Regulation of Bile Release


Bile is produced in the liver by hepatocytes. Bile contains phospholipids and bile salts, emulsifying agents that are necessary for fat absorption and digestion. Importantly, the bile is also a route for excretion of cholesterol and bile pigments. Bile pigments are metabolic breakdown products of hemoglobin and cytochromes that give bile its yellow-green color. Bile pigments are further metabolized by bacteria in the colon, causing feces to have a characteristic brown color. Additionally, bile contains water and bicarbonate ions that are secreted by duct cells that line the bile ducts within the liver.

Bile storage in the gallbladder

Whether or not bile is released into the small intestine depends upon the activity of the sphincter of Oddi (also known as the hepatopancreatic sphincter). During the interdigestive period, the sphincter of Oddi is contracted, preventing bile from flowing out into the duodenum. As a consequence, pressure increases in the common bile duct, and bile flows into the gallbladder. In the gallbladder, epithelial cells reabsorb water and electrolytes, causing the bile to become more concentrated.

Bile release into the small intestine

During the digestive period, intestinal phase signals stimulate the release of bile into the small intestine.

Enterohepatic circulation

The total pool of bile salts present in the body is not sufficient to fully process the fats in a typical meal, thus bile salts need to be recycled. This is achieved by the enterohepatic circulation. Specific transporters in the terminal ileum move bile salts from the lumen of the digestive tract to the intestinal capillaries. They are then transported directly to the liver via the hepatic portal vein. Hepatocytes take up bile salts from the blood, and increase the secretion of bile salts into the bile canaliculi, small passageways that convey bile into the larger bile ducts. 95% of the bile that is released to the small intestine is recycled via the enterohepatic circulation,while 5% of the bile salts are lost in the feces.


In the majority of cases, gallstones are precipitates of cholesterol. Cholesterol is a nonpolar molecule that is kept in solution in the bile by bile salts and phospholipids. Gallstones form when the level of cholesterol in the bile exceeds the capacity of the phospholipids and bile salts to keep it in solution. This might occur in someone with hypercholesterolemia (high circulating levels of LDL cholesterol), or in an older person in whom bile salt synthetic enzymes have become less active.

Gallstones can be completely asymptomatic. When they become a problem is when gallbladder contractions cause a stone to move into one of the bile ducts. The figure summarizes the pathological consequences of gallstones in different locations. Notably, a gallstone blocking the common bile duct will prevent the flow of bile into the small intestine. This causes decreased excretion of bile pigments and can lead to jaundice as bilirubin accumulates in tissues. If the gallstone is lodged in the duodenal papilla, it will block the release of pancreatic secretions. Inappropriate activation of pancreatic zymogens within the pancreas leads to acute pancreatitis (tissue damage and inflammation in the pancreas).

Gallstones are usually treated by surgical methods. Gallstones confined to the gallbladder and cystic bile duct can be treated with removal of the gallbladder (cholecystectomy). Endoscopic surgical methods can be used to remove gallstones lodged in the common bile duct or duodenal papilla. In patients that are not good candidates for surgery, shock waves can be used to break up stones. Oral bile salts are used to help solubilize cholesterol gallstones. This therapy works because oral bile salts are delivered to the bile ducts and gallbladder by the enterohepatic circulation.

Quick Quiz

Fill in Answer Correct False Correct Answer
1. Bile will end up in the gallbladder when the sphincter of Oddi is _______.
2. The sphincter of Oddi is relaxed during the ______ period.
3. What hormone has its secretion stimulated by the presence of acidic chyme in the lumen of the duodenum?
4. What hormone stimulates contraction of the gallbladder?
5. Bile salts are found in which of the following? [duodenum, feces, hepatic portal vein, all of the above]
6. A patient has jaundice caused by a gallstone. In which duct is the gallstone located?
7. A patient is given oral bile salts to solubilize a gallstone in the common bile duct. What delivers the bile salts to the common bile duct?

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