A definition of lithogenic bile
R. Thomas Holzbach, M.D.
Department of Gastroenterology Head, Gastrointestinal Research Unit
In recent years, the descriptive term lithogenic has come into common use when applied to bile obtained from a patient with cholesterol cholelithiasis. It is assumed that in the presence of cholesterol gallstones, conditions in the surrounding bile solution are physicochemically suitable for precipitation of cholesterol and thus ultimately for the beginning of stone formation. The difficulty is that despite extensive use of the word lithogenic, a rational definition in terms of process based on direct evidence remains unavailable.
In the mid- to late 1960s work was done which for the first time attempted to provide a definition of saturation in terms of maximum micellar capacity to dissolve cholesterol in bile.1 By inference, when the content of cholesterol in bile exceeded this limit, the system was said to be supersaturated. The latter indicated an unstable state in which cholesterol precipitation was likely to occur almost immediately so that supersaturation, thusly defined, was regarded as equivalent to lithogenic.2 Existence of a more prolonged state of metastable supersaturation in solubility systems was well known to physical chemists and biochemists who were familiar with such solutions, but applicability of this concept to biological systems had not been widely considered.
Work done within the past 5 years on precipitate formation in urolithiasis and cholelithiasis has indicated that both of these solubility systems are capable of and commonly exemplify the state of metastable supersaturation as applied to biological fluids,3 as indicated for normal human biles in Figure 1. This new concept has had some important. . .