Pathophysiology Of Asthma Flashcards
What is asthma?
It is a chronic, inflammatory and obstructive disease of the airways.
It is characterised by episodes of REVERSIBLE airflow limitation and bronchial hyperresponsiveness. This causes patients to experience difficulty in breathing (dyspnoea).
There are different types of asthma but this lecture is about allergic asthma, mediated by IgE and Th2.
Briefly, what causes breathlessness in asthma?
Airway dysfunction from inflammation triggered by allergen exposure.
This dysfunction involves airway smooth muscle contraction and mucus secretion which reduces airway lumen.
How can the basic pathophysiology of asthma be divided into 2 components?
- Inflammatory/immune response = person develops hypersensitivity to a specific stimulus (an allergen such as pollen) causing an inflammatory response when exposed to that stimulus
- Airway component = the allergen-induced inflammation release mediators that affect cellular function and produce limitations in tissue function (e.g airflow). This causes symptoms such as dyspnoea, excess mucus and cough.
What can cause increased chances of getting asthma?
- Genetics:
Parental asthma, susceptibility genes (ADAM33, GSTP1-)
(GSTP1+ is a protective gene) - Immunological development:
Infant respiratory virus infection and Caesarean delivery increase chances of asthma.
Helminth exposure, healthy microbiota and vaginal delivery decrease chances of asthma - Lifestyle:
Pollution exposure, poor diet and obesity increase chances of asthma.
Healthy diet reduces chances of asthma.
What are the twin concordance rates of getting asthma?
Identical twins: 0.5
Non-identical twins: 0.2
This shows that asthma isn’t all genetic
What does impaired airway function cause?
Causes insufficient ventilation —> reduced blood gas homeostasis and acid- base balance
Causes hypoxia
Explain the link between resistance and airflow
As resistance increases, airflow decreases.
Airflow § 1/resistance
As radius increases, resistance decreases.
Resistance § 1/r^4
So the larger the radius, the lower the resistance
So airflow is directly proportional to size of airway lumen
What are the differences in airways when they are relaxed and contracted?
Relaxed = larger smooth muscle cells, increased lumen diameter. Increased luminal area, reduced resistance and increased airflow
Contraction = contracted smaller smooth muscle cells, decreased lumen diameter, increased resistance and reduced airflow
What happens to the airways in an asthma attack?
- Contraction of smooth muscle (greatest factor)
- Excess mucus secretion - hypersecretion of mucus
- Swelling/oedema
- Irritation of sensory neurones causing cough
Overall effect = reduced luminal area = increased resistance = reduced blood flow
Causes levels of carbon dioxide to rise and causes levels of oxygen to fall
How are the changes in asthma reversible?
The reduced luminal area is caused by inflammation. When the inflammation goes down (usually using a bronchodilator), the airway resistance returns to normal.
Whereas in COPD, there is progressive decline in airway function.
What kind of flow increases airway resistance?
Turbulent flow.
Vibration causes wheezing sound.
What are the two stages allergic asthma involves? (Same as other allergies)
- Sensitisation - immune system first encounters allergen and develops an adaptive immune response (antibody-lymphocyte mediated)
- Allergic response - reencounter of allergen which triggers the adaptive response previously primed during sensitisation
Explain sensitisation in detail
- You inhale allergen which enters airway tissues
- This itself stimulates innate immune system, causing epithelium to release inflammatory signals.
- Dendritic cells and macrophages (antigen presenting cells) phagocytose the allergen to present to adaptive immune system. They do this by processing the allergen; the antigen is displayed externally.
- The processed antigen comes with contact with naive helper T cells, activating the native helper T cells, allowing them to mature into into Th2 cells
- The Th2 cells release cytokines to cause eosinophil proliferation.
- The Th2 cells interact with a B cell to initiate class switching,
proliferation and production of IgE antibodies that bind to the antigen present in the original allergen - The IgE antibodies circulate and bind to receptors on granulocytes such as mast cells so when the allergen is encountered again, it will bind to the antobodies there.
Explain allergic response in detail
- Allergen is inhaled and binds to the antibodies on mast cells.
- This causes degranulation of mast cell - the granules contain pro-inflammatory mediators e.g histamine, chemokines and prostaglandins. This basically creates a 2nd round of pathology because these pro-inflammatory mediators then activate more white blood cells sick as Th2 (which then produces more mediators) and eosinophils
- These mediators bind to multiple cell types in the airway that cause pathological changes such as contraction of airway smooth muscle, micro vascular leak (oedema) and activation of goblet cells.
What is the immediate effect of asthma attack?
Rapid bronchospasm and a sharp decrease in airflow due to increased resistance
