W5 Molecular Pathophysiology of Asthma Flashcards
What is Asthma?
What does the degree of resistance depend on? (2)
Asthma is an obstructive disease (Affects expiration more than inspiration)
* There is resistance to the flow of air through the airways during inspiration and expiration.
- The degree of resistance depends on:
– Airway diameter
– Laminar or turbulent flow
What are the FEV % when a patient has an obstructive disease?
FEV1/FVC ratio reduced in comparison to normal
FEV1 < 80% and FEV1/FVC <70%
What is FEV1?
Forced Expiratory Volume in 1 second
(amount of air you can blow out in one breath)
What are the symptoms of Asthma:
Recurrent episodes of: (4)
More symptoms?
- Dyspnoea (SOB/laboured breathing)
- Wheezing
- Tight chest
- Cough (sometimes)
- Shortness of breath
- Chest tightness or pain
- Wheezing during exhalation
- Coughing or wheezing attacks that are worsened by a respiratory virus
- Chronic unproductive cough
- Significantly variable breathlessness
- Night-time wakening with breathlessness and/or wheeze
- Significant diurnal or day-to-day variability of symptoms
- Acute Sever Asthma: (status asthmaticus) not easily reversed, causes
hypoxaemia, may require hospital treatment
Asthma facts (for info)
- UK prevalence: approx. 4% population
- Half are children
- Prevalence is increasing (since 70s)
- In children, more common in boys
- In adults, more common in women
- Diagnosis of asthma is a clinical one;
– there is no standardised definition of the
type, severity or frequency of symptoms, nor of the findings on investigation
What type of disorder is asthma?
What are the 3 main factors?
A chronic inflammatory disorder of the airways
* Airflow limitation is widespread, variable, and reversible
* In response to variety of stimuli
* Obstructive disorder
3 main factors:
* airway constriction
* airway hypersensitivity and responsiveness
* mucous hyper-secretion
What are the causes of asthma?
Host factors and environmental
exposures
Genetic factors:
Cytokine response profiles
Age
Environment:
Allergens
Pollutants
Infection
Stress
What does inflammation (in asthma) lead to? (3)
- Airway Obstruction
- AHR/bronchospasm (airway hyper responsiveness)
- Airway remodelling
What are the trigger factors for Asthma? (7)
- Allergens - house dust mite, pollen,
moulds, animals - Chemicals - paints, hair sprays
- Drugs - aspirin, ß-blockers, NSAIDs,
- Foods - colourings, nuts, preservatives
- Environmental chemicals - cigarette smoke, wood dust
- Infections - LRTI
- Miscellaneous - cold air, exercise, stress, workplace
Asthma can be categorised into Extrinsic or Intrinsic Asthma:
What is extrinsic also known as?
=Allergic asthma
Specific trigger causes EXTRINSIC asthma
Non-specific trigger causes INTRINSIC asthma
e.g. allergens = specific= extrinsic
so2/smoke/cigarete smoke= both
cold dry air, exercise, virus, drugs= non-specific= intrinsic
What is Atopy?
- The propensity to develop IgE antibodies to common antigens
- Associated to susceptibility to develop asthma, allergic rhinitis, eczema
- 1/3 of population have +ve skin tests
– 1/3 of these will develop asthma
– House dust mite, grass pollens, animal dander are commonest - Early onset asthma
– 98% have +ve skin tests
– more likely to have a history of eczema or family history of asthma - Late onset asthma
– 76% have +ve skin tests
dendritic cell=antigen-presenting cell
T helper cell stimulates immune response by
Asthma Attack: Biphasic
What are released in the early/symptomless phase?
What is the late phase driven by?
Early phase
* Increase in resistance to airflow
– peaks 30-60 min after allergen exposure
– subsides 30-90 min later (due to bronchoconstriction)
* Immediate response to release of
inflammatory mediators from MAST CELLS
Late phase
* Can occur a long time after allergen exposure
– 6+ hours
– night time asthma.
* Driven by a continuation of inflammation
characterised by an influx of EOSINOPHILS into the lungs
What is mucous plugging and hyperinflation?
Mucous blocking bronchus
- Inspiration air is allowed into alveolus
Inflammation causes swelling of tissue due to Oedema. What does this lead to?
Wall of bronchus swells so diameter of lumen decreases
Late phase bronchoconstriction:
Continuation of the inflammatory process
-Oedema begun during early phase is more prominent
-Sensory nerve fibres release inflammatory agents that can cause
bronchoconstriction
-Increased parasympathetic activation Ach + M3 receptors = bronchoconstriction
What are the therapeutic goals for Asthma?
How do bronchodilators and corticosteroids help?
- Minimal symptoms day & night
- Minimal need for reliever
medication - No exacerbations
- No limitation of activity
- Normal lung function
Reliever (bronchodilators)
=Open the airways of a patient suffering an asthma attack
Preventer (corticosteroids/glucorticoids)
=Intervene in the remodelling process
