Meal ingestion induces considerable gallbladder emptying (up to 70%-80% of fasting gallbladder volumes) by releasing the hormone cholecystokinin from the upper intestine. Impaired gallbladder emptying may prolong residence of bile in the gallbladder, allowing more time for nucleation of cholesterol crystals from supersaturated bile. Furthermore, in case of adequate emptying, cholesterol crystals that have nucleated may be ejected to the duodenum, whereas in case of impaired gallbladder emptying, these crystals may aggregate into macroscopic gallstones. Several studies have shown that gallstone patients may be divided into a group with severely impaired or even absent postprandial emptying ("bad contractors") and a group with good postprandial gallbladder emptying ("good contractors"). Patients with good postprandial contraction often have increased fasting and residual gallbladder volumes compared with normal controls.32 Prospective studies also indicate that impaired postprandial gallbladder motility is an independent risk factor for gallstone recurrence after successful treatment with extracorporeal shockwave lithotripsy.33 It is less well appreciated that significant periodic gallbladder emptying also occurs during the fasting state (20%-30% emptying in the fasting state vs 70%-80% emptying after a meal) at 1- to 2-hour intervals, associated with the cycle of the intestinal migrating motor complex and with a rise of plasma motilin levels.34 It has been found that gallstone patients show a pattern of less frequent migrating motor complex cycles, with absent interdigestive gallbladder emptying and altered motilin release compared with controls.35 A similarly prolonged migrating motor complex cycle has been found in the ground squirrel model of gallstone formation.36 The fasting state (ie, the night) seems to be the most vulnerable period for gallstone formation. During this period, biliary cholesterol saturation is highest, because of relatively low bile salt secretion and relatively high cholesterol secretion. There is also a progressive concentration of gallbladder bile during this period, which is partially counteracted by periodic interdigestive gallbladder contraction in association with antral phase 3 of the migrating motor complex of the intestine.
There is increasing insight into pathogenesis of impaired gallbladder motility. Significant absorbtion of cholesterol seems to occur from supersaturated bile in the gall-bladder.37,38 Excess cholesterol is then incorporated within the sarcolemmal plasma membrane of the gallbladder smooth muscle cell, with decreased membrane fluidity, impaired contractility, and impaired relaxation as a result.39 In addition, the gallbladder wall is exposed to detergent bile salts, unesterified cholesterol, and bacteria.40,41 As a result, a proinflammatory Th1 immune response may occur, which contributes to hypomotility. Although impaired motility could be in many cases secondary to biliary cholesterol supersaturation, it may still facilitate the process of gallstone formation. Gallbladder motility is often impaired in high-risk situations for gallstone formation, such as pregnancy, obesity, diabetes mellitus, gastric surgery, treatment with the somatostatin analogue octreotide, very low calorie dieting, and total parenteral nutrition.
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