Bilirubin is the by-product of heme metabolism when red cells are degraded by the reticuloendothelial system. The iron in heme is reutilized but the tetrapyrrole ring is degraded to bilirubin. Unconjugated bilirubin is insoluble in water and is transferred in blood bound to albumin. It is taken up by the hepatocytes in the liver, transported to the smooth endoplasmic reticulum, and undergoes conjugation to form a diglucuronide. Conjugated bilirubin is water soluble and is excreted via biliary canaliculi to the gut. Little conjugated bilirubin normally appears in the blood unless there is impaired hepatocyte excretion or biliary obstruction.

The normal range for total bilirubin is 3 to 15 mmol/l (0.16-0.88 mg/100 ml), with jaundice becoming clinically apparent above 35 mmol/l (2.0 mg/100 ml). Men have a slightly greater mean total bilirubin than women, with levels 3 to 4 mmol/l (0.16-0.23 mg/100 ml) higher.

Unconjugated hyperbilirubinemia occurs when the production of bilirubin exceeds the ability of the liver to remove and conjugate it ( TabJeJ..). The concentration of unconjugated hyperbilirubinemia in adults rarely exceeds 100 mmol/l (5.8 mg/100 ml).

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itg.tatft tytfwt. tollable 1 Causes of unconjugated hyperbilirubinemia

Conjugated hyperbilirubinemia occurs when there is leakage of bilirubin into the blood system, at or distal to the hepatocytes, when its normal route of excretion is blocked (Ta.ble.2). The water-soluble bilirubin then enters the blood system and is excreted in the urine. However, some of the conjugated bilirubin becomes covalently bound to serum albumin and other proteins; this portion is not filtered by the kidney and thus bilirubinuria is not always present with conjugated hyperbilirubinemia. With total biliary obstruction, bilirubin levels can reach up to 500 mmol/l (29.2 mg/100 ml) with the levels stabilizing due to renal excretion. The presence of renal failure or hemolysis with obstruction can lead to levels greater than 1000 mmol/l (58.5 mg/100ml).


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Table 2 Causes of conjugated hyperbilirubinemia

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