Porth's Essentials of Pathophysiology, 4e

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Respiratory Function

U N I T 6

Tuberculosis Pulmonary tuberculosis remains one of the deadliest dis- eases in the world. It is estimated that, if better methods to control infection are not developed, by the year 2020 nearly 1 billion people worldwide will be newly infected with tuberculosis, over 150 million will become clinically ill, and 36 million will die of the disease. 30 With the intro- duction of antibiotics in the 1950s, the United States and other Western countries enjoyed a long period of decline in the number of infections. However, since the mid-1980s the rate of infection has increased, particularly among HIV-infected people. In the United States, the biggest increase in new cases was from 1985 to 1993, after which the number of reported cases has again declined. 29 In part, this decline reflects the impact of resources committed to assist state and local control efforts, wider screening and prevention programs, and increased support for preven- tion programs among HIV-infected persons. Tuberculosis is more common among foreign-born persons from countries with a high incidence of tuber- culosis and among residents of high-risk congregate settings such as correctional facilities, drug treatment facilities, and homeless shelters. Outbreaks of a drug- resistant form of tuberculosis have emerged, complicat- ing the selection of drugs and affecting the duration of treatment. Etiology Tuberculosis is an airborne infection caused by the M. tuberculosis mycobacterium. The mycobacteria are slender, rod-shaped, aerobic bacilli that do not form spores 2,31–33 (Fig. 22-5). They are similar to other bac- teria except for a waxy cell wall that is responsible for many of the bacteria’s characteristics including its slow growth, antigenicity, and resistance to detergents, dis- infectants, and antibiotics. It also renders the bacteria resistant to common laboratory stains. Once stained,

the dye cannot be discolored with acid solution, hence the name acid-fast bacilli. Although M. tuberculosis can infect practically any organ of the body, the lungs are most frequently involved. Tuberculosis is an airborne infection spread by min- ute, invisible particles, called droplet nuclei, that are harbored in the respiratory secretions of persons with active tuberculosis. 32,33 Coughing, sneezing, and talking all create respiratory droplets; these droplets evaporate, leaving the organisms (droplet nuclei), which remain suspended in the air and are circulated by air cur- rents. Thus, living in crowded and confined conditions increases the risk for spread of the disease. Pathogenesis The pathogenesis of tuberculosis in a previously unex- posed, immunocompetent person is centered on the development of a cell-mediated immune response that confers resistance to the organism and development of tissue hypersensitivity to the tubercular antigens. 2,32,33 The destructive features of the disease result from a cell-mediated hypersensitivity response (see Chapter 16) rather than the destructive capabilities of the tubercle bacillus. Macrophages are the primary cell infected with M. tuberculosis. Inhaled droplet nuclei pass down the bronchial tree without settling on the epithelium and are deposited in the alveoli. Soon after entering the lung, the bacilli are phagocytosed by alveolar macrophages, but resist destruction. Although the macrophages that first ingest M. tuberculosis cannot kill the organisms, they initiate a cell-mediated immune response that eventually contains the infection. As the tubercle bacilli multiply, the infected macrophages degrade them and present their antigens to helper (CD4 + ) T lymphocytes. The sen- sitized helper T cells, in turn, stimulate the macrophages to increase their concentration of lytic enzymes. This boosts their ability to kill the bacilli; however, when released, these lytic enzymes also damage lung tissue. The development of a population of activated cytotoxic (CD8 + ) T cells and macrophages capable of ingesting and destroying the bacilli constitutes the cell-mediated immune response, a process that takes about 3 to 6 weeks to become effective. In immunocompetent persons, the cell-mediated immune response results in the development of a gray- white, circumscribed granulomatous lesion, called a Ghon focus, that contains the tubercle bacilli, modified macrophages, and other immune cells. 2,13 It is usually located in the subpleural area of the upper segments of the lower lobes or in the lower segments of the upper lobe. When the number of organisms is high, the hyper- sensitivity reaction causes the central portion of the Ghon focus to undergo necrosis, producing a soft, whit- ish core of dead cells referred to as a caseous (cheeselike) necrosis. During this same period, tubercle bacilli, free or inside macrophages, drain along the lymph channels to the tracheobronchial lymph nodes of the affected lung and there evoke the formation of caseous granulomas. The combination of the primary lung lesion and lymph

FIGURE 22-5. Scanning electron micrograph (SEM) depicting some of the ultrastructural details seen in the cell wall configuration of a number of gram-positive Mycobacterium tuberculosis bacteria. (From the Centers for Disease Control and Prevention Public Health Image Library. No. 9997. Courtesy of Ray Butler.)