The reason doing an activity at high altitude is difficult is because our bodies get starved of oxygen. Contrary to popular belief, the percentage of oxygen in the air doesn’t change significantly with altitude. This is all to do with pressure.
1. Physical environment: Altitude, pressure, latitude and season
A common misconception is that the percentage of oxygen in the air decreases at high altitude. Throughout the homosphere (up to ~80 km), the fractional concentration of inspired oxygen (FIO2) remains constant at 20.93%.
What changes drastically is the barometric pressure (PB). As altitude increases, the atmospheric column above shrinks, reducing total air pressure. The partial pressure of inspired oxygen (PIO2) is determined by Dalton’s Law and modified for tracheal water vapor pressure (PH2O≈47 mmHg at normal body temperature of 37 °C):
PIO2=FIO2×(PB−PH2O)
At sea level (PB=760 mmHg), PIO2≈0.2093×(760−47)≈149 mmHg. On the summit of Mount Everest (8,848 m), where mean barometric pressure is roughly 253 mmHg, PIO2 drops to roughly 43 mmHg—less than one-third of sea-level availability.
So although the percentage of oxygen doesn’t change, the number of oxygen molecules available to breath reduces the higher you climb.
The influence of latitude
Barometric pressure is not uniform across the globe at identical altitudes. Because of the Earth’s rotation and solar heating, the troposphere is significantly thicker and warmer near the equator and thinner and colder near the poles.
- Equatorial and Subtropical Latitudes (e.g., Everest, 28°N): Atmospheric columns are warmer, causing thermal expansion that yields a higher barometric pressure than predicted by standard atmosphere models.
- High Latitudes (e.g., Denali, 63°N; Mount Vinson, 78°S): The atmosphere is squashed cold air. A peak of 6,190 m near the poles exerts a PB equivalent to a peak of 6,700–7,000 m in the Himalayas.
Seasonal & weather dynamics
Cold air is denser than warm air. As temperature drops, the atmosphere contracts toward the Earth’s surface, lowering barometric pressure at a given elevation:
- Summer vs. Winter Climbs: On Mount Everest’s summit, mean barometric pressure drops from ∼255 mmHg in midsummer to ∼243 mmHg in midwinter (Wagner, 2010).
- Impact on Exercise Capacity: Because human arterial oxygenation at extreme altitude sits on the steep part of the oxygen-hemoglobin dissociation curve, a winter drop of 12 mmHg reduces maximal oxygen uptake (V˙O2max) by approximately 15%, placing winter climbs harder.
2. Physiological system responses to extreme hypoxia
Respiratory system
- Hypoxic ventilatory response (HVR): Decreased arterial PO2 (PaO2) is sensed by peripheral chemoreceptors in the carotid bodies, triggering hyperventilation to increase alveolar ventilation.
- Respiratory alkalosis: Excessive blowing off of carbon dioxide (CO2) causes arterial PCO2 (PaCO2) to plummet. In climbers near the summit of Everest, arterial PaCO2 can drop as low as 10–14 mmHg (sea level normal: 35–45 mmHg), driving systemic arterial pH above 7.55–7.60 (Grocott et al., 2009).
Cardiovascular system
- Sympathetic surge: Hypoxia stimulates release of catecholamines (epinephrine and norepinephrine), raising resting heart rate and stroke volume to maintain cardiac output.
- Hypoxic pulmonary vasoconstriction (HPV): Smooth muscle in pulmonary arterioles constricts in response to low alveolar PO2. While intended to redirect blood flow to better-ventilated lung segments, global lung hypoxia causes widespread constriction, raising mean pulmonary arterial pressure (PAP) and right-ventricular strain.
Hematological system
- Erythropoietin (EPO) activation: Renal cortical interstitial cells sense tissue hypoxia through Hypoxia-Inducible Factor 2$\alpha$ (HIF-2$\alpha$), releasing EPO within 12–24 hours of exposure.
- Polycythemia & viscosity: EPO stimulates bone marrow erythropoiesis, increasing red blood cell count, hemoglobin concentration (often rising from 14–15 g/dL to >18–22 g/dL), and hematocrit. While this increases oxygen-carrying capacity, hematocrit levels above 55–60% substantially increase blood viscosity, sluggish microvascular perfusion, and risk of thrombosis and frostbite.
Renal system & fluid balance
- Metabolic compensation: To compensate for severe respiratory alkalosis, the kidneys excrete renal bicarbonate (HCO3−) in urine while retaining hydrogen ions (H+).
- Altitude diuresis: Bicarbonate excretion is accompanied by sodium and water loss, causing altitude-induced diuresis. This lowers plasma volume by 10–20%, concentrating hemoglobin early in ascent before true erythropoiesis takes place.
Central nervous system (CNS)
- Cerebral blood flow: Hypoxia acts as a potent cerebral vasodilator, increasing CBF by 20–50% to preserve cerebral oxygen delivery. However, hyperventilation-induced hypocapnia acts as a vasoconstrictor; the net CBF depends on the balance between these forces.
- Intracranial pressure : Elevated Cerebral blood flow and microvascular pressure increase blood-brain barrier permeability, predisposing individuals to cerebral edema and impaired executive functioning, motor coordination, and decision-making.
3. Mechanisms and protocols for high-altitude acclimatization
Acclimatization is the process by which the body restores tissue oxygenation to tolerable levels despite reduced atmospheric pressure.
Timeline of physiological adaptation
- From when we reach a higher altitude: We increase our ventilation. So consequently we increase the CO2 production: Increases body acidity, this is regulated by the kidneys ( regulation of o2 and brain). So to have not a kidneys problem and stop this regulation of Co2 is important to drink a lot (6L/ day) or don’t lose water (breath warm- humid). If we stop pissing means that we have a kidney problem.
- 24h after reach the altitude: We have an EPO production to increase the red cells, to increase the transport of O2.
- 7 days: We can see an increase in the hematocrit and the effects of blood acclimatization
- 3 weeks / 400h: Hif 1 (diffusion O2 to muscles) Enzyme and diffusion acclimatization. All our body can do in acclimatization is done.
Is important to think that the SatO2 (Oxygen Saturation) decreases when we are sleeping (we breath less, our body is on a resting mode), so the body reacts worth at altitude, It will take 3-4h after wake up to come back to our normal SatO2 level. So think about this time when it will be hard/bad to do an activity or go higher up. In terms of acclimatization, the best way to recover in altitude is not sleeping but on an awake rest.
To increase the SatO2, we can do hyperventilation’s with a big amplitude, or find a method to have (breathe) Co2 during the sleep.
In the terrain it seems that 5500m is the maximum altitude where we can make a complete acclimatization (higher than that we consume more than we can recover), and we can refer to some experiences of high altitude exploits after an acclimatization “only” at this altitude: Messner in Everest solo (August 1980) and Lorettan and Troillet in Holbein Couloir (Everest, August 1986) did not climb higher than 6000m during the acclimatization but spend around 2 months around 5000- 6000m.
| Time | System | Key Adaptations |
|---|---|---|
| 0 – 48 Hours | Respiratory & Renal | HVR peak ventilation; renal bicarbonate excretion begins; arterial pH normalizes toward 7.40. |
| 3 – 7 Days | Hematological | EPO peaks at 24–48 hours; reticulocytes enter circulation; 2,3-diphosphoglycerate (2,3-DPG) increases, shifting the O2-Hb curve rightward to enhance tissue unloading. |
| 2 – 4 Weeks | Structural / Tissue | Microvascular angiogenesis; capillary density in skeletal muscle increases; muscle myoglobin levels rise. |
Pre-acclimatization protocols (Before traveling)
- Normobaric Hypoxic Tents:
- Mechanism: Compress nitrogen or filter oxygen to simulate altitudes from 2,500 m to 4,500 m while sleeping at sea level.
- Protocol: Minimum exposure of 7–8 hours per night for 3–4 consecutive weeks prior to expedition.
- Outcome: Pre-activates carotid body chemoreceptors, blunts initial Acute Mountain Sickness (AMS) symptoms, and raises initial EPO levels.
- Intermittent Hypoxic Exposure (IHE) / Training (IHT):
- Short sessions (60–90 minutes) breathing 10–12% O2 at rest or during interval exercise. Provides modest HVR priming, though less effective for hematological shifts than continuous nocturnal exposure.
The body can have a memory, if we have experienced an altitude before, the body can adapt mechanisms in a faster / more efficient way. That doesn’t mean that we will not have problems in altitude if we have been there before. Every time we go in altitude we will need to acclimatize and everybody can have problems (MAM, Edema) in altitude some time.
The altitude where we train / live will make a difference, a pre-acclimatization. If one has been training at 4000m during some month, probably we will be able to go straight to 5000m and climb 6000m summits in a short period of time. If we live at sea level, this period will be longer, and we will need to take more progressive. We can considerate that the altitude to reach without any effect is around the altitude we are (living – training) + 1000m.
A good shape, aerobic training will be good to assimilate the first stages of acclimatization but is not because we are more fit that we will acclimatize faster / better.
The anaerobic work can be interesting for altitude. In altitude, we are normally able to keep a pace (slow) but on the moment we want to increase the peace or work in anaerobic for some seconds (sprint), the recovery it will take really long. It will be really hard for our body to eliminate the lactate and the muscles will feel without energy for a long time. Is for that that the anaerobic work before will be interesting, to make the body better on eliminate lactate and on make higher the intensity when we produce lactate.
In-situ acclimatization protocols (On the mountain)
- Climb high, sleep low: Ascend to higher altitudes during the day to carry loads and trigger physiological stress, then descend to lower elevations to sleep and recover.
- Staged ascent:
- Above 3,000 m, limit sleeping elevation gain to 300–500 meters per 24 hours.
- Incorporate a dedicated rest day every 3–4 days (Luks et al., 2019).
- Rotational climbing (Himalayan expedition style): Establish successive high camps (e.g., Base Camp → Camp 1 → Camp 2 → Base Camp rest → Camp 3 → Base Camp rest → Summit push).
The classical acclimatisation is to go up 500m maximum per day and rest there to acclimatize before going up again. This is a long acclimatisation period with the advantage of being fairly secure but with the consequence of lots of fatigue due to the high altitude “sleeping”. The acclimatisation happens during the exposition at the altitude, because we spend a great amount of time at this altitude.
We can also acclimate in a THSL form. Training high and sleeping low. That means to go as high as it feels ok and down to sleep the lowest possible. This can be 1000-2000 or even more depending the physical capacities and pre-acclimatisation of the climber. With this our sleep will be great and we can fully (or almost) recover for the next day, and our shape will keep higher during a longer period than with a classical acclimatisation. Here the acclimatisation happens when we’re back down and the body is adpating to the stimuli recived some hours before.
The benefits of a THSL acclimatisation are the great recovery and the mantain of the performance levels, but they are also disadvantages. First the fact that to climb to a higher altitude than the one we’re already acclimatized we play with the fact that the negative effects to altitude (Edemas, MAM…) arrive with a delay of +- 8h after the exposition, what means that we need to climb fast and go down fast before this effects arrive, but if for some reason (weather, technical difficulties, problem, physical capacities) we’re not fast enought the consequences can be fatal. We need to also note that even if we have touched an altitude the amount of time spent at this altitude will not be sufficient to fully acclimatize at this altitude, but lower, so in the ascent we need to take this into account too.
For a lower 8000m summit some believe that it is necesary (or very recomended) to spend a night at 7500m, and for a high 8000m (8400-8800m) at 7900/8000m. To limit the probability of Edema on the climb if it takes longer than expected. It is also possible to do a THSL strategy touching one or several times this altitudes without sleeping to start the acclimatisation but knowing that during our climb above this altitude we need to move quickly.
Here some profiles of acclimatisations:
Kilian Jornet: I believe the Cho Oyu – Everest Expedition in 2017 was my best acclimatization profile: HERE
Book THE ALTITUDE EXPERIENCE: HERE
4. Mitigating extreme hypoxia above acclimatized zone
Above roughly 7,500 meters, human acclimatization is no longer sustainable. Metabolic consumption outpaces atmospheric oxygen supply, resulting in progressive cellular degradation, muscle wasting, and organ deterioration.
5. High-altitude nutrition and hydration
Hydration
Climbers lose between 4 to 6 Liters of fluid per day at high altitude due to:
- Respiratory vapor loss: Hyperventilation of dry, freezing air requires the upper respiratory tract to heat and humidify massive volumes of gas.
- Cold-induced diuresis: Peripheral vasoconstriction shifts blood to the core, suppressing anti-diuretic hormone (ADH) and increasing urinary output.
- Renal bicarbonate excretion: Excreting HCO3− carries water and electrolytes into urine.
Target: Maintain fluid intake of 4–5 L/day. Dehydration accelerates cold injury, frostbite, and hyperviscosity-induced altitude illness.
Base Camp diet
Hypobaric hypoxia suppresses appetite (hypobaric anorexia) by upregulating satiety hormones (leptin, PYY) and suppressing ghrelin.
Carbohydrates Fats / Lipids
┌────────────────────────┐ ┌────────────────────────┐
│ P/O Ratio: ~2.58 │ │ P/O Ratio: ~2.25 │
│ Produces ~10% MORE │ VS │ Requires MORE O₂ │
│ ATP per mole of O₂ │ │ per ATP generated │
└────────────────────────┘ └────────────────────────┘
- Carbohydrate priority: Carbohydrate oxidation yields more ATP per mole of oxygen consumed compared to fat oxidation (Phosphate-to-Oxygen [P/O] ratio advantage).
- Micronutrient Needs:
- Iron: Serum ferritin levels must be evaluated before expedition. Erythropoiesis requires robust iron stores (target ferritin >50–100 μg/L). Oral iron supplementation (100–200 mg elemental iron daily) can be interesting if deficit to avoid non-functional erythropoiesis, but also think to have in the diet the folic acid and Vitamin C.
- Antioxidants: High altitude induces severe oxidative stress via increased reactive oxygen species. Supplementing with Vitamins C, E, and zinc supports tissue repair.
Gut microbiota under hypoxia
Hypoxia causes splanchnic vasoconstriction, shunting blood away from the gastrointestinal tract to the brain and heart. This leads to:
- Microvascular ischemia & intestinal permeability: Degradation of mucosal epithelial tight junctions (leaky gut), predisposing climbers to systemic endotoxemia, systemic inflammation, and severe diarrhea.
- Dysbiosis: Hypoxia leads to a reduction in beneficial short-chain fatty acid (SCFA)-producing taxa (e.g., Faecalibacterium prausnitzii, Roseburia) and an enrichment of pathogenic inflammation-promoting bacteria
- Evidence-based probiotic strains: Studies show that specific strains of Lactobacillus (e.g., Lactobacillus rhamnosus, L. acidophilus) and Bifidobacterium (e.g., B. longum, B. animalis) maintain mucosal barrier integrity, preserve SCFA production, reduce gastrointestinal distress, and mitigate systemic inflammatory responses during high-altitude exposure.
Summit push fueling
At extreme altitude, delayed gastric emptying and severe nausea make solid foods unpalatable.
- Fuel Source: Glucose and simple sugars (maltodextrin, fructose mixtures).
- Strategies: Liquid calorie mixes, energy gels, sports chews, and sweetened hot drinks.
6. Altitude-related illnesses:
1. Acute Mountain Sickness (AMS)
- Pathophysiology: Hypoxia-induced increase in cerebral blood flow and vascular permeability causing mild, self-limiting cerebral edema.
- Diagnosis: If we have some of this symptoms and we add 6 points:
- head pain – 1
- nausea – 1
- appetite loss – 1
- vomit – 2
- persistent head pain – 2
- hight fatigue (not normal) – 3
- can not pis – 3
- Treatment: Rest, Go down, mild analgesics (Ibuprofen/Acetaminophen), Acetazolamide (125–250 mg). Halt ascent until symptoms resolve
2. High Altitude Pulmonary Edema (HAPE)
- Pathophysiology: Non-cardiogenic pulmonary edema triggered by exaggerated and non-uniform Hypoxic Pulmonary Vasoconstriction (HPV). High pulmonary capillary arterial pressures lead to capillary stress failure, endothelial leakage, and protein-rich fluid transudation into alveoli.
- Clinical Symptoms: Rapid loss of physical performance, dyspnea at rest, dry cough progressing to pink frothy sputum, cyanosis, and chest rales/crackles.
- Emergency Treatment:
- Immediate Descent: Mandatory descent of at least 500–1,000 meters.
- Pharmacology: Nifedipine (30 mg ER q12h) / Aalalat / Viagra to reduce pulmonary artery pressure (Hackett & Roach, 2001; Luks et al., 2019).
- Gamow Bag: Portable hyperbaric chamber if immediate descent is impossible.
- Go Down, sit upright. If persist, in 6h we can die.
3. High Altitude Cerebral Edema (HACE)
- Pathophysiology: Severe, end-stage progression of AMS. Marked microvascular leakage through the blood-brain barrier causes vasogenic cerebral edema, elevated intracranial pressure, and brain herniation.
- Clinical Symptoms: Truncated ataxia (inability to walk a heel-to-toe straight line), altered mental status, confusion, severe lethargy, halluncinations, and progression to coma.
- Emergency Treatment:
- Immediate Emergency Descent: Non-negotiable top priority.
- Dexamethasone: 8 mg IV/IM/Oral immediately, followed by 4 mg every 6 hours (Hackett & Roach, 2001; Luks et al., 2019).
- Supplemental Oxygen & Gamow Bag: Administer oxygen and use portable hyperbaric chamber while arranging descent.
Medical comparison overview
| Illness | Primary Mechanism | Key Cardinal Sign | First-Line Medication | Definitive Action |
|---|---|---|---|---|
| AMS / MAM | Mild vasogenic brain swelling | Headache + Nausea/Fatigue | Acetazolamide / Ibuprofen | Rest; stop ascent |
| HAPE | Pulmonary capillary stress failure | Dyspnea at rest, pink sputum | Nifedipine (30 mg ER) | Immediate descent (>500 m) |
| HACE | Severe cerebral edema / ICP | Ataxia, confusion | Dexamethasone (8 mgloading) | Immediate descent |
Other altitude / Expedition illnesses:
| Symptom | NAME | comercial name | treatment |
| INFECTION (teeth, fever…) | AZYTHROMICYNE 250 | Azytromax / Augmentine | 1 x day during 3 days |
| MAM / Altitude sickness | ACETAZOLAMIDE 250 | Dyamox | 2 x day |
| HACE | PREDNISOLONE 20 | Prednisolon | 4 tablets straigt / then 3 during 4 days |
| HACE | DEXAMETASON | Dexametason | 8mg + 4mg after 6h |
| HAPE | NIFEDIPINE | Adalate | 20mg every 8h |
| Bronchitis | BUDESONIDE 400 | Pulmicort | 2 dose x 2 day |
| INFECTION EYES | TOBRAMYCINE | Tobrex | 2 x day |
| EYES BURN | Vitamin A | Vitamin A | cream 3x day / 3 days |
| EXTREME PAIN (broken bone…) | TRAMADOL 50 | tramadol | 2-2-2-2 |
| DIARRHEA | RACECADOTRIL 100 | Loperamid / Ciprofloxacin 750mg | 2. 1 after every diarrhea / once or 500mg 2x day |
| APENDICITIS | AMOXICILIN | Amoxicillin / Augmentine | 1mg/8h |
| VOMIT | METOPIMAZINE 7,5 | Volagene | 1-1-1 |
| FROSTBITE | DICLOXACILLIN | 1-1-1 | |
| FROSTBITE | IBUPROFEN | 12mg/kg/day in 2 doses/day |
CASE STUDY OF AN ICTUS. https://elikarmet.com due to high Hematocrite / less hydration, the blood became less liquid and it is easy to have vascular problems or ictus.
Hyperbaric mitigation
- Portable Hyperbaric Chambers (Gamow Bag): Sealed inflatable bags pressurized with a foot pump to 1.5–2.0 psi above ambient pressure. This pressurization simulates an immediate descent of 1,000 to 1,500 meters, stabilizing a victim of HAPE or HACE when descent is physically impossible due to weather or terrain.
- To understand the difference of climbing without supplemental oxygen here is a good article about: https://8kpeak.com/pages/climbing-with-supplemental-oxygen-by-the-numbers
References
Grocott, M. P. W., Martin, D. S., Levett, D. Z. H., McMorrow, R., Windsor, J., & Montgomery, H. E. (2009). Arterial blood gases and oxygen content in climbers on Mount Everest. New England Journal of Medicine, 360(2), 140–149. https://doi.org/10.1056/nejmoa0801581 Cited by: 633
Hackett, P. H., & Roach, R. C. (2001). High-altitude illness. New England Journal of Medicine, 345(2), 107–114. https://doi.org/10.1056/nejm200107123450206 Cited by: 1889
Koivisto-Mørk, A. E., Paur, I., Paulsen, G., Garthe, I., Raastad, T., Bastani, N. E., Blomhoff, R., & Bøhn, S. K. (2020). Dietary adjustments to altitude training in elite endurance athletes; Impact of a randomized clinical trial with antioxidant-rich foods. Frontiers in Sports and Active Living, 2. https://doi.org/10.3389/fspor.2020.00106 Cited by: 14
Liu, D., Chen, D., Xiao, J., Wang, W., Zhang, L.-J., Peng, H., Han, C., & Yao, H. (2024). High-altitude-induced alterations in intestinal microbiota. Frontiers in Microbiology, 15. https://doi.org/10.3389/fmicb.2024.1369627 Cited by: 29
Luks, A. M., Auerbach, P. S., Freer, L., Grissom, C. K., Keyes, L. E., McIntosh, S. E., Rodway, G. W., Schoene, R. B., Zafren, K., & Hackett, P. H. (2019). Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2019 update. Wilderness & Environmental Medicine, 30(4S), S3–S18. https://doi.org/10.1016/j.wem.2019.04.006
Wagner, P. D. (2010). Operation Everest II. High Altitude Medicine & Biology, 11(2), 111–119. https://doi.org/10.1089/ham.2009.1084 Cited by: 66