To breathe or not to breathe

Abstract

Anyone who has ever had the misfortune of suffering from Acute Mountain Sickness (AMS) would never question the reality of this affliction. During the first night following rapid ascent to high altitude, being awakened from a restless sleep with a splitting headache, followed by a wave of nausea and perhaps vomiting, is an experience never to be forgotten. Of the millions who visit the mountainous regions of the western United States, approximately one person in four will experience AMS; it is very common. AMS strikes those guilty of "going too high too fast," and "too high" is any altitude above 8000 ft (2400 m). In considering the pathogenesis of AMS, the initiating event is unquestionably rapid ascent to high altitude. Unlike decompression sickness in divers, exposure to the decreased atmospheric pressure per se is probably of little consequence at moderate altitude. Rather, it is the associated decrease in the partial pressure of oxygen, i.e., atmospheric hypoxia, that is the culprit. From an evolutionary viewpoint, defenses against hypoxia probably developed to cope with airway obstruction. Impairment of ventilation would result in a fall in airway P02 combined with an increase in airway PC02• The resulting hypoxemia would stimulate the carotid chemoreceptors while, concurrently, hypercapnic acidosis would provide central stimulation. Together, the responses would produce a powerful increase in the effort, to breathe. However, when exposed to atmospheric hypoxia, the respiratory control system is presented with a dilemma. Increased ventilation in response to hypoxemia now lowers airway PC02, and the normal CO2 stimulus is withdrawn, thereby counteracting the hypoxic stimulus. Hence, "to breathe or not to breathe?" Those who develop AMS seem to favor the "not to breathe" option, for they exhibit less increase in ventilation, i.e., relative hypoventilation, and more severe hypoxemia than do their more fortunate colleagues. Because relative hypoventilation implies not only a greater fall in P02 but also less fall in PC02, the potential role of changes in PC02 in the pathogenesis of AMS should also be considered, as CO2 relates to the way in which the body handles fluid. Recall that one of the earliest responses following ascent to altitude is a rise in hematocrit. This results from removal of water from the plasma, i.e., hemoconcentration, followed by diuresis. The latter accounts in part for the usual loss of body weight at altitude. It has been observed that persons who have a diuresis and lower body weight are less likely to develop AMS [1]. Conversely, persons who gain weight at altitude, i.e., retain fluid, are more prone to develop not only the usual symptoms of AMS but also more serious manifestations, including high altitude pulmonary edema (HAPE) and cerebral edema (HACE). This has led to the concept that altitude illness, in general, reflects abnormal fluid retention, i.e., "the edemas of altitude" [2]. Fluid retention appears to be linked to changes in CO2• We demonstrated that the usual hemoconcentration at altitude did not occur if hypocapnia was prevented by adding CO2 to the atmosphere in a decompression chamber [3]. Furthermore, preventing the fall in PC02 also increased the severity of AMS symptoms [4]. Subsequently, we observed among