TBC (pathoma ir UW) 12/12

Question 1

4 drugs for TBC treatment?

Answer 1

RIPE:
Rifampin
Isoniazid
Pyrazinamide
Ethambutol

Question 2

Rifampin mechanism?

Answer 2

Inhibition of bacterial DNA-dependent RNA polimerase -> halts bacterial proteins synthesis

Question 3

Inhibition of bacterial DNA-dependent RNA polimerase.
Drug?

Answer 3

Rifampin

Question 4

Rifampin. 4 side effects?

Answer 4

GI, rash, red-orange body fliuds, cytopenias

Question 5

GI side effect?

Answer 5

Rifampin.

Question 6

Rash side effect?

Answer 6

Rifampin.

Question 7

red-orange body fliuds?

Answer 7

Rifampin.

Question 8

Cytopenias?

Answer 8

Rifampin.

Question 9

Isoniazid mechanism?

Answer 9

Inhibition of mycolic acid synthesis

Question 10

Inhibition of mycolic acid synthesis?

Answer 10

Isoniazid

Question 11

Isoniazid side effect?

Answer 11

Neurotoxicity (give vitB6/pyridoxine) -> peripheral neuropathy, therefore with drug give simultaneously pyridoxine

hepatotoxicity -> during first 4-6 months of treatment

Question 12

Neurotoxicity (give vitB6/pyridoxine)?

Answer 12

Isoniazid

Question 13

Hepatotoxicity (2)?

Answer 13

Isoniazid, Pyrazinamide

Question 14

Pyrazinamide mechanism?

Answer 14

Unclear

Question 15

Pyrazinamide side effects?

Answer 15

Hepatotoxicity, hyperuricemia

Question 16

hyperuricemia?

Answer 16

Pyrazinamide

Question 17

Ethambutol mechanism?

Answer 17

Inhibition of arabinosyl transferase

Question 18

Inhibition of arabinosyl transferase?

Answer 18

Ethambutol

Question 19

Ethambutol side effect?

Answer 19

optic neuropathy

Question 20

optic neuropathy?

Answer 20

Ethambutol

Question 21

Resistance (2)?

Answer 21

1. Mutations in genes that responsible for mycolic acid synthesis (isoniazid)
2. Mutations in genes responsible for mycobacterial RNA polymerase (rifampin)

Question 22

What are virulence factors? (3 were mentioned)

Answer 22

sulfatides, wax D, CORD FACTOR

Question 23

Severity of hepatotoxicity due to isoniazid?

Answer 23

Mild - elevated ALT/AST, tend to return to baseline.
Rare cases: frank hepatitis (resembles viral hepatitis, with fever, anorexia, nausea, jaudince) –> can progress to severe form with progressive liver dysfunction and death.

Question 24

M. Tuberculosis on microscopy?

Answer 24

arranged in long, slender, serpentine cords dur to cord factor.

Question 25

Cord factor - composition?

Answer 25

two mycolid acids bound to the disssacharide trehalose.

Question 26

Cord factor where is present?

Answer 26

its hydrophobic surface glycolipid

Question 27

Cord factor effect?

Answer 27

forms cylindrical micelles, that surround the organism and prevent macrophage -mediated destruction within phalolysosome.

Question 28

Cord factor other effect?

Answer 28

fors highly toxic crystaline monolayer hydrophobic surfaces (oir-water/air-water interface (eg edge of cavitation), that helps to drive the formation of caseating granulomas

Question 29

pathoma. Primary TB arises with ....

Answer 29

initial exposure

Question 30

pathoma. primary tuberculosis composed of?

Answer 30

Focal caseating necrosis in lower lung lober (subpleural) (GHON FOCUS) + caseosis of HILLAR LYMPH NODES --> BOTH TOGETHER CALLED GHON COMPLEX. When complex undergo fibrosis and CALCIFICATION, its called RANKE complex

Question 31

pathoma. Primary TB - symptoms?

Answer 31

asymptomatic or mild flu like symptoms Positive PPD

Question 32

pathoma. secondary arises due to....

Answer 32

reactivation of bacteria in immunocompromised patients (AIDS, elderly)

Question 33

pathoma. secondary occcurs where?

Answer 33

upper lobes (due to relatively poor lymphatic drainage and high oxygen tension)

Question 34

pathoma. what happens in secondary?

Answer 34

forms CAVITARY foci of caseous necrosis. It spreds disseminates in the lungs (man atrodo per lyphatics) --> cause tuberous bronchopneumonia or disseminates to vassular -> miliary TB.

Question 35

pathoma. miliary. meninges?

Answer 35

meningitis

Question 36

pathoma. miliary. cervical lymph nodes?

Answer 36

lymphadenitis in neck (scrofula)

Question 37

pathoma. miliary. kidneys?

Answer 37

sterile pyuria

Question 38

pathoma. miliary. lumbar vertebrae?

Answer 38

Pott disease

Question 39

pathoma. miliary. liver?

Answer 39

hepatitis

Question 40

pathoma. miliary. adrenal glands?

Answer 40

addison disease

Question 41

pathoma. biopsy?

Answer 41

caseating granulomas

Question 42

pathoma.AFB stain?

Answer 42

acid-fast balili

Question 43

pathoma. symptoms?

Answer 43

fever, night sweats, hemoptysis, weight loss

Question 44

What immunity?

Answer 44

Cell mediated.

Question 45

mechanism of cells/cytokines?

Answer 45

alveolar macrophage that contains bacteria within phagosome goes to lymph nodes, there presents (as APC) to naive T cell and release IL-12 -> naive converts to Th1 CD4 -> release IFN-gamma -> further activates macrophages -> become epithelioid cells and merge forming langhans giant cells.