Dilution acidosis : the effects of hyperosmolality on acid-base balance and ventilation

The effects of acute osmotic changes on acid-base balance and respiratory control were studied in the Pekin duck, Anas platyrhynchos. Acute hyperosmolality following intravascular injection of essentially non-penetrating solutes such as NaCl or sucrose caused an increase in extracellular fluid volume, a prolonged extracellular acidosis (so-called dilution acidosis), and a relative increase in extracellular Cl- concentration. In contrast, hyposmolality did not cause complementary changes in these variables. Studies in acute hyperosmotic stress were therefore undertaken to investigate both the nature of the acid-base disturbance and the implications for ventilatory control. 31P nuclear magnetic resonance spectroscopy (31P NMR) on duck pectoral muscle showed that the dilution acidosis caused by acute hyperosmolality was accompanied by an intracellular contraction alkalosis, implying the uncoupling of intra- and extracellular pH. The increase in extracellular [CF] and the pH changes suggested a primary role for CF/HCO3-exchange during this perturbation. However, both the anion-exchange blocker DIDS and the Na+/H+ exchange blocker amiloride reversed the intracellular pH change from alkalosis to acidosis, although they did not affect the extracellular acidosis caused by acute hyperosmolality. These results indicated that hyperosmolality altered both Cl/HCO3- andNa+/H+ exchange and also suggested the involvement of one or more additional exchange mechanisms. Despite the pronounced extracellular acidosis during hyperosmolality, there was no compensatory stimulation of ventilation. An extracellular pH decrease of similar magnitude and time course when caused by lactic acid infusion stimulated a 100% increase in ventilation, and decreased both extracellular and intracellular pH in contrast to the intracellular alkalosis during hyperosmolality. Although intracellular pH was not directly measured in chemoreceptor tissue, it is reasonable to assume that such well-perfused tissue would be exposed to any osmotic stress. Reversal of the intracellular alkalosis during hyperosmolality by DIDS and amiloride, so that both extra- and intracellular pH were acidotic, resulted in a significant increase in ventilation. These data are unique, since it is the first piece of clear, although indirect, evidence that intracellular pH plays a role in initiating ventilatory changes to acid-base disturbances at the peripheral chemoreceptors. Since brain intracellular pH as measured by 31P NMR during systemic hyperosmolality showed only a consistent trend towards an alkalosis, then central chemoreception, if based on intracellular pH, is unlikely to be affected by hyperosmolality. Acute hyperosmolality also increased the ventilatory threshold to acute hypercapnia, reaffirming a depression of peripheral chemoreception. However, the ventilatory threshold to hypoxia was decreasedand sensitivity to K+ was increased, indicating that the chemoreceptive mechanisms forCO2 and 02 are different, and that both intra- and extracellular pH are crucial to ventilatory control.Science, Faculty ofZoology, Department ofGraduat