We studied the effects of stasis of gallbladder bile in a dog model. Three days after cystic duct ligation, all gallbladders contained sludge, and the mucosa was covered by densely adherent mucus with solid particles 1-4 mm in diameter (gravel). Thirty percent of the animals developed stones (greater than 4 mm), which appeared grossly like human pigment stones and microscopically like condensed biliary sludge. Centrifugation of bile yielded colorless pellets (3.8 +/- 3.2 mg/ml) at day 0 and pigmented pellets (33.1 +/- 11.0 mg/ml) at day 3 (p less than 0.05). Pellets contained 73 +/- 8% mucin by weight. Dissolved mucin in supernatant bile increased from 7.46 +/- 1.19 mg/ml (day 0) to 27.36 +/- 3.05 mg/ml (day 3) (p less than 0.001), while bilirubin concentration decreased from 127 +/- 12 mg/dl (day 0) to 71 +/- 16 mg/dl (day 3) (p less than 0.001). Cholesterol concentration increased but did not reach saturation, while the concentration of bile salt and phospholipid did not change. Mucin-bilirubin complexes formed and remained suspended as sludge initially. As bile mucin content increased, sludge particles coalesced, precipitated, and eventually formed gravel and stones. We suspect that stone formation in this setting occurs because of sequestration of biliary lipids by mucin.
Animals Bile Acids and Salts