Haldane effect

The Haldane effect describes the physical equilibria of oxygen and CO2 in people who have adapted to living at different altitudes, where increased oxygen pressure decreases the amount of carbon dioxide retained by hemoglobin, and decreased oxygen pressure increases the amount of CO2 retained 1. This effect is a result of oxygen displacing carbon dioxide from hemoglobin, in proportion to its partial (specific) pressure 7. The increased retention of carbon dioxide at high altitude accounts for the "lactate paradox," where maximal exertion at high altitude doesn't increase lactic acid production in the normal way 2.

Carbon dioxide plays a crucial role in suppressing the formation of lactic acid, and its absence results in the syndromes of altitude sickness, and ventilator-induced lung damage 2. The excess production of lactate displaces carbon dioxide from the blood, partly as a compensation for acidity, and lactate can promote the adrenergic response, creating a vicious circle 4. The Haldane effect is also involved in the disposition of calcium, and adequate CO2 is essential for its regulation 5.

The Haldane effect is not limited to hemoglobin, as it applies to proteins in general, where a high concentration of carbon dioxide changes the pH or the isoelectric point of the protein, making it less accessible to oxygen 8. This effect provides a protection against the attack of oxygen against proteins. The increased retention of carbon dioxide at high altitude is a result of the Haldane effect, and it is essential for the adaptation to high altitude 1.