Metabolism of Bilirubin and Methods of Elimination of Its Toxicity
aInstitute of Clinical Biochemistry and Laboratory Diagnostics and 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, bInstitute of Biochemistry and Microbiology and Centre of Integrated Genomics, Institute of Chemical Technology, Prague, cMicrobiological Institute, Academy of Sciences of the Czech Republic, Prague
Bilirubin is the principal intravascular catabolic product of heme metabolism. In disorders of its degradation, bilirubin accumulates in serum, which leads to hyperbilirubinemia. If it exceeds a certain critical limit, a serious damage of central nervous system may result. There are two clinical situations when these complications may result: the rare Crigler-Najjar syndrome of type I, which is a disease caused by congenital deficiency of a liver enzyme conjugating bilirubin with glucuronic acid, thus enabling its elimination by liver, and, in particular, very frequent neonatal hyperbilirubinemia. This disease has a multifactorial etiology; in its pathogenesis participate primarily (1) overproduction of bilirubin in exchange of fetal for adult hemoglobin, (2) immature liver transport and conjugation systems for bilirubin and, last but not least, (3) absence of intestinal microflora reducing bilirubin in intestinal lumen. The absence of the microbial activity leads to accumulation of bilirubin in intestine and its subsequent resorption in portal and further in systemic circulation (enterohepatal and enterosystemic circulation of bilirubin), which manifests itself by elevation of bilirubin levels in serum. The basic therapeutical measure in treatment of neonatal hyperbilirubinemia and also of the Crigler-Najjar syndrome of type I is phototherapy. Its principle is photoisomerization and photodegradation of bilirubin to polar fragments, which can be excreted from the organism more easily. An alternative is the exsanguination transfusion. Due to the significance of intestinal metabolism of bilirubin, the possibility of affecting the enterohepatal and enterosystemic circulation of bilirubin seems very promising in the treatment of these hyperbilirubinemic conditions.
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