New aspects of acid-base balance influences of NH4Cl on intra- and extracellular acid-base equilibrium studies in the rat.

Though buffers are widely used in daily practice, there is little information about their effect on intracellular pH in vivo. In this study, the effects of NH4Cl on intra- and extracellular acid-base equilibria were examined. Intact male Sprague-Dawley rats were infused with 3 mmol NH4Cl per kg body weight. Arterial plasma pH and pCO2 were measured at intervals for six hours. In addition, the "mean whole body (intracellular) pHi", an overall estimate of the intracellular pH (complementary to the in vivo determined arterial plasma pH) was calculated from the distribution of 14C labeled DMO (5,5-dimethyl-2,4-oxazolidinedione). For evaluation of buffering, extra- and intracellular bicarbonate was calculated from the Henderson-Hasselbalch equation. Though a decrease of pHe (extracellular pH) by 0.12 pH units was found just after infusion of NH4Cl, pHi increased over the 6 hours of investigation by 0.08 pH units. Extracellular bicarbonate was reduced but there was little change in intracellular bicarbonate concentration. For the treatment of metabolic alkalosis, therapeutic agents are given to reduce intracellular pH and intracellular bicarbonate concentration.. However, it was found in this study that NH4Cl has no effect on intracellular bicarbonate concentration. In addition, infusion of NH4Cl causes an increase of intracellular pH which cannot be detected by blood-gas measurements. The intracellular pH increase that we have demonstrated may have adverse consequences for patients and raises objections to the use of NH4Cl in the treatment of metabolic alkalosis.