What is the basis of gas exchange in humans?

Basis of Gas Exchange in Humans

Gas exchange in humans fundamentally relies on four sequential processes: pulmonary ventilation (air movement into/out of lungs), pulmonary diffusion (O₂ and CO₂ exchange between alveoli and blood), blood transport of gases, and capillary gas exchange (O₂ and CO₂ exchange between blood and tissues). 1

The Four Core Processes

The American Heart Association defines gas exchange through an integrated system that can be divided into external and internal respiration 1:

External Respiration (Lungs to Blood)

• Pulmonary ventilation moves air into and out of the lungs, with only the portion reaching the alveoli participating in actual gas exchange 1
• Pulmonary diffusion occurs at the alveolar-capillary interface where O₂ moves from alveolar gas (high partial pressure) into pulmonary capillary blood (lower partial pressure), while CO₂ moves in the opposite direction 1, 2
• The alveolar partial pressures of O₂ and CO₂ are maintained by continuous tidal breathing, which brings fresh oxygen and removes carbon dioxide 2

Blood Transport

• Hemoglobin in erythrocytes serves as the primary oxygen carrier, binding O₂ as the terminal electron acceptor for cellular ATP synthesis 1
• Approximately 23% of CO₂ is transported bound to hemoglobin, while the majority travels as bicarbonate (HCO₃⁻) in plasma 1
• Erythrocytes contain carbonic anhydrase enzyme and anion exchanger 1 (AE1) protein, which facilitate CO₂ conversion to HCO₃⁻ in tissues and the reverse reaction in lungs 1

Internal Respiration (Blood to Tissues)

• Capillary gas exchange at the tissue level involves O₂ diffusion from blood into working muscles and CO₂ movement from tissues into blood 1
• This process is facilitated by increased cardiac output (up to 6-fold at peak exercise) and redistribution of blood flow to active tissues 1
• Greater O₂ extraction occurs as blood perfuses muscles, widening the arteriovenous oxygen difference 1

Critical Determinants of Effective Gas Exchange

Ventilation-Perfusion Matching

• Normal gas exchange requires matched ventilation and perfusion (V̇A/Q̇ ratio) in each alveolar unit 1, 3
• For each gas-exchanging unit, the alveolar and blood partial pressures of O₂ and CO₂ are determined by the ratio of alveolar ventilation to blood flow 3
• During inhalation, air that remains in respiratory passages (dead space volume) does not participate in gas exchange 1
• In healthy subjects, respiratory passage dilation during exercise increases dead space, but this is compensated by increased tidal volume to maintain adequate alveolar ventilation 1

Diffusion Capacity

• Passive diffusion drives gas movement based on partial pressure gradients across the alveolar-capillary membrane 2, 4
• Different gases have varying diffusion characteristics based on their solubility in the alveolar wall relative to their solubility in blood 5
• While diffusion limitation can occur in certain disease states or extreme conditions, it is less common than V̇A/Q̇ mismatch as a cause of impaired gas exchange 3, 4

Common Pitfalls and Clinical Considerations

Mechanisms of Hypoxemia

Six distinct causes of hypoxemia exist, each requiring different therapeutic approaches 4:

• Inspiratory hypoxia (low inspired O₂)
• Hypoventilation
• Ventilation/perfusion inequality (most common)
• Diffusion limitation
• Shunting
• Reduced mixed venous oxygenation

Disease-Specific Alterations

• Shunt and low V̇A/Q̇ regions are the most frequent causes of hypoxemia in disease states 3
• Hypoxemia due to shunt responds poorly to supplemental oxygen, unlike other causes 3
• High V̇A/Q̇ regions (alveolar dead space) result in wasted ventilation and increased work of breathing rather than hypercapnia, as respiratory drive compensates to maintain normal arterial PCO₂ 3
• The alveolar-arterial O₂ difference (P(a-a)O₂) reflects pulmonary gas exchange defects from V̇A/Q̇ mismatch, diffusion limitation, and shunt 1

Cardiovascular Integration

• The circulatory system links external and internal respiration, making cardiac output a critical determinant of overall gas exchange efficiency 1
• Cardiac output must increase proportionally with ventilation during exercise to maintain appropriate gas exchange 1
• Impaired cardiac output response (as in heart failure) leads to ventilation-perfusion mismatch where ventilation increases disproportionately to metabolic needs 1