Tuberculosis B&B Flashcards
2 truths and a lie - Tuberculosis:
a. obligate aerobes
b. reactivation disease prefers lower lobes
c. facultative intracellular pathogen
a. obligate aerobes - prefer lungs
c. facultative intracellular pathogen - infect macrophages
b. reactivation disease prefers UPPER lobes
how can TB be cultured/stained?
Lowenstein Jensen agar
Slow growing, mycolic acids inhibit Gram stain - acid fast
acid fast staining: stain with very concentrated dyes + heat, then rinse with acid decolorizer – TB resist decolorization
describe the function of the following virulence factors in TB:
a. trehalose dimycolate
b. sulfatides
c. catalase-peroxidase
a. trehalose dimycolate (“cord factor”): causes granuloma formation to evade immunity, triggers cytokine release
b. sulfatides: glycolipids, inhibit fusion of phagosome/lysosome
c. catalase-peroxidase: resist host cell oxidation
Primary tuberculosis is typically a disease of which patients?
Children or chemo patients – ineffective immune response
what type of immunity responds to/controls tuberculosis infection?
Cell mediated immunity - TH1 response —> IFN-y secretion and activation of macrophages and cytotoxic T lymphocytes
Type IV hypersensitivity reaction (delayed)
What kind of necrosis is associated with tuberculosis?
granulomatous inflammation —> caseating necrosis
macrophages transform to epithelioid cells and Langhans giant cells
fibroblasts produce collagen
Type IV (delayed) hypersensitivity - TH1 mediated
Ghon foci
Ghon foci: subpleural granulomas in the mid to lower lungs, seen in tuberculosis infection
Ghon foci + lymph node = Ghon complex
Calcified Ghon complex = Ranke complex
Pott’s disease
osteomyelitis (spine infection) associated with miliary TB
—> back pain, fever, night sweats, weight loss
what kind of autoimmune drugs can put a patient at risk for reactivation TB?
recalled tuberculosis is controlled with cell mediated immunity (TH1 and macrophages)
macrophages produce TNF-alpha (tumor necrosis factor alpha)
therefore, TNFa inhibitors (Etanercept, Infliximab) put patient at risk for reactivation tuberculosis
what type of fungal infection is commonly associated with pulmonary TB?
aspergilloma: fungus ball caused by Aspergillus fumigatus, non-invasive form of aspergillosis
grows in pre-formed cavities, often asymptomatic but can cause hemoptysis
In what kind of patients should you be wary of false negative PPD testing?
those taking immunosuppressive drugs - corticosteroids, TNF-a inhibitors
Immunocompromised - HIV, malnutrition
Diseased lymph system - sarcoidosis, lymphomas/leukemias
*this is because PPD skin test relies on cellular immune response to antigen (Type IV delayed hypersensitivity)
how does isoniazid work against TB and what are the associated toxicities?
isoniazid: blocks mycolic acid synthesis —> TB loses acid-fastness
katG-encoded catalase peroxidase needed to convert drug to active form
toxicities: neurotoxicity (administer with B6/pyridoxine), hepatotoxicity, drug-induced Lupus
how does rifampin work against TB and what are the associated toxicities?
rifampin: inhibits bacterial DNA-dependent RNA polymerase
adverse effects: liver/GI, red/orange fluids (harmless)
how does pyrazinamide work against TB and what are the associated toxicities?
Pyrazinamide (PZA) - trick question, mechanism unknown!
adverse effects: hepatotoxicity, hyperuricemia/gout (competes with uric acid for renal excretion)
how does ethambutol work against TB and what are the associated toxicities?
ethambutol: inhibits arabinosyl transferase (involved in cell wall synthesis)
adverse effects: optic neuropathy (red/green color blindness) - reversible
