Describe the functions of bile and the mechanisms controlling its formation and secretion.

Outline:

·        Composition of bile:

- bile acids

- bile pigments

- cholesterol, phospholipids

·        Role in:

- lipid digestion

- excretion of bilirubin, cholesterol

·        Regulation of formation by: reabsorbed bile salts

·        Regulation of secretion by: CCK, secretin, vagal stimulation

Essay:

            The hepatic function most important to the digestive tract is the secretion of bile. Bile, produced by hepatocytes, contains bile acids, cholesterol, phospholipids, and bile pigments. Bile acids are synthesized by the hepatocytes from cholesterol, from which they acquire their steroid nucleus. The major bile acids synthesized by the liver are the primary bile acids – cholic and chenodeoxycholic acid. Bile acids are normally conjugated with glycine or taurine. Conjugated bile acids are present almost entirely as salts of various cations and are often called bile salts. The components of bile pigments are bilirubin glucuronides, which are formed from bilirubin, a breakdown product of hemoglobin.

            Bile plays an important role in the digestion and absorption of dietary fats. Bile acids, together with phospholipids and monoglycerides, are responsible for the emulsification of fat preparatory to its digestion and absorption in the small intestine. Due to their amphipathic properties, the bile salts tend to form cylindrical disks called micelles, with the hydrophilic surfaces facing out and a hydrophobic core. When the concentration of bile salts in the intestine is high, as after a meal, lipids and bile salts interact spontaneously to form micelles. Lipids collect in the micelles, with cholesterol in the hydrophobic center and the amphipathic phospholipids and monoglycerides lined up with their hydrophilic heads on the outside and their hydrophobic tails in the center. Micellar formation further solubilizes the lipids and provides a mechanism for their transport to the enterocytes. Thus, the micelles move down their concentration gradient through the unstirred layer to the brush border of the mucosal cells. The lipids diffuse out of the micelles, and a saturated aqueous solution of the lipids is maintained in contact with the brush border of the mucosal cells. The lipids enter the cells by passive diffusion and are rapidly esterified inside the cells, maintaining a favorable concentration gradient from the lumen into the cells. Thus, the bile salt micelles solubilizes lipids, transport them across the unstirred layer, and keep a saturated solution of lipids in contact with the mucosal cells.

            Greater than 95% of the bile salts are reabsorbed back into the terminal ileum and returned to the liver via the enterohepatic circulation. Between 30 and 50g of bile salts are secreted by the liver into the duodenum each day and only 0.5g is lost daily in the feces. The secretion of bile is the major route for the excretion of cholesterol and bilirubin. Because the steroid nucleus of cholesterol cannot be degraded in the body, the excretion of bile salts serves as a major route for the removal of the steroid nucleus and thus of cholesterol from the body. The conjugated bilirubin secreted into the duodenum is reduced by fecal flora to a group of colorless tetrapyrrolic compounds called urobilinogens. Some urobilinogen is reabsorbed from the gut into the portal blood and transported to the kidney, where it is converted to the yellow urobilin and excreted in the urine. Most of the urobilinogens of the feces are oxidized by intestinal bacteria to stercobilin, giving stools their characteristic brown color.

            Bile is synthesized in the hepatocytes of the liver and secreted into the bile canaliculi, from where they travel down the bile duct. Between meals, the tone of the sphincter of Oddi, which guards the entrance of the common bile duct into the duodenum is high. Thus, most bile flow is diverted into the gallbladder, where the bile is stored temporarily and concentrated by absorption of water. The formation and release of bile by the hepatocytes is regulated chiefly by the levels of bile acid in the portal blood. The secretion of bile from the gall bladder into the duodenum is regulated by the hormones CCK and secretin and neural stimulation.

            The rate of return of the bile acids to the liver via the enterohepatic circulation affects the rate of synthesis and secretion of bile acids. Bile acids in the portal blood stimulate the uptake and resecretion of bile acids by the hepatocytes but inhibit the synthesis of new bile acids. 7a-hydroxylase, the rate-limiting enzyme that catalyzes the formation of 7a-hydroxycholesterol from cholesterol, the first step in the synthesis of bile acids, is strongly inhibited by cholic acid itself.

            Emptying of the gallbladder begins several minutes after the start of a meal. Intermittent contractions of the gallbladder force bile through the partially relaxed sphincter of Oddi. During the cephalic and gastric phases of digestion, gallbladder contraction and relaxation of the sphincter are mediated by cholinergic fibers in the vagus nerves and by gastrin released from the stomach. Stimulation of sympathetic nerves to the gallbladder and duodenum inhibits emptying of the gallbladder. The highest rate of gallbladder emptying occurs during the intestinal phase of digestion; the strongest stimulus for the emptying is CCK. CCK reaches the gallbladder via the circulation, and it causes strong contractions of the gallbladder and relaxation of the sphincter of Oddi. Secretin increases the water and bicarbonate content of bile.