Acclimitization - Physiological Responses
from Damon Vincent

(see the Diamox Page, or go back to the main Gear Page)

After lurking for several years, here's something I know about.... There are three physiologic responses to decreased atmospheric pressure and decreased partial pressure of inhaled oxygen.

  1. Increased respiration rate. This an immediate response. Hypoxemia (decreased oxygen in the blood) causes the brain (actually the medullopontine respiratory center) to increase rate of discharge of the phrenic nerve which innervates the diaphragm, and voila', your breathing faster, moving more air in and out of the alveoli, and maintaining the highest possible alveolar oxygen concentration. This compensatory mechanism responds rapidly to changes in blood oxygen saturation.

  2. Renal Compensation for Respiratory Alkalosis. As your respiratory rate increases to maintain alveolar oxygen concentration and blood oxygen saturation, you exhale increasing amounts of CO2. There is less resistance to CO2 diffusing across the alveolar and pulmonary capillaries than there is for O2. CO2 produced by metabolism combines with water to form carbonic acid (H2C03). This reaction (in both directions) is catalyzed by carbonic anhydrase, found mostly in the lungs, kidney, and red blood cells. The carbonic acid spontaneously deprotonates to form bicarbonate (HCO3-) and a proton (H+).

    In short: C02 + H20 <--> H2C03 <--> HCO3- + H+ Bicarbonate (HC03-) a a major pH buffer in the blood. Since CO2 and HC03- are in equilibrium with each other, blowing off more CO2 secondary to increased respiratory rate, bicarbonate is decreased, resulting in decreased pH buffering capacity. Also, formation of CO2 from bicarbonate requires a proton. Together all of this results in what's called respiratory alkalosis (serum pH >7.45).

    To compensate for this blood pH disturbance, the kidneys alkalinize the urine by recovering acids from the urineand dumping bases into the urine. The details are gory. The important part of this process is that it takes 2-3 days to adapt to increasing and decreasing elevation. A few people in this thread talked about "losing their acclimitization" in a few days. In reality, only their kidneys have readjusted to a new, lower altitude.

    Diamox or acetazolamide acts on this system by inhibiting carbonic anhydrase, resulting in less exhaled CO2 and increased bicarbonate in the urine.

  3. Hematopoeitic Adaptation: This is another adaptation to low blood oxygen saturation. The medulla of the kidney has very poor blood supply. When the renal medulla experiences chronic hypoxia, is secretes erythropoeitin (aka EPO) into the blood which activates erythroblast stem cells (the precursors of red blood cells ["RBCs"] in the bone marrow) to grow, divide, mature, leave the bone marrow, and enter the circulating blood more rapidly. Rate of formation of new RBCs is proportional to serum EPO levels. Hematocrit is the percentage of blood volume occupied by cells (overwhelmingly RBCs). Steady state hematocrit is also roughly proportional to EPO levels. It takes a day or two for the renal medulla to start kicking out EPO, 6-10 days for RBC precursors to become RBCs and increase your hematocrit, and 6-12 weeks before you reach a steady state hematocrit after becoming hypoxic and increasing serum EPO levels. RBCs have a half life of 110 days so once your hematocrit is elevated, your hematopoeitic adaptation to hypoxemia is in place for several weeks before these new RBCs dye off.
So yes, there are several systems, acting at different time scales that affect the acclimatization.

Steve Eckert notes:

There are two kinds of acclimatization: Short term where your body learns to deal with the changes, and long term where your body actually changes the chemistry of your blood. I'm sure someone will find some way to argue with that, but I believe it. The overnight acclimatization basically evaporates overnight. The longer-term changes in red blood cell count (etc) take 18 months to build up (according to one high-altitude guide book) and take similarly long to reverse. There isn't just one answer!

Anecdotally, after climbing Aconcagua (sleeping several nights at 19k), I spent two nights below 2.5k and felt terrible upon driving back to 14k on Ojos del Salado. After more than a week at altitude, just two nights were sufficient to reverse my gains.