Asthma is a chronic inflammatory disorder of the airway that causes recurrent episodes of wheezing, breathlessness, chest tightness and cough, particularly at night and or early in the morning. The symptoms are usually associated with widespread but variable broncho-constriction and airflow limitation that is at least partly reversible spontaneously or with treatment. The inflammation causes hyper-responsiveness. Rarely, a state of unremitting attack called status asthmaticus may prove fatal especially in individuals who have had long history of asthma. PATHOPHYSIOLOGY Asthma is mediated by reaginic immunoglobulin (1gE). The disease is provoked by environmental antigens (allergens) to which one is allergic to: house dusts, mites, cat dander, moulds, pollens, food or any potential antigen. In atopic asthma, the condition is often preceded by allergic rhinitis, urticaria or eczema. Initial sensitization to inhaled antigen (allergen) stimulates induction of TH2 type cells that release cytokine such as IL4 and IL5. IL-4 promotes growth of B cells and 1gE production by plasma cells, promote TH2 CD4+ T cells growth and inhibit TH 1 CD4+ T cell. IL-5 stimulate B cell growth and immunoglobulin secretion IgE binds to mast cell FcRI using the Fc portion sensitizing the mast cells. Re-exposure of pre-sensitized 1gE coated mast cells, to the same allergen or a cross-reacting antigen stimulates the mast cells by cross-linking the bound 1gE causing an intracellular cascade that cause mast cell degranulation and release of mediators on to the bronchial mucosal surface. The mediators are of two categories: Preformed mediators include: Histamine: Binds to H1 receptor on smooth muscles causing constriction, on endothelial cells causing separation at the junction resulting to increased vascular permeability. Via H2 receptor histamine causes increase in mucous secretion and vascular permeability. Serotonin has same effect as histamines Eosinophilic chemotactic factor of anaphylaxis attract eosinophils to the site of release of the peptides. The eosinophils are also involved in the asthma pathology. Heparin causes inhibition of coagulation which may be of use in subsequent recovery of mast cells and further introduction of antigen to the reaction area. Mediators synthesized de novo from mast cell membrane phospholipids includes: Leucotriene (LT) C4 and D4 prolongs constriction of smooth muscle and cause antihistamine resistant asthma. LTB4 facilitates binding of neutrophils to vascular endothelial cells and possesses potent chemotactic activity for neutrophils, eosinophils, coenocytes, lymphocytes and fibroblasts. They also increase vascular permeability and enhance 1gE production. Prostaglandin (PG) D2 – is 30 X as potent as histamine. PG D2 is vasoactive, and has effects of broncho-constriction and chemotaxis to inflammatory cells. PAF (Platelet Activating factor) induce platelet aggregation and release of platelet contents e.g. histamine. It also induces release of arachidonic acid augmenting mast cell effects. PAF also cause bronchoconstriction and vasodilatation. Direct stimulation of sub-epithelial vagal receptors by some of the mediators provokes bronchoconstriction through the central and local reflexes. The resultant effects due to the pre-formed mediators occur within minutes and constitute the acute phase. These pathological effects include bronchoconstriction, airway oedema, increased mucus secretion and in extreme cases hypotension. The late phase reaction is mediated by the swarm of leukocytes recruited by the chemotactic factors and cytokines released by mast cells during acute phase. These include more sustained bronchoconstriction associated with influx of inflammatory cell into bronchial mucosa and increased bronchial responsiveness and epithelial cell hyperplasia. Mediators from membrane phospholipids of mast cells help sustain some of the acute phase reactions. The effects may last for several weeks resulting in chronic inflammation and possibly connective tissue replacement processes. Some cytokines for example IL 5, 9, and 13 from Th2 cells also adds to chemoatractive effects to esosinophils, stimulating 1gE production by B cells and direct stimulation of mucus production by bronchial Goblet cells. Pathologically eosinophilic, lympocitic inflammation occurs characterised by remodelling of the bronchial mucosa: deposition of collagen beneath the lamina reticularis and hyperplasia of cells of, all structural elements – vessels, smooth muscle and secretory glands and goblet cells. NON-ATOPIC [INTRINSIC/IDIOSYNCRATIC] ASTHMA A type of asthma mostly frequently triggered by respiratory tract infections. Viruses (Rhinovirus, Para-influenza) are more commonly involved than bacteria. Positive family history is uncommon. 1gE levels in serum are normal and no associated allergies are experienced Usually skin tests results are negative. Other types of asthma Aspirin – induced asthma Occupational asthma DIFFERENCES BETWEEN ASTHMA AND ALLERGY TO PENICILLIN ASTHMA PENICILLIN ALLERGY Allergens are of numerous types Allergen is penicillin Allergens are inhaled Exposure is parenteral administration Effects are often in the bronchial tree Effects are systemic and widespread Antibody involved is 1gE mainly May involve 1gE and 1gG Local mast cell degranulation occur Widespread mast cell degranulation occur Pathology involves chronic inflammation and airflow limitation. Pathology involves wide spread increase in vascular permeability resulting in cardiovascular collapse, respiratory distress etc. INVESTIGATIONS Chest X-ray (CXR) CXR is usually normal in uncomplicated asthma. In severe asthma, hyperinflation is indicated by depression of diaphragm and abnormal lucent lung field. Also complications such as pneumothorax and pneumomediastinum can be traced. Reversibility test Using short acting bronchodilators to see whether the obstruction can be relieved or not. An improvement of 15% or more is diagnostic of asthma Exercise testing Peak flow is measured before hand and then after the exercise at intervals of 5, 10 and 15 minutes. The exercise lasts 6 minutes. A fall in peak flow of 15% or more after the exercise may be diagnostic of asthma. Immunological tests – skin sensitivity test Minute quantities of the suspected allergen are introduced intradermally. A wheel and flare reaction is confirmatory of an allergen. Spirometry FEV 1 is decreased in asthma Sputum findings Sputum may be clear or opaque with green or yellow tinge (colour in sputum may not necessarily indicates infections). Sputum has numerous eosinophils, Charcoat-Leyden Crystals, (Crystallized protein). Curschmann’s spirals (bronchiolar casts composed of mucus and cells) and Creola bodies (clusters of airway epithelial cells with identifiable cilia). Physical examination On observation the patient is in obvious respiratory distress, sitting upright, leaning forward, and using chest and neck muscles for respiration. In severe cases, patient may be blue around the lips (central cyanosis). Auscultation may reveal wheezing especially on expiration. POST-MORTEM FINDINGS IN ASTHMA Gross findings Lungs: Are over-distended because of over-inflation. Small areas of atelectasis (collapse of previously inflated lung). Cut surface show occlusion of many segmental bronchi and bronchioles by thick tenacious mucous plugs. Focal bronchiectasis may be present (abnormal and irreversible dilation of bronchi). Chronic emphysema is slight or absent i.e. permanent enlargement of air spaces distal to terminal bronchiole accompanied by destruction of the walls of the airspaces. Histological finding Mucous plugs contain eosinophils and normal or degenerate to respiratory columnar epithelial cells. . Cellular elements in the plug may form twisted strips, called Curschmann’s Spirals Charlot-Leyden crystals are present i.e. collections of crystalloid made up of eosinophil membrane protein. Hyaline thickening of basement membrane of the bronchial epithelium Oedema and inflammatory infiltrate in the bronchial walls, with prominence of eosinophils and mast cells. Hyperplasia of the submucosal glands Hypertrophy of bronchial smooth muscle. CYTOLOGIC FINDINGS OF SPUTUM The cytological findings may include Increased eosinophils Presence of apoptotic eosinophils Clusters of bronchiole epithelial cells with identifiable cilia (Creolas bodies) Crystallised eosinophilic proteins (Charcoat – Leyden Crystals). Curschmann’s spirals (bronchiolar casts composed of mucus and cells) Increased inflammatory cells – lymphocyte, macrophages and plasma cells. Increased IL – 5, and eotaxin. CONCLUSION. Asthma occurs in genetically predisposed individual with high susceptibility to immediate hypersensitivity reaction mediated by IgE to particular allergens. Mast cell pre-sensitization and eventual degranulations on re-exposure to same or cross-reacting allergen are vital processes in atopic asthma. If unattended, asthma can be very incapacitating and lead to complications such as: pneumothorax, eosinophylia, respiratory failure, pulsus paradoxus, chest hyperinflation, short stature in kids etc. Immediate interventions are necessary in preventing the adverse effect of asthma. Avoidance of allergen, patient education about the condition and pharmacology interventions is useful: bronchodilators [e.g. .antimuscurinic, beta 2 adrenergic agonist, methylxanthines] and corticosteroids for prophylaxis can be used. REFERENCES Muirs Textbook of Pathology Pathologic Basis of Disease by Kumar Abbas and Fausto [pg723-727]. Diagnostic Cytology and its Histopathologic Basis by Leopold G. Koss [pg700 and 712] HINARI; healthinternetwork.org/scipub.php books.google.co.ke/book http:/chestjournal.org. Textbook of Pathology [pg491-493]
Posted on: Sun, 10 Nov 2013 02:52:30 +0000
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