TB Alert + Pathophysiology

Question 1

key Myobacterium TB characteristics:

1) ___ (environment it likes so…)
2)
3) Doesn’t stain under acid/ alcohol and difficult to Gram stain because….
4)
5) spreads via?
6) gram? shape?

Answer 1

1) Aerobic (likes apex more as more air)
2) Mycolic acid within cell wall and high lipid content
3) Because its ACID FAST and needs Zeihl- Neelson staining (due to mycolic acid)
4) V. slow growing and metabolism so long living
5) spreads via droplets / airbourne

Question 2

Draw out all the routes/ consequences of someone being infected with TB

Answer 2

Person exposed -> no primary infection
I I
Macrophages infected
with organism -> 5-10% Primary TB
I I
90-95% sub-clinical Miliary TB
Granuloma Formed
(can be caessiating or ^
can calsify) -> Latent TB -> Post-primary
I TB
Resolves

Question 3

Pulmonary TB:

Primary TB chracterisitcs:
3 differences you’ll see on CXR compared to post-primary TB

-patient usually? (2)

Post-Primary TB
what characteristics will you see on CXR?
(3)

Definition of miliary TB
nodules seen, look like…

Answer 3

Primary TB 
Differences
1) lymph swelling 
2) plural effusion 
3) miliary shadowing 

-patient usually immunosurpressed and asymmptomatic

Post-primary TB
CXR:
Granulomma - could be calsified
apical scarring (potentially cavities + consolidation)

Miliary TB - TB that has spread via the blood to usually liver/ spleen/ kidneys/ bone marrow etc.

nodules look like millet seeds

Question 4

extrapulmonary TB

4 area that can be infected:

Answer 4

• urogenital (via kidneys from miliary)
• Spinal (thoracic + lumbar more common, needle biopsy needed to diagnose)
• TB lymphdenitis (cervical lymph nodes more common diagnose with fine needle aspiration)
• CNS (TB meningitis, diagnose with CSF lumbar puncture, 12 months of steroid needed for treatment)

Question 5

How to diagnose TB

• always do a ___
• __&___ and take a ___ sample -> ____ stain which shows…
• other samples 1/3
• molecular technique that may be used

Answer 5

• CXR!!
• microscopy & culture -> sputum sample and Zeihl Neelson stain which shows acid fact bacilli
• Bronchoscopy
• other samples: urine, pleural biopsy, lymph node
• rapid PCR

Question 6

Treatment
-Isoniazid -> target= (what does this enzyme do?
action -> ____ which…
only works with…..

Rifampicin-> target:
action
physiology
it kills both….

Ethambutol -> target:

                     action:  
                    physiology:  

Pyrazinamide ->

                     action:  
                    physiology:  

which one can interact with HIV med? and why?

Answer 6

-Isoniazid - catalase peroxidase (which normally helps TB survive in macrophages)
action: inhibited which also prevetns MYCOLC ACID SYNTHESIS
only works with active TB

Rifampicin-> target: RNA polymerase
action: inhibits
physiology: dec. transcription of DNA ->RNA
so dec. protein synthesis
kills both active and passive

Ethambutol -> target: orabinosy transferse

                     action: inhibit
                    physiology: inhib cell wall synthesis 

Pyrazinamide ->
action: inhibit
physiology: inhib fatty acid synthesis in cell
membrane

Rifampicin interacts with HIV med because TB med affect liver toxicity and HIV meds are metabolised in liver

Question 7

Clinical:
TST -> Tuberculin skin Test -> what is it? and what is result?
problems with this test (2/4)

IGRA - stands for?
what does it measure and when?
2 +ve’s and 2 -ve’s

a key prevention technique (type?) =
but it does not work if….

what gram is TB? but why doesn’t it act like one?
answer above does 2 things (2)

Answer 7

TST -> TB antigens given under skin, monitors cell mediated response -> red spot + oedema

• if BCG given cant use it as will cross-react
• cant distinguish betwenn active and latent
• low sens + selectivity
• need multiple visits, read after 48-72 hrs

Interferon Gamma Release Assay
- measures IFNy in response to stim. of Mtb antigens
+ve quick and specific
-ve doesnt distinguish active/latent and not approp. for HIV patients

m. bovis attenuated vaccination
doesn;;t work if TB levels in population are high

gram +ve but doesnt act like one because of lots of mycolic acid in cell wall: protection + survival in macrophages

Question 8

Actions:
Floroquinone 
Rifamycin
*streptomycin
macrolides
Isoniazol + ethionamide
ethambutol 
pyrzinamide 
TMC-207
PA-824

Answer 8

Floroquinone - inhib DNA syn. and supercoiling
Rifamycin - inhibs RNA syn. and targets RNA polymerase
streptomycin - inhibs 30s ribosome … inhib protein syn
macrolides - targets 23s ribosome subunit RNA, inhib ps
Isoniazol + ethionamide - inhib mycolic acid syn
ethambutol - inhib cell wall synthesis
pyrzinamide - inhib cell membrane synthesis
TMC-207 - inhib ATP synthesis
PA-824 - inhib mycolc acid and pprotein biosynthesis

Question 9

Reasons for why TB can emerge as resistant strain:
(4)

6 different methods that the bacteria prevents drug working

Answer 9

slow growing
drug find it difficult to treat and will damage
therfore more mutatios from damage
inc. selection pressure, inc. resistnce risk

1) mutation in DNA repair (drug target changes so cant bind)
2) alteration of enzyme to convert pro-drug to drug
3) drug exported out of efflux system
4) low pH turns drug inactive
5) drug cant pentrate cell wall
6) whe drug is latent, dec. in metabolic activity so drugs that affect metabolic process wont work

Question 10

Stages of disease pathology 
stage 1 
- what happens initially?
- how 
- 2egs and outcomes 
- then classic...
- but can survive due to...

stage 2- whats happening?
3 things happen to the phagosome

what forms? def->
what is a hallmark of the answer above?

stage 3- what is happening?

• biggest risk factor for this?
• why?

Answer 10

Stage 1
- mtb infects macrophages and can bind to a range of recpetors
recpetor bound determines outcome
FCyR-> pro-inflam and mtb dies
CR3 -> inhib of macrophage response and mtb lives!
induction of classic cellular immunity -> IFNy produced by CD4+ Th cells so death to macrophage
Mtb can survive resisting oxidative arrest due to having a lipid bilayer

stage 2- inhibition of phagosomal maturation

• impaired fusion of phagosome + lysosome
• dec. phagosome acidification
• modified phagosome maturation, Rab 5 over expressed as bacilli harbours within

granuloma formed- organised aggregate of immune cell, prevents spread of bacteria but allows for survival within
- MGCs are a hallmark

Stage 3: Mtb re-activation

• HIV most potent risk factor
• disruption in immune balance ca reactivate!

Question 11

types of granuloma

1) fibrinolytic granuloma (3/4)

2) ________ - lmtd. neutrophils
- express eNOS + NOS
- mod. Mtb load
lmtd. Arg1
3) casseous nectrotic granuloma (3/4)

4) supparitive granuloma (2/4)

5) ______ -key word
- abundant b cells
- poor CD25 expression

Answer 11

1) fibrinolytic granuloma - calsification
- mineralised fibrotic tissue
- no neutrophils
- lmtd Mtd load

2) non-necrotic granuloma - lmtd. neutrophils
- express eNOS + NOS
- mod. Mtb load
- lmtd. Arg1

3) casseous nectrotic granuloma - acellular necrotic centre
-foamy macrophages
significant Mtd load!
- express eNOS + NOS

4) supparitive granuloma - neutrophilic necrotic centre
-foamy macrophages
- express eNOS + NOS
significant Mtd load!

5) cavity granuloma -open cavity centre
- abundant b cells
- poor CD25 expression