Asthma (Exam III) Flashcards
Where is the point of maximum airway resistance?
Medium-sized Bronchi
What are the 3 basic functions of the conducting zone of the lungs?
- Warm air
- Trap Debris
- Produce Mucus
Which portion of the ANS directly innervates the bronchiole smooth muscle?
Which portion indirectly affects bronchiole tone?
- PSNS = direct innervation w/ vagus nerve
- SNS = indirect control of tone (think epi)
What is the transition structure from the conducting zone of the airways to the respiratory zone of the airways?
Terminal bronchioles
What pathophysiologies are the components of COPD?
Chronic Bronchitis + Emphysema
What characterizes the alveoli of someone who has Emphysema?
What usually causes Emphysema?
- The alveoli have enlarged and have ↓ surface area.
- Smoking
What is the most common chronic disease in children?
Can children grow out of it?
Asthma, and yes, most children grow out of it.
What are 3 hypotheses for increasing prevalence of asthma around the world?
- Infant second-hand smoke
- Worsening air quality
- Hygiene hypothesis
What are general symptoms of asthma?
When are symptoms generally worse?
- Dyspnea, wheezing, coughing, chest tightness
- Symptoms usually worse at morning and at night.
What histological change contributes to worse COPD symptoms in the morning?
- Columnar Epithelial Cells → COPD → Squamous Epithelial Cells.
- This change results in ↓ mucus and ↓ cilia causing mucus to settle deep in the lungs.
Which two measurements are used in the diagnosis of asthma?
Forced Expiratory Volume (FEV) & Peak Expiratory Flow (PEF)
Which two measurements are used in the diagnosis of asthma?
Forced Expiratory Volume (FEV) & Peak Expiratory Flow (PEF)
Which two drugs are used to provoke a fall in forced expiratory volume after being inhaled?
Histamine and methacholine
What are the two major categories of asthma treatment?
- Short Term: sympathomimetics (β₂-agonists)
- Longer Term: Anti-inflammatories (Corticosteroids)
Is α-1 stimulation beneficial in asthma treatment?
Yes, vasoconstriction of pulmonary arteries decreases congestion.
need to verify, he later says it makes things worse
What are the two sources of pathogenesis in asthma?
- Intrinsic = genetic
- Extrinsic = Type I Hypersensitivity Reaction (Allergen)
Degranulation of what cell is responsible for the release of inflammatory mediators?
Mast Cells
What inflammatory mediators are released from mast cell degranulation?
What response does cytokine release (from inflammatory mediators) cause?
- Histamines, Leukotrienes, & Prostaglandins.
- Diffuse response: bronchoconstriction, vascular leakage, mucus secretion, itching, anaphylaxis, etc.
What inflammatory mediator is responsible for attracting WBC’s for the later reaction?
PGD₂
What causes the late reaction of an immunologic hypersensitivity reaction? How much later does this usually occur?
- WBCs (T-lymphocytes, Eosinophils, & Neutrophils)
- 2-8 hours after initial event.
Which inflammatory mediator is considered the “slower-reacting” cytokine?
Leukotrienes
Describe the hypersensitivity reaction.
- Dendritic cell interacts w/ antigen.
- MCHII presents antigen to T-Helper 2 cell
- T-Helper
(needs work)
Briefly describe the early reaction portion of a hypersensitivity reaction.
- Allergen triggers IgE antibodies on Mast cell
- Mast cell degranulates & releases inflammatory mediators
- Histamine, LTC4, PGD₂ produce bronchostriction (and inflammation to a lesser degree).
Does a late reaction have the same intensity as an early reaction?
Yes
What characterizes the late reaction portion of a hypersensitivity reaction?
- Allergen triggers Mast cell
- Mast cell releases pro-inflammatory cytokines
- Cytokines + PGD₂ = release of WBC’s = ↑ inflammatory response.
What cells produce mucus?
What is the normal composition of mucus?
What is the composition of mucus in asthma?
- Goblet and Columnar Epithelial Cells
- 95% H₂O, 5% glycoproteins
- 90% H₂O, 10% glycoproteins
What structure maintains the normal resting tone of airway smooth muscle?
What ANS receptors are the primary receptors of bronchostriction?
- Vagal Nerve
- M3 Receptors
What is Croup?
Who is most often affected?
What is the hall-mark sign?
Does this condition resolve on its own or require treatment?
- Acute laryngotrachobronchitis
- Children (6 months - 5 years)
- Barking, seal-like, cough.
- Usually self-resolving, can require nebulized epi in severe cases.
What occurs with mucus specifically when one has chronic bronchitis?
- ↑ Number of mucus glands
- ↑ Size of mucus glands
- Thicker mucus
What β₂-agonists should be known?
Terbutaline, albuterol, metaproterenol, salmeterol, etc.
What would β₂-agonist toxicity cause?
Skeletal muscle tremor
When would nebulized epinephrine be utilized?
Is nebulized epi primarily used in children or adults?
- In a severe acute asthma attack.
- Primarily in children
What potent nebulized bronchodilator can cause arrhythmias and is potentially the cause of ↑ mortality rates?
Isoproterenol
Which drug is the most widely used SAβ₂A bronchodilator?
Albuterol, similar efficacy to isoproteronol w/ less side effects.
What two LAβ₂A’s should be known?
What is their duration of action and what makes them long acting?
- Salmeterol & Formoterol
- 12 hours, high lipid solubility
Which particle size from nebulizers is effective at actually delivering medicine?
How much dose is usually lost and what happens to the other sized particles?
- Medium-sized particles
- 80-90% of dose is usually breathed back out via small particles or deposited in the mouth via large particles.
Which methylxanthine is best for asthma?
Theophylline
What is the essential mechanism of action for methyxanthines?
Phosphodiesterase inhibition (PDE blocked from breaking down cAMP = ↑ cAMP = bronchodilation)
When does Theophylline become toxic?
> 20mg/L
What methylxanthine requires peak/trough monitoring?
Theophylline
Why would ipratropium bromide be preferred over atropine?
- More selective so no CNS effects.
What drugs does ipratropium bromide combine well with?
β₂ agonists = synergistic
Give the general duration of action of atropine, tiotropium, and ipratropium in order of shortest to longest.
- Atropine (shortest)
- Ipratropium Bromide
- Tiotropium (Longest)
What condition is less responsive to corticosteroids?
COPD
What is the use of corticosteroids for asthma?
What is their general mechanism of action?
- Anti-Inflammatory = prevention of acute attacks.
- Inhibition of production of cytokines & inhibition of lymphocytic and eosinophilic airway inflammation.
How do glucocorticoids work?
- Inhibition of immune response by blocking transcription/translation.
What are some bad side effects of corticosteroid use?
- ↑ osteoporosis w/ long term therapy
- ↓ rate of growth in children
- fluid retention
What nasty side effect occurs from oral corticosteroid use?
Oropharyngeal Candidiasis (fungus)
What long term effects are hopefully seen with usage of inhaled corticosteroids for asthma?
- ↓ symptoms
- ↑ lung function
- ↓ oral steroids
- ↓ bronchial activity.
What drugs are available for refractory asthma symptoms not well treated with long-term inhaled corticosteroid use?
How do these work?
Why are these not prescribed more often?
- Anti-IgE monoclonal antibodies.
- IgE MABs work by binding to mast cell receptors and preventing antigen binding.
- MABs are expensive.
What two ways do Leukotriene pathway inhibitors work?
- Inhibition of 5-Lipoxygenase pathway (zileuton)
- Inhibition of LTA4 receptor binding (Montelukast)
What would be a good choice of drug for mild asthma?
- Albuterol (β receptor agonist as needed)
What would be a good choice for moderate asthma with nocturnal symptoms?
- Anti-inflammatories like an inhaled corticosteroid or inhaled Cromolyn
- Oral Leukotriene receptor antagonists.
Is Cromolyn used for asthma now-a-days? What is its mechanism of action?
- Utilized for more for eyes
- Mast cell degranulation inhibitor
Increased levels of Annexin-1 (from glucocorticoid administration) is associated with what two things?
- Phospholipase A2 suppression
- Leukocyte response inhibition
