Is increased hematopoiesis needed at altitude?

The increased hemoglobin concentration in high-altitude dwellers is a double-edged sword. Increasing hemoglobin concentration is a response long considered to be a beneficial adaptation, whereby an increase in the oxygen-carrying capacity of the blood compensates for the arterial hypoxemia of altitude. Without such an adaptation, maintenance of the arterial oxygen delivery to the tissues would require an increased cardiac output, an energy-intensive response. Furthermore, the body seems to go to considerable lengths to raise hemoglobin when the arterial oxygen levels fall. As one goes to high altitude, plasma volume immediately begins to contract, quickly raising the hemoglobin concentration. As one remains at altitude, erythropoiesis increases both the hemoglobin concentration in the blood and the total amount in the body. Thus, by different mechanisms, both acute and chronic hypoxemia serve to increase blood hemoglobin concentration. However, at some point, the increase in hemoglobin concentration ceases to be a benefit and becomes a curse. That is, some individuals lose their ventilatory acclimatization to hyp-oxia after a decades-long residence at high altitude. They cease to hyperventilate, suffer central depression of respiration particularly at night, and develop severe hypoxemia, which over time stimulates excessive polycythemia. With hemoglobin concentrations usually above 23 g/100 ml, these individuals develop a potentially fatal syndrome called chronic mountain sickness. The combined effects of hypoxemia and impaired microcirculatory perfusion result in organ malfunction, particularly of the brain and lung. Dizziness, mental confusion, and even cerebral infarction occur. Pulmonary hypertension and impaired ventilation-perfusion relationships, leading to degradation of pulmonary gas exchange and further hypoxemia, also occur. The hypoxemia-polycythemia cycle can be interrupted by lowering the hemoglobin concentration (decreasing the degree of polycythemia), causing the patients to feel better, the arterial oxygen saturation to increase, and the pulmonary and systemic oxygen transport to improve at rest and during exercise. In altitude dwellers, there is a cost-benefit balance for an increased hemoglobin concentration, and the question arises as to the optimal hemoglobin level for the most favorable balance. It is not an idle question. Many millions of people are living at higher and higher altitudes, driven by world population pressures and the increasing need to retrieve mineral resources often found at high elevations. There is the opportunity, possibly even the mandate, for integrative physiologists to understand better optimal hemoglobin concentrations in response to the hypoxic stresses of residence at altitude. In this issue of the Journal, Villafuerte et al. (2) provide a theoretical …