Asthma Flashcards
What 3 things make up the respiratory system?
- airway passages
- lungs
- blood vessels
What is the purpose of the respiratory system?
- provide oxygen and CO2 exchange between air and blood
How many processes are in respiration and what are the sub categories?
- ventilation
- inspiration; diffusion and perfusion
- expiration
Definition: movement of air from the atmosphere into and out of the lungs
ventilation
What elements of the body compose the upper air passages?
- nose
- nasal passages
- mouth
- pharynx
- larynx
What elements of the body compose the lower air passages?
- trachea
- bronchi
- bronchioles
Definition: process of taking in air
inspiration
Definition: movement of blood through lungs
perfusion
Definition: movement of gases between 1 million alveoli in lungs and the capillaries that supply alveoli
diffusion
What are the steps in diffusion?
●Gases move across alveoli-capillary membrane
●Moves from the air that is in alveoli → blood in pulmonary capillaries
●C2 moves from blood into alveoli
Definition: process of expelling CO2
expiration
Asthma is known as
- chronic reactive airway disorder
T/F: asthma involves hyposensitivity to reaction to stimuli
false; hyper
T/F: asthma involves increase resistance to air flow due to airway obstruction
true
What does asthma cause a release of?
chemical mediators from mast cells
T/F: asthma can be classified as intrinsic or extrinsic based on trigger factors
true
Asthma involves:
- inflammation
- bronchospasms
- increased mucus secretion
- injury to mucosal lining of airways
What initiates extrinsic or atopic asthma?
- T1 hypersensitivity to extrinsic antigen
What does the antigen initiated by t1 hypersensitivity bind to?
mast cells; begins mast cell degranulates
The release of mast cell degranulates results in?
inflammation and bronchospasm resulting in edema, epithelial injury and impaired mucosilarily function
Intrinsic or non atopic asthma is initiated by
diverse non immune mechanisms
Which type of asthma has many types of overlapping symptoms?
intrinsic
What triggers intrinsic asthma?
- irritant receptors and vagal reflex
- viral infections
- inhaled irritants
- NSAIDS
- sulfites
- emotional stress
In what stage does asthma normally begin?
childhood
Can adults only get asthma with a previous history?
no; can get it without
What two factors are an arise to asthma?
hereditary and environmental
What is the time period of acute phase asthma?
- 10 to 20 min of trigger
Acute phase asthma breakdown
● Mast cells react to antigens and degranulate
● Airborne antigens = antigen binds to mast cells on mucosal surface of the airway
● Release of inflammatory mediators → infiltration of inflammatory cells
● Allows antigens to reach submucosal mast cells
● Direct stimulation of parasympathetic receptors:
○ Bronchoconstriction
○ Increased vascular permeability
■ Mucosal edema
■ Increased mucus secretion
What is the time period of late phase asthma?
develops 4-8 hours after exposure to asthmatic trigger
Late phase asthma breakdown
● Release inflammatory mediators induces migration and activation of other inflammatory cells: ○ Basophils ○ Eosinophils ○ Neutrophils Involves: ● Inflammation ● Increased airway responsiveness ● Renewed bronchospasm ● This leads to further air limitation and heightened airway responsiveness
Late phase asthma includes a vicious cycle of exacerbations including
- edema
- epithelial injury
- impaired mucocillary function
What are the two ways asthma patients treatment is approached?
- control factors contributing to asthma severity
- pharmacological treatment
Pharm treatment includes
- corticosteroids
- bronchodilators
- mast cell stabilizers
- beta agonists
- anticholinergic drugs
What is the percentage of the canadian population aged 12 years or older that have asthma?
10%
What nationality has a higher incidence of asthma in people 12 or older?
indigenous; greater by 12%
Globally asthma occurs in lower or higher income countries?
- lower and middle income
- due to undiagnosed and under-treatment
What two groups of people have a higher prevalence of asthma?
- boys and adult women
Where is asthma more and less prevalent in Canada?
■ HIGHER in Atlantic provinces (Ontario, Nova Scotia)
■ LOWER in BC and Prairies (Northwest territories, Yukon and Nunavut)
Risk factors for child asthma:
Family history of allergy and allergic disorders:
● Hay fever
● Asthma
● Eczema
● Genetic is complicated and multifactorial
● More than 100 genes play a role in susceptibility and pathogenesis
What specific gene is associated with asthma and bronchial hyper responsiveness?
Gene ADAM 33
High exposure of susceptible children to air-bone allergens including
● Pets
● House dust mites
● Cockroaches
● Mould
○ ALL IN FIRST YEARS OF LIFE
Exposure to tobacco smoke in utero or early in life
● Children are significantly more likely to have asthma than those in non-smoking houses
T/F: no links of asthma with income, urban or rural regions; in contrast to the US where prevelance of asthma is significantly higher in urban areas
true
Risk factors for adult onset asthma
- occupation exposure
- exposure to infectious agents, allergens or pollution
T/F: Atmospheric pollution is likely as a primary cause
false; unlikely
For women what are three factors that can lead to asthma
● Smoking
● Obesity
● Hormonal influences
When is asthma more prevalent in the hospital for children 2-15?
September; after summer vacation
When do young adults 16-49 experience a peak in asthma?
Fall and December ; Christmas epidemic
When do older adults 50+ experience it?
December; 6 days after christmas
T/F: asthma can be transient, intermittent, or persistant; mild, moderate or severe
true
t/f: lower airway obstruction is normally reversible
true; in contrast to other diseases
Triggers of extrinsic asthma include
● Known as atopic or allergy asthma
● Type 1 IgE Hypersensitivity
● Results from exposure to extrinsic antigen/allergen
triggers of intrinsic asthma
● Known as non-atopic asthma; not as well understood ● Different explanations ● Respiratory tract infections ● Exercise ● Hyperventilation ● Cold air = weather changes ● Drugs and chemicals ● Irritants ● Hormonal changes and emotional upsets ● Airborne pollutants ● GERD
Which type of asthma is thought to be due to parasympathetic stimulation through vagal paths?
intrinsic
Early phase begins and lasts up to
occurs within 10-20 min of trigger and lasts up to 2 hours
Early phase breakdown
● Allergen binds to preformed IgE on sensitized mast cells in mucosal surface of airway ● Mast cells are activated ● Results in degranulation of: ○ Histamine ○ Chemokines ○ Interleukins ○ TNF-a ● Mast cells begin synthesizing these for the late phase: ○ Leukotrienes ○ Prostaglandin D2 ○ TNF-a ○ Platelet activating factor ● Inflammatory mediators cause infiltration of inflammatory cells ● Open mucosal intercellular junctions ● Allow access to submucosal mast cells ● Results in more inflammation ● Increased mucus secretion ● Increased vascular permeability ● Increased bronchoconstriction ● Dendritic cells may receive antigen that will be processed and presented in late response ○ Present to naive T lymphocytes in lymph nodes or memory TH2 cells
Late phase begins and lasts up to
4-8 hours after trigger and may last for days or weeks
Late phase breakdown
● Release of inflammatory mediators
● Cause recruitment and persistent activation of:
○ Neutrophils
○ Eosinophils
○ Basophils
○ T-lymphocytes and TH2
● Causes epithelial injury and edema
● Increased mucus
● Changes in mucociliary function
○ Accumulation of mucus
● Increased airway responsiveness and bronchospasm
● Direct toxic effects of cellular products (eosinophils)
○ Causes epithelial damage and impaired mucociliary function
● Injury causes nerve endings to be stimulated through autonomic paths
○ May cause further bronchoconstriction and mucus secretion
● Macrophages are activated in resp tract
Mast Cells factors
● Found in large numbers in skin and lining of GI and resp tract
What activates mast cells?
○ Physical injury
○ Chemical agents
○ Immunologic
○ Infectious
What is classified as a degranulate
○ Histamine
○ Chemotactic factors
○ Cytokines
t/f: degranulates cause immediate effect
true
Activated mast cell results in
-synthesize inflammatory mediators (derived from plasma membrane lipid) ○ Platelet activating factor ○ Prostaglandin D2 ○ Leukotrienes ○ Cytokines ○ Growth factors
Histamine characteristics
● Potent vasodilator ● Retracts endothelial cells ○ Increases vascular permeability ● Cause smooth muscle contraction ○ Bronchoconstriction
Leukotrines characteristics
● Similar to histamine
● More potent
● Stimulate SLOWER and more prolonged effects
● Cysteinyl leukotrienes (LTC4, LTD4 and LTE4) cause slow and sustained bronchoconstriction
Prostagladins D2 characteristics
● Vasodilator
● Increases vascular permeability
● Bronchoconstriction
Chemokines characteristics
● Cytokines that attract immune and inflammatory cells
● Primarily function to attract leukocytes
Cytokines characteristics
● Proteins that modulate the function of other cells
● TNF-a, IL-4, 5, 8 and 13
● TNF-a increases activation and migration of inflammatory cells to express adhesion molecules
TNF alpha and IL-1
- alter muscarinic receptor function
○ Increases levels of Ach
○ Causes bronchoconstriction
○ Cause mucus secretion
1L-4, 5,8, 13 are
TH2 cytokines
● IL-4
stimulates activation, proliferation and production of antigen specific IgE by B cells
● IL-5
activates and promotes eosinophils
● IL-8
causes exaggerated inflammatory response through activation of basophils, neutrophils, and eosinophils
● IL-13
impairs mucus clearance, cause bronchoconstriction and increases fibroblasts
Platelet activating factor
● Induce platelet aggregation ● Increases vascular permeability ● Activates neutrophils ● Potent eosinophil chemoattractant ● Cause bronchospasm ● Cause eosinophil infiltration and non-specific bronchial hyperreactivity
Cysteinyl leukotrienes
● Initially called “slow reacting substance of anaphylaxis”
● Due to their effect on bronchial smooth muscle of slow and prolonged contraction
● Cause bronchoconstriction
● Mostly produced by mast cells, eosinophils, and basophils
T-Lymphocytes → TH2
● Important in pathogenesis of extrinsic asthma
● TH2 act as growth factors for mast cells
● Recruit and activate eosinophils by stimulating differentiation of B-cells into IgE-producing plasma cells
● In asthma = T-cell differentiation is skewed towards TH2 phenotype cells
Leukocytes → eosinophils, basophils, neutrophils, lymphocytes, and macrophages
● Known as white blood cells
● Neutrophils, eosinophils, and basophils are granulocytes
● Neutrophils are first on the scene
○ Predominant phagocytes in EARLY inflammatory phase
● Eosinophils control the release of specific mediators from mast cells
● Basophils bind to IgE which is secreted by plasma cells
○ Release histamine and mediators of inflammation
● Macrophages arrive after neutrophils
○ They arrive in late phase response
Bronchospasm results from
● Histamine
● Leukotrienes (late phase)
● Platelet activating factor
● Prostaglandins
Within a bronchospasm does parasympathetic control of airway function properly why or why not?
- does not function properly
● Due to heightened responsiveness to cholinergic mediators
● TNF-a and IL-1 cause an alteration of muscarinic receptor function
● Leads to increase in ACh
● This causes bronchoconstriction and mucus secretion
What is mucus secretion triggered by?
inflammatory response
Leukotrines in response to mucus stimulate or withhold mucus secretion?
stimulate
The function of IL-9 AND IL-12 in mucus secretion are
to upregulate
Mucus hypersecretion
● Submucosal glands and goblet cells produce mucus in the airways
● Both sources are effected in asthma
● Results in goblet cell hyperplasia and submucosal gland hypertrophy
What is the most damaging effect of mucus hyper-secretion
is airway obstruction by mucus plugs
How is airway obstruction by mucus plugs caused?
● This is caused by mucus hypersecretion and increased plasma exudation
● May also cause increased airway hyperresponsiveness
● Impaired mucociliary function worsens the situation
○ Not as able to clear the mucus as well
What is one of the major contributors in the patho of asthma
airway remodelling
When does airway remodelling begin?
early on in the disease process
Airway remodelling
● Declining lung function in children with asthma = attributed to airway remodelling
● Changes to airway due to inflammation may include:
○ Submucosal infiltration w/ activated lymphocytes and eosinophils
○ Mast cell activation
○ Epithelial changes
○ Basement membrane thickening
● Structural changes in airway occur in parallel with inflammation
○ More inflammation = more airway remodelling
More inflammation leads to more or less airway remodelling
more
Severe asthma makes things common to have
○ Goblet cell hyperplasia
○ Smooth muscle hypertrophy
○ Mucus plugging
Patho of asthma; understand its a big concept
● Allergen or irritant trigger mast cell degranulation
● Release of vasoactive mediators and chemokines
● Mast cell release histamine immediately
● Synthesize other vasoactive mediators for later release
○ Leukotrienes
○ Prostaglandin D2
○ PAF
● This results in:
○ Vasodilation
○ Increased capillary permeability
○ Bronchoconstriction
● Trigger causes immune activation
● TH2 cells release IL-4 which stimulates:
○ B cell activation
○ Proliferation
○ Production of antigen specific IgE
● IgE causes mast cell degranulation
● Mast cells release chemokines
● Chemokines cause cellular infiltration of other inflammatory cells
○ Neutrophils
○ Eosinophils
○ Lymphocytes
○ Cytokines
● Autonomic dysregulation results from alteration to muscarinic receptor function by TNF-a and IL-1
● This causes bronchoconstriction and mucus secretion
Direct toxic effects of cellular products cause epithelial damage and impaired mucociliary function
○ Injury causes local nerve ending stimulation
○ This may cause more bronchoconstriction
○ May cause more mucus secretion
Airway remodelling occurs b/c persistent inflammation and toxic effects of:
○ Eosinophils
○ Leukotrienes
○ TNF-a
Vasoactive mediators and inflammatory cell infiltration causes:
○ Bronchospasm ○ Vascular congestion ○ Mucus secretion ○ Impaired mucociliary function ○ Thickened airway walls ○ Increased contractile response of bronchial ○ Hyperresponsiveness and obstruction
Patho of Early phase response
● Triggered by activation of presensitized IgE coated mast cells
● Mast cell degranulation occurs
● Inflammatory mediators cause:
○ Increase mucus production
○ Open mucosal inter cell junctions with exposure of submucosal mast cells to the antigen
○ Bronchospasm
Patho of late response
● Involves release of other inflammatory mediators
● Recruit neutrophils, eosinophils, and basophils
● Increase vascular permeability
● Cause epithelial injury with decreased mucociliary function
● Increased airway responsiveness
● Bronchospasm
Clinical manifestations: usually related to narrowed airways due to lower airway obstruction caused by:
○ Bronchospasm
○ Edema of bronchial mucosa
○ Mucus hypersecretion
Clinical manifestations: air begins trapped or freed and there is impaired expiration
trapped
Clincial manifestations
● Obstruction will worsen
○ Air flows to less resistant portions because ventilation is uneven
● Lungs become hyperinflated
○ Put resp muscles at disadvantage
● Alveolar hypoventilation occurs as gas exchange is impeded
○ Increase intrapleural pressure
○ Increase alveolar gas pressure
○ Cause ventilation perfusion mismatch
● Mucus inhibits alveolar ventilation
● Hyperventilation is triggered by lung receptors responding to increase lung volume + alveolar hypoxia
Clinical manifestations: hypoxia causes
○ Decrease in serum CO2
○ Resp alkalosis
○ Accompanied by hypoxemia
Clinical manifestations: work of breathing increases
○ Pt breathes close to functional residual capacity
○ Worsen SOB
○ Increase O2 demand
○ Fatigue results
Clinical manifestations: cough becomes less effective
○ Due to air trapping and inspiration occurring at higher residual lung volume
○ Worsens hypoxemia
○ Retain CO2
○ Resp acidosis will result if obstruction persists
Clinical manifestations: resp failure ensues
● During full remission asthmatic patients are asymptomatic in pulmonary function tests are usually normal
Signs; objective and reported by HCP
● Physical assessment ● Lab findings ● Radiology ● Pulmonary function tests ● Peak flow monitoring
Symptoms: subjective and reported by patient
● SOB ○ Inability to adequately ventilate ○ Abnormal ventilation-perfusion relationship ● Chest tightness ○ Air trapping ○ Result from hyperinflation of lungs ● Cough ○ Pt tries to clear airway of mucus ● Noisy breathing or wheezing ○ Passing of air through narrowed airways
Physical Assessment Findings: Inspection
● Increased work of breathing ● Use of accessory muscles ● Prolonged expiration ● Wheezing ● Cough ● Inability to maintain a conversation
Physical assessment findings: Auscultation
● Wheezing ● Distant or quiet breath sounds ○ Mean that air is not moving ● Adventitious breath sounds ○ Crackles ○ May be related to infection
Physical Assessment Findings: Vital Signs
● Tachypnea
● Tachycardia
● Decreased oxygen saturations
○ Hypoxemia
Physical Assessment Findings: Tachycardia
● May be result of stress, anxiety, and use of ventolin
Lab Values
***most important result in asthma is arterial blood gas
● Provides information about ventilation
● Givens the pCO2 and pO2 values
Hyperventilation will cause
respiratory alkalosis
● May be accompanied with hypoxemia or low pO2 during an attack
Persistent worsening of ventilation and ventilation-perfusion mismatch cause
respiratory acidosis
● This is result of hypercapnia or retention of CO2
Acid Base Imbalances and Hypoxemia → address with O2 admin and pharm therapy
● Open airways and improve ventilation
● Mechanical ventilation and critical care management is required for severe acidosis and hypoxemia
Normal Values
pH → 7.35-7.45
pCO2 → 35-45
HCO3 → 22-26
pO2 → 80-100
Chest X-Ray
● Common to be done as a part of the work-up for patient in resp distress
● Hyperinflation flattening of hemidiaphragms are common radiological findings on chest x-ray
● May provide info on whether or not there is a resp infection
Bacterial infection suspected or confirmed = antibiotics used
Viral infection suspected or confirmed
DO NOT use antibiotics
Which is a more common trigger for asthma: bacteria or viral
• A viral respiratory infection is a more common trigger than a bacterial respiratory infection
Pulmonary Function Tests
● Use spirometry ● Used in initial diagnosis of asthma ● Monitor the ongoing response to therapy ● Assess airway function ● Validate peak flow monitoring
Spriometry offers??
the single most objective measurement of lung function available
Bronchial provocation tests use:
● Histamine ● Methacholine ○ Cholinergic agonist ○ Acts on PNS ○ Causes bronchoconstriction ● Or exposure to non-pharm agent (cold air)
Airway obstruction is assessed following bronchial provocation using baseline and post B-agonist measurements of:
● Forced vital capacity → FVC
● Forced expiratory volume in 1 second → FEV 1
● Ratio of forced expiratory volume in 1 sec and forced vital capacity → FEV1/FVC
● Forced expiratory volume 25-75% → FEV 25-75%
Reversible airway obstruction is confirmed when
post challenge data shows 12% or greater improvement
PEF can be used to
to validate peak flow monitoring results if value is multiplied by 60
Peak Flow Monitoring
● Measure the peak expiratory flow
● Measure how quickly a person can exhale
● Done at home using a handheld device comparing the result to the patient’s personal best
● Should be measure around the same time each day
● Best of three readings should be recorded
PEF greater than 80% of personal best indicates that the person is in the
green zone
● Asthma is well controlled
PEF btw 50-80% of personal best indicates the person is in the
yellow zone
● Caution should be taken
● Person should use their short acting bronchodilator
● Repeat PEF measurement
● Patient should contact their HCP if they do not return to green
PEF less than 50% of personal best indicates
medical alert and red zone
● Person should take their short acting bronchodilator
○ Increase if needed
● Should seek medical attention
Pharm Therapy
Long Term Control Medications or Controllers
● Address inflammation and airway obstruction
Quick Relief Medications
● Reverse acute airflow obstruction
T/F: all medications are given inhally
true; except for monoclonal antibody is given subq
Quick relief meds: beta 2 agonists
● Result in bronchodilation
● Act on beta 2 pulmonary receptors increasing levels of cAMP
● Relax smooth muscle
● They can affect beta 1 receptors in heart causing tachycardia
● Preferred quick relief medications
Quick Relief Medications;Anticholinergics
● Inhibit muscarinic cholinergic receptors
● Reduce vagal tone of airways
● Result in bronchodilation
● Add on therapy with others
Quick Relief Medications: Systemic Corticosteroids
● Used in severe asthma exacerbations
Long-term Control Medications: Long-term Control Medications
● Block COX and lipoxygenase paths in inflammation
● Decrease inflammation by suppression of polymorphonuclear leukocytes and fibroblasts
● Reduce capillary permeability
● LABA’s and SABA’s
What are the medications of choice?
***SABA and LABA are the medication choice for all individuals with persistent asthma
Long term control medications: leukotriene modifiers
● Interfere with leukotriene action
Long-term Control Medications: Mast Cell Stabilizers
● Stabilize membrane of sensitized mast cell after antigen IgE interaction
● Prevent release of inflammatory mediators such as histamine
Long-term Control Medications: Monoclonal antibody
● Subcut injection
● anti-IgE antibody that prevents binding of IgE to basophils and mast cells
Patient teaching:
● Avoid triggers; Recognize signs of impending asthma attack
● Participate in development of written action plan for med titration and symptom management
● Use peak flow monitoring
● Take medication as prescribed; Use proper inhaler technique
