Morphological observations on the gallbladder of ground squirrels fed a lithogenic diet.

Richardson's ground squirrels (Spermophilus richardsonii) of both sexes were fed a 2 per cent cholesterol-enriched rat chow diet for intervals of 1, 2, 10 and 20 weeks. Light microscopy and 3H-thymidine autoradiography revealed an increase in cell proliferation prior to the occurrence of macroscopically visible stones, but in the presence of crystals and microliths. Transmission electron microscopy studies showed that columnar epithelial cells undergo mitosis rather than basal cells and that oedematous cells were extruded from the epithelial sheet. Transmission and scanning electron microscopy studies on gallbladders of animals fed the lithogenic diet for 10 and 20 weeks revealed damaged epithelial cells either singly or in groups. Neighbouring cells often slide under the basal aspects of cells being extruded. Hypertrophy, hyperplasia, Rokitansky-Aschoff sinuses, thickening of the lamina propria around the muscle bundles and inflammatory cells in the lamina propria began to occur about the time macroscopically visible stones were present. The epithelium of the Richardson's ground squirrel gallbladder is damaged more slowly than that of other animal models by a cholesterol-enriched, lithogenic diet and may more accurately reflect changes occurring in human cholecystitis.