Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile

Rapid aggregation of cholesterol-phospholipid vesicles in
gallbladder bile seems to be the first event in the production of
cholesterol crystals, a prerequisite for cholesterol gallstone
formation. We examined the amount of these vesicles in 33 human
gallbladder biles in relation to biliary lipid composition and to
the presence of cholesterol crystals. Biliary microscopy detected
cholesterol crystals in all 19 biles from patients with cholesterol
gallstones but in none of 14 biles from patients with pigment
stones. Gel chromatography was used to separate vesicles and
micelles in the native bile with an eluting buffer containing 10 mM
sodium cholate to prevent disruption of micellar lipids.
Cholesterol, phospholipid and bile salt concentrations were
measured in every fraction collected. Bile acid, phospholipid,
cholesterol and total lipid concentrations were not significantly
different in samples with and without cholesterol crystals. The
cholesterol saturation index (1.4 ± 0.11 vs. 1.0 ± 0.08) was
significantly (p < 0.01) higher in biles with crystals than
without crystals. Gel filtration revealed a vesicular peak in
addition to micellar fraction in 18 (23.1 ± 3.2% of total
cholesterol) of the 19 biles with crystals but only in three (15.7
± 2.4% of total cholesterol) of 14 biles without crystals. There
was no relation between biliary lipid concentration or the
cholesterol saturation index and the percentage of vesicular
cholesterol in biles with or without crystals. The close
association of vesicles and crystals in human gallbladder bile
supports the contention that vesicles are important in the initial
nucleation of cholesterol monohydrate crystals.