Harrison's - Disturbances of Respiratory Function (Ch. 296)

Overview

1. Ventilate the lung tidally to freshen alveolar gas
2. Perfuse alveoli in proportion to their ventilation
3. Allow rapid diffusion of gases between alveolar air and capillary blood
4. Accommodate several-fold increases in O2 demand during exercise or metabolic derangement

PART 1: VENTILATION

The Three Components of the Respiratory System

Lung Volumes

• Total Lung Capacity (TLC): Volume at maximal inspiration - when inspiratory muscles exert maximum force
• Residual Volume (RV): Volume remaining after maximal expiration - when expiratory muscles exert maximum force
• Functional Residual Capacity (FRC): The resting volume - where outward chest wall recoil balances inward lung recoil (passive equilibrium, no muscle activity). This is the natural resting position of the respiratory system.

Statics: Volume-Related Mechanical Properties

• Lung: Always tends to collapse (inward recoil)
• Chest wall: Tends to spring outward at volumes below ~75% TLC
• At FRC, these opposing forces are equal and opposite
• The pressure-volume (P-V) relationship of the lung reflects its compliance (ΔV/ΔP). A stiffer lung (e.g., fibrosis) has reduced compliance; an emphysematous lung has increased compliance.

Dynamic Mechanics: Airflow

• Increased expiratory muscle effort compresses airways (dynamic airway compression)
• Beyond a "choke point," flow is limited by airway properties (caliber, recoil), not effort
• This is why the MEFV (Maximum Expiratory Flow-Volume) curve is reproducible and diagnostically useful

PART 2: GAS EXCHANGE

A. Diffusion

• The alveolar membrane has a huge surface area and minimal thickness - highly optimized for gas diffusion
• Oxygen uptake is normally perfusion-limited (not diffusion-limited): O2 fully equilibrates between alveolar gas and capillary blood before the RBC completes 1/3 of its journey through the alveolar capillary
• Diffusion limitation can occur in:
  • High altitude (low alveolar PO2 gradient)
  • Maximal exercise in elite athletes
  • Interstitial lung disease (thickened alveolar walls)

B. Ventilation/Perfusion (V/Q) Matching

Two Extreme V/Q Abnormalities:

Key Features of Shunt:

• Venous blood passes through lung unaltered (not reoxygenated)
• Mixes with oxygenated blood → lowers mixed arterial PaO2 disproportionately
• Refractory to supplemental O2 (raising FiO2 cannot oxygenate blood through non-ventilated alveoli)

V/Q Mismatch (more common in disease):

• Widening of the distribution of V/Q ratios
• Perfusion of low V/Q units (underventilated) → partial oxygenation → lowers PaO2
• Responds to supplemental O2 (unlike pure shunt), because these alveoli are still ventilated

C. Causes of Arterial Hypoxemia - Summary

PART 3: PATHOPHYSIOLOGY OF COMMON DISEASES

Alveolar Hypoventilation (Hypoventilation)

• PaCO2 is elevated (>45 mmHg), which displaces O2 in alveolar gas (Alveolar gas equation: PAO2 = PiO2 - PaCO2/R)
• Alveolar-arterial O2 difference (A-a gradient) is normal - hypoxemia is purely due to ↑ CO2
• Causes: CNS depression (drugs, brainstem lesions), neuromuscular disease, obesity (OHS), chest wall deformity

Causes of Elevated PaCO2 (Hypercapnia)

1. CO2 production increases AND ventilation fails to compensate
2. Alveolar ventilation decreases (dead space ↑ or minute ventilation ↓)

Obesity Hypoventilation Syndrome (OHS)

• BMI ≥30 + PaCO2 >45 mmHg during wakefulness + sleep-disordered breathing
• Mechanism: Increased load on respiratory muscles (excess weight), reduced respiratory drive
• Often coexists with obstructive sleep apnea

Central Hypoventilation Syndrome

• Failure of automatic respiratory drive from brainstem
• Normal voluntary breathing; fails during sleep
• Congenital (PHOX2B mutation) or acquired (brainstem injury)

Hyperventilation

• PaCO2 falls below normal (<35 mmHg)
• Causes: Anxiety/panic, pain, fever, pulmonary embolism, hypoxia stimulating peripheral chemoreceptors, salicylate toxicity, liver failure, early pregnancy
• Symptoms: Perioral and digital tingling (hypocalcemia due to alkalosis), carpopedal spasm, lightheadedness

PART 4: PULMONARY FUNCTION TESTS (PFTs)

Spirometry

Lung Volume Measurement

• Body plethysmography or gas dilution techniques
• TLC reduced in restriction; RV and TLC elevated in air trapping/obstruction

Pattern Recognition:

DLCO (Diffusing Capacity for CO)

• Measures the ability of the lung to transfer gas across the alveolar membrane
• Reduced DLCO with obstruction: emphysema (destroyed alveolar walls)
• Reduced DLCO with restriction: ILD (thickened alveolar walls), pulmonary vascular disease
• Normal or increased DLCO: Asthma, obesity
• Increased DLCO: Polycythemia, pulmonary hemorrhage (extra Hb in alveoli binds CO)

Bronchodilator Response

• Significant if FEV1 or FVC improves by ≥12% AND ≥200 mL after bronchodilator
• Suggests reversible obstruction (asthma > COPD)

PART 5: ASSESSMENT OF VENTILATORY FUNCTION IN DISEASE

Work of Breathing

• Normal breathing requires minimal effort. In disease, the work is increased by:
  • ↑ Airway resistance (obstruction)
  • ↓ Lung compliance (restriction/fibrosis)
  • Dynamic hyperinflation (air trapping in COPD - puts respiratory muscles at mechanical disadvantage)

Dynamic Hyperinflation (COPD)

• Expiratory flow limitation prevents complete exhalation before the next breath
• Auto-PEEP develops: positive alveolar pressure at end-expiration
• Diaphragm becomes flattened (less efficient)
• Sensation of air hunger and increased dyspnea

Hypoxemia vs. Hypercapnia in COPD

• Early COPD: V/Q mismatch → hypoxemia without hypercapnia
• Advanced COPD: Alveolar hypoventilation + V/Q mismatch → both hypoxemia AND hypercapnia

PART 6: KEY EQUATIONS TO KNOW

Alveolar Gas Equation:

PAO2 = FiO2 × (Patm - PH2O) - PaCO2/R where R (respiratory quotient) ≈ 0.8

Alveolar-Arterial (A-a) Gradient:

A-a gradient = PAO2 - PaO2

• Normal: ~10 mmHg in young adults (increases with age: ~4 + age/4)
• Elevated A-a gradient: V/Q mismatch, shunt, diffusion limitation
• Normal A-a gradient with hypoxemia: hypoventilation or low inspired O2

Dead Space Fraction (Bohr equation):

VD/VT = (PaCO2 - PECO2) / PaCO2

• Normal VD/VT ~0.30
• Elevated in pulmonary embolism, COPD

Clinical Pearls for Exams

1. Shunt hypoxemia is refractory to 100% O2 - the hallmark distinguishing it from V/Q mismatch
2. Pure hypoventilation gives normal A-a gradient; supplemental O2 fully corrects hypoxemia
3. DLCO is the key test for emphysema vs. asthma - both obstructive, but DLCO low in emphysema (destroyed alveolar walls) and normal/elevated in asthma
4. FRC = passive equilibrium point (no muscle activity) - set by lung vs. chest wall recoil balance
5. Dynamic compression makes expiratory flow effort-independent (the basis of the MEFV curve's diagnostic value)
6. In V/Q mismatch, high V/Q regions cannot compensate for low V/Q regions' contribution to hypoxemia due to hemoglobin's sigmoidal saturation curve - blood leaving high V/Q alveoli is already near-fully saturated, so extra O2 there is not helpful
7. The CO2 dissociation curve is more linear than the oxyhemoglobin curve, so high V/Q regions CAN blow off extra CO2 and compensate for low V/Q hypoventilation - this is why hypercapnia is a late finding in V/Q mismatch (the body compensates with increased ventilation to high V/Q units)

Elastic Recoil Pressure - Harrison's Ch. 296

What Is Elastic Recoil Pressure?

Why Does the Lung Have Elastic Recoil?

1. Surface tension at the air-liquid interface lining the alveolar wall (the dominant factor)
2. Elastic tissue within the lung parenchyma itself (collagen and elastin fibers)

Surfactant (produced by type II pneumocytes) dramatically reduces surface tension and prevents alveolar collapse - it directly opposes one component of lung elastic recoil.

Transpulmonary Pressure (Key Formula)

P_transpulmonary = P_alveolus - P_pleura

• This pressure difference is what holds the lung open
• At rest (FRC), P_pleura is negative (~-5 cmH₂O), which keeps the lung inflated
• The transpulmonary pressure equals the elastic recoil pressure of the lung at any static volume

The Pressure-Volume (P-V) Curve of the Lung

Reading the Lung Curve (Blue dashed line):

• The lung always requires positive transpulmonary pressure to stay inflated (curve stays to the right of zero)
• At low volumes: the lung is compliant (flat, small pressure change = large volume change) - this is the range of normal tidal breathing
• At high volumes (near TLC): the lung becomes stiff - large pressure changes yield small volume changes
• At zero pressure: some air remains in alveoli (small airways close, trapping gas = the basis of Residual Volume)

Reading the Chest Wall Curve (Red solid line):

• At volumes below ~75% TLC: chest wall recoil is outward (curve is to the left of zero = negative pressure) - it wants to expand
• At volumes above ~75% TLC: chest wall recoil becomes inward - it resists further expansion
• At FRC (~35% TLC): the chest wall recoil is outward (+), lung recoil is inward (-) and they are exactly equal and opposite

FRC: The Passive Equilibrium Point

FRC is where: Outward chest wall recoil = Inward lung recoil

What Shifts FRC?

Compliance: The Inverse of Stiffness

Compliance (C) = ΔVolume / ΔPressure (units: L/cmH₂O)

• High compliance (emphysema): lung distends easily, low recoil, flat P-V curve
• Low compliance (fibrosis): stiff lung, high recoil, steep P-V curve

Elastic Recoil in Disease - High-Yield Comparisons

Emphysema

• Destruction of alveolar walls → loss of elastic tissue AND reduced surface area → ↓ lung elastic recoil
• P-V curve shifts left (more volume for same pressure)
• FRC ↑, RV ↑, TLC ↑ (barrel chest)
• Small airways lose radial tethering from surrounding parenchyma → collapse during expiration → airflow obstruction even without intrinsic airway disease

Pulmonary Fibrosis (ILD)

• Collagen deposition stiffens lung → ↑ lung elastic recoil
• P-V curve shifts right (less volume for same pressure; requires higher transpulmonary pressure to inflate)
• FRC ↓, TLC ↓, FVC ↓ - restrictive pattern
• Interestingly, MEFV (flow-volume) loops show flows that are actually increased relative to volume because the high recoil drives rapid expiration

Neuromuscular Disease (e.g., Myasthenia Gravis)

• Lung and chest wall recoil are both normal → FRC is normal
• Respiratory muscles too weak to fully inflate (↓ TLC) or deflate (↑ RV) the system
• FVC and FEV1 are low as "innocent bystanders" - airways and parenchyma are unaffected
• DLCO and airway resistance are normal

Key Pearl: Radial Tethering of Airways

• In emphysema: destruction of alveolar walls removes this tethering support → airways collapse during expiration → gas trapping at abnormally high volumes
• In fibrosis: high recoil increases radial tethering → airways are pulled open → flow rates are preserved or increased relative to the reduced lung volumes

Summary Table