Physiology chapters
High altitude and acclimatisation
Why oxygen is short at high altitude, the immediate effects of hypoxia, how the body acclimatises over days to weeks, and the illnesses of altitude, including acute mountain sickness and high-altitude pulmonary and cerebral oedema.
- At altitude the barometric pressure falls, so inspired and alveolar PO2 fall, although air is still about 21% oxygen.
- Low PO2 stimulates the peripheral chemoreceptors: hyperventilation lowers CO2 and causes respiratory alkalosis, which at first limits the rise in breathing.
- Acclimatisation: kidneys excrete bicarbonate, breathing rises further, 2,3-BPG and erythropoietin rise (more red cells), capillaries and mitochondria increase.
On this page
Overview
As you climb, the barometric pressure falls. The air still contains about 21% oxygen, but each breath carries less oxygen because the total pressure is lower.
The result is hypoxic hypoxia. The body responds within minutes, and over days to weeks it acclimatises.
Pressures at altitude
| Altitude | Barometric pressure (mmHg) | Alveolar PO2 (approx., mmHg) | Arterial O2 saturation (approx.) |
|---|---|---|---|
| Sea level | 760 | 104 | 97% |
| 3,000 m (10,000 ft) | 523 | 67 | 90% |
| 6,000 m (20,000 ft) | 349 | 40 | 73% |
| 9,000 m (30,000 ft) | 226 | 21 (breathing air) | Very low |
Water vapour pressure stays at 47 mmHg at body temperature, so it takes up a bigger share of the lower total pressure, lowering alveolar PO2 further.
Altitude lowers PO2 because barometric pressure falls, not because the percentage of O2 changes.
Acute effects of hypoxia
At about 3,500 m and above, an unacclimatised person may notice:
- Drowsiness, tiredness, headache, nausea.
- Poor judgment and reduced night vision.
- At very high altitude: twitching, seizures and loss of consciousness.
Immediate responses
- Hyperventilation: low arterial PO2 stimulates the carotid and aortic bodies, increasing breathing.
- Respiratory alkalosis: hyperventilation lowers PCO2 and raises pH. The low CO2 and high pH damp the central chemoreceptors and limit how much breathing can rise at first.
- Increased heart rate and cardiac output.
- Hypoxic pulmonary vasoconstriction, raising pulmonary artery pressure.
The first response to altitude is hyperventilation, driven by the peripheral chemoreceptors, which produces respiratory alkalosis.
Acclimatisation (days to weeks)
| Change | Timing | Effect |
|---|---|---|
| Kidneys excrete bicarbonate | 2–5 days | Corrects the alkalosis; CSF pH also falls, so central chemoreceptors stop braking breathing; ventilation rises further (up to about five times normal) |
| 2,3-BPG increases | Hours to days | Right shift of the dissociation curve; more O2 released in tissues |
| Erythropoietin (from the kidney) rises | Within days; red cell mass rises over weeks to months | Polycythaemia; haematocrit can rise from 40–45 to about 60%; haemoglobin up to about 20 g/dL |
| More capillaries in tissues | Weeks | Shorter diffusion distance |
| More mitochondria and oxidative enzymes | Weeks | Cells use O2 more efficiently |
| Larger lung diffusing capacity | Long term | More capillary blood and larger lung volumes |
Acclimatisation includes increased ventilation (after renal bicarbonate loss), raised 2,3-BPG, erythropoietin-driven polycythaemia, and more capillaries.
Very high haematocrit makes blood more viscous, so beyond a point extra red cells do not help and can impair flow.
Natives of high altitude
People born and living at high altitude have large chests and lungs, larger hearts (especially the right ventricle), higher haemoglobin and more capillaries. They work far better at altitude than acclimatised lowlanders.
Illnesses of altitude
Acute mountain sickness
How it happens: rapid ascent above about 2,500 m.
What you see: headache, nausea, fatigue, poor sleep and dizziness within hours to a day.
High-altitude pulmonary oedema (HAPE)
How it happens: strong, uneven hypoxic pulmonary vasoconstriction raises capillary pressure in the areas still perfused, and fluid leaks out.
What you see: breathlessness at rest, cough, frothy sputum, low saturation. It can be fatal.
High-altitude cerebral oedema (HACE)
How it happens: hypoxia dilates brain vessels and makes them leaky, causing brain swelling.
What you see: confusion, unsteady walking (ataxia), drowsiness, coma.
Treatment of altitude illness: the most important step is descent; oxygen; drugs such as dexamethasone (HACE) and nifedipine (HAPE) as advised by expert guidance.
Prevention: acetazolamide
Acetazolamide inhibits carbonic anhydrase in the kidney, causing bicarbonate loss in urine. This produces a mild metabolic acidosis that stimulates breathing and speeds acclimatisation.
Chronic mountain sickness (Monge's disease)
How it happens: in some long-term residents, red cell mass rises too much.
What you see: very high haematocrit, pulmonary hypertension and right heart failure; it improves with moving to a lower altitude.
Clinical relevance
Air travel
Aircraft cabins are pressurised to about 1,800–2,400 m. Patients with severe lung or heart disease may need extra oxygen when flying.
Diving (contrast)
At depth, the pressure rises; problems include nitrogen narcosis, oxygen toxicity and decompression sickness when rising too fast. This is the opposite situation to altitude.
Expect: why PO2 falls with altitude, the first response (peripheral chemoreceptors and hyperventilation), the respiratory alkalosis and its renal compensation, 2,3-BPG and erythropoietin in acclimatisation, the mechanism of HAPE and HACE, and the action of acetazolamide.
Quick revision
- Barometric pressure falls; O2 stays 21%; alveolar PO2 falls.
- First response: hyperventilation via peripheral chemoreceptors.
- Respiratory alkalosis; kidneys excrete bicarbonate over days.
- Acclimatisation: more ventilation, more 2,3-BPG, more EPO and red cells, more capillaries.
- HAPE: uneven hypoxic pulmonary vasoconstriction. HACE: brain swelling.
- Acetazolamide: metabolic acidosis stimulates breathing.
- Best treatment of altitude illness: descent.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
Why is there less oxygen at high altitude?
The barometric pressure is lower, so the partial pressure of oxygen in the air and alveoli is lower, even though air is still about 21% oxygen.
What is the first response to high altitude?
Hyperventilation, triggered by low arterial PO2 acting on the peripheral chemoreceptors.
What acid-base change occurs at high altitude?
Respiratory alkalosis, compensated over a few days by renal excretion of bicarbonate.
How does acetazolamide prevent altitude sickness?
It causes bicarbonate loss in urine, producing a mild metabolic acidosis that stimulates breathing and speeds acclimatisation.