Causes
The majority of all emphysema cases are caused by smoking tobacco. Emphysema cases that are caused by other etiologies are referred to as secondary emphysema. Anything that causes the body to be unable to inhibit proteolytic enzymes occurring naturally in the lung can cause, or contribute to, the development of emphysema. This could include exposure to air pollution, second-hand smoke, and/or other chemicals and toxins.
In rare cases, emphysema develops due to a genetic mutation that leads to alpha 1-antitrypsin deficiency. Severe cases of A1AD may also develop cirrhosis of the liver, where the accumulated A1AT leads to a fibrotic reaction that produces scarring and dysfunction; longstanding cirrosis may eventually produce liver cancer (hepatocellular carcinoma. The hereditary form of emphysema illustrates the detrimental effects that can result from misfolding of proteins in the ER. This disease is caused by a point mutation in alpha1-antitrypsin, which normally is secreted by hepatocytes and macrophages. The wild-type protein binds to and inhibits trypsin and also the blood protease elastase. In the absence of alpha1-antitrypsin, elastase degrades the fine tissue in the lung that participates in the absorption of oxygen, eventually producing the symptoms of emphysema. Although the mutant alpha1-antitrypsin is synthesized in the rough ER, it does not fold properly, forming an almost crystalline aggregate that is not exported from the ER. In hepatocytes, the secretion of other proteins also becomes impaired, as the rough ER is filled with aggregated alpha1-antitrypsin .
Some types of emphysema occur as a normal part of aging, and are commonly found in the oldest old (85 years of age and older). At about 20 years of age, humans stop developing new alveolar tissue. In the years following the cessation of development of new alveoli, lung tissue starts to deteriorate (on a "net" basis) at a relatively slow rate. This deterioration of lung capacity and function is a normal and natural part of aging in healthy people. As alveoli die, the number of lung capillaries decreases, and the elastin of the lungs begins to break down, causing a loss of pulmonary elasticity. As people age, they also tend to lose strength and mass in their chest muscles, which weaken, bones and cartilage start to deteriorate, and posture changes. Together, all of these age-related changes in respiratory system structures can cause or contribute to the development of emphysema. Though not all elderly people will develop clinically evident emphysema, they are all at risk of decreasing respiratory function, which limits maximum performance and produces discomfort at higher levels of exertion.
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