| Jaundice is clinically obvious when plasma bilirubin concentrations exceed 50 μmol/L (3 mg/dL) (see Table 28.2). Hyper-bilirubinemia occurs when there is an imbalance between production and excretion. The causes of jaundice (Table 28.3) are conventionally classified as:
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- prehepatic: increased production of bilirubin (Fig. 28.10),
- intrahepatic: impaired hepatic uptake, conjugation, or secretion of bilirubin (Fig. 28.11),
- posthepatic: obstruction to biliary drainage (Fig. 28.12).
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| THE SIGNIFICANCE OF NEONATAL JAUNDICE |
| A normal, term baby developed jaundice on the third day of life, with a bilirubin concentration of 150 μmol/L (8.8 mg/dL), predominantly of the indirect form. The baby was otherwise well. |
| Comment. About 50% of normal babies become jaundiced 48 hours after birth. This physiologic jaundice is caused by temporary inefficiency in bilirubin conjugation, and resolves in the first 10 days. The hyperbilirubinemia is unconjugated in nature; if severe, it may require phototherapy (ultraviolet light to photoisomerize bilirubin into a nontoxic form) or exchange blood transfusion to prevent damage to the brain (kernicterus). Bruising from delivery, infection, or poor fluid intake may exaggerate the hyperbilirubinemia. Jaundice in the first 24 hours of life is abnormal and requires investigation to exclude hemolysis, as does physiologic jaundice severe enough to require phototherapy. Jaundice that presents later - after 10 days - is always abnormal, and is likely to indicate an inborn error of metabolism or structural defects of the bile ducts. |
| Figure 28.10 Prehepatic (hemolytic) jaundice. There is an increased concentration of plasma total bilirubin due to the excess of the unconjugated fraction (see Table 28.2 for details). |
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| Figure 28.11 Intrahepatic jaundice. Bilirubin in plasma is increased due to an increase in the conjugated fraction. Increased serum enzyme activities signify hepatocyte damage. See Table 28.2 for details. |
| Prehepatic jaundice results from excess production of bilirubin after hemolysis, or a genetic abnormality in the
hepatic uptake of unconjugated bilirubin. Hemolysis is commonly the result of immune disease, structurally abnormal red cells, or breakdown of extravasated blood. Intravascular hemolysis releases hemoglobin into the plasma, where it is either oxidized to methemoglobin or complexed with haptoglobin. More commonly, red cells are hemolyzed extravascularly, within phagocytes, and hemoglobin is converted to bilirubin; such bilirubin is unconjugated. Unconjugated and conjugated bilirubin can be chemically distinguished.
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| Intrahepatic jaundice reflects a generalized hepatocyte dysfunction. Hyperbilirubinemia is usually accompanied by other abnormalities in biochemical markers of hepatocellular function.
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| In neonates, transient jaundice is common, particularly in premature infants, and is due to immaturity of the enzymes involved in bilirubin conjugation. Unconjugated bilirubin is toxic to the immature brain, and causes a condition known as kernicterus. If plasma bilirubin concentrations are judged to be too high, phototherapy with blue-white light - which isomerizes bilirubin to more soluble pigments that might be excreted with bile - or exchange blood transfusion to remove the excess bilirubin are necessary to avoid kernicterus.
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| Figure 28.12 Posthepatic jaundice. Plasma bilirubin is elevated due to an increase in the conjugated fraction. Obstruction of the bile duct does not allow passage of bile to the gut. Stools are characteristically pale in color. See Table 28.2 for details. γGT-γ-glutamyl transpeptidase; ALP, alkaline phosphatase. |
| Posthepatic jaundice is caused by obstruction of the biliary tree. The plasma bilrubin is conjugated, and other biliary metabolites, such as bile acids, accumulate in the plasma. The clinical features are pale-colored stools, caused by the absence of fecal bilirubin and urobilin, and dark urine as a result of the presence of water-soluble conjugated bilirubin. In complete obstruction, urobilinogen/urobilin is absent from urine, as there can be no intestinal conversion of bilirubin to urobilinogen/urobilin, and hence no renal excretion of reabsorbed urobilinogen/urobilin.
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