Infections 1- TB/ CF (3)-Melissa**

Question 1

What is the #1 genetic disease amongst caucasians?
What is its inheritance pattern?
Describe the genetic mutation.

Answer 1

Cystic Fibrosis; 5% whites are heterozygous
Autosomal Recessive

Mutation:
3 nucleotide deletion in CFTR gene on chromosome 7–> deletion of single amino acid (Phe)

Question 2

What are the major organs affected by CF (2)?

Answer 2

#1 Lung
2. Exocrine glands (85% have pancreatic insufficiency) in pancreas and small intestine

Question 3

Three knee jerk findings for CF

Answer 3

1. Salty skin
2. NASAL POLYPS
3. malnourished & delayed puberty
   …other GI = meiconium ileus etc.

Question 4

CF patients suffer from chronic bronchopneumonia.

Describe how the microbes change in their lungs over time.

Answer 4

Infancy- Adolescence:
B. cepacia
H. Flu
S. Aureus

Adolescence- Adulthood:
P. aeruginosa (forms biofilm– THE POLYSACCHARIDE!!)

Question 5

Pseudomonas aeruginosa:

• gram stain + shape
• aerobic/anaerobic + growth requirements

Answer 5

• Gram (-) motile rod
• Facultative aerobic w/ simple growth requirements
• grape odor

A quick note for step:
-catalase positive, oxidase positive, burn victims, hospital; acquired UTIs and pneumonia

Question 6

How does pseudomonas bacteria live in the human lung?

Answer 6

Pseudomonas uses polysaccharide capsule to produce biofilm

Question 7

What is the pseudomonas phenotype living in CF lungs called?
What does it produce?

Answer 7

Mucoidy (pseudomonas phenotype) pseudomonas produce alginate (exopolysaccharide) biofilm

*This is energy expensive and would be unstable in any other environment

Question 8

What are the implications of biofilms upon ABX treatment?

Answer 8

Clinical doses of ABX are not sufficient to kill bacteria living in “exopolysaccharide matrix”; they were designed to kill bacteria in suspension

Question 9

Describe the chronic inflammatory cellular infiltrate seen in CF lungs:

Answer 9

^ neutrophils! (yes, neutros, even though its chronic. Yu prob. made this up just so he could say THE NEUTROPHILS!!!!!!!!!!)

Question 10

Do pseudomonas and other CF lung infections typically become systemic? What is the cause of death for most CF patients?

Answer 10

• Infections stay in the lung.

- CF patients die from asphyxiation

Question 11

Describe how neutrophils try to clean up pseudomonas biofilm infection in CF patients:

Answer 11

“Frustrated phagocytosis”

Neutro can’t phagocytose–> bursts and dies–> releases enzymes and intracellular contents that further destroy lung tissue

Question 12

Describe the steps made possible by the CFTR mutation that allow pseudomonas to colonize the CF lung.

Answer 12

CFTR mutation–> Secretion Defect–> P. aeruginosa colonization–> Nonmucoid P.a–> Mucoid P.a–> Chronic infection–> inflammation + Type III hypersensitivity–> Lung tissue destruction

Question 13

What two ways does the nonmucoid P.a differ from the mucoid P.a

Answer 13

Nonmucoid:

• Smooth LPS w/ ^ Proteases
• can colonize normal lung

Mucoid:

• Rough LPS w/LOW proteases (LESS virulent)
• only present in the CF lung

Question 14

What factor complicates treatment of P.a in the lung?

Answer 14

P.a is resistant to many ABX; esp. when it has a biofilm

Question 15

Which populations typically get infected with TB in the industrialized world? How common is TB infection

Answer 15

Homeless, HIV
#2 infectious disease cause of death ww (second to HIV)

Question 16

Describe how latent TB infections work and when they become dangerous:

Answer 16

• Bacteria stop growing and lesions calcify
• Immunosuppression allows reactivation of infection
• TB can now spread throughout lung and to other parts of body

Question 17

Describe how Primary TB infection works and how they are dangerous:

Answer 17

• Lesion forms and liquifies
• Bacteria coughed up in sputum and spreads systemically when swallowed
• Patients die from systemic TB infection

Question 18

In which part of the lung does reactivated TB like to reside?

Answer 18

Upper lobes (specifically the “apex”)–more O2 and this is an aerobic organism!

First AID,Rx, DIT, Pathoma, AND sketchy LOVE this little fact, so KNOW IT.

Question 19

What cytokines are released by the TB infected MQs?
Which cytokines do the TH1 helper cells release in response?
What is the result?

Answer 19

TB activated MQ–> TNF, IL-1
TH1 cell–> IFN-y
Results in formation of a granuloma

First aid note: INF-y is the primary activator of MACS

Question 20

Describe the morphology of a granuloma (3 layers from outside in):

Answer 20

1- FIBROBLAST wall
2- Layer of surrounding LYMPHOCYTES (TH1 cells)
3- CASEOUS NECROSIS center w/ MQs and EPITHELIOID (Giant) Cells

Note: intracellular bacteria within granuloma not killed by formaldehyde postmortem; this is dangerous for pathologists!

Question 21

Mycobacterium TB (MTB): 
Describe the cell wall; how does it protect MTB?
Describe the growth requirements/ growth pattern

Answer 21

• Gram + LIKE cell wall with waxes
• Waxes are RESISTANT to drying, chemicals, germicides
• Waxes cause MTB to grow very SLOWLY
• OBLIGATE AEROBE = APEX OF LUNG!!!!

Question 22

How do we stain MTB

Answer 22

• Acid fast stain for mycolic acid in MTB cell wall
  (lowenstien jensen; also zeihl neelsen; AND carbol fushin, i dont know why there are so many words for this, but sorry, there are. I have seen these three when step studying.)

Question 23

How is TB transmitted? What is a vital factor determining whether or not patient becomes infected?

Answer 23

• Aerosol transmission via prolonged contact between susceptible person and person with active disease
• Infectious dose is very important here!

Question 24

Inside what cells does TB grow?
How is this possible (3)?
How does TB cause lung damage?

Answer 24

Monocytes and MQs

• prevents phagosome/ lysosome fusion
• prevents acidification of phagosome/ escapes phagosome
• mycolic acids are toxic and stimulate immune response

Mycoloic acid= TNF-a release–> lung tissue damage

Question 25

What are other organisms that can cause caseous granulomas?

Answer 25

• syphilis and all dimorphic fungi

Question 26

What do we call a calcified caseous granuloma?

What is another term for giant cells within caseous granulomas?

Answer 26

Ghon Complex

Longhand’s cells

Question 27

What is miliary TB and which patients get it?

Answer 27

TB with small granulomas throughout body; occurs in immunosuppressed patients with low # TH1 cells (unable to wall off infection)

Question 28

Which patients die most rapidly from TB infection?
How does the infection manifest in these patients?
Why does this occur?
What other infections are these patients more prone to getting?

Answer 28

• TB kills AIDS patients die more rapidly and infects them 500x more often than general population
• Patients are more likely to have systemic infection
• Low CD4 T cells–> Can’t activate MQs
• Patients also susceptible to MAI infections

Question 29

How do we Dx TB? (4 steps)

Answer 29

• Careful Hx
• Acid fast stain of sputum/ exudate
• CXR
• PPD test (positive up to 4 weeks after infection)

Question 30

What are 3 caveats to PPD efficacy?

Answer 30

1. immunocompromised patients may not react
2. cross reactivity with other mycobacterium
3. foreign nationals who got BCG vaccine will be positive

Question 31

How long does it take to cultivate TB?

Answer 31

3-8 weeks!