Pathophysiology Of Respiratory Diseases Flashcards
What is asthma?
Chronic, inflammatory and obstructive airway disease
What is the asthma pathway?
Allergen inhalation or exercise -> immune system response-> airway inflammation -> impaired airway function -> symptoms
What are the symptoms of asthma?
Wheeze
Cough
Dyspnoea
Decreased FEV1/FVC
How does airway inflammation increase airway resistance and decrease airflow?
Smooth muscle contracts
Excess mucus secretion
Oedema/swelling
Irritation of sensory neurones (cough)
What is the overall effect of airway inflammation on the airway?
Decreased luminal area, increased airway resistance, decreased airflow
What is the main reason for reduced luminal area in asthma?
Contraction of airway smooth muscle
Why does the alveolar smooth muscle contract?
Allergen induced degranulation
How are the contracted alveolar smooth muscle relaxed again?
Beta 2 agonist reducing the airway obstruction by causing the alveolar smooth muscle to relax
Give an example of an airway relaxant
Salbutamol
What is the process for inflammatory mediators inducing alveolar smooth muscle contraction?
Contractile mediators attach to a GPCR-> intracellular signalling pathways cause Ca2+ to be released from the sarcoplasmic reticulum -> muscle contraction
How does allergen sensitisation work?
Allergen exposure -> allergen encountered and processed by the adaptive immune system-> antibodies generated and the immune system ‘primed’
How does the allergic response work?
Subsequent allergen exposure -> allergen binds to antibodies -> immune response triggered -> symptoms
Give the details of the immune response in asthma
Allergen binds to IgE on mast cells, inducing degranulation -> attracts more granulocytes (like eosinophils) -> more inflammatory mediators are released
What causes the late asthmatic response?
Allergen activates Thelper2 cell -> secretes IL4,5,13 -> attract more immune cells -> degranulation
How do corticosteroid drugs reduce asthmatic inflammation?
Modulating the function of multiple immune and structural cells
What effect do glucocorticoids have on cells?
Inhibits mucus secretion
reduces number of mast cells and dendritic cells
decreases release of cytokines from macrophages and T-lymphocytes
Cause apoptosis in eosinophils
Increased B2 receptors in airway smooth muscle
Decreased leak in endothelial cells
Decreased cytokine mediators in epithelial cells
What is the corticosteroid mechanism of action?
Diffuses through the membrane -> binds to intracellular glucocorticoid receptor -> drug receptor complex translocates to the nucleus and binds to the DNA where it affects transcription -> altered transcription of the gene -> translation of gene into protein
How do corticosteroids work?
Either increase or decrease expression of a gene dependant on what it does
What are the four endotypes of asthma?
- Aspirin associated respiratory disease
- cold air/exercise induced asthma
- allergic broncho-pulmonary mycosis
- allergic asthma
What is COPD?
Umbrella term used for a mixture of chronic bronchitis and emphysema, and encompasses a long-term, progressive and accelerated decline in respiratory function
What % of COPD is associated with long term tobacco smoke exposure?
90
What % of long-term smokers develop COPD?
30
What are other risk factors for COPD (not smoking)?
Genetic (alpha 1 antitrypsin deficiency) and environmental hazards (pollution)
How does tobacco smoke cause tissue damage?
Inhalation of toxic chemicals and reactive oxygen species -> tissue damage -> inflammatory response -> macrophage and neutrophil activation -> increased protease burden -> tissue damage
