Bile secretion and enterohepatic circulation

Bile is a greenish liquid that’s made by the liver and is stored in the gallbladder.

Bile is a bit like an alkaline soup and it’s ingredients include a variety of organic molecules.

Bile does a number of things including helping with digestion, absorption of fats, and excretion of various molecules.

Normally, lipids are insoluble in water, so that’s why bile is needed to help emulsify and solubilize them.

The organic composition of bile is mainly made up of bile salts and phospholipids, with cholesterol, and bile pigments called bilirubin, making up only a small percentage.

Bile is first manufactured in the liver by cells called hepatocytes.

Hepatocytes use an enzyme called 7-alpha-hydroxylase to convert cholesterol into two primary bile acids, called cholic acid and chenodeoxycholic acid.

In the intestines, some of these primary bile acids get dehydroxylated, giving rise to secondary bile acids - deoxycholic acid and lithocholic acid.

The liver can conjugate, or attach the amino acids glycine or taurine to all four of these bile acids and this ultimately gives rise to 8 different forms of bile salts. And it’s these bile salts that are the main component of bile.

So bile is made in the liver and flows into the intestines.

The journey starts when bile flows into the left and right hepatic ducts which eventually merge to form the common hepatic duct.

The common hepatic duct then leads to the cystic duct which brings the bile to the gallbladder.

The gallbladder is a small pear-shaped hollow organ located beneath the liver, and this is where bile is stored and becomes more concentrated.

Approximately 30 minutes after consuming a meal, the food is broken down into a slurry called chyme, and that chyme begins to enter the first part of the small intestine - the duodenum. When that happens, I-cells, which are in the mucosal lining of the intestine secrete a hormone called cholecystokinin, or CCK, into the bloodstream.

Cholecystokinin travels through the blood and reaches the gallbladder, causing it to contract really strongly. Those strong contractions cause the stored bile to be get squirted out of the gallbladder and into the common bile duct.

The bile ducts are lined by cells called cholangiocytes, which secrete bicarbonate-rich fluid into the biliary tree.

Cholecystokinin also causes the relaxation of the sphincter of Oddi, the muscular valve between the common bile duct and the duodenum. This allows the bile and the bicarbonate-rich fluid to flow through the sphincter of Oddi, into the duodenum.

Bile salts are amphipathic, meaning that the molecules have parts that are hydrophilic, or water loving, and other parts that are hydrophobic, or water fearing. This unique structure allows bile salts to self-assemble into mixed micelles when they enter the intestines.

Micelles have a hydrophilic exterior and a hydrophobic interior, and little droplets of fat from the diet can then settle within this hydrophobic interior. This is how bile salts emulsify or break down large fat globules into small emulsion droplets.

If you compare a large fat globule to many small ones, the biggest difference is surface area. In other words, by emulsifying the fat, micelles help generate a much greater surface area for the enzyme pancreatic lipase to digest lipids into fatty acids and monoglycerides.

Micelles move lipids to the brush border of the intestinal cells where they diffuse out and are absorbed through the intestinal villi.

Without the help of bile salts, lipids wouldn’t get digested and absorbed, and they’d get excreted in the feces causing steatorrhea, an oily-type of stool.

In addition to lipid digestion and absorption, bile acids also help with bilirubin excretion.