TB (1/29) Flashcards
What is used to treat TB?
Streptomycin– resistance developed
INH - magic bullet
Rifampin
Which organisms can cause TB?
Mycobacterium tuberculosis: most common
Mycobacterium bovis: comes from unpasteurized dairy
Mycobacterium africanum, canetti, microti
Impossible to distinguish these
They all have lipid in cell wall & are slow growing
How is TB transmitted?
Inhalation of droplet nuclei – sneezing
Inoculum size, strain variability/virulence, and being in a room with no ventilation
After it reaches alveoli, it replicates extracellularly and intracellularly, can seed to blood and travel to lymph nodes, kidney, bone
When does TB immune response develop?
CD4 cells are required for immune response!!! This is why AIDS patients get it so quickly
Alveolar macrophage infected with TB secretes IL-12 and 18
CD4 cells meet TB antigen macrophage presents to them
CD4 are transformed: proliferate & account for cutaneous hypersensitivity & release interferon gamma
IFN-gamma stimulates additional macrophage phagocytosis of TB & tells macrophage to release TNF alpha
TNF helps macrophage kill TB, required for granuloma formation!!!
Granulomas sequester the mycobacteria and prevent uncontrolled dissemination
What is a granuloma?
Macrophages secrete lytic enzymes that cause tissue necrosis
Epitheliod cell = highly stimulated macrophage
Langhans giant cell = fused macrophages with multiple nuclei
It’s a successful tissue reaction & healing
- Small antigen load & high hypersensitivity= Epithelioid cells, giant cells etc.
- Large antigen load & high hypersensitivity= Necrosis & Caseation
- Small or large antigen load & no hypersensitivity=few cells - No granuloma & huge #s of bacilli: AIDS patients
How does a primary infection that resolves present?
Patient is asymptomatic, enlargement of hilar/peri-bronchila nodes, hilar node calcification, positive PPD for 6-12 weeks
What is the most infectious type of TB?
Cavitary disease: cavity develops in the lung
Occurs more commonly in young people, especially adolescents
Which patients are most vulnerable to TB?
AIDS patients– if one gets it, everybody in the AIDS ward gets it
This is because they don’t have CD4 cells & can’t produce TNF-alpha & can’t make granulomas to contain the disease: no immunologic control of bacillus, rapid dissemination
How does reactivation develop?
Viable organisms remain alive & dormant for years; when cellular immune system can no longer contain MTB, disease occurs
Immunosuppression (i.e. transplant, rheumatologic Rx), immunocompromising diseases, malnutrition, age, hormones, stress
Caseating necrosis, liquefaction, drainage into bronchial tree, cavity formation
What are the most common sites for TB to spread?
Lymph: expecially cervical
Kidneys: hematogenous spread, forms granulomas here, caseating necrosis
Bones: spine, “Potts disease”– spreads to intervertebral disk & adjacent vertebra
Hematogenous spread from initial infection or lymphatic spread from pleural disease is possible
How is TB diagnosed?
Nonspecific systemic symptoms: fever, fatigue, night sweats, weight loss
Pulmonary symptoms: cough
Hemoptysis: coughing up blood. can be an emergency!! Suggests bronchial wall erosion
Take a sputum smear– if positive, means you have at least 10,000 organisms/mL
Culture = gold standard, slow growth in solid media, faster in liquid media
Nucleic acid amplification can detect MTB in fresh sputum; helps you know which strain you have - helps treatment & public health
Chest xray: upper lobe infiltrate wtih or without cavity (most common in reactivation TB); hilar adenopathy with or without infiltrates (most common presentation in HIV patients who have TB)