Differential effect of fixed acid and carbon dioxide on ammonia toxicity

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Abstract
Changes in pH have been found to alter the toxicity of ammonia. Most of the studies have been performed with fixed acid or base, but the use of CO2 has recently attracted attention. Theoretically, however, these two methods of altering pH may not have similar effects. Fixed acid or base will penetrate tissue barriers poorly, thus causing an alteration in extracellular fluid-intracellular fluid pH gradient and a change in ammonia distribution. The alteration of pH gradient on inhalation of CO2 is usually of a much smaller degree, as the gas crosses membranes with ease. Consequently, the redistribution of ammonia will tend to be less marked. A comparison was made, therefore, between the effect on ammonia toxicity of equivalent plasma pH changes produced by both methods. The greater the reduction of blood pH with HCl infusion the greater the degree of protection afforded to mice against ammonium bicarbonate toxicity. Similar changes in pH produced by CO2 inhalation either had no effect or exacerbated ammonia toxicity. Concomitantly, HCl caused a marked diminution in the passage of a test dose of ammonia into the brain whereas CO2 had little or no effect.