Pathophysiology of asthma Flashcards
Define asthma
chronic inflammatory condition categorised by episodes of reversible airflow limitation + bronchial hyperresponsiveness, where difficulty breathing (dyspnoea)
How can asthma be divided?
Inflammation
Airway dysfunction
How does the inflammatory response to asthma start?
hypersensitivity to stimulus (allergen - pollen, house dust mites)
Describe airway dysfunction of asthma
allergen-induced inflammation release mediators
affecting cellular function, produce limitations in tissue function (airflow) –> symptoms (dyspnoea, excess mucus, cough)
What happens to the airways during an asthma attack?
- inflammation –> pathological changes
- smooth muscle contraction + mucus hypersecretion
- reducing lumen size
- increases airway resistance + decreases airflow
What are the stages of allergic asthma?
Sensitisation
Allergic response
What’s sensitisation
immune system 1st encounters allergen + develops an
adaptive (antibody lymphocyte-mediated) immune response
What’s an allergic response
allergen re-encountered, triggering adaptive response generating inflammatory response within airways producing symptoms
Describe the process of sensitisation
-allergen enters airways
-stimulates epithelium releasing proinflammatory signals
-APCs (dendritic cells + macrophages) engulf + process allergen
-presents antigen to naïve (CD4+) Th
-activated, matured into Th2
-interacts w B cell, initiating class-switching,proliferation, production of IgE
-bind the antigen in allergen
-circulate, bind (via heavy chain/Fc region) to IgE
(FcεRI) receptors on mast cells
-light chain/Fab region still displayed for antigen binding
-Th2 cells secrete ‘Th2 cytokines’ : IL-4, IL-5, IL-13,
-modulates immune system
-IL-5 promotes survival, proliferation, trafficking (to airways) of eosinophils
How does Th mature into Th2?
depending on the cytokine environment- levels of inflammatory mediators (IL-4 +TNF-∝)
Define class-switching
class of Ig antibody the B cell produces
Role of mast cells?
immune cells has responses to parasitic helminths infections, contain granules containing pro-inflammatory mediators such as histamine, leukotrienes, prostaglandins
What are eosinophils + role?
polymorphonuclear granulocyte
parasite defence that’s heavily implicated in asthma
Describe allergic repsonse process
- re-exposure
- antigens recognised by IgE bound to mast cells within the airways
- multiple IgE molecules cross-linked by allergen
- triggers degranulation
- granulocyte releases contents of inflammatory mediators
- binds to receptors on multiple cell types in airway inducing pathological changes
- contraction of airway smooth muscle cells, microvascular leak (oedema), activation of goblet cells (mucus secretion)
- bronchospasm
- mediators also induce secondary proinflammatory changes
- Th2 + eosinophils activated
- triggering wave of inflammation as they migrate to airways + release further pro-inflammatory mediators
eg of inflammatory mediators in granulocytes?
prostaglandins, leukotrienes, cytokines
Immediate effect of pathological changes?
rapid bronchospasm =sharp decrease in airflow (due to airway resistance).
Why are anti-histamines ineffective in treating asthma?
histamine released from mast cells have small role in the pathophysiology of asthma
What do Th2 release?
IL-4, IL-5, IL-13,
What do eosinophils release?
reactive oxygen species, leukotrienes, toxic enzymes
Phases of airway dysfunction?
Early response (0-1 hrs) Late response
Describe early response of asthma attack
- (0-1 hrs) w acute bronchoconstriction by initial wave of degranulation,
- extended period (<12 hours)- symptoms improve before worsening
Describe late response of asthma attack
- secondary inflammation
- migration of Th2 + eosinophils to airways
What contributes to night-time asthma?
Early + late asthmatic responses
What’s night-time asthma?
worse symptoms at night, during sleep causing them to wake up
