Flashcards in 3.6.5. Pulmonary TB Deck (16)
What causes TB?
Mycobacterium tuberculosis, an aerobic, rod-shaped, acid-fast bacterium (termed "red snappers" due to their appearance on Ziehl-Neelson acid-fast stain). Transmitted by airborne droplets from infected patients
What forms of TB are there? Describe them
1. primary: at initial reaction, Ghon complex develops consisting of peripheral parenchymal lesion called a Ghon focus and granulomas in involved hilar lymph nodes. Ghon focus develops into a granuloma and eventually undergoes caseating necrosis which could eventually calcify
2. secondary (reactivation): results from reactivation of a prior site of infection where the bacteria became dormant but were not cleared. Lesions are localized to the lung apices (due to greater aeration) with hilar lymph node involvement
3. military: disseminated disease caused by hematogenous spread of bacteria. Lung appears of being filled with millet seeds. Prognosis is poor.
What is the typical presentation of TB?
cough, weight loss/anorexia, fever, night sweats, hemoptysis, chest pain, fatigue. Pulmonary symptoms include productive cough and hemoptysis.
Describe the pathogenesis of TB
It is an intracellular pathogen that survives within phagocytes. It causes local and disseminated tissue damage. Bacilli implant themselves during inhalation and multiply in alveolar spaces. The area of inflammation undergoes caseous necrosis as the Ghon complex and can reactivate. In fact, reactivation is it's most common form and this usually occurs in upper lung.
How does reactivation of TB occur?
Occurs as the disturbance of equilibrium between immune surveillance and microbial growth. Usually in upper lung. This is the most common form of TB in the US. Diminished immune response, malnutrition, and aging are risk factors.
What are examples of extrapulmonary TB?
1. Miliary TB: disseminated disease caused by hematogenous spread of bacteria. Lung appears filled with millet seeds.
2. Meningitis: inflammation of meninges
3. Pott's disease: micro-bacteria get into the vertebrae of the lower spine and can spread into the psoas muscle.
How do we screen for TB?
1. Purified Protein Derivative (PPD)
2. Interferon Gamma Release Assays: useful for those who have received vaccine
How do we distinguish a latent TB infection from an active one?
1. Radiographic evidence of lung pathology: Ghon complex is found in latent TB infection while interstitial infiltrates and cavitary lesions are found in active TB.
2. Culture and smear for acid fast bacilli
3. Probes, however, are faster detection models than culture
Discuss the microbiology of Mycobacterium
Gram positive cell envelop that lack an outer envelop. The do not Gram stain! The cell wall is exteremely rich in waxes and lipids which makes it acid fast.
What are the major components of the Mycobacterium cell envelope?
2. Mycolic acids -> virulence factor
3. Polysaccharides and peptidoglycan (murein)
4. PGL-1 = binds to complement to enter macrophages
5. LAM = toxic to macrophages
What is the treatment for TB?
1. Infection with no disease? 9 months of isoniazid therapy (this blocks synthesis of mycolic acids)
2. Infection with symptoms? RIPES (rifampin, isoniazid, pyrazinamide, ethambutol, streptomycin)
What are the 4 R's of rifampin?
Ramps up cytochrome p450 metabolism, causes Red or orange urine, leads to rapid Resistance when used alone, acts by inhibiting RNA polymerase
What are the side effects of isoniazid?
hepatotoxicity, peripheral neuropathy, CNS effects
What is MDR-TB?
Resistant strain to at least rifampin and isoniazid
What is XDR-TB?
Additional resistance to second line therapies in addition to rifampin and isoniazid