Respiratory Physiology and Pathophysiology
Domain 1 - Respiratory Physiology and Pathophysiology
This domain tests the physiology behind common thoracic findings: respiratory mechanics, gas exchange, acid–base balance and oxygen delivery. Board vignettes usually ask you to interpret an arterial blood gas, distinguish hypoventilation from shunt, or explain why a patient remains hypoxaemic despite supplemental oxygen. Answers must connect a calculation to a management step, not just quote a formula.
Core rules
- Compliance is Δvolume/Δpressure; it falls in fibrosis, oedema and atelectasis and rises in emphysema. Resistance rises in asthma and COPD and is proportional to 1/r⁴ by Poiseuille law.
- Alveolar oxygen tension: PAO₂ = FiO₂(Patm − 47) − PaCO₂/R, with R about 0.8. The A–a gradient is normally about age/4 + 4 mmHg and widens with V/Q mismatch, shunt or diffusion limitation.
- Hypoventilation raises PaCO₂ by about 1 mmHg for every 1 mmHg fall in PAO₂; the A–a gradient remains normal. Shunt does not correct with 100% oxygen because blood bypasses ventilated alveoli.
- Oxygen delivery: DO₂ = cardiac output × CaO₂ × 10, where CaO₂ = 1.34 × Hb × SaO₂ + 0.003 × PaO₂. Anaemia and low output can cause tissue hypoxia despite a normal PaO₂.
- Compensation is never complete. Acute respiratory acidosis raises HCO₃⁻ by about 1 mmol/L per 10 mmHg PaCO₂ above 40; chronic raises it by 3–4 mmol/L per 10 mmHg.
Worked example
A 60-year-old man with COPD has pH 7.28, PaCO₂ 65 mmHg, HCO₃⁻ 29 mmol/L and PaO₂ 50 mmHg on room air. Expected acute HCO₃⁻ is 24 + 2.5 = 26.5 mmol/L; expected chronic is about 34 mmol/L. The measured 29 lies between, so this is acute-on-chronic respiratory acidosis. PAO₂ = 0.21(760 − 47) − 65/0.8 = 68 mmHg, giving an A–a gradient of 18 mmHg. The mild gradient increase indicates V/Q mismatch added to hypoventilation. Management is controlled oxygen to 88–92%, bronchodilators and NIV if pH remains below 7.35 with hypercapnia.
Traps that cost marks
- Calling every low PaO₂ a shunt; if it corrects easily with oxygen, shunt is not the main mechanism.
- Forgetting that the A–a gradient rises with age and is normal in pure hypoventilation.
- Assuming a normal pH excludes severe chronic hypercapnia; chronic compensation can nearly normalise pH.
- Using actual body weight for physiological calculations where predicted body weight is required.
Key points
- A normal A–a gradient with hypercapnia points to hypoventilation.
- Shunt is refractory to supplemental oxygen; V/Q mismatch usually improves.
- Oxygen delivery depends on haemoglobin, saturation and cardiac output.
- Chronic hypercapnia produces greater bicarbonate retention than acute hypercapnia.
- Compliance falls in restrictive disease and rises in emphysema.