirubin monoglucuronide may also undergo nonenzymatic hydrolysis to form unconjugated bilirubin. Even in normal bile, therefore, the low concentration of unconjugated bilirubin still exceeds its aqueous solubility by 100-to 1000-fold.…”