Abstract

The primum movens in cholesterol gallstone formation is hepatic cholesterol hypersecretion and chronic supersaturation of bile. From this event a cascade of contributing factors can be differentiated: (i) Motility defects with impaired gallbladder contractility and gallbladder stasis, but also with small and large intestinal hypomotility. (ii) Multiple biochemical defects in gallbladder bile with increased biliary proteins, increased deoxycholic acid and rapid crystallization of biliary cholesterol from supersaturated unstable vesicles. There is considerable evidence that slow intestinal and colonic transit can increase the deoxycholic acid pool size and biliary cholesterol saturation. Changes in intestinal transit influence the anaerobic bacterial enzymatic biotransformation of conjugated cholate to more hydrophobic deoxycholate. This leads to biliary cholesterol hypersecretion and gallstone formation. Prokinetic drugs or administration of lactulose or fiber products like bran can change the slow intestinal transit favourably with subsequent reduction in deoxycholic acid formation and cholesterol saturation of bile. Whether these applications are indeed of value in the long-term prevention of gallstone disease, however, is doubtful, since fiber-rich diet in prevention of gallstone recurrence after complete gallstone dissolution was not successful.

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