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.
So yes, there are several systems, acting at different time scales that
affect the acclimatization.
- 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.
- 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
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.
- 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.
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.