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Updated: 03/13/08 01:44 PM |
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| HOME | HEAL | EDUCATE | RESEARCH | DIRECTORY | OUTREACH |
Authors: W. Volwiler, R.A. Willson, A.M. Larson, and J.D. Ostrow
Download Chapter ♦ Download Lecture Slides & Notes
Download Chapter ♦ Download Lecture Slides & Notes
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G. Bile Secretion and Its Control
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1. Bile formation by the hepatocytes and cholangiocytes. (Figure 11). |
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Bile is isotonic
Primary canalicular bile is modified by the cholangiocytes to form "hepatic" bile |
Bile is an isotonic solution containing inorganic electrolytes, bile acids, phospholipids (mainly lecithin = phosphatidylcholine), cholesterol, bile pigments (mainly bilirubin glucuronide conjugates), proteins (mainly albumin and IgA), and glycoproteins (mainly mucin) as well as detoxified xenobiotics and hormones. Bile formation is initiated by active secretion of bile salts and other organic anions from hepatocytes into the biliary canaliculi. This canalicular bile is then modified by bidirectional flux of water and electrolytes across the cholangiocytes as it passes through the ductules and intrahepatic biliary ductal system. This hepatic bile is further modified in the gallbladder.
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Canalicular bile has bile salt-dependent and -independent components
Bile salts regulate the excretion of lecithin and cholesterol into bile |
Canalicular bile has two components: a) the bile-salt dependent fraction, related to the active canalicular secretion of bile salts, mediated by the ATP-dependent bile salt export pump (BSEP); and b) the bile-salt independent fraction, related to the active canalicular secretion of other organic anions, principally glutathione, by the ATP-dependent multispecific organic anion transporter, MRP2. In both cases, the solutes generate osmotic gradients that induce both transcellular and paracellular water flow from the sinusoids. The bile-salt dependent fraction includes biliary lecithin (phosphatidylcholine) and cholesterol, since excretion of these biliary lipids is coupled to bile salt secretion (see Section N.2).
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| Modification of bile by cholangiocytes |
In the biliary ductules and bile ducts, some bile salts are reabsorbed by an apical bile salt transporter and the bile is alkalinized by secretion of bicarbonate.
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2. Regulation of bile flow.
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EHC of bile salts is major determinant of bile flow
Secretion of bicarbonate by cholangiocytes is stimulated by secretin Bile flow greatest during and shortly after eating |
Important controls are a) the supply of bile salts, b) vagal stimuli and c) gastrointestinal hormones. The major determinant of the flow of hepatic bile is the rate at which bile salts recirculate from the intestine via the portal venous blood (the enterohepatic circulation), to be re-secreted by the hepatocytes. Vagal stimulation, cholecystokinin and gastrin all are weak stimulants of bile production. Secretin is the most potent stimulant of ductular bicarbonate secretion. Glucagon modestly increases both canalicular bile formation and ductular bicarbonate secretion. Somatostatin, by contrast, is a potent inhibitor of secretion at both the canalicular and ductular levels. It is important to note that all factors that increase bile secretion are increased with eating and during the early postprandial period, so that bile flow is highest when its functions in intraluminal digestion are most needed. During the interdigestive period, the entero-hepatic circulation is decreased, because little bile empties into the duodenum and intestinal motility is sluggish.
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Figure 11 Hepatic Bile is Produced by Canalicular Secretion and Ductular Modification Schematic depiction of the formation of hepatic bile. Above: Canalicular bile is formed in response to the active transport of primary solutes (mostly bile salts and glutathione) from the hepatocytes into the canaliculi. Below: Bile is modified during its passage along the biliary ductules by absorption and secretion of bicarbonate, and limited absorption of bile salts, glucose and amino acids. Water moves passively into the bile by paracellular and transcellular routes in response to the osmotic gradients generated by solute transport. ©American Gastroenterological Assn., Undergraduate Teaching Project, Unit 27, Slide 25. Milner-Fenwick, Timonium, MD, 1993. |
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3. Modification of bile by the gallbladder.
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| Bile is modified in the gallbladder |
During the interdigestive phase, hepatic bile mainly enters the gallbladder, where it is concentrated, by absorption of water and electrolytes, and acidified by exchange of H+ for Na+ ions. (See Section N.3 and Table 4 for further details.)
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Next Section (H): Bile Salt Metabolism and Turnover » |
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