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High altitude illness: Physiology, risk factors, and general prevention

Scott A Gallagher, MD
Peter Hackett, MD
Jonathan M Rosen, MD
Section Editor
Daniel F Danzl, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM


The beauty and recreational opportunities of the mountains attract millions of visitors from lowland elevations to high-altitude destinations worldwide. Resort towns in the Western United States alone attract over 30 million visitors annually, generally to sleeping elevations in the 2000 to 3000 m (6500 to 9800 feet) range. Many millions more visit cities at these elevations, including several large cities in South America and Asia situated above 3000 m [1]. Most of these destinations can be reached within a day.

In addition, tens of thousands of climbers, trekkers, and skiers worldwide ascend to elevations in the 3000 to 5500 m (9800 to 18,000 feet) range, often at an ascent rate that exceeds an individual's ability to acclimatize. A growing number of mountaineers seek the summits of peaks over 5500 m. Military, rescue, and other professional personnel may also be called upon to ascend to high altitudes with little or no time for acclimatization. Such rapid ascents place the unacclimatized traveler at risk for developing high altitude illness (HAI).

Clinicians working in or near mountainous areas must familiarize themselves with the presentation and management of HAI, while all health care workers who advise travelers need to understand the best prevention strategies and treatment options. The different types of HAI, their pathophysiology, and general methods for prevention will be reviewed here. The diagnosis, treatment, and prevention of specific types of HAI are discussed separately. (See "Acute mountain sickness and high altitude cerebral edema" and "High altitude pulmonary edema" and "High altitude, air travel, and heart disease".)


Hypobaric hypoxia — The partial pressure of oxygen (PO2) is the driving force for the diffusion of oxygen down the oxygen cascade. Oxygen moves from inspired air to the alveolar space via the airways and then diffuses across the alveoli into the blood (figure 1 and figure 2), where it is carried mainly bound to hemoglobin but also in dissolved form. At the level of the capillaries, oxygen diffuses across vessel walls, through the tissues and into cells, and ultimately into the mitochondria. (See "Oxygen delivery and consumption" and "Oxygenation and mechanisms of hypoxemia".)

The partial pressure of oxygen of inspired air (PIO2) is given by the equation: PIO2 = FIO2 x (Pb - 47 mmHg), where FIO2 is the fraction of oxygen in inspired air, Pb is the barometric pressure, and 47 mmHg is the vapor pressure of H2O at 37°C. Inspired gas is 100 percent humidified by the time it reaches the alveoli and water vapor pressure is affected by temperature but, unlike other gases, is not dependent on altitude. The proportion of air comprised by oxygen (FIO2, 20.94 percent) remains constant at the highest terrestrial elevations and even into the upper troposphere. Hence the PIO2 and, therefore, the oxygen cascade, are directly affected by barometric pressure.

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Literature review current through: Nov 2017. | This topic last updated: Sep 20, 2017.
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  1. Roach RC, Lawley JS, Hackett PH. High-altitude physiology. In: Wilderness Medicine, 7th ed, Auerbach PS (Ed), Elsevier, Philadelphia 2017. p.2.
  2. West JB, American College of Physicians, American Physiological Society. The physiologic basis of high-altitude diseases. Ann Intern Med 2004; 141:789.
  3. Gallagher SA, Hackett PH. High-altitude illness. Emerg Med Clin North Am 2004; 22:329.
  4. Schoene RB. Illnesses at high altitude. Chest 2008; 134:402.
  5. MacInnis MJ, Wang P, Koehle MS, Rupert JL. The genetics of altitude tolerance: the evidence for inherited susceptibility to acute mountain sickness. J Occup Environ Med 2011; 53:159.
  6. West JB, Schoene RB, Luks AM, Milledge JS. High Altitude Medicine and Physiology, 5th ed, CRC Press, Boca Raton 2013.
  7. Wolff CB, Richardson N, Kemp O, et al. Near infra-red spectroscopy and arterial oxygen extraction at altitude. Adv Exp Med Biol 2007; 599:183.
  8. Anholm JD, Foster GP. Con: Hypoxic pulmonary vasoconstriction is not a limiting factor of exercise at high altitude. High Alt Med Biol 2011; 12:313.
  9. Naeije R. Pro: Hypoxic pulmonary vasoconstriction is a limiting factor of exercise at high altitude. High Alt Med Biol 2011; 12:309.
  10. Grimminger J, Richter M, Tello K, et al. Thin Air Resulting in High Pressure: Mountain Sickness and Hypoxia-Induced Pulmonary Hypertension. Can Respir J 2017; 2017:8381653.
  11. Storz JF. Hemoglobin-oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend? J Exp Biol 2016; 219:3190.
  12. Calbet JA, Lundby C. Air to muscle O2 delivery during exercise at altitude. High Alt Med Biol 2009; 10:123.
  13. West JB. Physiological Effects of Chronic Hypoxia. N Engl J Med 2017; 376:1965.
  14. Basnyat B, Murdoch DR. High-altitude illness. Lancet 2003; 361:1967.
  15. Stream JO, Grissom CK. Update on high-altitude pulmonary edema: pathogenesis, prevention, and treatment. Wilderness Environ Med 2008; 19:293.
  16. Johnson PL, Popa DA, Prisk GK, et al. Non-invasive positive pressure ventilation during sleep at 3800 m: Relationship to acute mountain sickness and sleeping oxyhaemoglobin saturation. Respirology 2010; 15:277.
  17. Bloch KE, Latshang TD, Turk AJ, et al. Nocturnal periodic breathing during acclimatization at very high altitude at Mount Muztagh Ata (7,546 m). Am J Respir Crit Care Med 2010; 182:562.
  18. Küpper T, Schöffl V, Netzer N. Cheyne stokes breathing at high altitude: a helpful response or a troublemaker? Sleep Breath 2008; 12:123.
  19. Hackett PH, Rennie D. Rales, peripheral edema, retinal hemorrhage and acute mountain sickness. Am J Med 1979; 67:214.
  20. Butler FK, Harris DJ Jr, Reynolds RD. Altitude retinopathy on Mount Everest, 1989. Ophthalmology 1992; 99:739.
  21. Lang GE, Kuba GB. High-altitude retinopathy. Am J Ophthalmol 1997; 123:418.
  22. Hackett PH, Roach RC. High-altitude illness. N Engl J Med 2001; 345:107.
  23. Bärtsch P, Swenson ER. Clinical practice: Acute high-altitude illnesses. N Engl J Med 2013; 368:2294.
  24. Duster MC, Derlet MN. High-altitude illness in children. Pediatr Ann 2009; 38:218.
  25. Durmowicz AG, Noordeweir E, Nicholas R, Reeves JT. Inflammatory processes may predispose children to high-altitude pulmonary edema. J Pediatr 1997; 130:838.
  26. Choudhuri JA, Ogden LG, Ruttenber AJ, et al. Effect of altitude on hospitalizations for respiratory syncytial virus infection. Pediatrics 2006; 117:349.
  27. Fasules JW, Wiggins JW, Wolfe RR. Increased lung vasoreactivity in children from Leadville, Colorado, after recovery from high-altitude pulmonary edema. Circulation 1985; 72:957.
  28. Lovering AT, Romer LM, Haverkamp HC, et al. Excessive gas exchange impairment during exercise in a subject with a history of bronchopulmonary dysplasia and high altitude pulmonary edema. High Alt Med Biol 2007; 8:62.
  29. Rios B, Driscoll DJ, McNamara DG. High-altitude pulmonary edema with absent right pulmonary artery. Pediatrics 1985; 75:314.
  30. Sebbane M, Wuyam B, Pin I, et al. Unilateral agenesis of the pulmonary artery and high-altitude pulmonary edema (HAPE) at moderate altitude. Pediatr Pulmonol 1997; 24:111.
  31. Oades PJ, Buchdahl RM, Bush A. Prediction of hypoxaemia at high altitude in children with cystic fibrosis. BMJ 1994; 308:15.
  32. Pashankar FD, Carbonella J, Bazzy-Asaad A, Friedman A. Prevalence and risk factors of elevated pulmonary artery pressures in children with sickle cell disease. Pediatrics 2008; 121:777.
  33. Hultgren HN, Honigman B, Theis K, Nicholas D. High-altitude pulmonary edema at a ski resort. West J Med 1996; 164:222.
  34. Das BB, Wolfe RR, Chan KC, et al. High-altitude pulmonary edema in children with underlying cardiopulmonary disorders and pulmonary hypertension living at altitude. Arch Pediatr Adolesc Med 2004; 158:1170.
  35. Niermeyer S. Going to high altitude with a newborn infant. High Alt Med Biol 2007; 8:117.
  36. Richalet JP, Chenivesse C, Larmignat P, Meille L. High altitude pulmonary edema, down syndrome, and obstructive sleep apneas. High Alt Med Biol 2008; 9:179.
  37. Röggla G, Moser B. High-altitude pulmonary edema at moderate altitude as first manifestation of pulmonary hypertension in a 14-year-old boy with Down Syndrome. Wilderness Environ Med 2006; 17:207.
  38. Durmowicz AG. Pulmonary edema in 6 children with Down syndrome during travel to moderate altitudes. Pediatrics 2001; 108:443.
  39. Ri-Li G, Chase PJ, Witkowski S, et al. Obesity: associations with acute mountain sickness. Ann Intern Med 2003; 139:253.
  40. Wu SH, Lin YC, Weng YM, et al. The impact of physical fitness and body mass index in children on the development of acute mountain sickness: A prospective observational study. BMC Pediatr 2015; 15:55.
  41. Nussbaumer-Ochsner Y, Latshang TD, Ulrich S, et al. Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial. Chest 2012; 141:131.
  42. McIntosh SE, Opacic M, Freer L, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of frostbite: 2014 update. Wilderness Environ Med 2014; 25:S43.
  43. Bloch KE, Turk AJ, Maggiorini M, et al. Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m. High Alt Med Biol 2009; 10:25.
  44. Beidleman BA, Fulco CS, Muza SR, et al. Effect of six days of staging on physiologic adjustments and acute mountain sickness during ascent to 4300 meters. High Alt Med Biol 2009; 10:253.
  45. Pesce C, Leal C, Pinto H, et al. Determinants of acute mountain sickness and success on Mount Aconcagua (6962 m). High Alt Med Biol 2005; 6:158.
  46. Schneider M, Bernasch D, Weymann J, et al. Acute mountain sickness: influence of susceptibility, preexposure, and ascent rate. Med Sci Sports Exerc 2002; 34:1886.
  47. Honigman B, Theis MK, Koziol-McLain J, et al. Acute mountain sickness in a general tourist population at moderate altitudes. Ann Intern Med 1993; 118:587.
  48. Dehnert C, Böhm A, Grigoriev I, et al. Sleeping in moderate hypoxia at home for prevention of acute mountain sickness (AMS): a placebo-controlled, randomized double-blind study. Wilderness Environ Med 2014; 25:263.
  49. Beidleman BA, Muza SR, Fulco CS, et al. Intermittent altitude exposures reduce acute mountain sickness at 4300 m. Clin Sci (Lond) 2004; 106:321.
  50. Fulco CS, Beidleman BA, Muza SR. Effectiveness of preacclimatization strategies for high-altitude exposure. Exerc Sport Sci Rev 2013; 41:55.
  51. Schommer K, Wiesegart N, Menold E, et al. Training in normobaric hypoxia and its effects on acute mountain sickness after rapid ascent to 4559 m. High Alt Med Biol 2010; 11:19.
  52. Graham LE, Basnyat B. Cerebral edema in the Himalayas: too high, too fast! Wilderness Environ Med 2001; 12:62.
  53. Roeggla G, Roeggla H, Roeggla M, et al. Effect of alcohol on acute ventilatory adaptation to mild hypoxia at moderate altitude. Ann Intern Med 1995; 122:925.
  54. Basnyat B, Lemaster J, Litch JA. Everest or bust: a cross sectional, epidemiological study of acute mountain sickness at 4243 meters in the Himalayas. Aviat Space Environ Med 1999; 70:867.
  55. Swenson ER, MacDonald A, Vatheuer M, et al. Acute mountain sickness is not altered by a high carbohydrate diet nor associated with elevated circulating cytokines. Aviat Space Environ Med 1997; 68:499.
  56. Roach RC, Maes D, Sandoval D, et al. Exercise exacerbates acute mountain sickness at simulated high altitude. J Appl Physiol (1985) 2000; 88:581.
  58. Conway R, Evans I, Weeraman D. Assessing travelers' knowledge and use of coca for altitude sickness. Wilderness Environ Med 2012; 23:373.
  59. Spielvogel H, Caceres E, Koubi H, et al. Effects of coca chewing on metabolic and hormonal changes during graded incremental exercise to maximum. J Appl Physiol (1985) 1996; 80:643.
  60. Salazar H, Swanson J, Mozo K, et al. Acute mountain sickness impact among travelers to Cusco, Peru. J Travel Med 2012; 19:220.