Asthma Flashcards
What are the three main characteristics of asthma?
- reversible airflow limitation
- airway hyper-responsiveness
- bronchial inflammation
Asthma aiway changes
- hypertrophy (increased mass of smooth muscle)
- oedema (accumulation of interstital fluid)
- Increased mucus secretion
- Epithelial damage
- Sub-epithelial fibrosis
What does the term ‘Atopy’ mean?
- genetic tendency to develop allergic tendancies, such as asthma, ezcema
- increased IgE levels
What are the causes and triggers of asthma?
- genetics (production of cytokines)
- environmental exposure to allergens
- viral infections
- cold air
- emotion
- drugs (NSAIDs - asprin)
- exercise
What is chronic asthma?
Pathological changes to the bronchioles –> long standing inflammation
What is an immediate asthmatic reaction?
- airflow limtation begins within minutes of contact with the allergen
- reaches maximum within 15-20mins
- subsided within an hour
- type I hypersensitivity reaction
What is dual and late-phase reactions, in asthma?
- Following an immediate reaction, asthmatics may have a prologed airflow limitation (responds less to bronchodilators)
- Symptoms persist after allergen is removed
- type IV hypersensitivity reaction
What is the main cell that drives airway inflammation?
- Th2-type T lymphocytes
What is the main cell that drives airway tissue damage?
- Th1 TNF-alpha
What cells are involved in inflammation?
- Mast cells
- Eosinophils
- Dendritic cells
- Lymphocytes
Explain mast cells during a reaction?
- Mast cell numbers are increased within the epithelium smooth muscles and mucous glands
- Release mediators –> histamine
- Acts on smooth muscles, small blood vessels, mucus-secreting cells and sensory nerves
- Release cytokines, chemokines and growth factors
Explain Eosinophils during a reaction?
- Found in large numbers at bronchial wall
- attracted to airways by cytokines (IL-3, IL-5)
- Release LTC4 –> toxic to epithelial cells
- Decreased effect by corticosteroids
Explain Dendritic cells and lymphocytes during a reaction?
- Th2 pattern of cytokine expression
- T-helper lympocytes activate mast cells, and eosinophils,
- Th1 cells more prominant in severe cases
- Th2 cells more prominant in less severe cases
- influenced by corticosteroids
Explain the remodling of epithlium in asthma
- loss of ciliated columnar cells
- More vulnerable to infection
Explain the remodling of epithlial basement membrane
- thickened basement membrane
- collagen deposition
Explain the remodling of smooth muscle
- hyperplasia
- actin and myosin cross links change –> increased contraction and stays contracted for longer
Clinical features of asthma
- wheezing
- shortness of breath
- worst at night
- cough
Atopic Vs Non-atopic
Atopic - extrinsic (environmental trigger) - IgE produced
Non-atopic- intrinsic - Inflammation
What T cell is assoiciated with asthma?
Th-2 cell
Explain the process of plasma cell production from antigen presentation
Antigen presentation Binds to CD4+ T cell Proliferates --> Th0 Proliferates --> Th1 and Th2 Th2 --> binds to B cell by IL-4 --> Plasma cell IgE secreted
IL-5 released from Th2 does what?
Recruits eosinophils
IL-13 and IL-4 from Th2 does what?
Mast cells express IgE receptors
Once the antigen binds to IgE receptor on mast cell what happens?
- stimulation of Ca+ into mast cells
- release of Ca2+ from storage
- release of histamine
Stimulation of the postganglionic cholinergic fibres causes what?
- bronchial smooth muscle contraction mediated by M3 muscarinic ACh receptors on ASM cells
- increased mucus secretion mediated by M3 muscarinic ACh receptors on gland (goblet) cells
Stimulation of the postganglionic noncholinergic fibres causes what?
- bronchial smooth muscle relaxation mediated by nitric oxide (NO) and vasoactive intestinal peptide (VIP)
Investigations into asthma
- Lung function tests (PEFR)
- diurnal PEFR
- Spirometry (FEV1)
- Exercise test
- Trial of corticosteriods
Management of asthma
- abolish symptoms
- restore normal lung function
Why are most asthmatic drugs given by aerosol?
- bypass the liver for metabolism
Drug treatment of asthma
- SABA (Salbutamol)
- ICS (Beclometasone dipropionate)
- LABA (Salmeterol or formoterol)
- ? LAMA - ipratropium
- ?steroids - methotrexate
What is an asthmatics FEV1/FVC ratio?
- <75%
- obstructive pattern
