Asthma Flashcards
Does asthma improve with age?
Yes, 30-70% of children are markedly improved or asymptomatic by early adulthood
Causes of airflow obstruction in asthma
Acute bronchoconstriction, mucus plugging of airways, bronchial wall edema, inflammatory cell infiltration, airways wall remodeling (fibrosis), smooth muscle hypertrophy
Flow euqation
Q=(Change in P * πr^4)/ 8nL
How does radial traction keep airways open?
On inflation, lung parenchyma pulls open airways like spokes on a wheel.
Do airways stay open or do they close on inspiration?
They close slightly because of positive pleural pressure
What FEV/FVC ratio defines obstruction?
<0.7, Can reverse with bronchodilator
What is air trapping and what are the consequences?
Because of bronchoconstriction, some air remains trapped in alveoli. Therefore, residual volume grows and vital capacity shrinks.
Is increased airway resistance uniformly distributed in the lung?
No, some airways affected more than others
Effect of asthma on V/Q
V/q mismatch causes hypoxemia. Perfusion does decrease due to hypoxia-induced vasoconstriction, but it doesnt happen perfectly.
What happens to pACO2 during a mild asthma attack?
It actually falls, the reason why is unclear
What happens to PACO2 during a severe asthma attack?
It increases, made worse by respiratory muscle fatigue
Pulsus paradoxus in asthma
Systemic arterial pressure falls by more than 10mmHg during inspiration due to large swings in pleural pressure. Increased RV return causes decreased LV preload, also increased pulmonary capacitance reduces LV preload. Increased LV afterload because negative thoracic pressure.
Asthma phenotypes
Allergic (atopic) asthma
Non-allergic (nonatopic) asthma
Aspirin-exacerbated respiratory disease
Exercise-induced asthma
Or by pathology:
Eosinophilic
Neutrophilic
Pauci-granulocytic
Does allergic asthma have a genetic component?
yes. Strong family history correlation
How does an allergic asthma reaction happen?
Allergen inhalation, causes eosinophil reaction and TH2 response, which causes the production of IgE. IgE’s cross link on mast cells then degranulate next time the antigen is encountered.
Late phase of allergic asthma reaction?
Occurs due to the recruitment of additional inflammatory cells like basophils and neutrophils.
Asthma pathology
Cellular infiltrates and edema within the bronchial wall. Epithelial damage. Smooth muscle layer hypertrophy and hyperplasia. Basement membrane thickening. Increased number of goblet cells and mucous gland hypertrophy
Hygiene hypothesis
Exposure to infections early in like causes the development of TH1 mediated response and shifts the balance away from TH2.
TH2 Cytokines
IL4 cause IgE synthesis in B cells
IL5 causes eosinophil maturation
IL-9 mediated mast cell recruitment and function
IL-13 causes airway hyperresponsiveness and mucous hypersecretion
Exercise induced asthma
Pathogenesis seems to involve cooling of the airway. High energy water molecules evaporate and lead to cooling. This causes bronchoconstriction.
Aspirin-Exacerbated respiratory disease
Aspirin inhibits COX, which shifts the pathway to the production of Leukotrienes in the lipoxygenase pathway. Leukotrienes C4/D4/E4 cause bronchospasm/congestion/mucous plugging.
Samter’s triad
Asthma
Aspirin sensitivity
Nasal polyps
Airway remodeling
Consists of smooth muscle mass increase, mucous secretion increase, persistence of inflammatory cells, collegen depositon, reduced elasticity of airway wall.
Signs of asthma
Wheezing, prolonged expiratory phase
Can severe asthma occur without wheezing?
Yes!
Status asthmaticus
Severe attack that is refractory to treatment with bronchodilators. Must be ventilated
Tests to check airway reactivity
Bronchoprovocation tests - where agents are delivered by nebulizer device
What is measured in bronchoprovocation tests?
PC20 (the provocative concentration for a fall in FEV1 by 20%.
Methacholine
Derivative of acetylcholine, directly stimulates smooth muscle receptors to cause bronchoconstriction
Mannitol
Increases osmolarity of airway surface, resulting in release of mast cell mediators to cause bronchoconstriction
Albuterol
Short acting B2 agonist that increases cAMP, which activates PKA which bronchodilates
Salmeterol, formoterol
Beta 2 agonists that are long lasting ~12 hours.
Ipratropium
Anticholinergic agent that decreases bronchoconstrictive tone to airways. Blocks M1 (constrictive), M2 (autoreceptor so dilatory), and M3 receptor. Lasts 6 hours
Tiotropium
Anticholinergic agent that decreases bronchoconstriction. Blocks M1 and M3 but not M2(which is bronchodilatory).
Theophylline/aminophylline
PDE inhibitors, increases cAMP so causes vasodilation. Decreased mediator release from mast cells as well.
Also inhibit adenosine receptors.
Many side effects that include nausea/diarrhea, arrhytmias, CNS excitation
Use of corticosteroids in asthma
Decrease airway inflammation through numerous mechanisms.
Omalizumab
Prevents IgE from binding to mast cells and cross linking. Can’t bind antigen and degranulate. The MAB binds IgE and prevents it from being stuck onto mast cells.
H1 receptor mediated actions
Increased vascular permeability. Bronchial and intestinal smooth muscle contraction. Increased nasal mucus production. Increased chronotropy and inotropy. Vasodilation. Flushing.
