Pulmonary Physiology

Pulmonary Physiology Overview

Primary Function of the Respiratory System

  • Maintain systemic arterial blood gas levels within normal range.
  • O2 uptake and CO2 excretion at the lungs must match the rates of O2 use and CO2 production by cellular respiration.

Main Components of the Respiratory System

  • Lungs
  • Chest wall
  • Pulmonary blood vessels
  • Muscles of the chest wall power the movement of air into the lungs.

Distribution of Pulmonary Blood Flow

  • Matches ventilation to ensure proper gas exchange.
  • Systemic O2 and CO2 levels are monitored by chemoreceptors.

Treatment Considerations

  • Requires understanding of factors governing ventilation, diffusion of gases, and perfusion in the lungs.

Blood-Gas Interface

  • The lung is specialized for gas diffusion with a large internal surface area of 50-100 ext{ m}^2.
  • Surface area is created by repeated branching of the airways, from the trachea to over 300 million alveoli.
  • Ventilation is the process where air enters the lungs and comes into contact with alveoli.
  • Each alveolus is surrounded by a dense network of pulmonary capillaries.

Structure of the Blood-Gas Interface

  • Thickness: less than 1 ext{ μm}
  • Consists of:
    • Thin layer of surface liquid.
    • Alveolar lining cells (type 1 pneumocytes) and basement membrane.
    • Thin layer of interstitial fluid.
    • Pulmonary capillary endothelial cells and basement membrane.

Gas Laws

  • Volume, pressure, and temperature of gases are related by physical laws explaining mechanics of air movement and gas diffusion.

Boyle's Law

  • Basis of gas flow during ventilation; mechanical events change lung volume, resulting in pressure gradients that drive gas flow.
  • Used in derivation of residual volume using whole-body plethysmography.

Charles’ Law

  • Gas volume varies in proportion to temperature; air expands as it is warmed during inspiration.

Dalton's Law

  • Each gas in a mixture exerts a partial pressure proportional to its concentration; the sum of partial pressures equals total pressure.
  • Used to estimate alveolar O2 partial pressure (P{O2}).

Henry's Law

  • The volume of dissolved gas is proportional to its partial pressure.
  • Example: If arterial blood's P{CO2} = 40 ext{ mm Hg} and K = 0.06 ext{ mL CO}2/ ext{dL blood/mm Hg CO}2, then:
    C{CO2} = K imes P{CO2} = 0.06 imes 40 = 2.4 ext{ mL/dL}.

Units and Terminology

  • Gas quantities referred to using standard notations:
    • Gas pressures reported in mm Hg (Torr) or cm (1 mm Hg = 1.36 cm).
    • Pascal: 1 kPa = 7.5 mm Hg.
    • Barometric pressure (P_b): Total gas pressure in the atmosphere, approximately 760 ext{ mm Hg} at sea level.

Gas Notations

  • Px: Partial pressure of gas x (e.g., P{CO_2}: partial pressure of carbon dioxide).
  • Fx: Fractional volume or pressure (e.g., F{N_2}: nitrogen fraction of gas mixture).
  • Saturation: Usually of hemoglobin with O2, expressed as decimal fraction or % (e.g., S{O2}: % saturation of hemoglobin with oxygen).
  • Cx: Concentration (content) of gas (e.g., C{O_2}: total oxygen content).

Locations in Blood

  • a: Arterial blood (e.g., P{aCO2}: carbon dioxide partial pressure of arterial blood).
  • v: Mixed venous blood (e.g., P{vCO2}: carbon dioxide partial pressure of mixed venous blood).
  • c: Pulmonary capillary blood (e.g., P{cO2}: oxygen partial pressure of pulmonary capillary blood).
  • A: Alveolar gas (e.g., P{A O2}: alveolar oxygen partial pressure).
  • I: Inspired air (e.g., F{I O2}: oxygen fraction of inspired gas).
  • E: Mixed expired air (e.g., P{E CO2}: carbon dioxide partial pressure in mixed expired air).

Water Vapor in Inspired Air

  • Air is humidified in the upper respiratory tract during inspiration.
  • Water vapor pressure (P{H2O}) in inspired air is 47 ext{ mm Hg} at 37°C.
  • Addition of water vapor reduces the partial pressure of other gases.
  • Inspired P{O2} at sea level is reduced:
    P{O2} = 0.21 imes (760 - 47) = 150 ext{ mm Hg}.

Standard Conditions

  • Body Temperature and Pressure, Saturated (BTPS) used clinically assumes:
    • Body temperature of 37°C (310 K)
    • Barometric pressure of 760 mm Hg
    • Water vapor pressure of 47 mm Hg.

Mechanics of Breathing

  • Airflow requires pressure gradients between the mouth and the alveolus.
  • Breathing becomes difficult if the lung or chest wall is stiff (low compliance) or if airway resistance is high.

Definitions of Compliance and Resistance

  • Resistance: Dynamic property determined during gas flow.
  • Compliance: Elastic property measured without gas flow.

Lung Volumes

  • Spirometer measures lung volumes and gas flow rates during pulmonary function testing.
  • Tidal volume (V_t): Amount of air breathed in and out during normal breathing.
  • Vital capacity (VC): Maximum possible volume that can be expired following a maximal breath inspired.
  • Residual volume (RV): Volume of gas remaining in the lung at the end of forceful expiration.
  • Functional residual capacity (FRC): Resting lung volume at the end of quiet expiration.
    • Normal FRC is approximately 40% of total lung capacity (TLC).
    • Variables are optimized at normal FRC including work of breathing, vascular resistance, and ventilation/perfusion matching.
    • Mechanical ventilation often corrects abnormal FRC.

Lung Volume Abnormalities

  • Restrictive lung diseases (e.g., pulmonary fibrosis) characterized by reduced lung volumes.
  • Obstructive lung diseases (e.g., asthma, emphysema) characterized by obstruction to airflow.

Muscles of Ventilation

  • Diaphragm: Most important muscle of inspiration; contraction increases the vertical height of the thoracic cavity.
  • External intercostal muscles: Produce a “bucket-handle” movement of the ribs, increasing the lateral and anteroposterior diameter of the chest.
  • Expiration is passive during quiet breathing but becomes active during exercise.
  • Muscles of expiration: Abdominal wall muscles.
  • Internal intercostal muscles: Assist expiration by pulling the ribs downward and inward.
  • Neuromuscular diseases (e.g., Guillain-Barré syndrome) can cause respiratory muscle weakness, potentially requiring mechanical ventilation.

Airway Anatomy

  • Air is distributed through a highly branched airway.

Conducting Zone

  • Comprises the first 16–17 generations of airway division (from trachea to terminal bronchioles).
  • Gas exchange occurs in the respiratory zone, distal to the terminal bronchioles.

Lung Acinus

  • A functional unit formed by the division of a terminal bronchiole into the respiratory bronchioles, alveolar ducts, and alveoli.
  • Gas moves by diffusion within lung acini.

Alveolar Damage in Emphysema

  • Centriacinar Emphysema: Damage primarily in the respiratory bronchioles; associated with smoking; most damage in the apical regions of upper lobes.
  • Panacinar Emphysema: The entire acinus is damaged; associated with α1-antitrypsin disease; typically involves the entire lung, with lung bases most diseased.
  • α1-Antitrypsin: A serum protein produced by the liver that combats damaging protease activity in the lung; deficiency leads to panacinar emphysema and liver cirrhosis.

Lung and Chest Wall Recoil

  • Subatmospheric pressure in the intrapleural space allows air to be drawn into the airway during inspiration.
  • Pressure is created by the opposing recoil of the lungs and chest wall.

Transpulmonary Pressure (P_tp)

  • The force acting across the wall of the lung to expand it; calculated as the difference in pressure between the alveoli (Pa) and the intrapleural space (P{ip}):
    P{tp} = Pa - P_{ip}.

Mechanics of Pressure Changes

  • During relaxed respiratory muscles:
    • Alveolar pressure is the same as atmospheric pressure (0 ext{ cm}), intrapleural pressure is about -5 ext{ cm}.
  • Inspiratory muscles contraction causes P{ip} to become more negative (e.g., P{ip} = -10 ext{ cm}).
  • Positive value indicates a force for lung expansion (inspiration); negative P_tp indicates a compression force during forced expiration.

The Ventilation Cycle

  • Air flows in/out of the lung due to pressure differences along the airway between the mouth and alveoli.
  • Airflow is driven by changes in alveolar pressure, which result from changes in intrathoracic pressure.
  • Contraction of inspiratory muscles reduces P{ip} and increases P{tp}, expanding the lung.
  • Increased lung volume decreases alveolar pressure, driving inspiration.
  • Passive recoil of lung and chest wall during quiet expiration decreases lung volume, increasing alveolar pressure and driving gas out of the lung.

Pressure-Volume Relation of the Lung

  • Compliance is the transpulmonary pressure change required to produce a unit change in lung volume.
  • Static compliance: Measured at the start and end of a tidal breath when gas flow has stopped.
    • Decreased lung compliance (e.g., pulmonary fibrosis) increases work of breathing, leading to dyspnea.
    • Increased lung compliance (e.g., pulmonary emphysema) causes airway obstruction on expiration.
  • Lung compliance is low at both high and low lung volumes:
    • High volume: Lung tissue is already stretched.
    • Low volume: Many lung acini are collapsed.
  • Compliance is largest at FRC (Functional Residual Capacity).
    • Hysteresis: Different path of expiration curve vs. inspiration curve.

Surfactants

  • Phospholipids (mainly dipalmitoyl phosphatidylcholine) secreted by type 2 pneumocytes in alveolar walls.
  • Line the inner surface of the alveoli.
  • As lung volume decreases during expiration, surfactant molecules are forced closer together and repel each other, resisting alveolar collapse.
  • Functions of surfactant:
    • Maintains alveoli open during expiration, allowing more time for gas diffusion.
    • Counters surface tension.
    • Prevents alveolar atelectasis (collapse).
  • Law of Laplace predicts smaller alveoli will have higher internal pressure, causing them to empty into larger alveoli unless maintained by lung surfactants that reduce surface tension.
  • Respiratory distress syndrome of the newborn (hyaline membrane disease) is caused by surfactant deficiency.
  • Corticosteroids given to the mother prior to delivery can increase surfactant production.

Elastic Properties of the Lung and Chest Wall

  • Compliance is optimal around FRC, minimizing the work of breathing.
  • FRC is controlled by the relative strength of lung and chest wall recoil forces.
  • Lungs tend to collapse; chest wall tends to expand.
  • Causes of low thoracic compliance includes:
    • Pulmonary fibrosis
    • Pulmonary edema
    • Pleural effusion
    • Thoracic musculoskeletal pain
    • Rib fracture
    • Morbid obesity
    • Increased abdominal pressure
  • Interstitial lung disease causes the lung to be stiff and fibrotic, with low compliance.

Airway Resistance

  • A dynamic property that manifests during gas flow.
  • Airway resistance (R) determines the rate of gas flow (V) for a given pressure gradient ( riangle P): R = rac{V}{ riangle P}.

Factors Affecting Airway Resistance

  1. Airway radius: Main component; bronchi and bronchioles are sites of variable resistance.
    • Parasympathetic nerves release acetylcholine, causing bronchoconstriction.
    • Catecholamines relax bronchial smooth muscle through β2 receptors.
    • Selective β2-receptor agonists induce bronchodilation in asthma patients.
  2. Lung volume: Low lung volume increases airway resistance.
  3. Turbulent gas flow: Occurs in larger airways and at branch points; bronchoconstriction and high velocity increase turbulence, causing wheezing.

Asthma

  • Key spirometry feature is reversible bronchoconstriction following treatment with a β2 agonist.
  • Characterized by inflammatory hyperreactive airways.
  • Triggers include allergens, infections, exercise, cold air, and drugs.
  • Methacholine can be given during pulmonary function testing to provoke bronchospasm when diagnosing airway hyperreactivity.

Breath Sounds

  • Wheezing: Musical sound, typically during expiration, created by high-velocity airflow from restricted airways; occurs during bronchospasm, airway edema, or airway partial obstruction.
  • Rales (crackles, crepitus): Inspiratory sounds created by forceful opening of alveoli; occurs in pulmonary edema, atelectasis, and interstitial lung disease.
  • Rhonchi: Low-pitched vibration (snoring), often rattling, occurring during inspiration and/or expiration; created by mucus-air interface; occurs in bronchitis or COPD.
  • Stridor: Harsh high-pitched wheeze during inspiration created by severe upper-airway obstruction; occurs in infants with croup, foreign body obstruction, epiglottitis, or laryngeal tumor or edema.

Dynamic Airway Compression

  • During forced expiration, intrapleural pressure becomes positive, compressing airways.
  • Distal bronchioles, lacking cartilaginous support, are at risk of collapsing.
  • Radial traction force helps resist collapse.
  • Emphysema patients experience increased airway resistance and gas trapping due to weakened radial traction forces.

Strategies to Reduce Dynamic Airway Collapse

  • Slow expiration reduces intrapleural pressure.
  • High resting lung volume increases airway diameter.
  • Pursed-lip breathing creates positive pressure in the mouth, increasing pressure inside the airways.

Clinical Signs of Emphysema

  • Increased anterior-posterior diameter = Barrel chest.
  • Hyperresonance.
  • Decreased breath sounds.
  • Large, hyperlucent lung fields, flattened diaphragm, and increased retrosternal airspace (observed in chest radiography).

Expiratory Flow Limitation

  • Maximal expiratory flow rate is achieved with relatively little expiratory effort due to dynamic airway compression.
  • Expiratory flow becomes independent of effort at medium to low lung volumes.
  • Patients with emphysema experience expiratory flow limitation during normal quiet breathing.

Static and Dynamic Compliance During Mechanical Ventilation

  • High airway pressure poses a risk of lung rupture.
  • Peak inspiratory pressure (PIP): Highest pressure recorded when a tidal volume is delivered during ventilation.
  • Plateau pressure (P_{PLAT}): Airway pressure recorded after a short pause before expiration, reflecting elastic (static) properties.
  • Static compliance can be calculated as:
    C{static} = rac{P{PLAT} - P{EEP}}{Vt}.
  • Dynamic compliance includes the pressure component due to airway resistance:
    C{dynamic} = rac{P{IP} - P{EEP}}{Vt}.

Clinical Spirometry Terms

  • Forced expiratory volume in 1 second (FEV1): Volume expired in the first second of a forced expiration test.
  • Forced vital capacity (FVC): Total volume expired under maximum effort.
    • Normally, FEV1 is about 80% of FVC (FEV1/FVC ratio = 0.8).
  • Expiratory flow through the middle 50% of the expired breath (FEF25-75) is also determined.

General Disease Patterns

  • Obstructive lung diseases (e.g., emphysema, chronic bronchitis, asthma): High airway resistance reduces both FEV1 and FVC, lowering the FEV1/FVC ratio.
  • Restrictive lung diseases (e.g., pulmonary fibrosis): Low lung compliance reduces virtually all lung volumes, particularly TLC and FVC, but the FEV1/FVC ratio is normal or increased.

Chronic Obstructive Pulmonary Disease (COPD)

  • Applies to patients with either emphysema or chronic bronchitis.

Equations for Compliance

  • Effective dynamic compliance (C{DYNE}) formula:
    C{DYNE} = rac{P{IP}-P{EEP}}{V_t}
  • Static compliance reflects the elastic properties of the lung.
  • Dynamic compliance reflects both elastic properties and airway resistance.

Bronchospasms Treatment

  • Can be treated with a bronchodilator to reduce peak airway pressure when the respirator delivers a tidal breath.