CR Week 3 Flashcards
Q1: Explain how inhalation of allergens may lead to shortness of breath in patients with asthma? (3 marks)
Allergens in the airways may cause airway inflammation (1 mark),
which may lead to airway narrowing (1 mark).
Narrowing of the airways will lead to reduced airflow (1 mark) and consequently shortness of breath.
Q2: Explain what a peak flow device measures. (2 marks)
A peak flow devise measures peak expiratory flow, the maximal flow of air (1 mark) during forced exhalation (1 mark).
Q3: Explain why patients with asthma may have a normal PEF? (2 marks)
Patients with well-controlled asthma (1 mark) may have normal PEF, as airflow limitation in asthma is variable (reversible) (1 mark).
Q4: Describe the role and mechanism of action of inhaled corticosteroids? (3 marks)
Inhaled corticosteroids (ICS) are used as preventer/maintenance therapy (1/2 mark) in asthma to reduce airway inflammation (1/2 mark)
ICS reduce airway inflammation by dampening gene expression of pro-inflammatory mediators (1 mark*) via the glucocorticoid receptor (GR) (1 mark)
*will accept the following: increase expression of anti-inflammatory genes
what is the difference in response to allergen in normal and healthy person?
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Normal:
- A low level T-helper (TH-2) response. This produces an IgG response
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Asthma:
- allergen digested by antigen presenting cellsdigested and presented by MHC Class II molecules
- CD4 cells activate the TH-2 lymphocytes through the release of IL4, IL5, IL13.
- The activated TH2 cells release cytokines (IL4) which recruit multiple inflammatory cells, NK cells eosinophils, mast cells, and IgE producing Cells causes the release of histamines
- IgE mediated mechanism: (IgE: antibody associated with allergic response)
- binding of an allergen to IgE-mast cells results in their rapid degranulation and the release of inflammatory compounds, including histamine, which contribute to local inflammation and the symptoms associated with allergy.
- The activated TH2 cells release cytokines (IL4) which recruit multiple inflammatory cells, NK cells eosinophils, mast cells, and IgE producing Cells causes the release of histamines
explain the difference between sensitisation and provacation of an allergy?
In type I HS sensitization, allergen triggers production of allergen-specific IgE that binds via its Fc region to mast cell and basophil FcεRs.
In the early effector stage, re-exposure of sensitized mast cells to allergen triggers immediate degranulation and release of pre-formed mediators, and synthesis of inflammatory molecules
what are the 3 causes of airflow limitation in asthma? [3]
Bronchoconstriction
Airway oedema
Airway remodelling
explain mechanism of bronchoconstriction occuring in asthma patients
- Ach binds to M3 receptor
- causes IP3 to be released
- IP3 binds to IP3 Receptor - IP3R on ER
- causes Ca2+ released into cytoplasm
- increase in intracellular Ca2+ binds to calmodulin & myosin light chain kinase (MCLK)
- phosphorylases light chain on myosin
- - actin-myosin cross link occurs & SMC occurs
in simple terms, what is bronchoconstriction caused by/
- In acute exacerbations of asthma, bronchial smooth muscle contraction (bronchoconstriction) occurs quickly to narrow the airways in response to exposure to a variety of stimuli including allergens or irritants. Allergen-induced acute bronchoconstriction results from an IgE-dependent release of mediators from mast cells that includes histamine, tryptase, leukotrienes, and prostaglandins that directly contract airway smooth muscle
what causes airway oedema in asthma patients
- As the disease becomes more persistent and inflammation more progressive, other factors further limit airflow. These include oedema, inflammation, mucus hypersecretion and the formation of inspissated mucus plugs, as well as structural changes including hypertrophy and hyperplasia of the airway smooth muscle. These latter changes may not respond to usual treatment.
what are risk factors for asthma?
- Family history: Multiple genes are implicated that predispose people to hyper-responsiveness to environmental aetiological triggers.
-
Allergens:
- cats, dogs, cockroaches, dust mites, fungal spores, tobacco smoke, fumes from chemicals (e.g., bleach), and pollen from trees, weeds, and grass.
- Workers commonly affected by occupational allergens include bakers, farmers, carpenters, and people involved in manufacturing plastics, foams, and glues.
- Atopic history: History of eczema, atopic dermatitis, allergic rhinitis is strongly associated.
what are Immunohistopathologic features of asthma? [5]
- Neutrophils (especially in sudden-onset, fatal asthma exacerbations; occupational asthma, and patients who smoke)
- Eosinophils
- Lymphocytes
- Mast cell activation
- Epithelial cell injury
what are signs of asthma? [4]
- Wheezing on auscultation
- Intercostal recession in children
- Severe attacks render people unable to speak
- Prolonged expiratory phase (respiratory and expiratory phases should be equal)
how do u treat asthma?
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Reliever inhalers: bronchodilators – blue inhaler
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SABAs
- Salbutamol
- Terbutaline
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SABAs
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Preventer inhalers:
- low dose inhaled cortical steroids (ICS) (anti-inflamm drugs) - take for rest of life
- Beclomethasone diproprionate – brown inhaler
- Budesonide
- Ciclesonide
- Fluticasone propionate
- LABAs
- low dose inhaled cortical steroids (ICS) (anti-inflamm drugs) - take for rest of life
- SAMA and LAMAs for severe asthma only
what is mechanism of SAMA & LAMA
and
SABA & LABA?
-
Mechanism of inhalers:
- Airway smooth muscle cells have both M3 muscarinic receptors & beta2 adrenergic receptors
- SAMA & LAMA: block the binding of ACh to M3 muscarinic receptors - bring about smooth muscle relaxation
- SABA & LABA: activate beta2-adrenergic receptors - induce cascade of signalling events = smooth muscle relaxation
what happens due to chronic asthma?
Chronicity
In response to persistent chronic inflammation, the airways lay down fibrous tissue. Over time airway remodelling occurs and manifests as fixed airway obstruction - i.e. airway narrowing that is irreversible.
