Pathophysiology of asthma

'Intrinsic' asthma is triggered by e.g. exercise, cigarette etc.

'Extrinsic' asthma is the allergic type of asthma which involves IgE antibodies and mast cell degranulation.

The pathogenesis of asthma involves both genetic and environmental factors, and is triggered by exposure of allergens. When come into contact with antigens (allergens), dendritic cells react and present the antigens to lymphocytes. Helper T cells are then activated, releasing cytokines (IL-2, IL-4), which results in the activation of B cells to secret IgE antibodies. In extrinsic asthma, patients have a tendency to form abnormally large amounts of IgE antibodies. Migration and activation of mast cells and eosinophils are also stimulated by lymphocytes activation and cytokines generation.

The IgE antibodies attach to mast cells present in the lung interstitium. As the antigens react with the mast cell attached-antibodies, the mast cell is activated and sends signal for 1) degranulation; 2) phospholipase activation; 3) cytokine gene activation.

1) Substances released in mast cell degranulation are primary mediators of the allergic response. One of which is histamine.
2) Phospholipase activation leads to the release of leukotrienes and prostaglandin.
3) Cytokine IL-5, secreted upon cytokine gene activation, is responsible in activation of eosinophils.

Mast cell activation or, the mediators released, thus results in spasms of smooth bronchial muscles, increased mucus secretions into bronchiolar lumens, and localized oedema in the walls of the small bronchioles. The increased airway resistance creates obstruction in respiration.

The obstruction is, however, more severe during expiration. Despite the occlusion in asthmatic lungs, during inspiration, the positive pressure of the lungs in compare to the atmospheric pressure keeps the airway open. Thus the effect of obstruction is less. In expiration, the partially obstructed airway is further compressed by the greater atmospheric pressure. This gives a more reduced bronchiolar diameter and patients experience great difficulty expiring.

The activated eosinophils release mediators such as eosinophil cationic proteins that are toxic to epithelial cells. Epithelial cell loss in the chronic phase of asthma makes it more vulnerable to irritant stimuli -- resulting in bronchial hypersensitivity.

The theory behind airway remodeling is unknown. Nevertheless, various growth factors cause hypertrophy and hyperplasia of the smooth muscles in the chronic phase. Increased deposition of collagens due to fibroblasts activation creates an environment for ongoing inflammation, and eventually structural and functional alterations.


Reference: Kumar & Clark, Rang & Dale, Guyton