Pathophysiology of Asthma and COPD Flashcards
Obstructive vs. Restrictive Lung Disease
Obstructive:
- Increased resistance to airflow
- Asthma, emphysema, bronchitis
Restrictive:
- Decreased expansion of the lungs due to alterations in the lung tissue, pleura, chest wall or neuromuscular function
- Pneumothorax, pneumonia, TB
What characteristics define asthma?
Chronic obstructive lung disease
- Airway inflammation
- Reversible airway obstruction
- Airway hyperresponsiveness
- Airway remodeling over time
- Episodic with acute exacerbations and symptom-free periods
Describe the pathogenesis of asthma:
Initiation: combo of genetics and environment, with symptoms, often beginning in childhood
Damage to lower airways due to inhaled agents stimulates abnormal immune responses in susceptible individuals
Recurrent episodes and aberrant repair lead to the sustained presence of inflammatory cells and mediators, airway remodeling, and airway hyperresponsiveness
Describe how the gut microbiota can be a risk factor for asthma
Gut microbiota trains the immune system to recognize pathogen vs. “friendly” bacteria
Dysbiosis is implicated in the dev. of allergies and asthma (skewing helper T cells toward increased type 2 TH cells)
Allergy has been associated with decreased gut microbiota diversity
What is atopy?
Predisposition toward developing allergic hypersensitivity
Typically associated with heightened immune responses to common allergens
What are some possible triggers in non-allergic asthma?
Cold air
Viral or bacterial infection
Exercise
GERD
What are some common atopy asthma triggers?
Pollen
Mold
Dust mites
Cigarette smoke
What kind of antibodies mediates allergic reactions?
IgE antibodies
What key cellular components promote airway remodeling?
Goblet cell hyperplasia
Smooth muscle hypertrophy and hyperplasia
Subepithelial fibrosis/stiffening of airway
What role do eosinophils have in an asthma attack?
They play a prominent role in the late phase of an asthma attack
Describe the role of these mediators in the early phase of bronchoconstriction, edema, mucosal thickening, and secretions:
ACh, histamine, leukotrienes, lipoxins, adenosine
ACh: bronchoconstrictor
Histamine: bronchoconstriction, vascular permeability, leakiness (edema), and increases mucus viscosity
Leukotrienes: bronchoconstriction, increased vascular permeability, increased mucus secretion, eosinophil recruitment
Lipoxins: anti-inflammatory DECREASED in asthma
Adenosine: AMP can cause bronchoconstriction in asthma and COPD patients
Describe the role of these mediators in the late phase of an asthma attack:
Eosinophil chemotactic factor, eotaxins, eosinophil major basic protein, ROS, interleukins, eosinophils
Eosinophil chemotactic factor: attracts additional eosinophils to the region of inflammation
Eotaxins: attracts eosinophils, mast cells
Eosinophil major basic protein: cause additional tissue damage
ROS: cause tissue damage
Interleukins: promote eosinophil survival activity (ex. IL-5)
Eosinophils: release numerous inflammatory mediators
Describe the airway remodeling that occurs in asthma and what causes it:
Bronchial smooth muscle hypertrophy and hyperplasia
Goblet cell (mucus-producing) hyperplasia, hypersecretion (thicker)
Subendothelial mucous gland hypertrophy: mucus plugs; partial or total occlusion of lumen, mucus in the airway lumen
Deposition of collagen and fibrocytes in epithelial basement membrane –> thickening and stiffening
Loss of ciliated epithelial cells –> more exposure of the airway to allergens, toxins, microbes
Increased number & size of blood vessels in bronchial tissue, tend to be leaky –> edema of airways
What can decrease the airway radius in asthma?
Bronchoconstriction
Mucus production
Inflamed thickened airway wall
What does increased airway resistance in asthma lead to?
Accumulation of air behind closed airways –> air trapping and lung hyperinflation
In severe cases, no gas exchange can occur –> hypoxia
Is inspiration or expiration more difficult for patients with asthma? Why?
Expiration
The closing tendency of the airways is greatly increased during expiration
Because the bronchioles of the asthmatic lungs are already narrowed, further narrowing during expiration creates more obstruction –> air trapping
Sympathetic B2 adrenergic receptor activation results in:
Bronchodilation
Parasympathetic M3 cholinergic receptor activation results in:
Bronchoconstriction
What causes the symptoms of an asthma attack?
Airway narrowing due to bronchospasm (sudden constriction)
Edema/swelling
Increased mucus production
Increased mucus thickening
What are the clinical manifestations of an asthma attack?
Cough, wheeze, SOB
Sensation of chest tightness
Anxiety, tachycardia, palpitations
Tachypnea, cyanosis, use of accessory muscles
What is status asthmaticus?
An acute exacerbation of asthma that remains unresponsive to initial treatment with bronchodilators
Wheezing may disappear as airways constrict more and more