Asthma physiology Flashcards
What is asthma?
Chronic disease of the airways causing inflammation of the lining and narrowing of the airways making it difficult to breathe due to increased responsiveness to a trigger or stimuli
• Hypersensitivity to stimuli
• Reversible obstructive lung disease: remove stimuli
• Contraction and constriction of airway smooth muscle
What causes asthma?
Exposure to allergens/triggers
What are the allergens/triggers that can cause asthma?
Pollen Dust mite Mould spores Respiratory infections: common cold Pollutants: smoke, car fume Pet hair Emotional stress Air pollution Medications- BB, NSAID, aspirin
What medicines induce bronchodilation?
Beta 2 agonist- salbutamol
PDE inhibitors- xanthines-theophylline
MOA of B2 agonists
a. B2 agonist binds B2 Gs protein coupled receptor
b. G-protein complex produced
c. Adenylate cyclase activated
d. Increase cAMP by converting ATP to cAMP
e. Activates PKA
f. Inhibits phosphorylation of ca channels so less intracellular calcium concentration
g. Myosin light chain kinase inactivated
h. Decrease i smooth muscle cell contraction
Bronchodilation/relaxation of smooth bronchial airway muscle
MOA of PDE inhibitors
Inhibit cAMP breakdown by inhibiting phosphodiesterase so no camp to amp
Increases Camp and Cgmp: inhibits myosin light chain kinase
Maintains and increases smooth muscle relaxation
Inhibit inflammation
Inhibit leukotriene synthesis
What drugs decrease inflammation?
Corticosteroids e.g. beclomethasone
MOA of corticosteroids
a. Allergen contact airway epithelial cell
b. Inflammatory cytokines: ILK1 and TNF produced
c. Causes inflammation
d. Corticosteroid binds glucorticoid receptor which is anchored to cytoplasm by heat shock protein
e. Beclomethasone/glucocorticoid receptor complex forms and travels to nucleus
f. Complex binds cytokines
g. Transcription inhibited
h. Reduced cytokines and inflammation
What are the specialist treatments for asthma?
Monoclonal antibody- Omalizumab
MOA of omalizumab
○ Allergen/IgE complex binds to FC receptor causing Inflammatory mediator production of histamine, cytokine and prostaglandins
○ Omalizumab inhibits IgE binding receptors on mast cell, basophil, dendritic cells by binding to Fc region IgE
Reduced inflammatory compound production
What structure regulates breathing?
Brain stem= pons and medulla
Describe the mechanism of breathing control?
Neurons extend from the pons and medulla of the brainstem to the spinal cord specifically the diaphragm and chest wall muscles
Neurons control muscle contraction and relaxation
Why is breathing controlled?
To maintain PaCO2 and PaO2 within normal ranges
What structures sense levels of CO2, O2 and ph in the body?
Chemoreceptors
What are the 2 types of chemoreceptors?
- Central chemoreceptors
2. Peripheral chemoreceptors
Where are Central chemoreceptors located?
brain stem medulla
Where are Peripheral chemoreceptors located?
carotid bodies of the common carotid arteries and in the aortic bodies at the arch of the aorta
What do Peripheral chemoreceptors detect?
Ph
PaCO2
What do Central chemoreceptors detect?
Ph
PaCO2
PaO2
At which location do Central chemoreceptors detect?
cerebrospinal fluid in the CNS
At which location do Peripheral chemoreceptors detect?
arterial blood
What are Central chemoreceptors sensitive to?
Low PaO2
High PaCO2
Low blood Ph/H+
What are Peripheral chemoreceptors sensitive to?
Low Ph/H+
High PaCO2
What muscles contract to adjust breathing?
intercostal muscle of the diaphragm
