Shared Flashcard Set


Day 8

Additional Biology Flashcards




What is the difference between extrinsic and intrinsic asthma?
Both involve "bronchial hyper-responsiveness," or bronchoconstriciton in response to nonspecific stimuli such as exercise, cold air and cigarette smoke.

1) Extrinsic asthma is exaggerated smooth muscle contraction caused by an inflammatory response to a particular inhaled allergen.

2) Intrinsic asthma occurs in non-allergic patients
What is the basic immunological response that causes chronic inflammation in asthma?
1) Dendritic cells take up allergen, process it and present it on MHC class II molecules to T cells in regional lymph nodes.

2) TCR activation leads to differentiation into TH2 lymphocytes that secrete IL-R and activate B cells.

2) B cells undergo heavy chain class switching to produce and secrete IgE antibodies.

4) IgE-dependent mast cell activation/degranulation produces early allergic response (EAR) within 10 minutes, lasting for 1-3h.

5) Inflammatory cells recruited by mast cell secretions produce IL-4, IL-5, IL-13 and TNF-a, which produce a late allergic response several hours later.
What is the pathophysiological basis of the early and late allergic responses seen in asthma?
Together, these responses lead to bronchial smooth muscle contraction, increased vascular permeability (airway edema) and increased mucous production

1) EAR
- IgE-dependent mast cell activation/degranulation produces early allergic response (EAR) within 10 minutes, lasting for 1-3h.

- Mast cells release histamine, proteases, leukotrienes and prostanoids, all of which produce inflammation and recruit other inflammatory cells.

2) LAR
- Inflammatory cells recruited by mast cell secretions produce IL-4, IL-5, IL-13 and TNF-a, which produce a late allergic response several hours later.
What are the 3 major pathophysiological features of asthma?
1) Airway smooth muscle contraction

2) Increased vascular permeability (airway edema)

3) Increased mucous production
What are the cardinal clinical symptoms of asthma?
Waxing and Waning symptoms

**severity and frequency are critical for diagnosis/treatment**

1) Wheezing
2) Coughing
3) Chest tightness
4) Shortness of breath

On PE, see prolonged expiratory phase
What are the 4 clinical classifications of asthma?
1) Intermittent

2) Mild persistent

3) Moderate persistent

4) Severe persistent
How can a methacholine challenge test assist in classifying asthma?
Provocation test that is useful in staging asthma in patients with normal lung function (e.g. no changes in FVC, FEV1 or FEV 25-75) where methacholine (ACh analogue) is added and resulting smooth muscle contraction is measured.
What 3 factors is an asthma management strategy based on?
Use bronchodilators (rapid symptom relief) and/or anti-inflammatory drugs (decrease underlying lung inflammation for long-term control).

1) Frequency of attacks

2) Severity of attacks

3) Previous response to treatments.
Why are bronchodilators used to treat asthma and how do they work?
1) Beta 2 adrenoreceptor agonists relax bronchial smooth muscle and treat bronchospasm in short term (Albuterol)

2) Salmeterol (partial agonist) and Formeterol (full agonist) also stimulate B2, but last up to 12 h (good when combined with inhaled corticosteroids).

3) Ipratropium is an anti-cholinergic that can be used as an adjunct therapy: it prevents muscarininc M3-receptor-dependent smooth muscle contraction (cGMP mediated).

4) Cromones like Cromoglycate and Nedocromil sodium inhibit IgE-mediated mast cell degranulation

5) Methylxanthines are rarely used, because beta agonists are better.
Why might you add Cromoglycate or Nedocromil to your Formoterol treatment of asthma?
These are Cromone drugs that inhibit IgE-dependent mast cell degranulation and therefore prevent the late allergic response and chronic airway inflammation.
Why might you add Ipratropium bromide to your Formoterol treatment of asthma?
Especially useful in ACUTE SEVERE asthma

It will inhibit M3 ACh receptors in bronchial smooth muscle, thereby preventing cGMP-mediated contraction.
Why are Corticosteroid drugs used to treat asthma?
Glucocorticoids suppress acute and chronic inflammation by

1) Reducing pro-inflammatory cytokine production in Th2 cells, mast cells and eosinophils

2) Reducing mast cell and eosinophil influx and maturation

3) Promoting inflammatory cell apoptosis
Why might you treat asthma with Zafirlukast or Zileutin?
These are Leukotriene modifiers.

Remember, cysteinyl leukotrienes (LT) like LTC4 and LTD4 are produced from AA following oxidation by 5-lipoxygenase and bind cysLT1 receptors, producing features of asthma

1) Zafirlukast and Montelukast block the cysLT1 receptor
2) Zileuton inhibitors LT production by inhibiting 5-lipoxygenase
What is Omalizumab and how is it used to treat asthma? What patients benefit from it most?
Only for moderate/severe asthma.

- Monoclonal IgE antibody that binds free serum IgE and leads to decreased mast cell activation.

- it also down-regualtes IgE receptors on mast cell surfaces and decreases eosinophils in the airways
Describe how the early and late allergic inflammatory responses occur in asthma.
Remember, asthma is bronchial constriction, increased permeability of vasculature (edema) and mucous production.

Early Response
1) DCs uptake and process allergens and then present them on MHC-II molecules to T cells in regional lymph nodes.

2) T cells differentiate into Th2 type cells and activate B cells by releasing Il-4

3) B cells undergo class-switching and make IgE, which binds and activates Mast cells, causing them to release inflammatory molecules like histamines, PGE and LCT.

Late Response

4) Mast cell activation recruits T cells and eosinophils that release IL-4, IL-5, IL-13 an TNF-a, leading to a secondary inflammatory response,
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