advances on high altitude physiology
TRANSCRIPT
NEURO AND MUSCULAR ADVANCES ON HIGH
ALTITUDE PHYSIOLOGYTYRLL ADOLF ITONG
BIO 220: CHEMICAL PHYSIOLOGY
WHAT IS HIGH ALTITUDE?
defined as:
intermediate altitude: 1500–2500 m
High Altitude: 2500–3500 m
very High Altitude: 3500–5800 m
extreme altitude: above 5800 m (Barry & Pollard, 2003)
Recently, there is an increase of lowlanders reaching
heights previously reserved for veteran climbers
For these climbers, higher risk of high altitude sickness,
leading to increase in injuries and fatalities
2014 Mt. Everest death tally: 16 deaths
HIGH ALTITUDE SICKNESS
Brought about by hypoxia, among other factors
Deprivation of adequate oxygen supply in the body
reduced O2 in the atmosphere due to lower total
barometric pressures
Lower partial pressure of gases, including oxygen
Creates “death zones” – oxygen pressure cannot sustain
human life
Symptoms include edema and physiological damage to
cognitive and cerebral areas of brain
Sleep and mood stage changes (Harris, et al., 2009)
neurobehavioral capacities impairment (Hornbein, et al., 1989)
Psychomotor ability and mental efficiency (Abraini, et al., 1998)
learning deficits and perceptive and memory retention (Kramer, Coyne, & Strayer, 1993)
Some authors argue the opposite
No cognitive changes found using brain imagery and
neuropsychological testing (Anooshiravani, et al., 1999)
No decline in neurophysiological tests of subjects exposed up
to 7500 m (Jason et al., 1989)
Resolved in recent high-altitude neurological research
Using saccadic eye performance, no significant effects on
cognitive performance in well-acclimatized climbers (Merz, et al.,
2013)
cognitive skills are affected in casual climbers (Lemos, et al., 2012)
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MUSCLE AND MITOCHONDRIAL PHYSIOLOGY
Muscles are highly plastic (Guggenheim, 1991)
Hypoxia has long been known to play a role in muscle
cellular changes, particularly harmful for skeletal muscle
mass (Holloszy and Coyle, 1984)
Significant muscle atrophy in m. quadriceps femoris and m. biceps
brachii and subsequent weight loss (Mizuno, et al., 2008)
Cardiac muscles are altered in response to altitude exposure (Holloway, et al., 2011)
Disproportionate change in left ventricular surface area
reduction of filling rate and stroke volume
cardiac phosphocreatine/ATP ratio decrease
How the body produces and responds to these structural
changes remains unclear
Phenotypic alterations of muscle tissue, including loss of
mitochondria previously believed to be the cause (Howald and
Hoppeler, 2003)
Decreased density of subsarcolemmal and intermyofibrillar
mitochondria (Levett, et al., 2012)
Brought about by increased production of lipofuscin
Reduction in capillarity and muscle tissue oxidative
capacity, thus aerobic capacity (Desplanches, 1996; Howald and Hoppeler,
2003)
Recent research suggest gene expression and protein levels
explains previously described changes (Levett, et al., 2012)
Plasticity of mitochondria facilitates these adaptations (Lynn, 2007)
up-regulation of UCP3, believed to be mitochondria’s main defense
against ROS (Brand, et al., 2002)
suppression of oxidative metabolism and mitochondrial biogenesis through down-regulation of complex I, IV, and PGC1α
Despite significant atrophy and weight loss, muscle function
is still maintained (Edwards, 2010)
Phosphocreatine recovery and inorganic phosphate
concentrations higher in veteran than in casual climbers
Changes in mitochondrial function a long term effect of
hypoxia
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Mitochondrial function remains largely unaltered despite
these extreme enzymatic changes (Jacobs, et al., 2013)
no significant change in skeletal muscle mitochondrial density after
19 days (Levett, et al., 2012)
Increased muscle turnover rate largely counterbalanced by elevated
myocontractile protein synthesis rate (Holm, 2010)
Capacity of complex I or II to oxidize fat and individually respire not
affected
WHERE DO WE GO FROM HERE?
Research continues on effects of high-altitude changes
possibility of cognitive impairment or long-term cerebral
damage occurring
long-term effects on mitochondria
Regulation of protein synthesis rates in mitochondria
Recovery of muscle atrophy after long-term hypoxic exposure
Normobaric vs hypobaric hypoxia (Girard, 2012)
LITERATURE CITED
Abraini, J., Bouquet, C., Joulia, F., Nicolas, M., & Kriem, B. (1998). Cognitive performance during a simulated climb of Mount Everest: implications for brain function and central adaptive processes under chronic hypoxic stress. Pflugers Arch., 436(4), 553-9.
Anooshiravani, M., Dumont, L., Mardirosoff, C., Soto-Debeuf, G., & Delavelle, J. (1999). Brain magnetic resonance imaging (MRI) and neurological changes after a single high altitude climb. Med Sci Sports Exerc., 31(7), 969-72.
Barry, P. W., & Pollard, A. J. (2003). Altitude illness. The British Medical Journal, 326(7395), 915-919.
Desplanches, D., Hoppeler, H., Tüscher, L., Mayet, M. H., Spielvogel, H., Ferretti, G., & Favier, R. (1996). Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia. Journal of Applied Physiology, 81(5), 194.
Edwards, L., Murray, A., Tyler, D., Kemp, G., & Holloway, C. (2010). The Effect of High-Altitude on Human Skeletal Muscle Energetics: 31P-MRS Results from the Caudwell Xtreme Everest Expedition. PLoS ONE, 5(5), e10681. doi:10.1371/journal.pone.0010681
Girard, O., Koehle, M. S., Guenette, J. A., Verges, S., Chapman, R. F., Conkin, J., . . . Taylor, B. J. (2012). Comments on Point:Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia. J Appl Physiol, 112, 1788-1794.
Guimarães-Ferreira, L., Nicastro, H., Wilson, J., & Zanchi, N. E. (2013). Skeletal Muscle Physiology. Scientific World Journal. doi:10.1155/2013/782352
Holloway, C. J., Montgomery, H. E., Murray, A. J., Cochlin, L. E., Codreanu, I., Hopwood, N., & Andr. (2011). Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp. The FASEB Journal, 25, 792-796.
Holm, L., Haslund, M. L., Robach, P., van Hall, G., Calbet, J. A., Saltin, B., & Lundby, C. (2010). Skeletal Muscle Myofibrillar and Sarcoplasmic Protein Synthesis Rates Are Affected Differently by Altitude-Induced Hypoxia in Native Lowlanders. PLoS ONE, 5(12), e15606. doi:10.1371/journal.pone.0015606
Hornbein, T. F., Townes, B. D., Sutton, J. R., & Houston, C. S. (1989). he cost to the central nervous system of climbing to extremely high altitude. N Engl J Med, 1714-1719.
Howald, H., & Hoppeler, H. (2003). Performing at extreme altitude: muscle cellular and subcellular adaptations. Eur J Appl Physiol., 90(3-4), 360-4.
LITERATURE CITED
Jacobs, R. A., Boushel, R., Wright-Paradis, C., Calbet, J. A., Robach, P., Gnaiger, E., & Lundby, C. (2013). Mitochondrial function in human skeletal muscle following high-altitude exposure. Exp Physiol, 98(1), 245–255.
Jason, G., Pajurkova, E., & Lee, R. (1989). High-altitude mountaineering and brain function: neuropsychological testing of members of a Mount Everest expedition. AviatSpace Environ Med, 60(2), 170-173.
Kramer, A. F., Coyne, J. T., & Strayer, D. L. (1993). Cognitive function at high altitude. Human Factors, 35(2), 329-344.
Lemos, V. d., Antunes, H. K., Vagner, R., Santos, T. d., Lira, F. S., Tufik, S., & de Mello, M. T. (2012). High altitude exposure impairs sleep patterns, mood, and cognitive functions. Psychophysiology, 49(9).
Levett, D. Z., Radford, E. J., Menassa, D. A., Graber, E. F., Morash, A. J., Hoppeler, H., . . . Murray, A. J. (2012). Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest. FASEB J., 26, 1431–1441.
Lynn, E., Lu, Z., Minerbi, D., & Sack, M. (2007). The regulation, control, and consequences of mitochondrial oxygen utilization and disposition in the heart and skeletal muscle during hypoxia. Antioxid Redox Signal. 2007 Sep;9(9):1353-61., 9(9), 1351-61.
Mason, N. (2000). The physiology of high altitude: an introduction to the cardio-respiratory changes occurring on ascent to altitude. Current Anaesthesia and Critical Care, 11, 34-41.
Merz, T. M., Bosch, M. M., Barthelmes, D., Pichler, J., Hefti, U., Schmitt, K.-U., . . . Schwarz, U. (2013). Cognitive performance in high-altitude climbers: a comparative study of saccadic eye movements and neuropsychological tests. European Journal of Applied Physiology, 113(8), 2025–2037. doi:10.1007/s00421-013-2635-6
Rodway, G. W., Hoffman, L. A., & Sanders, M. H. (2003). High-altitude-related disorders—part I: pathophysiology, differential diagnosis, and treatment. Heart & Lung: The Journal of Acute and Critical Care, 32(6), 353–359.
San, T., Polat, S., Cingi, C., Eskiizmir, G., Oghan, F., & Cakir, B. (n.d.). Effects of High Altitude on Sleep and Respiratory System and Theirs Adaptations. The Scientific World Journal. doi:10.1155/2013/241569
Xu, L., Wu, Y., Zhao, T., Liu, S., Zhu, L., Fan, M., & Wu, K. (2014). Effect of high altitude hypoxia on cognitive flexibility. Chinese Journal of Applied Physiology, 30(2), 106-9, 118.