Bile is formed by hepatocytes and modified by the specialized biliary epithelium. It is an exocrine secretion necessary for digestion, an excretion product for removal of toxins and metabolic waste and a part of the host defence system.
The common bile duct lies adjacent to the hepatic artery and portal vein and joins the main pancreatic duct before entering the duodenum through the ampulla of Vater, which is kept closed by the sphincter of Oddi. The biliary epithelium lining the major ducts and the gallbladder is composed of a single layer of columnar or cuboidal cells resting on a basement membrane. It can secreteCl-and water and in the gallbladder the same cells absorb water, to concentrate bile.
The biliary canaliculus is the primary site of bile production. It is a channel formed from apposed surfaces of adjacent hepatocytes. Tight junctions separate the canalicular membrane from the basolateral surface of the hepatocyte, allowing transport proteins to create and maintain concentration gradients. As biliary canaliculi converge and enlarge, specialized biliary epithelial cells replace hepatocytes.
Function Each day, 600·mL of thick, mucoid, alkaline bile is produced.
Its main constituents are:
• primary bile acids: cholic and chenodeoxycholic acid;
• secondary bile acids: deoxycholic and lithocholic acid;
• phospholipids;
• cholesterol;
• bilirubin;
• conjugated drugs and endogenous waste products;
• electrolytes: Na+, Cl-, HCO3-and trace metals, such as copper;
• secretory dimeric immunoglobulin A(sIgA) and other antibacterial proteins;
• mucinglycoproteins.
Transporter proteins on the basolateral surface of the hepatocyte, such as the organic acid transport (OAT) protein, facilitate uptake of substances such as bilirubin and bile salts from the circulation. Transporters in the canalicular membrane then secrete compounds from the hepatocyte into bile. Important canalicular transporters include the bile acid transporter (BAT) and the multi specific organic anion transporter (MOAT). Specific transporters help to excrete potential toxins; for example, excess copperis excreted by an adenosine triphosphate (ATP) -dependent copper transporter that is defective in Wilson’s disease, causing accumulation of copper in the brain and liver.
Active secretion of bile acids, electrolytes and organic compounds draws waterwith it and bile flow is encouraged by coordinated contraction of cytoskeletal proteinsadjacent to the canalicular membrane. The canaliculi secrete 450·mL/day and bile ducts add 150·mL/day. About 60·mLof bile is stored in the gallbladder.
Cholesterol is a major insoluble constituent of bile and it is stabilized by incorporation into mixed micelles, formed by bile salts and phospholipids. Abnormal bilemay be formed if hepatocytes are overloaded with one or other component; for example, haemolysisresults in overproduction of bilirubin, which may crystallize to form gallstones. Cholecystokininis released from the duodenum when food arrives in it, stimulating contraction of the gallbladder and relaxation of the sphincter of Oddi, thus delivering bile to the duodenum just when it is needed. Bile promotes the digestion and absorption of fats and fat-soluble vitamins in several ways. The alkaline bile promotes emulsificationof fats, which allows greater access to digestive enzymes, and bile acids, cholesterol and phospholipids form mixed micelles, into which digested fatty acids and other lipids are incorporated. The alkaline pH is also optimal for pancreatic lipases. Primary bile acidsare synthesized in the liver from cholesteroland 95% of the secreted bile acids are reabsorbed in the terminal ileum and carried into the portal venous circulation. These secondary bile acids, which have been metabolized by bacteria in the intestine, are taken up by hepatocytes and resecreted into the bile. This constitutes the enterohepatic circulation. Bile is the main pathway for excretionof hydrophobic wastes such as bilirubin.
Autoimmune damage to intrahepatic bile ducts, in primary biliary cirrhosis (PBC), causes progressive jaundice and liver damage. Gallstones are very common and may remain asymptomatic. They form when constituents, such as cholesterol or bile pigments, that are partially soluble, reach supersaturated concentrations and crystallize around a nidus, such as a stray bacterial cell. They can cause cholecystitis in the gallbladder and cholangitis or pancreatitis when they lodge in the bile ducts, causing obstruction and superadded infection.
Structure
Macroscopically, the intrahepatic bile ducts, common hepatic duct, cystic duct, gallbladder and common bile duct constitute the biliary system. The gallbladder is a pouch-like structure with a thin fibromuscular wall located under the anterior edge of the liver. Its epithelium is thrown up in complex fronds, increasing the surface area. The neckof the gallbladder leads to the cystic duct, which joins the common hepatic duct, formed from the union of the right and left intrahepatic ducts, to form the common bile duct, which leaves the liver at the hilum.The common bile duct lies adjacent to the hepatic artery and portal vein and joins the main pancreatic duct before entering the duodenum through the ampulla of Vater, which is kept closed by the sphincter of Oddi. The biliary epithelium lining the major ducts and the gallbladder is composed of a single layer of columnar or cuboidal cells resting on a basement membrane. It can secreteCl-and water and in the gallbladder the same cells absorb water, to concentrate bile.
The biliary canaliculus is the primary site of bile production. It is a channel formed from apposed surfaces of adjacent hepatocytes. Tight junctions separate the canalicular membrane from the basolateral surface of the hepatocyte, allowing transport proteins to create and maintain concentration gradients. As biliary canaliculi converge and enlarge, specialized biliary epithelial cells replace hepatocytes.
Function Each day, 600·mL of thick, mucoid, alkaline bile is produced.
Its main constituents are:
• primary bile acids: cholic and chenodeoxycholic acid;
• secondary bile acids: deoxycholic and lithocholic acid;
• phospholipids;
• cholesterol;
• bilirubin;
• conjugated drugs and endogenous waste products;
• electrolytes: Na+, Cl-, HCO3-and trace metals, such as copper;
• secretory dimeric immunoglobulin A(sIgA) and other antibacterial proteins;
• mucinglycoproteins.
Transporter proteins on the basolateral surface of the hepatocyte, such as the organic acid transport (OAT) protein, facilitate uptake of substances such as bilirubin and bile salts from the circulation. Transporters in the canalicular membrane then secrete compounds from the hepatocyte into bile. Important canalicular transporters include the bile acid transporter (BAT) and the multi specific organic anion transporter (MOAT). Specific transporters help to excrete potential toxins; for example, excess copperis excreted by an adenosine triphosphate (ATP) -dependent copper transporter that is defective in Wilson’s disease, causing accumulation of copper in the brain and liver.
Active secretion of bile acids, electrolytes and organic compounds draws waterwith it and bile flow is encouraged by coordinated contraction of cytoskeletal proteinsadjacent to the canalicular membrane. The canaliculi secrete 450·mL/day and bile ducts add 150·mL/day. About 60·mLof bile is stored in the gallbladder.
Cholesterol is a major insoluble constituent of bile and it is stabilized by incorporation into mixed micelles, formed by bile salts and phospholipids. Abnormal bilemay be formed if hepatocytes are overloaded with one or other component; for example, haemolysisresults in overproduction of bilirubin, which may crystallize to form gallstones. Cholecystokininis released from the duodenum when food arrives in it, stimulating contraction of the gallbladder and relaxation of the sphincter of Oddi, thus delivering bile to the duodenum just when it is needed. Bile promotes the digestion and absorption of fats and fat-soluble vitamins in several ways. The alkaline bile promotes emulsificationof fats, which allows greater access to digestive enzymes, and bile acids, cholesterol and phospholipids form mixed micelles, into which digested fatty acids and other lipids are incorporated. The alkaline pH is also optimal for pancreatic lipases. Primary bile acidsare synthesized in the liver from cholesteroland 95% of the secreted bile acids are reabsorbed in the terminal ileum and carried into the portal venous circulation. These secondary bile acids, which have been metabolized by bacteria in the intestine, are taken up by hepatocytes and resecreted into the bile. This constitutes the enterohepatic circulation. Bile is the main pathway for excretionof hydrophobic wastes such as bilirubin.
Common disorders
Jaundice, caused by accumulation of bilirubin, is the classic symptom of biliary disease. Interrupting bile flow to the intestine causes pale stool and dark urineas bilirubin is excreted via the urine. Itchingis caused by accumulation of pruritogenic substances that are normally excreted in bile. Longstanding obstruction interferes with fat absorption and may cause steatorrhoea, weight loss and nutritional deficiency. Obstruction and inflammation of the biliary tract can cause pain, fever and malaise. Damage to hepatocytes, for example by viral hepatitis, may inhibit bile secretion, by decreasing ATP levels, interfering with transporter function and damaging cytoskeletal proteins. This causes intrahepatic cholestasis, with no macroscopic blockage to the biliary system. Certain drugs can produce a similar effect.Autoimmune damage to intrahepatic bile ducts, in primary biliary cirrhosis (PBC), causes progressive jaundice and liver damage. Gallstones are very common and may remain asymptomatic. They form when constituents, such as cholesterol or bile pigments, that are partially soluble, reach supersaturated concentrations and crystallize around a nidus, such as a stray bacterial cell. They can cause cholecystitis in the gallbladder and cholangitis or pancreatitis when they lodge in the bile ducts, causing obstruction and superadded infection.
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BILIARY SYSTEM: MAJOR FUNCTION OF LIVER |
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