Pathophysiology of asthma

Question 1

Method of sensitisation

Answer 1

Exposure of genetically predisposed individuals to allergen
Mediated through Th2 lymphocytes
Cytokines from lymphocytes cause mast cell to produce IgE-R
Endothelial cells express receptors to attract eosinophils

Question 2

Triggers and specificity

Answer 2

Allergens are specific
Occupational agents e.g. SO2, cigarette smoke are specific and non-specific
Cold, dry air, exercise, viruses, psychology (stress and anxiety) and drugs are all non-specific

Question 3

Difference between specific and non-specific triggers

Answer 3

Specific trigger causes extrinsic asthma

Non specific trigger causes intrinsic asthma

Question 4

Early phase of an asthma attack

Answer 4

Increase in resistance to airflow that peaks 30-60 mins after allergen exposure
Response to release of inflammatory mediators from mast cells

Question 5

Late phase of an asthma attack

Answer 5

Can occur a long time after allergen exposure (6+hours) and maybe the cause of much night time asthma
Driven by a continuation of inflammation characterised by an influx of eosinophils into the lungs

Question 6

Paradigm of asthma pathophysiology

Answer 6

Mast cell activation/ degranulation
Immediate inflammatory responses
Late inflammatory responses
All stages cause inflammation-induced airway remodelling

Question 7

How do mast cells degranulate?

Answer 7

Cross linking IgE receptor by binding antigen
Mast cell degranulation
Release of histamine and other inflammatory mediators

Question 8

Inflammatory cascade

Answer 8

Histamine release causes bronchoconstriction, increased mucus production, leukocyte recruitment, increased vascular permeability and vasodilation

Question 9

How does bronchoconstriction occur and what are the effects?

Answer 9

An increase in mucus decreases airway diameter
Smooth muscle contraction narrows airway
Air trapping leads to hyperinflation
Narrowing of airway makes it harder to breath due to increased resistance

Question 10

Mucous plugging

Answer 10

During expiration mucous gets stuck in the alveolus causing it to hyperinflate
Alveolus will fill up with CO2 causing oxygen to run out

Question 11

Vasodilation and increased permeability

Answer 11

Inflammation causes swelling of the tissue due to oedema

When the wall of the bronchus swells, the diameter of the lumen decreases&raquo_space;> cannot solve with bronchodilators

Question 12

Late phase bronchoconstriction

Answer 12

Oedema begun during early phase is more prominent
Sensory nerve fibres release inflammatory agents that can cause bronchoconstriction
increased parasympathetic activation ACh and M3 receptors = bronchoconstriction

Question 13

Therapeutic goals

Answer 13

Reliever (bronchodilators) open the airways of a patient suffering an asthma attack
Preventer (corticosteroids) intervene in the remodelling process