Pathophysiology of Asthma Flashcards
Basic pathology can be divided into 2 related components
1) An inflammatory/immune system component, in which the individual develops a hypersensitivity to a specific stimulus, causing an inflammatory response upon subsequent exposures to that stimulus.
2) An airway component, where the allergen-induced inflammation release mediators that affect cellular function, produce limitations in tissue function, resulting in the generation of symptoms (dyspnoea, excess mucus, and cough).
Hagen Poiseuille
Airway radius decreases, the resistance increases dramatically
Pathological changes in asthma
Primarily airway smooth muscle contraction and mucus hypersecretion which reduce the size of the airway lumen and therefore increases airway resistance and decreases airflow.
Majority asthma patients this is reversible
Allergic asthma involves 2 stages
1) Sensitisation - where the immune system first encounters the allergen and develops an adaptive (antibody- and lymphocyte-mediated) immune response.
2) The allergic response - where the allergen is subsequently re-encountered, triggering the adaptive response previous primed during sensitisation. This generates an inflammatory response within the airways, producing symptoms.
Sensitisation
- Allergen is inhaled and enters the airway tissue
- Allergen encountered by APCs to present to the adaptive immune system
- After engulfing and processing the allergen, the antigen is displayed externally so APC encounters a helper T cell
- T cell is activated and matures in Th2 cell
- Th2 cell interacts with a B cell to initiate proliferation and production of IgE antibodies
- IgE antibodies circulate and bind to receptor on mast cells
Airway remodelling
- long term, negative structural changes that are irreversible
- can occur in patients with severe, poorly-controlled asthma, which results from repeated inflammation-induced tissue injury.
What does airway remodelling involve
- A progressive and irreversible decline in airway and respiratory function
- Increase obstruction. And decrease FEV1
- Occurs in patients with severe, poorly controlled asthma
Role of mast cells in asthma pathophysiology
Allergen induces degranulation - release inflammatory mediators
Role of eosinophils in asthma pathophysiology
Chemokine induced degranulation - release of inflammatory mediators
Inflammatory mediators produced by mast cells
Leukotrienes, prostaglandis
Inflammatory mediators produced eosinophils
Reactive oxygen species, proteolytic enzymes, leukotrienes