Emphysema Pathogenesis

By Dr. Ananya Mandal, MDReviewed by Sally Robertson, B.Sc.

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

• All Emphysema Content
• Emphysema Pathophysiology, Causes, Diagnosis & Treatment
• Emphysema Pathology and Function
• Emphysema Treatment
• Emphysema Diagnosis