Chemistry versus compensation: comparing integrated respiratory-renal blood acid-base responses between acute inspired normobaric hypoxia versus sustained hypobaric hypoxia.

During acute exposure to hypoxia, peripheral respiratory chemoreceptors detect decreases in blood oxygenation, eliciting a hypoxic ventilatory response (HVR), which is enhanced with the duration and intensity of exposure (ventilatory acclimatization). The HVR protects oxygenation, but a secondary consequence is the elimination of arterial partial pressure of carbon dioxide ([Formula: see text]), resulting acutely in hypocapnia and respiratory alkalosis. With sustained exposure to hypobaric hypoxic conditions (e.g., high-altitude ascent; HA), the renal tubules reduce [Formula: see text] reabsorption and H excretion, excreting [Formula: see text] and retaining H, returning arterial pHa toward normal values. We aimed to characterize and compare blood oxygenation and acid-base homeostasis between two models of hypoxic exposure with matching inspired partial pressure of oxygen ([Formula: see text]) (∼74-76 mmHg): acute hypoxic exposure eliciting an HVR-mediated hypocapnia over 24 min versus sustained hypoxic-hypocapnia with incremental ascent to HA over 10 days. Using arterial blood draws, we measured arterial partial pressure of oxygen, [Formula: see text], [Formula: see text], [[Formula: see text]]a, and pHa, obtained before and following ) acute stepwise reductions in fraction of inspired oxygen ([Formula: see text]) for ∼24 min, with the last step being an [Formula: see text] of 0.12 ([Formula: see text] ≅ 74 mmHg) and ) sustained exposure to hypoxia during incremental ascent to 5,200 m over 10 days ([Formula: see text] ≅ 76 mmHg). We found that ) acute normobaric hypoxia elicited hypocapnia and respiratory alkalosis, as expected, and ) after sustained exposure to hypobaric hypoxia, there was persistent alkalosis, despite appreciable renal compensation. These findings highlight the time course and magnitude of integrated respiratory responses and subsequent renal compensation mounted by the kidneys, specifically that the hypoxia-mediated hypocapnia and respiratory alkalosis experienced at 5,200 m is likely beyond the threshold for a full renal compensation in healthy lowlanders. No studies have directly compared differences in oxygenation and acid-base balance after differential time courses of exposure to inspired hypoxia. We show that after exposure to the same hypoxic stimulus ([Formula: see text] ∼ 74-76 mmHg) over acute (24 min; [Formula: see text] of 0.12) versus sustained (10 days; 5,200 m) exposures, sustained exposure resulted in a persistent alkalemia, despite appreciable renal compensation. These findings highlight the time course and magnitude of integrated respiratory-renal responses and acid-base compensations in response to hypoxic exposure in healthy individuals.