Altitude sickness pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Farima Kahe M.D. [2]


Altitude sickness caused by an increase in pulmonary artery pressure due to the normal pulmonary vasoconstriction induced by hypoxia. Hypoxia leads to increase oxygen delivery to the tissues and increases ventilation, cardiac output and haemoglobin concentrations. These changes improve ventilation-perfusion matching and gas exchange and lead to high altitude pulmonary hypertension.


  • It is believed that altitude sickness is secondary to body's response to hypoxia due to low pressure at high altitude; not just normobaric hypoxia.
  • This belief is due the the facts including:[1]
    • Onset of symptoms occurs after a delay from onset of hypoxia; ranging from hours to days
    • It takes time for symptoms to reverse after oxygen therapy
  • Physiological responses in mild to moderate altitude sickness includes:
    • Relative hypoventilation[2][3]
    • Impaired gas exchange[4]
    • Fluid retention and redistribution
    • Increased sympathetic drive[5]
  • Physiological responses in moderate to severe altitude sickness includes:
    • Raised intracranial pressure
    • Cerebral edema[6]
Algorithm showing pathogenesis of high altitude sickness[7]

Abbreviations: CBV= Cerebral blood volume, CBF= Cerebral or coronary blood flow, Pcap= Pulmonary capillary pressure, HACE= High-altitude cerebral edema, HAPE= High-altitude pulmonary edema [8][9][10][11]

Altitude hypoxemia
Uneven vasoconstriction
Focal/regional overperfusion
Vasogenic edema
Capillary leak


Monge disease

  • Monge disease is also known as chronic mountain disease, commonly present in individuals acclimatized to high altitudes.[12]
  • Monge disease is a maladaptive state due to hypoxia on high altitudes.
  • SENP1 (an erythrocyte regulator) and ANP32D (an oncogene) present on chromosome 12q13 are commonly involved in Monge disease.
  • Symptoms include severe polycythemia, headache, fatigue, somnolence, and depression.
  • Blood viscosity is increased due to polycythemia leading to complications such as strokes and myocardial infarctions in early adulthood.

Gross Pathology

There is no gross pathologic findings associated with altitude sickness.

Microscopic Pathology

There is no microscopic findings associated with altitude sickness.


  1. Singh I, Khanna PK, Srivastava MC, Lal M, Roy SB, Subramanyam CS (1969). "Acute mountain sickness". N Engl J Med. 280 (4): 175–84. doi:10.1056/NEJM196901232800402. PMID 5782719.
  2. Moore LG, Harrison GL, McCullough RE, McCullough RG, Micco AJ, Tucker A; et al. (1986). "Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness". J Appl Physiol (1985). 60 (4): 1407–12. doi:10.1152/jappl.1986.60.4.1407. PMID 3084449.
  3. Matsuzawa Y, Kobayashi T (1992). "[Exposure to high altitude: ventilatory control in relation to syndromes of high altitude]". Nihon Kyobu Shikkan Gakkai Zasshi. 30 Suppl: 139–46. PMID 1306217.
  4. Ge RL, Matsuzawa Y, Takeoka M, Kubo K, Sekiguchi M, Kobayashi T (1997). "Low pulmonary diffusing capacity in subjects with acute mountain sickness". Chest. 111 (1): 58–64. PMID 8995993.
  5. Hansen J, Sander M (2003). "Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia". J Physiol. 546 (Pt 3): 921–9. PMC 2342582. PMID 12563015.
  6. Schoonman GG, Sándor PS, Nirkko AC, Lange T, Jaermann T, Dydak U; et al. (2008). "Hypoxia-induced acute mountain sickness is associated with intracellular cerebral edema: a 3 T magnetic resonance imaging study". J Cereb Blood Flow Metab. 28 (1): 198–206. doi:10.1038/sj.jcbfm.9600513. PMID 17519973.
  7. Imray, Chris; Wright, Alex; Subudhi, Andrew; Roach, Robert (2010). "Acute Mountain Sickness: Pathophysiology, Prevention, and Treatment". Progress in Cardiovascular Diseases. 52 (6): 467–484. doi:10.1016/j.pcad.2010.02.003. ISSN 0033-0620.
  8. Imray C, Wright A, Subudhi A, Roach R (2010). "Acute mountain sickness: pathophysiology, prevention, and treatment". Prog Cardiovasc Dis. 52 (6): 467–84. doi:10.1016/j.pcad.2010.02.003. PMID 20417340.
  9. Taylor AT (January 2011). "High-altitude illnesses: physiology, risk factors, prevention, and treatment". Rambam Maimonides Med J. 2 (1): e0022. doi:10.5041/RMMJ.10022. PMC 3678789. PMID 23908794.
  10. Hackett PH (1999). "High altitude cerebral edema and acute mountain sickness. A pathophysiology update". Adv. Exp. Med. Biol. 474: 23–45. PMID 10634991.
  11. Murdoch D (March 2010). "Altitude sickness". BMJ Clin Evid. 2010. PMC 2907615. PMID 21718562.
  12. Zhou D, Udpa N, Ronen R, Stobdan T, Liang J, Appenzeller O; et al. (2013). "Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders". Am J Hum Genet. 93 (3): 452–62. doi:10.1016/j.ajhg.2013.07.011. PMC 3769925. PMID 23954164.

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