Special Grand Rounds Contributor SOUTHWESTERN INTERNAL MEDICINE CONFERENCE Physiology and Pathophysiology With Ascent to Altitude

With increasing altitude, there is a fall in barometric pressure and a progressive fall in the partial pressure of oxygen. Acclimatization describes the physiologic changes that help maintain tissue oxygen delivery and human performance in the setting of hypobaric hypoxemia. These changes include a marked increase in alveolar ventilation, increased hemoglobin concentration and affinity, and increased tissue oxygen extraction. In some individuals, these physiologic changes may be inadequate, such that the sojourn to altitude and the attendant hypoxia are complicated by altitude-associated medical illness. The rate of ascent, the absolute change in altitude, and individual physiology are the primary determinants whether illness will develop or not. The most common clinical manifestations of altitude illness are acute mountain sickness, high altitude pulmonary edema, and high altitude cerebral edema. Key Indexing Terms: Barometric pressure; Hypobaric hypoxemia; Acute mountain sickness; High altitude pulmonary edema; High altitude cerebral edema. [Am J Med Sci 2010;340(1):69–77.] Ascending to high altitude is accompanied by a series of physiologic changes elicited by a fall in the partial pressure of oxygen. These changes help to maintain oxygen delivery to tissues relatively well preserved despite the hypoxic environment. The process by which an individual adapts to altitude is known as acclimatization. The success of the acclimatization process shows a large degree of individual variability. At a given altitude, one individual may thrive quite readily, whereas another may develop a life-threatening complication. Although a number of factors are known to increase the risk of altitude related illness in many instances no underlying predisposition can be identified. Because greater than 30 million people visit high altitude regions annually, it is important for physicians to be familiar with the physiologic changes that accompany travel to altitude and be aware of strategies available to both prevent and treat altitude specific illness.1 Barometric Pressure, Hypoxia, and Altitude Barometric pressure is a measure of the downward force exerted by the atmosphere at a given point. This force is greatest at sea level because the mass of air above this point is at its greatest. At progressively higher altitudes, the barometric pressure falls because the atmospheric mass above the measurement point becomes smaller. A consequence of this decrease in pressure is less compression of the surrounding air, and thus a decrease in air density or, stated differently, the air becomes thinner with altitude. At sea level, the fraction of inspired oxygen is 0.21. This value remains the same with increases in altitude. In other words, the percentage of oxygen in the atmosphere is the same at 30,000 feet as it is at sea level. What changes is the barometric pressure. The fall in barometric pressure leads to a decline in the partial pressure of oxygen. Because the transfer of oxygen from the alveolar space to the pulmonary capillary is in part determined by the partial pressure gradient, this decline will lead to impaired oxygenation. Another way to view these changes is to consider the decrease in air density that accompanies the fall in barometric pressure. In a given volume of air, there will be a decrease in the total number of molecules. The percentage of the existing molecules made up of oxygen remains the same; however, the absolute number of oxygen molecules has decreased. One additional factor worth considering is the effect of solar radiation to cause upwelling of the atmosphere at the equator. This results in the column of air being higher at locations closer to the equator, such that a given altitude near the equator will have a higher barometric pressure compared with the same altitude closer to one of the poles. In terms of barometric pressure, the summit of Denali at 20,320 feet is far enough north to be the rough equivalent of 23,000 feet on Mount Everest. Acclimatization Under normal circumstances, there is a fall in the partial pressure of oxygen as it is transported from the air through the lungs and, ultimately, to the tissues. This decline in partial pressure is known as the oxygen cascade. Because the starting point of the cascade is reduced with altitude, oxygen delivery to the tissues can be significantly reduced. The process of acclimatization serves to minimize any decrease in tissue oxygen delivery, so that human performance is maintained near that of sea level. The physiologic responses that comprise the acclimatization process primarily affect the 2 determinants of tissue oxygen delivery, namely, arterial oxygen content and, to a lesser extent, cardiac output (Table 1). Oxygen delivery can be calculated as follows: Oxygen delivery (DO2) Cardiac output (Q) Arterial oxygen content (CaO2) Oxygen Delivery (DO2) (Heart rate stroke volume) [([Hg] SaO2 H) (PaO2 S)] where [Hg] is hemoglobin concentration, SaO2 is arterial oxygen saturation of hemoglobin, H is Hufners constant, PaO2 is From the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Submitted November 10, 2009; accepted in revised form January 6, 2010. Correspondence: Biff F. Palmer, MD, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 (E-mail: [email protected]). The American Journal of the Medical Sciences • Volume 340, Number 1, July 2010 69 arterial partial pressure of oxygen, and S is the solubility coefficient of oxygen. The arterial oxygen content (CaO2) reflects the total number of oxygen molecules in arterial blood, both bound and unbound to hemoglobin. The greatest contributor to the maintenance of CaO2 during acclimatization is the involuntary increase in ventilation.1 A drop in the PO2 of the arterial blood leads to hypoxic stimulation of peripheral chemoreceptors primarily in the carotid and aortic bodies causing an increase in the depth and rate of breathing. This effect is known as the hypoxic ventilatory response. Increased ventilation lowers the alveolar PCO2 and increases the alveolar PO2 as the 2 are inversely related for a fixed rate of CO2 production according to the alveolar gas equation: