asthma dan fisiology

7/29/2019 Asthma Dan Fisiology

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WHAT IS ASTHMA?

A reversible, obstructive lung disease caused by anexcessive reaction of the airways to certain stimuli ortriggers

Asthma is a disease of airways that is characterized byincreased responsiveness of the tracheobronchial tree tovarious stimuli; resulting in spasmodic narrowing of theair passages


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Asthma is a chronic inflammatory disorder of theairwaysin which many cells and cellular elementsplay a role, in particular, mast cells, eosinophils,T-lymphocytes, macrophages, neutrophils,and epithelial cells.


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Asthma Types

1. Extrinsic (atopic, allergic) asthma

2. Intrinsic (non-atopic, idiosyncratic) asthma


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Extrinsic (atopic, allergic) asthma

Most common type

Begins in childhood or in early adult life

Patients have family history/personal preceding ofallergic

diseases like rhinitis, urticaria, eczema

Hypersensitivity to allergens is usually present

IgE in serum (initiating acute immediate response and a latephase reaction )


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Acute Immediate Response

Initiated by IgE-sensitised mast cells on the mucosal surfa

Mast cells on degranulation release Histamine, LTs, PGs,

PAF, chemotactic factors for eosinophils and neutrophils

Net effects are bronchoconstriction, oedema, mucus

hypersecretion, accumulation of eosinophils and neutrophi


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AllergenIgE

Mast cells (on the mucosal surface)sensitise

Histamine, LTs, PGs, PAF, chemotactic

factors for eosinophils and neutrophils

Degranulate and Release

bronchoconstrictionoedema Mucus hypersecretion

Accumulation of eosinophils and neutrop


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Disease pattern

Episodic --- acute exacerbations interspersed withsymptom-free periods

Chronic --- daily AW obstruction which may be mild,moderate or severe superimposed acute exacerbations

Life-threatening--- slow-onset or fast-onset (fatal withinhours)


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INFLAMMATION

Airflow Limitatio

SYMPTOMS

Cough, WheezeDyspnoea

TRIGGERS

Allergens, Exercise,

Cold Air, SO2 Particulates

Pathogenesis:

Airway

HyperresponsivenessGenetic*

INDUCERSAllergens,Chemical sensitiser

Air pollutants, Virus infection


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3 Components of an Asthma Attack

1. Bronchospasm

The smooth muscles that wrap around the

windpipe (bronchi) tighten, reducing the size of the

airway.

normal

Asthma attack


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Components of an

Asthma Attack

2. Inflammation

The mucosal lining of the windpipe becoinflamed and swells, thereby reducing the sizof the airway even further.

3. Mucus

Increased mucus production takes up mo

space; causing airway constriction.


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Pathophysiology

Airway inflammation

Intermittent airflow obstruction

Bronchial hyper responsiveness


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Hypersecretion of mucous

Mucous gland hypertrophy

Mucous is thick

Airways can be blocked by mucous plugs


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Inflamatory cell infiltration

Eosinophils, mast cells, neutrophils, macrophages,

basophils all implicated Lymphocytes, including T-cells

Inflamatory mediators including cytokines

Abnormal antibodies including IgE


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Other constituent airway cells: Fibroblasts

Endothelial cells

Epithelial cells

Contribute to the chronicity of the disease.


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Airway inflammation

Principal cells in airway inflammation include mast cells, eosinophilsepithelial cells, macrophages and activated T lymphocytes.

T lymphocytes release numerous cytokines.

fibroblasts, endothelial cells, and epithelial cells, contribute to thechronicity of the disease.

Adhesion molecules (eg. selectins, integrins) are critical in directing inflammatory changes in the airway.

Finally, cell-derived mediators influence smooth muscle tone andproduce structural changes and remodeling of the airway.


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Airflow obstruction

Can be caused by acute bronchoconstriction, airway edema, chronic mucouplug formation and airway remodeling.

Acute bronchoconstriction results from IgEdependent mediator release upexposure to aeroallergens and is the primary component of the early asthmaresponse.

Airway edema occurs 6-24 hours following an allergen challenge and isreferred to as the late asthmatic response.

Chronic mucous plug formation consists of an exudate of serum proteins ancell debris

Airway remodeling is associated with structural changes due to long-standiinflammation and may profoundly affect the extent of reversibility of airwa

obstruction.


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During acute attack

Antigen antibody interaction

Stimulation/degranulation of mast cells with release of: Histamine Leukotriens

Chemotactic factors Bradykinin

Resulting in: Smooth muscle contraction (decreased camp) Increased capillary permeability, causing edema


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SIGNS AND SYMPTOMS OF AN ASTHMA

ATTACK

Wheezing, coughing

Shortness of breath

Chest tightness

Dry mouth Fatigue

Itchy chin or clipped speech

Headache


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ASTHMA ATTACK TRIGGERS!

Pets Indoorpollution

Exercise

Pollens

Weather

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