Pathophysiology of aspirin overdosage toxicity, with implications for management.
The principal pathophysiologic effect of toxic doses of salicylates are characterized by (1) stimulation of the respiratory center of the brain, leading to hyperpnea and respiratory alkalosis; (2) uncoupling of oxidative phosphorylation, leading to increased oxygen utilization and glucose demand, increased oxygen utilization and glucose demand, increased glyconeogenesis, and increased heat production; (3) inhibition of Krebs cycle enzymes, leading to decreased glucose availability and increased organic acids; (4) alterations in lipid metabolism and amino acid metabolism, enhancing metabolic acidosis; and (5) increased fluid and electrolyte losses, leading  to dehydration, sodium depletion, potassium depletion, and loss of buffer capacity. The principal toxic manifestations of respiratory alkalosis and metabolic acidosis, altered glucose availability and depletion, fluid and electrolyte losses, and hypermetabolism result in serious morbidity and are potentially fatal. Therapy of salicylate intoxication should be aimed principally at replacement of fluid electrolytes, correction of acidemia, administration of glucose, and prevention of further salicylate absorption and enhancement of salicylate elimination.
D000138:Acidosis / Q000139:chemically induced; D000472:Alkalosis, Respiratory / Q000139:chemically induced; D001241:Aspirin / Q000506:poisoning*; D005334:Fever / Q000139:chemically induced / Q000628:therapy; D005440:Fluid Therapy; D005947:Glucose / Q000378:metabolism; D006801:Humans; D014883:Water-Electrolyte Imbalance / Q000139:chemically induced
D005947:Glucose; D001241:Aspirin