Asthma Flashcards
what is the pathophysiology of asthma?
inflammatory disease of the medium sized airway
associated with
-loss of airway epithelium
-thickening of BM
-hypertrophy of the smooth muscle layer
resulting in;
-hyper responsiveness to normal triggers of contraction
-abnormal contraction in response to usually benign triggers
what happens to the smooth muscle in athsma?
hypertrophy (increase in the size of cells): increase in the amount of smooth muscle which forms a lattice work underneath the epithelial layer
what can athsma result in?
- Hyper-responsiveness to normal triggers of contraction (eg ACh or Histamine)
- Abnormal contraction in response to usually benign triggers (triggers which normally would cause a resposne)
what are some of the inflammatory triggers for athsma?
allergy
viral/bacterial infection
exercise
what are some of the drug triggers for athsma?
- Beta-blockers (for Hypertension or Anxiety)
- Non-steroidal anti-inflammatory drugs (which interfere with normal control of inflammation)
what is the management of asthma symptoms?
- Bronchorelaxation – beta2 Agonists - Salbutamol relaxes smooth muscle tightening
- Anti-inflammatories – corticosteroids, leukotriene receptor blockade, monoclonal antibodies - cuts down inflammation and cuts down inflammation related symptoms
what are the consequences of the lungs only having one orifice?
Since same orrifice, we maximise inspiration is at the expense of expriation
- Lower curve is inspiration and upper is expiration
- Inspiration - a plateu is formed fairly quicky
- Expiration - fast increase then as airways are compressed, flow rate dec slowly until lungs are emptied
maximise time spent during inspiration, at the expense of expiration - resulted in rapid flow rates
what has the single orrifice done for our flow rates?
- this single orrifce has allowed us to generate very large flow rates of 900 litres/min
- Achieved by firm but flexible airway walls
what would happen if we had no firm and flexible airways?
if here was no tension/tightness, expiration would compress the airway walls
what happens to the airways in athsma?
-
Dynamic: (come and go)
- Rapid muscle contraction (Ach by vagus, and Histamine)
- Medium timescale – secretions
-
Fixed: Stiff airway wall
- Smooth muscle bulk
- Thickened basement membrane
- therefore reduced ccompliance aand failure of relaxation
what is asthma pathology?
- Weakened and ‘denuded’ airway epithelium - due to inflammation causing it to die
- Thickened BM - pink - more collagen which is tensile, non elastic and doesnt easily relax
- Increased Smooth Muscle -pink and red- trying to work hard against narrow lumen
- Mast cells within Smooth Muscle meshwork- Histamine released which causes smooth muscle contractions
describe asthma physiology?
- Increased smooth muscle - Increased force contraction (by histamine and Mch like Ach)
- Mast cells in smooth muscle (in airways now due to inflammotry infitration) - Twitchy smooth muscle variable airway calibre (changing sensitivity and activity and changes in width of airways)
- Increased basement membrane - Loss of relaxation after contraction (poor elasticity due to more collagen. Chronic reduction in airway callibre leads to chronic damge to airways and long term breathlessness)
what are the symptoms of asthma?
- Triggered breathlessness/wheeze
- Eg – histamine (allergy)or cold
- Diurnal variation – nightime or early morning
- Cough
- Variable airway calibre
- Bronchial Hyper-reactivity
- Exaggerated response to usually constricting stimuli eg metacholine or histamine
- Bronchial Hyper-reactivity
- Inflammatory secretions
what are bronchial airway hyperactivity tests?
- much faster drop/reaction in asthmatic individuals compared to normal when exposed to histamine or mannitol.
- In asthmatic individuals - A drop of ≥ 20% FEV1 by ≤ 8mg/ml metacholine (may also use histamine or mannitol)
what can variable airway calibre cause?
- More smooth muscle so therefore more peak flow variability - by peak flow diary
- usually in normaly people, morning peak flow is lower than evening
Diurnal Variability – lower in morning than midday
Day to Day variability
what are the differences in peak flow variability between asthmatic and normal people?
overall decline in lung funtion over the week (as this student had a cat)
what type of inflammation happens during asthma?
- type of inflammation is usually Eosinophillic - granulocyte usually present in allergic responses, parasites foreign bodies
- These eosinophils make Nitric Oxide increase
- The exhaled NO can be measured and normal Value 30 ppb (parts per billion!)
what is the difference between asthma and COPD?
Reversible airflow contraction in asthma with salbutamol
why is athsma a 3 phase disease?
- (need all 3 and one alone is suffient for asthma)
- Smooth muscle only – triggered by direct mediator release eg histamine – rare wheezy episodes
- Chronic Inflammation – irritates the smooth muscle and causes regular wheezy episodes
- Acute Inflammation – viral infection – ‘clinical exacerbations’
why is inflammation a good thing?
- Inflammation leads to tissue repair and return of normal organ function
- Network of cells and chemical signals (cytokines, prostaglandins, leukotrienes, immunoglobulins) carefully regulated (with on and off cytokines)
- In an abnormal organ (eg asthmatic airways) or in the wrong place inflammation can cause harm
Which inflammation type is associated with Asthma- and what does it contain?
- Type 2 inflammation – commonly associated with asthma and allergy
- Cells – lymphocytes, eosinophils and mast cells, TH2
- Cytokines – IL-4, IL-5, GMCSF
- Prostanoids – PGELeukotriene D4
- Immunoglobulins – specific IgE (eg House dust mite - drives type 1)
how does immunity drive inflammation?
- Immunity is a reaction to an external factor
- Inflammation is a reaction to trauma like a cut
APC = antigen presenting cell
nature of response is dependant on the cytokine environment
what happens with inflammation in asthma?
- the Mast cells as we know are now in the lungs smooth muscle
- these mast cells have memory IgE receptors on them
- During the secondary response, the APC recognises the allergy, and stimulates an IL-4 IL-33 response which generates IgE.
- IgE is avidly bound to receptors on the surface of mast cells
- memory is retained within the IgE, which is used by B lymphocytes
- IgE is retained long term on the surface of mast cells, and on B lymphocytes
