Pathology of Bronchial Asthma

BY

Dr. Amira Kamal El-Hawary

:Introduction

Non-Specific immunity

Humoral Immunity

Neutrophils, Macrophages B lymphocytes - Antibody T lymphocytes

Cell mediated Immunity

:Introduction

Primary response slow, weak.

Learning period, memory cells.

Secondary response rapid, strong

Immunodeficiency disorders

:Immune Disorders

Hypersensitivity Disorders (allergy)

AIDS, antibody deficiency

excessive or altered reaction to an antigen producing adverse effects on the body. it is classified into 4 types

Autoimmune disorders

Type-I (IgE), Type II-IgG, Type III-Immune complex, Type IV-Cell mediated. SLE, Rheumatoid, Rheumatic fever.

Type I hypersensitivity reaction ((Atopy

Pathogenesis:-- First exposure to an antigen stimulation of B-lymphocytes to transform to IgE secreting plasma cells ( helped by CD4+ T-lymphocytes) IgE binds to the surface of mast cells and basophils

First exposure

Type I hypersensitivity reaction

Second exposure to the same antigenresults in cross-linking of Ig E on the surface of mast cells Degranulation of the cells with release of chemical mediators

FIRST EXPOSURE

SECOND EXPOSURE

Chronic obstructive pulmonary (disease (COPD

COPD is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to particles or gases.

Obstructive Pulmonary Diseases

Classical COPDs Emphysema Chronic Bronchitis

Bronchial Asthma

Bronchial asthma

Increased responsiveness of the bronchial tree to various stimuli that results in paroxysms of Bronchospasm reversible bronchospasm later chronic bronchial inflammation develop obstructive lung disease develop

and airflow is limited by bronchoconstriction, mucus plugs, and increased inflammation and

Incidence of asthma
It is a common disease affecting 5% of . adults and 7-10% of children There has been a significant increase in the incidence of asthma in the Western world in the past three decades

-Clinically

, it is manifested by recurrent episodes of wheezing, breathlessness, and cough that is at least partly reversible, either spontaneously or with treatment. Between the attacks, patients may be virtually asymptomatic

?What are the Triggering Factors

Domestic dust mites Air pollution Tobacco smoke Occupational irritants Cockroach Animal with fur Pollen

Respiratory (viral) infections Chemical irritants Strong emotional expressions Drugs ( aspirin, beta blockers)

Pathogenesis
Common denominator underlying all forms of asthma is an exaggerated bronchoconstrictor response (airway hyperresponsiveness) to a variety of stimuli. Airway hyperresponsiveness can be readily demonstrated in the form of increased sensitivity to bronchoconstrictive agents

Pathogenesis

Most current evidence suggests that bronchial inflammation is the substrate for hyperresponsiveness.

What causes the bronchial inflammation? In extrinsic (allergic) asthma, it is readily explained by type I hypersensitivity reactions, but the cause is much less clear in patients with intrinsic asthma

Pathogenesis
Type I hypersensitivity

INDUCERS Allergens, Air pollutants, Virus infections

INFLAMMATION
Airflow Limitation

TRIGGERS Allergens, Exercise, Cold Air, SO2 Particulates

SYMPTOMS Cough Wheeze Dyspnoea

Pathogenetic Types Atopic and non atopic asthma

There are two types of asthma, atopic ( with evidence of allergen sensitization) non atopic (without evidence of allergen sensitization) This distinction is useful from the point of pathophysiology, but in clinical practice it is not always possible to classify asthma.

FIRST EXPOSURE

SECOND EXPOSURE

Bronchial Asthma - Pathophysiology

Pathogenesis of extrinsic (atopic) asthmaMeeting the specific allergen causes sensitization- 1 of CD4+ (T 2) cells resulting in release of cytokines (IL-4,5, and 13). 2- IL-4,5 and 13 cause a. Stimulation of IgE production b. Growth of mast cells. 3- Meeting the specific allergen for the second time results in an immune reaction which passes into two phases i- An early phase starting 30-60 min.after inhalation of the antigen then .ii- A late phase develops after 4-8 hours

Pathogenesis of extrinsic (atopic) asthma

During the early phase,- 4 primary mediators are released. They include - Leucotriens which are sythesized from phospholipid by phospholipase enzyme - Histamine - Platelet Activating Factor These mediators produce ..bronchoconstriction, vasodilatation, increased vascular permeability and .increased mucin secretion

Pathogenesis of extrinsic (atopic) asthma

During the late phase secondary- 5 mediators are released including - Eosinophil and neutrophil chemotactic factors - IL-4 &5 - Platelet Activating factor - These mediators produce..eosinophil and neutrophil infiltration to the site of the lesion these cells produce a- More mediators that activate mast cells and intensify the initial response. . b. Epithelial cell damage

:Pathogenesis - Atopic Asthma

Airway inflammation with mucosal oedema Mucus plugging

Pathogenesis of non atopic asthma

In which the triggering factors include aspirin; pulmonary infections, especially those caused by viruses; cold; psychological stress; exercise; and inhaled irritants such as ozone and sulfur dioxide. These agents increase airway hyperreactivity in both normal and asthmatic subjects. In the latter, however, the bronchial response, manifested as spasm, is much more severe and sustained There is usually no personal or family history of allergic manifestations, and serum IgE levels are normal.

Bronchial Asthma
Extrinsic Type-I (IgE-mediated)hyper-sensitivity or allergic reaction Triggered byenvironmental antigens , ..( (dust, pollens, food Family history of Atopy. Begins in childhoodIntrinsic

Not allergicTriggered byrespiratory tract infections &drugs (.(aspirin

No family history-

Lung Morphology in Asthma

Mucous plugging Bronchospasm Over inflation

Lung Hyperinflation in Asthma

Thick bronchi with Mucous plugs

Asthma - Microscopic Pathology

Patchy necrosis of epithelium Sub-mucosal glandular hyperplasia Hypertrophy of bronchial smooth muscle Eosinophils, mast cells; lymphocyte Mucous plugs, Whorled mucous plugs (Curschmanns spirals) Debris of eosinophils (Charcot-Leyden crystals

Microscopic Pathology

Asthma Microscopic Pathology

Obstructed Inflammed Bronchi

Asthma - Bronchial morphology

inflammation Gland hyperplasia Mucous plug in lumen

Inflammation

epithelial damage

:Eosinophils in Asthma

:Curschmann's spirals

Bronchial Asthma

Complications

1. Bronchpneumonia 2. Emphysema 3. Rarely Death may occur in status asthamaticus. 4. Massive Lung Collapse due to bronchial obstruction by the mucus plug.

Immunological Mechanisms
Type hypersensitivity - allergen binds to IgE on surface of mast cells Degranulation (histamine)

muscle spasm inflammatory cell influx (eosinophils) mucosal inflammation/oedema

Inflammatory infiltrate tends to chronicity

Eosinophils are key inflammatory cells found in asthma. Airway remodeling (basement membrane thickening and hypertrophy of bronchial smooth muscle) adds to the element of obstructive disease.