digitonin and Cholelithiasis

Gallbladders with cholesterolosis removed surgically for cholelithiasis were studied by light and electron microscopy as well as by cytochemical methods to demonstrate the presence of free cholesterol in the epithelial cells. Lipid droplets were found not only in the submucosa, but also in the infranuclear cytoplasm of epithelial cells. These contained well developed mitochondria and an agranular endoplasmic reticulum. Macrophages were often present between the epithelial cells and the submucosa, and protruded numerous processes, which also contained well developed cell organelles, abundant lysosomes and lipid droplets. With the excessive lipid deposition, macrophages were filled with lipid droplets and became foam cells. In the epithelial cells, many reaction precipitates occurred after digitonin treatment and some of them were observed in the endoplasmic reticulum. It is suggested, therefore, that free cholesterol is absorbed by epithelial cells and thereafter becomes esterified in the endoplasmic reticulum and thus appears as lipid droplets. Lipid droplets synthesized in the epithelial cells may then be released into the intercellular space, and phagocytosed there by macrophages. It is thus suggested that macrophages filled with lipid droplets may become too large and rigid to pass through the endothelium of lymph vessels, and those large "foam cells" may cause the destruction of lymph vessels. Those sequential events should eventually advance the accumulation of foam cells in the submucosa.

Topics: Cholelithiasis; Cholesterol; Cytoplasm; Digitonin; Endoplasmic Reticulum, Rough; Epithelial Cells; Epithelium; Gallbladder; Humans; Indicators and Reagents; Lipid Metabolism; Lysosomes; Macrophages; Microscopy, Electron; Mitochondria

In this study, we report for the first time the presence of many noncholesterol sterols in human gallstones. Gallstones were obtained from 17 patients at cholesystectomy. They were rich in sterol composition, some 52.8% by weight. A number of different sterols were found: 22-dehydrocholesterol 0.29% of total sterols; cholestanol, 1.54%; lathosterol, 1.92%; 24-methylene cholesterol and campesterol, 0.64%; stigmasterol, 0.02%; beta-sitosterol, 0.21%; and cholesterol, 95.33%. These individual sterols were identified by a variety of methods which included final verification by combined gas chromatography-mass spectroscopy. These unusual sterols were derived either from the diet or from the metabolism of cholesterol in the body. Their presence might well affect the lithogenicity of the bile and raises questions about their metabolism and function generally in the body.

Topics: Cholelithiasis; Cholestanols; Cholesterol; Chromatography, Gas; Dehydrocholesterols; Diet; Digitonin; Humans; Mass Spectrometry; Sterols