Respiratory Physiology
1. What this chapter covers, and how NEET PG actually tests it
Respiratory questions usually arrive as a blood gas, a spirometry result, or a description of a patient who is hypoxic.
All three are answered by a small number of tools.
The alveolar-arterial gradient separates the causes of hypoxaemia into two groups, and the response to supplemental oxygen then splits the second group again. Two calculations therefore replace a list of five diagnoses.
Spirometry works the same way. The ratio of forced expiratory volume to forced vital capacity divides obstruction from restriction before any other value is considered.
The recurring theme is that lung disease is either a problem of getting air in and out, or a problem of matching air to blood — and almost every question is asking which.
This chapter covers mechanics and lung volumes, ventilation-perfusion matching, gas transport, and the control of breathing with the causes of hypoxaemia.
| In scope here | Deliberately out of scope |
|---|---|
| Lung volumes, compliance, surfactant, spirometric patterns | Detailed pulmonary function test protocols |
| Regional ventilation and perfusion, dead space, shunt | Ventilator management (see Anesthesia) |
| Oxygen and carbon dioxide carriage, curve shifts, carbon monoxide | Asthma and COPD pharmacotherapy (see Pharmacology) |
| Chemoreceptors, altitude adaptation, hypoxaemia mechanisms | Radiological interpretation (see Radiology) |
2. Mechanics and lung volumes
2.1 The volumes, and which ones spirometry cannot measure
Four volumes combine into four capacities, and one distinction carries most of the exam weight.
| Quantity | Composition | Approximate value |
|---|---|---|
| Tidal volume | — | 500 mL |
| Residual volume | — | 1200 mL |
| Inspiratory capacity | Tidal + inspiratory reserve | 3500 mL |
| Functional residual capacity | Expiratory reserve + residual | 2400 mL |
| Vital capacity | Inspiratory capacity + expiratory reserve | 4600 mL |
| Total lung capacity | Vital capacity + residual | 5800 mL |
Spirometry measures airflow, so it cannot measure any volume that never leaves the lung.
Residual volume is therefore unmeasurable by spirometry, and so is any capacity containing it — functional residual capacity and total lung capacity.
Those require helium dilution or body plethysmography instead, and questions ask this directly.
2.2 Functional residual capacity is a balance point
At the end of a quiet expiration, the lung's inward elastic recoil is exactly balanced by the chest wall's outward recoil.
Functional residual capacity is that equilibrium volume, which is why it is altered by anything changing either recoil force.
Emphysema destroys elastic tissue, so inward recoil weakens and functional residual capacity rises.
Fibrosis stiffens the lung, so inward recoil strengthens and it falls.
2.3 Compliance and surfactant
Compliance is the change in volume per unit change in pressure, so a compliant lung is easy to inflate.
Compliance is increased in emphysema — a floppy lung inflates easily but recoils poorly — and decreased in fibrosis, pulmonary oedema and respiratory distress syndrome.
Most of the pressure needed to inflate a lung overcomes surface tension at the air-liquid interface, not tissue elasticity.
Surfactant, secreted by type II pneumocytes and consisting chiefly of dipalmitoylphosphatidylcholine, reduces that surface tension.
Its second function matters more and is more often tested. Laplace's law states that the collapsing pressure of a sphere is:
So for a given surface tension, a small alveolus generates a higher collapsing pressure than a large one and would empty into its neighbour.
Surfactant prevents this because its molecules are more concentrated in a small alveolus, so it lowers tension disproportionately where the radius is smallest.
Alveolar stability is therefore not a fixed property but an actively balanced one.
Surfactant production begins around 24 to 28 weeks and is usually adequate by about 35 weeks, and a lecithin to sphingomyelin ratio above 2 indicates maturity.
2.4 Obstructive versus restrictive patterns
The distinction is made on the ratio, not the absolute values.
Obstructive disease reduces the ratio of forced expiratory volume in one second to forced vital capacity, conventionally below 0.7, because airflow is limited disproportionately. Total lung capacity and residual volume rise from air trapping.
Restrictive disease reduces both volumes together, so the ratio is normal or even raised, while total lung capacity falls.
The ratio tells you which pattern; the total lung capacity confirms it.
3. Ventilation-perfusion matching
3.1 Why the apex and base behave differently
Gravity distributes both ventilation and perfusion unevenly, but not to the same degree.
Both ventilation and perfusion are greater at the base than at the apex, but perfusion varies far more.
The consequence is that the ratio is higher at the apex, around 3, and lower at the base, around 0.6, with a whole-lung average near 0.8.
A high ratio means relatively more air than blood, so the apex has a higher alveolar oxygen tension and a lower carbon dioxide tension.
This is why post-primary tuberculosis favours the apices — the organism is a strict aerobe and the apex is the most oxygen-rich region of the lung.
The base, being better perfused, is where an embolus and most consolidations preferentially land.
3.2 Dead space and shunt as the two extremes
The ratio has two limiting values, and each names a clinical entity.
Dead space is ventilation without perfusion, so the ratio is infinite. Alveolar gas resembles inspired air.
Shunt is perfusion without ventilation, so the ratio is zero. Blood leaves resembling mixed venous blood.
Anatomical dead space, the conducting airways, is roughly 150 mL. Physiological dead space adds any alveoli that are ventilated but not perfused, as in pulmonary embolism.
3.3 The oxygen test that separates them
Giving 100% oxygen distinguishes shunt from ventilation-perfusion mismatch, and this is the most useful single discriminator in the chapter.
In ventilation-perfusion mismatch, poorly ventilated units still receive some air, so raising the inspired oxygen concentration raises their alveolar oxygen tension and hypoxaemia improves.
In a true shunt, blood bypasses ventilated alveoli entirely. No amount of inspired oxygen reaches it, so hypoxaemia is refractory.
The reason the correction is incomplete rather than partial deserves a moment. Because the oxyhaemoglobin curve is flat at its top, blood from well-ventilated units cannot carry extra oxygen to compensate for the shunted blood, however high the inspired concentration.
Refractory hypoxaemia on high-flow oxygen therefore means shunt, as in consolidation, atelectasis or an intracardiac right-to-left shunt.
4. Gas transport
4.1 The oxyhaemoglobin dissociation curve
The curve is sigmoid because haemoglobin binds oxygen cooperatively — each molecule bound increases the affinity of the remaining sites.
The P50, the tension at which haemoglobin is half saturated, is normally about 27 mmHg.
The flat upper portion is a safety margin: arterial oxygen tension can fall considerably before saturation drops meaningfully, which is why saturation is an insensitive early warning.
The steep lower portion is the working range in tissues, where a small fall in tension releases a large amount of oxygen.
A right shift means reduced affinity and easier unloading, and its causes are all markers of metabolically active tissue: raised carbon dioxide, acidity, temperature and 2,3-bisphosphoglycerate.
The logic is that tissue which is working hard signals its own need, and the haemoglobin passing through responds by releasing more oxygen. The effect of acidity and carbon dioxide is the Bohr effect.
A left shift means tighter binding and reluctant unloading: fetal haemoglobin, carbon monoxide, methaemoglobin, hypothermia, alkalosis and stored blood depleted of 2,3-bisphosphoglycerate.
Fetal haemoglobin's left shift is functional rather than pathological, allowing it to extract oxygen from maternal blood across the placenta.
4.2 Carbon monoxide and methaemoglobin
Carbon monoxide binds haemoglobin with roughly 240 times the affinity of oxygen.
Two separate harms follow, and the second is often forgotten. It reduces the oxygen-carrying capacity, and it shifts the remaining curve to the left, so the oxygen that is carried is released less readily.
The critical clinical point is diagnostic. Dissolved oxygen is unaffected, so the arterial oxygen tension is normal, and standard pulse oximetry cannot distinguish carboxyhaemoglobin from oxyhaemoglobin.
A normal saturation reading therefore does not exclude carbon monoxide poisoning, and co-oximetry is required.
Methaemoglobin contains iron in the ferric state, which cannot bind oxygen at all. It produces chocolate-brown blood, a saturation reading that sits near 85% regardless of the true value, and responds to methylene blue.
4.3 Carbon dioxide carriage
Carbon dioxide is carried in three forms, and the proportions are examinable.
About 70% travels as bicarbonate, formed in the red cell by carbonic anhydrase and exported in exchange for chloride — the chloride shift.
About 23% is carried as carbamino compounds bound to haemoglobin, and about 7% is dissolved.
The Haldane effect is the counterpart of the Bohr effect: deoxygenated haemoglobin carries carbon dioxide more readily.
The two effects work together in a single circuit. In tissues, oxygen unloading improves carbon dioxide uptake; in the lung, oxygen loading drives carbon dioxide off.
5. Control of breathing and hypoxaemia
5.1 Two sets of chemoreceptors
Central chemoreceptors in the medulla respond to hydrogen ion concentration in the cerebrospinal fluid.
They do not sense carbon dioxide directly. Carbon dioxide crosses the blood-brain barrier, is hydrated to carbonic acid, and the resulting hydrogen ions are what the receptors detect.
Because hydrogen ions cross the barrier poorly, an acute metabolic acidosis stimulates them far less than an equivalent respiratory acidosis — a mechanistic point that questions use.
Central chemoreceptors provide the dominant minute-to-minute drive.
Peripheral chemoreceptors in the carotid and aortic bodies respond chiefly to a fall in arterial oxygen tension below about 60 mmHg, and also to acidity and carbon dioxide.
The carotid bodies signal through the glossopharyngeal nerve and the aortic bodies through the vagus.
Their oxygen threshold explains the shape of the response: ventilation barely changes until oxygen tension falls onto the steep part of the dissociation curve, then rises sharply.
5.2 The alveolar gas equation and the A-a gradient
Alveolar oxygen tension is calculated as:
The alveolar-arterial gradient is the difference between this calculated value and the measured arterial tension, normally about 5 to 15 mmHg and rising with age.
The gradient answers one question: is the problem inside the lung or outside it?
5.3 Five causes of hypoxaemia, separated by two tests
| Cause | A-a gradient | Corrects with oxygen |
|---|---|---|
| Hypoventilation | Normal | Yes |
| Low inspired oxygen (altitude) | Normal | Yes |
| Diffusion impairment | Raised | Yes |
| Ventilation-perfusion mismatch | Raised | Yes |
| Shunt | Raised | No |
A normal gradient means the lung is working correctly and the problem lies elsewhere — either too little air is moving, or the air itself contains too little oxygen.
A raised gradient localises the fault to gas exchange, and the oxygen response then isolates shunt from the rest.
Two tests therefore resolve all five causes, which is far faster than recalling the list.
5.4 Adaptation to altitude
Low inspired oxygen at altitude produces hypoxaemia with a normal gradient, since the lung itself is healthy.
The immediate response is hyperventilation driven by peripheral chemoreceptors, which produces a respiratory alkalosis.
That alkalosis is itself a brake, since it suppresses the central chemoreceptors and limits further hyperventilation.
Renal compensation over the following days excretes bicarbonate, correcting the pH and releasing the brake — which is why acclimatisation improves over about a week.
Longer-term changes include a rise in 2,3-bisphosphoglycerate, which right-shifts the curve to improve tissue unloading, and erythropoietin-driven polycythaemia.
Hypoxic pulmonary vasoconstriction, which normally diverts blood away from poorly ventilated regions, becomes global at altitude and can cause pulmonary hypertension.
Worked clinical vignettes
Q1. A patient with dense consolidation remains hypoxic despite high-flow oxygen. What is the mechanism, and why does oxygen fail?
Pick an option to check your answer.
Show explanation
Solution. Consolidated lung is perfused but not ventilated, so the ratio is zero — a true shunt.
Inspired oxygen never reaches that blood. The remaining well-ventilated units are already near full saturation on the flat part of the curve, so they cannot compensate by carrying more.
Refractory hypoxaemia on high-flow oxygen is the signature of shunt. Answer: (b).
Q2. A patient rescued from a house fire has a normal arterial oxygen tension and a pulse oximetry reading of 98%, but is confused and has a headache. What is the explanation?
Pick an option to check your answer.
Show explanation
Solution. Carbon monoxide binds haemoglobin with about 240 times the affinity of oxygen, reducing carrying capacity while leaving dissolved oxygen — and therefore the measured tension — normal.
Standard pulse oximetry reads carboxyhaemoglobin as though it were oxyhaemoglobin, producing a falsely reassuring value. Co-oximetry is required.
Carbon monoxide also left-shifts the remaining curve, worsening delivery further. Answer: (b).
Q3. Why does post-primary tuberculosis preferentially affect the lung apices?
Pick an option to check your answer.
Show explanation
Solution. Both ventilation and perfusion are greater at the base, but perfusion varies far more with gravity, so the ratio is highest at the apex — around 3, versus about 0.6 at the base.
A high ratio means relatively more air than blood, giving the apex the highest alveolar oxygen tension.
Mycobacterium tuberculosis is a strict aerobe, so it thrives there. Answer: (b).
7. Common exam traps
- Trying to measure residual volume by spirometry. Spirometry cannot measure any volume that never leaves the lung, so residual volume, functional residual capacity and total lung capacity all require dilution or plethysmography.
- Assuming higher perfusion at the apex. Both ventilation and perfusion are greater at the base; it is the ratio that is higher at the apex.
- Expecting shunt to correct with oxygen. It does not, and that is the defining test separating it from ventilation-perfusion mismatch.
- Trusting pulse oximetry in carbon monoxide poisoning. It reads carboxyhaemoglobin as oxyhaemoglobin, so the saturation is falsely normal.
- Forgetting carbon monoxide's second effect. It also left-shifts the curve, impairing release of the oxygen that is still carried.
- Reversing the curve shifts. Raised carbon dioxide, acid, temperature and 2,3-bisphosphoglycerate all shift right and improve unloading.
- Saying central chemoreceptors sense carbon dioxide. They sense hydrogen ions in cerebrospinal fluid, which is why acute metabolic acidosis stimulates them poorly.
- Ignoring the A-a gradient in a hypoxic patient. A normal gradient means the lung is intact and the cause is hypoventilation or low inspired oxygen.
Summary
- Spirometry cannot measure residual volume, and therefore cannot measure functional residual capacity or total lung capacity; these need helium dilution or plethysmography.
- Functional residual capacity is the volume at which lung inward recoil balances chest wall outward recoil, so it rises in emphysema and falls in fibrosis.
- Compliance rises in emphysema and falls in fibrosis, pulmonary oedema and respiratory distress syndrome.
- Surfactant from type II pneumocytes reduces surface tension and, by Laplace's law, stabilises small alveoli by lowering tension disproportionately where the radius is smallest.
- Obstruction lowers the forced expiratory ratio and raises total lung capacity; restriction preserves or raises the ratio while lowering total lung capacity.
- Ventilation and perfusion are both greater at the base, but perfusion varies more, so the ratio is highest at the apex — which is why tuberculosis favours it.
- Dead space is ventilation without perfusion and shunt is perfusion without ventilation, the two limiting values of the ratio.
- Ventilation-perfusion mismatch corrects with supplemental oxygen while true shunt does not, because the flat top of the curve prevents compensation.
- The oxyhaemoglobin curve is sigmoid from cooperative binding, with a P50 near 27 mmHg, a flat safety margin above and a steep working range below.
- Right shifts from carbon dioxide, acid, temperature and 2,3-bisphosphoglycerate improve unloading where metabolism is active; the acid and carbon dioxide component is the Bohr effect.
- Carbon monoxide reduces carrying capacity and left-shifts the curve while leaving oxygen tension and pulse oximetry falsely normal.
- Carbon dioxide travels about 70% as bicarbonate with a chloride shift, 23% as carbamino compounds and 7% dissolved, and the Haldane effect lets deoxygenated haemoglobin carry more.
- Central chemoreceptors respond to cerebrospinal fluid hydrogen ions rather than carbon dioxide directly, which is why metabolic acidosis stimulates them less.
- Peripheral chemoreceptors respond mainly below an oxygen tension of about 60 mmHg, signalling through the glossopharyngeal and vagus nerves.
- A normal alveolar-arterial gradient indicates hypoventilation or low inspired oxygen; a raised gradient indicates a gas exchange problem, and the oxygen response then isolates shunt.
- Altitude causes hypoxaemia with a normal gradient, hyperventilation with respiratory alkalosis, renal bicarbonate excretion over days, and later a rise in 2,3-bisphosphoglycerate with polycythaemia.
