L1 Respiratory Physiology and Asthma Flashcards
List some triggers of asthma.
Allergens (eg dust), drugs, exercise, emotions (stress), GORD, irritants, infections, smoking and temperature changes.
What is the link between respiratory infection in infancy, and the development of asthma?
Infants who have had respiratory infections may be up to 40% more likely to develop asthma.
Describe the characteristics of asthma.
Airway obstruction, airway hyper-responsiveness, inflammation of bronchioles.
Chronic asthma can lead to inflammation associated with irreversible bronchoconstriction.
What are the risk factors for developing asthma?
Atopy and positive family history
Over-active IgE response to common environmental factors
Occupational hazards, such as exposure to isocyanates or allergens.
NSAIDs such as aspirin
Beta-blockers, eg propanalol
Describe the physiology or airway smooth muscle contraction.
Beta-2 adrenergic agonists such as adrenaline cause bronchodilation. This is a sympathetic effect.
Cholinergic receptor agonists cause bronchoconstriction, thus have a parasympathetic effect. Eg acetylcholine activates M3 receptors on smooth muscle causing bronchoconstriction. Vagus nerve provides parasympathetic innervation of lungs. Anti-cholinergic agents cause relaxation of the bronchial smooth muscle.
Non-adrenergic, non-cholinergic (NANC) nerve fibres also innervate lungs. Some NANC transmitters are bronchoconstrictors (tachykinins, substance P), and some are bronchodilators (nitric oxide and vasoactive intestinal peptide (VIP) ).
What are the clinical features of asthma?
More than one of the following symptoms: wheeze, breathlessness, chest tightness and cough.
Symptoms worse at night and early morning.
Symptoms are in response to exercise, allergen exposure or cold air, or occur after taking aspirin or beta blockers.
History of atopy, or family history of asthma.
wide-spread wheeze heard in chest
Otherwise unexplained low FEV or PEF
peripheral blood eosinophilia or raised IgE
Describe bronchial hyper-reactivity and how it can be quantitated.
Increase in bronchoconstrictor response to antigens and irritants caused by bronchial inflammation.
Quantitation: measuring fall in FEV1 after inhaling increasing doses of histamine or methacholine.
Describe the physiology of the asthmatic bronchiole.
Mucus plug containing eosinophils. Inflammatory cell infiltration (eosinophils, mononuclear cells) Hypertrophied smooth muscle. Oedema of the mucosa Dilated blood vessels in submucosa thickened basement membrane mast cell infiltration
What are the mechanisms of bronchial hyper-responsiveness?
Eosinophil products (leukotiene C4 and Platelet activating factor) cause epithelial damage and increase contractile responsiveness of airway SM. Nerves are exposed, and their activation (by irritants or exertion) causes bronchoconstriction, mucus secretion and airway vasodilation.
How do cromolyn sodium and nedocromil act?
Depresses the exaggerated neuronal reflexes that are triggered by the stimulation of irritant receptors.
Describe the early-phase response in asthma.
immediate bronchospasm.
Antigens trigger the release of inflammatory mediators such as leukotrienes and histamine, causing bronchospastic response, characterised by SM contraction, mucous secretion and recruitment of inflammatory cells such as basophils, eosinophils and macrophages.
Describe the late phase response in asthma.
Inflammatory response occurring within hours or days.
Levels of inflammatory mediators rise and may induce bronchospasm and eventually fibrin and collagen deposition, and tissue destruction.
Cytokines produced by lymphocytes and mast cells produce the late phase.
Describe the development of allergic asthma.
- patient is sensitised through initial exposure to antigen and type 1 hypersensitivity results from subsequent antigen exposure.
- Th2 lymphocytes are activated, and cytokines are generated
- eosinophils are activated
- IgE is produced and released, and IgE receptors are unregulated.
What is the role of Th2 cells in allergic asthma?
- generate cytokines that stimulate the production and release of IgE by B cells.
- Produce IL-4 and IL-13 which induce IgE receptor expression. IL-4 also responsible for mast cell proliferation and adhesion of eosinophils to endothelium.
- Generate IL-5 which promotes differentiation and activation of eosinophils
- produce chemokines to attract eosinophils to mucosa
What is the mechanism of action f glucocorticoids?
Eg cortisol. inhibits the action of IL-5, IL-4 and IL-13.
