Clinical meaning
Gas exchange occurs at the alveolar-capillary membrane through passive diffusion driven by partial pressure gradients (Fick's law of diffusion). Oxygen diffuses from alveoli (PAO2 ~100 mmHg) into pulmonary capillary blood (PvO2 ~40 mmHg), while CO2 diffuses from capillary blood (PvCO2 ~46 mmHg) into alveoli (PACO2 ~40 mmHg). CO2 diffuses 20 times more readily than O2 (higher solubility coefficient), so CO2 retention indicates severe hypoventilation or V/Q mismatch. The alveolar gas equation calculates expected PAO2: PAO2 = FiO2 × (Patm - PH2O) - PaCO2/R, where R = respiratory quotient (~0.8). The A-a gradient (PAO2 - PaO2, normally < 15 mmHg in young adults, increases with age) differentiates causes of hypoxemia: normal A-a gradient = hypoventilation (CNS depression, neuromuscular disease) or low FiO2 (altitude); elevated A-a gradient = V/Q mismatch (COPD, asthma, PE), shunt (ARDS, pneumonia, atelectasis), or diffusion impairment (pulmonary fibrosis). Ventilation-perfusion (V/Q) matching is critical: areas of high V/Q (dead space — ventilated but not perfused, as in PE) waste ventilation; areas of low V/Q (shunt effect — perfused but not ventilated, as in pneumonia) cause hypoxemia. True shunt (V/Q = 0) does NOT improve with supplemental O2 because blood bypasses alveoli entirely. Hypoxic pulmonary vasoconstriction (HPV) diverts blood away from poorly ventilated areas to optimize V/Q matching.