Porth's Essentials of Pathophysiology, 4e

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Disorders of Ventilation and Gas Exchange

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of persons are older than 60 years of age at the time of presentation. A number of conditions and risk factors are associ- ated with the disease. 15,56 Cigarette smoking increases the risk, as do certain occupations such as farming, hairdressing, stonecutting, and metal cutting. Although viruses have not been clearly implicated in the patho- genesis of idiopathic pulmonary fibrosis, several viral proteins and antibodies to viruses are associated with the disease. In addition, some people may have a genetic predisposition to the disease. The disease is characterized by patchy interstitial fibrosis that causes collapse of alveolar walls and forma- tion of cystic spaces lined by hyperplastic type II alveolar cells or bronchial epithelium. Secondary hypertensive changes due to intimal fibrosis and medial thickening of the pulmonary arteries are often present. Idiopathopathic pulmonary fibrosis usually presents insidiously, with gradual onset of a nonproductive cough and progressive dyspnea. Cyanosis, cor pulmonale, and peripheral edema may present late in the disease. Diagnosis is confirmed by surgical biopsy. Unfortunately, the progress of the disease is relentless despite current methods of treatment. The mean survival after diagnosis is 3 to 5 years. Sarcoidosis Sarcoidosis is a multisystem disorder in which granulo- mas are found in many tissues and organs, particularly the lung. 15,16,57,58 The disorder predominantly affects adults younger than 40 years of age, although it can occur in older persons. The incidence is highest among North American blacks and northern European whites; and women are affected more frequently than men. The cause of sarcoidosis remains unclear. It is thought that the disorder may result from exposure of genetically predisposed persons to specific environmen- tal agents. Defective human leukocyte antigen (HLA) genes located in the major histocompatibility complex may be linked to disease susceptibility and progno- sis. Multiple lines of evidence suggest that the inciting agent triggers an immune response that depends on host susceptibility. The immune response is characterized by chronic inflammation, monocyte recruitment, and granuloma formation in which multinucleated giant cells are fre- quently seen. These granulomas do not show evi- dence of necrosis or caseation. The inflammation often involves the alveoli (alveolitis). It is composed largely of macrophages and lymphocytes, with the latter thought to be of particular importance in the pathogenesis of the disease. Sarcoidosis has variable manifestations and an unpredictable course of progression in which any organ system can be affected. The three systems that most commonly manifest symptoms are the lungs, eyes, and skin. Persons with sarcoidosis frequently seek health care either as a result of abnormalities detected on an incidental chest film or because of insidious onset of

interstitial lung diseases have dyspnea, tachypnea, and eventual cyanosis, without evidence of wheezing or signs of airway obstruction. Usually, there is an insid- ious onset of breathlessness that initially occurs dur- ing exercise and may progress to the point at which the person is totally incapacitated. Typically, the per- son breathes with a tachypneic pattern of breathing, in which the respiratory rate is increased and the tidal volume is decreased. This pattern of breathing serves to maintain minute volume yet reduces the work of breath- ing because it takes less work to move air through the airways at an increased rate than it does to stretch a stiff lung to accommodate a larger tidal volume. A nonpro- ductive cough may develop, particularly with continued exposure to the inhaled irritant. Clubbing of the fingers and toes may develop. Lung volumes, including vital capacity and total lung capacity, are reduced in interstitial lung disease. In contrast to COPD, in which expiratory flow rates are reduced, the FEV 1.0 usually is preserved, even though the ratio of FEV 1.0 to FVC may increase. Although rest- ing arterial blood gases usually are normal early in the course of the disease, arterial PO 2 levels may fall during exercise. In persons with advanced disease, hypoxemia often is present, even at rest. In the late stages of the disease, hypercapnia and respiratory acidosis develop. The impaired diffusion of gases is thought to be caused by alterations in the alveolar–capillary membrane as well as an increase in shunt resulting from unventilated regions of the lung. The diagnosis of interstitial lung disease requires a careful personal and family history, with particular emphasis on exposure to environmental, occupational, and other injurious agents. 55,56 Chest radiographs may be used as an initial diagnostic method, and to follow the progress of the disease. A biopsy specimen for his- tologic study and culture may be obtained by surgi- cal incision, bronchoscopy, or bronchoalveolar lavage, in which fluid is instilled into the alveoli through a bronchoscope and then removed by suction for laboratory study. The treatment goals for persons with interstitial lung disease focus on identifying and removing the injurious agent, suppressing the inflammatory response (typically with corticosteroids), preventing progression of the dis- ease, and providing supportive therapy for persons with advanced disease. Many of the supportive treatment measures, such as oxygen therapy and measures to pre- vent infection, are similar to those discussed for persons with COPD. Idiopathic Pulmonary Fibrosis The most common diagnosis among persons with interstitial lung disease is idiopathic pulmonary fibro- sis. The disease is characterized by diffuse interstitial fibrosis, which in severe cases results in severe hypox- emia and cyanosis. As the name implies, the cause of the disorder is unknown. Men are affected more commonly than women and approximately two thirds