This document discusses various biochemical changes that occur in the body during high altitude mountaineering. It explains that decreased oxygen levels at altitude can cause illnesses like altitude sickness. The body responds through acclimatization over days or weeks, including increases in red blood cells, kidney compensation through water loss, and improved mitochondria in muscles. Genetic adaptations are seen in Tibetan Sherpas, like variants of the EPAS1 gene that regulate oxygen carrying capacity of the blood and reduce risks of illness.

1. Biochemical
Changes during
High Altitude
Mountaineering
RYAN ATKINS
BIO209 XZ

2. Table of Contents
 HIGH ALTITUDE MOUNTAINEERING
 ALTITUDE-RELATED ISSUES
 CAUSES OF ALTITUDE-RELATED ILLNESS
 ACCLIMATIZATION
 BIOCHEMICAL CHANGES AT ALTITUDE
 GENETIC VARIATIONS IN TIBETAN SHERPAS
 WORKS CITED

3. What is High Altitude Mountaineering?
“Because it’s there.”
- British mountaineer George Mallory, when asked during a 1923 interview
why he wanted to climb Mt. Everest.

4. What is High Altitude Mountaineering?
▪ The International Society of Mountain Medicine recognizes three
distinct altitude brackets, although the term “high altitude
mountaineering” can be loosely applied to all of them.
▪ High Altitude Mountaineering is any climbing/trekking at an
altitude > 1,500 m (~4,000 ft).
▪ Greater than 3,500 m (~11,500 ft) above sea level is considered
very high altitude.
▪ Greater than 5,500 m (~18,000 ft) above sea level is considered
extreme altitude.

5. Altitude-Related Issues
▪ At elevations > 2500 m (~8,000 ft) altitude illness becomes a
problem that climbers must anticipate.
▪ Altitude-related illnesses include (in order of seriousness):
- Acute and Chronic mountain sickness (AMS, CMS)
- High altitude pulmonary edema (HAPE)
- High altitude cerebral edema (HACE)
▪ If these problems are not treated promptly, they can progress from
one to the next, ultimately leading to death.
▪ The best treatment, especially in the early stages of AMS, is simply
for the climber(s) to descend to a lower altitude, although Gamow
bags and medications like dexamethasone may also help.

6. Causes of Altitude-Related Illness
▪ One of the primary (and most most
widely studied) causes of altitude-
related illnesses is the systemic
hypoxia that mountaineers encounter
at altitude.
▪ This hypoxia is caused primarily by a
decrease in barometric pressure, and
consequently, the partial pressure of
O2 (PO2).
▪ Shown to the right, the decrease of
PO2 in the ambient air, inspired air,
alveolar air, and arterial blood gas as
altitude increases.

7. Causes of Altitude-Related Illness (cont.)
▪ At sea level, (PO2) is ~159 mmHg.
▪ As altitude is gained, this number continues to decrease.
▪ By the time a climber reaches the summit of Mt. Everest , PO2 is only
~53 mmHg, one third of the pressure at sea level.
▪ This drastic decrease in the PO2 results in the hypoxic environment
that causes AMS, CMS, HAPE, and HACE in mountaineers.
▪ Hypoxia (and its related illnesses) can be staved off to a degree by
acclimatization – a number of biochemical changes that fight to
maintain homeostasis in the face of decreased oxygen availability.

8. Acclimatization
▪ Acclimatization is the (relatively slow) process of the body adjusting to
the decreased availability of oxygen at high altitude
▪ Proper acclimatization takes place over a period of days or weeks to
depending on the altitude.
▪ Acclimatization aids such as hypobaric chambers, supplemental
oxygen, and prophylactic medications like acetazolamide (Diamox®)
can be used to lessen the physiologic changes that climbers undergo
during initial exposure to altitude.
▪ Some populations are also better suited to acclimatization and high
altitudes due to genetic changes.

9. Acclimatization (cont.)

10. Acclimatization (cont.)
Condition Altitude Physiological Features
Acclimatization to High Altitude Up to 5,000 m Hyperventilation
Nearly complete renal compensation for respiratory alkalosis
Polycythemia
Increase in intracellular oxidative enzymes
Reduced intercapillary diffusion distances in some tissues
Evolutionary Adaptation Up to 5,000 m Hyperventilation (Reduced in some populations, including Tibetans)
Complete renal compensation for respiratory alkalosis
Polycythemia (Reduced in some populations, including Tibetans)
Changes in intracellular enzymes
Exposure to Extreme Altitude Above 7,000 m Extreme hyperventilation
Marked respiratory alkalosis and alkalemia
Increased O2 affinity of hemoglobin due to alkalosis
Decreased VO2 Max
Large reduction in anaerobic metabolism
Increased weight loss due to altitude-induced anorexia

11. Biochemical Changes - Kidneys
▪ In a hypoxic environment the kidneys increase local production of
endothelin and adrenomedullin, which suppresses ADH, renin, and
aldosterone – this results in a decrease in total body water of 1-3 L.
▪ The decrease in plasma volume results in a higher hemoglobin
concentration prior to erythropoiesis, as well as reducing intravascular
pressure.
▪ It is currently being debated whether this altitude-induced
“dehydration” is potentially adaptive or harmful.
▪ As part of the hypoxic response, the kidneys will also begin to excrete
erythropoietin to increase the number of red blood cells and the
oxygen carrying capacity of the blood, although this occurs at a slower
rate.

12. Mechanisms of Plasma Volume Reduction

13. Biochemical Changes – Skeletal Muscle
▪ Experienced, acclimatized mountaineers display significantly shorter
phosphocreatine (PCr) recovery halftimes when compared to trekkers
without prior high altitude experience.
▪ This decreased halftime results in better mitochondrial function at
altitude, even in older climbers.
▪ Previously well-trained mountaineers also exhibited better O2
extraction by skeletal muscle at high altitudes than their altitude-naïve
counterparts.
▪ It is hypothesized that altitude exposure may induce stable changes in
phenotype through epigenetic modifications.

14. Biochemical Changes – Skeletal Muscle
The chart at right shows a
comparison of PCr recovery times
between “Climbers” – individuals
that had previously acclimatized to
altitudes > 6,800 m and were well
trained mountaineers, and
“Trekkers” – altitude-naïve
individuals that had never been to
high elevation. This was done
during the Caudwell Xtreme
Everest Expedition in 2007.

15. Genetic Variations in Tibetan Sherpas

16. Genetic Variations in Tibetan Sherpas
▪ Tibetans, when compared to lowland populations, maintain higher
arterial oxygen saturation at altitude both while resting and exercising.
▪ They also display a decreased loss of aerobic performance with
increasing elevation.
▪ It has been hypothesized that these differences are due to epigenetic
modification and natural selection acting on a specific set of genes in
high-altitude populations like the Tibetan Sherpas.
▪ The most likely candidates for the modified genes that allow for these
advantages are EPAS1 (endothelial PAS domain protein 1), EGLN1
(early growth response 1), and PPARA (peroxisome proliferator
activated receptor alpha).

17. Genetic Variations in Tibetan Sherpas (cont.)
▪ EPAS1, in particular, plays an important role in regulating
erythropoiesis and hemoglobin (Hb) levels.
▪ Researchers have been able to isolate three significant Sherpa-
specific allelic variations in EPAS1 - an A/G/A sequence on
rs13419896/4953354/4953388 as opposed to the G/A/G that most
populations exhibit, including lowland Tibetans.
▪ This genetic mediation of erythropoietin levels is important for
maintaining a healthy hematocrit level, which can reduce the risk of
health problems at altitude due to high blood viscosity (which would
be an issue in individuals exhibiting polycythemia).

18. Genetic Variations in Tibetan Sherpas (cont.)
▪ In a 2004 study, it was also shown that Tibetans born and living at
high altitude were, through metabolic adaptation, less prone to
oxidative damage to their cells.
▪ Through proteomics, the researchers also found that Sherpa
populations exhibited ratios of pyruvate kinase and lactate
dehydrogenase in their muscles similar to that seen in hummingbird
flight muscles.
▪ This would allow for an exceptionally high ATP turnover rate in the
muscle compared to other individuals.
▪ These many differences are what has made Sherpas highly sought
after as high-altitude mountaineering guides since the first summit of
Everest in 1953.

19. Works Cited
▪ Dietz, T. "ISMM Non-Physician Altitude Tutorial." International Society of Mountain Medicine. ISMM, 29
Jan. 2006. Web. 05 May 2016
▪ Edwards, L., and Murray, A. “The Effect of High Altitude on Human Skeletal Muscle Energetics: P-MRS
Results from the Caudwell Xtreme Everest Expedition.” PLoS ONE 5.5 (2010): 1-8. Web. 20 Mar. 2016
▪ Goldfarb-Rumyantzev, A., and Alper, S. "Short-term Responses of the Kidney to High Altitude in Mountain
Climbers." NDT (2013): 1-8. Web. 20 Mar. 2016
▪ Masayuki, H., and Yunden, D. “Genetic Variations in EPAS1 Contribute to Adaptation to High-Altitude
Hypoxia in Sherpas.” PLoS ONE 7.12 (2012) 1-8. Web. 20 Mar. 2016
▪ Reeves, J. Young, A. "Human Adaptation to High Terrestrial Altitude." Medical Aspects of Harsh
Environments. Vol. 2.: Office of the Surgeon General, 2002. 645-79. Print.
▪ West, J. "Human Responses to Extreme Altitudes." Integrative and Comparative Biology 46.1 (2006): 25-
34. Web. 20 Mar. 2016
▪ Wu, T., and Bengt, K. "High Altitude Adaptation in Tibetans." High Altitude Medicine & Biology 7.3 (2006):
193-208. Web. 20 Mar. 2016