Respiratory System: Respiratory Disease Flashcards
What are the 2 components of asthma pathophysiology?
(1) Inflammatory component: patient develops hypersensitivity to a specific stimulus (eg pollen), causing an inflammatory response.
(2) An airway component: allergen-induced inflammation releases mediators. These affect cellular function and airflow, causing symptoms (dyspnoea, excess mucus, cough).
What happens during an asthma attack?
- inflammation of the airways generates airway smooth muscle contraction and mucus hypersecretion.
- This reduces airway lumen size, increasing airway resistance and decreases airflow.
Draw a healthy vs asthmatic airway
allergic asthma involves 2 stages: sensitisation, and the allergic response. Describe sensitisation
Inhaled allergen enters airway tissue. The innate i.system releases pro-inflammatory signals.
APCs engulf the allergen, displaying its antigen to its specific T helper cell. Activated T cell matures into Th2.
Th2 interacts w a B cell to produce IgE which binds the original allergic antigen. IgE circulate and bind to its receptors on mast cells.
Th2 cells also secrete IL-4, 5 and 13. IL-5 esp promotes survival, proliferation and eosinophil trafficking to the airways.
allergic asthma involves 2 stages: sensitisation, and the allergic response. Describe the allergic response process
Upon re-exposure, IgE bound to mast cells in the airways recognise allergen antigens and trigger degranulation: the granulocyte releases inflammatory mediators which bind to cell receptors in the airway.
This induces airway sm contraction, oedema, mucus secretion + eosinophil activation (releases more inflammatory mediators). This causes rapid bronchospasm + sharp airflow decrease.
Presence of allergen within the airways also activates Th2 which induces secondary pro-inflammatory changes.
Outline the role of key immune cells and inflammatory mediators in allergic asthma.
How can asthma cause airway remodelling?
Asthma can have repeated episodes of inflammation. The noxious mediators released from immune cells cause cellular damage.
Repeated episodes mean cycles of injury and repair lead to irreversible structural changes (e.g. fibrosis, smooth muscle hypertrophy, epithelium disruption), called ‘airway remodelling’.
Airway remodelling= ↑obstruction, ↓FEV1, resp failure. Occurs in patients with severe, ‘poorly controlled’ asthma.
The drugs most commonly used in asthma for this purpose are beta-2 adrenergic receptor agonists. Discuss its mechanism of action
Activation of beta-2 receptors increase activation of AC, which catalyses conversion of ATP to cAMP.
The increase in cAMP in turn activates protein kinase A, which phosphorylates multiple intracellular targets. This decreases intracellular calcium levels, inducing smc relaxation.
What are the different classes of B2 receptor agonists?
Short-acting beta-2 agonists (SABAs) eg salbutamol. A reliever therapy (e.g. when the patient experiences an asthma attack) by metered-dose inhaler.
Long-acting beta-2 agonists (LABAs) eg salmeterol or formoterol. A preventer treatment in combo w inhaled corticosteroids. Twice daily, continual dosing.
Describe a 2nd class of bronchodilator drug
Long-acting muscarinic antagonists, such as tiotropium. LAMA= an add-on, preventer therapy in asthma. Dosed on a daily, continual basis via metered-dose inhalers.
Ach binds to M3 receptors in the membrane of ASM cells to induce contraction. Blocking this receptor w LAMAs reduces contraction.
But they’re less effective bc Ach has a minor role in ASM contraction. LAMAs may also reduce mucus secretion and cough.
How do corticosteroids function to treat inflammation in asthma?
Corticosteroids, eg Fluticasone bind to anti-inflammatory glucocorticoid receptors inside immune and structural cells (steroids diffuse through cell membranes as they’re lipid soluble).
The bound drug-receptor complex migrates to the nucleus and binds to DNA, modulating gene expression. Hay ↓ expression of pro-inflammatory mediators, ↑ expression of anti-inflammatory mediators
How do Leukotriene antagonists treat asthma inflammation?
Leukotriene antagonists block leukotriene receptors, so pro-inflammatory LT mediators can’t act on the receptor. This reduces inflammation
eg drug: Montelukast
What is COPD and what causes it?
COPD: umbrella term for resp disease involving both chronic bronchitis and emphysema.
Long-term, progressive, accelerated decline in resp function.
Most cases are associated w long term smokers. The rest are due to pollution/other chemicals, or genetic disorders eg alpha-1-antitrypsin deficiency.
Describe the key pathophysiological changes associated with COPD.
Tobacco smoke damages resp tissue, starting an infl.response by macrophages + neutrophils. These release proteases that degrade structural proteins.
Some smoke chemicals inactivate antiprotease enzymes, increasing protease burden in the lung, further damaging tissue.
Airway tissue damage increases mucus secretion and damages cilia, impairing mucociliary clearance and host defence.
Pathological changes within airways generate chronic bronchitis symptoms, changes within the lung tissue + alveoli =emphysema.
What happens to the airways in the long-term with a COPD patient?
Long term COPD leads to tissue remodelling that reduce ventilation and gas exchange.
In tissue remodelling hay loss of cilia and mucus hypersecretion. This impairs defensive pathways within airways such as mucociliary clearance, so the resp system is vulnerable to infections
What is emphysema?
Emphysema: pathological enlargement of alveolar airspaces due to lung tissue destruction.
This results in loss of structural fibres eg elastin (increasing compliance).
Also hay reduced surface area and damage to pulmonary vasculature (decreasing gas exchange)
Draw a diagram to show the pathophysiology of pulmonary heart disease
What is the clinical significance of alveolar injury?
