Solitary versus multiple cholesterol gallbladder stones

Abstract

The development and growth pattern of solitary and multiple cholesterol gallbladder stones was defined using cholecystography in a prospective study of 48 patients whose initial cholecystograms indicated a stone-free gallbladder and who developed gallstones within the subsequent 5 years. Radiological observations performed over 365 patient-years were complemented by macroscopic examination, radiograms, scanning electron microscopy, and chemical analysis of gallstones from these and other patients obtained at cholecystectomy. Solitary gallstones were found to develop after a precursor phase of over 2 years during which free-floating crystal laminae of cholesterol formed. These laminae subsequently aggregated loosely and underwent external compaction and internal remodeling by movement of cholesterol molecules to form compact spheroids. A single lamina was observed to function as a nucleus for the development of a solitary stone shaped as an ellipsoid. About 10% of solitary stones were found to have a solitary pigment stone in their center. In contrast, multiple cholesterol gallstones formed without a precursor phase. Innumerable, very thin cholesterol crystals appeared which very abruptly aggregated to form spheres of up to 1 mm in diameter. Within 3 months a second aggregation took place in which these spheres colaesced to form mulberry stones. Mulberry stones in turn were transformed either to faceted stones (if many were present in the gallbladder) or to barrel stones (if few were present) over a period of 3 years. It is proposed that temporary occlusion of the cystic duct leads to supersaturation of bile with calcium bilirubinate and/or calcium carbonate which in turn promotes deposition of either or both of these calcium salts on the surface of single or multiple gallstones. For multiple gallstones, this process or the deposition of additional cholesterol crystals seals the gallstone surface and is followed by metamorphosis of the stone center.

A new subgroup of lectin-bound biliary proteins binds to cholesterol crystals, modifies crystal morphology, and inhibits cholesterol crystallization.

“…In human gallstone disease, highly correlated with gallbladder motor dysfunction (51), these crystals may accumulate in bile and provide the substrate for gallstone formation. The observed crystal morphologies correlate to scanning electron microscopy studies of human gallstones (52), showing a well-ordered arrangement of compact crystals in slowly growing solitary cholesterol gallstones. In contrast, in fast-growing multiple cholesterol stones, unsettled crystals forming random aggregates were found being radially arranged in a perpendicular position to the center of the hemisphere.…”

Comparative morphology of the gallbladder and biliary tract in vertebrates: Variation in structure, homology in function and gallstones

“…Bile acid composition of gallstones from man was also studied by Schoenfield et al (1966). The development and growth pattern of solitary and multiple cholesterol gallbladder stones has been studied in an informative paper of Wolpers and Hofmann (1993). Calcium salts have been observed in the nucleus (Bills and Lewis, 1975;Cowie et al, 1973) as well as in concentric layers suggesting the sequential growth of the gallstone (Kaufman et al, 1990;Gilloteaux et al, 1997).…”

Bile acids: Trying to understand their chemistry and biology with the hope of helping patients #

“…Third, it did not always work. Research by the late Karlheinrich Wolpers in Germany 103 suggested that when acute cholecystitis occurred, a noncholesterol layer was deposited on the cholesterol gallstone, precluding or at least slowing dissolution. Furthermore, analyses of the natural history of gallstone disease indicated that the asymptomatic gallstone should not be treated.…”