As mentioned, the ventilatory response begins immediately upon climbing to altitude from sea level and continue over several days at altitude. Hyperventilation changes the blood acid base balance (with a respiratory alkalosis) which in turn stimulates the kidneys to excrete bicarbonate to compensate. This renal compensatory response takes about a week.

The sympathetic nervous system is activated almost immediately with an increase in both sympathetic nerve activity and an increase in blood epinephrine levels - resulting in an increase in heart rate and cardiac output to maintain tissue oxygen delivery at near sea level values. By two to three weeks, blood flow returns toward sea level values as oxygenation improves as a result of the other compensatory mechanisms.

The hematocrit level increases within 24 to 48 hours because of a reduction in plasma volume, not an increase in red cell mass. Erythropoietin levels increase within hours, peak at about 48 hours, and remain elevated for 1 to 2 weeks. The red cell mass increases slowly and may take several years to reach levels equal to natives living permanently at these altitudes.

The vast majority of these metabolic changes are complete by 3 to 4 weeks at altitude, but the structural changes (capillary density, mitochondrial number) take weeks to months to complete.