The terms biliary sludge and cholesterol microlithiasis(hereafter referred to as microlithiasis)were originated from different diagnostic techniques and may represent different stages of cholesterol gall-stone disease...The terms biliary sludge and cholesterol microlithiasis(hereafter referred to as microlithiasis)were originated from different diagnostic techniques and may represent different stages of cholesterol gall-stone disease.Although the pathogenesis of biliary sludge and microlithiasis may be similar,micro-lithiasis could be preceded by biliary sludge,followed by persistent precipitation and aggregation of solid cholesterol crystals,and eventually,gallstone formation.Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis,including total parenteral nutrition,rapid weight loss,pregnancy,organ transplantation,administration of certain medications,and a variety of acute and chronic illnesses.Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40%of patients,a cyclic pattern of disappearing and reappearing in about 40%,and progression to gallstones in nearly 20%.Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones,it is still a matter of controversy whether micro-lithiasis could eventually evolve to cholesterol gallstones.Biliary sludge and microlithiasis are asymp-tomatic in the vast majority of patients;however,they can cause biliary colic,acute cholecystitis,and acute pancreatitis.Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis.Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population.Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge.Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis.Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis.展开更多
Background:Cholesterol crystallization is an essential step toward gallstone formation.Although model bile studies showed that competition occurs between the gallstone surface and the surrounding aqueous phase for cho...Background:Cholesterol crystallization is an essential step toward gallstone formation.Although model bile studies showed that competition occurs between the gallstone surface and the surrounding aqueous phase for cholesterol molecules available for crystallization,this has not been investigated in human bile.Methods:Fresh gallbladder bile was obtained during laparoscopic cholecystectomy from 13 patients with cholesterol(n紏10)or pigment(n紏3)stones.Small cholesterol gallstones were collected from another two patients.Both native and ultrafiltered bile with or without added gallstones was analysed by polarized light microscopy for the presence of arc-like and needle-like anhydrous cholesterol crystals and classic cholesterol monohydrate crystals.Weight of the added stones was evaluated before and after 21 days of bile incubation.Results:In unfiltered bile,the presence of stones was associated with a trend towards less anhydrous cholesterol crystals,but significantly more aggregated cholesterol monohydrate crystals.In ultrafiltered bile,the presence of stones tended to inhibit the formation of arc-like or needle-like crystals and was associated with significantly greater amounts of both platelike and aggregated cholesterol monohydrate crystals.After 21 days of the incubation,stone weight was decreased in both unfiltered(–4.561.6%,P紏0.046)and ultrafiltered bile(–6.561.5%,P紏0.002).Bile from pigment-stone patients was clear in the absence of stones,but showed early appearance of plate-like and aggregated cholesterol monohydrate crystals in all samples to which cholesterol gallstones were added.Conclusions:The physical presence of cholesterol gallstones in both native and filtered bile greatly influences cholesterol crystallization pathways.Whereas cholesterol monohydrate crystals increase,anhydrous cholesterol crystals tend to be inhibited.Detachment of solid cholesterol crystals from the gallstone surface may explain these findings.展开更多
Cholesterol crystals have long been recognized as part of atherosclerotic plaques.They have been visualized by light microscopy as empty spaces or imprints where crystals were once present and then dissolved by tissue...Cholesterol crystals have long been recognized as part of atherosclerotic plaques.They have been visualized by light microscopy as empty spaces or imprints where crystals were once present and then dissolved by tissue processing.Thus,until now,their role in atherosclerosis and plaque rupture had been considered to be inert.However,by the processing of tissue without ethanol it was possible to visualize their extensiveness and potential role in tissue injury.Also,it was demonstrated that cholesterol expands in volume when crystallizing from the liquid to the solid state,which is the presumed cause of plaque rupture by sharp-tipped crystals growing out of the plaque's necrotic core.Specifi cally,in patients who died of myocardial infarction,all culprit coronary lesions had extensive cholesterol crystals perforating the fibrous cap and intima,while those patients who died of other causes and had plaques did not have crystals perforating the cap and intima.Additionally,cholesterol crystals traveling downstream from the plaque rupture site can scrape the endothelium and promote vasospasm.Moreover,cholesterol crystals lodging into the muscle can trigger an inflammation with necrosis independent of circulatory compromise or ischemia.These findings suggest that cholesterol crystals could play a critical role in plaque rupture,as well as vascular and myocardial injury.展开更多
基金This work was supported in part by research grants DK101793,DK114516 and DK106249,and AA025737(to D.Q.-H.Wang),as well as P30 DK020541(to Marion Bessin Liver Research Center),all from the National Institutes of Health(United States Public Health Service).
文摘The terms biliary sludge and cholesterol microlithiasis(hereafter referred to as microlithiasis)were originated from different diagnostic techniques and may represent different stages of cholesterol gall-stone disease.Although the pathogenesis of biliary sludge and microlithiasis may be similar,micro-lithiasis could be preceded by biliary sludge,followed by persistent precipitation and aggregation of solid cholesterol crystals,and eventually,gallstone formation.Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis,including total parenteral nutrition,rapid weight loss,pregnancy,organ transplantation,administration of certain medications,and a variety of acute and chronic illnesses.Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40%of patients,a cyclic pattern of disappearing and reappearing in about 40%,and progression to gallstones in nearly 20%.Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones,it is still a matter of controversy whether micro-lithiasis could eventually evolve to cholesterol gallstones.Biliary sludge and microlithiasis are asymp-tomatic in the vast majority of patients;however,they can cause biliary colic,acute cholecystitis,and acute pancreatitis.Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis.Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population.Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge.Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis.Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis.
基金The present chapter is written in the context of the project FOIE GRAS,which has received funding from the European Union’s Horizon 2020 Research and Innovation program under the Marie Sklodowska-Curie Grant Agreement No.722619.
文摘Background:Cholesterol crystallization is an essential step toward gallstone formation.Although model bile studies showed that competition occurs between the gallstone surface and the surrounding aqueous phase for cholesterol molecules available for crystallization,this has not been investigated in human bile.Methods:Fresh gallbladder bile was obtained during laparoscopic cholecystectomy from 13 patients with cholesterol(n紏10)or pigment(n紏3)stones.Small cholesterol gallstones were collected from another two patients.Both native and ultrafiltered bile with or without added gallstones was analysed by polarized light microscopy for the presence of arc-like and needle-like anhydrous cholesterol crystals and classic cholesterol monohydrate crystals.Weight of the added stones was evaluated before and after 21 days of bile incubation.Results:In unfiltered bile,the presence of stones was associated with a trend towards less anhydrous cholesterol crystals,but significantly more aggregated cholesterol monohydrate crystals.In ultrafiltered bile,the presence of stones tended to inhibit the formation of arc-like or needle-like crystals and was associated with significantly greater amounts of both platelike and aggregated cholesterol monohydrate crystals.After 21 days of the incubation,stone weight was decreased in both unfiltered(–4.561.6%,P紏0.046)and ultrafiltered bile(–6.561.5%,P紏0.002).Bile from pigment-stone patients was clear in the absence of stones,but showed early appearance of plate-like and aggregated cholesterol monohydrate crystals in all samples to which cholesterol gallstones were added.Conclusions:The physical presence of cholesterol gallstones in both native and filtered bile greatly influences cholesterol crystallization pathways.Whereas cholesterol monohydrate crystals increase,anhydrous cholesterol crystals tend to be inhibited.Detachment of solid cholesterol crystals from the gallstone surface may explain these findings.
文摘Cholesterol crystals have long been recognized as part of atherosclerotic plaques.They have been visualized by light microscopy as empty spaces or imprints where crystals were once present and then dissolved by tissue processing.Thus,until now,their role in atherosclerosis and plaque rupture had been considered to be inert.However,by the processing of tissue without ethanol it was possible to visualize their extensiveness and potential role in tissue injury.Also,it was demonstrated that cholesterol expands in volume when crystallizing from the liquid to the solid state,which is the presumed cause of plaque rupture by sharp-tipped crystals growing out of the plaque's necrotic core.Specifi cally,in patients who died of myocardial infarction,all culprit coronary lesions had extensive cholesterol crystals perforating the fibrous cap and intima,while those patients who died of other causes and had plaques did not have crystals perforating the cap and intima.Additionally,cholesterol crystals traveling downstream from the plaque rupture site can scrape the endothelium and promote vasospasm.Moreover,cholesterol crystals lodging into the muscle can trigger an inflammation with necrosis independent of circulatory compromise or ischemia.These findings suggest that cholesterol crystals could play a critical role in plaque rupture,as well as vascular and myocardial injury.
