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| − | == Bile formation: == | + | == [[Bile Formation]] == |
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| − | *Osmotic secretory process
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| − | *Driven by active concentration of bile salts in the bile canaliculi
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| − | *Transport mechanisms in the basolateral (sinusoidal) and apical (canalicular) surfaces of the hepatocytes. There are absolutely stacks of these on both membranes. Transport on the across the canalicular membrane side of the hepatocyte is the rate limiting step.
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| − | **Sinusoidal membrane
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| − | ***Na/K ATPase maintains –35mV charge which drives the Na/H+ pump (protons out of the cell), HCO3-/Na+ (bicarbonate entry) and Na+ dependent uptake of conjugated bile salts or bile acids.
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| − | ***Bile salts are the most abundant solutes in bile
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| − | ***Transport from plasma into hepatocytes is mediated by the sodium taurocholate cotransporter.
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| − | ***Other non-conjugated bile salt (cholate) and lipophilic albimin-bound compounds are transported from plasma into hepatocytes via a sodium-independent transporter.
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| − | **Canalicular membrane
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| − | ***Rate limiting step
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| − | ***Transport via ATP-dependent pumps (ATP-binding cassette family of membrane transporters)
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| − | E.g.: multidrug resistance-1 P-glycoprotein (MDR1) – mediates transport of bulky lipophilic cations (e.g.: anticancer drugs, cyclosporine A, etc).
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| − | ***Physiological role – unclear, ?substrate
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| − | MDR3 – liver specific function cf: MDR1, it transports phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane.
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| − | ***Canalicular multispecific organic-anion transporter – a canalicular form of the multidrug resistance-associated protein (MDP2) – mediates transport of leukotriene C4, glutathione-S conjugates, glucuronides (bilirubin diglucuronide, estrodiol-17β- glucuronide) largely responsible for generation of bile flow independent of bile salts within the bile canaliculi.
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| − | ***Canalicular bile salt transporter – probably a member of the ATPase binding cassette family.
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| − | *Bile flow also affected by exocytosis of transcytotic and subcanalicular vesicles; activities of peptidases, nulceotidases, periodic contractions of bile canaliculi, bile ductule and hepatocyte ion channels, etc.
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| − | *Chloride is excreted by the chloride/bicarbonate anion exchanger and the cystic fibrosis transmembrane regulator (CFTR) (Cl- channel on the luminal surface of the bile duct epithelial cells).
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| | *cAMP mediated signaling in the hepatocyte is impaired due changes in G protein expression and localization. This together with changes in membrane composition and the detergent effects of the bile salts – contribute to decreased adenylate cyclase activity. Also therefore decrease effects of glucagons and VIP that normal stimulate bile secretion. | | *cAMP mediated signaling in the hepatocyte is impaired due changes in G protein expression and localization. This together with changes in membrane composition and the detergent effects of the bile salts – contribute to decreased adenylate cyclase activity. Also therefore decrease effects of glucagons and VIP that normal stimulate bile secretion. |
| | [[Category:Liver_-_General_Pathology]] | | [[Category:Liver_-_General_Pathology]] |
| | + | Infectious Canine Hepatitis |