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Flashcards in Asthma Deck (38):
1

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

2

Signs and Symptoms 

Cough, dyspnea, tight feeling in chest • Wheezing • Rapid, labored breathing • Thick, sticky mucus coughed up • Tachycardia • Hypoxia • Respiratory acidosis • Respiratory failure

3

Classifications of Asthma Severity 

FEV1

- Persisitent has daily symptoms and at least 4 times per month 

4

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 

5

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.

6

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

7

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 

8

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 

9

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 

10

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 

11

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.

12

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.

13

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

 

14

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 

15

Physiology of Airway smooth muscle contraction 

Starts with ANS

16

beta adreno receptor s

17

Mechanism of Smooth muscle relaxation by B2 agnosts 

Activation of β2-adrenergic receptors leads to the activation of adenyl cyclase and to an increase in cAMP. This causes smooth muscle relaxation and bronchodilation in the combination of 2 factors:

  • cAMP leads to the activation of Protein kinase A (PKA)
  • cAMP lowers intracellular ionic concentrations
    • Inactive myosin light chain kinase activate myosin light chain phophatase causes relaxations 

18

Antiasthma Drugs 

Epinephrine

 

Selectivity  

SEs? That are caused by its non selectivity 

Isoproterenol 

SEs 

Selectivity 

 

b2 agonists 

19

Short acting agonists 

6 what are the SEs

20

Long acting B2agonists 

21

Summary of Agonists

SEs

22

Antimuscarinics 

MOA

Used with?

used when? ABC

23

Methylxanthines 

24

Summary of MOA of Bronchodilators 

25

Antiinflammatory agents 

By 2 actions 

  1.  

26

Anti-inflammatory drugs Corticosteroids 

MOA 

Inhaled 

Oral 

 

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Combo B2 and antiinflammatory 

28

Long acting bronchodilators have been associated with?

  • Increased risk of worsening wheezing 

29

Leukotriene pathways in asthma

Leukotrienes are products of? 

Potent?

Released by what type of cells?

Why does aspirin induce Asthma? 

A-D

30

Leukotriene Antagonists 

5-lipoxygenase inhibitor:

Leukotriene Receptor Antagonists: 

Therapeutic Uses:

Modest?

Good for someone with?

ASA

Not indicated for?

Advantages?

AEs

31

Mast cell stabilizer 

32

Anti-IgE antibody 

33

Targeted therapy for Asthma Cytokines 

34

Management of asthma chart 

35

Control of asthma during preganancy 

36

Key concepts 

37

Bronchodilators Table 

38

Antiinflammatory Table