As distance from the sea level increases, barometric pressure of the air falls; however, the O2 concentration remains unchanged as does water vapor pressure. At sea level barometric pressure is 760mmHg, with 47mmHg vapor pressure, leaving PO2 as 0.21 * (760-47) ≈ 150mmHg. At 19,000ft (Mount Kilimanjaro) the barometric pressure is 380mmHg and thus PO2: 0.21 * (380-47) = 70mmHg.
Thus, the PO2 of the inspired air decreases with increasing altitude (decreasing barometric pressure) and the body begins to adapt. These adaptations can be thought of as immediate and delayed (over days to weeks). The most important immediate adaptation is hyperventilation and thus increase in minute ventilation due to the decrease in PaO2, this via stimulation of the peripheral chemoreceptors (central chemoreceptors are not sensitive to falls in PaO2). This results in a respiratory alkalosis. This respiratory alkalosis inhibits breathing, however over the next 2-3 days the pH of the CSF compensates via bicarbonate loss and bicarbonate is further excreted by the kidneys to return blood to normal pH. This allows a continued increase in minute ventilation (via both increasing RR and TV).
At altitude the inspired pO2 may fall sufficiently that oxyhemoglobin dissociation curve is no longer in its upper flat portion. The body compensates by increasing cardiac output to compensate in the short term. In the long term, compensation includes increases in hemoglobin concentration via hypoxia-mediated renal secretion of erythropoietin, thus maintaining DO2 at the expense of increasing viscosity of blood.
The oxyhemoglobin dissociation curve shifts rightwards at moderate altitude to assist in unloading of O2, but shifts leftwards with continued increases in altitude to assist in pulmonary oxygen loading. This first rightward shift is caused by increases in 2,3-DPG resulting from the metabolic alkalosis. This adaptation occurs over hours to days.
The long-term adaption with sustained presence at altitude causes arterial pH to return to normal and arterial pO2, pCO2 and HCO3- to remain reduced. The body’s sensitivity to rises in pCO2 increases. PVR becomes increased chronically due to hypoxic vasoconstriction. The CO returns to normal with a few days of acclimatization. With continued presence at altitude, vital capacity and FRC is unchanged from baseline, but MV remains elevated.