3.3 Respiratory Mechanics, Gas Exchange, Gas Transport, Control of Breathing & Extreme Environments

Why this area matters

The respiratory TOS area lists:

• mechanics of breathing;
• pulmonary gas exchange and its disorders;
• blood gas transport;
• control of respiration;
• acid-base balance;
• the effects of exercise;
• the effects of "extreme environment such as flying, place and diving".

These topics underpin asthma and COPD in Medicine, neonatal respiratory distress in Pediatrics, and ventilator and trauma care in Surgery.

Respiratory Mechanics, Lung Volumes & Compliance

Static Lung Volumes & Capacities

• Tidal Volume ($V_T \approx 500\text{ mL}$): Normal volume inspired and expired at rest.
• Inspiratory Reserve Volume ($IRV \approx 3000\text{ mL}$): Maximal additional volume inspired after a normal tidal inspiration.
• Expiratory Reserve Volume ($ERV \approx 1100\text{ mL}$): Maximal additional volume exhaled after a normal tidal expiration.
• Residual Volume ($RV \approx 1200\text{ mL}$): Volume remaining in lungs after maximal forced expiration. Cannot be measured by simple spirometry; requires helium dilution, nitrogen washout, or body plethysmography.
• Vital Capacity ($VC = IRV + V_T + ERV \approx 4600\text{ mL}$).
• Functional Residual Capacity ($FRC = ERV + RV \approx 2300\text{ mL}$): Volume remaining in the lungs at the end of a passive tidal expiration. At FRC, the inward elastic recoil of the lungs precisely equals the outward elastic recoil of the chest wall, generating a resting subatmospheric intrapleural pressure of $-5\text{ cm H}_2\text{O}$.
• Total Lung Capacity ($TLC = VC + RV \approx 5800\text{ mL}$).

Spirometry: Obstructive vs. Restrictive Patterns

Pulmonary Compliance, Surface Tension & Surfactant

Compliance ($C = \Delta V / \Delta P$) measures distensibility. According to the Law of Laplace for a spherical alveolus:

$P = \frac{2T}{r}$

Where $P$ is the inward collapsing pressure, $T$ is surface tension, and $r$ is alveolar radius. Without surfactant, smaller alveoli ($r$ small) would generate higher collapsing pressures than adjacent larger alveoli, emptying their contents into larger alveoli and causing widespread atelectasis.

• Pulmonary Surfactant: Synthesized and stored in lamellar bodies by Type II alveolar pneumocytes starting around 24 to 28 weeks of gestation. Composed primarily of dipalmitoylphosphatidylcholine (DPPC) and surfactant proteins (SP-A, B, C, D).
• Mechanism: Surfactant molecules interlock at the air-water interface, reducing surface tension $T$ proportionally more as alveolar surface area shrinks. This equalizes collapsing pressures across alveoli of differing radii, prevents alveolar collapse at end-expiration (atelectasis), increases lung compliance, and decreases the work of breathing.
• Neonatal Respiratory Distress Syndrome (NRDS): Occurs in premature infants with inadequate surfactant production (lecithin-sphingomyelin ratio $< 2.0$ in amniotic fluid). Presents with tachypnea, grunting, intercostal retractions, and diffuse "ground-glass" atelectasis on chest radiography. Managed with maternal antenatal corticosteroids (betamethasone) to accelerate Type II pneumocyte maturation, and exogenous intratracheal surfactant at birth.

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Ventilation-Perfusion ($V/Q$) Matching & Oxygen-Hemoglobin Dissociation

Regional $V/Q$ Ratios in the Upright Lung

Gravity exerts hydrostatic effects on both ventilation ($V$) and pulmonary blood flow ($Q$):

• Apex (West Zone 1/2): Both $V$ and $Q$ are lower than at the base, but blood flow is reduced far more drastically by hydrostatic pressure gradients. Consequently, the $V/Q$ ratio is high ($\sim 3.0$), resulting in high alveolar $PO_2$ ($130\text{ mmHg}$) and low $PCO_2$ ($28\text{ mmHg}$). Mycobacterium tuberculosis preferentially infects lung apices due to high oxygen tension.
• Base (West Zone 3): Both $V$ and $Q$ are highest, but perfusion outstrips ventilation. The $V/Q$ ratio is low ($\sim 0.6$), resulting in lower $PO_2$ ($89\text{ mmHg}$) and higher $PCO_2$ ($42\text{ mmHg}$). The global average resting lung $V/Q$ is roughly $0.8$.

Pathological Extremes of $V/Q$

• Right-to-Left Shunt ($V/Q = 0$): Perfusion without ventilation. Occurs in alveolar consolidation (lobar pneumonia), complete atelectasis, foreign body aspiration, and cyanotic congenital heart disease (Tetralogy of Fallot). Venous blood bypasses ventilated gas exchange surfaces. Clinical Hallmark: Severe hypoxemia that fails to correct significantly with $100\%$ supplemental oxygen, because the administered gas cannot contact shunted blood.
• Alveolar Dead Space ($V/Q = \infty$): Ventilation without perfusion. Occurs in pulmonary embolism where an occlusive thromboembolus blocks downstream arterial flow. Dead space fraction is calculated using the Bohr-Enghoff Equation: $\frac{V_D}{V_T} = \frac{PaCO_2 - P_E CO_2}{PaCO_2}$ Where $PaCO_2$ is arterial $PCO_2$ and $P_E CO_2$ is mixed expired $PCO_2$.
• Hypoxic Pulmonary Vasoconstriction (HPV): Unlike systemic arterioles, which dilate in response to hypoxia, pulmonary arterioles undergo vigorous vasoconstriction when alveolar $P_A O_2$ drops below $70\text{ mmHg}$. This redistributes pulmonary blood flow away from poorly ventilated alveoli toward well-ventilated regions, preserving $V/Q$ matching. Generalized alveolar hypoxia (high altitude, severe COPD) induces global pulmonary vasoconstriction, producing pulmonary arterial hypertension and cor pulmonale.

The Oxygen-Hemoglobin Dissociation Curve

The sigmoidal shape of the curve reflects positive cooperativity among the four heme subunits of adult hemoglobin ($HbA$, $\alpha_2\beta_2$). Oxygen binding to one subunit relaxes the quaternary structure from the low-affinity Tense (T) state to the high-affinity Relaxed (R) state.

• Normal $P_{50}$: The partial pressure of oxygen at which hemoglobin is 50% saturated is approximately $26.8\text{ mmHg}$. Normal arterial blood ($PaO_2 = 100\text{ mmHg}$) is $98\%$ saturated; mixed venous blood ($PvO_2 = 40\text{ mmHg}$) is $75\%$ saturated.

• Bohr Effect: Increased tissue $PCO_2$ and $[H^+]$ promote carbaminohemoglobin formation and proton binding to globin chains, stabilizing the deoxygenated T-state and releasing oxygen into peripheral capillary beds.
• Haldane Effect: Deoxygenation of hemoglobin in peripheral tissues increases its capacity to carry $CO_2$ and buffer protons. In the lungs, oxygen binding to hemoglobin displaces $CO_2$ and $H^+$, facilitating carbon dioxide exhalation.

Ventilation and dead space

Not all inspired air reaches gas-exchanging alveoli.

• Anatomic dead space is about 150 mL in an adult, roughly 2 mL/kg.
• Physiologic dead space is anatomic dead space plus alveolar dead space.
• Alveolar ventilation = (tidal volume - dead space) x respiratory rate.

Worked example. With a 500-mL tidal volume, 150-mL dead space and 12 breaths per minute, alveolar ventilation is 350 x 12 = 4.2 L/min. Rapid shallow breathing wastes ventilation: 250 mL x 24 gives the same 6 L/min minute ventilation, but only 100 x 24 = 2.4 L/min reaches the alveoli.

Arterial PCO2 is inversely proportional to alveolar ventilation. Halving alveolar ventilation doubles PaCO2.

The five causes of hypoxemia

The alveolar gas equation estimates alveolar PO2 on room air at sea level:

$$P_AO_2 = F_iO_2(P_{atm} - 47) - \frac{PaCO_2}{0.8}$$

which is about 0.21 x 713 - 40/0.8, or roughly 100 mmHg. The normal A-a gradient is under about 10 to 15 mmHg in young adults and widens with age.

Carbon dioxide transport

Oxygen content is $1.34 \times \text{Hb} \times S_aO_2 + 0.003 \times P_aO_2$ (mL O2/dL), so hemoglobin and saturation, not dissolved oxygen, carry almost all of it. In anemia, PaO2 and saturation stay normal but oxygen content falls. In carbon monoxide poisoning, pulse oximetry reads falsely normal while oxygen content and delivery fall, and the curve shifts left.

Control of breathing

• Brainstem centers:
  • The dorsal respiratory group in the medulla sets the inspiratory rhythm.
  • The ventral group is recruited for forced breathing.
  • The pneumotaxic center in the upper pons limits inspiration.
  • The pre-Bötzinger complex generates the basic rhythm.
• Central chemoreceptors on the ventral medulla respond to the H+ of cerebrospinal fluid. CO2 crosses the blood-brain barrier and forms H+, so PaCO2 is the dominant minute-to-minute stimulus.
• Peripheral chemoreceptors in the carotid bodies (afferents in CN IX) and aortic bodies (CN X) respond mainly to PaO2 below about 60 mmHg, and also to H+ and PCO2.
• In chronic CO2 retention, such as severe COPD, CSF bicarbonate compensates and the hypoxic drive matters more. Uncontrolled high-flow oxygen can therefore worsen hypercapnia, mainly through V/Q changes and the Haldane effect. That is why oxygen is titrated to a target saturation of about 88% to 92% in these patients.
• Lung stretch receptors (the Hering-Breuer reflex), J receptors and irritant receptors adjust the pattern of breathing.

Exercise, altitude, flying and diving

• Exercise: ventilation rises in proportion to metabolism, so arterial PO2, PCO2 and pH stay nearly normal until the anaerobic threshold. Above it, lactic acid drives extra ventilation. Oxygen extraction widens, and the curve shifts right (temperature, CO2, H+).
• High altitude and flying:
  • Lower barometric pressure lowers inspired PO2. Peripheral chemoreceptors trigger hyperventilation, producing respiratory alkalosis, which the kidney compensates by excreting bicarbonate over days.
  • Acclimatization adds erythropoietin-driven polycythemia, a rise in 2,3-BPG and more capillaries.
  • Hypoxic pulmonary vasoconstriction can lead to high-altitude pulmonary edema.
  • Acetazolamide speeds acclimatization by inducing a mild metabolic acidosis.
  • Commercial cabins are pressurized to an altitude equivalent of about 1,800 to 2,400 m, which can unmask hypoxemia in patients with lung disease.
• Diving:
  • Pressure rises by about 1 atmosphere for every 10 m of seawater. By Boyle's law, gas volume falls as pressure rises, so trapped gas in the ears, sinuses or lungs causes barotrauma.
  • A breath-holding diver ascending with a closed glottis can rupture alveoli and cause arterial gas embolism.
  • At depth, more nitrogen dissolves (Henry's law), causing nitrogen narcosis. Rapid ascent lets that nitrogen form bubbles, causing decompression sickness ("the bends"), which is treated with hyperbaric oxygen recompression.
  • High oxygen partial pressures at depth can cause oxygen toxicity.