Response hypoxia (Part 1)For over a century, scientific investigation at high altitude has provided so many clues to understanding the pathophysiology of hypoxemic states at low altitude that it is difficult to pick just a few for a manageable presentation. Somewhat arbitrarily, and for reasons of personal familiarity, I have selected a few issues out of a large universe of possibilities that illustrate the impact of high-altitude research on the development of concepts of, and investigation into, pathogenesis of respiratory failure or hypoventilation at low altitude. As an example, the functional and ventilatory adaptation to high altitude is variable and reflects, at least in part, a variation in ventilatory responsiveness to the hypoxic stimulus. This adaptation leads to a consideration of the sources of variation in hypoxic chemosensitivity at high and low altitude and how such variation in chemical control of breathing might influence or determine clinical adaptation to chronic obstructive pulmonary disease. Finally, such adaptation leads to a consideration of some important unanswered questions concerning general aspects of adaptation to hypoxia. buy ampicillin
The ambient hypoxia of high altitude triggers a number of responses with potential adaptive value (Fig 1). These range from adjustments that are immediately available, active, and energy costly (such as increased ventilation and cardiac output) on the one hand, or to passive, potentially energy efficient responses (such as polycythemia and changes in peripheral tissue architecture, and increased capillary and mitochondrial density) on the other. There are important differences among individuals and species as to which of these are evoked. Often, these varying alternatives seem to develop in a reciprocal or complementary fashion illustrated by the common observation, both at high altitude and in patients with lung disease, that polycythemia is often minimal when ventilation is high and vice versa.

Figure_1

Figure 1. Spectrum of potentially adaptive responses to hypoxia. These range from early, energy-costly adjustments (such as increased ventilation and cardiac output) to later, possibly more efficient changes, including polycythemia and tissue adaptation (such as increased capillary and mitochondrial density)