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Bile acid synthesis occurs in liver cells, which synthesize primary bile acids (cholic acid and chenodeoxycholic acid in humans) via cytochrome P450-mediated oxidation of cholesterol in a multi-step process. Approximately 600 mg of bile salts are synthesized daily to replace bile acids lost in the feces, although, as described below, much ...
Bile is secreted by the liver into small ducts that join to form the common hepatic duct. [4] Between meals, secreted bile is stored in the gallbladder. [5] During a meal, the bile is secreted into the duodenum (part of the small intestine) to rid the body of waste stored in the bile as well as aid in the absorption of dietary fats and oils. [5]
In the human liver, bile is composed of 97–98% water, 0.7% bile salts, 0.2% bilirubin, 0.51% fats (cholesterol, fatty acids, and lecithin), and 200 meq/L inorganic salts. [ 2 ] [ 3 ] The two main pigments of bile are bilirubin , which is orange-yellow, and its oxidised form biliverdin , which is green.
Finally, the conjugated bile acids which remained un-ionized conjugated bile acids are passively absorbed. Venous blood from the ileum goes straight into the portal vein and then into the liver sinusoids. There, hepatocytes extract bile acids very efficiently, and little escapes the healthy liver into systemic circulation.
Jaundice is commonly caused by conditions such as pancreatic cancer, which causes blockage of the bile duct passing through the cancerous portion of the pancreas; cholangiocarcinoma, cancer of the bile ducts; blockage by a stone in patients with gallstones; and from scarring after injury to the bile duct during gallbladder removal.
Cholangiocarcinoma can affect any area of the bile ducts, either within or outside the liver. Tumors occurring in the bile ducts within the liver are referred to as intrahepatic, those occurring in the ducts outside the liver are extrahepatic, and tumors occurring at the site where the bile ducts exit the liver may be referred to as perihilar.
A prospective study found that increased hepatocellular cancer risk is associated with higher levels of major circulating bile acids that were measured in people several years prior to tumor diagnosis. [104] In another study using a mouse model, it was found that dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. [105]
Cholangiocytes act through bile-acid independent bile flow, which is driven by the active transport of electrolytes. In contrast, hepatocytes secrete bile through bile-acid dependent bile flow, which is coupled to canalicular secretion of bile acids via ATP-driven transporters. This results in passive transcellular and paracellular secretion of ...