Abnormal gallbladder emptying in a subgroup of patients with gallstones

doi:10.1016/0016-5085(85)90152-0

Gastroenterology

Volume 88, Issue 3, March 1985, Pages 787-791

https://doi.org/10.1016/0016-5085(85)90152-0 Get rights and content

Abstract

Gallbladder stasis has been implicated in gallstone formation. Gallbladder filling and emptying were quantitated by computer-assisted cholescintigraphy in 41 normal subjects versus 26 patients with gallstones. Gallbladder contraction was induced by low-dose (1.2 U/kg · h) cholecystokinin infusion. Gallstone patients exhibited normal gallbladder filling, but emptying was significantly (p < 0.01) reduced compared with controls. On closer inspection, the patients fell into two subgroups, separated by t_1/2, the time to empty 50% of gallbladder contents, 19.1 min ( $\bar{x}$ + 2 SD of control). Fifteen patients (57.7%) with a normal t_1/2 (< 19.1 min) exhibited both normal filling and normal emptying. The remaining 11 patients (43.3%) with t_1/2 > 19.1 min had grossly abnormal gallbladder emptying, significantly (p < 0.001) different from both the previous patient subgroup and the controls. There was no significant difference in age, sex, prevalence of obesity, presence or absence of biliary colic, and gallstone size, number, or calcification between these two subgroups. Thus, defective gallbladder emptying is evident in a subgroup of gallstone patients, and is independent of clinical features, stone size, and number. Impaired emptying should be considered when assessing pathogenesis or medical therapy.

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The role of the gallbladder in gallstone formation

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Cholecystokinin-Cholescintigraphy in Adults: Consensus Recommendations of an Interdisciplinary Panel
2011, Clinical Gastroenterology and Hepatology
Citation Excerpt :
Gallstones, regardless of type, are typically classified into symptomatic or asymptomatic. It has been previously demonstrated that GBEF is frequently reduced in patients with gallstones,49,50 although the role this plays in the pathogenesis of gallstone disease remains unclear as does its association with symptoms. Two major questions have emerged regarding the possible use of CCK-CS in patients with cholelithiasis: (1) can CCK-CS predict which asymptomatic patient will progress to symptoms; and, (2) can CCK-CS determine whether atypical symptoms are of gallbladder origin?
Cholecystokinin-cholescintigraphy (CCK-CS) provides a physiologic, noninvasive, and quantitative method for assessing gallbladder contraction and calculation of a gallbladder ejection fraction (GBEF). At present, it is used most commonly to identify patients with suspected functional gallbladder disorder. However, the methodology of CCK infusion and normal values differ markedly among imaging centers.
This document represents the consensus opinion of an interdisciplinary panel that gathered to assess the current optimal method for performing CCK-CS in adults, potential uses and limitations of CCK-CS, and questions that require further investigation.
The panel recommended the use of a single, standardized, recently described CCK-CS protocol that involves infusion of 0.02 μg/kg of sincalide over 60 minutes with a normal gallbladder ejection fraction defined as ≥38%. The panel emphasized the need for a large, multicenter, prospective clinical trial to establish the utility of CCK-CS in the diagnosis of functional gallbladder disease. Although not without controversy regarding its clinical utility, the primary indication for CCK-CS at present is the well-selected patient with suspected functional gallbladder disorder.
Agreement was reached that the adoption of this standardized protocol is critical to improve how CCK-CS is used to direct patient care and will represent an improvement over the diverse methods currently in use by eliminating the current lack of uniformity and adding both reliability and credibility to the results.
Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK-deficient mice
2010, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
We investigated the effect of gallbladder hypomotility on cholesterol crystallization and growth during the early stage of gallstone formation in CCK knockout mice. Contrary to wild-type mice, fasting gallbladder volumes were enlarged and the response of gallbladder emptying to a high-fat meal was impaired in knockout mice on chow or the lithogenic diet. In the lithogenic state, large amounts of mucin gel and liquid crystals as well as arc-like and tubular crystals formed first, followed by rapid formation of classic parallelogram-shaped cholesterol monohydrate crystals in knockout mice. Furthermore, three patterns of crystal growth habits were observed: proportional enlargement, spiral dislocation growth, and twin crystal growth, all enlarging solid cholesterol crystals. At day 15 on the lithogenic diet, 75% of knockout mice formed gallstones. However, wild-type mice formed very little mucin gel, liquid, and solid crystals, and gallstones were not observed. We conclude that lack of CCK induces gallbladder hypomotility that prolongs the residence time of excess cholesterol in the gallbladder, leading to rapid crystallization and precipitation of solid cholesterol crystals. Moreover, during the early stage of gallstone formation, there are two pathways of liquid and polymorph anhydrous crystals evolving to monohydrate crystals and three modes for cholesterol crystal growth.
Orlistat reduces gallbladder emptying by inhibition of CCK release in response to a test meal
2007, Regulatory Peptides
Orlistat is a covalent inhibitor of digestive lipase derived from lipstatin, the natural product of Streptomyces toxytricini. By blocking the active site of intestinal lipase, orlistat inhibits hydrolysis of dietary triglycerides and thus reduces the intestinal lipid absorption. It is uncertain whether intestinal inhibition of lipase by orlistat also interferes with nutrient-induced CCK release from intestinal I-cells. The aim of the present study was therefore to assess whether oral administration of orlistat inhibits CCK release in response to a test meal and thus causes impaired gallbladder emptying.
22 healthy volunteers were given a test meal consisting of 200 ml dairy cream and two teaspoons of chocolate powder (552 kcal = 2328 kJ; 56.0 g fat; 5.2 g proteins, 6.6 g carbohydrates), with and without oral application of 120 mg orlistat. Gallbladder volume was determined by ultrasound before and 5, 10, 20, 30 and 40 min after meal ingestion. In parallel, a venous blood sample was collected for the measurement of bioactive CCK. CCK activity was assessed using a bioassay with isolated rat pancreatic acini cells.
Oral administration of orlistat significantly impairs gallbladder emptying. After ingestion of the test meal the gallbladder contracted by 78.5% in the control group, whereas the test group with orlistat only showed a contraction of 45.7% (p < 0.01). Maximal contraction was reached after 35 to 40 min, the maximal gallbladder emptying was delayed up to 10 min by orlistat. Orlistat induced a significant reduction of bioactive CCK levels in response to a test meal (CCK_max with orlistat = 4.1 pmol/l; CCK_max without orlistat = 7.8 pmol/l). CCK levels were reduced by 47% and the onset of maximal CCK secretion was delayed up to 10 min.
The inhibition of intestinal lipolytic activity by orlistat results in reduced gallbladder emptying through inhibition of meal-mediated CCK release. We therefore hypothesize that impaired gallbladder motility may represent a risk factor in chronic treatment of severe obesity using orlistat.
Symptoms and diagnosis of gallbladder stones
2006, Best Practice and Research: Clinical Gastroenterology
Citation Excerpt :
In this context, EUS shows a sensitivity range of 94–98%.39,40 Biliary scintigraphy and, later, “functional” ultrasonography, have been employed to study gallbladder motility in vivo.41–45 Whereas scintigraphy is costly, not widely available and exposes the patients to radiations, functional ultrasonography allows easy measurement of time-related changes of fasting and postprandial gallbladder volumes to assess the gallbladder motor function profile.43,46–51
The clinical aspects and the diagnostic features of gallstone disease are described. The natural history of silent gallstones is overviewed, and the risk of developing symptoms and complications is also discussed. The importance of colicky pain as a specific gallstone symptom is highlighted, and the role of both laboratory tests and diagnostic investigations for differential diagnosis is discussed. Finally, we describe the diagnostic features of gallbladder stone disease, including indications, sensitivity, specificity, and limitations of different test investigations under special circumstances.
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: This research was supported by the Alberta Heritage Foundation for Medical Research and the Medical Research Council of Canada.

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Abnormal gallbladder emptying in a subgroup of patients with gallstones

Abstract

Gastroenterology

Gastroenterology

Am J Obstet Gynecol

Gastroenterology

Gastroenterology

Gastroenterology

J Surg Res

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

The role of the gallbladder in gallstone formation