Ventilation-perfusion ratio
Ventilation–perfusion (V/Q), diffusion, shunt and gas exchange in the lung
V/Q mismatch is the commonest cause of hypoxaemia, and true shunt is the one cause that extra oxygen cannot fix. Learn Fick's law, the gas laws, apex versus base V/Q, the A–a gradient, TLCO and KCO.
The gas laws behind respiratory physiology
| Law | Statement | Where it matters |
|---|---|---|
| Boyle | At constant temperature, pressure × volume is constant | Breathing itself; body plethysmography |
| Charles | At constant pressure, volume is proportional to absolute temperature | Gas volumes corrected to body temperature (BTPS) |
| Dalton | Total pressure is the sum of the partial pressures | PO₂ = fraction × (barometric − water vapour pressure) |
| Henry | Dissolved gas is proportional to its partial pressure (× solubility) | Dissolved O₂ is 0.003 mL/100 mL/mmHg; decompression sickness |
| Graham | Diffusion rate is inversely proportional to the square root of molecular weight | Smaller, lighter molecules diffuse faster |
| Fick | Diffusion rate ∝ area × partial pressure difference × solubility ÷ thickness | Gas transfer across the alveolar membrane |
Diffusion across the alveolar membrane
- By Fick's law, gas transfer rises with surface area (about 70 m²), the partial pressure gradient and the gas's solubility, and falls with membrane thickness (normally under 0.5 µm).
- CO₂ diffuses about 20 times faster than O₂ because it is far more soluble, even though its molecule is heavier and its gradient smaller. So diffusion problems lower PaO₂ long before PaCO₂ rises.
- The diffusing capacity for oxygen is about 21 mL/min/mmHg at rest and rises about threefold in exercise, by recruiting closed capillaries and matching V/Q better.
- Perfusion versus diffusion limitation: at rest, blood equilibrates with alveolar O₂ in about the first third of its 0.75 s in the capillary, so O₂ transfer is normally perfusion-limited (more uptake needs more blood flow). In fibrosis, or in heavy exercise at altitude, equilibration may not finish: transfer becomes diffusion-limited. Carbon monoxide binds haemoglobin so avidly that its blood partial pressure stays near zero, so its uptake is purely diffusion-limited; this is why CO is used to measure the transfer factor.
Transfer factor (TLCO) and transfer coefficient (KCO)
TLCO is the total CO uptake; KCO = TLCO ÷ alveolar volume, the uptake per unit of lung that was reached.
| Pattern | TLCO | KCO | Meaning |
|---|---|---|---|
| Pulmonary fibrosis | ↓ | ↓ | Thick, damaged membrane |
| Emphysema | ↓ | ↓ | Lost alveolar surface and capillaries |
| Pulmonary embolism, pulmonary hypertension | ↓ | ↓ | Lost capillary blood |
| Chest wall or neuromuscular restriction (kyphoscoliosis, obesity), pneumonectomy | ↓ | Normal or ↑ | Small but normal lungs; blood is concentrated in the lung that is there |
| Anaemia | ↓ | ↓ | Less haemoglobin to bind CO; correct for Hb |
| Polycythaemia, alveolar haemorrhage, asthma | ↑ | ↑ | More haemoglobin or blood in the lung |
A low TLCO alone cannot separate lung from chest wall disease; always look at KCO.
Ventilation and perfusion in the upright lung
Both ventilation and perfusion are greater at the base, because of gravity, but perfusion falls much more steeply towards the apex.
| Region | Ventilation | Perfusion | V/Q | Alveolar PO₂ | Alveolar PCO₂ |
|---|---|---|---|---|---|
| Apex | Low | Very low | High (about 3) | Highest | Lowest |
| Base | High | Very high | Low (about 0.6) | Lower | Higher |
| Whole lung | About 0.8 (4 L/min alveolar ventilation, 5 L/min blood flow) |
The apex's high PO₂ is one explanation for why reactivated tuberculosis favours the upper lobes. Lying flat or exercising makes distribution more even.
The two extremes
| Problem | V/Q | Examples | Effect of 100% oxygen |
|---|---|---|---|
| Dead space: ventilation without perfusion | ∞ (high) | Pulmonary embolism, low cardiac output, emphysema | No effect on the dead space itself |
| Shunt: perfusion without ventilation | 0 | Consolidated lobe, collapse, ARDS, TRALI, intracardiac right-to-left shunt, pulmonary AV malformation | Little rise in PaO₂ |
- A true shunt does not respond to oxygen because the shunted blood never meets it; adding oxygen to normal alveoli barely helps because their blood is already nearly saturated.
- A physiological (normal) shunt of about 2% of cardiac output exists in health: bronchial venous blood draining into pulmonary veins and Thebesian veins opening into the left heart. This is why arterial PO₂ is slightly lower than alveolar.
- Physiological dead space = anatomical + alveolar dead space; measured by the Bohr equation.
- Pulmonary embolism: the blocked segment is dead space (high V/Q), but the hypoxaemia comes mainly from blood being diverted to the rest of the lung, creating low V/Q units, plus some shunt. A stable patient with likely PE (Wells score) needs a CT pulmonary angiogram; massive PE with shock is thrombolysed without waiting.
- TRALI (transfusion-related acute lung injury) appears within 6 hours of a plasma-rich product: donor antibodies activate recipient neutrophils in lung capillaries, causing non-cardiogenic pulmonary oedema with fever, hypotension, bilateral infiltrates, hypoxaemia and a normal JVP (unlike fluid overload, which raises it). Flooded alveoli act as shunt.
- Hepatopulmonary syndrome (cirrhosis): nitric oxide and other vasodilators dilate intrapulmonary capillaries, so O₂ cannot diffuse to the centre of the wide stream of blood (diffusion–perfusion defect), plus true AV shunts. The dilated vessels are mainly at the bases, so saturation falls on sitting or standing (orthodeoxia) and dyspnoea worsens upright (platypnoea). Contrast echo shows bubbles in the left atrium a few beats after the right (intrapulmonary, not intracardiac). Unlike a fixed shunt, it partly improves with high-flow oxygen.
Causes of hypoxaemia and the A–a gradient
The alveolar–arterial (A–a) gradient compares alveolar O₂ (from the alveolar gas equation: PAO₂ = FiO₂ × (Patm − PH₂O) − PaCO₂/0.8) with arterial O₂. Normal is under about 2 kPa (15 mmHg) in young adults and rises with age.
| Cause | A–a gradient | Corrects with O₂? |
|---|---|---|
| Hypoventilation (opioids, neuromuscular weakness) | Normal | Yes |
| Low inspired O₂ (altitude) | Normal | Yes |
| V/Q mismatch (asthma, COPD, PE, pneumonia) | Raised | Yes |
| Diffusion limitation (fibrosis) | Raised | Yes |
| Shunt | Raised | No |
V/Q mismatch is the commonest cause of hypoxaemia, and low V/Q units are the usual culprit in COPD and asthma. Anaemia and CO poisoning lower O₂ content but leave PaO₂ normal.
Local matching
- Hypoxic pulmonary vasoconstriction reduces blood flow to poorly ventilated alveoli.
- Low alveolar CO₂ in under-perfused regions causes local bronchoconstriction, reducing wasted ventilation.
Remember Fick: area times gradient over thickness; shunt ignores oxygen; apex has high V/Q and the highest PO₂.
Exam trap Hypoventilation and altitude cause hypoxaemia with a normal A–a gradient.
Exam trap In kyphoscoliosis TLCO is low but KCO is normal or high: the lungs are small, not diseased.
How FCPS asks about this
- Commonest cause of hypoxaemia: V/Q mismatch (mostly low V/Q units).
- Cause not corrected by 100% oxygen: true shunt (V/Q = 0); physiological shunt is about 2% of cardiac output.
- V/Q at the apex: high (about 3), with the highest PO₂, which favours TB; base has low V/Q.
- V/Q increased (dead space): pulmonary embolism, low cardiac output.
- Why CO₂ diffuses faster than O₂: about 20 times greater solubility; CO is used to measure diffusing capacity.
- Charles' versus Boyle's law: Charles at constant pressure (V ∝ T); Boyle at constant temperature (PV constant).
- Cirrhosis with orthodeoxia and delayed bubbles in the left atrium: hepatopulmonary syndrome, dilated intrapulmonary capillaries.
Test yourself on this topic
5 of the 36 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A man found after a heroin overdose breathing 5 times per minute on room air has PaO₂ 7.5 kPa and PaCO₂ 9.0 kPa. His alveolar PO₂ is calculated as 8.5 kPa. What do these results show?
Answer: Hypoventilation; normal A–a gradient
The alveolar gas equation gives PAO₂ ≈ PiO₂ − PaCO₂/0.8. On air at sea level, PiO₂ is about 20 kPa, so with PaCO₂ 9 kPa, PAO₂ ≈ 20 − 11.25 ≈ 8.7 kPa. The A–a gradient is 8.5 − 7.5 = 1 kPa, which is normal (under about 2 kPa). The lungs are exchanging gas normally; there is simply too little fresh air entering the alveoli, so CO₂ builds up and displaces oxygen. Hypoventilation and low inspired oxygen (altitude) are the two causes of hypoxaemia with a normal A–a gradient, and both correct easily with supplemental oxygen. A widened gradient points to a problem in the lung itself: V/Q mismatch, diffusion limitation or shunt. If aspiration pneumonia develops later, the gradient will widen.
A–a gradient
- PAO₂ ≈ PiO₂ − PaCO₂/0.8
- Normal gradient: hypoventilation, altitude
- Raised gradient: V/Q mismatch, diffusion, shunt
- Shunt: no response to O₂
Remember A normal gradient means healthy lungs that are not being used.
Exam trap High CO₂ with low O₂ and a normal gradient means a ventilation problem, not a lung problem.
Why the other options are wrong
- Right-to-left shunt A shunt widens the gradient and does not correct with oxygen.
- Diffusion impairment Diffusion problems widen the gradient.
- V/Q mismatch; wide A–a gradient The gradient here is normal.
- Low inspired oxygen He is breathing room air at a normal inspired oxygen.
A 55-year-old woman with severe kyphoscoliosis is breathless. FEV₁ and FVC are both reduced with a ratio of 0.85, and TLC is low. TLCO is low, but the transfer coefficient (KCO) is raised. Which of the following best explains this pattern?
Answer: Small but normal lungs inside a stiff chest wall
In chest wall or neuromuscular restriction the lungs themselves are normal but cannot expand fully. Total gas transfer (TLCO) falls because alveolar volume is small, but per litre of lung the uptake of CO is normal or high, because the pulmonary capillary blood volume is spread through less expanded lung, so KCO rises. In fibrosis both TLCO and KCO are usually low because the alveolar–capillary membrane itself is damaged. Emphysema, emboli and anaemia all lower KCO.
Extrapulmonary restriction
- Low TLC, ratio normal or high
- TLCO low from small alveolar volume
- KCO normal or raised
- Fibrosis: KCO low
Remember Low TLCO with a high KCO: look at the chest wall.
Exam trap Always look at KCO as well as TLCO; a low TLCO alone cannot separate lung disease from chest wall disease.
Why the other options are wrong
- Thickened alveolar walls from fibrosis Fibrosis lowers KCO as well as TLCO.
- Loss of alveolar capillary bed in emphysema Emphysema lowers KCO.
- Pulmonary emboli blocking capillaries Emboli reduce capillary blood volume and lower KCO.
- Anaemia lowering uptake of carbon monoxide Anaemia lowers KCO.
A woman 10 days after a hip replacement has sudden breathlessness and pleuritic pain. Wells score suggests PE is likely. She is haemodynamically stable with normal kidney function. What is the next investigation?
Answer: CT pulmonary angiogram
When PE is likely on Wells score, CT pulmonary angiography (CTPA) is the diagnostic test, with anticoagulation started while waiting if there is a delay. D-dimer is used only when PE is unlikely, and it is often raised after surgery. A V/Q scan is an alternative in pregnancy, contrast allergy or kidney impairment. Echocardiography helps in unstable patients.
Suspected PE
- PE likely: CTPA
- PE unlikely: D-dimer first
- Start anticoagulation if delay
- V/Q scan in pregnancy, CKD
Remember Likely PE: CTPA.
Exam trap Massive PE with shock needs thrombolysis without waiting for CT.
Why the other options are wrong
- D-dimer only Not useful when PE is likely or after surgery.
- Chest X-ray only to diagnose PE Cannot confirm PE.
- Echocardiogram first For unstable patients.
- Spirometry Not relevant.
For laparoscopic surgery in adults, at what pressure is the abdomen usually insufflated with CO₂?
Answer: 12–15 mmHg
Pneumoperitoneum is kept at about 12–15 mmHg. Higher pressures compress the IVC, reducing venous return and cardiac output, raise airway pressure, reduce renal blood flow and increase CO₂ absorption. CO₂ is used because it is very soluble, does not support combustion and is rapidly cleared, though its absorption raises end-tidal CO₂ and may cause acidosis.
Pneumoperitoneum
- Pressure 12–15 mmHg
- Gas: CO₂ (soluble, non-flammable)
- High pressure: less venous return
- Raises end-tidal CO₂
Remember Twelve to fifteen keeps the IVC open.
Exam trap Shoulder-tip pain after laparoscopy comes from residual CO₂ irritating the diaphragm.
Why the other options are wrong
- 25–30 mmHg Too high; harms circulation.
- 40 mmHg Far too high.
- 2–3 mmHg Too low to see.
- 5 cmH₂O Too low.
A man with idiopathic pulmonary fibrosis has reduced FVC and TLC with a normal FEV₁/FVC ratio. Which gas transfer finding is expected?
Answer: Reduced TLCO
Pulmonary fibrosis thickens the alveolar-capillary membrane and destroys capillaries, reducing gas transfer (TLCO, DLCO). Lung volumes are reduced (restrictive pattern) and the FEV₁/FVC ratio is normal or high. TLCO is also reduced in emphysema and pulmonary vascular disease, but raised in alveolar haemorrhage and polycythaemia.
Gas transfer
- Fibrosis: TLCO reduced
- Emphysema: TLCO reduced
- Haemorrhage: TLCO raised
- Restriction with low TLCO: lung disease
Remember Thick membrane, poor transfer.
Exam trap Anaemia lowers TLCO; correct for haemoglobin.
Why the other options are wrong
- Raised TLCO Seen in alveolar haemorrhage, polycythaemia.
- Normal TLCO Abnormal in fibrosis.
- Raised KCO only Not typical.
- TLCO cannot be measured It is routinely measured.
Where this sits in the CPSP syllabus
- Paper 1: Respiratory system, Ventilation-perfusion and gas exchange; diffusion
- Surgery & Allied, Paper 2: Respiratory system, Ventilation-perfusion and gas exchange; diffusion
- Medicine & Allied, Paper 2: Respiratory system, Ventilation-perfusion and gas exchange; diffusion