12/6 Asthma - Martin Flashcards
types of lung disease & examples
- obstructive lung disease: diseases of airflow/airway resistance
- asthma
- COPD
- bronchiectasis
- *asthma-COPD overlap syndrome
- restrictive lung disease
- fibrosis
- interstitial diseases
- vascular lung disease
- pulmonary HTN
- pulmonary thromboembolism
asthma
key features
heterogeneous disease, usually characterized by chronic airway infl, defined by
- hx of resp sx (wheeze, SOB, chest tightness and cough) varying in time/intensity
- variable expiratory airflow limitation
reiteration: 3 key features
- presence of airway infl
- variable airway obstruction
- symptoms vary over time
pathogenesis of asthma
2 key features
cellular players, mediators of fx
- inflammation
- airway obstruction
cells:
- smooth muscle
- hypertrophy and contraction → airway narrowing, airflow obstruction
- eosinophils
- lymphocytes
- mast cells
- autonomic nerves
mediators:
- histamine
- leukotrienes
- IgE
- IL5
- acetylcholine
role of:
airway smooth muscle
what happens?
innervation?
mediators
airway smooth muscle hypertrophy and contraction → episodic airway narrowing
innervation:
- beta2 adrenergic receptors → relaxation
- PSNS muscarinic ACh receptors → constriction
mediators:
- histamine
- leukotrienes
- acetylcholine
pathology of asthma
- epithelial desquamation (even in mild cases)
- smooth muscle hypertrophy
- mucus plugging
- inflammatory infiltration: eosinophilic
- (neutrophils more prominent in COPD)
- basement membrane thickening
- no destruction of alveoli or fibrosis
T Helper cell subsets
diff T helper subsets differ in triggers, cytokine production, target pops, and types of immunity elicited
asthma inflammation is Th2 mediated
Th1 : triggered by IL2, IL12
- produce mainly IFNgamma
- act on macrophages
- elicit cell-mediated immunity
_Th2_ : triggered by IL4
- produce IL4, IL5, IL9, IL10, IL13
- act primarily on eosinophils, basophils, mast cells, and B cells
- elicit humoral immunity
graphic of asthmatic rxn
chronic inflammation
can be result of exposure to irritants/pollution, infection , external allergens, auto-immune mechs
results in…
- incr capillary permeability
- mucosal edema
- excess mucus production
- epithelial damage leading to luminal cellular debris
asthma triggers
infection
allergy
- pollen
- cats
- meds
- house dust mites
- cockroach feces
cold air
GERD
emotion
exercise
aspirin
irritants
- nitrous oxide
- ozone
- particulates and aerosols
- smoke
airway mucosal disease and mucus characteristics
asthma: labs
- possible eosinophilia (sputum, blood) and high IgE levels
- spirometry (variable, may be normal)
- decr FEV1/FVC: defines obstruction
- normal/decr FEV1
- normal/decr FVC
- incr TLC, RV, FRC signify air trapping
- gas exchange → hypoxemia and hypercapnea during exacerbations
- VQ mismatch
- hypoventilation
- incr exhale nitric oxide (marker of Th2 eosinophil mediated infl)
- CXR: possibly hyperinflation
- chest CT: occasionally rules out other disease
flow volume chart:
obstructive disease
“scooping” present
flow preferentially affected at low lung volumes
goal response to bronchodilators
12% incr in FVC or FEV1
and
absolute increase > 200cc
provacative testing for asthma
demonstrable decr in FEV1 in response to:
- methacholine (20%)
* tested w increasing conc; measure PCO2 - exercise (10%)
- can be delayed (1, 3, 5, 10, 15, 20 min after exercise)
- false negs occur with too little, too much exercise
- occupational exposure
- cold air
causes of hyperinflation
1. dynamic
- decr expiratory flow and increased respiratory rate = not enough time to exhale
2. static (in emphysema, not asthma)
- equilibrium between chest wall expansion and lung contraction is upset in favor of higher resting volume
risk factors for exacerbations of asthma:
- ever intubated for asthma
- uncontrolled asthma sx
- having 1+ exacerbation in last 12mo
- law FEV1 (measure lung fx at start of treatment, at 3-6mo, periodically after)
- incorrect inhaler tecnhique and/or poor adherence
- smoking
- obesity, pregnancy, blood eosinophilia
asthma tx
- smoking cessation
- education (trigger avoidance, proper inhaler technique)
- medications
- bronchial thermoplasty (bronchoscopy procedure - warming to 140F makes smooth muscle regress)
asthma medications:
2 broad categories
- controllers
- anti-inflammatory
- inhaled corticosteroids (ICS)
- long acting bronchodilators
- long acting beta2 agonists
- anti-leukotrienes
- anti-muscarinics (tiotropium)
- methylxanthines (theophylline)
- relievers
- short acting beta2 agonists
- systemic steroids for severe exacerbations
steps in asthma treatment
“step up therapy”
- as-needed inhaled short-acting beta2 agonist
- add low dose ICS
- low dose ICS/long acting beta2 agonist
- med/hi ICS/LABA
- refer for add-on treatment (anti-IgE, anti-IL5, thermoplasty)
exacerbations
acute or subacute worsening of symptoms and lung fx compared with pt’s usual status
ventilatory failure
acute respiratory failure in severe asthma
gas exchange abnormalities
- VQ mismatch → hypoxemia
- decr ventilation → hypercapnea
high lactate levels due to severe resp muscle fatigue
mental status changes due to hypercapnea and/or fatigue (BAD)
HYPOXEMIA:
5x physiological basis (what you’ll see in each case)
R → L shunt (does not current w O2)
VQ mismatch (DOES correct with O2)
hypoventilation (see normal Aa gradient)
low PiO2
diffusion issue
evolution of hypercapneic respiratory failiure
- hi pH, lo PCO2: pt feels bad, but has reserve
- NORMAL PH, NORMAL PCO2
- lo pH, hi PCO2
key: normal blood gas in a distressed pt…sign of impending resp failure!
effect of oxygen
takeaway: pulse oximeter gives you info about ease of oxygenation
DOESN’T TELL YOU WHETHER ADEQUATE VENTILATION IS OCCURING!
hyperoxygenation can impair VQ matching → makes ventilation less efficient
- increases alveolar wasted ventilation/dead space
→→ can lead to CO2 retention in pt with limited reserve → can’t increase total ventilation to make up for cecrease in effective alv ventilation
Haldane effect: actually displaces CO2 bound to Hb
