The liver cells synthesize about 6 grams of bile salts daily. The precursor of the bile salts is cholesterol, which is either present in the diet or synthesized in the liver cells during the course of fat metabolism. The cholesterol is first converted to cholic acid or chenodeoxycholic acid in about equal quantities. These acids in turn combine principally with glycine and to a lesser extent with taurine to form glyco- and tauro-conjugated bile acids. The salts of these acids, mainly sodium salts, are then secreted in the bile.
The bile salts have two important actions in the intestinal tract:
First, they have a detergent action on the fat particles in the food. This action, which decreases the surface tension of the particles and allows agitation in the intestinal tract to break the fat globules into minute sizes, is called the emulsifying or detergent function of bile salts.
Second, and even more important than the emulsifying function, bile salts help in the absorption of (1) fatty acids, (2) monoglycerides, (3) cholesterol, and (4) other lipids from the intestinal tract. They help in this absorption by forming small physical complexes with these lipids; the complexes are called micelles, and they are semisoluble in the chyme because of the electrical charges of the bile salts. The intestinal lipids are “ferried” in this form to the intestinal mucosa, where they are then absorbed into the blood, as will be described in detail in Chapter 66. Without the presence of bile salts in the intestinal tract, up to 40 percent of the ingested fats are lost into the feces and a metabolic deficit often develops because of this nutrient loss.
Enterohepatic Circulation of Bile Salts. About 94 percent of the bile salts are reabsorbed into the blood from the small intestine, about one half of this by diffusion through the mucosa in the early portions of the small intestine and the remainder by an active transport process through the intestinal mucosa in the distal ileum. They then enter the portal blood and pass back to the liver. Upon reaching the liver and during first passage through the venous sinusoids, these salts are absorbed almost entirely back into the hepatic cells and are then resecreted into the bile.
In this way, about 94 percent of all the bile salts are recirculated into the bile, so on average these salts make the entire circuit some 17 times before being carried out in the feces. The small quantities of bile salts lost into the feces are replaced by new amounts formed continually by the liver cells. This recirculation of the bile salts is called the enterohepatic circulation of bile salts.
The quantity of bile secreted by the liver each day is highly dependent on the availability of bile salts—the greater the quantity of bile salts in the enterohepatic circulation (usually a total of only about 2.5 grams), the greater the rate of bile secretion. Indeed, ingestion of supplemental bile salts can increase bile secretion by several hundred milliliters per day.
If a bile fistula empties the bile salts to the exterior for several days to several weeks so they cannot be reabsorbed from the ileum, the liver increases its production of bile salts 6- to 10-fold, which increases the rate of bile secretion most of the way back to normal. This demonstrates that the daily rate of liver bile salt secretion is actively controlled by the availability (or lack of availability) of bile salts in the enterohepatic circulation.
Role of Secretin in Controlling Bile Secretion. In addition to the strong stimulating effect of bile acids to cause bile secretion, the hormone secretin—which also stimulates pancreatic secretion—increases bile secretion, sometimes more than doubling its secretion for several hours after a meal. This increase in secretion consists almost entirely of secretion of a sodium bicarbonate–rich watery solution by the epithelial cells of the bile ductules and ducts and does not represent increased secretion by the liver parenchymal cells themselves. The bicarbonate in turn passes into the small intestine and joins the bicarbonate from the pancreas in neutralizing the hydrochloric acid from the stomach. Thus, the secretin feedback mechanism for neutralizing duodenal acid operates not only through its effects on pancreatic secretion but also to a lesser extent through its effect on secretion by the liver ductules and ducts.
Liver Secretion of Cholesterol and Gallstone Formation
Bile salts are formed in the hepatic cells from cholesterol in the blood plasma. In the process of secreting the bile salts, about 1 to 2 grams of cholesterol are removed from the blood plasma and secreted into the bile each day.
Cholesterol is almost completely insoluble in pure water, but the bile salts and lecithin in bile combine physically with the cholesterol to form ultramicroscopic micelles in the form of a colloidal solution, as explained in more detail in Chapter 66. When the bile becomes concentrated in the gallbladder, the bile salts and lecithin become concentrated along with the cholesterol, which keeps the cholesterol in solution.
Under abnormal conditions, the cholesterol may precipitate in the gallbladder, resulting in the formation of cholesterol gallstones, as shown in Figure 1. The amount of cholesterol in the bile is determined partly by the quantity of fat that the person eats, because liver cells synthesize cholesterol as one of the products of fat metabolism in the body. For this reason, people who consume a high-fat diet over a period of years are prone to development of gallstones.
Inflammation of the gallbladder epithelium, often resulting from a low-grade chronic infection, may also change the absorptive characteristics of the gallbladder mucosa, sometimes allowing excessive absorption of water and bile salts but leaving behind the cholesterol in the gallbladder in progressively greater concentrations. The cholesterol then begins to precipitate, first forming many small crystals of cholesterol on the surface of the inflamed mucosa, but then progressing to large gallstones.
Fig1. Formation of gallstones.
