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The effects of high altitude on humans are considerable. The percentage saturation of hemoglobin with oxygen determines the content of oxygen in our blood. After the human body reaches around 2,100 m (7,000 feet) above sea level, the saturation of oxyhemoglobin begins to plummet. However, the human body has both short-term and long-term adaptations to altitude that allow it to partially compensate for the lack of oxygen. Athletes use these adaptations to help their performance. There is a limit to the level of adaptation; mountaineers refer to the altitudes above 8,000 metres (26,000 ft) as the "death zone", where no human body can acclimatize.
The human body can perform best at sea level, where the atmospheric pressure is 101,325 Pa or 1013.25 millibars (or 1 atm, by definition). The concentration of oxygen (O2) in sea-level air is 20.9%, so the partial pressure of O2 (pO2) is 21.136 kPa. In healthy individuals, this saturates hemoglobin, the oxygen-binding red pigment in red blood cells.
Atmospheric pressure decreases exponentially with altitude while the O2 fraction remains constant to about 100 km, so pO2 decreases exponentially with altitude as well. It is about half of its sea-level value at 5,000 m (16,000 ft), the altitude of the Everest Base Camp, and only a third at 8,848 m (29,029 ft), the summit of Mount Everest. When pO2 drops, the body responds with altitude acclimatization.
Mountain medicine recognizes three altitude regions that reflect the lowered amount of oxygen in the atmosphere:
Travel to each of these altitude regions can lead to medical problems, from the mild symptoms of acute mountain sickness to the potentially fatal high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The higher the altitude, the greater the risk. Research also indicates elevated risk of permanent brain damage in people climbing to extreme altitudes. Expedition doctors commonly stock a supply of dexamethazone, or "dex," to treat these conditions on site.
Humans have survived for two years at 5,950 m (19,520 ft) [475 millibars of atmospheric pressure], which is the highest recorded permanently tolerable highest altitude; the highest permanent settlement known, La Rinconada, is at 5,100 m (16,700 ft). At extreme altitudes, above 7,500 m (24,600 ft) [383 millibars of atmospheric pressure], sleeping becomes very difficult, digesting food is near-impossible, and the risk of HAPE or HACE increases greatly.
The death zone, in mountaineering, refers to altitudes above a certain point where the amount of oxygen is insufficient to sustain human life. This point is generally tagged as 8,000 m (26,000 ft) [less than 356 millibars of atmospheric pressure]. The concept of the death zone (originally the lethal zone) was first conceived by Edouard Wyss-Dunant, a Swiss doctor, in an article about acclimatisation published in the journal of the Swiss Foundation for Alpine Research.
Many deaths in high-altitude mountaineering have been caused by the effects of the death zone, either directly (loss of vital functions) or indirectly (wrong decisions made under stress, physical weakening leading to accidents). In the death zone, the human body cannot acclimatize. An extended stay in the zone without supplementary oxygen will result in deterioration of bodily functions, loss of consciousness and, ultimately, death.
Scientists at the High Altitude Pathology Institute in Bolivia dispute the existence of a death zone, based on observation of extreme tolerance to hypoxia in patients with chronic mountain sickness and normal fetuses in-utero, both of which present PaO2 levels similar to those at the summit of Mount Everest.
One hundred and forty million people live at altitudes above 2,500 metres (8,200 ft). Studies have found that these populations, especially people living in the Andes and in the Himalayas, have ways of compensating for the lower oxygen levels that are different from people living at sea level. Compared with acclimatized newcomers, native Andean and Himalayan populations have better oxygenation at birth, enlarged lung volumes throughout life, and a higher capacity for exercise. Tibetans demonstrate a sustained increase in cerebral blood flow, lower haemoglobin concentration, and less susceptibility to chronic mountain sickness (CMS) than other high altitude populations. These adaptations may reflect their longer history of high altitude habitation.
There is a significantly lower mortality rate for permanent residents at higher altitudes. Similarly, there is a dose response relationship between increasing elevation and decreasing obesity prevalence in the United States. This is not explained by migration alone.  On the other hand, people living at higher elevations also have a higher rate of suicide in the United States. Similar findings were observed for both firearm-related suicides (59% of suicides) and nonfirearm-related suicides. The correlation between elevation and suicide risk was present even when the researchers control for known suicide risk factors, including age, gender, race and income. Research also indicates that oxygen levels are unlikely to be a factor, considering that there is no indication of increased mood disturbances at high altitude in those with sleep apnea or in heavy smokers at high altitude. The cause for the increased suicide risk is unknown so far.
The human body can adapt to high altitude through immediate and long-term acclimatization. At high altitude, in the short term, the lack of oxygen is sensed by the carotid bodies, which causes an increase in the breathing rate (hyperventilation). However, hyperventilation also causes the adverse effect of respiratory alkalosis, inhibiting the respiratory center from enhancing the respiratory rate as much as would be required. Inability to increase the breathing rate can be caused by inadequate carotid body response or pulmonary or renal disease.
In addition, at high altitude, the heart beats faster; the stroke volume is slightly decreased; and non-essential bodily functions are suppressed, resulting in a decline in food digestion efficiency (as the body suppresses the digestive system in favor of increasing its cardiopulmonary reserves).
Full acclimatization, however, requires days or even weeks. Gradually, the body compensates for the respiratory alkalosis by renal excretion of bicarbonate, allowing adequate respiration to provide oxygen without risking alkalosis. It takes about four days at any given altitude and can be enhanced by drugs such as acetazolamide. Eventually, the body has lower lactate production (because reduced glucose breakdown decreases the amount of lactate formed), decreased plasma volume, increased hematocrit (polycythemia), increased RBC mass, a higher concentration of capillaries in skeletal muscle tissue, increased myoglobin, increased mitochondria, increased aerobic enzyme concentration, increase in 2,3-BPG, hypoxic pulmonary vasoconstriction, and right ventricular hypertrophy. Pulmonary artery pressure increases in an effort to oxygenate more blood.
Full hematological adaptation to high altitude is achieved when the increase of red blood cells reaches a plateau and stops. The length of full hematological adaptation can be approximated by multiplying the altitude in kilometers by 11.4 days. For example, to adapt to 4,000 metres (13,000 ft) of altitude would require 45.6 days. The upper altitude limit of this linear relationship has not been fully established.
For athletes, high altitude produces two contradictory effects on performance. For explosive events (sprints up to 400 metres, long jump, triple jump) the reduction in atmospheric pressure means there is less resistance from the atmosphere and the athlete's performance will generally be better at high altitude. For endurance events (races of 800 metres or more), the predominant effect is the reduction in oxygen, which generally reduces the athlete's performance at high altitude. Sports organizations acknowledge the effects of altitude on performance: the International Association of Athletics Federations (IAAF), for example, have ruled that performances achieved at an altitude greater than 1,000 metres will be approved for record purposes, but carry the notation of "A" to denote they were set at altitude. The 1968 Summer Olympics were held at altitude in Mexico City. With the best athletes in the world competing for the most prestigious title, most short sprint and jump records were set there at altitude. Other records were also set at altitude in anticipation of those Olympics. Bob Beamon's record in the long jump held for almost 23 years and has only been beaten once without altitude or wind assistance. Many of the other records set at Mexico City were later surpassed by marks set at altitude.
Athletes can also take advantage of altitude acclimatization to increase their performance. The same changes that help the body cope with high altitude increase performance back at sea level. However, this may not always be the case. Any positive acclimatization effects may be negated by a de-training effect as the athletes are usually not able to exercise with as much intensity at high altitudes compared to sea level.
This conundrum led to the development of the altitude training modality known as "Live-High, Train-Low", whereby the athlete spends many hours a day resting and sleeping at one (high) altitude, but performs a significant portion of their training, possibly all of it, at another (lower) altitude. A series of studies conducted in Utah in the late 1990s by researchers Ben Levine, Jim Stray-Gundersen, and others, showed significant performance gains in athletes who followed such a protocol for several weeks. Other studies have shown performance gains from merely performing some exercising sessions at high altitude, yet living at sea level.