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Liver and intrahepatic bile ducts-nontumor

Normal physiology


Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 31 March 2012, last major update March 2012
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.

General
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Bile:
● Liver produces about 500 ml/day of bile
● Promotes dietary fat absorption via detergent action of bile salts; eliminates waste products (bilirubin, excess cholesterol, xenobiotics) that are insufficiently water soluble to be excreted into urine

Bile acids:
● Carboxylate steroid molecules, derived from cholesterol, that promote bile flow and secretion of phospholipid and cholesterol
● Primary bile acids are cholic acid and chenodeoxycholic acid, secreted as tuarine and glycine conjugates; two secondary ones (deoxycholic and lithocholic acid) are formed in the colon by bacterial action


Bile acids


Bile acid circulation:
● All bile acids are reabsorbed via sodium-bile acid cotransporter in apical membrane of ileal enterocytes, and transported back to liver
● Enterohepatic circulation of bile acids maintains a large endogenous pool of bile acids for digestive and excretory purposes


Enterohepatic circulation


Jaundice:
● Also called icterus
● Discoloration of skin and sclera due to disruption of bile formation by either retention of pigmented bilirubin or block in bilirubin secretion (cholestasis)

Bilirubin:
● End product of heme degradation
● 200 mg produced daily from old red blood cells broken down via monocyte phagocytic system in spleen, liver, marrow
● Also from turnover of P450 cytochromes and premature destruction of marrow red blood cells (with ineffective erthyropoiesis)
● Red blood cells are broken down and produce hemoglobin
● Globin proteins are removed, leaving heme molecule
● Heme is converted to biliverdin via heme oxygenase
● Biliverdin is converted to bilirubin via biliverdin reductase
● Bilirubin is bound to serum albumin since it is insoluble in blood at physiologic pH; the % unbound increases in severe hemolytic disease or if protein-binding drugs displace bilirubin
● Hepatocytes take in bilirubin at sinusoidal membrane, conjugate it with glucuronic acid using bilirubin uridine diphosphate-glucuronosyltransferase (UGT) in endoplasmic reticulum, then bilirubin is excreted into bile
● Bacteria have beta glucuronidases which deconjugate and degrade bilirubin to colorless urobilinogens, excreted in feces as stercobilin, a brown pigment that colours stools
● 20% of urobilinogens are reabsorbed in ileum/colon, returned to liver, re-excreted into bile
● Some urobilinogen is reabsorbed and excreted by the kidney, oxidized to urobilin a pigment that gives amber colour to urine

End of Liver and intrahepatic bile ducts-nontumor > Normal physiology


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