Oct 1, 2001: What is the pathophysiology of salicylate toxicity?

Salicylate toxicity seems to be increasing.  We are receiving an increased number of calls at the Poison Center.  I addressed the treatment of salicylate toxicity last week.  This week and next week we will address other aspects of salicylate toxicity.

Salicylates directly stimulate the respiratory center in the medulla causing an increase in rate and depth of respiration.  Salicylates uncouple mitocondrial oxidative phosphorylation (Krebs’s cycle-used to make high energy bonds of ATP) which increases oxygen consumption and CO2 production.  This further increases respiratory drive.  The kidney begins to excrete bicarbonate in response.  Salicylates also cause a passive efflux of potassium from the renal tubules. Acidosis increases from increased pryuvic and lactate acids and the metabolism of salicylate to salicyluric acid. Glycolysis leads to gluconeogenesis and lipolysis, with increased ketone formation.

Salicylates increase permeability of the pulmonary vasculature which can lead to noncardiac pulmonary edema.  They also cause vasoconstriction of the auditory microvasculature causing tinnitus.   Hypoglycemia or hyperglycemia can occur.  Although platelets aggregation may be inhibited, bleeding rarely occurs.