Explain ventilation‑perfusion (V/Q) mismatch, its mechanisms and clinical implications.

Ventilation-Perfusion (V/Q) Mismatch: Mechanisms and Clinical Implications

V/Q mismatch occurs when alveolar ventilation and pulmonary blood flow are not optimally matched, resulting in impaired gas exchange that manifests as hypoxemia, increased dead space ventilation, or both. 1, 2

Fundamental Concept

The V/Q ratio represents the relationship between alveolar ventilation (ml air/min) and regional blood flow (ml blood/min) in any given lung unit. 3, 2 In healthy lungs, this ratio averages approximately 0.8-1.0, though regional variations exist from apex to base. 1

Normal Regional Distribution

• Both ventilation and perfusion are greatest at the lung bases in the upright position, with perfusion having a steeper gradient than ventilation. 1
• This creates lower V/Q ratios at the bases (around 0.6) and higher V/Q ratios at the apices (around 3.0) in normal physiology. 1
• The bases are more compressed due to lung weight and lower intrapleural pressure, causing greater expansion during inspiration. 1
• Perfusion follows gravity due to relatively low pulmonary circulation pressures. 1

Types of V/Q Mismatch

Low V/Q Units (Shunt-like)

Low V/Q regions occur when perfusion exceeds ventilation, creating areas where blood flow is relatively excessive compared to air delivery. 2, 4

• These units receive blood flow but inadequate ventilation, leading to venous admixture and hypoxemia. 2
• Common causes include airway obstruction, atelectasis, pneumonia, and pulmonary edema. 2, 4
• In COPD, low V/Q areas represent regions with partially blocked airways and can receive up to 50% of alveolar ventilation but only 5% of cardiac output. 5, 6
• Hypoxemia from low V/Q units typically responds to supplemental oxygen, distinguishing it from true shunt. 2

High V/Q Units (Dead Space-like)

High V/Q regions occur when ventilation exceeds perfusion, creating wasted ventilation that does not participate in effective gas exchange. 5, 2

• These areas receive ventilation but little or no blood flow, increasing physiological dead space. 5, 2
• In COPD with emphysema, high V/Q ratios develop due to alveolar destruction and loss of pulmonary vasculature. 1, 6
• The normal dead space to tidal volume ratio (VD/VT) is 0.34 at rest; values >0.6 indicate pathologically elevated dead space. 5
• In ARDS, VD/VT >0.6 is associated with significantly higher mortality (OR = 17.9). 5, 4

True Shunt (V/Q = 0)

True shunt represents complete absence of ventilation to perfused lung units, where blood passes through the lungs without any gas exchange. 2, 4

• Hypoxemia from shunt responds poorly to supplemental oxygen, a key distinguishing feature. 2
• Causes include atelectasis, consolidation, and intrapulmonary arteriovenous malformations. 2, 4

Compensatory Mechanisms

Hypoxic Pulmonary Vasoconstriction (HPV)

HPV is the primary physiological mechanism that matches perfusion to ventilation by constricting precapillary pulmonary arterioles in response to low alveolar oxygen tension. 1

• This redirects blood flow away from poorly ventilated regions toward better ventilated areas, minimizing V/Q mismatch. 1
• HPV effectiveness varies with disease severity and can be impaired in chronic lung disease. 1

Clinical Manifestations by Disease State

Chronic Obstructive Pulmonary Disease (COPD)

V/Q inequality is the major mechanism impairing gas exchange and causing arterial hypoxemia in COPD. 1, 7

• Three distinct patterns exist: (1) predominantly high V/Q areas (type A/emphysema), (2) predominantly low V/Q areas (type B/chronic bronchitis), or (3) mixed patterns. 6
• V/Q imbalance is disproportionately greater than airflow limitation in early COPD (GOLD stage 1), suggesting initial involvement of smallest airways, parenchyma, and pulmonary vessels. 7
• Patients require abnormally high ventilation to maintain eucapnia even at rest due to increased dead space. 5
• The relationship between FEV1 and V/Q mismatch is modest (r = -0.48), indicating that spirometry alone poorly predicts gas exchange abnormalities. 7

Acute Respiratory Distress Syndrome (ARDS)

V/Q mismatch in ARDS manifests as both intrapulmonary shunt (from collapsed/consolidated units) and increased dead space (from non-perfused ventilated zones). 4

• Elevated dead space reflects ventilated but not perfused alveolar areas due to microvascular injury and thrombosis. 5, 4
• VD/VT >0.6 has strong prognostic value and should guide ventilator management. 5, 4
• V/Q mismatch contributes to ventilation-induced lung injury and worsening lung edema beyond its gas exchange effects. 4

Chronic Heart Failure

Impaired cardiac output response to exercise leads to V/Q mismatch where ventilation must increase disproportionately to metabolic needs to compensate for inadequate perfusion. 3

• The degree of abnormally heightened ventilation during exercise directly relates to disease severity and is a strong prognostic marker. 3
• Left pulmonary hypertension causes VD/VT that does not decrease appropriately during exercise. 5

Idiopathic Pulmonary Fibrosis

Honeycomb cystic spaces are unperfused (due to vascular obliteration) but normally ventilated, creating high V/Q mismatch. 8

• This pattern can mimic pulmonary embolism on V/Q scintigraphy unless CT imaging is obtained. 8
• The large physiologic dead space explains exercise intolerance in these patients. 8

Clinical Assessment

Quantitative Measures

The modified Bohr equation calculates VD/VT: (PaCO2 - PECO2)/PaCO2, requiring arterial blood gas and mixed exhaled CO2 measurement. 5

• A VE/VCO2 slope >38 indicates excessive ventilation for metabolic requirement, reflecting increased dead space. 5
• Alveolar-arterial oxygen gradient (AaPO2) quantifies the effect of V/Q mismatch on oxygenation. 2, 7

Bedside Imaging

Electrical impedance tomography (EIT) allows real-time bedside assessment of regional V/Q distribution with advantages over CT, SPECT, or multiple inert gas elimination technique. 3

• EIT-based V/Q assessment uses hypertonic saline bolus injection during breath-hold to measure perfusion, combined with ventilation imaging. 3
• EIT shows better agreement with SPECT and PET and is currently the reference for bedside V/Q assessment. 3

Critical Clinical Pitfalls

Do not assume normal oxygen saturation rules out V/Q mismatch—dead space reflects wasted ventilation, not oxygenation. 5

Do not use end-tidal CO2 (ETCO2) instead of PaCO2 in the Enghoff equation, especially in pulmonary disease where ETCO2 may exceed PaCO2 due to dead space. 5

Do not rely on arterial blood gases alone to infer V/Q patterns—patients with similar PaO2 and PaCO2 often have dissimilar V/Q distributions. 6

Recognize that disproportionate dyspnea relative to pulmonary function tests suggests elevated dead space, as seen in pulmonary embolism or pulmonary vascular disease. 5