It is the rate at which the steps occur that determines who develops gallstones. The liver manufactures bile and secretes cholesterol in the form of lecithin-cholesterol vesicles. These vesicles allow biliary transport of cholesterol, which is otherwise insoluble in water and partitions into the oily vesicle bilayer. Hepatic bile contacts bile salt as it flows into the gallbladder. The micellization process favors transport of lecithin, however, and the remaining vesicles are cholesterol-enriched relative to the starting vesicles.
Small embryos dissolve, but some exceed a critical size and continue to grow.
At right is a cartoon that summarizes their findings and provides the thermodynamic reasoning behind gallstone formation. The cartoon is a schematic ternary phase diagram, where any point within the triangle denotes a given composition of the three lipids and each apex denotes a pure lipid. These vesicles will ultimately attain equilibrium, however, and may land at different points on the phase diagram depending on their composition. Technically speaking, cholesterol supersaturation is a necessary but insufficient condition for gallstone formation, and thermodynamics alone cannot predict who will develop gallstones. We have recently developed a technique to detect cholesterol nucleation in bile.