Lec 10 Asthma Flashcards
Which pts most prevalently have asthma?
mostly children/young adults
low SES more at risk
What is radial traction?
idea that as you inhale –> pull airway and increase cross sectional area of airway
What happens to pleural pressure with inspiration?
decreases = bigger airway
Is ashtma obstructive or restrictive?
obstructive
What is intrathoracic vs extrathoracic obstruction?
intrathoracic: expiratory airway flow limitation; have wheeze on expiration
extrathoracic = wheezing on inspiration
What happens with asthma on pulm function test? what if you give bronchodilator?
FEV1/FVC < 07 or lower limit of normal
have scooped out look on pulm function graph
with bronchodilator have normalization of FEV1/FVC or FEV1 increase by 200 mL
What is peak expiratory flow?
if tubes have high resistance = can’t have flow as big
What is air trapping? What does this mean to lung volumes
increase resistance to expiration –> less flow out –> more air left in alveoli
= same TLC but bigger residual volume and smaller vital capacity
What happens to gas exchange in asthma?
- increased airway resistance not evenly distributed
will have some degree of hypoxemia from V/Q mismtach
What happens to gas exchagne in mild vs severe asthma attack?
mild = pCO2 falls b/c other alveoli able to participate in gas exchange = primary respiratory alkalosis
severe = pCO2 rises b/c can’t ventilate properly; exacerbated by respiratory muscle fatigue
What is pulsus paradoxus?
systemic atrial P falls by < 10 during inspiration
can be caused by large swings in pleural pressure by asthma
How does asthma cause pulus paradoxus
negative intrathoracic P in inspiration –> increase blood return to RV –> septal bulging and decrease LV preload
increase LV afterload b/c of negative intrathoracic P
in expiration –> reversal
What is allergic asthma?
- have underlying allergies, eczema, elevated IgE
- exacerbated by exposure to allergens
- family history of asthma or allergies
What is mech of allergic asthma
- allergen inhaled
- TH2 response –> eosinophils –> IgE
- IgE cross-links on mast cells at re-challenge –> increase vascular permeability, bronchoconstriction, inflammatory cell recruitment, etc
What is pathology of asthma?
- cellular infiltrates and edema within bronchial wall
- epithelial damage
- smooth muscle layer hypertrophy
- increase mucous glands
What is hygiene hypothesis?
- if exposure to microbes earlier in life –> TH1 mediated immune response down regulated TH2 response
- if lack of exposure to microbes early in life –> overactive TH2 mediated immune response
What is action of each of the following TH2 cytokines?
IL4
- IL-5
- IL-9
- IL-13
- IL4 directs B cells to synthesizes IgE
- IL-5 essential for eosinophil maturation
- IL-9 mediates mast cell recruitment and function
- IL-13 causes airway hyperresponsiveness and mucous hypersecretion
What happens in exercise induced asthma?
pathogenesis involves cooling of airway = breathing and hyperventilating –> dry cold air enters –> dries mucosa
–> bronchoconstriction
provokes bronchoconstriction in pt with hyperreactive airways
What is aspirin-exacerbated respiratory disease?
- involved arachidonic acid path
- inhibit cyclooxygenase path –> produce bronchoconstrictor leukotrienes
What is samter’s triad for aspirin exacerbated respiratory disease?
- asthma
- aspirin/NSAID sensitivity
- nasal polyposis
What kind of remodelling with asthma
- increase smooth muscle mass
- inflammatory cell persistence
- muscle gland increase
What are symptoms of asthma?
- cough, dyspnea, wheezing, chest tightness
What do you see on physical exam with asthma?
wheezing, prolonged expiratory phase
or may have no wheezing if not in midst of asthma attack or because no flow
What is status asthmaticus?
severe asthma attack
doesnt respond to bronchodilators
may require assisted ventilation
What are the 2 substances administered in bronchoprovocation tests? what do you test?
- methacholine
- mannitol
give the substance then measure PC20 = provocative concentration for a fall in FEV1 by 20% with methacholine
normal PC20 < 8 for asthmatics
What is methacholine?
- derivative of ACh
directly stimulates airway smooth muscle receptors
What is manniotol?
increases osmolarity of airway surface and causes realease of mast cell mdiators
How do you diagnose asthma?
no features really unique and universal
What is treatment for asthma?
- bronchodilators
- anti-inflammatory agnets
- targeted therapy
What is action of sympathomimetics in asthma?
activate B receptor –> increase cAMP –> airway smooth muscle relaxation + inhibition of chemical mediator release from mast cells
B2 specific preferred to avoid adverse cardiac effects of B1
What are examples of sympathomimetics used in asthma?
step1
albuterol = short acting 3 hrs
salmetrerol, formoterol = long action, for prophylaxis
What is action of anticholinergics in asthma? 2 examples?
- decrease bronchoconstrictor cholinergic tone to airways
ipratropium = lasts 6 hrs; blocks M1, M2, M3 tiotropium = lasts 24 hrs; blocks M1, M3
What is action of methylxanthines in asthma? 2 examples? down sides?
- inhibit phosphodiesterase which degrades cAMP –> increase cAMP –> bronchodilation
- inhibits adenosine receptors
- may be antiinflammatory
theophylline = oral aminophylline = IV or PO
down sides = many side effects –> nausea, diarrhea, arrhythmias, CNS excitation
What is action of corticosteroids in asthma treatment?
step1
inhibit synthesis of cytokines; inactivate NF-kB the transcription factor that induces production of TNF-alpha
1st line therapy for chronic asthma
What are the 2 main corticosteroids used in chronic asthma?
- beclomethasone
- fluticasone
What is use of predinosine in asthma?
used for acute asthma attacks then tapered off
What is action of montelukast/zafirlukast?
step1
both antileukotrienes
block leukotriene receptors
good for aspirin induced asthma
What is action of zileuton?
step1
an antileukotriene
inhibits 5-lipoxygenase pathway
blocks conversino of arachidonic acid to leukotrienes
What is action of omalizumab in astham?
- monoclonal IgE antibody
binds mostly unboudn serum IgE and blocks bindg to FceRI
used in allergic asthma resistant to inhaled steroids and long acting B2 agonists
What is action of antihistamines in asthma?
- block H1 receptor which mediates: bronchila smooth muscle contraction, increased nasal mucus production, vasodilation, increased vascular permeability etc
What are the 2 first gen H1 blockers? downside?
diphenhydramin and hydroxyzine
cause significant sedation b/c easily cross BBB
What are the three 2nd gen H1 blockers?
- loratadine, fexofenadine, certirizine
lipophobic so don’t have the bad CNS effects
What is action of IL-4
- IL4 directs B cells to synthesizes IgE
What is action of IL-5
- IL-5 essential for eosinophil maturation
What is action of IL-9
- IL-9 mediates mast cell recruitment and function
What is action of IL-13
- IL-13 causes airway hyperresponsiveness and mucous hypersecretion
