📘 Respiratory Physiology A Complete Reference for Medical Students · USMLE / Clinical Focus
1. Functional Anatomy of the Respiratory System
Conducting Zone vs. Respiratory Zone
- Conducting Zone: Trachea → Bronchi → Bronchioles → Terminal Bronchioles.
→ Function: Warms, humidifies, filters air. Anatomic dead space (~150 mL).
→ Histology: Cartilage + smooth muscle; ciliated pseudostratified columnar → simple cuboidal.
- Respiratory Zone: Respiratory Bronchioles → Alveolar Ducts → Alveolar Sacs.
→ Function: Gas exchange.
→ Histology: Thin simple squamous (Type I) and surfactant-producing Type II pneumocytes.
Pleura and Chest Wall
- Visceral pleura (lung surface) · Parietal pleura (thoracic cavity).
- Intrapleural pressure normally negative (~ -5 cm H₂O at rest), keeps lungs expanded.
Alveolar Cell Types
| Cell Type | Function | Clinical Relevance |
|---|
| Type I Pneumocyte | Thin barrier for diffusion (95% of surface) | Damaged in ARDS → pulmonary edema |
| Type II Pneumocyte | Produces surfactant (dipalmitoylphosphatidylcholine); progenitor | Deficiency → Neonatal RDS |
| Alveolar Macrophage | Phagocytosis | Hemosiderin-laden in heart failure ("heart failure cells") |
2. Mechanics of Breathing
Lung Volumes and Capacities
| Volume / Capacity | Definition | Normal Adult |
|---|
| Tidal Volume (TV) | Quiet breathing volume | ~500 mL |
| Inspiratory Reserve Volume (IRV) | Max air beyond TV | ~3000 mL |
| Expiratory Reserve Volume (ERV) | Max air exhaled beyond TV | ~1200 mL |
| Residual Volume (RV) | Air after maximal exhalation | ~1200 mL |
| Vital Capacity (VC) | TV + IRV + ERV | ~4700 mL |
| Total Lung Capacity (TLC) | VC + RV | ~5900 mL |
| Functional Residual Capacity (FRC) | ERV + RV (resting end‑exhalation) | ~2400 mL |
Key Spirometry measures TV, IRV, ERV, VC — cannot measure RV (helium dilution / plethysmography).
Pressure-Volume & Compliance
- Transpulmonary pressure (Ptp) = Palv − Ppl (distending force).
- Compliance (C) = ΔV / ΔP · normal ~200 mL/cm H₂O.
- ↑ Compliance: Emphysema (easy inflate, hard exhale). ↓ Compliance: Fibrosis, ARDS (stiff lung).
Surfactant & Laplace
- Law of Laplace: P = 2T/r → small alveoli would collapse. Surfactant reduces surface tension, prevents atelectasis.
Airway Resistance
- Poiseuille: R ∝ 1/r⁴. Primary resistance site: medium bronchi.
- Parasympathetic (M3) → bronchoconstriction; Sympathetic (β₂) → bronchodilation.
Flow-Volume Loops
| Pattern | Disease | Key Finding |
|---|
| Obstructive | COPD, Asthma | Scooped expiratory limb, ↓ FEV₁/FVC |
| Restrictive | ILD, Obesity | Tall narrow loop, ↓ FVC, normal/high ratio |
| Fixed obstruction | Tracheal stenosis | Flattening both limbs |
| Variable extrathoracic | Vocal cord paralysis | Flattened inspiratory limb |
| Variable intrathoracic | Tracheomalacia | Flattened expiratory limb |
3. Ventilation
- Minute Ventilation (V̇E) = TV × RR
- Alveolar Ventilation (V̇A) = (TV − Dead Space) × RR
- Dead Space: Anatomic (~150 mL) + Alveolar (ventilated but not perfused) = Physiologic dead space.
Bohr equation (physiologic dead space): Vᴅ / Vᴛ = (PaCO₂ − PᴇCO₂) / PaCO₂
Regional differences: Gravity → base has higher perfusion (V/Q < 1), apex higher ventilation (V/Q > 1).
4. Pulmonary Circulation
- Low-pressure, low-resistance (mean PA ~15 mmHg).
- Hypoxic Pulmonary Vasoconstriction (HPV): Low alveolar PO₂ → vasoconstriction (opposite of systemic). Redirects flow away from poorly ventilated areas.
- Chronic hypoxia → pulmonary hypertension, cor pulmonale.
West Zones
| Zone | Location | Pressure relation | Flow |
|---|
| Zone 1 | Apex (rare) | PA > Pa > Pv | No flow |
| Zone 2 | Mid-lung | Pa > PA > Pv | Intermittent (waterfall) |
| Zone 3 | Base | Pa > Pv > PA | Continuous |
5. Diffusion and Gas Exchange
Fick's law: V̇gas = (A × D × ΔP) / T
CO₂ diffuses ~20× faster than O₂ (higher solubility).
Diffusion Capacity (DLCO)
- Uses CO (diffusion-limited).
- ↓ DLCO: Emphysema, ILD, pulmonary vascular disease.
- ↑ DLCO: Alveolar hemorrhage, polycythemia, early CHF.
O₂ and CO₂ Transport
| Gas | Mechanism | Note |
|---|
| O₂ | Dissolved (1.5%) + Hb‑bound (98.5%) | O₂ content = (1.34 × Hb × SaO₂) + (0.003 × PaO₂) |
| CO₂ | Bicarbonate (70%), carbamino (23%), dissolved (7%) | Carbonic anhydrase in RBC |
O₂-Hb Dissociation Curve
- Sigmoidal; P₅₀ ~27 mmHg.
- Right shift (↓ affinity, ↑ unloading): ↑ Temp, ↑ CO₂, ↑ 2,3-DPG, ↓ pH.
💡 Mnemonic: CADET face Right — CO₂, Acid, DPG, Exercise, Temperature.
- Left shift (↑ affinity): ↓ Temp, ↓ CO₂, ↓ 2,3-DPG, ↑ pH, fetal Hb, CO poisoning, MetHb.
Haldane effect: Deoxygenated Hb binds CO₂ more avidly.
6. Ventilation‑Perfusion (V/Q) Relationships
- Normal V/Q ≈ 0.8 (V̇A ~4 L/min, Q̇ ~5 L/min).
| Abnormality | V/Q | Examples | ABG effect |
|---|
| Dead space (high V/Q) | >0.8 | PE, high PEEP | ↑ PaCO₂, ↓ PaO₂ |
| Shunt (low V/Q) | <0.8 | Pneumonia, atelectasis | ↓ PaO₂ (refractory to O₂) |
Alveolar gas equation: PAO₂ = FiO₂ × (Patm − 47) − (PaCO₂ / R) (R ≈ 0.8)
Simplified sea level: PAO₂ ≈ 150 − (PaCO₂ / 0.8)
A-a gradient = PAO₂ − PaO₂ · normal ≈ age/4 + 4. ↑ gradient → V/Q mismatch, shunt, diffusion defect. Normal gradient → hypoventilation, low FiO₂.
7. Control of Breathing
Brainstem Centers
| Center | Location | Function |
|---|
| Dorsal Respiratory Group (DRG) | Medulla (NTS) | Inspiratory rhythm, sensory input |
| Ventral Respiratory Group (VRG) | Medulla | Contains pre‑Bötzinger (pacemaker), active expiration |
| Pontine centers | Pons | Modulate rhythm (apneustic, pneumotaxic) |
| Pre‑Bötzinger complex | Rostral ventrolateral medulla | Primary central pattern generator |
Chemoreceptors
| Receptor | Location | Stimulus | Response |
|---|
| Central | Medulla (ventral surface) | ↑ PaCO₂ / ↓ CSF pH | ↑ Ventilation |
| Peripheral | Carotid (CN IX) & aortic bodies (CN X) | ↓ PaO₂ (<60 mmHg), ↑ PaCO₂, ↓ pH | ↑ Ventilation |
COPD & hypoxic drive: Chronic CO₂ retention blunts central response; peripheral hypoxic drive becomes dominant. Over‑oxygenation risks apnea.
- Hering‑Breuer reflex (stretch, prevents overinflation). J receptors (interstitium, rapid shallow breathing).
8. Acid‑Base Physiology in Respiration
| Disorder | Primary | Compensation | Expected formula |
|---|
| Respiratory acidosis | ↑ PaCO₂ | ↑ HCO₃⁻ (renal) | Acute: ↑1 mEq HCO₃ per 10 mmHg CO₂
Chronic: ↑4 per 10 mmHg |
| Respiratory alkalosis | ↓ PaCO₂ | ↓ HCO₃⁻ | Acute: ↓2 per 10 mmHg
Chronic: ↓5 per 10 mmHg |
| Metabolic acidosis | ↓ HCO₃⁻ | ↓ PaCO₂ (hyperventilation) | Winter's formula: PaCO₂ = (1.5 × HCO₃) + 8 ± 2 |
| Metabolic alkalosis | ↑ HCO₃⁻ | ↑ PaCO₂ | PaCO₂ ↑ 0.7 per 1 mEq HCO₃ rise |
Anion Gap (AG) = Na − (Cl + HCO₃) · normal 8–12.
- High AG acidosis: MUDPILES (Methanol, Uremia, DKA, Propylene glycol, Isoniazid, Lactic, Ethylene glycol, Salicylates).
- Normal AG (hyperchloremic): USED CARP (Ureteral diversion, Saline, Endocrine, Diarrhea, CA inhibitors, RTA, Pancreatic fistula).
9. Integrated Clinical Correlations
Obstructive vs. Restrictive
| Feature | Obstructive | Restrictive |
|---|
| FEV₁/FVC | ↓ (<0.7) | Normal or ↑ |
| TLC | ↑ (air trapping) | ↓ |
| RV | ↑ | ↓ |
| Examples | COPD, Asthma, Bronchiectasis | ILD, Obesity, Neuromuscular |
PFT Patterns (high yield)
| Condition | FEV₁ | FVC | FEV₁/FVC | TLC | DLCO |
|---|
| Emphysema | ↓ | ↓ | ↓ | ↑ | ↓ |
| Chronic Bronchitis | ↓ | ↓ | ↓ | N/↑ | N/↓ |
| Asthma | ↓ | ↓ | ↓ | N/↑ | N/↑ |
| ILD | ↓ | ↓↓ | N/↑ | ↓ | ↓ |
| Obesity | N/↓ | ↓ | N/↑ | ↓ | N |
10. Key Equations Summary
| Equation | Formula | Use |
|---|
| Alveolar gas | PAO₂ = FiO₂(Patm − 47) − (PaCO₂ / 0.8) | A-a gradient |
| A-a gradient | PAO₂ − PaO₂ | Hypoxemia differential |
| Bohr (dead space) | Vᴅ/Vᴛ = (PaCO₂ − PᴇCO₂) / PaCO₂ | Dead space fraction |
| O₂ content | CaO₂ = (1.34 × Hb × SaO₂) + (0.003 × PaO₂) | O₂ delivery |
| Minute ventilation | V̇E = TV × RR | Total ventilation |
| Alveolar ventilation | V̇A = (TV − Vᴅ) × RR | Effective ventilation |
| Winter's formula | PaCO₂ = (1.5 × HCO₃) + 8 ± 2 | Metabolic acidosis compensation |