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Studies utilizing balloon-occludable T or duodenal tubes in subjects with and without gallbladders were undertaken to identify the contribution of the gallbladder, the sphincter of Oddi, and bile salts to the delivery of bile to the duodenum. Patients with and without a functional sphincter of Oddi and with and without a gallbladder were compared. The presence of a functional sphincter of Oddi in duodenal tube patients reduced bile salt output by more than 67% from that observed in T-tube patients. When cholecystectomized and normal patients were compared using the duodenal tube, peak bile salt output was significantly increased in normal subjects, reflecting gallbladder contraction, but total bile salt output was not significantly increased suggesting that the gallbladder has a minor role in bile delivery. Exogenous infusion of cholecystokinin produced much more stable bile secretion than did endogenous release of cholecystokinin by intraduodenal infusion of essential amino acids. This rhythmic release of bile after endogenous cholecystokinin release was related to the concentration of bile salts in the intestinal lumen. Thus, delivery of bile to the duodenum is wave-like and is predominantly controlled by the sphincter of Oddi.

Despite wide variations in bile secretion and biliary tract capacitance, the pressure in the bile ducts is fairly constant. Recent studies have demonstrated that both inhibitory and excitatory nerves regulate the activity of the sphincter of Oddi. In the present study, it was consistently found that the resistance by the choledochoduodenal junction to a constant flow, within the physiologic range of hepatic bile output, is reduced when the hydrostatic pressure in the gallbladder and bile ducts is increased from 0 to 10, 0 to 15, and 0 to 20 cmH2O. This response was eliminated by tetrodotoxin or infiltration of the junction between the common bile duct and the cystic duct by mepivacaine, a local anesthetic. The results suggest a homeostatic mechanism during the interprandial periods, when the activity of the sphincter of Oddi is regulated by the distending pressure in the biliary tract. This reflex regulation is mediated by modulation of the activity of inhibitory nerves running along the common bile duct.

Arachidonic acid metabolites are involved in a wide spectrum of hepatobiliary physiologic functions and disease. Prostanoids alter hepatic bile flow. Prostaglandins with a C9 ketooxygen stimulate a bicarbonate-rich choleresis and those with a C9 hydroxyloxygen produce a chloride-rich choleresis. Prostaglandin F2 alpha stimulates the release of the potent choleretic glucagon and the stimulatory effect of prostaglandin F2 alpha on bile flow is inhibited by cyclooxygenase inhibitors, suggesting that prostaglandins play a role in the release of choleretic hormones as well as in their action. Prostanoids are involved in gallbladder contraction and water absorption. Prostaglandins produce gallbladder contraction in various species and cause gallbladder relaxation in other species. Prostaglandins also may be mediators of cholecystokinetic hormone action; however, cyclooxygenase inhibitors do not inhibit the effect of cholecystokinetic hormones in all species. Prostanoids alter the normal process of water absorption by gallbladder mucosa and induce net water secretion. The inflamed gallbladder secretes rather than absorbs fluid. The demonstration that prostaglandin E2 inhibits gallbladder fluid absorption has led to subsequent studies that demonstrated that the secretion of fluid into the inflamed gallbladder lumen may be mediated by prostanoids. In cholecystitis, the prostanoids may mediate the distention produced by mucosal fluid secretion and the contraction of the diseased gallbladder. The inflammatory changes produced in various experimental models of cholecystitis can be prevented by cyclooxygenase inhibitors. Cyclooxygenase inhibitors decrease gallbladder prostaglandin formation and are effective in producing relief of the symptoms of gallbladder disease. In experimental cholesterol gallstone formation, prostaglandins are involved in the production of mucin, which acts as a nidus for stone formation, and cyclooxygenase inhibitors prevent the formation of experimental cholesterol gallstones. Prostaglandins have been shown to be cytoprotective in various types of experimental hepatic injury and leukotrienes have been shown to be injurious to hepatocytes and biliary tract tissues. Specific prostanoids and lipoxygenase inhibitors may be valuable in treating patients with various acute hepatic inflammatory disease processes. Continued evaluation of the role of arachidonic acid metabolites in hepatobiliary physiology and disease may lead to important new therapeutic modalities.

Most of the gastrointestinal tract and the biliary tract have a cyclic motor activity. The electric counterpart of this motor activity is called cyclic myoelectric activity. A typical motor cycle in the LES, stomach, and small intestine is composed of a quiescent state, followed by progressively increasing amplitude and frequency of contractions culminating in a state of maximal contractile activity. The colonic motor cycle has only the quiescent and the contractile states. In the small intestine, these motor complexes migrate in an aborad direction, and in the colon in both orad and aborad directions. The mechanisms of initiation and migration of these complexes are best understood in the small intestine. Both the initiation and migration of these complexes seem to be controlled by enteric neural mechanisms. The functions of the enteric mechanisms may be modulated by the central nervous system and by circulating endogenous substances. The mechanisms of initiation of these complexes are not completely understood in the rest of the gastrointestinal tract and in the biliary tract. The physiologic function of these motor complexes that occur only after several hours of fast in the upper gastrointestinal tract of nonruminants may be to clean the digestive tract of residual food, secretions, and cellular debris. This function is aided by a coordinated secretion of enzymes, acid, and bicarbonate. In ruminants, phase III activity is associated with the distal propulsion of ingested food. The function of colonic motor complexes that are not coordinated with the cyclic motor activities of the rest of the gastrointestinal tract may be only to move contents back and forth for optimal absorption.