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External respiration occurs in the lungs, where oxygen diffuses from alveoli into pulmonary capillaries and carbon dioxide moves from blood into alveoli. Internal respiration happens at body tissues, where oxygen transfers from systemic capillaries to tissue cells for ATP production, while CO2 produced by cellular metabolism diffuses from cells back into capillaries. Both processes follow partial pressure gradients.

Gas always moves from higher to lower partial pressure. In external respiration, alveolar oxygen at 105 mmHg diffuses into pulmonary capillaries at 40 mmHg. Simultaneously, blood carbon dioxide at 45 mmHg moves into alveolar air at 40 mmHg. These pressure differences create the driving force for gas exchange across the alveolar membrane.

Tissue cells consume oxygen rapidly during ATP production through cellular respiration, lowering their oxygen partial pressure below that of systemic capillaries. This pressure gradient causes oxygen to diffuse from capillaries into cells. Conversely, CO2 accumulates in cells from metabolism, creating a higher PCO2 in cells than capillaries, driving CO2 diffusion outward.

Decreased partial pressure gradients, reduced surface area, and increased diffusion distance all slow gas exchange. Conditions like emphysema reduce alveolar surface area, while pulmonary edema extends diffusion distance by accumulating interstitial fluid. Drugs such as morphine slow respiratory rate, decreasing oxygen and carbon dioxide exchange rates between alveoli and blood.

At higher altitudes, both total atmospheric pressure and oxygen partial pressure decline, reducing the pressure gradient between alveolar air and pulmonary capillaries. This slower oxygen diffusion results in decreased blood oxygen levels, causing high-altitude sickness symptoms including breathlessness, headache, fatigue, insomnia, nausea, and dizziness.

The vast surface area provided by alveoli, combined with abundant surrounding capillaries, enables efficient gas exchange between air and blood. This extensive interface maximizes the opportunity for oxygen and carbon dioxide molecules to cross the thin respiratory membrane. Conditions reducing this surface area, such as emphysema, significantly impair gas exchange efficiency.

The thin respiratory membrane minimizes diffusion distance, allowing oxygen and carbon dioxide to cross quickly between alveolar air and blood. Red blood cells pass single-file through narrow capillaries, further reducing diffusion distance and maximizing contact time with the alveolar membrane. This structural efficiency enables rapid, effective gas exchange during both external and internal respiration.