Porth's Essentials of Pathophysiology, 4e

579

Disorders of Ventilation and Gas Exchange

C h a p t e r 2 3

B

A

FIGURE 23-7. Panacinar emphysema. (A) A whole mount of the left lung from a patient with severe emphysema reveals widespread destruction of pulmonary parenchyma that in some areas leaves behind a lacy network of supporting tissue. (B) The lung from a patient with α 1 -antitrypsin deficiency shows a panacinar pattern of emphysema.The loss of alveolar walls has resulted in markedly enlarged air spaces. (From Bearsley MB,TravisWD, Rubin E.The respiratory system. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2012:569.)

Emphysema is thought to result from the break- down of elastin and other alveolar wall components by enzymes, called proteases, which digest proteins. The proteases—particularly elastase, which is an enzyme that digests elastin—are released from polymorpho- nuclear leukocytes (i.e., neutrophils), alveolar macro- phages, and other inflammatory cells. 16,17 Normally, the lung is protected by antiprotease enzymes, including α 1 - antitrypsin. Cigarette smoke and other irritants stimu- late the movement of inflammatory cells into the lungs, resulting in increased release of elastase and other prote- ases. In smokers in whom COPD develops, antiprotease production and release may be inadequate to neutralize the excess protease production such that the process of elastic tissue destruction goes unchecked (Fig. 23-8). A hereditary deficiency in α 1 -antitrypsin accounts for approximately 1% of all cases of COPD and is more common in young persons with emphysema. 40 The type and amount of α 1 -antitrypsin that a person has are determined by a pair of codominant genes referred to as protein inhibitor (PI) genes. Homozygotes who carry two defective PI genes have only about 15% to 20% of the normal plasma concentration of α 1 -antitrypsin. 16 Smoking and repeated respiratory tract infections, which also decrease α 1 -antitrypsin levels, contribute to the risk for emphysema in persons with α 1 -antitrypsin deficiency. Laboratory methods are available for mea- suring α 1 -antitrypsin levels. Human α 1 -antitrypsin is

Attraction of inflammatory cells

Smoking

Release of elastase

1

1

1

Macrophages and neutrophils

Destruction of elastic fibers in lung

Emphysema

FIGURE 23-8. Protease (elastase)–antiprotease (antitrypsin) mechanisms of emphysema.The effects of smoking and an inherited α 1 -antitrypsin deficiency on the destruction of elastic fibers in the lung and development of emphysema are shown.