The pathogenesis of sodium chloride toxicity in the young chicken

Abstract

Sodium chloride(NaCl) toxicity was induced in two-week old chickens given either 1% or 1.5% NaCl in the drinking water. Chickens given 1.5% NaCl developed a severe encephalopathy characterized clinically by depression, ataxia, seizures and death with a median survival time of 5 days. Clinicopathologically, affected chickens had significant increases in serum sodium (204.8[plus or minus]16 vs 141.7[plus or minus]2.3 mEg/l in controls), chloride (176.6[plus or minus]14 vs 108.5[plus or minus]2.6mEq/l in controls) and osmolarity (422[plus or minus]27 vs 306.4[plus or minus]5.5m0sm/kg in controls) and pathologically had spongiform degeneration (status spongiosus) of the grey and white matter, degeneration of putative oligodendroglia and splitting (separation) of myelin sheaths, apparently at the intraperiod line. The encephalopathy was similar to the lesions associated with certain other intoxications effecting the central nervous system (e.g. tetraethyl tin, hexachlorophene, lead and the intoxication in man associated with deranged serum sodium causing central pontine myelinolysis). The NaCl induced encephalopathy was proposed to most likely have resulted from a direct toxic effect of Na+ or NaCl on oligodendroglia and/or the myelin sheath. Chickens given 1% did not develop clinical signs of encephalopathy but did have mild clinicopathologic and pathologic lesions that were comparable to chickens given 1.5% NaCl. To further explore the mechanism of the NaCl induced encephalopathy, young chickens administered 1.5% NaCl in the drinking water were given either dexamethasone (corticosteroid) or ethacrynic acid (nonosmotic diuretic) which are compounds used to reduce or prevent the development of cerebral edema. Dexamethasone (40mg/kg/day), known to stabilize membranes of the blood-brain barrier and stimulate electrolyte shifts in the CNS of mammals, had no beneficial effect and actually enhanced the severity of the salt toxicity (reducing the median survival time from 5 to 2 days). The mechanism of this enhancement was possibly the result of corticosteroid induced sodium and water retention or cardiopulmonary complications. Ethacrynic acid (0.1mg/kg/day), previously shown to block Cl- transport and possibly Na+ and water across cell membrane in mammals, had no significant effect on the encephalopathy and exacerbated the toxicity when given at higher concentrations. No definitive explanation was found for the enhanced toxicity but a toxic metabolite or direct interaction of the drug with NaCl was considered.