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Pulmonary Biology in Health and Disease pp 306–331Cite as

High-Altitude Physiology and Pathophysiology

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Abstract

Altitude exposure provides a natural laboratory for the study of the effects of low oxygen (hypoxia). Oxygen is the most necessary of substances in our environment, and without it we become unconscious within seconds. When O2 is available, but in low concentrations, the body has elaborate defense systems and compensatory mechanisms that are progressively called into play as the duration of hypoxia increases. When these mechanisms fail or when they are stretched beyond their capacity, organ malfunction occurs. This chapter will focus primarily on the mechanisms of response to hypoxia and to a lesser extent on the disorders that result when the response is inadequate. For more information the reader is referred to other reviews (Penulosa and Sime, 1971; Reeves, 1973; Reeves and Grover, 1974; Dempsey and Forster, 1982; Winslow and Monge, 1987; Kawashima, 1989; Hackett and Roach, 1990; Weil, 1990; Reeves and Groves et al., 1991; Moore, 1992; Oelz et al, 1992; Honigman, 1993; Ward, 1995).

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References

  • Anand, I.S., and Chandrashekhar, Y. (1992) Subacute mountain sickness syndromes: role of pulmonary hypertension. In: Sutton, J.R., Coates, G., and Houston, C.S. (eds.), pp. 241–251. Hypoxia and mountain medicine. Queen City Printers, Burlington, VT.

    Google Scholar 

  • Brooks, G.A., Butterfield, G.E., Wolfe, R.R., Groves, B.M., Mazzeo, R.S., Sutton J.R. et al. (1990) Increased dependence on blood glucose after acclimatization to 4300 m. J. Appl. Physiol. 70, 919–927.

    Google Scholar 

  • Brooks, G.A., Butterfield, G.E., Wolfe, R.R., Groves, B.M., Mazzeo, R.S., Sutton J.R. et al. (1991) Decreased reliance on lactate during exercise after acclimatization to 4300m. J. Appl. Physiol. 71, 333–341.

    PubMed  CAS  Google Scholar 

  • Brooks, G.A., Wolfel, E.E., Groves, B.M., Bender, PR., Butterfield, G.E., Cymerman, A. et al. (1992) Muscle accounts for glucose disposal but not blood lactate appearance during exercise after acclimatization to 4300m. J. Appl. Physiol. 72, 2435–2445.

    PubMed  CAS  Google Scholar 

  • Brooks, G.A., Wolfel, E.E., Butterfield, G.E., Cymerman, A., Roberts, A.C., R., Mazzeo, R.S., and Reeves, J.T. (1998) Poor relationship between arterial [lactate] and leg net release during exercise at 4300m altitude. Am. J. Physiol. 275, R1192–R1201.

    PubMed  CAS  Google Scholar 

  • Btilbring, E., Burn, J.H., and de Elio, F.J. (1934) The secretion of adrenaline from the perfused suprarenal gland. J. Physiol. 107, 222–232.

    Google Scholar 

  • Butterfield, G.E., Gates J., Fleming, S., Brooks, G.A., Sutton, J.R., and Reeves, J.T. (1992) Increased energy intake minimizes weight loss in men at high altitude. J. Appl. Physiol. 72, 1741–1748.

    PubMed  CAS  Google Scholar 

  • Christensen, E.H. (1937) Sauerstoff aufnahme and respiratorische Functionen in gross Hohen. Skand. Arch. Physiol. 76, 88–100.

    CAS  Google Scholar 

  • Cymerman, A., Reeves, J.T, Sutton, J.R., Rock, PB., Groves, B.M., Malkonian, M.K. et al. (1989) Operation Everest II: maximal oxygen uptake at extreme altitude. J. Appl. Physiol. 66, 262–331.

    Article  Google Scholar 

  • Dempsey, J.A., and Forster, H.V. (1982) Mediation of ventilatory adaptations. Physiol Rev. 62, 262–331.

    PubMed  CAS  Google Scholar 

  • Droma, T.S., McCullough, R.G., McCullough, R.E., Zhuang, J.G., Cymerman, A., Sun, S.F., et al. (1991). Increased vital and total lung capacities in Tibetan compared to Han residents of Lhasa (3658m). Am. J. Phys. Anthro. 86, 341–351.

    Article  CAS  Google Scholar 

  • Grover, R.F., Selland, M.A., McCullough, R.G., Dahms, T.E., Wolfel, E.E., Butterfield, G.E., et al. (1998) β-Adrenergic blockade does not prevent polycythemia or decrease in plasma volume in men at 4300m altitude. Eur. J. Appl. Physiol. 77, 264–270.

    Article  CAS  Google Scholar 

  • Grover, R.F., Weil, J.V., and Reeves, J.T. (1986) Cardiovascular adaptations at high altitude. In: Pandolf, K.B. (ed.) pp. 269–302, Exercise, sport, science reviews, vol. 14. Macmillan Publishing Co., New York.

    Google Scholar 

  • Groves, B.M., Droma, T.S., Sutton, J.R., McCullough, R.G., McCullough, R.E., Zhuang, J.G., et al. (1993). Minimal hypoxic pulmonary hypertension in normal Tibetans at 3658m. J. Appl. Physiol. 74, 312–318.

    PubMed  CAS  Google Scholar 

  • Groves, B.M., Reeves, J.T, Sutton, J.R., Wagner, P.D., Cymerman, A., et al. (1987) Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen. J. Appl. Physiol. 63, 521–530.

    PubMed  CAS  Google Scholar 

  • Hackett, P.H., and Rennie, D. (1976) The incidence, importance and prophylaxis of acute mountain sickness. Lancet 2, 1149–1155.

    Article  PubMed  CAS  Google Scholar 

  • Hackett, P.H., and Roach, R.C. (1990) High altitude pulmonary edema. J. Wilderness Med. 1, 3–26.

    Google Scholar 

  • Hochackka, PW, Rupert, J.L., and Monge, C. (1999) Adaptation and conservation of physiological systems in the evolution of human hypoxia tolerance. Comp. Biochem. Physiol. 124 (Part A), 1–17.

    Google Scholar 

  • Hochstrasser, J., Nanzer, A., and Oelz, O. (1986) Altitude edema in the Swiss Alps. Observations on the incidence and clinical course of 50 patients. Schweiz. Med. Wochenschr. 28, 866–873.

    Google Scholar 

  • Honigman, B., Theis, M.K., Koziol-McLain, J., Roach, R., Yip, R., Houston, C, and Moore, L.G. (1993) Acute mountain sickness in a tourist population at moderate altitudes. Ann. Int. Med. 118, 587–592.

    PubMed  CAS  Google Scholar 

  • Houston, C.S., Sutton, J.R., Cymerman, A., and Reeves, J.T. (1987) Operation Everest II: man at extreme altitude. J. Appl. Physiol. 63, 877–882.

    PubMed  CAS  Google Scholar 

  • Hughson, R.L., Yamamoto Y., McCullough, R.E., Sutton, J.R., and Reeves, J.T. (1994) Sympathetic and parasympathetic indicators of heart rate control at altitude studied by spectral analysis. J. Appl. Physiol. 77, 2537–2542.

    PubMed  CAS  Google Scholar 

  • Hultgren, H.N., Grover, R.F., and Hartley, L.H. (1971) Abnormal circulatory responses to high altitude in subjects with a history of high altitude pulmonary edema. Circulation 44, 759–770.

    PubMed  CAS  Google Scholar 

  • Johnson, R.L., Cassidy, S.S., Grover, R.F., Schutte, J.E., and Epstein, R.H. (1985) Functional capacities of lungs and thorax in beagles after prolonged residence at 3100m. J. Appl. Physiol. 59, 1773–1782.

    PubMed  Google Scholar 

  • Kawashima, A., Kubo, K., Kobayashi, T, and Sekiguchi, M. (1989) Hemodynamic responses to acute hypoxia, hypobaria, and exercise in subjects susceptible to high altitude pulmonary edema. J. Appl. Physiol. 67, 1982–1989.

    PubMed  CAS  Google Scholar 

  • Kryger, M., Glas, R., Johnson, V.D., Scoggin, C.S., Grover, R.F., and Weil, J.V. (1978) Impaired oxygenation during sleep in excessive polycythemia of high altitude: improvement with respiratory stimulation. Sleep 1, 3–7.

    PubMed  CAS  Google Scholar 

  • Lopez-Barneo, J., Lopez-Lopez, J.R., Urena, J., and Gonzales, C. (1988) Chemotransduction in the carotid body: K+ modulated by Po2 in type 1 chemoreceptor cells. Science 242, 580–582.

    Article  Google Scholar 

  • Mazzeo, R.S., Bender, PB., Brooks, G A., Butterfield, G.E., Groves, B.M., Sutton, J.R., et al. (1991) Arterial catecholamine responses during exercise with acute and chronic high altitude exposure. Am. J. Physiol. 261, E419–E424.

    PubMed  CAS  Google Scholar 

  • Mazzeo, R.S., Brooks, G.A., Butterfield, G.E., Podolin, D.A., Wolfel, E.E., and Reeves, J.T. Acclimatization to high altitude increases muscle sympathetic activity both at rest and during exercise. (1995) Am. J. Physiol. 269, R201–R207.

    PubMed  CAS  Google Scholar 

  • Monge, C, Arregui, A., and Leon-Velarde, F. (1992) Pathophysiology and epidemiology of chronic mountain sickness. Int. J. Sports Med. 13, S79–S81.

    Google Scholar 

  • Moore, L.G, Curran-Everett, L., Droma, T,S., Groves, B.M., McCullough, R.G, McCullough R.E., et al. (1992) Are Tibetans better adapted? Int. J. Sports Med. 13, S86–S88.

    PubMed  Google Scholar 

  • Oelz, O., Howald, H., di Prampero, P.E., and Reeves, J.T. (1986) Physiological profile of world-class high-altitude climbers. J. Appl. Physiol. 60, 1734–1742.

    PubMed  CAS  Google Scholar 

  • Oelz, O., Maggiorini, M., Ritter, M., Noti, C., Waber, U., Vock, P., and Bartsch, P. (1992) Prevention and treatment of high altitude pulmonary edema by a calcium channel blocker. Int. J. Sports Med. 13, S65–S68.

    PubMed  Google Scholar 

  • Penulosa, D., and Sime, F. (1971) Chronic cor pulmonale due to loss of altitude acclimatization (chronic mountain sickness). Am. J. Med. 50, 728–743.

    Article  Google Scholar 

  • Post, J.M., Hume, J.R., Archer, S.L., and Weir, E.K. (1992) Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am. J. Physiol. 262, C882–C890.

    PubMed  CAS  Google Scholar 

  • Reeves J.T. (1973) Pulmonary vascular responses to high altitude. Cardiovasc. Clin. 5 Clinical-pathological correlations 2, 81–95.

    Google Scholar 

  • Reeves, J.T., and Schoene, R.B. (1991) When lungs on mountains leak. N. Engl. J. Med. 325, 1306–1307.

    Article  PubMed  CAS  Google Scholar 

  • Reeves, J.T., and Grover, R.F. (1974) High-altitude pulmonary hypertension and pulmonary edema. In: Yu, P.N., and Goodwin J.F. (eds.) pp. 99–118. Progress in cardiology IV Febiger, Philadelphia.

    Google Scholar 

  • Reeves, J.T, Groves, B.M., Cymerman, A., Sutton, J.R., Wagner, P.D., Turkevich, D., and Houston, C.S. (1990) Cardiac filling pressures during cycle exercise at sea level. Resp. Physiol. 80, 147–154.

    Article  CAS  Google Scholar 

  • Reeves, J.T, Groves, B.M., Sutton, J.R., Wagner, P.D., Green H.J., Cymerman, A., and Houston, C.S. (1991) Adaptations to hypoxia: lessons from Operation Everest II. In: Simmons, D.H. (ed.) pp. 23–50, Current pulmonology, Mosby Year Book Publishers, St. Louis.

    Google Scholar 

  • Reeves, J.T, Houston, C.S., and Sutton, J.R. (1989) Operation Everest II: resistance and susceptibility to chronic hypoxia in man. J. R. Soc. Med. 82, 513–514.

    PubMed  CAS  Google Scholar 

  • Reeves, J.T, Mazzeo, R.S. Wolfel, E.E., and Young, A.J. (1992) Increased arterial pressure after acclimatization to 4300m: possible role of norepinephrine. Int. J. Sports Med. 13, S18–S21.

    Article  PubMed  CAS  Google Scholar 

  • Reeves, J.T, Groves, B.M., Sutton, J.R., Wagner, P.D., Cymerman, A., et al. (1987) Operation Everest II: preservation of cardiac function at extreme altitude. J. Appl. Physiol. 63, 531–539.

    PubMed  CAS  Google Scholar 

  • Reeves, J.T, Houston, C.S., Sutton, J.R. (1989) Operation Everest II: resistance and susceptibility to chronic hypoxia in man. J. R. Soc. Med. 82, 513–514.

    PubMed  CAS  Google Scholar 

  • Reeves, J.T., Wagner, W.W., McMurtry, I.F., and Grover, R.F. (1979) Physiological effects of high altitude on the pulmonary circulation. In: Robertshaw, D. (ed.) pp. 289–310. Int. Rev. Physiol. Ill, vol. 20. University Park Press, Baltimore.

    Google Scholar 

  • Reeves, J.T, Wolfel, E.E., Green, H.J., Mazzeo, R.S., Young, A.J., Sutton, J.R., and Brooks, G.A. (1992) Oxygen transport during exercise at altitude and the lactate paradox: Lessons from Operation Everest II. In: Holloszy, J.O. (ed.) pp. 275–296. Exercise & sports sciences review, vol. 20. Williams & Wilkins, Baltimore.

    Google Scholar 

  • Reeves, J.T, Monge, C.C., Leon-Velarde, F, Moore, L.G., Asmus, I., Curran, L., et al. (1998) Symposium on chronic exposure to hypoxia and chronic mountain sickness (CMS). In: Ohno, H., Kobayashi, T., Masuyama, S., and Nakashima, M. (eds.) Press Committee pp. 105–166. Progress in mountain medicine and high altitude physiology. Third World Congress on Mountain Medicine and High Altitude Physiology, Matsumoto, Japan.

    Google Scholar 

  • Roberts, A.C., Reeves, J.T, Butterfield, G.E., Mazzeo, R.S., Sutton, J.R., Wolfel, E.E., and Brooks, G.A. (1996) Acclimatization to 4300-m altitude decreases reliance on fat as a substrate. J. Appl. Physiol. 80, 605–615.

    PubMed  CAS  Google Scholar 

  • Roberts, A.C., Butterfield, G.E., Cymerman, A., Reeves, J.T, Wolfel, E.E., and Brooks, G.A. (1996) Acclimatization to 4300-m altitude decreases reliance on fat as a substrate. J. Appl. Physiol. 81, 1762–1771.

    PubMed  CAS  Google Scholar 

  • Schoene, R.B. Swenson, E.R., Pizzo, C.J., Hackett, PH., Roach, R.C., Mills, WJ., et al. (1988) The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and high altitude pulmonary edema. J. Appl. Physiol. 64, 2605–2613.

    PubMed  CAS  Google Scholar 

  • Selland, M.A., Stelzner, T.J., Stevens, T., Mazzeo, R.S., McCullough, R.S., and Reeves, J.T. (1993) Pulmonary function and hypoxic ventilatory response in subjects susceptible to high-altitude pulmonary edema. Chest 103, 111–116.

    PubMed  CAS  Google Scholar 

  • Singer, D. (1999) Neonatal tolerance to hypoxia: a comparative-physiological approach. Comp. Biochem. Physiol. (Part A), 123, 221–234.

    Article  CAS  Google Scholar 

  • Suarez, J., Alexander, J.K., and Houston, C.S. (1987) Enhanced left ventricular systolic performance at high altitude during Operation Everest II. Am. J. Cardiol. 60, 137–142.

    Article  PubMed  CAS  Google Scholar 

  • Sutton, J.R., Reeves, J.T., Wagner, P.D., Groves, B.M., Cymerman, A. Malcoman, M.K., et al. (1988) Operation Everest II: oxygen transport during exercise at extreme simulated altitude. J. Appl. Physiol. 64, 1309–1321.

    PubMed  CAS  Google Scholar 

  • Tenney, S.M. (1962) Physiological adaptations to life at high altitude. Mod. Concepts Cardiovasc. Dis. 31, 713–718.

    Google Scholar 

  • Tenney, S.M. (1990) Avian Physiology and performance at high altitude. In: Sutton, J.R., Coates, G., Houston, C.S. (eds.) pp. 2–3. Hypoxia: the adaptations. BC Dekker, Philadelphia.

    Google Scholar 

  • Tucker, C.E., James, W.E., Berry, M.A., Johnstone, C.J., and Grover, R.F. (1976) Depressed myocardial function in goats at high altitude. J. Appl. Physiol. 41, 356–361.

    PubMed  CAS  Google Scholar 

  • Vogel, J.A., Hartley, L.H., Cruz, J.C., and Hogan, R.P(1974) Cardiac output during exercise in sea level residents at sea level and high altitude. J. Appl. Physiol. 36, 169–172.

    PubMed  CAS  Google Scholar 

  • Wagner, P.D., Sutton, J.R., Reeves, J.T, Cymerman, A., Groves, B.M., and Malkonian, M.K. (1987) Operation Everest II: pulmonary gas exchange during simulated ascent of Mt. Everest. J. Appl. Physiol. 63, 2348–2359.

    PubMed  CAS  Google Scholar 

  • Wagner, P.D. (1988) An integrated view of the determinants of maximum oxygen uptake. In: Oxygen transfer from atmosphere to tissues, pp. 245–256. Plenum Press, New York.

    Google Scholar 

  • Ward, M.P., Milledge, J.S., and West, J.B. (1995) High Altitude medicine and physiology. Chapman & Hall Medical, New York.

    Google Scholar 

  • Weil, J.V. (1990) Lesson from high altitude. Chest 97, 70S–76S.

    PubMed  CAS  Google Scholar 

  • Weil, J.V, Jamieson, G, Brown, D.W., and Grover, R.F. (1968) The red cell mass—arterial oxygen relationship in normal man. J. Clin. Invest. 47, 1627–1639.

    Article  PubMed  CAS  Google Scholar 

  • West, J.B., and Mathieu-Costello, O. (1992) Stress failure in pulmonary capillaries: a mechanism for high altitude pulmonary edema. In: Sutton, J.R., Coates, G, and Houston, C.S., (eds.) pp. 229–240. Hypoxia and mountain medicine. Queen City Printers, Burlington, VT.

    Google Scholar 

  • Winslow, R.M., and Monge, C. (1987) Hypoxia, polycythemia, and chronic mountain sickness. The Johns Hopkins University Press, Baltimore, MD.

    Google Scholar 

  • Wolfel, E.E., Groves, B.M., Brooks, G A., Butterfield, G.E., Mazzeo, R.S., Moore, L.G., et al. (1991) Oxygen transport during steady-state submaximal exercise in chronic hypoxia. J. Appl. Physiol. 70, 1129–1136.

    PubMed  CAS  Google Scholar 

  • Wolfel, E.E., Selland, M., Mazzeo, R.S., and Reeves, J.T. (1994) Systemic hypertension at 4300m is related to sympatho-adrenal activity. J. Appl. Physiol. 76, 1643–1651.

    PubMed  CAS  Google Scholar 

  • Wolfel, E.E., Selland, M.A., Cymerman, A., Brooks, G.A., Butterfield, G.E., Mazzeo, R.S., et al. (1998) O2 extraction maintains O2 uptake during submaximal exercise with beta-adrenergic blockade at 4300m. J. Appl. Physiol. 85, 1092–1102.

    PubMed  CAS  Google Scholar 

  • Young, A.J., Young, P.M., McCullough, R.E., Moore, L.G., Cymerman, A., and Reeves, J.T. (1991) Effect of beta-adrenergic blockade on plasma lactate concentration during exercise at high altitude. Eur. J. Appl. Physiol. 63, 315–322.

    Article  CAS  Google Scholar 

Recommended Readings

  • Gibbs, J.S. (1999) Pulmonary hemodynamics: implications for high altitude pulmonary edema (HAPE). Adv. Exptl. Med. Biol. 474, 23–45.

    Google Scholar 

  • Hackett, P.H. (1999) High altitude cerebral edema and acute mountain sickness. A pathophysiology update. Adv. Exptl. Med. Biol. 474, 23–45.

    CAS  Google Scholar 

  • Heath, D., and Williams, D.R. (1997) Man at high altitude. Churchill Livingstone, Edinburgh.

    Google Scholar 

  • Ramirez, G., Bittle, P.A., Rosen, R., Ralde, H., and Pineda, D. (1999) High altitude living: genetic and environmental adaptation. Aviation Space Envtl. Med. 70, 73–81.

    CAS  Google Scholar 

  • Ward, M.P., Milledge, J.S., and West, J.B. (1995) High altitude medicine and physiology. Chapman & Hall, New York.

    Google Scholar 

  • Weibel, E.R. (1999) Understanding the limitation of O2 supply through comparative physiology. Resp. Physiol. 118, 85–93.

    Article  CAS  Google Scholar 

  • West, J.B. (1998) High life. Oxford University Press, New York.

    Google Scholar 

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  1. John T. Reeves
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Editors and Affiliations

  1. Department of Physiology, University of Wisconsin Medical School, Madison, WI, 53706, USA

    E. Edward Bittar MD

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Reeves, J.T. (2002). High-Altitude Physiology and Pathophysiology. In: Bittar, E.E. (eds) Pulmonary Biology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-0-387-22435-0_17

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