Bile Salts Definition
Bile salts are one of the primary components of bile, a greenish-yellow fluid made by the liver and stored in the gallbladder. They are made up of bile acids that are conjugated with glycine or taurine and produced directly from cholesterol in the liver. Bile salts function as an emulsifier of lipids and fatty acids for absorption in the duodenum. They are also used as liver stimulants and laxatives.
Bile Salts Function
Bile salts are a primary component of bile, which is produced in the liver and stored in the gallbladder. The function of bile salts in the duodenum is to solubilize ingested fat and fat-soluble vitamins, facilitating their digestion and absorption.
Bile salts play a crucial role in hepatobiliary and intestinal homeostasis and digestion. They allow the body to excrete cholesterol and potentially toxic compounds like bilirubin and drug metabolites.
Bile salts are synthesized in liver cells called hepatocytes, then stored in the gallbladder until they are needed for digestion.
After we eat, our bile duct opens, allowing bile, enzymes, and secretions to do their jobs. Bile salts are components of bile that allow it to mix fats with water, electrolytes, and other organic molecules found in bile. Bile needs bile salts to break down fats and prevent them from crystallizing.
If the gallbladder is removed or there are diseases of the bowel, it can lead to a deficiency of bile salts. A deficiency of bile salts can cause digestive problems such as diarrhea or malabsorption of fat-soluble vitamins.
Bile Salts Types
There are four types of bile salts: primary, secondary, conjugated, and non-conjugated.
1. Primary
The primary bile salts in humans are cholate and chenodeoxycholate, which are synthesized de novo from cholesterol in the liver.
Taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile salts in humans.
These bile salts play a crucial role in emulsifying fat-soluble vitamins to enable their absorption, eliminating cholesterol from the body, driving the flow of bile to eliminate certain catabolites (including bilirubin), aiding in motility, reducing bacterial flora found in the intestine, and regulating the flow of bile from the liver into the bile capillaries by way of osmosis.
Bile acids have other functions such as forming and repairing cellular membranes, brain tissue formation, vision, immunity, inflammatory reaction regulation, and blood clotting. The enterohepatic circulation of bile acids allows a low rate of synthesis but with large amounts being secreted into the intestine.
Variations in the pool of primary bile salts occur among vertebrates: for instance, in humans and rats, the primary bile salts are cholate and chenodeoxycholate while in mice they are cholate and muri cholate. Secondary bile salts are synthesized by intestinal flora.
2. Secondary
Secondary bile acids are formed from bacterial actions in the colon on primary bile salts, cholate, and chenodeoxycholate.
In humans, taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile salts.
Intestinal bacteria transform primary bile salts into secondary bile salts by removing the hydroxyl group at C7. Secondary bile acids increase hydrophobicity and Pka of bile salts, facilitating their recovery by passive transport in the distal ileum during enterohepatic circulation.
Bile acids have several functions in the body. They eliminate cholesterol from the body, drive the flow of bile to eliminate certain catabolites (including bilirubin), emulsify fat-soluble vitamins to enable their absorption, aid in motility, and reduce bacteria flora found in the gallbladder.
Secondary bile acids and short-chain fatty acids are two major types of bacterial metabolites in the colon that cause opposing effects on colonic health.
While secondary bile acids promote colon cancer development, short-chain fatty acids have anti-inflammatory properties that protect against colon cancer development.
3. Conjugated
Bile salts are synthesized and conjugated in the liver, secreted into bile, stored temporarily in the gallbladder, and passed from the gallbladder into the duodenum. Conjugated bile acids are water-soluble, amphipathic, membrane-impermeable end products of cholesterol metabolism.
They have a hydrophobic and hydrophilic side that allows them to function as surfactants. Conjugated bile salts prevent passive reabsorption through the ileum wall and eliminate cholesterol from the body.
They also drive the flow of bile to eliminate certain catabolites (including bilirubin), emulsify fat-soluble vitamins to enable their absorption, aid in motility, and reduce bacterial flora found in the liver.
Bacterial deconjugation and dehydroxylation can cause disturbances in bile acid circulation. Biliary obstruction causes bile acid retention in hepatocytes leading to hepatocyte necrosis or apoptosis. When bile acids accumulate in hepatocytes, conjugates of CDCA undergo sulfation at C-3.
4. Non-Conjugated
Bile acids are amphipathic steroidal molecules derived from cholesterol catabolism. They are synthesized and conjugated in the liver, secreted into bile, stored temporarily in the gallbladder, passed from the gallbladder into the duodenum, and then reabsorbed in the ileum.
Bile acids have two forms: conjugated and unconjugated. Conjugated bile acids are those that are bonded to taurine or glycine.
In contrast, unconjugated bile salts are primary or secondary salts found within the biliary system that are not bonded to taurine or glycine either through the action of bacteria or through a lack of conjugation by the liver.
Bile salts function as lipid-emulsifying agents and help regulate the flow of bile from the liver into the bile capillaries (bile canaliculi) by way of osmosis.
This particular flow is known as bile salt-dependent flow (BDSF). Working together with bile salt-independent flow (BSIF), they help maintain a steady-state concentration of bile acids in hepatocytes and cholangiocytes.
Bile acids also have other functions such as eliminating cholesterol from the body, driving the flow of bile to eliminate certain catabolites (including bilirubin), emulsifying fat-soluble vitamins to enable their absorption, aiding in motility, and reducing bacterial flora found in the intestine.
Disturbances in bile acid circulation can cause various pathologies. For example, biliary obstruction causes bile acid retention in hepatocytes leading to hepatocyte necrosis or apoptosis.
When bile acids accumulate in hepatocytes, conjugates undergo sulfation at C-3. Sulfated and unsulfated bile acids regurgitate from the gallbladder.
Bile Salts and Bile Secretion
Bile is a greenish-yellow fluid produced and secreted by the liver. It consists mainly of bile salts, phospholipids, cholesterol, and other solutes such as glutathione and bicarbonate.
Bile secretion has two major roles: (1) to deliver bile acids to assist in the digestion of fats and (2) to excrete certain substances, including bilirubin.
Bile salts are synthesized and conjugated in the liver, secreted into bile, stored temporarily in the gallbladder, passed from the gallbladder into the duodenum, absorbed throughout the small intestine but especially in the ileum, and returned to the liver via the portal vein.
Bile secretion is regulated by hormones such as cholecystokinin (CCK), which is released from intestinal cells when food enters the duodenum.
CCK stimulates the contraction of smooth muscle cells in the gallbladder wall and the relaxation of sphincter muscles at both ends of the common bile duct. This allows bile to flow into the duodenum.
Bile salts are one of the primary components of bile. They aid digestion by emulsifying fats so that they can be more easily broken down by enzymes.
Bile salts also help absorb important vitamins and eliminate toxins from the body. If a person has a deficiency in bile salts due to disease or removal of their gallbladder, it can increase their risk of forming kidney stones and gallstones.
Biliary System Anatomy
The biliary system is a network of organs and ducts that produce, store, secrete, and transport bile to aid in digestion. The biliary system includes the liver, gallbladder, bile ducts, and associated structures.
Bile is a digestive fluid produced by the liver that is transported by a series of branching bile ducts known collectively as the biliary tree.
The common hepatic duct collects bile from these ducts and joins with the cystic duct from the gallbladder to form the common bile duct. This runs from the liver to the duodenum (the first section of the small intestine).
The gallbladder is a pear-shaped organ located directly below the liver that stores about 50% of the bile produced by the liver. When food enters the small intestine, hormones signal the gallbladder to contract and release stored bile into the duodenum to aid in digestion.
The biliary system originates embryologically from the foregut. Early in development, the hepatic diverticulum arises from the endodermal epithelium of the ventral foregut. The hepatic diverticulum serves as an anlage for extrahepatic ducts, gallbladder, liver, and ventral pancreas.
Bile Salt Pathology
Bile salt pathology is a condition in which bile salts accumulate in the body due to an interruption or suppression of the flow of bile from the liver (cholestasis). Bile salts are amphipathic molecules that are produced by the liver and stored in the gallbladder.
They are essential for the digestion and absorption of fats and fat-soluble vitamins, as well as for the excretion of cholesterol and other waste products.
Bile salt pathology can be caused by mutations in genes involved in bile acid synthesis, such as the BSEP gene, or by obstruction or paucity of small bile ducts, resulting in functional obstruction of the entire biliary system.
Symptoms include jaundice, itching, fatigue, abdominal pain, dark urine, and pale stools. Treatment may involve medications to reduce symptoms and improve liver function, as well as dietary changes to reduce fat intake.