Gas Exchange

Efficient gas exchange at the alveolus depends on matching ventilation to perfusion throughout the lung. When these are mismatched, hypoxaemia results through mechanisms that differ in their response to supplemental oxygen.

Ventilation-perfusion (V/Q) matching is the central concept of pulmonary gas exchange. In an ideal lung, every alveolus receives ventilation and blood flow in exact proportion (V/Q = 1). In practice, there is regional variation even in healthy lungs, with better perfusion in dependent zones due to gravity. Disease substantially worsens this mismatch.

In V/Q mismatch, some alveoli are relatively over-ventilated compared to their perfusion (high V/Q) and others are under-ventilated relative to their perfusion (low V/Q). Low V/Q units are the primary cause of hypoxaemia in most lung diseases (pneumonia, asthma, COPD, pulmonary oedema). Because blood passing through low V/Q regions returns with lower PO2, it dilutes the output of normal regions, lowering overall arterial PO2. Importantly, supplemental oxygen corrects V/Q mismatch hypoxaemia because it raises the alveolar PO2 even in low V/Q regions, allowing those regions to oxygenate blood more fully.

A true shunt is the extreme of V/Q mismatch where V/Q = 0: blood passes through areas of completely unventilated lung (atelectasis, consolidation) or through anatomical channels that bypass the lungs entirely (intracardiac right-to-left shunts, pulmonary arteriovenous malformations). Shunt hypoxaemia does not respond significantly to supplemental oxygen because the shunted blood never contacts alveolar gas regardless of its oxygen content. This is the key clinical distinction: failure to correct hypoxaemia with high-flow oxygen strongly suggests significant shunt.

Impaired diffusion reduces the rate of gas equilibration across the alveolar-capillary membrane. At rest, equilibration is normally complete within one-third of the capillary transit time. Diffusion impairment becomes clinically apparent during exercise (when transit time is shorter) before it causes resting hypoxaemia. It responds to supplemental oxygen because increasing the driving gradient overcomes the reduced diffusion rate. Causes include pulmonary fibrosis, sarcoidosis, and emphysema (reduced surface area).