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Respiratory Physiology: Complete Notes

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1. Surfactant

What Is It?

How It Works — Law of Laplace

P = 2T / r

• A small alveolus has a small radius → high collapsing pressure → tends to collapse (atelectasis)
• Surfactant reduces T, thus reduces P even in small alveoli, keeping them open

Mechanism of DPPC

Functions of Surfactant

1. Prevents alveolar collapse (atelectasis) — especially in small alveoli
2. Increases lung compliance — reduces work of breathing during inspiration
3. Keeps alveoli of different sizes stable (prevents large alveoli from emptying into small ones)

Clinical Significance — Neonatal Respiratory Distress Syndrome (NRDS)

• Surfactant synthesis begins at gestational week 24, almost always present by week 35
• Premature infants (<35 weeks) may lack surfactant
• Consequences: alveolar collapse, hypoxemia (shunt physiology), decreased compliance, increased work of breathing
• Treatment: exogenous surfactant therapy

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2. Hemoglobin–Oxygen Dissociation Curve

The Curve

Key Values

Physiological Significance of the Sigmoid Shape

• Flat upper portion (PO₂ 60–100 mmHg): Hb remains ~90% saturated even with drops in PaO₂ — protects loading of O₂ in the lungs
• Steep lower portion (PO₂ 20–60 mmHg): Large amounts of O₂ are released with modest drops in PO₂ — facilitates O₂ unloading at tissues

Shifts of the Curve

• At rest, only 25% of delivered O₂ is extracted (normal extraction fraction)

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3. Functional Residual Capacity (FRC)

Definition

FRC = Expiratory Reserve Volume (ERV) + Residual Volume (RV)

Measurement

• Nitrogen washout (open-circuit)
• Helium dilution (closed-circuit)
• Body plethysmography (most accurate, measures all gas including trapped gas)

Factors That Alter FRC

Clinical Importance

• FRC serves as the oxygen reservoir during apnea — at FRC, the lungs contain ~450 mL O₂
• Reduced FRC → rapid O₂ desaturation during apnea (critical in obstetric/obese patients)
• FRC determines the closing capacity relationship — when FRC < closing capacity, small airways close during normal tidal breathing → V/Q mismatch and hypoxemia

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4. Vital Capacity (VC) and Lung Volumes

Lung Volume Subdivisions

TLC (Total Lung Capacity)
├── VC (Vital Capacity)
│   ├── IC (Inspiratory Capacity)
│   │   ├── TV (Tidal Volume, ~500 mL)
│   │   └── IRV (Inspiratory Reserve Volume)
│   └── ERV (Expiratory Reserve Volume)
└── RV (Residual Volume) — cannot be measured by spirometry

Vital Capacity

• Definition: Maximum volume of air that can be exhaled after a maximal inspiration (or inhaled from RV to TLC)
• Measured by spirometry: subject inhales maximally, then exhales completely (no time limit = "slow VC")
• FVC (Forced Vital Capacity) = VC performed with maximal effort and speed

VC Can Be Reduced By Two Mechanisms

1. ↓ TLC — restrictive disease (pulmonary fibrosis, chest wall deformity, neuromuscular weakness)
2. ↑ RV — obstructive disease (emphysema, asthma → air trapping)

• Only by measuring both TLC and RV can these two causes be differentiated

Combined VC vs. Simple VC

• In severe airflow obstruction: combined VC > simple VC — reflects trapped gas in poorly ventilated regions (increased transmural pressure causes airway closure during the single exhalation maneuver near RV)

Normal Reference Values (approximate)

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5. Transport of Respiratory Gases

Oxygen Transport

Form 1: Dissolved O₂

• Governed by Henry's Law: concentration = solubility coefficient × partial pressure
• Solubility coefficient for O₂ = 0.003 mL/dL/mmHg
• At PaO₂ = 100 mmHg: only 0.3 mL/dL dissolved — physiologically small but essential for diffusion

Form 2: Bound to Hemoglobin

• Each gram of Hb carries up to 1.39 mL O₂; normal Hb = 15 g/dL
• Hb molecule: 4 heme + 4 protein subunits; only ferrous iron (Fe²⁺) binds O₂

CaO₂ = (0.003 × PaO₂) + (SaO₂ × Hb × 1.31)

• Normal CaO₂ ≈ 19.5 mL/dL
• Normal CvO₂ ≈ 14.8 mL/dL
• A-V O₂ difference ≈ 4.7 mL/dL

O₂ Delivery (DO₂)

DO₂ = CaO₂ × Cardiac Output Normal = ~1000 mL O₂/min (20 mL/dL × 50 dL/min)

• Normal extraction fraction = 25% (body uses 25% of delivered O₂)
• When DO₂ falls critically, VO₂ becomes supply-dependent → lactic acidosis from cellular hypoxia

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Carbon Dioxide Transport

Bicarbonate Formation

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

• In tissue capillaries: CO₂ enters RBCs → carbonic anhydrase converts to HCO₃⁻ → HCO₃⁻ exits RBC into plasma; Cl⁻ enters RBC (Hamburger / chloride shift)
• In pulmonary capillaries: reverse occurs — Cl⁻ exits RBC, HCO₃⁻ re-enters, converted back to CO₂ which is exhaled

Haldane Effect

• Deoxygenated Hb has 3.5× greater affinity for CO₂ as carbaminohemoglobin, and acts more as a base — takes up H⁺, driving bicarbonate formation
• At lungs: oxygenation of Hb → it acts as an acid, releases H⁺ → drives CO₂ formation and exhalation
• Net result: venous blood carries more CO₂ than arterial blood

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6. Neural Regulation of Respiration

Overview

Respiratory Centers

A. Medullary Centers (primary rhythm generators)

1. Dorsal Respiratory Group (DRG)
   • Located in the nucleus tractus solitarius
   • Primarily drives inspiration
   • Receives input from peripheral chemoreceptors (CN IX/X) and stretch receptors
   • Sets the baseline inspiratory rhythm
2. Ventral Respiratory Group (VRG)
   • Located in the nucleus ambiguus and nucleus retroambigualis
   • Contains both inspiratory and expiratory neurons
   • Active mainly during forced/active breathing
   • The pre-Bötzinger complex (within VRG) is the key rhythmogenesis center — pacemaker for breathing

B. Pontine Centers

1. Pneumotaxic Center (Pontine Respiratory Group, PRG)
   • Located in the upper pons (nucleus parabrachialis)
   • Limits inspiration — sends inhibitory signals to DRG, shortening inspiratory duration
   • Controls respiratory rate and pattern; increases respiratory frequency
2. Apneustic Center
   • Located in the lower pons
   • Tends to prolong inspiration (apneusis = sustained inspiratory gasp)
   • Normally inhibited by the pneumotaxic center
   • If pneumotaxic center is damaged and vagus nerve is cut → apneustic breathing

Chemoreceptor Inputs

Central Chemoreceptors

• Located on the ventrolateral surface of the medulla
• Respond to changes in CSF pH (H⁺ concentration) — NOT directly to CO₂
• CO₂ crosses the blood-brain barrier → combines with H₂O → H⁺ + HCO₃⁻ → ↓ CSF pH → stimulates ventilation
• Primary driver of resting ventilation
• Do NOT respond to hypoxia

Peripheral Chemoreceptors

• Carotid bodies (CN IX — glossopharyngeal) — most important
• Aortic bodies (CN X — vagus)
• Respond to: ↓ PaO₂ (most potent stimulus), ↑ PaCO₂, ↓ pH, ↓ blood flow
• Main defense against hypoxia
• In COPD with chronic CO₂ retention: central receptors become desensitized; peripheral chemoreceptors become the primary drive ("hypoxic drive")

Mechanical/Reflex Inputs

Pattern of Normal Breathing

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Summary Table