High Altitude Respiration In Mammals

Pressure at high Altitude

At sea level, there is approximately 0.2 atmospheres (20 kPa) of pressure driving oxygen from the atmosphere to the mitochondria where it is metabolized; above 8000 m this pO2 is reduced to 0.07 atmospheres (7 kPa). Thus the ‘driving force’ for oxygen is reduced. Humans can live permanently at 5000 m and can ascend briefly to above 8000 m (e.g. Mount Everest, 8900 m, has been climbed without pressurized oxygen apparatus). Humans can acclimatize to high altitudes.

Initial responses

  • On exposure to high altitude, lowlanders hyperventilate (up to 50% above the sea-level rate over the first 7 days of exposure). Later, there is some compensation (also seen in native Andean highlanders) through deeper breathing.
  • Hyperventilation increases arterial oxygen levels but also reduces blood carbon dioxide levels and raises the proportion of oxygen in the alveolar gas mixture (since the alveolar gases are more or less in equilibrium with the pulmonary blood gases).
  • Thus the pO2   gradient between inspired air and the gas mixture in the alveoli is reduced, and a sufficiently high pO2 level is maintained in the alveoli to allow oxygen diffusion into the blood. The reduction in blood pCO2 causes respiratory alkalosis, corrected by increased kidney excretion of HCO3.
  • Before this compensation occurs, alkalosis can inhibit the respiratory center of the brain leading to hypoxia (shortage of oxygen), characterized by cyanosis (blueing of the extremities such as the lips and ear lobes due to deoxygenated arterial blood) and impaired mental performance, such as judgement and concentration. The cardiac rate increases transiently to improve oxygen transport to the tissues.


  • In time, red blood cells are released from reserves in the spleen (leading to polycythemia), and new red cells are produced under the influence of the hormone erythropoietin.
  • Thus the oxygen content per unit volume of blood in a highlander can be much the same as in a lowlander. Hyperventilation tends to be maintained (highlanders frequently develop ‘barrel chests’) because of the increased sensitivity of central chemoreceptors to carbon dioxide.
  • The oxygen–hemoglobin dissociation curve in acclimatized lowlanders tends to shift to the right in the tissues because of the build-up of 2,3-diphosphoglycerate, a glycolysis intermediate, and an exaggerated Bohr shift is seen.
  • This assists oxygen unloading at the tissues. Interestingly, in some peoples, such as Tibetans, living at very high altitudes, and in high-altitude artiodactyl species such as yaks, llamas and vicunas, the dissociation curve shifts to the left: this is probably an evolutionary adaptation (rather than acclimatization) and assists loading of oxygen at the lungs. Increased capillary density and mitochondrial numbers are seen, as are elevated myoglobin levels.


  1. https://pubmed.ncbi.nlm.nih.gov/25446936/
  2. https://pubmed.ncbi.nlm.nih.gov/17561448/