Respiratory Tract Infections - Tb and Chemo

Question 1

why do majority of people with tb not know they’re infected?

Answer 1

-Tb is contained by immune system so remains latent/dormant.

Question 2

cell wall of tb?

Answer 2

waxy cell wall from mycolic acid

Question 3

why can tb survive inside macrophages?

Answer 3

release proteins which stop lysosomes binding to phagosome containing the tb therefore preventing their destruction.

Question 4

what is the effect of having HIV and tb?

Answer 4

• HIV compromises the immune system making the dormant tb, held in the Ghon complex, to become activated.
• this spreads tb to upper lobes lungs, due to greater oxygenation

Question 5

what happens in stage 1 of tb infection?

Answer 5

• Inhalation through the air

- tb reaches macrophages in lungs

Question 6

what happens in stage 2 of tb infection?

Answer 6

• tb ingested by macrophage and some are killed.

- those that aren’t killed, due to preventing lysosome binding, reproduce inside macrophage. (primary tb)

Question 7

what happens in stage 3 of tb infection?

Answer 7

• immune cells surround site of infection creating a granuloma
• this kills cells inside the granuloma via a process called caseous necrosis
• this area of the lung is now called a Ghon focus

Question 8

how does tb spread to lymph nodes

Answer 8

-tb can spread to lymph nodes by being carried by the immune cells or by extension of the ghon focus. It the causes caseation in the lymph nodes.

Question 9

what makes the Ghon complex?

Answer 9

• caseating tissue in lungs (ghon focus) and the caseation of the lymph nodes.
• occurs in lower lung lobes

Question 10

what happens to the tissue in the granuloma after caseous necrosis?

Answer 10

undergoes fibrosis and calcification forming scar tissue

Question 11

what do we call a calcified ghon complex?

Answer 11

a Ranke complex

Question 12

what happens when immunity is compromised (stage 4)?

Answer 12

1. ghon focus reactivated (no longer latent tb)
2. infection spreads to upper part of lungs (active tb) due to more oxygen
3. memory t-cells release cytokines to control replication
4. this causes more areas of caseous necrosis
5. can also spread to blood stream

Question 13

what happens in stage 5 of tb infection?

Answer 13

1. cavities form round areas of caseous necrosis
2. this allows tb to disseminate/liquefy and spread through airways and lymphatic channels to other parts of lungs
3. can also spread to other tissues in body via systemic circulation

Question 14

if tb is latent/dormant do you have to treat it?

Answer 14

yes otherwise can become active in future

Question 15

how does tb spread?

Answer 15

by someone with an active infection who discharges it into the air

Question 16

what is the tuberculin skin test (TST)

Answer 16

1. inject small amount of purified protein derivative (PPD)
   tuberculin into the skin of the forearm
2. latent TB infection = skin sensitive to PPD tuberculin and a small, hard red bump will develop at the site of the injection.
3. a stronger reaction = chest x-ray to see if active or dormant. active = more calcified tissue

Question 17

what is the usual treatment of tb?

Answer 17

-2 antibiotics e.g. isoniazid and
rifampicin for 6 months
-and 2 antibiotics in the first 2 months of the 6months (pyrazinamide and ethambutol)

Question 18

what are 2nd line treatment of tb?

Answer 18

1. Aminoglycosides: e.g., amikacin (AMK), kanamycin (KM);
2. Polypeptides: e.g., capreomycin,
   viomycin, enviomycin;
3. Fluoroquinolones: e.g. ciprofloxacin (CIP), levofloxacin,
   moxifloxacin (MXF);
4. Thioamides: e.g. ethionamide, prothionamide
5. Cycloserine

Question 19

what are 3rd line treatment of tb?

Answer 19

1. Rifabutin
2. Macrolides: e.g., clarithromycin (CLR)
3. Linezolid (LZD)
4. Thioacetazone (T)
5. Thioridazine
6. Arginine
7. Vitamin D
8. Bedaquiline

Question 20

what is the mechanism of action of isoniazid (1st line) and ethionamide (2nd line)?

Answer 20

inhibits cell wall synthesis so no mycolic acid

Question 21

what is rifampicin’s mechanism of action?

Answer 21

-targets RpoB on RNA polymerase complex inhibiting transcription

Question 22

what is Ethambutol mechanism of action?

Answer 22

inhibits Arabinogalactan biosynthesis hence inhibiting EmbA and EmbB attaching to mycolic acid so no outer membrane

Question 23

what is MDR-Tb resistance?

Answer 23

resistance to isoniazid and rifampicin (1st line treatment) without resistance to other 1st line treatment

Question 24

what is XDR-Tb resistance?

Answer 24

resistance to at least isoniazid, rifampicin, any fluoroquinolones and to one of the 3 second line injectables (amikacin, capreomycin, kanamycin)