Porth's Essentials of Pathophysiology, 4e

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Respiratory Function

U N I T 6

CHART 23-1   Causes of Interstitial Lung Disease* Occupational and Environmental Inhalants Pneumoconioses (coal miner’s pneumoconiosis, silicosis, asbestosis) Hypersensitivity pneumonitis (farmer’s lung, bird breeder’s lung) Talcosis (talc inhalation in injection drug users) Smoking related Drugs andTherapeutic Agents Cancer drugs (e.g., bleomycin, busulfan,

SUMMARY CONCEPTS (continued)

Interstitial Lung Diseases The diffuse interstitial lung diseases, also called diffuse parenchymal lung diseases , are a diverse group of lung disorders that produce similar inflammatory and fibrotic changes in the interstitium or interalveolar septa of the lung. Because the interstitial lung diseases result in a stiff and noncompliant lung, they are commonly classified as restrictive lung disorders . In contrast to the obstructive lung diseases, which primarily involve the airways of the lung, the intersti- tial lung disorders exert their effects on the collagen and elastic connective tissue found in the delicate interstitium of the alveolar walls. 10,15,54–56 Many of these diseases also involve the airways, arteries, and veins. The clinical hallmark of these widespread lung changes is dimin- ished lung compliance, which presents as restrictive lung disease. The lungs are stiff and difficult to inflate. More pressure is needed to expand the lungs, which in turn necessitates more effort in breathing. Damage to alveolar epithelium and interstitial vasculature produces impaired gas exchange and hypoxemia. With progres- sion, persons develop respiratory failure, often in associ- ation with pulmonary hypertension and cor pulmonale. The interstitial lung diseases may be acute or insidi- ous in onset; they may be rapidly progressive, slowly progressive, or static in their course. Over 100 distinct entities of interstitial lung diseases have been recog- nized including hypersensitivity pneumonitis (discussed in Chapter 16); lung diseases caused by medications (e.g., the cancer drug bleomycin and the antiarrhythmic drug amiodarone) and radiation therapy; the occupa- tional lung diseases, including the pneumoconioses that are caused by the inhalation of inorganic dusts such as silica, coal dust, and asbestos; immunologic lung disor- ders, such as those that accompany rheumatoid arthri- tis and scleroderma; and granulomatous diseases such as sarcoidosis. 15,58 Examples of interstitial lung diseases and their causes are listed in Chart 23-1. The discussion in this chapter focuses on idiopathic pulmonary fibro- sis and sarcoidosis, two of the most common interstitial lung diseases seen in the clinical setting. 55 ■■ Cystic fibrosis (CF) is an autosomal recessive genetic disorder manifested by chronic lung disease, pancreatic exocrine deficiency, and elevation of sodium chloride in the sweat. The defect causes exocrine gland secretions to become exceedingly viscid, and promotes colonization of the respiratory tract with P. aeruginosa and other organisms such as S. aureus. Accumulation of viscid mucus in the bronchi, impaired mucociliary function, and infection contribute to the development of chronic lung disease and a decreased life expectancy.

cyclophosphamide, methotrexate) Antiarrhythmic drugs (amiodarone) Ionizing radiation (i.e., radiation therapy) Granulomatous Disorders Sarcoidosis Immunologic Disorders Systemic lupus erythematosus Rheumatoid arthritis Scleroderma Unknown Causes Idiopathic pulmonary fibrosis

*This list is not intended to be inclusive.

Pathogenesis Current theory suggests that most interstitial lung dis- eases, regardless of their cause, have a common patho- genesis. 15 It is thought that these disorders are initiated by some type of injury to the alveolar epithelium, fol- lowed by an inflammatory process that involves the alveoli and interstitium of the lung. If the injury is mild and self-limited, resolution with restoration of normal lung structures follows. However, with persistence of the injurious agent, an accumulation of inflamma- tory and immune cells causes continued damage to lung tissue and replacement of normally functioning lung tissue with fibrous scar tissue. Alveolar macro- phages secrete a host of fibrogenic factors, including fibroblast growth factor, transforming growth factor- β (TGF- β ), and platelet-derived growth factor, which can attract fibroblasts as well as stimulate their prolifera- tion. Alveolar cells also appear to play a role in the process. Destruction of type I alveolar cells is often accompanied by proliferation of type II alveolar cells (see Chapter 21). These cells secrete chemotactic fac- tors that attract additional macrophages, growth fac- tors, and cytokines such as TGF- β that contribute to fibrotic changes. Clinical Features In general, the interstitial lung diseases are character- ized by clinical changes consistent with restrictive rather than obstructive changes in the lung. Persons with