Regional hypoxia: a normoxic destination exists
When one lobe is hypoxic, for example because of a mucus plug or a localized pneumonia, HPV constricts the arterioles of that lobe and diverts its share of cardiac output to the remaining normoxic lung. The normoxic region has low vascular resistance and can accept the extra flow, so the diverted blood still equilibrates with a high alveolar PO2. The result is that the shunt fraction falls and arterial oxygenation is partly protected. The total pulmonary arterial pressure rises only modestly, because the increase in resistance is confined to a small fraction of the vascular bed and the remaining vessels recruit and distend.
Global hypoxia: no normoxic destination
When alveolar PO2 falls everywhere, as at high altitude or in severe diffuse lung disease, HPV constricts vessels throughout the lung. There is no normoxic region to receive the diverted flow, so the redistribution cannot improve matching; it only raises pulmonary vascular resistance. Because the entire cardiac output must pass through the constricted bed, pulmonary arterial pressure rises substantially, and if the hypoxia persists the right ventricle faces a sustained afterload. This is the setting in which HPV becomes maladaptive: the reflex that protects matching in a focal defect contributes to pulmonary hypertension when the hypoxic stimulus is global.
Bronchovascular coupling: the ventilation-side partner
The airways respond in the opposite direction to complete the matching. When a region is poorly perfused, the local PCO2 falls and the local PO2 rises in the airway, and the bronchial smooth muscle in that region constricts. This reduces ventilation to the underperfused region, so ventilation is withdrawn from where it would be wasted. The effect is to limit dead space in the same way that HPV limits shunt. The two responses are complementary: HPV moves perfusion toward ventilation, and bronchovascular coupling moves ventilation toward perfusion.
When the defense is blunted or overwhelmed
HPV is not a fixed property. It is attenuated by chronic hypoxia, which is one reason patients with chronic mountain sickness or chronic obstructive pulmonary disease can have poorly matched V/Q despite an intact reflex. It is also blunted by many vasodilator drugs, including calcium channel blockers and inhaled anesthetics, and by inflammatory mediators released in sepsis and acute lung injury. Finally, it can be overwhelmed when the hypoxic fraction of the lung is large: if most of the lung is hypoxic, there is little normoxic tissue to accept diverted flow, and the reflex cannot restore matching no matter how strongly it acts.