Biliary Secretion And Excretion

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Functions of the liver

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uptake of products of digestion (carbs, peptides, lipids, vits)

storage and release of carbs, peps, lipids, and vits

biotransformation and degradation of substances taken up from the blood
endogenous compouds (steroids and hormones)
exogenous substances (drugs and toxins)

removal of foreign body particulates matter from the blood (bacteria, parasite, and aging RBC's)

conversion of hormonse and vits to more active form

Front 2

Functions of the liver - synthesis

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synthesis - plasma prtoteins, cholesterol, glucose, FA's, triacylglycerides, phospholipids, bile acis

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functions of the liver - bile

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bile acids, phospholipids, cholesterol, organic anions (bilirubin) heavy metals, lipophilic endobiotics or xenobiotics in conjugated or unconjugated forms

Front 4

composition of hepatic bile

Back 4

conjugated bile acids:
Primary: cholic acid and chenodeoxycholic acid
Secondary: deoxycholic acid and lithocholic acid
both primary and secondary bile acids are conjugated with glycine or taurine
phospholipids
cholestorol
organic anions (bile pigments, steroid metabolits)
electrolytes
water

Front 5

Primary Bile acids

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are synthesized by hepatocytes
cholic acid
chenodeoxycholic acid (synthesised by addition of hydroxyl groups and a corboxyl group to cholesterol
rate limiting step is 7alpha-hydroxylation of cholesterol
amphiphatic molecules - form micelles
weak acids: poorly spluble in protonated form, but more soluble in anion form

Front 6

conjugation of bile acids

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conjugation with an amino acid ( glycine or taurine)
converts the bile acid from a weak acid to a strong acid
increases aquesous solubility at pH of bile ducts, gallbladder, and intestinal lumen
decreases ability to be passively absorbed
conjugated cholic acid - cholytaurine
conjugated chenodeoxycholic acid - chenodeoxycholyglycine
prevents the formation of insoluble salts
calcium salts of conjugated bile acids are fully water soluble

Front 7

secretion of conjugated bile acids

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an increase in the intracellular concentration of conjugated bile acids within hepatocytes results in:
transport by intracellular binding proteins or diffusion to the canalicular membrane
insertion of bile salt export proteins (bsep) into the canalicular membrane
active transport of conjugated bile acids intro the bile canaliculus

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most of the conjugated bile acids secreted into the small intestine are efficiently absorbed in tact

HOWEVER

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conjugated primary bile acids may be acted upon b the bacteria in the lumen of GI tract in two different wats

1. 7alpha - dehydroxylation of primary bile acids converts them to secondary bile acids
conjugated deoxycholic acid
conjugated lithocholic acid

2. removal of the conjugated taurine or glycine (i.e. deconjugation) from either primary or secondary conjugated bile acids
deconjugation decreases the aqueous solubility of the bile acids

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Hepatocyte uptake of bile acids from the blood

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conjugated bile acids (primary and secondary) are actively reabsorbed from the lumen of the terminal ileum only TERMINAL ILEUM ONLY
ileal enterocyte apical membrane uptake
Na-dependent secondary active transport via the apical sodium - dependent bile acid transporter (ASBT)
ileal enterocyte basolateral membrane efflux (facilitated diffusion via a heterodimeric organic solute transporter (Ostalpha - Ostbeta)

deconjugated bile acids (pri and sec) may be reabsorbed by passive diffusion from the lume nof the small and large intestin

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Conjugated and deconjugated primary and secondary bile acids return to the liver via

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the hepatic portal blood bound to albumin

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hepatocytes remove conjugated and deconjugated primary and secondary bile acids from the blood and return them to the

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bile

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If the conjugated bile acids exceeds a critical concentration (i.e. the crutucal micelle concentration) then they will associate to form

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micelles

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Simple micelles

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those composed of bile acid and anions alone, do not occur in mammals

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hepatic bile

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contains mixed micelles composed of:
conjugated bile acids
phospholipids
cholesterol
other liophilic molecules

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in the small intestinal
mixed micelles are composed of

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conjugated bile acids
phospholipids
cholesterol
FA's
2-monoglycerides
fat-soluble vitamins
plant sterols

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biliary lipids

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the flux of conjugated biles through the hepatocte also includes:
ATP-dependent exocytosis of unilamellar lipid vesicles containing:
Phospholips, primary phosphotidylcholine
cholesterol

whithin the bile canaliciula

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mixed micelle

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phopholipid associates with the bile acids
cholestero is solubilized int he lipid-like mixed micelle interior

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Bile pigment secretion: bilirubin

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during the degradaion of RBC's by reticuloendothelial cells found in hepatic sinusoids and other areas
unconjugated bilirubin is released into the blood and becomes bound to albumin

in the liver:
bilirubin is removed from the blood b hepatoctes
it is conjugated to glucuronic acids and are then secreted into the canaliculus by an ATP-dependent process mediated by canalicular multiple organix anion transport protein (cMOAT)

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Jaundice

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prehepatic or hemolytic jaundice due to excessive breakdown of RBC's
hepatic jaundice due to diseased liver and inability to deal with normal load of bilirubin
posthepatic or obstructive jaundice due to obstructin of the bile ducts

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screted accross canalicular membrane by active transports using cMOAT

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sulfated conjugated bile acids,