📘 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.

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

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)

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

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