Pulmonary Mycetoma With a Concomitant Reactivation of Pulmonary Tuberculosis Infection: A Case Report and Clinical Pathological Review

Emphysema Pathology And Function

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease. It is typically characterized by cough, breathlessness and production of mucus. Emphysema and bronchitis (chronic) may both lead to COPD. In both conditions there is severe lack of oxygen in the air sacs of the lungs.

Gross pathology of lung showing centrilobular emphysema characteristic of smoking. Closeup of fixed, cut surface shows multiple cavities lined by heavy black carbon deposits.

Pathology

There is gross destruction of the air sacs or the alveoli in emphysema. There is persistent over-inflation that leads to damage to the elasticity of the lungs.

The lungs are like a balloon. In emphysema the lungs are over-inflated so that they lose their elasticity and elastic recoil. There are balloon-like bullae or blisters in the lung tissues. Because carbon dioxide is trapped in the bullae, the body is deprived of fresh air flowing into the lungs.

The lungs begin to cope with this lack of fresh air by taking deeper breaths. This further expands the lung tissues and makes it lose its elasticity. With loss of elasticity more carbon dioxide accumulates in the lungs leaving less space for fresh air and this leads to shortness of breath.

With time the muscles and ribs begin to expand to contain the expanded lungs. The diaphragm that lies beneath the lungs and is normally dome shaped also flattens and lose their functional capacity.

Causes of emphysema and its relation with pathology

One of the most important causes of emphysema is cigarette smoking. Other causes include air pollutants, inhalation of chemicals, fumes, dust etc.

Cigarette smoke changes the structure and function of the lungs by causing irritation and inflammation of the narrow airways. This leads release of enzymes in the lungs that destroy lung tissues and an increased size in the air sacs eventually leading to emphysema. The destroyed lung tissues form bullae (holes) and lose elasticity.

Alpha-1 antitrypsin deficiency is a rare genetic condition where there are decreased levels of the protective protein, alpha-1 antitrypsin. Alpha-1 antitrypsin protects the lungs from the destructive effects of enzymes. Patients who lack this enzyme thus have lungs that are damaged by enzymes called elastases at an early age.

Apart from chronic inflammation caused by irritation there is also a theory of increased oxidative stress that can contribute to increased destruction and/or impaired lung maintenance and repair in emphysema.

The major consequence of the oxidative stress is thought to be the activation of the transcription factor nuclear factor-kB. This in turn activates proinflammatory cytokine transcription that causes destruction of the lungs. Cigarette smoking also inhibits histone deacetylase. This also promotes the release of proinflammatory cytokines.

A theory goes that there is an imbalance between proteases (protein break down enzymes) and antiproteases in emphysema. A delicate balance between protease and antiprotease activity is required for proper lung maintenance. When this balance changes there is increased destruction and inappropriate repair of lungs leading to emphysema.

Further Reading

Emphysema Pathogenesis

Emphysema refers to the irreversible damage caused to the delicate air sacs in the lungs called alveoli. The exact pathogenesis of emphysema has been an important subject of research, although the exact mechanisms is still not clear. Factors that have been found to cause emphysema are described below.

Alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AAT) is a rare genetic condition associated with emphysema, although it accounts for a minority of emphysema cases, compared with smoking. AAT is a protein circulated in the blood that prevents leukocytes from damaging normal body tissue. Leukocytes contain destructive substances inside them such as the serine protease elastase, which is known to cause the connective tissue damage associated with emphysema. Research has suggested that AAT is the main inhibitor of neutrophil elastase, a concept that is referred to as the protease-antiprotease theory. Other proteases such as the matrix metalloproteases may be significant in the development of non-hereditary emphysema.

In emphysema, the damage caused to the alveoli eventually leads to their decreased elasticity and over-inflation. Swellings or air pockets called bullae develop in which carbon dioxide becomes trapped. This deprives the flow of oxygen into the lungs, which automatically triggers deeper breathing. This, in turn, further expands the lung tissue, increasing further loss of elasticity. More carbon dioxide then accumulates and there is even less space for oxygen intake, causing shortness of breath to worsen.

Smoking

One of the most significant causes of emphysema is cigarette smoking. Cigarette smoke changes the structure and function of the lungs by causing irritation and inflammation of the narrow airways. This leads to the release of enzymes that destroy lung tissue, which expands the alveoli and eventually leads to emphysema.

Oxidative stress

Oxidative stress is another purported contributor in the pathology of emphysema. The main mechanism here is thought to be activation of the transcription factor nuclear factor-kB, which, in turn, activates proinflammatory cytokine transcription and leads to destruction of the lung tissue.

Further Reading

Aberrant Fibrillin-1 Expression In Early Emphysematous Human Lung: A Proposed Predisposition For Emphysema

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