Respiratory physiology
Lung mechanics, gas exchange and transport, and the control of breathing
Breathing depends on the balance of elastic forces in lung and chest wall, on matching ventilation to blood flow, and on chemoreceptor feedback that holds arterial PCO₂ steady. CPSP asks for dead space and alveolar ventilation sums, for the mechanism of each kind of hypoxaemia, and for the normal respiratory changes of pregnancy that every radiologist and obstetrician meets.
Volumes and elastic forces
- Functional residual capacity (FRC) is the volume left after a quiet expiration, where the inward recoil of the lung equals the outward recoil of the chest wall (the breath-hold position for chest CT).
- Compliance = change in volume ÷ change in pressure. Low in fibrosis (stiff lungs, honeycombing on HRCT). High in emphysema: alveolar walls are destroyed, recoil is lost, and poorly tethered airways collapse on expiration (air trapping on expiratory CT, raised RV and RV/TLC, pursed-lip breathing).
- In the upright lung, basal alveoli start smaller and sit on the steeper part of the compliance curve, so they receive more ventilation per unit volume.
Surfactant
- Made by type II pneumocytes (dipalmitoyl lecithin). By Laplace's law, P = 2T/r, small alveoli would empty into large ones; surfactant lowers surface tension most in small alveoli and keeps them open.
- Fetal cortisol is the main stimulus to maturation (antenatal betamethasone acts on type II cells). Fetal insulin delays it, so babies of diabetic mothers are at risk even near term. A lecithin:sphingomyelin ratio of 2 or more indicates maturity.
- Respiratory distress syndrome: small-volume lungs with uniform ground-glass shadowing and air bronchograms.
Airway resistance
- Most resistance is in the medium-sized bronchi; small airways have a huge total cross-section and contribute little, so early small airway disease leaves FEV₁ normal.
- Turbulent resistance depends on gas density: helium–oxygen eases upper airway narrowing.
- A fixed tracheal stenosis (after intubation) flattens both inspiratory and expiratory limbs of the flow–volume loop.
Ventilation and dead space
- Alveolar ventilation = (tidal volume − dead space) × rate. 500 mL, 150 mL, 12/min gives 4.2 L/min; rapid shallow breathing of 250 mL at 32/min with the same dead space gives only 3.2 L/min, so PaCO₂ rises despite a normal minute volume (rib fractures, pleurisy).
- Neck extension lengthens the airway and increases anatomical dead space.
- PaCO₂ ∝ CO₂ production ÷ alveolar ventilation.
- Hypoventilation (opioid overdose) raises PaCO₂ and lowers PaO₂ with a normal A–a gradient.
Ventilation–perfusion matching
| V/Q | Example | Effect |
|---|---|---|
| Zero (shunt) | Collapsed or consolidated lobe | Hypoxaemia that does not correct with 100% oxygen |
| Low | COPD, over-perfused lung beside an embolus | Hypoxaemia that does improve with oxygen |
| Infinite (dead space) | Segment beyond a pulmonary embolus | Alveolar PCO₂ falls towards zero; end-tidal CO₂ falls well below PaCO₂ |
- The apex has the highest V/Q and highest alveolar PO₂, favouring reactivated tuberculosis.
- Hypoxic pulmonary vasoconstriction diverts blood away from collapsed lung. High-flow oxygen in COPD releases it, worsening V/Q matching and raising PaCO₂.
- West zone 1 (alveolar pressure above arterial) appears with haemorrhage plus positive-pressure ventilation, adding dead space.
- In fibrosis, desaturation on exercise reflects a shortened red cell transit time across a thickened membrane.
Oxygen and carbon dioxide transport
- Right shift of the dissociation curve (raised P50): high PCO₂, H⁺, temperature and 2,3-DPG (Bohr effect in exercising muscle). Maternal 2,3-DPG rises in late pregnancy, releasing more oxygen at the placenta; fetal haemoglobin binds 2,3-DPG poorly and sits to the left.
- Carbon monoxide occupies haem and shifts the curve left; globus pallidus necrosis is typical.
- CO₂ is carried mainly as bicarbonate (about 70%), then carbamino compounds and dissolved gas. Haldane effect: oxygenated haemoglobin binds less CO₂ and H⁺, so CO₂ unloads in the lungs.
- Hyperventilation alkalosis lowers ionised calcium (perioral tingling, carpopedal spasm).
Control of breathing
| Structure | Role |
|---|---|
| Pre-Bötzinger complex | Generates the basic rhythm |
| Dorsal respiratory group | Inspiratory drive |
| Ventral respiratory group | Active mainly in forced breathing (active expiration) |
| Pontine groups | Smooth the pattern |
| Central chemoreceptors | CSF H⁺ from PaCO₂: main minute-to-minute control |
| Peripheral chemoreceptors (carotid bodies) | Hypoxaemia; bilateral removal abolishes the hypoxic ventilatory response |
| J receptors | Interstitial fluid in pulmonary oedema: rapid shallow breathing |
- At altitude the first adaptation is hyperventilation driven by hypoxaemia.
- A paralysed hemidiaphragm (phrenic nerve invaded by a hilar mass) moves upwards on sniffing, sucked up by negative intrathoracic pressure.
- In ARDS, ventilating with 6 mL/kg predicted body weight limits overdistension of the remaining normal alveoli.
Pregnancy
| Measure | Change |
|---|---|
| Tidal volume | Up 30–40% (minute ventilation up about 40%; 15 × 700 mL = 10.5 L/min) |
| Respiratory rate | Unchanged |
| FRC | Down about 20% (diaphragm elevated) |
| FEV₁/FVC | Unchanged |
| Lung compliance | Unchanged; chest wall compliance reduced |
| Airway resistance | Falls (progesterone relaxes bronchi) |
| PaCO₂ | About 4.0 kPa (30 mmHg); bicarbonate about 20 mmol/L (compensated respiratory alkalosis) |
- Progesterone sensitises the respiratory centre to CO₂ (also in the luteal phase). Ventilation rises more than CO₂ production, so PaCO₂ falls.
- Small FRC with high ventilation: faster pre-oxygenation, but faster desaturation.
- In labour, hyperventilation with contractions lowers PaCO₂ below the apnoeic threshold, so she stops breathing between contractions; hypocapnia also constricts uterine vessels.
- In suspected pulmonary embolism with a normal chest X-ray, a perfusion scan gives a lower breast dose than CT pulmonary angiography.
Remember Shunt does not respond to oxygen; dead space does not exchange CO₂.
Exam trap Rapid shallow breathing can raise PaCO₂ even with a normal minute volume, because dead space takes a larger share of each breath.
Exam trap In pregnancy, a PaCO₂ of 5.3 kPa (40 mmHg) is already abnormal and suggests ventilatory failure.
Test yourself on this topic
5 of the 62 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
Six months after three weeks of intubation in ICU, a 38-year-old woman has stridor on exertion from a short, rigid, circumferential tracheal stenosis 2 cm below the cords. Which flow-volume loop pattern is expected?
Answer: Flattening of both inspiratory and expiratory limbs
A fixed narrowing does not change its calibre with the pressure changes of breathing. Flow is therefore limited to the same maximum in both inspiration and expiration, giving a box-shaped loop with flat plateaus on both limbs. A variable extrathoracic lesion flattens only the inspiratory limb, and a variable intrathoracic lesion flattens only expiration. A scooped expiratory curve is typical of small airway obstruction such as COPD.
Fixed airway obstruction
- Rigid stenosis: calibre does not change
- Both limbs flattened
- Variable extrathoracic: inspiration flat
- Variable intrathoracic: expiration flat
Remember Fixed narrowing, flat top and flat bottom.
Exam trap In a variable lesion, the flat limb is the one in which pressures push the airway inwards.
Why the other options are wrong
- Scooped expiratory limb with normal inspiration This pattern indicates diffuse small-airway disease.
- Flattened inspiratory limb only Seen with a variable extrathoracic obstruction.
- Flattened expiratory limb only Seen with a variable intrathoracic obstruction.
- Small loop of normal shape Seen in restrictive lung disease.
In pulmonary capillaries, blood unloads CO2 more readily than its PCO2 gradient alone would predict, because haemoglobin is being oxygenated as it passes the alveoli. Which property of haemoglobin explains this?
Answer: Oxygenated haemoglobin binds less CO2 and H+
The Haldane effect means that oxygenation of haemoglobin lowers its capacity to carry CO2, both as carbamino compounds and by buffering hydrogen ions. In the lungs, as haemoglobin takes up oxygen it releases CO2 and H+, which helps CO2 leave the blood. In the tissues the reverse occurs: deoxygenated haemoglobin binds more CO2 and buffers more H+. CO2 binds to globin amino groups, not to the haem iron.
Haldane effect
- Oxy-Hb carries less CO2
- Deoxy-Hb is a better buffer
- Lungs: CO2 released
- CO2 binds globin, not haem
Remember Oxygen pushes CO2 off haemoglobin in the lungs.
Exam trap Carbon monoxide competes for haem; carbon dioxide does not.
Why the other options are wrong
- Oxygenated haemoglobin binds more 2,3-BPG 2,3-BPG binds deoxygenated haemoglobin, not oxygenated.
- Deoxygenated haemoglobin is a weaker buffer Deoxygenated haemoglobin is the better buffer.
- Carbonic anhydrase is activated by oxygen Carbonic anhydrase is not switched on by oxygen.
- CO2 competes with oxygen for the haem iron CO2 binds globin chains, not the haem iron.
A family in Quetta is found drowsy after sleeping with a gas heater in a closed room. One adult later develops parkinsonism from bilateral necrosis of the globus pallidus. Apart from occupying haem binding sites, what change in oxygen handling worsens tissue hypoxia?
Answer: Left shift of the dissociation curve
Carbon monoxide binds haemoglobin about 200 to 250 times more avidly than oxygen, lowering oxygen content. It also raises the oxygen affinity of the remaining haem groups, shifting the dissociation curve to the left. The oxygen that is carried is therefore released less readily to tissues. Arterial PO2 is usually normal, which is why pulse oximetry and PaO2 can mislead. The globus pallidus is very sensitive to this hypoxia.
Carbon monoxide
- Binds Hb over 200x more than O2
- Oxygen content falls
- Curve shifts left: poor unloading
- PaO2 normal; globus pallidus necrosis
Remember CO steals haem sites and makes the rest hold on tighter.
Exam trap A normal PaO2 or SpO2 does not exclude CO poisoning.
Why the other options are wrong
- Fall in arterial PO2 PaO2 is usually normal because dissolved oxygen is unaffected.
- Right shift of the dissociation curve CO shifts the curve the opposite way.
- Less oxygen dissolved in plasma Dissolved oxygen depends on PO2, which is normal.
- Thickening of the alveolar membrane CO does not damage the membrane.
A 55-year-old man has complete collapse of the left lower lobe from a mucus plug. His PaO2 is lower than before but much better than would be expected if the lobe were still fully perfused. What limits the fall in PaO2?
Answer: Diverting flow away from the collapsed lobe
Low alveolar PO2 constricts the small pulmonary arteries supplying that region, a response unique to the pulmonary circulation. In a collapsed lobe this hypoxic vasoconstriction diverts blood to ventilated lung, reducing the shunt fraction and limiting the fall in PaO2. Vasodilator drugs and some anaesthetic agents can blunt the response and worsen oxygenation. When hypoxia is widespread, as in COPD or high altitude, the same reflex raises pulmonary artery pressure.
Hypoxic vasoconstriction
- Low alveolar PO2 constricts arterioles
- Unique to the lung
- Reduces shunt in collapse
- Global hypoxia: pulmonary hypertension
Remember The lung sends blood where the oxygen is.
Exam trap Systemic arterioles dilate in hypoxia; pulmonary arterioles do the opposite.
Why the other options are wrong
- Collateral ventilation through pores of Kohn Collateral channels cannot ventilate a lobe collapsed by plugging.
- Rise in cardiac output More cardiac output does not correct a shunt and can increase it.
- Rightward shift of the dissociation curve A right shift does not improve oxygen loading in the lungs.
- Increased diffusion in the other lobes Diffusion in normal lung is already complete at rest.
A 58-year-old woman with interstitial pulmonary fibrosis has an oxygen saturation of 95% at rest, but it falls to 84% when she walks briskly. Which mechanism best explains the desaturation on exercise?
Answer: Short transit time across thick membrane
Normally blood equilibrates with alveolar oxygen within about a third of the 0.75 s it spends in the pulmonary capillary, leaving a large reserve. A thickened alveolar membrane slows diffusion (Fick's law), so equilibration takes longer but may still finish at rest. During exercise, cardiac output rises and transit time shortens, and blood leaves the capillary before equilibration is complete. This is why fibrotic lungs desaturate on exertion and why the DLCO is low.
Diffusion limitation
- Thick membrane: slower diffusion
- Rest: still equilibrates
- Exercise: short transit time
- Low DLCO on testing
Remember Fibrosis shows itself when the blood is in a hurry.
Exam trap Normal resting saturation does not exclude significant interstitial lung disease.
Why the other options are wrong
- Rise in anatomical dead space Anatomical dead space does not change with fibrosis.
- Bronchospasm induced by exercise Fibrosis does not cause exercise bronchospasm.
- Fall in inspired oxygen tension Inspired PO2 is unchanged.
- Greater oxygen affinity of haemoglobin Exercise lowers affinity through the Bohr effect.
Where this sits in the CPSP syllabus
- Diagnostic Radiology, Paper 2: Cardiovascular, respiratory and renal physiology, Lung mechanics, gas transport and regulation of breathing
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