Supersaturation with Bilirubin followed by Colloid Formation and Disposition, with a Hypothesis on the Etiology of Kernicterus

Abstract

Colloidal bilirubin-albumin particles are formed in vitro when sodium salicylate is added to a solution containing bilirubin and human serum albumin in molar ratios bilirubin/albumin less than 1:1, at pH 7.4. By determining the lower limit of salicylate concentration necessary for the aggregation as a function of the bilirubin/albumin ratio, it is found that one molecule of bilirubin is displaced from the high-affinity binding site on albumin by one molecule of salicylate, resulting in formation of colloid particles containing bilirubin and albumin in a molar proportion about 200:1. In vivo a colloidal solution of bilirubin, injected intravenously into rats, gives higher amounts of unconjugated bilirubin in liver and lungs, as compared with the amounts found after injection of an alkaline bilirubin solution. Theoretically, a process of crystalline colloid formation may be a step in the bilirubin metabolism in icterus neonatorum. If crystallization fails to take place, supersaturation may result in high plasma levels of unconjugated bilirubin with increased risk of kernicterus. The hypothetical possibility of triggering crystallization as a preventive measure in threatening kernicterus is pointed out.