Pathophysiology- Asthma PDF

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Pathophysiology: Asthma

Learning Outcomes:      

Describe the current Canadian trends in the prevalence of asthma Describe the etiology of asthma Describe the pathophysiology of asthma Link the pathogenesis of asthma to the clinical manifestations and evaluation of the disease Provide scientific rationale for interventions Provide scientific rationale for patient teaching

Conception of Action - Asthma:  Ventilation: is the movement of air from the atmosphere into and out of the lungs o

Air must be taken in through the upper passages which is composed of the nose, nasal passages, mouth, pharynx and larynx

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The air must travel to the lower airway consisting of the trachea, the bronchi, and the bronchioles of the lungs

 Inspiration: is the process of taking air in  Perfusion: is the movement of blood though the lungs  Diffusion: is the movement of gases between the one million alveoli or air-filled sacs within the lungs and the capillaries that supply the alveoli o

Gas moves across the alveolar capillary membrane. Oxygen moves from the air that is in the alveoli to the blood flowing through the pulmonary capillaries

Prevalence: The Faces of Asthma  The prevalence of asthma among Canadians 12 years and older has increased from over 2.2 million in 2005 to over 2.4 million in 2014 o

10% of the Canadian population aged 12 years and older (in 2011 there was a peak in physician –

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The prevalence of asthma in off reserve aboriginal people 12 years of age and over is higher than the

diagnosed asthma) general population at 11.9%  The National Longitudinal Survey of Children and Youth or NLSCY is a longitudinal study that began in 1994 which included information about the health, development, and social environment of the participants from birth to early adulthood o

Data found that 586,000 Canadians aged 11 and under had been diagnosed with asthma (this represents 13.4% of Canadian children)

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This has increased since 1994/95 data where 11.1% of Canadian children under 11 years of age had been diagnosed with asthma 

This increase was most present for children aged 5 and younger and children aged 10-11

 The prevalence of physician diagnosed asthma among adults is also increasing o

There is a 60% increase in woman aged 35-44 years; 80% increase in woman aged 45-64 years and 41% increase in men aged 35-44 years between 1994/95 in 2005

 There is a higher prevalence in boys and women o

There is higher asthma rated in Atlantic provinces and lowest in British Colombia and the Prairie provinces

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These rates are steadily increasing around the world

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Mortality rates have been steadily declining in Canada since 1987

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Hospitalization rates have decreased in children and adults along with ER visits

Etiology  Risk factors for developing childhood asthma include: o Family history of allergy and allergic disorders including hay fever, asthma and eczema. 

The genetic basis of asthma is complicated and multifactorial as there have been several genetic loci on a variety of different chromosomes

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Some of these genes influence the production of IL-4, IL-5, IL-13; IgE, eosinophils, mast cells, adrenergic receptors, leukotrienes, and bronchial hyper responsiveness. In particular the gene ADAM 33 has been associated with asthma and bronchial hyperresponsiveness

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High exposure to airborne allergens such as pets, house dust mites, cockroaches and mold in the first years of life

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Exposure to tobacco smoke in utero or early life

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NLSCY found that Canadian children living in household where either patient smoked daily were significantly more likely to be diagnosed with asthma compared to non-smoking households

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Low birth weight and respiratory distress syndrome

 Risk Factors for developing adult onset asthma include: o Occupational exposures to low molecular weight sensitizers (isocyanates)

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Exposure to infectious agents, allergens or pollution

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Form woman – smoking, obesity, hormonal influences may be a risk factor

Pathophysiology of Asthma  Definition of Asthma: o

“asthma is characterized by paroxysmal or persistent symptoms, such as dyspnea, chest tightness, wheezing, sputum production and cough associated with variable airflow limitation and airway hyperresponsiveness to endogenous or exogenous stimuli. Inflammation and its resultant effects on airway structure are considered the main mechanism leading to the development and persistence of asthma”

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A chronic airway disease characterized by episodic and reversible bronchoconstriction

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This description is used in both adult and pediatric Canadian asthma consensus guidelines and has not changed in over a decade 

Asthma can be classified as mild, moderate or severe. Symptoms can be transient, intermittent or persistent

 Triggers: Intrinsic Vs. Extrinsic o

Extrinsic Asthma (allergies): also known as atopic or allergy asthmas is a type I IgE hypersensitivity reaction resulting from exposure to an extrinsic antigen/allergen 

Early Phase Response:  

Occurs within 10-20 min of triggering stimuli and can last up to 2 hrs. The allergen binds to preformed IgE on sensitized mast cells on mucosal surfaces of airways

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Mast cell activation releasing inflammatory mediators specifically histamine, chemotactic chemokines, interleukins and tumor necrosis factor alpha o

This immediate response is called mast cell degranulation: mast cells begin synthesizing leukotrienes, prostaglandin D2, further tumor necrosis factor alpha and platelet activating factor for release in the late phase response

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The release of these mediator’s cause infiltration of inflammatory cells causes an increase of mucus secretions, increased vascular permeability and bronchoconstriction

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NOTE: dendritic cells may receive antigen at this time that will be processed and presented later in the late phase response to naïve T lymphocytes in the lymph nodes or memory TH2 cells in the airway mucosa, causing further immune activation o

Histamine does not cause vasoconstriction BUT it causes bronchospasm, increased vascular permeability, increased GI motility and mucus hypersecretion

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Late Phase Response  

occurs 4-8 hrs. after triggering stimuli which may persist for days or even weeks release of inflammatory mediators causes recruitment of neutrophils, eosinophils, basophils, T lymphocytes (TH2)

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these inflammatory cells cause epithelial injury and edema, increased mucus, changes in mucocilary function resulting in the accumulation of mucus and increased airway responsiveness and bronchospasms

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epithelial damage and impaired mucociliary function is caused because of direct toxic effects of cellular products, specifically from eosinophils such as basic proteins

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Intrinsic Asthma (my body doesn’t like this): also known as atopic asthma results from a variety of triggers – sometimes allergic  

Respiratory tract infection (viral)

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Hyperventilation

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Exercise

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Irritants

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Hormonal changes & emotional upset

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Airborne pollutants

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GERD

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The pathophysiology of intrinsic asthma is not as well understood or straight forward as

Exercise Cold air, weather changes Drugs & chemicals

extrinsic asthma  Inflammatory Cells o

Mast cells 

Are cellular bags of granules found in large numbers in the skin and lining of the GI and

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They are activated by several means including physical injury, chemical agents, immunologic

respiratory tract and infectious means 

They release histamine, chemotactic factors and cytokines which cause an immediate effect

Cell Derived Mediators: (from mast cells) 

Histamine: 

Potent vasodilator that causes increased vascular permeability through retraction of

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Causes smooth muscle contraction which causes bronchoconstriction when

endothelial cells stimulated in the bronchi (important part of asthma) 

Leukotrienes: 

Similar function to histamine

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They are more potent and stimulated slower and more prolonged effects compared to histamine

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Cysteinyl leukotrienes (LTC4; LTD4 <E4) cause slow and sustained (continued for a long period of time) constriction of the bronchioles which is important in asthma

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Prostaglandin D2

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Chemotactic Chemokines  

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Causes vasodilation, increases vascular permeability and bronchoconstriction Are cytokines that attract immune and inflammatory cells Primarily work to attract leukotrienes

Cytokines  Proteins that modulate the function of other cells – TNF-alpha, IL-4, 5, 8 & 13 (key mediators in the pathogenesis of asthma)

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TNF-alpha increases the activation and migration of inflammatory cells (specifically eosinophils and neutrophils) and contribute to airway remodeling o

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this also causes endothelial cells to express adhesion molecules

TNF-alpha and IL-1 alter muscarinic receptor function resulting in increased level of acetylcholine which causes bronchial smooth muscle contraction and mucus secretion

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Platelet Activating Factor  Induces platelet aggregation, increases vascular permeability through endothelial cell retraction, activates neutrophils and is a potent eosinophil chemoattractant

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Causes bronchospasm, eosinophils infiltrate and non-specific bronchial hyperactivity

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Cytokines

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Cysteinyl Leukotrienes

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This are mainly produced by mast cells, eosinophils and basophils (which play a large role in asthma patho)

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Were called the “slow reacting substance of anaphylaxis” due to their effect on bronchial smooth muscle of slow and prolonged contraction and hence bronchoconstriction

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T Lymphocytes (T Helper 2)

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Play an important role in the pathogenesis of extrinsic asthma TH2 lymphocytes act as growth factors for mast cells as well as recruiting and activating eosinophils by stimulating the differentiation of B cells into IgE-producing plasma cells

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Leukocytes (i.e. eosinophils, basophils, neutrophils, lymphocytes, macrophages – white blood cells/granulocytes)  Neutrophils are the first one on the scene and the predominant phagocyte in the early inflammatory phase

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In asthma eosinophils play an important role by controlling the release of specific mediators from mast cells

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Basophils bind to IgE which is secreted by plasma cells and release histamine and mediators of inflammation such as IL-4

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Macrophages arrive after neutrophils (which means that they arrive in the late phase of

asthma)  Bronchospasm o This is a result of the action of several mediators being released:

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Histamine (early phase)

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Leukotrienes (late phase) Platelet aggregation factor

Parasympathetic control of airway function appears to not function appropriately due to heightened responsiveness to cholinergic mediators

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This is caused by an alteration of muscarinic receptor function by TNF-alpha and IL-1 leading to an

increase in ACTH which causes bronchial smooth muscle contraction and further mucus secretions  Mucus Hypersecretion o this is a major pathophysiological feature of asthma o

Submucosal glands and goblet cells produce mucus in the airways, these are affected in patients with asthma which results in goblet cell hyperplasia and submucosal gland hypertrophy

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mucus secretions are triggered by the inflammatory response

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Leukotrienes are known to stimulate the mucus production

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Interleukin-9 and 13 are the 2 most relevant cytokines that up regulate mucus secretions

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Other meditators such as TNF-alpha and IL-1 beta and ligands of the epidermal growth factor receptors are known to have a role on mucus hypersecretion

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The most damaging effect of mucus hypersecretion is airway obstruction by mucus plugs which is caused by mucus hypersecretion and increased plasma exudation

 Mucus may also cause increased airway hyperresponsiveness  Airway Remodeling o The structural changes in the airway wall appears to occur in parallel with inflammation (more inflammation = more airway remodeling) o

Airway remodeling begins early on in the disease process of asthma and declining lung function which is attributed to airway remodeling is found in young children and asthmatics

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Changes to the airway due to inflammation may include submucosal infiltration which active lymphocytes and eosinophils, mast cell activation, epithelial changes and basement membrane thickening

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Mehrotra and Henderson stated that:

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“increase in goblet cells, hyperplasia & hypertrophy of smooth muscle cells leading to a thickened smooth muscle cell layer, increased airway deposition of collagen and other proteins resulting in a thickening of the lamina reticularis with subepithelial fibrosis and increased vascularity in the airway walls”

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Clinical Manifestations  Signs o

Physical assessment findings

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Lab results

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Radiological findings

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Pulmonary function tests

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Peak flow monitoring

 Symptoms o

Dyspnea/SOB – is the result if an inability to adequately ventilate and an abnormal ventilation – perfusion relationship where parts of the lung that are well perfused are not adequately ventilated

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Chest tightness – results from air trapping and resultant hyperinflation of the lungs

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Cough – result as the asthmatic patient tries to clear his or her airway of mucus

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In the absence of a respiratory infection, the cough will be initially be nonproductive during an asthma attack

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“noisy breathing”; wheezing – wheezing is the result of the passing of air through narrowed airways, it will be initially heard in the lower airways

 During an asthma attack: o During an asthma attack are related to narrowed airways because of lower airway obstruction die to bronchospasms, edema of the bronchial mucosa and mucus hypersecretion o Air becomes trapped with impaired expiration as the obstruction worsens and air flows to the less resistant portions because ventilation is uneven o

The lungs become hyperinflated putting respiratory muscles at a disadvantage, as hyperinflation progresses alveolar hypoventilation occurs as gas exchange is impeded by increasing intrapleural and alveolar gas pressure causing ventilation perfusion mismatch

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Hyperventilation causes a decrease in serum carob dioxide resulting in respiratory alkalosis usually accompanied with hypoxemia

Physical Assessment Findings  Inspection o

when inspecting the patient during a respiratory assessment you may note increased work of breathing, use of accessory muscles, prolonged expiration, wheezing, cough and an inability to maintain a conversation

 Auscultation o

When listening to the patient’s chest you may note wheezing, distant breath sounds, other

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If you cannot hear any breathing sounds, you must intervene and seek help from appropriate

adventitious breath sounds such as crackles (can be caused by an infection) members of the health team  Vital Signs o

You may note tachypnea, tachycardia and decreased oxygen situation

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Tachycardia may be the result of anxiety, stress and/or the use of quick relief medications like Ventolin

Lab Values  Arterial Blood Gases (identifies pCO2 and pO2 values) o

Hyperventilation will cause respiratory alkalosis which may be accompanied with hypoxemia or low

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With persistent worsening of ventilation and ventilation perfusion mismatch the patient will progress

pO2 during an asthma attack to respiratory acidosis due to hypercapnia or retention of CO2

Chest X-rays  Chest x-rays are to be done as part of the work up for a patient in respiratory distress such as an asthmatic patient experiencing acute exacerbation of the disease

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 Chest x-rays can also provide information on whether or not there is a respiratory infection component  If a bacterial infection is suspected or confirmed, antibiotics are warranted

Pulmonary Function Test  Using spirometry may be used in the initial diagnosis of asthma, monitoring ongoing response to therapy, assessing airway function and to validate peak flow monitoring  Conner & Meng State that: o

“spirometry offers the single most objective measurement of lung function available”

 Bronchial provocation test use histamine, methacholine or exposure to a nonpharmacological agent like cold air to cause bronchoconstriction o

Methacholine is a cholinergic agonist which means that it acts on the parasympathetic nervous system and causes bronchoconstriction

 Bronchial responsiveness and bronchial obstruction should be reversible following administration of short acting bronchodilators (beta 2 agonist) in asthmatic patients

Peak Flow Monitoring  Measures the peak expiratory flow or how quickly a person can exhale  It can be done at home using a handheld device comparing the result to the patient’s personal best o

Three readings should be recorded

 a PEF between >80% of personal best indicated that the person is in the green zone and asthma is well controlled o

between 50-80% of personal best is considered in the yellow or caution zone 

the person should use a short acting bronchodilator and repeat PEF measurement. The patient should contact their health provider if their PEF does not return to green zone

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