infectious diseases
Tuberculosis (TB)
Pathophysiology of TB
Tuberculosis may occur in 3 stages: Primary infection Latent infection Active infection M. tuberculosisbacilli initially cause a primary infection, a small percentage of which eventually progress to clinical disease of variable severity. However, most (about 95%) primary infections are asymptomatic. An unknown percentage of primary infections resolve spontaneously, but the majority are followed by a latent (dormant) phase. A variable percentage (5 to 10%) of latent infections subsequently reactivate with symptoms and signs of disease. Infection is usually not transmissible in the primary stage and is never contagious in the latent stage. Infection requires inhalation of particles small enough to traverse the upper respiratory defenses and deposit deep in the lungs, usually in the subpleural airspaces of the middle or lower lobes. Larger droplets tend to lodge in the more proximal airways and typically do not result in infection. Infection usually begins from a single droplet nucleus, which typically carries few organisms. Perhaps only a single organism may suffice to cause infection in susceptible people, but less susceptible people may require repeated exposure to develop infection. To initiate infection,M. tuberculosisbacilli must be ingested by alveolar macrophages. Bacilli that are not killed by the macrophages actually replicate inside them, ultimately killing the host macrophage (with the help of CD8 lymphocytes); inflammatory cells are attracted to the area, causing a focal pneumonitis that coalesces into the characteristic tubercles seen histologically. In the early weeks of infection, some infected macrophages migrate to regional lymph nodes (eg, hilar, mediastinal), where they access the bloodstream. Organisms may then spread hematogenously to any part of the body, particularly the apical-posterior portion of the lungs, epiphyses of the long bones, kidneys, vertebral bodies, and meninges. Hematogenous dissemination is less likely in patients with partial immunity due to vaccination or to prior natural infection withM. tuberculosisor environmental mycobacteria. occurs after most primary infections. In about 95% of cases, after about 3 weeks of uninhibited growth, the immune system suppresses bacillary replication, usually before symptoms or signs develop. Foci of bacilli in the lung or other sites resolve into epithelioid cell granulomas, which may have caseous and necrotic centers. Tubercle bacilli can survive in this material for years; the balance between the host’s resistance and microbial virulence determines whether the infection ultimately resolves without treatment, remains dormant, or becomes active. Infectious foci may leave fibronodular scars in the apices of one or both lungs (Simon foci, which usually result from hematogenous seeding from another site of infection) or small areas of consolidation (Ghon foci). A Ghon focus with lymph node involvement is a Ghon complex, which, if calcified, is called a Ranke complex. The Skin testing and interferon-gamma release blood assays ( Less often, the primary focus progresses immediately, causing acute illness with pneumonia (sometimes cavitary), pleural effusion, and marked mediastinal or hilar lymph node enlargement (which, in children, may compress bronchi). Small pleural effusions are predominantly lymphocytic, typically contain few organisms, and clear within a few weeks. This sequence may be more common among young children and recently infected or reinfected immunosuppressed patients. Extrapulmonary Tuberculosis (TB) at any site can sometimes manifest without evidence of lung involvement. TB lymphadenopathy is the most common extrapulmonary manifestation; however, meningitis is the most feared because of its high mortality in the very young and very old. Healthy people who are infected with tuberculosis have about a 5 to 10% lifetime risk of developing active disease, although the percentage varies significantly by age and other risk factors. In 50 to 80% of those who develop active disease, TB reactivates within the first 2 years, but it can also reactivate decades later. Any organ initially seeded may become a site of reactivation, but reactivation occurs most often in the lung apices, presumably because of favorable local conditions such as high oxygen tension. Ghon foci and affected hilar lymph nodes are much less likely to be sites of reactivation. Conditions that impair cellular immunity (which is essential for defense against TB) significantly facilitate reactivation. Thus, patients coinfected with Human Immunodeficiency Virus (HIV) Infection and not receiving appropriate antiretroviral therapy (ART) have about a 10% annual risk of developing active disease. Other risk factors that facilitate reactivation, but to a lesser extent than HIV infection, include Diabetes Mellitus (DM) None Overview of Head and Neck Tumors None Gastrectomy Jejunoileal bypass surgery Dialysis-dependent Chronic Kidney Disease None Significant weight loss Use of drugs that suppress the immune system Patients who require immunosuppression after solid organ transplantation are at the highest risk, but other immunosuppressants such as corticosteroids and tumor necrosis factor (TNF) inhibitors also commonly cause reactivation. Tobacco use also is a risk factor. In some patients, active disease develops when they are reinfected rather than when latent disease reactivates. Reinfection is more likely to be the mechanism in areas where TB is prevalent and patients are exposed to a large inoculum of bacilli. Reactivation of latent infection predominates in low-prevalence areas. In a given patient, it is difficult to determine whether active disease resulted from reinfection or reactivation. TB damages tissues through Type IV (DTH), typically producing granulomatous necrosis with a caseous histologic appearance. Lung lesions are characteristically but not invariably cavitary, especially in immunosuppressed patients with impaired DTH. Pleural effusion is less common than in progressive primary TB but may result from direct extension or hematogenous spread. Rupture of a large tuberculous lesion into the pleural space may cause empyema with or without bronchopleural fistula and sometimes causes pneumothorax. In the prechemotherapy era, TB empyema sometimes complicated medically induced pneumothorax therapy and was usually rapidly fatal, as was sudden massive hemoptysis due to erosion of a pulmonary artery by an enlarging cavity. The course of TB varies greatly, depending on the virulence of the organism and the state of host defenses. The course may be rapid in members of isolated populations (eg, Native Americans) who, unlike many Europeans and their American descendents, have not experienced centuries of selective pressure to develop innate or natural immunity to the disease. The course is often more indolent in these European and American populations. Acute Hypoxemic Respiratory Failure (AHRF, ARDS) (ARDS), which appears to be due to hypersensitivity to TB antigens, develops rarely after diffuse hematogenous spread or rupture of a large cavity with spillage into the lungs. 