High-altitude Physiology and Pathophysiology: Implications and Relevance for Intensive Care Medicine

Overview

Journal Crit Care

Specialty Critical Care

Date 2007 Feb 13

PMID 17291330

Citations 67

Authors

Michael Grocott

Hugh Montgomery

Andre Vercueil

Affiliations

Soon will be listed here.

Abstract

Cellular hypoxia is a fundamental mechanism of injury in the critically ill. The study of human responses to hypoxia occurring as a consequence of hypobaria defines the fields of high-altitude medicine and physiology. A new paradigm suggests that the physiological and pathophysiological responses to extreme environmental challenges (for example, hypobaric hypoxia, hyperbaria, microgravity, cold, heat) may be similar to responses seen in critical illness. The present review explores the idea that human responses to the hypoxia of high altitude may be used as a means of exploring elements of the pathophysiology of critical illness.

Citing Articles

Heterogeneity of treatment effect: the case for individualising oxygen therapy in critically ill patients.

Martin D, Grocott M Crit Care. 2025; 29(1):50.

PMID: 39875948 PMC: 11776231. DOI: 10.1186/s13054-025-05254-5.

How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.

Mirchandani A, Sanchez-Garcia M, Walmsley S Nat Rev Immunol. 2024; 25(3):161-177.

PMID: 39349943 DOI: 10.1038/s41577-024-01087-5.

Consequences of Exposure to Hypobaric Hypoxia Associated with High Altitude on Spermatogenesis and Seminal Parameters: A Literature Review.

Cornejo-Guerra C, Salazar-Ardiles C, Morales P, Andrade D Cells. 2024; 13(7.

PMID: 38607031 PMC: 11011536. DOI: 10.3390/cells13070592.

Metabolomics and transcriptomics of embryonic livers reveal hypoxia adaptation of Tibetan chickens.

Xue M, Yu R, Yang L, Xie F, Fang M, Tang Q BMC Genomics. 2024; 25(1):131.

PMID: 38302894 PMC: 10832288. DOI: 10.1186/s12864-024-10030-w.

Tau Protein Alterations Induced by Hypobaric Hypoxia Exposure.

Pena E, San Martin-Salamanca R, El Alam S, Flores K, Arriaza K Int J Mol Sci. 2024; 25(2).

PMID: 38255962 PMC: 10815386. DOI: 10.3390/ijms25020889.

References

Marshall R, Webb S, Bellingan G, Montgomery H, Chaudhari B, McAnulty R . Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002; 166(5):646-50. DOI: 10.1164/rccm.2108086. View

Bailey D, Kleger G, Holzgraefe M, Ballmer P, Bartsch P . Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness. J Appl Physiol (1985). 2003; 96(4):1459-63. DOI: 10.1152/japplphysiol.00704.2003. View

Schoene R, Swenson E, Pizzo C, Hackett P, Roach R, MILLS Jr W . The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and pulmonary edema. J Appl Physiol (1985). 1988; 64(6):2605-13. DOI: 10.1152/jappl.1988.64.6.2605. View

Murdoch D . Symptoms of infection and altitude illness among hikers in the Mount Everest region of Nepal. Aviat Space Environ Med. 1995; 66(2):148-51. View

Weiss J, Haefeli W, Gasse C, Hoffmann M, Weyman J, Gibbs S . Lack of evidence for association of high altitude pulmonary edema and polymorphisms of the NO pathway. High Alt Med Biol. 2003; 4(3):355-66. DOI: 10.1089/152702903769192313. View

Hartmann G, Tschop M, Fischer R, Bidlingmaier C, Riepl R, Tschop K . High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein. Cytokine. 2000; 12(3):246-52. DOI: 10.1006/cyto.1999.0533. View

Hotta J, Hanaoka M, Droma Y, Katsuyama Y, Ota M, Kobayashi T . Polymorphisms of renin-angiotensin system genes with high-altitude pulmonary edema in Japanese subjects. Chest. 2004; 126(3):825-30. DOI: 10.1378/chest.126.3.825. View

Singer M, De Santis V, Vitale D, Jeffcoate W . Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet. 2004; 364(9433):545-8. DOI: 10.1016/S0140-6736(04)16815-3. View

Bertges D, Fink M, Delude R . Hypoxic signal transduction in critical illness. Crit Care Med. 2000; 28(4 Suppl):N78-86. DOI: 10.1097/00003246-200004001-00009. View

10.

Aldashev A, Sarybaev A, Sydykov A, Kalmyrzaev B, Kim E, Mamanova L . Characterization of high-altitude pulmonary hypertension in the Kyrgyz: association with angiotensin-converting enzyme genotype. Am J Respir Crit Care Med. 2002; 166(10):1396-402. DOI: 10.1164/rccm.200204-345OC. View

11.

Sun S, Droma T, Zhang J, Tao J, Huang S, McCullough R . Greater maximal O2 uptakes and vital capacities in Tibetan than Han residents of Lhasa. Respir Physiol. 1990; 79(2):151-61. DOI: 10.1016/0034-5687(90)90015-q. View

12.

Brealey D, Singer M . Mitochondrial Dysfunction in Sepsis. Curr Infect Dis Rep. 2003; 5(5):365-371. DOI: 10.1007/s11908-003-0015-9. View

13.

Fleming A, Bishop M, SHOEMAKER W, Appel P, Sufficool W, Kuvhenguwha A . Prospective trial of supranormal values as goals of resuscitation in severe trauma. Arch Surg. 1992; 127(10):1175-9; discussion 1179-81. DOI: 10.1001/archsurg.1992.01420100033006. View

14.

Harding D, Dhamrait S, Marlow N, Whitelaw A, Gupta S, Humphries S . Angiotensin-converting enzyme DD genotype is associated with worse perinatal cardiorespiratory adaptation in preterm infants. J Pediatr. 2003; 143(6):746-9. DOI: 10.1067/S0022-3476(03)00582-1. View

15.

Zhuang J, Droma T, Sutton J, GROVES B, McCullough R, McCullough R . Smaller alveolar-arterial O2 gradients in Tibetan than Han residents of Lhasa (3658 m). Respir Physiol. 1996; 103(1):75-82. DOI: 10.1016/0034-5687(95)00041-0. View

16.

Howald H, Hoppeler H . Performing at extreme altitude: muscle cellular and subcellular adaptations. Eur J Appl Physiol. 2003; 90(3-4):360-4. DOI: 10.1007/s00421-003-0872-9. View

17.

Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R . Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002; 360(9328):219-23. DOI: 10.1016/S0140-6736(02)09459-X. View

18.

Harding D, Baines P, Brull D, Vassiliou V, Ellis I, Hart A . Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism. Am J Respir Crit Care Med. 2002; 165(8):1103-6. DOI: 10.1164/ajrccm.165.8.2108089. View

19.

Calbet J, Boushel R, Radegran G, Sondergaard H, Wagner P, Saltin B . Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content?. Am J Physiol Regul Integr Comp Physiol. 2002; 284(2):R304-16. DOI: 10.1152/ajpregu.00156.2002. View

20.

Yellon D, Downey J . Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev. 2003; 83(4):1113-51. DOI: 10.1152/physrev.00009.2003. View