Physiology & Pathophysiology

Physiology: The Pulmonary System 

In order to understand what affect asthma has on the lungs, we must first understand the functions of the affected areas during an unaffected state. 

Overview of gas exchange 

• Perfusion: A process controlled by the cardiovascular system in which blood moves into and out of the capillary beds of the lungs to the body’s tissues and organs 
• Diffusion: A pulmonary system controlled process in which gas moves between lungs’ air spaces and the blood stream 
• Ventilation: A process controlled by the pulmonary system that allows for air to move into and out of lungs (Cordell, 2019). 

Anatomy of Breathing 

• Diaphragm and external intercostal muscles are the major muscles allowing for inspiration
• Sternocleidomastoid and scalene muscles are the accessory muscles for inspiration
• Passive expiration does not require any major muscles 
  • Abdominal and internal costal muscles may be triggered in response to depth of expiration (Cordell, 2019).

O2 transport

1. 1. Getting gases into alveoli through ventilation of the lungs 
   2. Oxygen diffusion from alveoli to capillary blood 
   3. Oxygenated blood perfusion from systemic capillaries 
   4. Oxygen diffusion from capillaries to cells

      ** CO2 diffusion occurs in reverse order (Cordell, 2019).

Bronchial Mucosa Production

• Bronchi = conducting airways of the lungs 
  • Branched into two main bronchi/airways at the trachea, right bronchi and left bronchi
  • Due to the sensitivity of the bronchi, when stimulated they trigger coughing and airway narrowing
  • Right bronchi is larger than the left bronchi allowing foreign particles to aspirate easier
  • At the hila, the right and left bronchi enter the lungs

    

    • Each bronchi branches further:
      • Lobar bronchi → segmental bronchi → subsegmental bronchi → terminal bronchi (smallest conducting airways)
  • Bronchioles subdivide to form tiny tubes, alveolar ducts, that end and become alveolar sacs/clusters
• Mucous production occurs at the submucosal glands of the bronchial to protect it’s epithelium lining
  • Ciliated epithelial cells rhythmically beat pushing mucous blanket towards trachea and pharynx (McCance & Huether, 2019).

Pulmonary and Bronchial Circulation Functions (Asthmatic Event Prevention)

• Effective gas exchange 
  • Even ventilation and perfusion in all portions of the lung
• Filtration of air and debris from circulation 
• Capillaries and alveoli share wall and allow for gas (O2 & CO2) exchange (Cordell, 2019).

Ventilation Mechanism 

• Goal of ventilation: to ensure effective diffusion of O2 from alveoli into blood and diffusion of CO2 from blood to alveoli
• Under the control of the central nervous system (CNS) and autonomic nervous system (ANS) 
• CNS’ role in ventilation: 
  • Brainstem holds the respiratory center 
  • Division of respiratory center: dorsal respiratory group, ventral respiratory group, pontine centers, and apneustic centers  
    • Dorsal respiratory group’s function: determines the basic automatic ventilation rhythm 
    • Ventral respiratory group’s function: activates when a need for increased ventilation is required and holds the inspiratory and expiratory neurons
    • Pontine center: located in the pons of the brain and modifies inspiratory depth
    • Apneustic center: located in medullary centers and establishes ventilatory rate
• ANS’ role in ventilation: 
  • Parasympathetic receptors are the primary controllers of airway caliber and cause smooth muscles to contract
    • Determine the width and narrowness of bronchi 
  • Sympathetic receptors allow for bronchodilation by allowing smooth muscles of bronchi to relax
• Neurochemical control of ventilation involves central chemoreceptors, peripheral chemoreceptors, and lung receptors

  

  • Role of central chemoreceptors: respond to increased PaCO2 and increase the respiratory rate and depth by triggering the brain to trigger the ventilatory system
    • This process in the CNS is stimulated by hydrogen ion in the cerebrospinal fluid 
  • Role of peripheral chemoreceptors: control the increase in ventilation in response to any arterial hypoxemia event through the stimulation of decreased PaCO2 
    • These receptors are located in carotid bodies and the aorta 
  • The lung receptors are made up of irritant receptors, stretch receptors, and juxtapulmonary capillary (J) receptors 
    • Role of the irritant receptors: During stimulation of noxious substances they cause cough, increased respiratory rate, and bronchoconstriction 
    • Role of the stretch receptors: decrease respiratory rate and volume as alveoli are stretched in order to protect against excess lung inflation 
    • Role of the J receptors: provide sensitivity to any increased pulmonary capillary pressure (Cordell, 2019). 

Childhood Asthma 

• Chronic obstructive pulmonary disorder of the bronchial mucosa 
• Episodes of bronchospasm and inflammation in the bronchial airways.
• Familial disease 
  • >100 genes identified as playing a role in the development
• In the United States, there are 6.3 million reported cases of childhood asthma (McCance & Huether, 2019).

Early Asthmatic Responses

• IgE is activated, leading to:

  

  • Degranulation of mast cells; 
  • Release of inflammatory mediators
• IgE release causes: 
  • Vasodilation;
  • Bronchospasm;
  • Mucosal edema;
  • Increased capillary permeability;
  • Tenacious mucous secretions (McCance & Huether, 2019).

Early Asthmatic Response: Immune Response Stimulation 

• Dendritic cells
  • Activated by antigen exposure to the bronchial mucosa 
  • Present antigen to CD4+ T cells 
• IL-4 
  • B-cell activation 
  • Production of IgE 
• IL-5
  • Activation of eosinophils 
    • Bronchial hyperresponsiveness 
    • Fibroblast proliferation 
    • Epithelial injury 
    • Airway scarring 
• IL-8
  • Activates neutrophils 
    • Exaggerates the inflammatory response 
• IL-13 
  • Lessens mucociliary clearance 
  • Boosts fibroblast secretion
  • Contributes to bronchoconstriction 
• IL-17 
  • Increases neutrophilic inflammation 
• IL-22
  • Triggers airway epithelial cells 
    • Further innate and adaptive immune responses 
      • Cytokine release 
      • Chemotaxis of inflammatory mediators (Cordell, 2019). 

Late Asthmatic Response 

• Occurs within 4-8 hours of early response and includes:

  

  • Air trapping/continued bronchoconstriction 
  • Hyperinflation distal to obstructions
    • Increases work of breathing and hypoxemia 
      • Leads to dyspnea from inability of air to release due to lingering obstruction 
  • Chemotactic recruitment of lymphocytes, eosinophils, and neutrophils
    • Prolonged smooth muscle contraction
    • Airway scarring
    • Increased bronchial hyperresponsiveness
    • Impaired mucociliary function
    • If untreated → airway modeling 
      • Tissue made of collagen matrix (McCance & Huether, 2019).

Clinical Manifestations of Childhood Asthma

• Constriction of the chest wall 
• Expiratory wheezing 
• Dyspnea
• Prolonged expiration
• Nonproductive cough
• Substernal, subcostal, intercostal, suprasternal, and sternocleidomastoid retractions 
• Nasal flaring
• Pulsus Paradoxus  
• Status Asthmaticus
  • Bronchospasm that is not reversed by typically treatments and can be life threatening 
• Signs of impending death:
  • Silent chest (no audible air movement upon auscultation of the chest)
  • PaCO2 >70mmHg (Cordell, 2019). 

Risk Factors of Childhood Asthma

• Inhalation of tobacco smoke including cigarettes, pipes, and cigars
• Occupational dusts and chemicals
• Outdoor air pollution
• Indoor air pollution with cooking
• Low birth weight
• Respiratory Tract infections
• Obesity
• Family History
• Allergies (McCance & Huether, 2019).

Diagnosing Childhood Asthma 

• Pulmonary Function Tests (Spirometry):
  • Diagnosis is confirmed by if the patient’s FEV1 (amount of air forced from lungs in one second) improves by 12% or 200ml after receiving a bronchodilator 
  • Indicates that it is reversed with treatment (McCance & Huether, 2019).