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home - Liver - Bilirubin Metabolism - Bilirubin Metabolism 4 Written by Dr Sebastian Zeki

Bilirubin Metabolism 4

Indication of the severity of hepatic dysfunction —[Serum bilirubin] may be normal despite severe parenchymal injury or partial CBD obstruction as max excretion of bilirubin is approximately 55.2 mg/kg/d which is x10 production. Urinary BilirubinUnconjugated bilirubin is tightly bound to albumin therefore not excretedConjugated less tightly bound so is excretedTherefore urinary bilirubin detection indicates inc conjugated bilirubin in the plasma. Excretion of conjugated bilirubin —Conjugated bile actively excreted using (mostly) cMOAT transporterPhenobarbital increases excretionExcretion impaired by acquired(eg, alcoholic or viral hepatitis, cholestasis of pregnancy) and inherited disorders (eg, Dubin-Johnson syndrome, Rotor syndrome, BRIC) and drugs (eg, alkylated steroids, chlorpromazine). Degradation of bilirubin in the digestive tract —The unconjugated bilirubin fraction is partially reabsorbed and undergoes enterohepatic circulation .This fraction increases during phototherapy because of the excretion of photoisomers of bilirubin.Oral administration of charcoal, agar, or cholestyramine may interfere with the absorption of unconjugated bilirubin, thereby increasing the efficacy of phototherapy.In contrast, excessive amounts of bilirubin are available for reabsorption in neonates with obstruction of the upper intestinal tract, delayed passage of meconium, or fasting; this may increase the intensity and duration of neonatal jaundice. Urobilinogen —Undergoes hepatobiliary recirculation.If not cleared by liver, then excreted in urine.Urinary urobilinogen inc. in:-Excessive bilirubin production (eg, hemolysis/haematoma absorption)-Inefficient hepatic clearance of reabsorbed urobilinogen (eg, in cirrhosis/hepatitis)-Excessive exposure of bilirubin to intestinal bacteria (eg, constipation or bacterial overgrowth).Urinary urobilinogen excretion dec in:-Near-complete biliary obstruction (eg, carcinoma of the pancreas) or severe cholestasis (eg, in early stages of viral hepatitis).Tests for urinary urobilinogen are usually not useful in the differential diagnosis of liver diseases. Correlation of [bilirubin]with jaundice —In a steady state,:[bilirubin] reflects total body bilirubinRelationship altered by displacement of bilirubin’s attachment to albumin egsalicylates, sulfonamides, or free fatty acids.Converse occurs if there’s an increase in [albumin] Value of fractionating the bilirubin —Fractionate bilirubin to determine unconjugated hyperbilirubinemia states- consider if conjugated fraction is <20% total bili and unconjugated is >n 1.2 mg/dL (20.5 micromol/L). Urine bilirubin —Kidneys have poor reabsorptive capacity for bilirubinBilirubinuria= early sign of liver disease, while its clearance = early sign of recovery (delta bilirubin is protein-bound- prevents filtration across glomerulus). Extrahepatic cholestasis Bilirubin is reduced by colonic bacteria enzymes to urobilino-gens.The urobilinogens: urobilinogen and stercobilinogen, are colorless and turn orange-yellow only after oxidation to urobilins.Absence of urobilinogen in stool and urine in a jaundiced patient indicates complete biliary obstruction.Urobilinogens and their derivatives are partly absorbed from the bowel, undergo enterohepatic recycling, and are eventually excreted in urine and feces . Small Intestine Large Intestine Stercobilin Urobilinogen Urobilin Conjugated Bile Bilirubin Bilirubin Clinical Points Bile Salt Malabsorption Types:Type 1: Ileal resection/ bypass.Type 2: Primary (idiopathic) disease.Type 3: Misc causes: radiation enteritis, post PUD surgery, post cholecystectomy. SeHCAT scan normal in >15%C4 - if increased more likely to have bile acid malabsorption Treatment: Colestyramine, colestipol, colesevalam Causes of extrahepatic cholestasis:Choledocholithiasis.Intrinsic and extrinsic tumours.PSC. AIDS cholangiopathy.Acute and Chronic pancreatitis.Benign biliary strictures.Parasitic infection. Written by Dr Sebastian Zeki

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