Abstract
To examine some common concepts concerning the development of kernicterus a scanning ultracentrifugation technique (450 mμ region) was used to clearly identify that fraction of bilirubin (BR) migrating with the protein (bound BR) and the free fraction. Titration data showed that bovine serum albumin (BSA) and human serum albumin (HSA) at pH 7.4 had an initial binding of 1:1 BR to protein. When more BR was added, binding continued, showing breaks at 4 and 10 in the case of BSA and 3 and 5 with HSA. A significant proportion of BR was in “solution” as aggregates at pH 7.4. As the BR to albumin ratio increased, the BR in “solution” increased. When the pH was reduced to 6.9 the binding of BR to albumin hardly changed but there was a dramatic decrease in the amount of BR in “solution.” It is postulated that the development of kernicterus at acidotic pH is associated with the decrease of solubility of the free BR with partition into lipoidal sites, rather than decreased binding ability of albumin at pH 6.9. Sulfisoxazole and salicylate did not alter BR binding. This is in accord with tissue culture data showing the necessity of drug concentrations 200-300 fold higher than the BR before BR partitioned into cells. Another mechanism is being sought for the enhancement of the development of kernicterus in the presence of these drugs rather than competition. However, hemin did offer competition once a 1:1 ratio was exceeded. (Supported by NIH.)
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Cowger, M., Lee, J. THE MECHANISM OF KERNICTERUS—WHO ARE THE REAL CULPRITS?. Pediatr Res 8, 431 (1974). https://doi.org/10.1203/00006450-197404000-00547
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DOI: https://doi.org/10.1203/00006450-197404000-00547