A person remaining at high altitudes for days, weeks, or years becomes more and more acclimatized to the low PO2, so it causes fewer deleterious effects on the body. After acclimatization, it becomes possible for the person to work harder without hypoxic effects or to ascend to still higher altitudes.
The principal means by which acclimatization comes about are (1) a great increase in pulmonary ventilation, (2) increased numbers of red blood cells, (3) increased diffusing capacity of the lungs, (4) increased vascularity of the peripheral tissues, and (5) increased ability of the tissue cells to use O2 despite low PO2.
Increased Pulmonary Ventilation—Role of Arterial Chemoreceptors. Immediate exposure to low PO2 stimulates the arterial chemoreceptors, and this stimulation increases alveolar ventilation to a maximum of about 1.65 times normal. Therefore, compensation occurs within seconds for the high altitude, and it alone allows the person to rise several thousand feet higher than would be possible without the increased ventilation. If the person remains at a very high altitude for several days, the chemoreceptors increase ventilation still more, up to about five times normal.
The immediate increase in pulmonary ventilation upon rising to a high altitude blows off large quantities of CO2, reducing the PCO2 and increasing the pH of the body fluids. These changes inhibit the brain stem respiratory center and thereby oppose the effect of low PO2 to stimulate respiration by way of the peripheral arterial chemoreceptors in the carotid and aortic bodies. However, this inhibition fades away during the ensuing 2 to 5 days, allowing the respiratory center to respond with full force to the peripheral chemoreceptor stimulus from hypoxia, and ventilation increases to about five times normal.
The cause of this fading inhibition is believed to be mainly a reduction of bicarbonate ion concentration in the cerebrospinal fluid, as well as in the brain tissues. This reduction in turn decreases the pH in the fluids sur rounding the chemosensitive neurons of the respiratory center, thus increasing the respiratory stimulatory activity of the center.
An important mechanism for the gradual decrease in bicarbonate concentration is compensation by the kidneys for the respiratory alkalosis, as discussed in Chapter 31. The kidneys respond to decreased PCO2 by reducing hydrogen ion secretion and increasing bicarbonate excretion. This metabolic compensation for the respiratory alkalosis gradually reduces plasma and cerebrospinal fluid bicarbonate concentration and pH toward normal and removes part of the inhibitory effect on respiration of low hydrogen ion concentration. Thus, the respiratory centers are much more responsive to the peripheral chemoreceptor stimulus caused by the hypoxia after the kidneys compensate for the alkalosis.
Increase in Red Blood Cells and Hemoglobin Con centration During Acclimatization. As discussed in Chapter 33, hypoxia is the principal stimulus for causing an increase in red blood cell production. Ordinarily, when a person remains exposed to low O2 for weeks at a time, the hematocrit rises slowly from a normal value of 40 to 45 to an average of about 60, with an average increase in whole blood hemoglobin concentration from normal of 15 g/dl to about 20 g/dl.
In addition, the blood volume also increases, often by 20 to 30 percent, and this increase multiplied by the increased blood hemoglobin concentration gives an increase in total body hemoglobin of 50 percent or more.
Increased Diffusing Capacity After Acclimatization. The normal diffusing capacity for O2 through the pulmonary membrane is about 21 ml/mm Hg/min, and this dif fusing capacity can increase as much as threefold during exercise. A similar increase in diffusing capacity occurs at high altitude.
Part of the increase results from increased pulmonary capillary blood volume, which expands the capillaries and increases the surface area through which O2 can diffuse into the blood. Another part results from an increase in lung air volume, which expands the surface area of the alveolar-capillary interface still more. A final part results from an increase in pulmonary arterial blood pressure, which forces blood into greater numbers of alveolar capillaries than normally, especially in the upper parts of the lungs, which are poorly perfused under usual conditions.
Peripheral Circulatory System Changes During Acclimatization—Increased Tissue Capillarity. The cardiac output often increases as much as 30 percent immediately after a person ascends to high altitude but then decreases back toward normal over a period of weeks as the blood hematocrit increases, so the amount of O2 transported to the peripheral body tissues remains about normal.
Another circulatory adaptation is growth of increased numbers of systemic circulatory capillaries in the non-pulmonary tissues, which is called increased tissue capillarity (or angiogenesis). This adaptation occurs especially in animals born and bred at high altitudes but less so in animals that later in life become exposed to high altitude.
In active tissues exposed to chronic hypoxia, the increase in capillarity is especially marked. For instance, capillary density in right ventricular muscle increases markedly because of the combined effects of hypoxia and excess workload on the right ventricle caused by pulmonary hypertension at high altitude.
Cellular Acclimatization. In animals native to altitudes of 13,000 to 17,000 feet, cell mitochondria and cellular oxidative enzyme systems are slightly more plentiful than in sea-level inhabitants. Therefore, it is presumed that the tissue cells of high altitude–acclimatized human beings also can use O2 more effectively than can their sea-level counterparts.
