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Asthma Pathophysiology · Acedra
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Asthma Pathophysiology
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0:04
Asthma comes from the Greek word for “panting”, which makes sense because it causes chronic inflammation of the airways, making them narrow and more difficult to breathe through. People with asthma can have asthma exacerbation or asthma attacks, which are usually triggered by something in the environment which causes immune cells to generate inflammation in the lungs which can make them even narrower and potentially be life-threatening.
0:26
So, if we take a look at the lungs, you’ve got the trachea, which branches off into right and left bronchi, and then continues to branch into thousands of bronchioles. In the bronchioles you’ve got the lumen, the mucosa, which includes the inner lining of epithelial cells, as well as the lamina propria, and the submucosa which is where the smooth muscle lives. The molecular pathway that leads to asthma is actually pretty complex but it is often initiated by an environmental trigger.
0:57
In asthma there is often an excessive reaction from type 2 helper cells or Th2 cells against specific allergens. Th2 cells, are an immune cell subtype, which are known to be involved in asthma, as well as atopic dermatitis, and allergic rhinitis, making up what’s called the atopic triad. What can happen with asthma is allergens from environmental triggers, like cigarette smoke, are picked up by dendritic cells which present them to a Th2 cell which produce cytokines
1:29
like IL-4 and IL-5 leading to a number of features of asthma. For example IL-4 leads the production of IgE antibodies which coat mast cells and stimulate them to release granules containing things like histamines, leukotrienes and prostaglandins. IL-5, on the other hand, activates eosinophils which promote an immune response by releasing more cytokines and leukotrienes. In this case, since IgE antibodies are being produced this is an example of a Type 1 hypersensitivity reaction.n
2:05
This leads to two series of events. Early on, minutes after the exposure to the allergen, smooth muscle around the bronchioles start to spasms and there is increased mucus secretion. This narrows the airways making it difficult to breathe, and this is why asthma is considered to be a type of obstructive pulmonary disease. There is also an increase in vascular permeability and and recruitment of additional immune cells from the blood.
2:33
So, a few hours after exposure, these immune cells, particularly eosinophils, release chemical mediators that physically damage the endothelium of the lungs. Initially these inflammatory changes are completely reversible, but over the years irreversible changes start to take place—edema, scarring, and fibrosis build up, leading to thickening of the epithelial basement membrane, which permanently reduces the airway diameter.
2:59
Although the specific causes of asthma are ultimately unknown, it’s thought to be caused by a combination of genetic and environmental factors, since certain genes have been identified that increase the risk of developing asthma and having a family history of asthma seems to increase risk as well. For environmental factors, there’s the hygiene hypothesis, which suggests that reduced early immune-system exposure to bacteria and viruses which might actually increase the risk of
3:26
later developing asthma, possibly by altering the overall proportion of immune cell subtypes. In general, causes of childhood asthma diagnosed before age 12 are thought to be due to a stronger genetic influence, whereas later onset asthma is more likely to be largely due to environmental factors. Now, the triggering substance that leads to the asthma attack can differ from person to person, but some common ones include air pollution, like cigarette smoke and car exhaust, as well
3:55
as allergens like dust, pet dander, cockroaches, and mold. Medications like aspirin and beta-blockers have also been known to trigger symptoms in some individuals with asthma. That said, symptoms of asthma include coughing, a feeling of chest tightness, dyspnea, or difficulty breathing, and wheezing, or a high-pitched whistling sound that usually happens during exhalation. Occasionally in the sputum there might curschmann spirals, which are spiral shaped mucus plugs
4:26
which are basically elongated mucous casts from small bronchi of people with bronchial asthma. Mucus plugs can be particularly dangerous because they not only block exchange of air, but they also block inhaled medications from getting to the site of inflammation. The mucus may also contain Charcot-Leyden crystals which are shaped like needles and are formed by the breakdown of eosinophils. Now, asthma can be classified according to the frequency of symptoms, in particular night-time
4:56
and early morning symptoms, the FEV1, or forced expiratory volume in one second, the PEFR, or peak expiratory flow rates, both of which measure the amount of obstruction in the airways, and finally how often a person is using asthma medication to help with the symptoms. From least to most severe, the types of asthma are intermittent asthma, mild persistent asthma, moderate persistent asthma, and finally severe persistent asthma.
5:26
While there is no cure for asthma, there are treatments available that can manage the symptoms and prevent the development of an asthma attack. First, people with asthma should avoid or minimize contact with triggering substances by vacuuming, removing carpets and rugs, and changing the environmental conditions, like for example drying out a room in the case of molds that grow well in moist areas. There are also a number of medications that can reduce the symptoms of asthma.
5:53
Bronchodilators such as short-acting beta-adrenoceptor agonists and anticholinergic medications are often administered through emergency inhalers. These fast-acting medications cause the smooth muscles in the lungs to relax and therefore dilate the airways, opening them up so that a person can breath. Individuals with more severe forms of asthma might need additional treatments like daily corticosteroids, long-acting beta-adrenoceptor agonists, or leukotriene antagonists.
6:23
In very severe cases, intravenous corticosteroids, magnesium sulfate, and oxygen therapy might be needed. Alright, as a quick recap, asthma is characterized by chronic inflammation in the lungs as well as asthma exacerbations or attacks, where certain triggers starting up more inflammation which leads to smooth muscle spasms and mucus production, both of which make it hard to breathe.
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