Pathophysiology of Bronchial Asthma - What happens in asthma
Bronchial asthma is a chronic inflammatory disorder of the small airways (bronchioles) associated with airway hyper-reactivity or bronchial hyper responsiveness, characterized by wide-spread but variable obstruction to the air-flow (leading to wheezing, cough, chest tightness and difficulty in breathing), which may be partially or completely reversible for a considerable period (evidenced by recurrent attacks of remissions and exacerbations) with or without specific therapy. This article is aimed at educating the medical professionals and medical students who are keen to learn about the pathophysiology of asthma.
Two main processes are seen in the pathophysiology of asthma in the airways.
1. Inflammatory reaction
Physiology of respiratory system
- Lung Pressures and Lung Compliance
Air flow between the lungs and the environment occurs via a pressure gradient. This hub is on the changes in alveolar and pleural pressure changes in a breathing cycle and the resulting volume changes
- Lung Volumes and Lung Capacities in Health and Respiratory Diseases
Lung volumes and capacities tend to vary with age, sex, ethnicity and built. Alterations in the lung volumes are used to diagnose obstructive and restrictive lung diseases.
- Pulmonary Mechanics
Bulk flow of air in between the environment and the lungs is an important respiratory function. Coordinated, active movements of the thorax and the diaphragm, result in inspiration and expiration.
- Lung Volumes and Capacities
Breathing (inspiration and expiration) occurs in a cyclical manner due to the movements of the chest wall and the lungs. The resulting changes in pressure, causes changes in lung volumes.
- Non-respiratory Functions of the Respiratory System
In addition to serving the function of respiration, the respiratory system is involved in providing immunity, in olfaction, in phonation, as a reservoir and a filter for CVS and as a metabolic ground
The inflammatory reaction in bronchial asthma is brought about by four types of cells: namely the dendritic cells and macrophages, T-helper lymphocytes, mast cells and eosinophils. Dendritics cells and macrophages present antigens to T-helper cells and induce the switching of B lymphocytes to produce immunoglobulin E (IgE). These cells are influenced by corticosteroids (e.g. – beclamethasone, prednisolone) though beta receptor antagonists have no influence on them.
T helper lymphocyte is the key in the pathogenesis of bronchial asthma. They induce B cells to synthesize and secrete IgE through the production of interleukin 4 (IL-4) and induce eosinophilic inflammation via interleukin 5 (IL-5). T helper cells are also influenced by corticosteroids but not by the beta receptor agonists.
Mast cells contribute to the inflammatory reaction by the production and release of histamine, tryptase, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). These cells are involved in the early phases of asthma known as the early reaction. Unlike other types of cells mast cell membranes are stabilized by beta receptor agonists (such as salbutamol and terbutaline) and cromones (such as sodium cromoglycate).
Eosinophils are involved in the late phase reaction of bronchial asthma. They are attracted to the bronchial walls by interleukins 3 and 5 (IL-3, IL-5) and the granulocyte monocyte colony stimulating factor (GM-CSF) secreted by the T helper cells. Corticosteroids are effective in decreasing the entry of eosinophils as well as the number of eosinophils in circulation. In addition cortecosteroids prevent activation of eosinophils which have entered the bronchial walls.
Remodeling of the airways occurs when the inflammatory reaction goes on for a long period. Changes are seen to occur in epithelial cells, the basement membrane, smooth muscle cells and the neurons. Epithelial cells are damaged and the cilia are lost making them susceptible for infection by viruses. The number of goblet cells in the epithelium is increased leading to an increase in the secretions. With the loss of cilia, secretions tend to accumulate in the lungs as the normal function of the muco-ciliary escalator is lost. Basement membrane is thickened. Smooth muscle cells undergo division (hyperplasia) and acquire the ability to secrete. In addition, the contractility of the smooth muscles is also increased resulting in airway hyper-responsiveness. Local reflexes are developed due to the modification of the arrangement and synapses of neurons.
When a susceptible individual is exposed to a precipitating factor there can be several responses in the acute stage. These responses are classified as early reaction (immediate asthma), dual phase reaction, late phase reaction and recurrent asthmatic reaction. The early reaction is a result of mast cell activation and gives rise to bronshospasm within minutes of exposure. The response usually peaks within 15-20 minutes and subsides within 1 hour. As the key cell involved is mast cell there is a good response to salbutamol and cromones. A late phase reaction may occur due to activation of eosinophils occurring 12-24 hours after exposure. Here the response to salbutamol is poor though cortecosteroids are very effective in the treatment as this phase is mediated by eosinophils. Dual phase reaction is the occurrence of the early reaction and the late phase reaction in the same individual. Sometimes the individual may exhibit airway hyper-responsiveness for the subsequent days after the exposure. This is known as the recurrent asthmatic reaction.
When a susceptible individual is exposed to one or more precipitating factors for a long period of time, a response is seen which includes bronchospasm, mucosal oedema and mucus plug formation. This leads to airway obstruction particularly during expiration resulting in decreased flow rates of air during expiration. This leads to trapping of air within the alveoli and hence the lungs leading to hyperinflation of the alveoli and lungs at the expense of proper ventilation. This leads to a ventilation perfusion mismatch in the lungs. Initially the blood gas analysis would show a hypoxaemia with normal or reduced carbon dioxide tensions due to compensatory hyperventilation. However, with the failure of these compensatory mechanisms retention of carbon dioxide occurs, giving rise to a respiratory acidosis.
Understanding of the pathophysiology of asthma is important to understand the disease process and the rationale of the pharmacological management in different situations and phases of asthma in the same individual. This basic knowledge may therefore be used as a foundation to learn the pharmacological management of asthma.
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