8.1 Respiratory Physiology

Mechanics: pressures, muscles, and the resting lung

Respiratory anatomy of airways, pleura, and mediastinum is covered in 4.1 Respiratory System. This section is the physics and control that turn that anatomy into alveolar ventilation. Air moves only down a pressure gradient. Boyle's law (P × V is constant at a given temperature) is why expanding the thorax lowers alveolar pressure (Palv) below atmospheric pressure and draws air in.

At rest the lung sits at functional residual capacity (FRC). Intrapleural pressure is about −5 cm H2O, alveolar pressure is atmospheric (0 when the glottis is open and flow has stopped), and transpulmonary pressure (Palv − Ppl, or more strictly alveolar minus intrapleural) keeps alveoli open. The lung's inward elastic recoil exactly balances the chest wall's outward recoil. Inspiration is active: the diaphragm (phrenic, C3–C5) drops, the external intercostals raise the ribs in a bucket-handle and pump-handle pattern, and accessory muscles (SCM, scalenes) recruit when demand rises. Quiet expiration is passive recoil. Forced expiration recruits internal intercostals and abdominal wall muscles, raising intrapleural pressure well above atmospheric—the same maneuver that sets up dynamic airway compression.

Chiropractic relevance is mechanical, not diagnostic theater: restricted costovertebral and costosternal motion, a rigid thoracic cage, or a high resting diaphragm from abdominal distention all lower chest-wall compliance and raise the work of breathing even when the lung parenchyma is normal. Part I will still ask the lung side of the same equation.

Compliance, surfactant, and airway resistance

Compliance is ΔV/ΔP. High compliance means a large volume change for a small pressure change (emphysema, aging loss of recoil). Low compliance means a stiff lung (fibrosis, pulmonary edema, atelectasis, surfactant deficiency). The pressure–volume curve shows hysteresis: at any given volume, transpulmonary pressure is higher during inflation than deflation because extra pressure is spent opening collapsed units and overcoming surface tension. The chest wall and lung have separate curves; the combined system is most compliant near FRC, which is why tidal breathing lives there.

Surfactant is a phospholipid–protein mixture, chiefly dipalmitoyl phosphatidylcholine (DPPC), secreted by type II pneumocytes. By Laplace's law, collapsing pressure P = 2T/r (or 4T/r for a soap bubble with two surfaces). Without surfactant, smaller alveoli would empty into larger ones. Surfactant lowers surface tension more in small alveoli (molecules pack tighter as radius falls), increases compliance, keeps alveoli dry by reducing the hydrostatic pull that would suck fluid out of capillaries, and is the reason a first breath is possible. Fetal lung fluid is cleared at birth; infant respiratory distress syndrome is surfactant failure in premature type II cells. Deep sighs and yawns spread surfactant; prolonged shallow breathing lets alveoli collapse.

Airway resistance follows Poiseuille's law in laminar segments: R = 8ηL / πr^4. Radius dominates. The medium-sized bronchi, not the terminal bronchioles, contribute most of the resistance because the smallest airways are so numerous that their parallel cross-section is huge. Parasympathetic acetylcholine and histamine constrict; sympathetic β2 agonists and circulating epinephrine dilate. Radial traction from surrounding parenchyma pulls airways open as lung volume rises, so resistance falls from RV toward TLC. That is why an obstructive patient purses the lips and why forced expiration can worsen obstruction.

During a forced vital-capacity maneuver, intrapleural pressure becomes positive. At the equal pressure point, airway pressure equals surrounding pleural pressure. Downstream of that point the airway is compressed (dynamic compression), flow becomes effort-independent, and the flow–volume loop shows the classic obstructive scoop. Loss of radial traction (emphysema) moves the equal pressure point toward the alveoli and collapses small airways early.

Volumes, capacities, and what spirometry can actually see

A volume is a single slice; a capacity is two or more volumes added. Typical resting adult-male values (order-of-magnitude numbers Part I expects, not a personal prediction): tidal volume (TV) ~500 mL, inspiratory reserve volume (IRV) ~3000 mL, expiratory reserve volume (ERV) ~1100 mL, residual volume (RV) ~1200 mL. Capacities: inspiratory capacity (IC) = TV + IRV; FRC = ERV + RV (~2300 mL); vital capacity (VC) = IRV + TV + ERV; total lung capacity (TLC) = VC + RV (~5800–6000 mL).

Simple spirometry measures only what the mouth can expire or inspire from a starting volume. It gives TV, IRV, ERV, VC, IC, FEV1, FVC, and peak flow. It cannot measure RV, FRC, or TLC because those include gas that never leaves. Measure FRC (then add IC for TLC, or subtract ERV for RV) by helium dilution, nitrogen washout, or body plethysmography. Dilution methods miss trapped gas behind closed airways; the body box (Boyle's law in a sealed cabin) includes trapped gas, so FRC by plethysmography exceeds FRC by dilution in obstruction.

Minute ventilation = TV × respiratory rate. Alveolar ventilation VA = (TV − VD) × rate. Anatomic dead space is the conducting zone, ~1 mL per pound of ideal body weight (~150 mL). Physiologic dead space is anatomic plus alveolar dead space (ventilated alveoli with no perfusion). Bohr equation: VD/VT = (PaCO2 − PECO2) / PaCO2. Fowler's single-breath N2 method estimates anatomic dead space. Rapid shallow breathing raises the dead-space fraction and can drop VA even when minute ventilation looks high.

Flow–volume loops: obstruction scoops the expiratory limb and may show a high TLC; restriction is a miniature loop shifted right (low volumes) with a steep, often tall, expiratory limb. A plateau on the expiratory limb suggests variable intrathoracic obstruction (trachea); a plateau on inspiration suggests variable extrathoracic obstruction (vocal fold, goiter). Fixed obstruction flattens both limbs. DLCO (diffusing capacity for carbon monoxide) falls in emphysema, interstitial disease, anemia, and loss of capillary bed; it rises in polycythemia, alveolar hemorrhage, and some asthma.

Quick Answer: RV and FRC are not on a simple spirogram. Obstruction is a low FEV1/FVC with air trapping; restriction is small TLC with a preserved or high ratio. Type II surfactant lowers surface tension; medium bronchi, not terminal bronchioles, dominate resistance.

Regulation: medulla, pons, and chemoreceptors

The dorsal respiratory group (DRG) in the nucleus tractus solitarius is the inspiratory core and the landing site for vagal and glossopharyngeal afferents. The ventral respiratory group (VRG) contains the pre-Bötzinger rhythm generator plus inspiratory and expiratory lower motor neurons recruited when ventilation rises. The pontine pneumotaxic center (Kölliker–Fuse / medial parabrachial) cuts inspiration short and raises rate; an apneustic pattern (prolonged inspiration) appears if that brake is lost and vagal input is cut. Automatic ventilation can fail with medullary lesions even when the cortex can still take a voluntary breath.

Central chemoreceptors on the ventral medulla sense H+ in brain interstitial fluid, not arterial H+ directly. Arterial CO2 crosses the blood–brain barrier, hydrates to carbonic acid, and supplies that H+. A chronic high PCO2 (COPD) lets choroid-plexus bicarbonate rise, so the same PCO2 produces less central drive—these patients lean on hypoxic drive. Peripheral chemoreceptors in the carotid bodies (CN IX, the dominant ventilatory sensors) and aortic bodies (CN X) respond to low PO2, high PCO2, and low pH. The hypoxic ventilatory response is almost entirely peripheral and is weak until PaO2 falls below about 60 mmHg. Metabolic acidosis stimulates ventilation mainly via peripheral sensors (H+ does not cross the BBB well).

Other afferents: Hering–Breuer inflation (slowly adapting stretch receptors, CN X) terminates inspiration, more important in infants than in quiet adult breathing; irritant receptors trigger cough and bronchoconstriction; juxtacapillary (J) receptors in the alveolar wall fire with interstitial edema and produce rapid shallow breathing; muscle and joint receptors raise ventilation at the start of exercise before blood gases change. Exercise hyperpnea is still not a single-receptor story: feed-forward from motor cortex, proprioception, and later humoral signals all participate. Hypoxic pulmonary vasoconstriction (HPV) is local smooth-muscle behavior, not a chemoreflex: low alveolar PO2 constricts pulmonary arterioles and redirects blood toward better-ventilated units—the opposite of systemic hypoxic vasodilation.

O2 and CO2 transport: the hemoglobin curve, Bohr, and Haldane

Dissolved O2 is 0.003 mL/dL per mmHg PO2—about 0.3 mL/dL in arterial blood, useless as a cargo but the only form that sets PaO2 and therefore hemoglobin saturation. Bound O2 is 1.34 mL O2 per gram of hemoglobin times saturation. With hemoglobin 15 g/dL and SaO2 ~97%, arterial content is about 20 mL/dL. Oxygen delivery = content × cardiac output. Anemia and carbon monoxide can leave PaO2 normal (dissolved O2 unchanged) while content collapses.

The oxyhemoglobin dissociation curve is sigmoid because of cooperative binding. P50 (PO2 at 50% saturation) is about 26–27 mmHg for adult hemoglobin A. A right shift (higher P50, easier unloading) is produced by increased PCO2, increased H+ (lower pH), increased temperature, and increased 2,3-bisphosphoglycerate (2,3-BPG)—the Bohr effect at the tissue capillary. A left shift (lower P50, tighter binding) is produced by the opposite changes, by fetal hemoglobin, by carbon monoxide, and by methemoglobin. CO occupies binding sites and left-shifts remaining sites, a double insult; PaO2 is still normal because dissolved O2 is normal. High altitude raises 2,3-BPG and right-shifts the curve after a delay, favoring unloading.

CO2 travels three ways: dissolved (~7–10%, 0.03 mmol/L per mmHg—this is the term in Henderson–Hasselbalch), carbamino compounds on hemoglobin (~20–30%), and bicarbonate (~60–70%). In the red cell, carbonic anhydrase makes H2CO3; HCO3− exits in exchange for Cl− (chloride shift); deoxyhemoglobin buffers the leftover H+. The Haldane effect is the companion of Bohr: oxygenation of hemoglobin in the lung decreases CO2 affinity and decreases H+ buffering, so CO2 is unloaded; deoxygenation in tissue does the reverse. Bohr unloads O2 where CO2 is high; Haldane unloads CO2 where O2 is high.

Gas exchange, A-a gradient, and V/Q

Fick's law: transfer ∝ area × diffusivity × (P1 − P2) / thickness. O2 uptake can become diffusion-limited in fibrosis, edema, or extreme exercise; N2O is perfusion-limited; CO is so diffusion-limited it is used to measure DLCO. Alveolar gas equation: PAO2 = PIO2 − (PACO2 / R), with R typically 0.8. At sea level PIO2 is about 150 mmHg, so PAO2 ≈ 150 − 40/0.8 = 100 mmHg. The A-a gradient is PAO2 − PaO2, normally about 5–15 mmHg (rises with age). An increased A-a gradient means the lung is not transferring O2 as a perfect ideal compartment.

Five causes of hypoxemia:

1. Low inspired PO2 (altitude)—A-a normal, PaCO2 usually low from hyperventilation.
2. Hypoventilation (narcotics, neuromuscular, severe kyphoscoliosis)—A-a normal, PaCO2 high; 100% O2 fixes the hypoxemia easily.
3. Diffusion impairment—A-a increased; uncommon as an isolated cause at rest.
4. V/Q mismatch—the most common; A-a increased; 100% O2 usually raises PaO2 substantially because even low-V/Q units still get some ventilation.
5. Right-to-left shunt (anatomic or true alveolar shunt, V/Q = 0)—A-a increased; 100% O2 does not fully correct PaO2 because shunted blood never meets alveolar gas.

Ideal V/Q ≈ 0.8–1. West zones of the upright lung: Zone 1 (apex, possible in hemorrhage or PEEP) PA > Pa > Pv, alveolar dead space; Zone 2 Pa > PA > Pv, intermittent flow; Zone 3 (base) Pa > Pv > PA, continuous flow. Both ventilation and perfusion are higher at the base, but perfusion increases more, so basal V/Q is lower than apical V/Q. A pulmonary embolus converts a unit toward dead space (V/Q → ∞). Airway plugging converts a unit toward shunt (V/Q → 0). Mixed venous blood from shunt dilutes arterial O2; wasted ventilation from dead space raises the minute ventilation needed to keep PaCO2 normal.

Exam traps: PaO2 is not O2 content. Anemia and CO poisoning are hypoxic at the mitochondrion with a normal PaO2. Cyanide blocks utilization with a high venous PO2. FEV1/FVC down is obstruction even if the patient is a young asthmatic with a normal TLC between attacks. Central chemoreceptors do not sense arterial PO2. Surfactant is type II, not type I. Resistance is not highest in the tiniest tubes. HPV is pulmonary, not systemic. When cardiovascular and respiratory items collide (right-to-left shunt, mixed venous O2), use 7.3 Cardiovascular Physiology for the pump and this section for the gas.