Impaired Gallbladder Emptying Before Gallstone Formation in the Prairie Dog

Hawkins

et al. 1997

Microsc. Res. Tech.

Although there is a large body of data on the gallbladder and the importance of the cystic duct in surgical procedures, there is insufficient data regarding the morphology of the human cystic duct. In the present study, transmission electron microscopic (TEM) and scanning electron microscopic (SEM) survey of several surgical and autopsy cystic ducts in cholelithiasis and cholesterolosis is reported. In cholelithiasis, similar to gallbladder epithelium, the cystic duct epithelial cells display minor‐to‐severe alterations of the epithelial surface accompanied by variable erosion of the epithelium. Areas of intact surface epithelium demonstrate microvilli‐covered cells coated by a rich glycocalyx and mucous production. In other areas, apical excrescences are associated with mucus hyperproduction and secretory events. Lipoid bodies are also present in many cells and especially in many of the cells' subluminal apical areas. In cholesterolosis, mucous secretory granules appear dilated, fatty deposits are infrequent, and peculiar intracellular cholesterol deposits can be detected in the apical and subapical region of cells and around condensed mitochondria. Following elective cholecystectomies, predominantly in association with cholelithiasis, eroded areas were detected; therefore, it appears that the action of intraluminal calculi may be a principal causative factor in discrete epithelial erosions of the cystic duct. Intraluminal calculi/debris, along with the alteration of mucus, cell sloughing, and a decreased pool of bile acids and motility may participate in the gallstone nucleation process. The peculiar cholesterol inclusions may also play a role in that nucleating process. Microsc. Res. Tech. 39:22–38, 1997. © 1997 Wiley‐Liss, Inc.

Section: Discussionmentioning

confidence: 76%

Ultrastructural aspects of human cystic duct epithelium as a result of cholelithiasis and cholesterolosis

Hawkins

et al. 1997

Microsc. Res. Tech.

Molecular Medicine Reports

“…The gallbladder, and particularly its dysfunctions regarding its contraction, have a key role in cholesterol-associated gallstone formation (18). In 1983, Doty found that the emptying function of the gallbladder decreased significantly during the formation of cholesterol monohydrate crystals (CMCs) (19). Further evidence provided by flash radiography and ultrasound analysis indicated that the emptying and refilling of the gallbladder with bile and bile metabolism were clearly inhibited in patients with cholecystolithiasis (20).…”

Section: Discussionmentioning

confidence: 99%

Role of ROCK expression in gallbladder smooth muscle contraction

Wang

Ding

Wang

et al. 2015

Cholelithiasis is a common medical condition whose incidence rate is increasing yearly, while its pathogenesis has yet to be elucidated. The present study assessed the expression of Rho-kinase (ROCK) in gallbladder smooth muscles and its effect on the contractile function of gallbladder smooth muscles during gallstone formation. Thirty male guinea pigs were randomly divided into three groups: The control group, the gallstone model group and the fasudil interference group. The fasting volume (FV) and bile capacity of the gallbladder (FB) as well as the total cholesterol (TC) and triglyceride (TG) contents of the gallbladder bile were determined. In addition, the gallbladder was dissected to identify whether any gallstones had formed. Part of the gallbladder tissue specimens were used for immunohistochemical analysis of ROCK expression in gallbladder smooth muscles. The results showed that four guinea pigs in the model group and eight in the fasudil group displayed gallstone formation, while there was no gallstone formation in the control group. The FV and FB were significantly increased in the model and fasudil groups. Similarly, the TC and TG contents of gallbladder bile were increased in these groups. The positive expression rate of ROCK in gallbladder smooth muscles in the model and fasudil groups was significantly reduced compared with that in the control group (P<0.05). The results of the present study indicated that the reduction of ROCK expression in guinea pig gallbladder smooth muscles weakened gallbladder contraction and thereby promoted gallstone formation.

Eur J Clin Investigation

“…Employing scintigraphic methods [28], it has been demonstrated that gallbladder emptying in gallstone patients is reduced to two-thirds of the values in a matched control group. New results from studies with the prairie dog model strongly suggest that gallbladder stasis is a primary gallbladder defect related to a loss of intrinsic muscle activity [25, 84,85]. Preliminary data indicate that this also applies to human gallbladder function.…”

Section: Gallbladder Hypomotility-residence Time Defectmentioning

confidence: 99%

Current concepts in cholesterol gallstone pathogenesis

Busch¹,

Matern²

1991

Summary Pathogenesis of cholesterol gallstones is related to the failure of bile to maintain cholesterol in micellar solution. The predominant defect is supersaturation of bile with cholesterol caused mainly by hepatic secretion of free cholesterol. A measure for this defect is the conventional cholesterol supersaturation index (CSI). This parameter seems to over‐estimate the ‘effective supersaturation’ in terms of thermodynamic activity of cholesterol monohydrate in bile. The basic information about cholesterol solubilization has been derived from systematic studies of model bile systems at equilibrium. The various cholesterol carriers in bile are summarized in Fig. 8. Mixed micelles and unilamellar vesicles appear to be the major cholesterol carriers. The absolute amount, however, carried by each lipid aggregate cannot be precisely determined by the current methodology. Fusion of cholesterol‐rich vesicles and aggregation into large lamellar liquid crystals is correlated with appearance of solid cholesterol crystals. Therefore, it has been postulated that cholesterol crystals nucleate from these liquid crystalline aggregates. Further growth occurs by apposition of cholesterol molecules, presumably derived from unilamellar vesicles. Recently, however, evidence has been provided that the lecithin and cholesterol of liquid crystalline aggregates may derive directly from both micelles and vesicles [87]. In contrast to static model bile systems, native bile is a dynamic open system with changing influxes and effluxes of the various lipids causing a fluctuation of lipid concentration and aggregation over time. Although valuable information has been gained from equilibrium studies, the question remains yet unsolved whether native bile systems are really at equilibration. Also no information exists about the relaxation times for the native system to re‐equilibrate to a new configuration, and by which pathways cholesterol is redistributed between the various carriers. This is directly related to the influence of functional defects of the gallbladder. Gallbladder hypomotility, as demonstrated in the gallstone‐bearing group, leads to a prolonged reaction time for the multifactorial processes involved in gallstone formation. In addition, the enlarged biliary residual volume is likely to prevent an effective clearing of debris and microcrystals that are involved in biliary sludge formation. A change in secretory function of the gallbladder epithelium, preferentially mucin hypersecretion, seems also to be involved in sludge and finally gallstone formation. Mucus gel may provide the matrix for cholesterol crystal nucleation. Gallbladder mucin itself has been shown to have a nucleation‐promoting effect. Considering the high mucin concentration in the mucus gel, this effect may be important, although the specific promoting activity of mucin on cholesterol crystallization is by about 100‐fold less potent than the effect reported for other promoting factors. The modulation of metastability under the influence of kinetic factors ha...