Accelerating Gallstone Dissolution

Abstract

The dissolution rates of cholesterol in model bile salt solutions are controlled by diffusion in slowly flowing bile and by interfacial kinetics in rapidly flowing bile. At low flow, dissolution varies with the square root of bile flow and can be predicted, apriori, from existing correlations of mass transfer. At high bile flow, dissolution is independent of bile flow and is probably dominated by the rate of micelle adsorption. These results show that cholesterol gallstone dissolution, a potential nonsurgical therapy for cholelithiasis, can be accelerated little in slow bile, but more significantly in rapidly flowing bile.

The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man.

“…The results which satisfied these criteria were indistinguishable from experimental or interpolated data by the multiple mixture method. However, the rates of dissolution were progressively retarded in proportion to the molar ratio of lecithin to bile salt, a phenomenon previously recognized (29,52) so that systems containing appreciable lecithin contents failed to reach equilibrium as demonstrated by the lack of agreement with the results of the multiple mixture study (Fig. 12) and by the continued increase in micellar cholesterol content up to the end of the experiments (Fig.…”

“…llC). It has been suggested that micellar diffusion to and from the crystal interface and an interfacial barrier are the major rate limiting steps in cholesterol dissolution (52). The former should be the most important in our "unstirred" experiments whereas the interfacial resistance is rate limiting in our "stirred" experiments.…”

“…The flow rates in the stirred dissolution experiments were designed to be faster than the estimated diffusion controlled limit (52) so that the overall dissolution rates should only be controlled by the interfacial resistance. Two observations support this possibility.…”

Explaining solubilization kinetics

“…The two diffusion steps (1) and (5) both depend on the properties of the solution but not on the properties of fatty acid surface (Tao et al, 1974). When the h i d flow across the surface is well defined, as in the case with the rotating disk, the speed of these steps can be t:alculatetl a priori from fluid mechanics.…”

Dissolution of common bile duct stones

“…The three steps may be compared to three electrical resistors in series and be described by the equation: With high rates of flow, k and k, are large and k, will be rate-limiting. When solute flow is dow or absent, k , and k, will be small and limit the rate of dissolution (32).…”