Respiratory System

For a fixed quantity of gas at constant temperature, pressure × volume is constant (P1V1 = P2V2). Air moves down a pressure gradient between the atmosphere and the alveoli, and alveolar pressure changes only because thoracic volume changes.

Inspiration (active): the diaphragm contracts and descends 1–2 cm in quiet breathing (up to ≈10 cm in deep breathing); external intercostals elevate the ribs (pump-handle movement of upper ribs increases the anteroposterior diameter; bucket-handle movement of lower ribs increases the transverse diameter). Intrapleural pressure falls from ≈ −5 to ≈ −8 cmH2O, the lungs expand, and alveolar pressure becomes ≈ −1 cmH2O, so ≈500 mL of air flows in. Expiration (quiet): passive elastic recoil; alveolar pressure rises to ≈ +1 cmH2O. Forced expiration recruits the abdominal wall muscles (rectus abdominis, obliques, transversus abdominis) and internal intercostals; intrapleural pressure becomes positive and can compress airways (dynamic airway compression — the basis of the effort-independent part of the flow–volume loop).

Transpulmonary pressure (alveolar − intrapleural) is the distending pressure of the lung. Accessory muscles of inspiration (sternocleidomastoid, scalenes, pectoralis minor and major, serratus anterior) are recruited in exercise and respiratory distress.

Four volumes (typical young adult male): tidal volume (TV) ≈500 mL, inspiratory reserve volume (IRV) ≈3000 mL, expiratory reserve volume (ERV) ≈1100–1200 mL and residual volume (RV) ≈1200 mL. Capacities are sums of volumes: inspiratory capacity (IC = TV + IRV ≈3500 mL), functional residual capacity (FRC = ERV + RV ≈2300–2400 mL), vital capacity (VC = IRV + TV + ERV ≈4600–4800 mL) and total lung capacity (TLC ≈5800–6000 mL). Values are ≈20–25% lower in women and vary with height, age and ethnicity.

Spirometry cannot measure RV, so FRC and TLC require helium dilution, nitrogen washout or body plethysmography. FRC is the equilibrium volume at which inward lung recoil exactly balances outward chest-wall recoil. FEV1/FVC is normally ≈0.75–0.8; < 0.7 indicates obstruction. In obstruction RV, FRC and TLC rise (air trapping, hyperinflation); in restriction all volumes fall proportionally.

Compliance (C = ΔV/ΔP) of the lungs is ≈200 mL/cmH2O; chest wall ≈200 mL/cmH2O; combined respiratory system ≈100 mL/cmH2O. Compliance is increased in emphysema (loss of elastin) and old age, and decreased in pulmonary fibrosis, oedema, ARDS and neonatal surfactant deficiency. About two-thirds of lung elastic recoil comes from surface tension at the air–liquid interface rather than from elastic fibres (saline-filled lungs inflate far more easily).

Law of Laplace: P = 2T/r. Without surfactant, small alveoli (small r) would have higher collapsing pressures and empty into larger ones. Surfactant (DPPC-rich, from type II pneumocytes) lowers surface tension, more so in smaller alveoli where it is more concentrated, stabilising alveoli of different sizes, increasing compliance, reducing the work of breathing and keeping alveoli dry.

Airway resistance follows Poiseuille's law (R ∝ 1/r⁴). Most resistance lies in the medium-sized bronchi (≈generations 2–7); small airways contribute little because of their huge combined cross-sectional area — hence early small-airway disease is "silent". Resistance falls with lung volume (radial traction) and is altered by bronchial smooth muscle tone (parasympathetic M3 → constriction; β2 agonism → dilation).

Gas transfer across the blood–gas barrier obeys Fick's law: V̇gas ∝ (A × D × ΔP)/T, where A is surface area (≈70 m²), T is thickness (≈0.5 µm), ΔP is the partial-pressure gradient and D the diffusion constant (∝ solubility/√molecular weight). CO2 diffuses ≈20 times faster than O2 because of its far greater solubility, so CO2 transfer is rarely diffusion-limited.

Partial pressures (Dalton's law): dry air PO2 ≈160 mmHg (0.21 × 760); humidified tracheal air ≈150 mmHg (0.21 × [760 − 47]); alveolar PAO2 ≈100–104 mmHg (alveolar gas equation PAO2 = PIO2 − PaCO2/0.8); mixed venous PO2 ≈40 mmHg and PCO2 ≈45–46 mmHg; alveolar and arterial PCO2 ≈40 mmHg. Red cells spend ≈0.75 s in a pulmonary capillary at rest but equilibrate in ≈0.25 s, leaving a large reserve for exercise. O2 uptake is normally perfusion-limited; it becomes diffusion-limited with thickened membranes (fibrosis), at altitude and in strenuous exercise. Diffusing capacity is measured with carbon monoxide (DLCO), which is reduced in emphysema, fibrosis and pulmonary vascular disease.

Arterial O2 content CaO2 = (1.34 × Hb × SaO2) + (0.003 × PaO2) ≈ 20 mL O2/dL; ≈98.5% is bound to haemoglobin and ≈1.5% dissolved. Delivery (cardiac output × CaO2) is ≈1000 mL/min against a consumption of ≈250 mL/min (extraction ≈25%); mixed venous saturation ≈75%.

The oxyhaemoglobin dissociation curve is sigmoid because of cooperative binding (deoxy T state → oxy R state). Landmarks: PO2 100 mmHg → ≈97–98%; 60 mmHg → ≈90% (the "shoulder": below this, saturation falls steeply); 40 mmHg → ≈75% (mixed venous); P50 ≈26–27 mmHg. Right shift (lower affinity, enhanced unloading in tissues): ↑PCO2, ↑H+ (Bohr effect), ↑temperature, ↑2,3-BPG (altitude, anaemia, chronic hypoxia), exercise. Left shift (higher affinity): fetal haemoglobin (binds 2,3-BPG poorly), carbon monoxide, methaemoglobin, alkalosis, hypothermia, stored blood (depleted 2,3-BPG). Carbon monoxide binds Hb ≈200–250 times more avidly than O2, reduces O2 content and shifts the curve left; PaO2 and standard pulse oximetry may be falsely reassuring.

CO2 is carried in three forms: bicarbonate (≈70%), carbamino compounds with haemoglobin and other proteins (≈20–23%) and dissolved CO2 (≈7–10%). In systemic capillaries CO2 enters erythrocytes, where carbonic anhydrase catalyses CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3−. H+ is buffered by deoxyhaemoglobin, and HCO3− leaves the cell in exchange for Cl− through the band 3 anion exchanger (AE1) — the chloride (Hamburger) shift. The process reverses in the lungs.

The Haldane effect: deoxygenated haemoglobin carries more CO2 (better H+ buffer, more carbamino formation), so oxygenation of blood in the lungs actively unloads CO2. The Bohr effect is its mirror image — CO2 and H+ reduce Hb affinity for O2 in the tissues. Because PCO2 is the main driver of ventilation, arterial PCO2 is the best single index of alveolar ventilation (PaCO2 ∝ V̇CO2/V̇A).

Overall alveolar ventilation (≈4.2 L/min) and pulmonary blood flow (≈5 L/min) give a V/Q ratio of ≈0.8. In the upright lung both ventilation and perfusion increase towards the base, but perfusion increases more steeply, so V/Q is ≈3 at the apex and ≈0.6 at the base; apical alveoli therefore have a higher PO2 (≈130 mmHg) — one reason reactivation tuberculosis favours the apices. West zones: zone 1 (PA > Pa > Pv; no flow — only in pathology such as haemorrhage or positive-pressure ventilation), zone 2 (Pa > PA > Pv; "waterfall") and zone 3 (Pa > Pv > PA; continuous flow).

Extremes: dead space (V/Q = ∞; e.g. pulmonary embolism) and shunt (V/Q = 0; e.g. atelectasis, consolidation, ARDS, intracardiac right-to-left shunt). Hypoxaemia due to shunt corrects poorly with 100% O2. Hypoxic pulmonary vasoconstriction — unique to the pulmonary circulation — diverts blood away from poorly ventilated alveoli; when generalised (altitude, COPD) it causes pulmonary hypertension and cor pulmonale.

Medulla: the dorsal respiratory group (in the nucleus of the solitary tract) is mainly inspiratory and integrates afferents from CN IX and X; the ventral respiratory group contains the pre-Bötzinger complex (the rhythm generator) and neurons for forced inspiration and expiration. Pons: the pontine respiratory group (formerly "pneumotaxic centre", upper pons) limits inspiration and fine-tunes rate; the "apneustic centre" (lower pons) prolongs inspiration. Voluntary control bypasses the brainstem via corticospinal fibres.

Central chemoreceptors on the ventral medullary surface respond to H+ in CSF generated from CO2 that crosses the blood–brain barrier; they provide ≈70–80% of the ventilatory response to CO2 and do not respond to hypoxia. Peripheral chemoreceptors (carotid bodies → CN IX; aortic bodies → CN X) respond to ↓PaO2 (mainly < 60 mmHg), ↑PaCO2 and ↓pH (carotid). Mechanoreceptors: pulmonary stretch receptors (Hering–Breuer inflation reflex, vagal; important in neonates), irritant receptors (cough, bronchoconstriction) and juxtacapillary (J) receptors (rapid shallow breathing in pulmonary oedema). Normal ventilation rises ≈2–3 L/min for each 1 mmHg increase in PaCO2.

Chronic airway inflammation with reversible bronchoconstriction, airway hyperresponsiveness and mucus plugging. Typically type 2 (Th2) inflammation: IL-4 (IgE class switching), IL-5 (eosinophils), IL-13 (mucus); mast-cell mediators (histamine, leukotrienes) cause the early phase and eosinophil-rich inflammation the late phase. Wheeze, cough worse at night, chest tightness; triggers include allergens, exercise, cold air, NSAIDs/aspirin and β-blockers. Spirometry: obstructive, with ≥12% and ≥200 mL improvement in FEV1 after a bronchodilator; raised FeNO and blood eosinophils support the diagnosis. Sputum may show Curschmann spirals and Charcot–Leyden crystals. Treatment: inhaled corticosteroid-containing regimens (ICS–formoterol), β2 agonists, LTRAs, biologics (anti-IL-5, anti-IgE). Severe attack: inability to complete sentences, silent chest, pulsus paradoxus; a normal or rising PaCO2 in an acute attack signals exhaustion.

Persistent, poorly reversible airflow limitation (post-bronchodilator FEV1/FVC < 0.7), mainly from tobacco smoke (also biomass fuel, occupational dusts). Components: chronic bronchitis (productive cough ≥3 months in each of 2 consecutive years; mucous gland hyperplasia with Reid index > 0.4) and emphysema (destruction of alveolar walls distal to terminal bronchioles — centriacinar, upper-lobe predominant, in smokers; panacinar, lower-lobe, in α1-antitrypsin deficiency). Physiology: loss of elastic recoil, ↑compliance, dynamic airway collapse, air trapping (↑RV, FRC and TLC), ↓DLCO in emphysema, V/Q mismatch, hypercapnia and pulmonary hypertension (cor pulmonale). Smoking cessation and long-term oxygen therapy (in chronic hypoxaemia) are the interventions shown to improve survival. In CO2 retainers, oxygen is titrated to SpO2 ≈88–92%: excess O2 worsens hypercapnia mainly by releasing hypoxic vasoconstriction (worse V/Q) and via the Haldane effect.

Infection of the lung parenchyma with alveolar exudate (consolidation). Community-acquired: Streptococcus pneumoniae is the commonest cause; also Haemophilus influenzae, Moraxella (COPD), Staphylococcus aureus (post-influenza), Klebsiella (alcohol use; "currant-jelly" sputum) and "atypicals" (Mycoplasma, Legionella, Chlamydophila). Patterns: lobar (classically pneumococcal — congestion, red hepatisation, grey hepatisation, resolution), bronchopneumonia (patchy, around bronchioles) and interstitial (viral, atypical). Signs: fever, productive cough, pleuritic pain, dullness, bronchial breathing, crackles. Consolidation creates a shunt (V/Q ≈ 0), so hypoxaemia responds incompletely to oxygen. Severity scoring with CURB-65 (Confusion, Urea > 7 mmol/L, Respiratory rate ≥ 30, low Blood pressure, age ≥ 65).

Air in the pleural cavity breaks the pleural coupling and the lung recoils. Primary spontaneous — rupture of apical subpleural blebs in tall, thin young men (smoking increases risk); secondary — underlying lung disease (COPD, CF, TB, Pneumocystis); traumatic/iatrogenic. Signs: sudden pleuritic pain, dyspnoea, ↓breath sounds, hyperresonance. Tension pneumothorax — a one-way valve traps air, raising intrathoracic pressure, shifting the mediastinum to the opposite side (tracheal deviation away), impairing venous return → hypotension, tachycardia, distended neck veins; it is a clinical diagnosis treated by immediate needle decompression (2nd intercostal space midclavicular line, or 4th/5th space anterior to the mid-axillary line in adults) followed by a chest drain inserted in the "safe triangle", just above a rib to avoid the intercostal neurovascular bundle.

Excess fluid in the pleural space. Transudates (low protein) arise from altered Starling forces — heart failure (commonest overall), cirrhosis, nephrotic syndrome, hypoalbuminaemia. Exudates arise from increased capillary/pleural permeability — pneumonia (parapneumonic effusion, empyema), malignancy, TB, PE, rheumatoid arthritis. Light's criteria (exudate if any): pleural/serum protein > 0.5; pleural/serum LDH > 0.6; pleural LDH > ⅔ of the upper limit of normal serum LDH. Signs: stony dullness, ↓breath sounds, ↓tactile fremitus. On an erect PA chest radiograph ≈200–500 mL is needed to blunt the costophrenic angle (the fluid first fills the costodiaphragmatic recess); ultrasound detects much smaller volumes and guides thoracentesis.

Usually thrombus from deep leg or pelvic veins (Virchow's triad: stasis, endothelial injury, hypercoagulability) lodging in the pulmonary arteries. Embolised segments are ventilated but not perfused (alveolar dead space), while redistribution of blood flow and atelectasis produce V/Q mismatch and hypoxaemia; hyperventilation causes hypocapnia and respiratory alkalosis. Presentation: sudden dyspnoea, pleuritic chest pain, tachycardia, haemoptysis; massive PE causes acute right ventricular failure, hypotension and syncope. ECG most often shows sinus tachycardia (the S1Q3T3 pattern is uncommon). Diagnosis: clinical probability (Wells), D-dimer to exclude in low-probability patients, CT pulmonary angiography (or V/Q scan). Treatment: anticoagulation; thrombolysis for haemodynamically unstable PE.

Leading cause of cancer death worldwide; ≈85% of cases are linked to smoking. Non-small-cell (≈85%): adenocarcinoma (most common type overall and in never-smokers, peripheral; EGFR, ALK, KRAS drivers), squamous cell carcinoma (central, cavitating, PTHrP → hypercalcaemia) and large-cell carcinoma. Small-cell (≈15%): central, neuroendocrine, rapidly growing and early metastasising; paraneoplastic SIADH, ectopic ACTH and Lambert–Eaton syndrome. Local effects: haemoptysis, collapse/obstructive pneumonia, effusion, left recurrent laryngeal nerve palsy (hoarseness), phrenic nerve palsy (raised hemidiaphragm), SVC obstruction. A Pancoast (superior sulcus) tumour at the apex can invade the lower brachial plexus (C8–T1; hand weakness, ulnar-side pain) and sympathetic chain (Horner's syndrome: ptosis, miosis, anhidrosis).

Autosomal recessive disorder of the CFTR gene (chromosome 7q31), which encodes a cAMP-regulated chloride/bicarbonate channel; F508del (misfolded protein degraded in the ER) is the commonest variant. Reduced Cl− secretion and increased ENaC-mediated Na+ absorption dehydrate the airway surface liquid, so mucociliary clearance fails, thick mucus accumulates and recurrent infection (S. aureus, later Pseudomonas aeruginosa) leads to bronchiectasis and respiratory failure. Other features: exocrine pancreatic insufficiency, meconium ileus, biliary cirrhosis, CF-related diabetes, male infertility (congenital bilateral absence of the vas deferens) and salty sweat. Diagnosis: newborn screening (immunoreactive trypsinogen), sweat chloride ≥ 60 mmol/L, genetic testing. CFTR modulators (e.g. elexacaftor–tezacaftor–ivacaftor) have transformed the outlook.

Infection with Mycobacterium tuberculosis, spread by airborne droplet nuclei. Primary TB: a subpleural Ghon focus (typically lower part of an upper lobe or upper part of a lower lobe) plus hilar lymph node involvement forms the Ghon complex; usually contained by cell-mediated immunity (caseating granulomas with Langhans giant cells) as latent infection. Post-primary (reactivation) TB favours the apices (high V/Q, high PO2, relatively poor lymphatic clearance), causing cavitation, haemoptysis, night sweats, weight loss and fever. Miliary spread occurs in the immunocompromised. Diagnosis: sputum smear (acid-fast bacilli), culture, nucleic-acid amplification; latent infection by tuberculin skin test or interferon-γ release assay. Standard drug-sensitive treatment: rifampicin, isoniazid, pyrazinamide and ethambutol for 2 months, then rifampicin and isoniazid for 4 months.

Neonatal (infant) respiratory distress syndrome is caused by surfactant deficiency in preterm infants (risk rises sharply below ≈32–34 weeks; also maternal diabetes — fetal insulin inhibits surfactant synthesis — and elective caesarean section). High surface tension causes progressive atelectasis, ↓compliance, shunt and hypoxaemia: grunting, nasal flaring, recession; chest radiograph shows a "ground-glass" appearance with air bronchograms. Prevention: antenatal corticosteroids to the mother; treatment: CPAP and exogenous surfactant. Fetal lung maturity was assessed by the amniotic lecithin:sphingomyelin ratio (≥ 2 = mature).

Acute respiratory distress syndrome in adults follows sepsis, pneumonia, aspiration, trauma or pancreatitis: diffuse alveolar damage with protein-rich oedema and hyaline membranes, bilateral opacities not explained by heart failure, and severe hypoxaemia (classified by PaO2/FiO2). Management is supportive with lung-protective ventilation (low tidal volume ≈6 mL/kg predicted body weight) and prone positioning.