Physiology

Pulmonary Physiology

Ventilation, gas exchange, V/Q matching, lung volumes, and respiratory control

Lung Volumes and Capacities

Volume / CapacityNormal ValueDefinition
Tidal volume (TV)500 mLVolume with normal breath
IRV3000 mLExtra air inhaled after normal inspiration
ERV1200 mLExtra air exhaled after normal expiration
RV1200 mLAir remaining after maximal exhalation (cannot measure with spirometry)
VC (IRV+TV+ERV)4700 mLMaximum air moved in one breath
FRC (ERV+RV)2400 mLVolume at end-expiration (lung at rest)
TLC (all volumes)6000 mLTotal lung capacity
⭐ Spirometry PatternsObstructive (asthma, COPD): FEV1 decreased, FVC normal or decreased, FEV1/FVC ratio less than 0.7, TLC increased (air trapping). Restrictive (IPF, obesity, NMD): FEV1 decreased, FVC decreased, FEV1/FVC ratio normal or increased, TLC decreased.

Breathing Mechanics

Inspiration is active (diaphragm + external intercostals contract). Normal expiration is passive (elastic recoil). Forced expiration uses internal intercostals and abdominals.

  • Compliance = change in volume / change in pressure. High compliance = easy to stretch (emphysema). Low compliance = stiff lung (pulmonary fibrosis, pulmonary edema).
  • Surfactant (produced by type II pneumocytes) reduces surface tension → increases compliance → prevents alveolar collapse. Deficient in RDS of newborn (premature infants).
  • Airway resistance — increases in small airways (asthma, mucus, edema). Bronchodilators (beta-2 agonists) decrease resistance.
🩹 Surfactant PhysiologySurfactant prevents collapse of small alveoli (LaPlace law: P = 2T/r; small r = high pressure → collapse without surfactant). Lecithin:sphingomyelin ratio (L:S ratio) greater than 2 = fetal lung maturity. Betamethasone given to mother to stimulate fetal surfactant production.

Gas Exchange

Gas exchange occurs at the alveolar-capillary membrane by passive diffusion (Fick's law: rate proportional to area, pressure gradient, and diffusion coefficient; inversely proportional to membrane thickness).

GasAlveolar LevelArterial LevelVenous Level
PO2PAO2 ~100 mmHgPaO2 ~95 mmHgPvO2 ~40 mmHg
PCO2PACO2 ~40 mmHgPaCO2 ~40 mmHgPvCO2 ~46 mmHg

A-a gradient = PAO2 - PaO2 (normal: less than 10-15 mmHg on room air). Elevated in V/Q mismatch, diffusion impairment, R-to-L shunt. Normal in hypoventilation (PaCO2 elevated, PaO2 decreased).

V/Q Matching

Ventilation-perfusion (V/Q) ratio determines gas exchange efficiency. Normal V/Q ~0.8.

V/Q StateV/Q RatioExampleEffect
Normal~0.8Healthy lung base (better perfusion)Efficient gas exchange
V/Q = 0 (shunt)0Pneumonia, atelectasis, ARDSBlood passes without gas exchange; hypoxia does NOT improve with O2
V/Q = infinity (dead space)InfinityPulmonary embolismVentilated but not perfused; CO2 retention
V/Q mismatchBetween 0 and infinityCOPD, asthmaMost common cause of hypoxia; responds to supplemental O2

O2 and CO2 Transport

Oxygen transport: 97% bound to hemoglobin (1 Hgb carries 4 O2); 3% dissolved in plasma. Oxyhemoglobin dissociation curve: S-shaped (cooperative binding). Right shift (decreased affinity — offloads O2 to tissues): increased temperature, increased CO2, increased 2,3-DPG, acidosis.

CO2 transport: 70% as bicarbonate (CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-; catalyzed by carbonic anhydrase in RBCs). 20% as carbaminohemoglobin. 10% dissolved.

🧐 Ox-Hgb Curve Right Shift — CADET face right!CO2 increase, Acid (H+), 2,3-DPG increase, Exercise, Temperature increase → Right shift → decreased O2 affinity → more O2 released to tissues.

Respiratory Control

The respiratory center is in the medulla (pre-Botzinger complex for rhythm) and pons (apneustic and pneumotaxic centers for rate modification).

  • Central chemoreceptors (medulla): respond primarily to PaCO2 (via CO2 crossing BBB → H+ production). Main driver of respiratory drive in healthy individuals.
  • Peripheral chemoreceptors (carotid bodies, aortic arch): respond to PaO2 less than 60 mmHg, PaCO2, pH. Primary driver in COPD patients (hypoxic drive).
⭐ COPD and O2 TherapyChronic COPD patients are CO2 retainers — their respiratory drive shifts from CO2 sensitivity to hypoxic drive. High-flow O2 can suppress this drive → apnea. Use controlled O2 (target SpO2 88-92%) in COPD exacerbations. Do NOT withhold O2 if the patient is critically hypoxic — correct hypoxia first.

Clinical Pearls

⭐ Hypoxemia vs HypoxiaHypoxemia = decreased PaO2 in arterial blood (measurable). Hypoxia = inadequate O2 delivery to tissues. Causes of hypoxemia: hypoventilation (high PaCO2), V/Q mismatch, shunt, diffusion impairment, low FiO2. Causes of hypoxia with normal PaO2: anemia, CO poisoning, shock.
🩹 Pulmonary Embolism ABG PatternClassic PE ABG: low PaO2, low PaCO2 (hyperventilating to compensate), respiratory alkalosis, elevated A-a gradient. ECG: sinus tachycardia (most common); S1Q3T3 (classic but uncommon); right heart strain pattern.