Asthma Flashcards
A chronic_______ disorder of the____, in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T-lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes_____ episodes of wheezing, restlessness, chest tightness, and coughing, particularly at night or early morning. These episodes are usually associated with widespread but variable ______ _____ that is often______ either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial________ to a variety of stimuli.”–Expert Panel of the NIH National Asthma Education and Prevention Program (NAEPP)
- inflammatory
- airway
- recurrent
- airflow obstruction
- reversible
- hyperresponsive
- Asthma
Signs and Symptoms
Cough, dyspnea, tight feeling in chest • Wheezing • Rapid, labored breathing • Thick, sticky mucus coughed up • Tachycardia • Hypoxia • Respiratory acidosis • Respiratory failure
Classifications of Asthma Severity
FEV1
- Persisitent has daily symptoms and at least 4 times per month
Asthma Pathophysiology
4 things
- Bronchoconstriction
- Airway edema
- Increased mucus
- Airway remodeling
The end result of this is narrowing of the airways and decrease in air flow and O2 supply
Airway hyperresponsiveness
Hypersensitivity
Hyperreactivity
- the propensity of asthmatic airways to constrict in response to a wide variety of stimuli.
- a normal response at abnormally low levels of stimuli.
- an exaggerated response at normal to high levels of stimuli.
Asthma as an Inflammatory disease
WHat are the initial sympstoms of asthma?
What is the underlying cause of it though?
What is key in the expression of asthma?
How is airway inflammation characterized?
Increased number of?
- Although the primary and initial symptoms of asthma are due to bronchoconstriction, the underlying cause of asthma is inflammation of the airways
- Inflammation is central to the development and expression of asthma
- is characterized by an increased number of activated eosinophils, mast cells, macrophages and T-lymphocytes in the airway mucosa and lumen. There is also evidence that noninflammatory cells, including airway epithelial cells, contribute to the inflammation
Immune system in Asthma
Antibodies
Inflammatory cells:
Inflammatory mediators:
The antibody class of allergic disease is? Fundamental to?
- (IgM, IgG, IgA, IgD, and IgE) An antibody, or an immunoglobulin (Ig), is a small protein molecule created by the immune system to have a close structural “fit” to the surface of a foreign substance. The foreign substance is an antigen. Five classes of antibodies, namely IgM, IgG, IgA, IgD, and IgE, depending on their particular functions in the immune response
- Granulocytes: mast cells, eosinophils Agranulocytes: lymphocytes…
- Chemical substances that are secreted by immune cells to induce (or respond to) an ongoing immune response generated against a specific exposure to the body.
- IgE fundamental to the allergic response
Mast cells
close to? Found where?
Express large number of a high affinity receptor for the ___ region of IgE
Binding to IgE is essentially?
When acitivated by interaction with antigen mast cells release?
- Closely related to Basophil granulocytes found in the blood
- Fc region of IgE Recptor is FceRI
- irreversible mast cells are coated with IgE
- a wide array of mediators to initiate an acute bronchospasm and also to release proinflammatory cytokines to perpetuate underlying airway inflammation
IgE and Mast Cells in Asthma
____ is the bodies response to allergic Rxn
____ is produced by ____ cells
Allergen?
Minute concentrations
- IgE
- IgE is produced by B-cells, IgE is specific for one antigen
- An antigen that stimulates an IgE antibody response
Vesicular Release of mast cells
Perfromed mediators (from the granules)
_____- has 3 effects
____ has 2 effects
Newly formed lipid mediators (eicosanoids)
____ D2 increases cytokine and induces bronchoconstriction
____ (LTC4 and LTD4 and LTE4: central to the pathophysiology of asthma because they induce marked bronchoconstriction mucus hypersections and capillary leakagem vasegenic edemam recruit additional inflammatory cells
- Histamin
- Causes localized inflammatory immune response
- Increase blood vessel permeability and promotes leakage, leading to airwat EDEMA
- Tryptase
- Activates receptors on epithelia and endothelial cells, inducing the expression of adhesion molecules that attract eosinophils and basophils
- Causing hyperplasia of airway smooth muscle cells and contributing to aiway hyperresponsiveness
- Prostaglandins
- Leukotriene
Activation of mucosal mast cells releases bronchoconstrictor mediators such as
Activation of mucosal mast cells releases bronchoconstrictor mediators such as histamine, cysteinyl-leukotrienes, prostaglandin D2.
T cells
Divided into?
One type causes a low level of IgG response
Other produces (IL4,5,6,9, and 13)
Asthma is cause by a cellular imbalance favoring>
- T lymphocytes are divided into CD8+ TC (cytotoxic) cells and CD4+ TH (helper) cells. T helper cells are further divided into TH1 and TH2 cells based on the cytokines they produce.
- TH1 cells cause a low-level of IgG response.
- TH2 cells, which produce IL-4, IL- 5, IL-6, IL-9, and IL-13, guide the immune response toward a humoral response.
- Asthma is caused by a cellular imbalance favoring TH2 over TH1 and a humoral response involving strong IgE-mediated reactions rather than low-level IgG responses.
Eosinophils
Stimulated by?
Secrete?
5 secretions
- • are stimulated by interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by TH2 lymphocytes and mast cells.
- adhesion molecules, particularly vascular cell adhesion molecule (VCAM-1), and by traveling along chemokine gradients to sites of inflammation.
- secrete cytotoxic granules that cause local tissue damage and induce airway remodeling, directly and indirectly to airway hyperresponsiveness
- major basic protein (MBP)
- matrix metalloproteinases
Sumamary
The primary and initial symptoms of most pts are seen due to?
Underlying causes of asthma is an allergic ____ of the airways. _____ ____ ___ to the development and expression of asthma and its pathophysiology.
- Bronchoconstriction
- Inflammation
- Inflammation is central
Physiology of Airway smooth muscle contraction
Starts with ANS
beta adreno receptor s
Antiasthma Drugs
Epinephrine
Selectivity
SEs? That are caused by its non selectivity
Isoproterenol
SEs
Selectivity
b2 agonists
Short acting agonists
6 what are the SEs
Long acting B2agonists
Summary of Agonists
SEs
Antimuscarinics
MOA
Used with?
used when? ABC
Methylxanthines
Summary of MOA of Bronchodilators
Antiinflammatory agents
By 2 actions
1.
Anti-inflammatory drugs Corticosteroids
MOA
Inhaled
Oral
Combo B2 and antiinflammatory
Leukotriene pathways in asthma
Leukotrienes are products of?
Potent?
Released by what type of cells?
Why does aspirin induce Asthma?
A-D
Leukotriene Antagonists
5-lipoxygenase inhibitor:
Leukotriene Receptor Antagonists:
Therapeutic Uses:
Modest?
Good for someone with?
ASA
Not indicated for?
Advantages?
AEs
Mast cell stabilizer
Anti-IgE antibody
Targeted therapy for Asthma Cytokines
Management of asthma chart
Control of asthma during preganancy
Key concepts
Bronchodilators Table
Antiinflammatory Table
