Gas Exchange & Respiratory Physiology – Comprehensive Notes

Gas-Exchange Surfaces: General Properties

• Permeability
  • Surfaces must allow free diffusion of respiratory gases (O₂ & CO₂)
  • Thin epithelial barriers minimize diffusion distance (≈ 0.2$–$0.6\,\mu m in human alveoli)
• Large surface area
  • Maximizes total flux (Fick’s Law: \text{Rate}\propto \dfrac{A\,(P1-P2)}{d})
  • Human lungs ≈ 70\,m^2 (about a tennis court)
• Moisture
  • Gases must dissolve before diffusing through membranes
  • Pulmonary surfactant provides thin aqueous film while lowering surface tension
• Thinness
  • Single‐cell layers prevent multi-layer diffusion delays
• Distinction of physiological steps
  • Ventilation ≈ bulk movement of air in/out of lungs
  • Gas exchange ≈ diffusion across respiratory surface into blood
  • Cellular respiration ≈ mitochondrial O₂ use & ATP production

Anatomy of the Human Respiratory System

• Upper structures
  • Nasal cavity, pharynx, larynx (contains vocal cords)
  • Trachea (cartilaginous “C” rings keep airway open)
• Bronchial tree
  • Primary (main) bronchi → secondary (lobar) bronchi → tertiary (segmental) bronchi → bronchioles → terminal & respiratory bronchioles → alveolar ducts → alveolar sacs
• Lungs
  • Right lung: 3 lobes (superior, middle, inferior)
  • Left lung: 2 lobes (superior, inferior) + cardiac notch + lingula
  • Hilum: entry/exit of bronchi, arteries, veins, lymphatics
• Pleurae
  • Visceral pleura adheres to lung surface
  • Parietal pleura lines thoracic cavity & diaphragm
  • Pleural cavity (≈ <5\,\text{mL} fluid) creates negative pressure & lubricates

Relationship to the Cardiovascular System

• Pulmonary artery delivers deoxygenated blood from right ventricle
• Pulmonary capillaries envelope each alveolus (≈ 300 million per lung)
• Pulmonary veins return oxygenated blood to left atrium
• Close anatomical proximity reduces diffusion distance for gases

Ventilation Mechanics

• Principle: pressure changes within the thorax (Boyle’s Law P\alpha \dfrac{1}{V})
• Major muscle groups
  • Diaphragm (dome-shaped at rest)
    • Contraction → flattens → thoracic volume ↑ → intrapulmonary pressure ↓ (air in)
    • Relaxation → domes → volume ↓ → pressure ↑ (air out)
  • External intercostals (inspiration)
    • Contract → ribs & sternum lift outward & upward
  • Internal intercostals + abdominal muscles (forced expiration)
    • Contract → ribs depress, abdominal organs push diaphragm upward
• Antagonistic action ensures rhythmic cycle ≈ 12–20 breaths min⁻¹ at rest

Alveolar Structure and Function

• Conducting pathway ends in clusters of alveoli (sacs)
  • Each sac comprised of multiple alveoli interconnected by pores (of Kohn) to equalize pressure
• Pneumocytes (alveolar epithelial cells)
  • Type I (≈ 95 % surface area)
    • Extremely thin & squamous (diffusion barrier ≈ 0.2\,\mu m)
  • Type II (≈ 5 %) surfactant-secreting, cuboidal
    • Produce phospholipoprotein mixture lowering surface tension (Law of Laplace P=\dfrac{2\gamma}{r}; ↓γ prevents collapse at low r)
    • Serve as progenitors that can differentiate into type I after injury
• Resident macrophages patrol lumen → phagocytose debris & microbes

Microscopic Gas-Exchange Process

• Diffusion driven by partial-pressure gradients
  • Inspired air: P{O2}\approx 13\ kPa; venous blood P{O2}\approx 5\ kPa
  • CO₂ gradient reversed (venous P{CO2}\approx 6\ kPa → alveolar 5.3\ kPa → expired 4.7\ kPa)
• Blood–gas barrier layers
  1. Surfactant film
  2. Type I pneumocyte membrane & cytoplasm
  3. Shared basal laminae (fused basement membranes)
  4. Capillary endothelial cell
  5. Plasma & erythrocyte membrane
• Total diffusion path ≲ 0.6\,\mu m → extremely fast equilibration (< 0.25 s)

Chemical Transport of CO₂ & O₂ in Blood

• Carbon dioxide (typical venous content ≈ 52\,mL\,100\,mL^{−1} blood)
  • \approx 7\% dissolved as CO_2
  • \approx 23\% bound to globin chains → carbamino-hemoglobin (HbCO₂)
  • \approx 70\% converted in erythrocytes via carbonic anhydrase
    CO2 + H2O \leftrightarrow H2CO3 \leftrightarrow HCO3^- + H^+ • Bicarbonate exchanged for Cl^- (Hamburger shift) • Reaction reversed in lungs; CO2 diffuses into alveoli
• Oxygen transport
  • >98\% carried by hemoglobin (Hb) in RBCs: Hb + 4O2 \rightarrow Hb(O2)_4 (oxyhemoglobin)
  • Dissolved O2\approx 1.5\% (establishes P{O_2})

Oxygen-Hemoglobin Dissociation Curves

• Sigmoidal shape due to cooperative binding
  • Initial O₂ binding ↑ affinity for subsequent molecules (conformational change)
• Normal ranges
  • Lung capillaries: P{O2}=10$–$13\,kPa → Hb ≈ 97$–$100\% saturated
  • Systemic tissues: P{O2}=5$–$10\,kPa → Hb releases ≈ 20$–$25\% of carried O₂ at rest; more during exercise
• Bohr effect (rightward shift)
  • Elevated P{CO2}, ↓pH, ↑temperature, ↑2,3-BPG → ↓affinity (facilitates unloading)
  • Expressed mathematically: HbO2 + H^+ \leftrightarrow HHb + O2
• Fetal vs adult hemoglobin
  • HbF curve lies left of HbA (higher O₂ affinity) to extract O₂ from maternal circulation
  • Graphically: at P{O2}=4\,kPa, HbF ~80\% saturated vs HbA ~60\%

Neural & Chemical Regulation of Ventilation

• Central pattern generator: medulla oblongata (spinal bulb) & pons
• Chemoreceptors
  • Central (medullary) respond to [H^+] in cerebrospinal fluid (reflects P{CO2})
  • Peripheral (carotid & aortic bodies) respond to P{O2} < 8\,kPa & pH changes
• Reflex arc
  1. Excess CO_2 / ↓pH detected
  2. Medulla increases action potential frequency via phrenic & intercostal nerves
  3. Diaphragm/intercostals contract harder → ventilation ↑
  4. Blood gases normalize (negative feedback)

Effects of Smoking

• Tar & particulate matter
  • Destroy ciliary epithelium → impaired mucociliary clearance (Fig. 10.6)
• Chronic bronchitis: hypersecretion of mucus, narrowed airways
• Emphysema: alveolar wall destruction → ↓surface area, ↓elastic recoil
• Carcinogens (e.g., benzo[a]pyrene) → lung cancer (pages 343-345 reference)

Pulmonary Volumes & Spirometry

• Vital capacity (VC): max air exhaled after max inspiration (~4.5\,L male)
• Inspiratory reserve volume (IRV): extra inspired above tidal (~3\,L)
• Expiratory reserve volume (ERV): extra expired below tidal (~1\,L)
• Residual volume (RV) not in list but implied (~1.2\,L)
• Class activity: design simple water-displacement spirometer & test peer values

Plant Gas-Exchange Adaptations (Leaves)

• Cross-section anatomy
  • Upper epidermis (cuticle reduces water loss)
  • Palisade mesophyll: tightly packed, rich in chloroplasts, major site of photosynthesis
  • Spongy mesophyll: loose, interconnected air spaces facilitate diffusion of gases
  • Vascular bundles: xylem (water up), phloem (sugars down/up)
• Stomatal apparatus
  • Two guard cells flank pore
    • High turgor (K⁺ influx → water follows) → stomata open
    • Low turgor → close
  • Aperture ≈ 20\,\mu m wide when fully open
  • Regulate transpiration & CO₂ uptake

Summary of Alveolar Adaptations (Page 14 Table)

• Spherical geometry → maximal surface-to-volume ratio
• Single flattened cell layer → minimal diffusion path
• Moist internal lining → dissolves gases for diffusion
• Dense capillary network in immediate contact → rapid gas uptake/removal

Key Equations & Numerical Facts (Collected)

• Fick\,Law:\;Rate = \dfrac{A\,D\,(P1-P2)}{d}
• P = \dfrac{2\gamma}{r} (Law of Laplace for alveolar stability)
• Carbonic anhydrase reaction:
  CO2 + H2O \leftrightarrow H2CO3 \leftrightarrow HCO_3^- + H^+
• Bohr shift chemical:
  HbO2 + H^+ \leftrightarrow HHb + O2
• Average adult breath: ~500\,mL (tidal volume)
• Number of alveoli: ≈ 3\times10^8 per lung
• Surface area: ≈ 70\,m^2; Barrier thickness: 0.2\text{–}0.6\,\mu m

Ethical & Health Relevance

• Smoking cessation reduces risk of COPD & carcinomas; educational campaigns critical
• Premature infants lack surfactant → neonatal respiratory distress syndrome; surfactant replacement therapy saves lives
• Altitude adaptation: ↑2,3-BPG, polycythemia, rightward curve shift; informs athletic training & hypoxia research