Asthma Flashcards
What type of hypersensitivity reaction is Asthma?
Type 1 hypersensitivity reaction
(IgE hypersensitivity)
Asthma is an inflammatory disease
What nerve system is dominant in the airways?
Parasympathetic division
It is carried by Nerve X (Vagus nerve) - The ganglia of the nerves are inside the bronchi and bronchioles
Parasympathetic division causes contraction of smooth muscle
What is the effect of parasympathetic innervation of the bronchioles/airways?
Bronchial smooth muscle contraction mediated by ACh acting upon the M3 muscarinic receptors
Increased mucus secretion mediated by ACh acting upon M3
What types of transmitters can be used to dilate the airways?
Vasoactive Intestinal peptide
Nitric oxide
What effect does the sympathetic system have on the bronchial smooth muscle?
Dilation of smooth muscle - Activated by Beta 2 receptors.
Decreased mucus secretion by Beta 2 adrenoceptors
Increased mucociliary clearance - mediated by Beta 2 adrenoceptors
What are the pathological changes associated with chronic asthma?
Increased mass of smooth muscle (Hyperplasia and hypertrophy) - narrowing the airways Basement membrane thickening Hyperresponsiveness Colagen disposition Accumulation of interstitial fluid Increased secretion of mucus
How does hyper-responsiveness and hyper-reactivity of the airways occur in asthma?
Exposure of C fibres (Irritant receptors)
How can the hyper-responsiveness of the airways be tested?
Provocation tests with inhaled bronchoconstrictors (Spasmogens)
e.g. histamine or methacholine
The less drug needed to induce hyper-reactivity the more severe the asthma
Explain the phases of an asthma attack?
Early phase - caused by the bronchospasm in relation to a stimulation
Late phase - Inflammatory response
Explain the development of allergic asthma?
Presentation of antigen
Phagocytosis of antigen by dendritic cells
T -helper 2 cells produce IL 4 to activate B cells
B cells become plasma cells and secrete IgE
T helper 2 cells produce IL 5 and activate Eosinophils
Mast cells activated by IL4 and IL 13 from TH2
Dendritic cell presents antigen to Mast cell - causes degranulation and release of Histamines and Leukotrienes (LTC4 and LTD4)
Release of what factors promote inflammation in the airways?
LTC4
Platelet activating factor (PAF)
What are the two different types of drugs in Asthma?
Relievers:
SABA - salbutamol
LABA - salmeterol
CysLT1 antagonists - Montelukast
Controllers:
Describe how Beta 2 agonists work? (e.g. salbutamol/salmeterol)
Antagonists to all spasmogens
Acton the Beta 2 receptor
Causes phosporylation of Protein Kinase A - inhibits enzyme
Prevents MLCK causing contraction
Increase mucus clearance and decrease release from Mast cells and Neutrophils
Increase cGMP - promotes broncho dilation
Help with nocturnal symptoms
What are LABA’s useful for (salmeterol) ?
Nocturnal asthma
What type of medications are contraindicated in asthma?
Beta blockers
ACE inhibitors
How do cysteinyl leukotrienes receptor antagonists cause bronchodilation?
Antagonise competitvely on the CystLT1 receptor on Mast cells.
e.g. Montelukast/Zafirlukast
This is used as an add on therapy for mild/persistent asthma and Exercise induced asthma
What are the effects of Xanthines?
e.g. Theophylline and Aminophylline
Combine bronchodilator and anti-inflammatory actions
Inhibits release from mast cells
Increases mucus clearance
What are the side effects of Beta 2 agonists?
Tachycardia
Tremor
Anxiety
What are the two types of asthma ?
Extrinsic asthma - trigger factor known
Intrinsic asthma - no known trigger
What is the histopathology of inflammation in asthma?
Epithelial detached
Disordered cells
What is the clinical syndrome of asthma?
Episodic symptoms
Diurnal variability
Associated atopy
Wheeze
How is asthma diagnosed?
Reduced forced expiratory ratio (<75%) Provocation testings (with exercise/histamine)
What are two types of steroids the adrenal gland prodces?
Mineralocorticoids - e.g. aldosterone. Regulates salt and water
Glucocorticoids - e.g. cortisol. Reduce inflammation
What are the effects of inhaled steroids and how do they work?
e.g. Beclomethosone
Steroids are lipophilic molecules and they enter the cells by diffusion of the plasma membrane
Steroid combines with GR-alpha
Transports to the nucleus
Combines with the Glucocorticoid response elements in the promoter regions (GRE)
Switch on or switch off specific genes
Reduce Inflammation
Decrease the formation of TH 2 cells
Reduces Interleukin cytokines
Reduce the recruitment of inflammatory cells
What are the side effects of steroids in the oropharynx?
Dysphonia - hoarse and weak voice
Oropharyngeal candidiasis
What effects do cromolins have and who are they usefull for?
They are Mast cell stabilisers e.g. sodium cromoglicate
Weak anti-inflammatory effect
Decrease the sensitivity with irritant receptors with sensory C fibres
Most effective in young children
What are the effects of monoclonal antibodies in asthma and how do they work?
Monoclonal antibodies direct against IgE (e.g. Omalizumab)
Binds the IgE via the FC region to prevent attached of FC epsilon receptors on Inflammatory cells
What is fexofenadine and what is it used for?
Useful for seasonal asthma
Anti-histamine
What are features of a severe asthma attack?
Peak flow < 50
Tachycardia > 110
Tachyponea
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What type of spirometry does asthma show?
Obstructive spirometry
What is the treatment for acute asthma?
- Oxygen - high flow
- Bronchodilators (Nebulise with Oxygen)
- Nebulised Ipratropium
- IV bronchodilators
- Steroids - IV Prednisolone/ IV hydrocortisone
- Magnesium
- Aminophylline
- CXR
What are precipitate an asthma attack?
Exercise
Beta blockers
Ibuprofen
What treatment can be given if an allergenic trigger is found for the asthma?
H1 receptors antagonists
What is the function of the M1, M2, M3 receptor?
M1 - enhance the cholinergic response
M2 - inhibit ACh release
M3 - Mediate bronchoconstriciton and Muscus secretion
Part of Parasympathetic system
What anticholinergics are used in asthma?
SAMA (short acting Muscarnic antagonist) - Ipratropium
LAMA (long acting) - Tiotropium
What are the features of a fatal asthma attack?
Peak flow < 33%
Cyanosis
Silent chest
PaCO2 >6
