17–20 THE HEMOGLOBIN SATURATION CURVE AT ALTITUDE When blood is exposed to a high oxygen pressure in the lungs, oxygen rapidly and reversibly combines with hemoglobin to form oxyhemoglobin. At sea-level where the PO2 is approximately 100 mmHg, the arterial oxygen saturation of

hemoglobin (SaO2) is 95%–98%. The oxygen–hemoglobin dissociation curve (Figure 2) shows the changes in hemoglobin saturation as the partial pressure of O2 decreases.21 Its sigmoidal shape arises from the fact that the hemoglobin molecule contains four heme groups which each Inhibitors,research,lifescience,medical react with a molecule of O2; oxygenation of the first heme group increases the affinity of O2 for the remaining groups. This characteristic shape facilitates oxygen loading in the lungs and oxygen release in the tissues. With increasing altitude, the SaO2 is initially well maintained compared to the PO2 due Inhibitors,research,lifescience,medical to the relatively flat component of the upper portion of the oxygen–hemoglobin dissociation curve. As altitude

increases, the steeper section of the oxyhemoglobin dissociation curve assumes a greater importance, resulting in a more rapid decrease in SaO2. At 8,400 m on Mount Everest where the partial pressure of arterial oxygen (PaO2) drops to 25 mmHg, Inhibitors,research,lifescience,medical hemoglobin saturation is only 50%.22 Figure 2 Oxygen-hemoglobin dissociation curve (adapted from reference 21 and used with permission). Inhibitors,research,lifescience,medical The increased oxygen demands of actively metabolizing tissues lead to an increased production of CO2 and hydrogen ion concentration accompanied by an increase in local temperature and increased levels of 2,3-diphosphoglycerate, all of which shift the oxygen–hemoglobin dissociation curve to the right and facilitate oxygen release in the tissues, while shifts

to the left occur under the reverse conditions. At high altitude, the acute respiratory alkalosis arising from hyperventilation causes a leftward shift in the Inhibitors,research,lifescience,medical oxygen–hemoglobin dissociation curve, increasing arterial saturation for any given PaO2. This leftward shift improves oxygen uptake in the lungs more than it impairs off-loading in the tissues. Under conditions of extreme hypoxia when Necrostatin-1 ic50 pulmonary loading is at a premium, the left-shifted increase in hemoglobin oxygen affinity helps maximize the level of tissue oxygenation for a given difference in oxygen tension between the sites of oxygen loading in Linifanib (ABT-869) the pulmonary capillaries and sites of oxygen unloading in the tissue capillaries.23 AMS: CLINICAL FEATURES The hypoxia of high altitude can lead to sleep disturbances, impaired mental performance, weight loss, and reduced exercise capacity. SLEEP Humans rapidly ascending from sea-level to sleep at altitudes above 2,500 m often experience disturbances in sleep quantity and quality caused by a combination of low arterial oxygen levels and periodic breathing.