Pathophys of Asthma Flashcards
3 classic signs and symptoms of asthma
Intermittent dyspnea
Cough
Wheezing
Hygiene hypothesis
Exposure to infection early in life
Development of a predominately Th1 mediated immune response
Down regulation of a Th2 response
Does Th1 or Th2 cells contribute to asthma?
Th2
2 infections that decrease of incidence and 3 infections that increase the incidence
decrease: croup, otitis
increase: bronchiolitis, RSV, rhinovirus
Atopy
Genetic predisposition to produce specific IgE following exposure to allergens
How does obesity act as a risk factor for asthma?
Not sure, there are some hypotheses
Common genetic etiologies
Comorbidities (sleep disordered breathing and GERD)
Effect of obesity on lung mechanics (lung volume)
Inflammatory mediators secreted by adipose tissue
4 host risk factors
Genetic (including predisposition to atopy)
Obesity
Sex
Preterm or small size for gestational age
7 environmental factors
Allergens Occupational sensitizers and allergens Infections Exposure to tobacco smoke Outdoor or indoor air pollution Diet Stress
Cells involved in asthma
Neutrophils Basophils Eosinophils Mast cells Macrophages Structural cells
2 core mechanisms of asthma
Airway inflammation
Airway remodelling
3 main interleukins in airway inflammation
IL4, 5, 13
Extrinsic vs intrinsic asthma
Ex: typically develops in childhood and is accompanied by IgE mediated allergic inflammation
In: typically develops later in life and is not associated with allergic sensitization
Airway remodelling
Structural alteration of the airway
The degree of remodelling correlates with the severity of asthma
4 major changes in airway remodelling
Proliferation and hyperplasia of goblet cells and submucosal glands
Increased deposition of subepithelial collagen
Airway smooth muscle hyperplasia
Microvascular changes
How does the epithelium change with airway remodelling
Disruption of tight junctions (allows entry of allergens, activation of inflammatory cells, and propagation of inflammation)
Proliferation and hyperplasia of goblet cells (mucus hypersecretion)
How does the epithelial basal lamina change in airway remodelling
Sub-basement membrane thickening (collagen deposition)
Increased number of myofibroblasts (producing matrix)
How does airway smooth muscle change in remodelling
Increased smooth muscle mass (hypertrophy and hyperplasia)
Causes airway lumen narrowing, airway hyper-responsiveness, and promotes further airway remodelling)
Microvascular changes in remodelling
Bronchial neovascularization
Dilated and tortuous mucosal blood vessels
Increased permeability
Associated with increased mucosal edema
Airflow obstruction in asthma
Variable narrowing of the airway lumen causing variable airflow obstruction is a cardinal feature of asthma
Mechanisms: contraction of ASM (inflammation/bronchoconstriction), thickening of the airway (remodelling and edema), mucus plugging)
