Pathophysiology

Mycobacterium tuberculosis is a small, slow-growing bacterium that is transmitted by inhalation of droplet nuclei. As infected persons talk, cough, or sneeze, numerous nuclei are expelled into the surrounding air. Only a few inhaled droplets are needed to infect, so an increased length of exposure to the pathogen and the number of bacilli present correlate with infectivity.¹

Inhaled bacilli travel down the bronchi and lodge within an alveolus. Activated macrophages then ingest the bacilli, which replicate and ultimately cause lysis. Monocytes are attracted and differentiate into macrophages, which again consume the mycobacteria and form a tubercle. The tubercle travels through the lymphatic and hematogenous systems and lodges in the lung apices, lymph nodes, meninges, vertebra, long bones, or kidney.

Two to 3 weeks after infection, cell-mediated immunity converts the tubercle to a granuloma by means of CD4 helper T cells. This process arrests the local infection for most immunocompetent hosts. At that time, the only sign of the disease may be a positive reaction to the purified protein derivative (PPD) skin test.

A delayed hypersensitivity response uses cytotoxic killer CD8 suppressor T cells to kill the other nonactivated macrophages with bacilli. This process creates local tissue destruction and the formation of a caseating granuloma. In immunocompromised patients, this caseous center may expand and then calcify to form a Ghon complex in the lung. If the infection is uncontrolled, primary tuberculous pneumonia may ensue, or infection may spread through blood and lymph, with resulting disseminated TB.²

Active TB develops months to years later in those patients with decreased capacity for cell-mediated immunity, such as patients with malnutrition, comorbidities, and immunosuppression. Patients with acquired immunodeficiency syndrome are especially prone to develop active disease. As the caseating granuloma liquefies and releases numerous bacilli, a delayed hypersensitivity response is initiated, and local tissue destruction follows. Ultimately, erosion through a bronchial wall creates a cavitary lesion and the development of pneumonia. The high oxygen tension of the cavity lends itself to replication of bacilli and persistent disease.

Classic Presentation

The symptom constellation of cough, night sweats, and hemoptysis, commonly associated with TB, is of little benefit in the early identification of disease because TB often has no early symptoms. Late symptoms are wide ranging and do not always involve the respiratory tract. Extrapulmonary manifestations of TB are seen in 20% of patients when the host is immunocompetent and are even more common when the host is immunocompromised.³ In patients with one or more risk factors for TB (Table 181.1 and Box 181.1),⁴ a detailed history helps to refine the pretest probability for the diagnosis of TB.

Table 181.1 Tuberculosis Rates (per 100,000 Population) Among Five Racial and Ethnic Populations: United States, 2003

^* Numbers in parentheses represent risk for tuberculosis compared with white non-Hispanics.

From American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep 2003:52:1-77 [erratum appears in MMWR Recomm Rep 2005;53:1203; dosage error in text].

Early stages of infection are most often asymptomatic in the normal host. Unless cell-mediated immunity is impaired, symptoms may manifest only after reactivation of the infection. Patients may present with a combination of systemic symptoms including cough, fatigue, fever, anorexia, malaise, and weight loss. An indolent cough that has progressed over more than 2 weeks should raise the clinical suspicion of pulmonary TB.⁵ Hemoptysis signifies erosion into the bronchial tree and is unlikely to be an early symptom of pulmonary TB. When the clinical suspicion is raised, the physical findings in pulmonary TB may include fever, pleural effusion, focal pneumonic ausculatory findings, and adenopathy.

Differential Diagnosis

Depending on the clinical symptoms at presentation, TB may mimic numerous systemic diseases. Radiographic findings, sputum smears, and skin tests help in the diagnosis of TB. The “gold standard” diagnostic test is culture, and results may not be available for several weeks (Table 181.2).

Table 181.2 Differential Diagnosis of Tuberculosis

HIV, Human immunodeficiency virus.