Asthma pathophys Flashcards
What symptoms sudden or persistent is associated with asthma (4)
- Dyspnea (difficult breathing)
- Chest tightness
- Wheezing
- Sputum production and cough
What is the main cause of asthma? What does this cause?
Inflammation
- bronchial hyper-resonsiveness/reactiveness
Is asthma reversible
Yes
Why is asthma still causing death? (4)
- Under-diagnosis of asthma
- Under-treatment of asthma
- Lack of public understanding and education of asthma
- Inadequate asthma supervision and poor monitoring
Asthma prevalence in boys vs girls and men vs women
More common in boys (children)
More common in women (adult)
T/F asthma is primarily an adult disease
False
Is life span affected with asthma patients?
No
What is considered a significant predisposing factor for asthma?
Atopy
What is the etiology of asthma (2)
Genetic factors + environmental risk factors/triggers
Define Atopy
The GENETIC tendency to develop IgE antibodies to encountered environmental allergens by natural exposure (pollens, grass)
- route of entry is mucosal surfaces and skin
When a patient experiences an intense immune response due to allergens.. what allergic diseases can it lead to? (5)
- Allergic rhinitis
- Asthma
- Atopic dermatitis (eczema)
- Hives
- food allergies
Do all patients with atopy develop asthma?
Do all patients with asthma have atopy?
No
No
Explain the hygiene hypothesis
During pregnancy, women have more TH2 than TH1
- this is so she does not reject the fetus
The baby’s immune system must be rebalanced at birth to make TH2 = TH1 to decrease risks for atopy/asthma
What factors favour the Th2 phenotype which is not ideal (creating an imbalance) (5)
- Antibiotics
- Hand sanitizers
- Urban environment
- western lifestyle
- Diet
- Sensitization to house-dust mites
Which factors favour the Th1 phenotype (IDEAL)
- presence of older siblings
- Early exposure to day care
- Tuberculosis, measles, or hepatitis A
- Rural environment
What are some host factors that influence development of asthma?
- Genetic
- Obesity
- Gender
- Emotional factors/stress
- Medical conditions
- Perinatal factors (maternal smoking, maternal asthma)
- Medical conditions (GERD, chronic sinusitis, URTI)
- Exercise (cold air)
What are environmental factors that affect asthma
- Allergens
- Infections
- Occupational sensitizers (paint fumes)
- Tabacco Smoke (passive + active)
- Outdoor/indoor pollution
- Diet (food allergies like milk, soy, nuts, eggs, shellfish)
- Medications (Aspirin or NSAID, use of beta-blockers)
What is asthma caused by?
Bronchioal hyper-responsiveness
- bronchospasm, tissue edema, mucus hypersecretion
- narrowing airways
Is asthma obstructive/restrictive
Obstructive
What are 3 components that move debris out of lungs
- Cilia
- Sol layer
- Gel layer
What are the 4 steps to allergic cascade?
- Sensitization to an allergen
- early/immediate phase response upon re-exposure to allergen (IAR)
- Late phase response to allergen (LAR)
- Chronic inflammation
Explain how sensitization to allergen works
- Initial exposed to allergen
- If Atopic: T cells stimulate B cells to plasma cells to produce IgE antibodies for that antigen
- IgE antibodies bind to mast cells (mast cell-IgE complex)
- Allergen crosslinks IgE on mast cells
This complex is now sensitized (tiny ticking bombs). It is prepared to recognize and react to allergens
When does Immediate Asthma response occur? How long does it last?
- Occurs within minutes with re-exposure
- lasts a few hours
How does Immediate-phase asthma response work (IAR)? What is the result
- Incoming allergen binds to IgE on mast cells creating a cross linking of IgE antibodies
- With sufficient cross-linking, mast cells explode and degranulate
- release histamine + inflammatory mediators - The inflammatory mediators will cause
- bronchoconstriction
- vasodilation (edema)
- increase mucous secretion
- induce plasma exudation (leaking) into airways
Result:
- thickened, edematous airways & narrowing of airway lumens
What is the solution to IAR?
Can spontaneously reverse on its own OR
with inhaled B2-agonist
When does late Asthma response occur (LAR)? How long does it last?
Occurs within several hours
- can last 3-10 hours (sometimes 24+ hours)
Starts at the SAME TIME as IAR but takes longer to fully manifest
How does late asthma response work (LAR)? What is the result?
- Recruits and activates immune cells (eosinophils, basophils, neutrophils, macrophages, Th cells)
- Immune cells release more inflammatory mediators
- Inflammatory mediators cause MORE activation of EOSINOPHILS
Result: Damage to epithelial cells and further bronchoconstriction
What is the solution to LAR
corticosteroids
- difficult stage to reverse with bronchodilators
How does chronic asthma occur. What is the result
- Repeated exposure to allergens and allergic response
- Permanent damage occur in lung tissue
Result
- airway remodelling
- scarring over time
Is chronic asthma curable?
No
- it is treatable AND preventable
What are the effects of chronic inflammation on airways? (6)
- epithelial damage –> airway hyper-reactivity
- Loss of relaxant factors –> exposure of sensory nerves
- FIBROSIS: thickening of basement membrane due to sub-epithelial fibrosis + deposition of collagen below the basement memrbane
- Hypertrophy and hyperplasia of airway smooth cells (inc # of cells = thickened = not functional)
- Increased sensitivity of smooth muscle cells (from chemical mediators)
- increased mucous: from goblet cells
Explain aspirin induced asthma? What is the triad? What occurs? What is the solution?
Triad =
- Asthma + aspirin sensitivity + nasal polyps
How
1. Single dose during 30-40s can provoke an acute asthma exacerbation,
- + rhinorrhea, conjunctival irritation, flushing of head and neck
2. leads to overproducing leukotrienes
Treatment
- avoid these meds BUT
- leukotriene receptor antagonists can work (montelukast) OR
- desensiztization to ASA
What is the role of mast cells?
INITIATE (happens 1st) the acute bronchoconstriction to allergens
- allergens combine with IgE antibodies to sensitize mast cells then release mediators
What is the role of macrophages?
Amplify inflammatory response via release of cytokines
What is the role of dendritic cells?
Take allergen to introduce to the rest of the body to fight it
- interacts with undifferentiated Th cells and stimulate more Th2 –> leads to formation of ANTIBODIES and MORE EOSINOPHILS
What is the role of T lymphocytes
- release specific cytokines that drive eosinophils to the inflammation and maintenance of mast cells
What is the role of B lymphocytes?
Secrete IgE antibodies
What is the role of eosinophils? (3)
secrete proteins that:
- damage epitheliel cells
- cause epithelial remodelling
- airway hyper-reactivity
What is the role of neutrophils?
Seen in COPD
What are the 4 structural cells? What are their roles?
- Epithelial cells
- interact with inhaled allergen to secrete Thymic Stromal Lymphopoietin (TSLP) to acitvate dendritic cells
Endothelial cells, smooth muscle cells, fibroblasts
What are the chemical mediators?
Cytokines (most important are interleukins)
- IL-3, 4, 5, 8, 13
Chemokines
- Attract th2 to the bronchioles
Arachidonic acid
- leukotrienes: important mediator for cytokine function
- inc. mucous secretion, recruit more inflammatory cells etc.. (look at table with 6)
