In one breath
Ventilation tests say how much air moves; these tests say whether that air actually reaches blood. Gas exchange is judged by how evenly ventilation and perfusion are matched (normal ratio 0.8, checked by nitrogen washout), by diffusing capacity, and by arterial blood gases (PaO₂ 90–95 mmHg, PaCO₂ 36–44 mmHg). The circulation is judged by pulmonary artery and wedge pressures through a Swan–Ganz catheter, with PVR calculated from them. All of it converges on one question: why is this patient’s PaO₂ low — and the A–aO₂ gradient, normally 5–15 mmHg, is what answers it.
Builds on: Gas exchange in the lungs · Ventilation–perfusion ratio · Pulmonary circulation · Leads to: Hypoxia · Oxygen therapy
Ventilation–perfusion relationship
- Even in health, inspired air is not spread evenly through the lungs. Standing up, resting ventilation per unit lung volume is highest at the bases and least at the apices, and that gap narrows lying down and during exercise.
- In disease the unevenness worsens, giving hypoventilated and hyperventilated areas, and that non-uniform distribution lowers arterial O₂ tension.
- How it is measured — nitrogen washout. After the subject has breathed O₂ for 7 minutes, an alveolar sample normally contains under 2.5% nitrogen. The higher the nitrogen, the more uneven the distribution of inspired gas.
- Perfusion is uneven too in the erect posture, because of gravity. The normal ventilation-to-perfusion ratio is 0.8 (see Ventilation–perfusion ratio).
- Perfusion becomes far more uneven in pulmonary embolism and in diseases that destroy lung tissue.
- Arterial blood gas tensions are set mainly by how ventilation matches perfusion, and disturbing the ratio affects PaO₂ more than PaCO₂.
Diffusion
- Diffusion is the physical movement of a gas across a membrane from higher to lower partial pressure. In the lung O₂ moves from alveoli into pulmonary capillaries to join hemoglobin, and CO₂ moves the other way (see Oxygen transport, Carbon dioxide transport).
- The diffusing capacity of CO₂ is 20 times that of O₂, so diffusion problems usually do not cause CO₂ retention — they show up as hypoxemia.
- Arterial blood gas measurement is essential in any assessment of lung function:
| Gas tension | Normal value |
|---|---|
| PaO₂ | 90–95 mmHg |
| PaCO₂ | 36–44 mmHg |
Hypoxemia
Hypoxemia is a fall in PaO₂. It arises in four situations:
- Reduced inspired PO₂.
- Hypoventilation.
- Shunting — desaturated blood effectively bypasses oxygenation at the alveolar–capillary level; cyanotic congenital heart disease is the usual example.
- Ventilation–perfusion mismatching — as in COPD and asthma.
Conditions that change diffusing capacity
Diffusing capacity falls for two kinds of reason:
- Less total alveolar–capillary surface area: emphysema; pulmonary embolism; thrombosis of pulmonary capillaries; after surgical removal of lung tissue.
- A defective, thickened alveolar–capillary membrane: asbestosis; sarcoidosis; progressive systemic sclerosis; collagen diseases; interstitial edema; interstitial fibrosis; diffuse metastatic lesions of the lung.
Diffusing capacity rises in exercise.
Two ways to lose diffusing capacity
Both lists reduce the same thing, so viva answers blur them. Area diseases delete lung units (emphysema, embolism, capillary thrombosis, resection). Membrane diseases keep the units but thicken the barrier (asbestosis, sarcoidosis, sclerosis, collagen disease, interstitial edema and fibrosis, metastases). Name the group, then the examples.
Gas sampling and analysis
Sampling alveolar air
- Haldane–Priestley method. The subject blows out as hard as he can down a long narrow tube, about 3 feet long and 2.5 cm wide, then closes off the mouthpiece with his tongue. A sample is drawn from near the mouthpiece through a side tube into a sampling tube. The logic: the last air out of the lung is alveolar air.
- Rahn–Otis method. Continuous sampling. The subject breathes through a mouthpiece carrying one inspiratory and one expiratory valve, which collects an end-tidal sample, and the samples pass into gas analyzers.
Sampling expired air
A Douglas bag is used. A two-way valve on the bag is connected to the subject’s mouth; atmospheric air is inhaled, and the expired air goes into the bag.
Respiratory gas analysis
Three samples are compared in gas analyzers, which give the partial pressures of O₂, CO₂ and N₂:
| Sample | Where it comes from |
|---|---|
| Inspired air | Atmosphere |
| Mixed expired air | Douglas bag |
| Alveolar air | Haldane–Priestley method |
Blood gas analysis
- O₂ content of blood: Haldane’s gas analyzer, on collected venous blood.
- O₂ carrying capacity: the Van Slyke gasometric method.
- PCO₂: also measured with gasometers.
- Of all these tests, blood gas analysis detects the smallest change in lung function, and it is especially sensitive to diffusing capacity — which is why it settles an unclear case.
Worth knowing, though not in your pages: in modern practice all of this is done in minutes by an automated blood gas analyzer using electrodes — a Clark electrode for PO₂, a Severinghaus electrode for PCO₂, and a glass electrode for pH. The Haldane and Van Slyke methods are the classical, examinable ones.
Whose measurement this is: Heinrich Gustav Magnus (1802–1870) was the first to measure blood gases quantitatively, and he worked out how much O₂ and how much CO₂ arterial blood and venous blood each carry.
Assessment of pulmonary circulation
Assessing lung function is incomplete without the circulation. Measuring pressures, vascular resistance, blood volume and the distribution of flow across the pulmonary and systemic circuits reveals venoarterial shunts, vascular occlusion and loss of pulmonary capillary volume.
| Feature of the pulmonary circuit | Value or behaviour |
|---|---|
| Flow it accommodates | 5 L/min (right ventricular output) |
| Vessel walls | Thin; resistance far below systemic |
| Mean pulmonary artery pressure | 15 mmHg |
| Pressure when upright | Lowest at the apex, highest at the bases |
Measuring flow and pressure
-
The assessment rests on pulmonary vascular pressures plus cardiac output, and is usually done in an intensive care unit with invasive monitoring.
-
A flow-directed pulmonary arterial (Swan–Ganz) catheter measures the pulmonary arterial and pulmonary capillary wedge pressures directly.
-
Cardiac output is measured by thermodilution.
-
Pulmonary vascular resistance is then calculated:
PVR = 80 × (PAP − PCW) ÷ CO
where PAP is mean pulmonary arterial pressure in mmHg, PCW is pulmonary capillary wedge pressure in mmHg, and CO is cardiac output in L/min.
-
Normal PVR is 50–150 dynes·s/cm⁵.
Four mechanisms that raise PVR
- Pulmonary vasoconstriction — pulmonary arteries and arterioles constrict in response to alveolar hypoxia.
- Pulmonary thromboembolism — intraluminal thrombi cut the luminal cross-sectional area.
- Vascular hypertrophy — smooth muscle proliferates in the vessel wall and narrows the lumen.
- Pulmonary injury — small vessels are destroyed as scar tissue forms and alveolar walls are lost, cutting the total cross-sectional area of the vascular bed.
A rise in PVR raises pulmonary arterial pressure, which in turn lowers right ventricular output.
Conditions that raise PVR
- Heart disease: anything that raises left atrial pressure, such as mitral stenosis.
- Lung disease causing chronic pulmonary hypoxemia: COPD; interstitial lung disease; chest wall disease such as kyphoscoliosis; obesity hypoventilation; sleep apnea syndrome.
- Disease of the pulmonary vessels: recurrent pulmonary embolism; scleroderma, which occludes small pulmonary arteries and arterioles.
Worth knowing, though not in your pages: your book prints “left arterial pressure” for mitral stenosis. It means left atrial pressure — mitral stenosis dams blood behind the valve in the left atrium, and the pressure passes back into the pulmonary veins.
Respiratory causes of hypoxemia
Hypoxemia has both respiratory and non-respiratory causes, and in adults the respiratory ones are much the commonest.
- Non-respiratory causes: anemia; carbon monoxide poisoning; reduced inspired O₂ tension, as at high altitude.
The A–aO₂ gradient
- Hemoglobin leaves the pulmonary capillaries 100% saturated, so end-capillary PO₂ equals alveolar PO₂. But the blood arriving in the left atrium through the pulmonary veins has a lower PO₂ than end-capillary blood, so systemic arterial blood averages a PaO₂ of about 95 mmHg with Hb 98% saturated.
- The alveolar–arterial O₂ gradient is that loss: A–aO₂ gradient = PAO₂ − PaO₂.
- With alveolar PO₂ normally 100–102 mmHg and arterial PO₂ 85–95 mmHg, the normal gradient is 5–15 mmHg.
The five respiratory causes
| Cause | A–aO₂ gradient | The giveaway |
|---|---|---|
| Regional hypoventilation | Raised | Commonest of all |
| Large pulmonary clot | Raised | Over-perfusion elsewhere |
| Shunt | Raised | 100% O₂ does not correct it |
| Generalized hypoventilation | Normal | PaCO₂ up, pH down |
| Diffusion block | Raised | Least common; often pulmonary edema |
- Regional hypoventilation is the commonest physiological reason, and reflects a local ventilation–perfusion imbalance behind a partly obstructed airway. Some of the blood crossing the lung is not fully oxygenated, so venous admixture rises (a small amount of admixture is normal). These patients have a low ventilation–perfusion ratio, a high A–aO₂ gradient, a low PO₂ and a low O₂ content.
- Occlusion of a major pulmonary artery by a large blood clot creates a regional low ventilation–perfusion ratio the other way round: the cardiac output is forced into the rest of the lung, which is then over-perfused relative to its ventilation, and venous admixture rises again.
- Shunt — the next commonest cause — is either cardiac, a right-to-left shunt inside the heart, or intrapulmonary, from obstruction by a foreign body or a tumour. It gives a high A–aO₂ gradient with low PO₂ and low O₂. Breathing 100% O₂ does not correct the low arterial PO₂, because the enriched gas never meets the shunted blood.
- Generalized hypoventilation is a common cause, and occurs whenever alveolar ventilation as a whole is low: COPD such as emphysema, or respiration depressed by head injury or drug overdose (for example morphine). As ventilation falls, arterial PCO₂ rises and pH falls. Its distinguishing feature is a normal A–aO₂ gradient — the hypoxemia is entirely due to the underventilation. Treated best by mechanical ventilation with room air, not by extra O₂.
- Diffusion block is the infrequent cause, and arises when gas has further to travel across the alveolar–capillary membrane, or when that membrane becomes less permeable. Your book characterises it by a low PaO₂, a high A–aO₂ gradient and a high PaCO₂. Pulmonary edema is among its commonest causes.
The one cause with a normal gradient
Every respiratory cause of hypoxemia raises the A–aO₂ gradient except generalized hypoventilation. That single fact is what the gradient is for: normal gradient + high PaCO₂ = hypoventilation, so ventilate the patient with room air. Raised gradient = the lung itself is at fault (regional hypoventilation, clot, shunt or diffusion block).
Shunt vs the rest: the 100% O₂ test
Giving 100% O₂ improves hypoxemia from regional hypoventilation and from diffusion block, but not from a shunt, because shunted blood never touches alveolar gas. This is the bedside test that separates them, and the reason a cyanosed newborn with a right-to-left shunt stays cyanosed on O₂ (see Oxygen therapy).
Worth knowing, though not in your pages: the book’s “high PaCO₂” for diffusion block sits oddly against its own statement that CO₂ diffuses 20 times better than O₂, so diffusion problems do not cause CO₂ retention. Quote the book’s high PaCO₂ if asked from this chapter, but know that in a pure diffusion defect PaCO₂ is usually normal or low, because the hypoxemia drives hyperventilation and CO₂ still crosses easily.
Exam-answer skeleton: "Hypoxemia: its causes, and how the A–aO₂ gradient tells them apart" (short note)
- Define hypoxemia as a fall in PaO₂, and give normal PaO₂ (90–95 mmHg) and PaCO₂ (36–44 mmHg).
- Classify the causes into respiratory and non-respiratory, naming anemia, CO poisoning and low inspired PO₂ as non-respiratory.
- Define the A–aO₂ gradient, with alveolar PO₂ 100–102, arterial 85–95, gradient 5–15 mmHg.
- List the five respiratory causes: regional hypoventilation, large pulmonary clot, shunt, generalized hypoventilation, diffusion block.
- Give the discriminator — every one of them raises the gradient except generalized hypoventilation, which also raises PaCO₂ and lowers pH.
- Add the 100% O₂ test: a shunt does not respond, because the O₂ never reaches the shunted blood.
- Close with treatment in one line: ventilate the hypoventilating patient on room air; correct the shunt or the underlying lung disease.