Biliary Sludge Is Formed by Modification of Hepatic Bile by the Gallbladder Mucosa

Background & Aims We studied 22 patients with symptomatic microlithiasis to determine whether a contributory role of the gallbladder in the early stage of cholesterol gallstone formation exists. We compared the merits of different methods (ultrasonography and microscopy) and sources (hepatic or gallbladder) of bile samples for diagnosing microlithiasis. Methods: Paired hepatic and gallbladder bile samples were studied with polarizing microscopy. Nucleation time, bile salts, phospholipid, cholesterol, cholesterol saturation index (CSI), bilirubin, total protein, albumin and mucin concentration were measured. All patients had abdominal ultrasound examination. Results: With polarizing microscopy as the standard, ultrasonography was positive in 13 patients (59%) and negative in 9 (41%). All gallbladder bile samples were positive for microlithiasis by microscopy. Only one hepatic bile sample was positive (P < .0001). There was a disproportional enrichment of total protein, albumin, and mucin (P < .05) in the gallbladder bile and a conversion of bilirubin diglucuronide to monoglucuronide (P < .01). Gallbladder samples had lower CSI but a faster nucleation time (P < .001), which correlates inversely with CSI, total protein, and mucin concentration. Conclusion Biochemical composition and physical chemical behavior of hepatic bile are modified during residence in the gallbladder, contributing to sludge formation. Gallbladder bile has a lower calculated CSI, higher deconjugation of bilirubin, protein and mucin concentration and crystals were present. Hepatic bile samples are inappropriate for microscopic detection of microlithiasis.