Gallstone formation and gallbladder mucosal changes in mice fed a lithogenic diet

To investigate the pathologic change of gallbladder mucosa related to galls tone formation, 52 mice were fed a lithogenic diet containing 1% cholestero l and 0.5% cholic acid and we evaluated the sequential morphologic changes in the gallbladder from two days to 40 weeks. Cholesterol gallstones began to appear after two weeks and all the mice had gallstones after eight weeks . At two days, the mitotic index was at its highest. The gallbladder mucosa showed progressive hyperplastic change with earlier papillary projection o f the folds and later inward proliferation. At the same time of stone forma tion, mucous cells forming glands appeared. Their histochemical profile of mucin was different from that of normal epithelium. Numbers of mucous cells increased gradually until 24 weeks but slightly decreased afterward. These results suggest hyperplasia and metaplasia are closely related to the gall stone formation. Hyperplasia is probably reactive to irritating effect of l ithogenic bile or stone. Metaplasia and cholesterol gallstone may develop s imultaneously, and act synergistically.