Pathophysiology of Asthma Flashcards
What is Asthma?
Paroxysms of breathlessness (dyspnoea) which is associated with:
Variable and reversible bronchoconstriction
Airway inflammation
Airway hyper-responsiveness
Cough (unproductive) & wheezing
**All the above do not occur always
Describe the prevalence of Asthma in children and adults.
More common in kids (21% in children, referred to as early onset) than adults. It is often outgrown. 15% of adults have asthma.
What type of diseases is Asthma and what does this mean?
An obstructive and inflammatory disease (increased resistance). Pipes are being narrowed.
Why is asthma considered an obstructive diseases?
Contraction of smooth muscle (during attack) around airways. This narrows airway.
Inflammation also occurs which leads to plasma leak and fluid. Plasma is good because it releases of compliments etc. but it also blocks path.
Epithelium is also damaged, can lead to permanent damage.
Thick Mucus in airways.
What is the difference in the inhalers given to those with benign asthma and those with severe asthma?
Benign asthmatics are given a blue inhaler (like Ventolin), which is a bronchodilator. More severe asthmatics are given glucocorticoids (brown inhaler) which drops them back into the benign category reducing inflammation more permanently.
What is the difference between Intrinsic and Extrinsic Asthma?
In 60-70% of cases it is caused by some outside factor (e.g. pollen, pets). This is referred to as extrinsic. In this case Immunoglobulin E is abundant.
Intrinsic asthma is a rarer form because there are no identifiable triggers for the attacks and there is no IgE.
What is Atopy and therefore what is Allergy?
Atopy is the tendency to produce IgE antibodies. Allergy is when that tendency is associated with symptoms. E.g. 40% of people are atopic but some of these people are completely asymptomatic.
What changes can trigger a response from airways and why?
Sudden changes in temperature or humidity. For example, when exercising. This happens because they are always inflamed in the background.
Name the cells which are involved in Asthma and describe how they contribute to it.
Mast cells (have receptors for IgE) + Eosinophils (only present in people who are allergic). Some of the mediators released by eosinophils are damaging to host. In asthma because there are no worms the mediators are just leading to the death of tissue in the host.
How does an allergen (e.g. a dust particle) trigger the process which leads to asthma?
Triggered by an antigen presenting cells. Which comes across a dust particle thinking it a foreign invader.
What is the hygiene hypothesis?
A hypothesis that states a lack of early childhood exposure to infectious agents, symbiotic microorganisms (such as the gut flora or probiotics), and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system.
Explain, using the hygiene hypothesis, how asthma can occur.
- Different types of T-helper cells (Th) mediate different immune responses and inhibit each other.
- Potential allergen is inhaled - recognised by macrophages/dendritic cells, therefore act as APC’s.
- These go to lymph glands —> extrinsic.
- Something goes wrong with cell signalling —> leads to Th2 response —> attracted to lungs.
- Produces IL-4, and IL-13.
- Stimulates B-cells to release IgE into circulation.
- These bind to receptors on mast cells in lungs.
- 2nd exposure to same allergen triggers mast cell degranulation.
- Th2 also produces IL-5 (mediator of eosinophil attraction), therefore will degranulate.
What is the inflammatory soup?
The inflammatory mediators which are released by cells (e.g. Eosinophils) and lead to the symptoms of Asthma.
What makes up the inflammatory soup?
¥ Cytokines ¥ Thromboxane ¥ Leukotrienes (IL-4,5,13) ¥ Prostaglandins ¥ Histamine
