Gallbladder and Small Intestinal Regulation of Biliary Lipid Secretion during Intraduodenal Infusion of Standard Stimuli

Abstract

A B S T R A C T The gallbladder and small intestine are reservoirs for the bile acid pool during its enterohepatic circulation and, as such, may regulate biliary secretion of bile acid. During studies of biliary bile acid secretion, a stimulus to gallbladder contraction is continuously infused into the duodenum. Under these conditions, it is assumed that the gallbladder is tonically contracted and that the rate of bile acid secretion into the duodenum equals the hepatic bile acid secretion rate. However, secretion rates vary by as much as 100%, depending upon which of two standard stimuli is used. Therefore, we studied the role of gallbladder emptying and small intestinal transit in determining biliary lipid secretion rate and composition during infusion of these stimuli in five healthy subjects. Each subject was studied with a liquid formula containing 40% of calories as fat, and with an amino acid solution for 10 h. Bile acid, phospholipid, cholesterol, and markers were measured in duodenal bile and hourly secretion rates were calculated by marker dilution technique. Real-time gallbladder sonographs and serum pancreatic polypeptide levels were obtained every 30 min. Small bowel transit time was estimated by the breath hydrogen response after giving lactulose intraduodenally.During liquid formula infusion, gallbladder emptying was more complete, small intestinal transit was faster, and pancreatic polypeptide levels were higher. Secretion rates of all lipids were greater and molar

Effect of the prokinetic agent, erythromycin, in the richardson ground squirrel model of cholesterol gallstone disease

“…5,34 This results in higher cholesterol saturation of gallbladder bile, posing a risk for gallstone formation. 5,[8][9][10]34 In the present study, the high-cholesterol diet significantly impaired gallbladder motility and prolonged small intestinal transit. These motility defects most likely resulted from the excess accumulation of cholesterol in the sarcolemmal membrane of the involved organs as a result of a sustained exposure to bile supersaturated with cholesterol.…”

“…1,2,[4][5][6][7] Gallbladder filling/emptying and small intestinal transit, the two ratelimiting steps in the enterohepatic circulation of bile salts, govern the cycling frequency of bile salts and their hepatic secretion rate. [1][2]5,8,9 The motor functions of the gallbladder and small intestine thus have a profound impact on bile salt secretion and pool size, and biliary lipid composition, influencing the propensity to gallstone formation. 3,4,[8][9][10][11][12] Among the growing list of pathogenic events implicated in cholesterol gallstone formation, prolonged intestinal transit and gallbladder stasis both impede enterohepatic cycling and are thus able to lower the bile salt secretion, predisposing to the formation of bile with an increased cholesterol saturation.…”

“…This in turn should enhance their hepatic secretion and reduce the risk of developing bile saturated with cholesterol. [8][9][10] Such improved bile composition, plus enhanced gallbladder emptying, should prevent gallstone formation.…”

Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones.

“…Biliary lipid composition and secretion rates were measured by established procedures and methods, described in detail by us and others (23,24). After insertion ofa nasoduodenal tube, a sample ofduodenal content, "hepatic bile," was obtained and gallbladder contraction was stimulated by an intravenous infusion ofthe octapeptide ofcholecystokinin (CCK; Squibb CCK-8, 0.02 ,g/kg per h) and a sample of concentrated bile "gallbladder bile" was collected.…”

Bile Acid Diarrhea

“…The corresponding bile acid pool size is 2-4 g and it circulates 5-10 times each day [6]. Enterohepatic circulation of bile acids depends on minimal passive absorption of deconjugated bile acids from the jejunum and ileum, but much more importantly, the active transport of conjugated bile acids from the ileum.…”