Medscape is available in 5 Language Editions – Choose your Edition here.


High-Altitude Pulmonary Edema

  • Author: Rohit Goyal, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
Updated: Dec 31, 2015


High-altitude illness may result from short-term exposures to altitudes in excess of 2000 m (6560 ft). This illness comprises a spectrum of clinical entities that are probably the manifestations of the same disease process. High-altitude pulmonary edema (HAPE) and cerebral edema are the most ominous of these symptoms, while acute mountain sickness, retinal hemorrhages, and peripheral edema are the milder forms of the disease. The rate of ascent, the altitude attained, the amount of physical activity at high altitude, and individual susceptibility are contributing factors to the incidence and severity of high-altitude illness.

Also see Altitude Illness, Cerebral Syndromes and Altitude Illness, Pulmonary Syndromes.



The pathophysiology high-altitude pulmonary edema (HAPE) is not well understood.{ref1-INVALID REFERENCE} HAPE is a noncardiogenic form of pulmonary edema resulting from a leak in the alveolar capillary membrane. The various mechanisms believed to be responsible are pulmonary arterial vasoconstriction resulting in circulatory shear forces and a consequent permeability leak and antidiuresis possibly mediated by increased antidiuretic hormones, which contribute to fluid retention. The inciting factor appears to be excessive hypoxia.[1]

A number of compensatory mechanisms improve oxygen delivery when its inspired concentration is reduced. The first adaptation to high altitude is an increase in minute ventilation. The ventilatory response to a relatively hypoxic stimulus can be divided into 4 phases: (1) initial increase on ascent, (2) subsequent course over hours and weeks, (3) deacclimatization on descent, and (4) long-term response of high-altitude natives.

The barometric pressure decreases with distance above the Earth's surface in an approximately exponential manner. The pressure at 5500 m (18,000 ft) is only half the normal 760 mm Hg, so that the partial pressure of oxygen (PO2) of moist inspired gas is (380-47) X 0.2093 = 70 (47 mm Hg is the partial pressure of water vapor at body temperature [ie, 37ºC]). At the summit of Mount Everest (altitude 8848 m or 29,028 ft), the inspired PO2 is only 43. In spite of hypoxia associated with high altitude, approximately 15 million people live at elevations over 3050 m, and some permanent residents live higher than 4900 m in the Andes. A remarkable degree of acclimatization occurs when humans ascend to these altitudes. Climbers have lived for several days at altitudes that would cause unconsciousness within a few seconds in the absence of acclimatization.

Spirometric studies have shown that with increasing altitude, both forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) are reduced by up to 25% (74.8% / 74.6% of baseline). In the same study, peak expiratory flow (PEF) initially increased up to 4451 m and returned to baseline values above 5000 m. After descent below 2000 m, all values normalized within one day. These findings were consistent with increasing pulmonary restriction at high altitudes (without a marked reduction of PEF). Portable spirometry may provide clinically relevant information (impending pulmonary edema) in high-altitude travelers.[2, 3, 4]

Bronchoalveolar lavage fluid (BALF) studies have shown that after heavy exercise, under all conditions, athletes develop a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. Exercise at altitude (3810 m) caused significantly greater leakage of RBCs (92,000 [SD 3.1] cells/mL) into the alveolar space than that seen with normoxic exercise (54,000 [SD 1.2] cells/mL). At altitude, the 26-hour postexercise BALF had significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.[5]

Autopsy studies performed on patients who died of HAPE have shown a proteinaceous exudate with hyaline membranes. The studies have shown areas of pneumonitis with neutrophil accumulation, although none was noted to contain bacteria. Pulmonary veins were not dilated. Most reports mention capillary and arteriolar thrombi with deposits of fibrin, hemorrhage, and infarcts. The findings suggest a protein-rich edema with a possibility that clotting abnormalities may be partially responsible for this illness.

Bronchoalveolar lavages performed on patients with HAPE have also shown the fluid to have a high protein content, higher than in patients with adult respiratory distress syndrome (ARDS). The fluid was also highly cellular. Unlike ARDS, which primarily has neutrophils in the lavage fluid, HAPE fluid contains a higher percentage of alveolar macrophages. Additionally, chemotactic (leukotriene B4) and vasoactive (thromboxane B2) mediators were present in the lavage.




United States

In one study on Colorado skiers, the incidence of acute mountain sickness was as high as 15-40%. The incidence of high-altitude pulmonary edema (HAPE) is much lower, at about 0.1-1%.


In a study on Mount Everest trekkers, the incidence of high-altitude pulmonary edema (HAPE) was about 1.6%. The incidence of mountain sickness appears to be unusually high in trekkers on Mount Rainier; however, the incidence of pulmonary edema is the same as in other places. One study reported that Everest region trekkers were more likely to be evacuated for altitude illness than trekkers in other regions.[6]


High-altitude pulmonary edema (HAPE) may be fatal within a few hours if left untreated. Patients who recover from HAPE have rapid clearing of edema fluid and do not develop long-term complications. One study has shown that the estimated incidence of altitude illness–related death was 7.7 deaths in 100,000 trekkers. The mortality has been increasing over the last decade.[6]


Men and women are equally susceptible to acute mountain sickness, but women may be less likely to develop high-altitude pulmonary edema (HAPE). In addition to individual differences in susceptibility, other factors, such as alcohol, respiratory depressants, and respiratory infections, may enhance vulnerability to altitude illness.


The typical patient with high-altitude pulmonary edema (HAPE) is a young person who is otherwise physically fit. HAPE is rare in infants and small children.

Contributor Information and Disclosures

Rohit Goyal, MD Fellow, Division of Pulmonary Medicine, Lenox Hill Hospital, New York University School of Medicine

Rohit Goyal, MD is a member of the following medical societies: American College of Chest Physicians, American Medical Association, American Thoracic Society

Disclosure: Nothing to disclose.


Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Samia Qazi, MD, MD 

Samia Qazi, MD, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Laurie Ward, MD 

Laurie Ward, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Qazi Qaisar Afzal, MD Clinical Instructor, Department of Medicine, State University of New York at Stony Brook

Qazi Qaisar Afzal, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Mir Omar Ali, MD Fellow, Department of Pulmonary Medicine, Lenox Hill Hospital, New York University

Mir Omar Ali, MD is a member of the following medical societies: American College of Physicians, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Mir Mustafa Ali Deccan College of Medical Sciences, Owaisi Hospital and Research Center, Princess Esra Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

  1. Alam P, Pasha MA, Saini N. microRNAs: an apparent switch for high-altitude pulmonary edema. Microrna. 2015 Nov 3. [Medline].

  2. Fischer R, Lang SM, Bergner A, Huber RM. Monitoring of expiratory flow rates and lung volumes during a high altitude expedition. Eur J Med Res. 2005 Nov 16. 10(11):469-74. [Medline].

  3. Guo L, Tan G, Liu P, Li H, Tang L, Huang L, et al. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema. Sci Rep. 2015 Oct 13. 5:15126. [Medline].

  4. Wu AL, Xiong YS, Li ZQ, Liu YG, Quan Q, Wu LJ. Correlation between single nucleotide polymorphisms in hypoxia-related genes and susceptibility to acute high-altitude pulmonary edema. Genet Mol Res. 2015 Sep 28. 14 (3):11562-72. [Medline].

  5. Eldridge MW, Braun RK, Yoneda KY, Walby WF. Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema. J Appl Physiol. 2006 Mar. 100(3):972-80. [Medline].

  6. Leshem E, Pandey P, Shlim DR, Hiramatsu K, Sidi Y, Schwartz E. Clinical features of patients with severe altitude illness in Nepal. J Travel Med. 2008 Sep-Oct. 15(5):315-22. [Medline].

  7. Hartmann G, Tschop M, Fischer R, et al. High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein. Cytokine. 2000 Mar. 12(3):246-52. [Medline].

  8. Grunig E, Mereles D, Hildebrandt W, et al. Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol. 2000 Mar 15. 35(4):980-7. [Medline].

  9. Fagenholz PJ, Gutman JA, Murray AF, Noble VE, Thomas SH, Harris NS. Chest ultrasonography for the diagnosis and monitoring of high-altitude pulmonary edema. Chest. 2007 Apr. 131(4):1013-8. [Medline].

  10. Maggiorini M. Prevention and treatment of high-altitude pulmonary edema. Prog Cardiovasc Dis. 2010 May-Jun. 52(6):500-6. [Medline].

  11. Zhou Q. Standardization of methods for early diagnosis and on-site treatment of high-altitude pulmonary edema. Pulm Med. 2011. 2011:190648. [Medline]. [Full Text].

  12. Fagenholz PJ, Gutman JA, Murray AF, Harris NS. Treatment of high altitude pulmonary edema at 4240 m in Nepal. High Alt Med Biol. 2007 Summer. 8(2):139-46. [Medline].

  13. Maggiorini M, Brunner-La Rocca HP, Peth S, et al. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med. 2006 Oct 3. 145(7):497-506. [Medline].

  14. Mounier R, Amonchot A, Caillot N, Gladine C, Citron B, Bedu M, et al. Pulmonary arterial systolic pressure and susceptibility to high altitude pulmonary edema. Respir Physiol Neurobiol. 2011 Dec 15. 179(2-3):294-9. [Medline].

  15. [Guideline] Hill DR, Ericsson CD, Pearson RD, et al. The practice of travel medicine: guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Dec 15. 43(12):1499-539. [Medline].

  16. [Guideline] Rice SG. Medical conditions affecting sports participation. Pediatrics. 2008 Apr. 121(4):841-8. [Medline].

  17. Bärtsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med. 1991 Oct 31. 325(18):1284-9. [Medline].

  18. van Patot MC, Leadbetter G 3rd, Keyes LE, Maakestad KM, Olson S, Hackett PH. Prophylactic low-dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Alt Med Biol. 2008 Winter. 9(4):289-93. [Medline].

  19. Bärtsch P. High altitude pulmonary edema. Med Sci Sports Exerc. 1999 Jan. 31(1 Suppl):S23-7. [Medline].

  20. Bärtsch P. High altitude pulmonary edema. Respiration. 1997. 64(6):435-43. [Medline].

  21. Goetz AE, Kuebler WM, Peter K. High-altitude pulmonary edema. N Engl J Med. 1996 Jul 18. 335(3):206-7. [Medline].

  22. Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet. 1976 Nov 27. 2(7996):1149-55. [Medline].

  23. Klocke DL, Decker WW, Stepanek J. Altitude-related illnesses. Mayo Clin Proc. 1998 Oct. 73(10):988-92; quiz 992-3. [Medline].

  24. Krieger BP, de la Hoz RE. Altitude-related pulmonary disorders. Crit Care Clin. 1999 Apr. 15(2):265-80, viii. [Medline].

  25. Naeije R. Pulmonary circulation at high altitude. Respiration. 1997. 64(6):429-34. [Medline].

  26. Nayak NC, Roy S, Narayanan TK. Pathologic features of altitude sickness. Am J Pathol. 1964 Sep. 45:381-91. [Medline].

  27. Schoene RB. Lung disease at high altitude. Adv Exp Med Biol. 1999. 474:47-56. [Medline].

  28. Schoene RB, Hackett PH, HornBein TF. High altitude. Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine. Philadelphia, Pa: WB Saunders; 2000. Vol 2: 2062-98.

  29. Singh I, Khanna PK, Srivastava MC, Lal M, Roy SB, Subramanyam CS. Acute mountain sickness. N Engl J Med. 1969 Jan 23. 280(4):175-84. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.