L4, Resp Pathology PDF

pathology - respiratory Bronchial Asthma LECTURE (4) Bronchial Asthma Dr. M. Shalaby  pathology - respiratory Bronchial Asthma  Increased responsiveness of the bronchial tree to...

pathology - respiratory Bronchial Asthma LECTURE (4) Bronchial Asthma Dr. M. Shalaby  pathology - respiratory Bronchial Asthma  Increased responsiveness of the bronchial tree to various stimuli that results in paroxysms of Bronchospasm.  Reversible bronchospasm → later chronic bronchial inflammation develop and airflow is limited by bronchoconstriction and mucus plugs, and obstructive lung disease develop.  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 ① Domestic dust mites ⑦ Pollen ② Air pollution ⑧ Respiratory (viral) infections ③ Tobacco smoke ⑨ Chemical irritants ④ Occupational irritants ⑩ Strong emotional expressions ⑤ Cockroach ⑪ Drugs ( aspirin, beta blockers) ⑥ Animal with fur Dr. M. Shalaby pathology - respiratory Bronchial Asthma ATOPIC NON ATOPIC With Family history of Atopy. Without Family history of Atopy.  This distinction is useful from the point of pathophysiology,  But in clinical practice it is not always possible to classify asthma.  In two forms of asthma, there is an exaggerated bronchoconstrictor response (airway hyper-responsiveness) to the trigging factors.  Hyperresponsiveness of airways is caused by bronchial inflammation.  Bronchial inflammation is caused by: ① In extrinsic (allergic) asthma, it is readily explained by type I hypersensitivity ② In intrinsic asthma, the cause is much less clear.  Stimulation of B-lymphocytes to transform to IgE secreting plasma FIRST EXPOSURE TO cells ( helped by CD4+ T-lymphocytes) → IgE binds to the surface of ANTIGEN mast cells and basophils SECOND EXPOSURE  Results in cross-linking of Ig E on the surface of mast cells TO SAME ANTIGEN degranulation of the cells with release of chemical mediators Dr. M. Shalaby pathology - respiratory Bronchial Asthma ① Meeting the specific allergen causes sensitization of CD4+ (Tн2) 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 immune reaction which passes into two phases: EARLY PHASE LATE PHASE  Starting 30-60 min. After inhalation of the  Develops after 4-8 hours. antigen.  Primary mediators are released:  Secondary mediators are released: ① Leucotriens: synthesized from ① Eosinophil and neutrophil chemotactic phospholipid by phospholipase factors enzyme ② IL-4 &5 ② Histamine ③ Platelet Activating factor ③ Platelet –Activating Factor  These mediators produce eosinophil and  These mediators produce neutrophil infiltration to the site of the bronchoconstriction, vasodilatation, lesion these cells produce increased vascular permeability and a. More mediators that activate mast increased mucin secretion. cells and intensify the initial response. b. Epithelial cell damage. Dr. M. Shalaby  pathology - respiratory Bronchial Asthma  Triggering factors: ① Aspirin ② Pulmonary infections, especially those caused by viruses ③ Cold ④ Psychological stress ⑤ Exercise. ⑥ Inhaled irritants such as ozone and sulfur dioxide.  These agents increase airway hyperreactivity in asthmatic subjects.  Usually no personal or family history of allergic manifestations, and serum IgE levels are normal. EXTRINSIC (IMMUNOLOGICAL, ATOPIC, INTRINSIC (NON-IMMUNOLOGICAL, NON- ALLERGIC) ASTHMA ATOPIC, NON ALLERGIC) ASTHMA AGE Children and young Any age, mainly in late adults. FAMILY HX Present. No OF ATOPY  Type I hypersensitivity reaction to ① Respiratory tract infections TRIGGER environmental antigens (dust, ② Drugs (aspirin). pollens, food) Dr. M. Shalaby pathology - respiratory Bronchial Asthma a. LUNG: ① Over inflation ② Mucous plugging ③ Bronchospasm b. BRONCHI AND BRONCHIOLES:  Hyperaemic oedematous mucosa.  Thick walled and narrow lumen plugged with mucus. N/E LUNG HYPERINFLATION IN ASTHMA THICK BRONCHI WITH MUCOUS PLUGS ① Patchy necrosis of epithelium ② Sub-mucosal glandular hyperplasia ③ Hypertrophy of bronchial smooth muscle ④ Eosinophils, mast cells & lymphocyte ⑤ Mucous plugs, Whorled mucous plugs (Curschmann’s spirals) ⑥ Debris of eosinophils (Charcot-Leyden crystals). M/E Dr. M. Shalaby pathology - respiratory Bronchial Asthma ASTHMA - BRONCHIAL MORPHOLOGY  Inflammation ASTHMA – M/E  Gland hyperplasia  Mucous plug in lumen ASTHMA – M/E EOSINOPHILS IN ASTHMA INFLAMMATION EPITHELIAL DAMAGE Dr. M. Shalaby pathology - respiratory Bronchial Asthma CURSCHMANN'S SPIRALS EOSINOPHILIS AND STAPHYLOCOCCI IN STAINED CHARCOT-LEYDEN CRYSTALS SMEAR ASTHMA MICROSCOPIC PATHOLOGY ASTHMA MICROSCOPIC PATHOLOGY Dr. M. Shalaby pathology - respiratory Bronchial Asthma ① Bronchpneumonia ② Emphysema ③ Rarely Death may occur in status asthamaticus. ④ Massive Lung Collapse due to bronchial obstruction by the mucus plug.  Type Ι hypersensitivity - allergen binds to ige on surface of mast cells  Degranulation (histamine) ① Muscle spasm ② Inflammatory cell influx (eosinophils) ③ Mucosal inflammation/oedema  Inflammatory infiltrate tends to chronicity Dr. M. Shalaby