Bile secretion and enterohepatic circulation

Definitions & Key takeaways

Bile is a greenish liquid secreted by the liver cells and stored in the gallbladder. Its purpose is the excretion of various compounds, digestion, and absorption of fats. Bile consists mainly of bile salts, phospholipids, cholesterol, conjugated bilirubin, electrolytes, and water. From the liver cells, bile moves through a series of ducts and exits through the common hepatic duct to get stored and concentrated in the gallbladder.

When the gallbladder is stimulated by cholecystokinin (CCK) hormone, it contracts and pushes bile through the cystic duct and into the common bile duct. The sphincter of Oddi relaxes, allowing bile to enter the intestinal (duodenal) lumen to fulfill its functions. Enterohepatic circulation refers to the substances metabolized in the liver, excreted through this bile to get into the intestinal lumen, and then reabsorbed and returned to the liver through the portal circulation.

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Introduction0:00–0:46

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 Production0:46–1:35

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.

Bile Secretion1:35–3:18

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.

Bile Salts3:18–4:40

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. Bilirubin is the pigment that gives bile its color and it’s actually a byproduct of hemoglobin metabolism.

Bilirubin Excretion4:40–6:52

As red blood cells near the end of their lifespan—which is about 120 days, they’re destroyed by immune cells like macrophages.
Macrophages break down hemoglobin, which are iron rich proteins inside red blood cells that binds oxygen, into heme and iron.
Next, an enzyme called heme oxidase converts heme into biliverdin, which is green in color. Then, the enzyme biliverdin reductase converts biliverdin into bilirubin, which is yellow, and the bilirubin leaves the macrophage and enters the blood.
The bilirubin leaving the macrophage is not water-soluble and is therefore referred to as indirect or unconjugated bilirubin.
Albumin in the blood, binds to the unconjugated bilirubin in order to give it a lift over to the liver where it’s taken up by hepatocytes.
Within the hepatocytes, the enzyme uridine glucuronyl transferase conjugates or attaches the unconjugated bilirubin to glucuronic acid, turning it into conjugated bilirubin.
And the conjugation of bilirubin allows the bilirubin to become more soluble. As a result, conjugated bilirubin can be secreted into bile, whereas unconjugated bilirubin is typically not found in bile.
So ultimately, bile containing the conjugated bilirubin flows into the intestines. In the intestines, certain bacteria hydrolyze and reduce conjugated bilirubin into a colorless compound called urobilinogen.
Urobilinogen can enter various pathways. Most of the urobilinogen, also called stercobilinogen when it’s in the intestines, becomes oxidized by gut bacteria to form stercobilin.
Stercobilin is what makes feces brown in color. Now there’s a system by which both bilirubin and bile acids get recycled - called enterohepatic circulation.

Enterohepatic Circulation6:52–8:05

A small amount of urobilinogen that’s not excreted in the feces, gets reabsorbed from the gut into the bloodstream. Some of that urobilinogen travels through the blood to the kidneys where it’s converted to urobilin, which is very water soluble and therefore excreted into the urine and gives urine its yellow color.
The rest goes right back to the liver to get sent out into the intestines once again. Now unlike bilirubin, where only a little bit is recycled through enterohepatic circulation, it turns out that 95% of the bile acids get recycled in that way, and only about 5% are lost in feces.
In fact, there are sodium-bile salt cotransporters within the intestine which specifically bring bile salts back into the enterocytes.
These bile acids get into the blood and ultimately get back to the liver so that they can get added back into the bile once again.
Alright, as a quick recap...bile is formed by the liver, stored in the gallbladder, and released into the duodenum. Bile salts are able to emulsify large lipid globules into smaller droplets to create a greater surface area upon which pancreatic lipase is able to work.

Review8:05–8:44

Aside from bile salts, another component of bile is a pigment known as bilirubin, which is a byproduct of red blood cell degradation.
Both bile salts and bilirubin can be recycled via enterohepatic circulation where they’re transported from the intestines back to the liver.