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Mechanism of Respiration

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1. Definition and Overview

• External (Pulmonary) Respiration - gas exchange between the atmosphere and the blood at the alveoli
• Internal (Tissue) Respiration - gas exchange between blood and tissue cells at the mitochondrial level

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2. Anatomy of the Respiratory System

Conducting Zone (Anatomical Dead Space)

• This zone does not participate in gas exchange
• It filters, warms, and humidifies incoming air
• Volume = ~150 mL (anatomical dead space)

Respiratory Zone (Gas Exchange Zone)

• Each lung contains ~300 million alveoli, each ~200 μm in diameter
• Total alveolar surface area = ~70 m² (size of a tennis court)
• Lined by:
  • Type I pneumocytes - thin, flat cells ideal for gas diffusion (~95% of surface)
  • Type II pneumocytes - secrete surfactant to reduce surface tension; also regenerate Type I cells
  • Alveolar macrophages - phagocytose dust and debris (the "scavengers" of the lung)

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3. Mechanics of Breathing (Ventilation)

Key Pressures

The intrapleural pressure is always subatmospheric (negative). This negative pressure keeps the lungs inflated against their natural tendency to recoil inward.

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A. INSPIRATION (Active Process)

1. Inspiratory muscles contract:
   • Diaphragm (primary muscle) - contracts and descends ~1.5 cm (during quiet breathing), increasing the vertical dimension of the thoracic cavity
   • External intercostal muscles - contract, elevating the ribs ("bucket handle" movement) and sternum ("pump handle" movement), increasing AP and transverse diameters
   • During forced/deep inspiration, accessory muscles are recruited: sternocleidomastoid (elevates sternum), scalenes (elevate first 2 ribs), pectoralis minor
2. Thoracic volume increases → intrathoracic and intrapleural pressure falls further (from -4 to ~-8 mmHg)
3. Lungs expand (held to chest wall by negative intrapleural pressure) → lung volume increases
4. Alveolar pressure falls below atmospheric (from 760 to ~758 mmHg)
5. Air flows in from atmosphere into alveoli (down the pressure gradient) until Palv = Patm

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B. EXPIRATION (Passive at Rest)

1. Inspiratory muscles relax - no active muscle contraction required during quiet breathing
2. Elastic recoil of the lungs (due to elastic fibers and surface tension) drives the lungs back to their resting position
3. Thoracic volume decreases → intrapleural pressure rises back to -4 mmHg
4. Alveolar pressure rises above atmospheric (760 → ~762 mmHg)
5. Air flows out from alveoli to atmosphere

• Internal intercostal muscles - depress ribs
• Abdominal muscles (rectus abdominis, obliques) - increase intraabdominal pressure, force diaphragm upward

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4. Lung Compliance

• Normal compliance = ~200 mL/cmH₂O
• Decreased compliance (stiff lungs) - pulmonary fibrosis, pulmonary edema, ARDS (more effort needed to breathe)
• Increased compliance - emphysema (lung tissue destroyed, elastic recoil lost; lungs overinflate but cannot expel air)

Surface Tension and Surfactant

• Composition: Dipalmitoylphosphatidylcholine (DPPC) - the main active component
• Function: Reduces surface tension, especially at low lung volumes; prevents alveolar collapse (atelectasis)
• Clinical: Deficiency in premature neonates causes Infant Respiratory Distress Syndrome (IRDS/RDS) - treated with exogenous surfactant

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5. Lung Volumes and Capacities

RV cannot be measured by spirometry - requires gas dilution or body plethysmography

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6. Dead Space and Alveolar Ventilation

• Minute ventilation (VE) = Tidal volume × Respiratory rate = 500 mL × 14 = 7000 mL/min
• Anatomical dead space = ~150 mL (conducting airways that don't exchange gas)
• Physiological dead space = Anatomical dead space + Alveolar dead space (perfused but not ventilated alveoli)
• Alveolar ventilation (VA) = (TV - Dead space) × Rate = (500 - 150) × 14 = 4900 mL/min

Bohr Equation (Dead Space Calculation)

Alveolar Ventilation Equation

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7. Diffusion of Gases (Alveolar-Capillary Exchange)

Rate of diffusion ∝ (Surface area × Partial pressure gradient × Solubility) / (Thickness × √Molecular weight)

• Partial pressure gradient (driving force): O₂ moves from alveolus (PAO₂ ~100 mmHg) → capillary blood (PaO₂ ~40 mmHg); CO₂ moves from blood (~46 mmHg) → alveolus (~40 mmHg)
• Surface area - ~70 m² for both lungs
• Membrane thickness - ~0.5 μm (alveolar epithelium + basement membranes + capillary endothelium)
• Solubility - CO₂ is 20× more soluble than O₂, hence CO₂ diffuses much more readily despite a smaller gradient

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8. Transport of Gases in Blood

Oxygen Transport

• Right shift (reduced O₂ affinity, easier O₂ unloading at tissues): ↑ CO₂, ↑ H⁺ (Bohr effect), ↑ temperature, ↑ 2,3-DPG
• Left shift (increased O₂ affinity, reduced O₂ delivery): ↓ CO₂, ↓ H⁺, ↓ temperature, ↓ 2,3-DPG, fetal Hb (HbF)

Carbon Dioxide Transport

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

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9. Ventilation-Perfusion (V/Q) Matching

• Normal V/Q ratio = ~0.8 (VA ~4.2 L/min, Q ~5 L/min)
• V/Q = 0 (Shunt): Alveolus perfused but not ventilated (e.g., collapsed alveolus, pneumonia) - causes hypoxemia not correctable by supplemental O₂
• V/Q = ∞ (Dead space): Alveolus ventilated but not perfused (e.g., pulmonary embolism)
• V/Q mismatch is the most common cause of hypoxemia in clinical practice

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10. Control of Respiration

Central Respiratory Centers

Chemoreceptors (Chemical Control)

• Respond to CO₂ (via changes in CSF H⁺ concentration)
• Most important in minute-to-minute regulation
• Equation: CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻ (CO₂ crosses blood-brain barrier freely; H⁺ does not)
• ↑ PCO₂ → ↑ CSF [H⁺] → ↑ ventilation

• Carotid bodies (cranial nerve IX) and aortic bodies (cranial nerve X)
• Respond primarily to: ↓ PaO₂ (<60 mmHg), also ↑ PaCO₂, ↓ pH
• Important during hypoxemia (e.g., high altitude, chronic lung disease)
• In COPD with CO₂ retention, the hypoxic drive via peripheral chemoreceptors becomes the primary driver of breathing (basis of the "O₂ toxicity" concern)

Other Reflexes

• Hering-Breuer reflex: Pulmonary stretch receptors (in airway smooth muscle) activated on inflation → inhibit further inspiration (via vagus nerve) - prevents overinflation
• Irritant receptors: Triggered by noxious stimuli → bronchoconstriction, cough, hyperpnea
• J-receptors (juxtacapillary): In alveolar walls, stimulated by pulmonary congestion/edema → rapid shallow breathing, dyspnea
• Exercise: Increases ventilation via joint/muscle proprioceptors, CO₂ production, and lactic acidosis

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11. Summary Flow Chart

Inspiratory muscle contraction (diaphragm + external intercostals)
        ↓
Thoracic cavity enlarges
        ↓
Intrapleural pressure falls (more negative)
        ↓
Lung expands → Alveolar pressure falls below atmospheric
        ↓
Air flows in (inspiration)
        ↓
O₂ diffuses across alveolar-capillary membrane into blood
CO₂ diffuses from blood into alveoli
        ↓
Inspiratory muscles relax → Elastic recoil expels air (expiration)
        ↓
CO₂ expelled; O₂-loaded blood returns to systemic circulation

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12. Clinical Correlations (High-Yield for MBBS)

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What's inside (21 slides)