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home - Liver - Bilirubin Metabolism - Bilirubin Metabolism 1 Written by Dr Sebastian Zeki

Bilirubin Metabolism 1

Written by Dr Sebastian Zeki Bilirubin uptake reduced in:Some Gilbert syndrome pts and certain drugs, eg, rifampin, flavaspidic acid, and cholecystographic dyes.In cirrhotics, some bilirubin produced in the spleen bypasses the liver via portosystemic collaterals.Also the normally fenestrated sinusoidal endothelium may lose the fenestrae (capillarization), so get the plasma-hepatocytes boundary. with inc unconjugated [bilirubin]. Utilization Succinyl CoA Glycine Protoporphyrin Fe Haem Haem proteins Haem oxygenase Destabilisation Synthesis Fe CO Biliverdin Biliverdin reductase Bilirubin IX-alpha Bilirubin Metabolism Albumin Bilirubin-glutathione S-transferases (GSTs) bound Facilitated Diffusion Bilirubin IX alpha Uptake Into Hepatocytes Bilirubin IX alpha Albumin Bilirubin IX alpha-Albumin complex Irreversible albumin bindingAlbumin binding of bilirubin is usually reversible.Irreversible binding (=delta-bilirubin)) occurs with prolonged conjugated hyperbilirubinemia, eg, during biliary obstruction.Delta-bilirubin isn’t cleared by liver/ kidney and has the long half-life of albumin; therefore get prolonged hyperbilirubinemia after biliary obstruc-tion relief.Delta-bilirubin gives absent urine bilirubin excre-tiondespite direct hyperbilirubinemia. Confirm by high performance liquid chromatography of serum. Bilirubin displacementSulfonamides, warfarin, antiinfla-matory drugs, and cholecysto-graphic contrast media also bind albumin at same site as bilirubin so can precipitate bilirubin encepha-lopathy in the newborn with the same total bilirubin conc Bilirubin is bound to albumin or HDL’s to make it solubleOnly small amount in free state.Dissociates from albumin at the hepatocyte surface Causes of increased bilirubin production:Extravascular haemolysis.Extravasation of blood into tissues.Intravascular haemolysis.Dyserythropoesis. Alternative pathways of bilirubin elimination:-Oxidation of bilirubin by mixed function oxidases in liver and other organs.-If inc conjugated plasma bilirubin concentrations (eg, intrahepatic or extrahepatic cholestasis), the kidney clears 70%-bile remains the main excretion route for unconjugated hyperbilirubinemia. Uptake and storage of bilirubin by hepatocytes In liver sinusoids, the albumin-bilirubin complex dissoci-ate; bilirubin is taken up by hepatocytes (facilitated difusion)-albumin stays circulating.Within the hepatocyte, bilirubin + other organic anions bind to glutathione.S-transferases (GSTs)- reduce efflux of internalized bilirubin. Albumin binding of bilirubin in plasma —Plasma bilirubin content increases after albumin infusion because of transfer of the pigment from tissue stores to the intravascular space. Heme oxygenase It is present in high concentration in the spleen and liver Kupffer cells.It is induced in haemolytic states).It opens haem porphyrin ring (catalyzes the oxidation of the alpha-carbon bridge).It results in green biliverdin which is then reduced by biliverdin reductase to orange-yellow bilirubin IX-alpha.Iron is released and oxidized alpha-bridge carbon is eliminated as carbon monoxide (CO)-CO production has been used to quantify bilirubin production.Heme oxygenase is the rate-limiting in bilirubin production. Heme present in hemoglobin, myoglobin, cytochromes, catalase, peroxidase and tryptophan pyrrolase.

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