New concepts in bilirubin encephalopathy

J. D. Ostrow, L. Pascolo, S. M. Shapiro, C. Tiribelli

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Revised concepts of bilirubin encephalopathy have been revealed by studies of bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats. Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated bilirubin (Bf), of which the dominant species at physiological pH is the protonated diacid, which can passively diffuse across cell membranes. As the binding affinity of plasma albumin for bilirubin decreases strikingly as albumin concentration increases, previously reported Bf values were underestimated. Newer diagnostic tests can detect reversible neurotoxicity before permanent damage occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at Bf only modestly above aqueous saturation and affects astrocytes and neurons, causing mitochondrial damage, resulting in impaired energy metabolism and apoptosis, plus cell-membrane perturbation, which causes enzyme leakage and hampers transport of neurotransmitters. The concentrations of unbound bilirubin in the cerebro-spinal fluid and CNS cells are probably limited mainly by active export of bilirubin back into plasma, mediated by ABC transporters present in the brain capillary endothelium and choroid plexus epithelium. Intracellular bilirubin levels may be diminished also by oxidation, conjugation and binding to cytosolic proteins. These new concepts may explain the varied susceptibility of neonates to develop encephalopathy at any given plasma bilirubin level and the selective distribution of CNS lesions in bilirubin encephalopathy. They also can suggest better strategies for predicting, preventing and treating this syndrome.

Original languageEnglish
Pages (from-to)988-997
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume33
Issue number11
DOIs
Publication statusPublished - Nov 2003

Fingerprint

Kernicterus
Bilirubin
Cell membranes
Gunn Rats
Cell Membrane
Toxicity
Choroid Plexus
ATP-Binding Cassette Transporters
Vascular Endothelium
Brain Diseases
Plasmas
Jaundice
Routine Diagnostic Tests
Serum Albumin
Astrocytes
Energy Metabolism
Neurotransmitter Agents
Cerebrospinal Fluid
Albumins
Cultured Cells

Keywords

  • Bilirubin
  • Encephalopathy
  • Jaundice
  • Kernicterus
  • Neonates
  • Nuerotoxicity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

New concepts in bilirubin encephalopathy. / Ostrow, J. D.; Pascolo, L.; Shapiro, S. M.; Tiribelli, C.

In: European Journal of Clinical Investigation, Vol. 33, No. 11, 11.2003, p. 988-997.

Research output: Contribution to journalArticle

Ostrow, J. D. ; Pascolo, L. ; Shapiro, S. M. ; Tiribelli, C. / New concepts in bilirubin encephalopathy. In: European Journal of Clinical Investigation. 2003 ; Vol. 33, No. 11. pp. 988-997.
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