11.1 Pulmonary Mechanics & Gas Exchange

11.1 Pulmonary Mechanics & Gas Exchange

Quick Answer: Lung volumes partition static size (TLC, FRC, RV, VC); compliance and surfactant determine how easily alveoli inflate; resistance and equal-pressure-point dynamics govern flow. Gas exchange fails from low V/Q, shunt, diffusion barrier, or hypoventilation. Use PAO2 = PIO2 − (PaCO2/R), O2–Hb curve shifts, and CO2 carriage forms to explain hypoxemia and cyanosis patterns.

Respiratory physiology on the CBSE is mechanism-first. Items rarely ask for a definition alone; they pair a volume change with a disease, a curve shift with tissue O2 delivery, or a V/Q mismatch with an A–a gradient pattern. Build a scaffold from static mechanics → dynamic flow → matching of ventilation to perfusion → gas transport.

Lung Volumes and Capacities

Static volumes describe how much air the respiratory system can hold at defined points of the breathing cycle. Tidal volume (TV) is the quiet breath. Inspiratory reserve volume (IRV) and expiratory reserve volume (ERV) are the extra volumes that can be inspired or expired beyond tidal breathing. Residual volume (RV) remains after maximal expiration and cannot be exhaled; it keeps alveoli from collapsing completely. Capacities are sums of volumes: vital capacity (VC) = IRV + TV + ERV; inspiratory capacity (IC) = IRV + TV; functional residual capacity (FRC) = ERV + RV (volume at end of quiet expiration, where inward lung elastic recoil balances outward chest-wall recoil); total lung capacity (TLC) = VC + RV.

Spirometry measures exhaled and inspired volumes that pass the mouth, so it reports TV, IRV, ERV, VC, FEV1, and FVC, but not RV, FRC, or TLC. Those require body plethysmography, helium dilution, or nitrogen washout. On CBSE vignettes, elevated TLC/RV with air trapping suggests obstructive disease with loss of elastic recoil or early airway closure; reduced TLC with proportionally reduced volumes suggests restriction.

Compliance, Elastance, and Surfactant

Compliance is ΔV/ΔP: how much volume change occurs for a given transmural pressure change. High compliance means easy inflation (emphysema: destroyed alveolar walls, ↓ elastic recoil). Low compliance means stiff lungs (interstitial fibrosis, pulmonary edema, ARDS, lack of surfactant). Elastance is the inverse of compliance; elastic recoil drives passive expiration.

The chest wall prefers a larger volume and the lung prefers a smaller volume; their balance sets FRC. In emphysema, loss of lung recoil shifts FRC upward (hyperinflation). In fibrosis, stiff lungs reduce FRC and TLC.

Surfactant, produced by type II pneumocytes, is rich in dipalmitoyl phosphatidylcholine (DPPC). It lowers alveolar surface tension, increases compliance, and stabilizes alveoli of different sizes (Laplace: P = 2T/r — smaller alveoli would collapse into larger ones without surfactant reducing T more at smaller radii). Surfactant deficiency causes neonatal respiratory distress syndrome (especially premature infants before adequate type II maturation), with atelectasis, hyaline membranes, and hypoxemia. Glucocorticoids accelerate fetal surfactant production—high-yield antenatal physiology.

Airway Resistance and Dynamic Compression

Airway resistance is highest in medium-sized bronchi in normal physiology (very small airways have huge total cross-sectional area in parallel). Resistance rises with airway narrowing (bronchoconstriction, mucus, edema, dynamic compression) and with lower lung volumes (airways tether open less). Poiseuille’s law (R ∝ 1/r⁴ for laminar flow) explains why small radius changes matter clinically.

During forced expiration, intrapleural pressure becomes positive and can compress airways downstream of the equal pressure point, limiting flow. Loss of radial traction in emphysema moves this point peripherally and promotes dynamic airway collapse and air trapping. Asthma increases resistance via smooth muscle contraction, inflammation, and mucus; flow-volume loops show scooped expiratory limbs and reduced FEV1/FVC.

Dead Space, Alveolar Ventilation, and V/Q Relationships

Anatomic dead space is conducting airway volume that does not participate in gas exchange (~1 mL/lb ideal body weight conceptually). Physiologic dead space = anatomic + alveolar dead space (ventilated alveoli with inadequate perfusion, classic in PE). Minute ventilation = TV × RR, but alveolar ventilation = (TV − dead space) × RR and is what clears CO2.

V/Q matching optimizes gas exchange. Ideal V/Q ≈ 1. Low V/Q (airway obstruction, atelectasis, pneumonia filling) acts toward shunt: blood leaves under-oxygenated. High V/Q (PE, low cardiac output to a region) wastes ventilation (dead space). True shunt (V/Q = 0) does not correct fully with supplemental O2 because shunted blood never contacts alveolar gas; low V/Q regions still show some O2 responsiveness. Gravity creates apex-to-base gradients: apex has higher V/Q (relatively more ventilation than perfusion), base lower V/Q (more perfusion).

Hypoxic pulmonary vasoconstriction (HPV) is a local arteriolar response to low alveolar PO2 that diverts blood from poorly ventilated units. It is adaptive in focal disease but harmful when hypoxia is global (high altitude, diffuse lung disease), raising pulmonary vascular resistance and right-heart afterload (cor pulmonale risk). HPV is inhibited by many systemic vasodilators and by some volatile anesthetics—useful integrated pharm/phys links.

Alveolar Gas Equation and Hypoxemia Framework

The simplified alveolar gas equation: PAO2 ≈ PIO2 − (PaCO2 / R), where R (respiratory exchange ratio) is often taken as 0.8. PIO2 falls with altitude (lower barometric pressure). Hypoventilation raises PaCO2 and therefore lowers PAO2. The A–a gradient (PAO2 − PaO2) rises with V/Q mismatch, shunt, and diffusion limitation, and is normal/near-normal in pure hypoventilation and pure low inspired O2 (after accounting for age).

Five classic causes of hypoxemia: (1) low inspired O2, (2) hypoventilation, (3) diffusion impairment, (4) shunt, (5) V/Q mismatch. Only shunt is relatively refractory to 100% O2. Hypercapnia primarily reflects inadequate alveolar ventilation relative to CO2 production.

Diffusion vs Perfusion Limitation

Gas transfer across the blood–gas barrier depends on surface area, thickness, partial pressure gradient, and gas solubility/diffusivity. N2O is perfusion-limited: equilibrates early along the capillary, so uptake depends on blood flow. O2 is normally perfusion-limited (equilibrates with reserve) but can become diffusion-limited in exercise, fibrosis, edema, or emphysema (↓ surface area). CO is diffusion-limited and is used to measure DLCO. Low DLCO appears in emphysema, ILD, PE, anemia (less Hb to bind CO), and pulmonary vascular disease; high DLCO can occur in polycythemia, left-to-right shunts, or alveolar hemorrhage (extra Hb in alveoli).

O2–Hemoglobin Dissociation Curve

The sigmoid O2–Hb curve reflects cooperative binding. P50 is the PO2 at 50% saturation. A right shift (↑P50) decreases affinity and favors unloading at tissues: increased 2,3-BPG, increased CO2, increased temperature, decreased pH (Bohr effect). A left shift increases affinity and impairs unloading: alkalosis, hypothermia, decreased 2,3-BPG (stored blood), fetal hemoglobin, and carbon monoxide. CO also binds with very high affinity, occupies binding sites, and left-shifts remaining sites, so oxygen content falls dramatically even when PaO2 (dissolved) is relatively preserved—classic “normal PaO2, low content, cherry-red” mechanism vignette. Anemia lowers O2 content with normal PaO2 and usually normal saturation of remaining Hb.

CO2 Transport and the Haldane Effect

CO2 is carried as bicarbonate (~70%), carbamino compounds on Hb (~20%), and dissolved CO2 (~10%). In tissues, CO2 enters RBCs, carbonic anhydrase forms H2CO3 → H+ + HCO3−; HCO3− exits in exchange for Cl− (chloride shift). Deoxygenated Hb buffers H+ better and binds CO2 more readily (Haldane effect), facilitating CO2 loading in tissues and unloading in the lung where oxygenation of Hb releases CO2. The Bohr and Haldane effects are reciprocal partners linking O2 and CO2 exchange.

Integrated Clinical Snapshots

Emphysema: ↑ compliance, ↓ recoil, air trapping (↑RV/TLC), V/Q mismatch, often ↓DLCO (lost surface). Fibrosis: ↓ compliance, ↓TLC, diffusion limitation, ↓DLCO, rapid shallow breathing. PE: increased alveolar dead space, high V/Q regions, hypoxemia from V/Q inequality and sometimes low mixed venous O2 with limited compensation. High altitude: low PIO2 → hypoxemia → hyperventilation (↓PaCO2) → respiratory alkalosis; chronic acclimatization raises 2,3-BPG (right shift) and polycythemia (content).

Mastery check: if you can compute a qualitative A–a pattern, state why shunt vs hypoventilation differ on 100% O2, explain right vs left O2–Hb shifts including CO, and link surfactant, compliance, and FRC to disease geometry, you have the CBSE core of pulmonary mechanics and gas exchange.