Asthma Physiology and Breathing Control Flashcards
Describe the appearance of an asthmatic airway normally and during attack.
Asthmatic airway walls are always thick and inflamed, but when not under attack the smooth muscles are relaxed
During an asthma attack, the smooth muscles and tightened and this traps air in the alveoli, preventing the patient from breathing
What triggers asthma?
An array of allergens such as pollen, dust mites
Where can dust mites be found and how do they trigger asthma?
Can be found throughout the house in bedding, carpets, stuffed toys
It is not the dust mites themselves that trigger asthma, its their products that cause the allergic reaction
Such as their casts (carbohydrate skin like structure), secretions (saliva) and faeces (contains proteins or enzymes which trigger the allergic reaction)
What is one characteristic of asthma inflammation?
Increased production of IgE (a type of antibody)
An increase in IgE is associated with inflammation and constriction of airways
What is meant by the term bronchodilation?
The opening up of bronchioles
Which drugs work by bronchodilation?
β2-adrenergic receptor agonists
PDE inhibitors
What do β2-adrenergic receptors mimic?
Adrenaline
How can we decrease inflammation in asthma?
Corticosteroids e.g. beclomethasone
How do allergens interact with cells?
Allergen (i.e. dust mites, pollen) bind to the airway epithelium
This binding triggers production and release of pro-inflammatory cytokines by cells in the airways such as IL-1 and TNF-α
These result in inflammation at the airways
How do corticosteroids work?
At rest, the glucocorticoid receptor is locked in place by heat shock proteins
On binding of beclomethasone to the receptor, the structure changes and the heat shock proteins dissociate
This dissociation allows the drug-receptor complex to go and sit at the start of a gene
This region is called the ‘promoter region’
By sitting at the promoter region, the drug-receptor complex prevents the binding of RNA polymerase, this means IL-1 and TNF-α cannot be produced
How is asthma allergic?
Has an allergic component in that there is an overproduction of the IgE antibody
What is Omalizumab?
A monoclonal antibody (large protein)
How does Omalizumab work?
Works by binding to IgE (an antibody binding to another antibody) at the Fc region
This prevents the attachment of IgE to the Fcε receptors on mast cells, basophils and dendritic cells
In preventing attachment, Omalizumab reduces the release of inflammatory mediators such as histamines, cytokines, prostaglandins and leukotrienes (involved in muscle contraction more than inflammation)
Which area of the brain is important in controlling breathing?
The brain stem, made up of the pons and medulla
What is the brain stem made up of?
Different types of nerves in different areas
These nerves control inspiration and expiration
In the pons, there are inspiratory neurones, expiratory neurones and mixed neurones
How does the brain stem control breathing?
Neurons run down from the brain stem into the thorax to control breathing
What happens if there is serve damage to the area of the brain stem?
Adequate brain stem function is vital
Any damage to this area would result in the patient being put on life support (a ventilator)
Extreme damage can result in death as breathing is not controlled
How do we sense oxygen and carbon dioxide levels and adjust our breathing accordingly?
Do so with a specialised type of cell called chemoreceptors
There are 2 general types, central (in CNS) and peripheral (in PNS)
Where are central chemoreceptors found?
Brain stem medulla
What is the role of central chemoreceptors?
Sense how much CO2 is present in the CNS - pH (H+), PCO2 (partial pressure)
Detect changes in the cerebrospinal fluid
Most important
Where are peripheral chemoreceptors found?
Carotid bodies (common carotid arteries), aortic bodies (arch of aorta)
What is the role of peripheral chemoreceptors?
Sense O2 and CO2 levels in the body (periphery), sends messages into the brain that are then processed - pH (H+), PCO2, PO2
Detects changes in arterial blood
How do CO2 levels impact neurons?
High levels of CO2 inhibit neurons (are toxic) and suppress breathing
