Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
113 Biliary Physiology The liver produces bile continuously and excretes it into the bile canaliculi. The normal adult produces 500 to 1,000 mL of bile daily. The secretion of bile is responsive to neurogenic, humoral, and chemical stimuli. Parasympathetic stimulation via the vagus nerve increases bile secretion, whereas sympathetic stimulation via splanchnic nerves decreases bile flow. Hydrochloric acid, partly digested proteins, and fatty acids in the duodenum stimulate the release of secretin from the duodenum that subsequently increases bile production and flow. Bile flows from the liver through to the hepatic ducts, into the common hepatic duct, through the common bile duct, and finally into the duodenum. With an intact sphincter of Oddi, bile flow is directed into the gallbladder. Bile is mainly composed of water, electrolytes, bile salts, proteins, lipids, and bile pigments. Bile concentrations of sodium, potassium, calcium, and chloride are equal to plasma or extracellular fluid. The pH of hepatic bile is usually neutral or slightly alkaline but varies with diet; an increase in protein shifts the bile to a more acidic pH. The primary bile salts cholate and chenodeoxycholate are synthesized in the liver from cholesterol.They are conjugated there with taurine and glycine and act within the bile as anions (bile acids) that are balanced by sodium. Cholesterol and phospholipids from the liver are the principal lipids found in bile. The synthesis of phospholipids and cholesterol by the liver is in part regulated by bile acids. Bile color is due to the pigment bilirubin diglucuronide, a metabolic product from hemoglobin breakdown. In the intestine, bacteria convert it into urobilinogen, a small fraction of which is absorbed and secreted into the bile and may be secreted in urine. Bile salts are excreted into the bile by the hepatocytes and aid in the digestion and absorption of fats in the intestines. Eighty percent of the conjugated bile acids are absorbed in the terminal ileum. The remainder is dehydroxylated (deconjugated) by gut bacteria, forming the secondary bile acids deoxycholate and lithocholate.These are absorbed in the colon, transported to the liver, con- jugated, and secreted into the bile. Eventually, about 95% of the bile acid pool is reabsorbed and returned via the portal venous system to the liver. Five percent is excreted in the stool, leaving the relatively small amount of bile acids to have maximum effect. The gallbladder, the bile ducts, and the sphincter of Oddi act together to store and regulate bile flow. The gallbladder’s main function is to concentrate and store hepatic bile and deliver bile into the duodenum in response to a meal. In the fasting state, 80% of bile is stored in the gallbladder. This storage is due to the absorptive capacity of the gallbladder. It rapidly absorbs sodium, chloride, and water against significant concentration gradients, concentrating the bile 10-fold and leading to a marked change in bile composition. This rapid absorption is one mechanism that prevents a rise in pressure within the biliary system under normal circumstances. Gradual relaxation and emptying of the gallbladder during the fasting period also plays a role in maintaining a relatively low intraluminal pressure in the biliary tree. The gallbladder’s epithelial cells secrete two important products: glycoproteins and hydrogen ions. Glycoproteins are believed to protect the mucosa from the lytic action of bile and to facilitate the passage of bile through the cystic duct. Hydrogen ions transported in the lumen lead to a decrease in the gallbladder bile pH. The acidification promotes calcium solubility, thereby preventing its precipitation as calcium salts. Gallbladder filling is facilitated by tonic contraction of the sphincter of Oddi, which creates a pressure gradient between the bile ducts and the gallbladder. During fasting the gallbladder does not simply fill passively. In association with phase II of the interdigestive migrating myenteric motor complex in the gut, the gallbladder repeatedly empties small volumes of bile into the duodenum. This process is mediated in part by the hormone motilin. In response to a meal, the gallbladder empties by a coordinated motor response of gallbladder contraction 263 264 and sphincter of Oddi relaxation. One of the main stimuli to gallbladder emptying is the hormone cholecystokinin (CCK), which is released endogenously from the duodenal mucosa in response to a meal. When stimulated by eating, the gallbladder empties 50% to 70% of its contents within 30 to 40 minutes. Over the following 60 to 90 minutes the gallbladder gradually refills, correlated with a reduced CCK level. Defects in the motor activity of the gallbladder are thought to play a role in cholesterol nucleation and gallstone formation. The vagus nerve stimulates contraction of the gallbladder, and splanchnic sympathetic stimulation is inhibitory to its motor activity. Parasympathomimetic drugs contract the gallbladder, whereas atropine leads to relaxation. Neurally mediated reflexes link the sphincter of Oddi with the gallbladder, stomach, and duodenum to coordinate the flow of bile into the duodenum.Antral distention of the stomach causes both gallbladder contraction and relaxation of the sphincter of Oddi. Hormonal receptors are located on the smooth muscles, vessels, nerves, and epithelium of the gallbladder. Cholecystokinin is released into the bloodstream by acid, fat, and amino acids in the duodenum. Cholecystokinin acts directly on smooth muscle receptors of the gallbladder and stimulates gallbladder contraction. It also relaxes the terminal bile duct, the sphincter of Oddi, and the duodenum. Cholecystokinin stimulation of the gall- Part XII. Gastrointestinal Disorders bladder and the biliary tree also is mediated by cholinergic vagal neurons. Vasoactive intestinal peptide (VIP) inhibits contraction and causes gallbladder relaxation. Somatostatin and its analogues are potent inhibitors of gallbladder contraction. Other hormones such as substance P and enkephalin affect gallbladder motility; however, the physiologic role is unclear. The sphincter of Oddi regulates flow of bile (and pancreatic juice) into the duodenum, prevents the regurgitation of duodenal contents into the biliary tree, and diverts bile into the gallbladder. It is a complex structure that is functionally independent of the duodenal musculature and creates a high-pressure zone between the bile duct and the duodenum. The sphincter of Oddi is 4 to 6 mm in length and has a basal resting pressure of about 13 mm Hg above the duodenal pressure. On manometry, the sphincter shows phasic contractions with a frequency of about four per minute and an amplitude of 120 to 140 mm Hg. The sphincter primarily controls the regulation of bile flow. Relaxation occurs with a rise in CCK level, leading to diminished amplitude of phasic contractions and reduced basal pressure, thereby allowing increased flow of bile into the duodenum. During fasting, the sphincter of Oddi activity is coordinated with the periodic partial gallbladder emptying and an increase in bile flow that occurs during phase III of the migrating myoelectric complexes.