Asthma Flashcards
How does inflammation cause airway dysfunction? (briefly)
→ Allergen inhalation → Immune system response → Airway inflammation → Impaired airway function → Wheezing, coughing, dyspnoea
What lifestyle factors make it more likely to get asthma?
→ Urban dwelling
→ Pollution
→poor diet
→ obesity
What is Ohms law?
→ Airflow is proportional to 1/resistance
What does the Hagen-Poiseuille law state?
→ As an airways radius decreases the resistance increases and airflow decreases dramatically
What determines the radius of the lumen?
→ The level of contraction of smooth muscle
What factors decrease the radius of the lumen even further?
→ Hypersecretion of mucus
→ Swelling
What is wheezing caused by?
→ Turbulent airflow
→ Increases resistance and decreases airflow
What is the first stage in the allergic response?
→sensitization
→ person breathes in allergen
→ Gets stuck in the airways
→ APC recognizes allergen as being harmful
→ Processes antigen to a helper T cell
→T cells mature and become TH2 cells
→ TH2 cells secrete cytokines like IL5
→ IL4 interacts with B cells and stimulates them
→ B cells proliferate and produce IgE antibodies
→ Antibodies bind to mast cells
What is the second stage in the allergic response?
→ Exposure → Allergen binds to antibodies → Mast cells degranulate →Prostaglandins, LTs and chemokines are secreted → Mediators bind to receptors →cause smooth muscle to contract → Mediators attract TH2 and eosinophils → Eosinophils migrate to airways and release reactive O2 species → Second round of inflammation occurs
What is the early phase of the asthmatic response?
→ Initial degranulation of mast cells
→ After the first response the mediators are cleared and effects resolve themselves
What is the secondary phase of the asthmatic response?
→ Eosinophils and T cells being recruited several hours later
What are the changes in respiratory function observed in asthma?
→ FEV1 decreases
→ FVC is unchanged
→ FEV/FVC decreases <70%
What are the long term changes caused by uncontrolled asthma?
→ Smooth muscle is being constantly worked → Hypertrophy of smooth muscle → More muscle takes up more space and contracts harder → More goblet cells and mucus glands → Infiltration of immune cells → Epithelium Distruption → Basement Membrane thickening → ECM deposition and Fibrosis
What are the most effective treatments for asthma?
→ Beta 2 agonists and corticosteroids
What happens during sensitisation?
→the allergen is inhaled and enters the airway tissue
→stimulates parts of the innate immune system, such as the epithelium
→allergen is them encountered by antigen presenting cells (APCs), such as dendritic cells and macrophages
How is class switching initiated?
→The activated Th2 cell then interacts with a B cell to initiate class-switching
What do the released IgE do?
circulate and bind (via their heavy chain/Fc region) to IgE (FcεRI) receptors on granulocytes such as mast cells
What does IL-5 particularly do?
promotes survival, proliferation and trafficking (e.g. to the airways) of eosinophil
What is the result of inflammatory responses?
rapid bronchospasm and a sharp decrease in airflow
What role does histamine play in asthma?
→histamine release from mast cells appears to play a very limited role in the pathophysiology of asthma
What do eosinophils release?
reactive oxygen species, leukotrienes and proteolytic enzymes
What is hyper-responsiveness?
a period where the threshold of allergen exposure required to elicit further asthma attacks is greatly reduced
What is airway remodelling?
→the inflammation triggered within the airway can result in tissue injury as the noxious mediators released from immune cells cause cellular damage.
→the cycles of tissue injury and repair can lead to irreversible structural changes
(↑obstruction, ↓FEV1, respiratory failure
What are some structural changes that can occur due to repeated asthma cycles?
fibrosis, smooth muscle hypertrophy, goblet cell hyperplasia, epithelium disruption
