Infections 1- TB/ CF (3)-Melissa** Flashcards
What is the #1 genetic disease amongst caucasians?
What is its inheritance pattern?
Describe the genetic mutation.
Cystic Fibrosis; 5% whites are heterozygous
Autosomal Recessive
Mutation:
3 nucleotide deletion in CFTR gene on chromosome 7–> deletion of single amino acid (Phe)
What are the major organs affected by CF (2)?
#1 Lung 2. Exocrine glands (85% have pancreatic insufficiency) in pancreas and small intestine
Three knee jerk findings for CF
- Salty skin
- NASAL POLYPS
- malnourished & delayed puberty
…other GI = meiconium ileus etc.
CF patients suffer from chronic bronchopneumonia.
Describe how the microbes change in their lungs over time.
Infancy- Adolescence:
B. cepacia
H. Flu
S. Aureus
Adolescence- Adulthood:
P. aeruginosa (forms biofilm– THE POLYSACCHARIDE!!)
Pseudomonas aeruginosa:
- gram stain + shape
- aerobic/anaerobic + growth requirements
- 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
How does pseudomonas bacteria live in the human lung?
Pseudomonas uses polysaccharide capsule to produce biofilm
What is the pseudomonas phenotype living in CF lungs called?
What does it produce?
Mucoidy (pseudomonas phenotype) pseudomonas produce alginate (exopolysaccharide) biofilm
*This is energy expensive and would be unstable in any other environment
What are the implications of biofilms upon ABX treatment?
Clinical doses of ABX are not sufficient to kill bacteria living in “exopolysaccharide matrix”; they were designed to kill bacteria in suspension
Describe the chronic inflammatory cellular infiltrate seen in CF lungs:
^ neutrophils! (yes, neutros, even though its chronic. Yu prob. made this up just so he could say THE NEUTROPHILS!!!!!!!!!!)
Do pseudomonas and other CF lung infections typically become systemic? What is the cause of death for most CF patients?
- Infections stay in the lung.
- CF patients die from asphyxiation
Describe how neutrophils try to clean up pseudomonas biofilm infection in CF patients:
“Frustrated phagocytosis”
Neutro can’t phagocytose–> bursts and dies–> releases enzymes and intracellular contents that further destroy lung tissue
Describe the steps made possible by the CFTR mutation that allow pseudomonas to colonize the CF lung.
CFTR mutation–> Secretion Defect–> P. aeruginosa colonization–> Nonmucoid P.a–> Mucoid P.a–> Chronic infection–> inflammation + Type III hypersensitivity–> Lung tissue destruction
What two ways does the nonmucoid P.a differ from the mucoid P.a
Nonmucoid:
- Smooth LPS w/ ^ Proteases
- can colonize normal lung
Mucoid:
- Rough LPS w/LOW proteases (LESS virulent)
- only present in the CF lung
What factor complicates treatment of P.a in the lung?
P.a is resistant to many ABX; esp. when it has a biofilm
Which populations typically get infected with TB in the industrialized world? How common is TB infection
Homeless, HIV #2 infectious disease cause of death ww (second to HIV)
Describe how latent TB infections work and when they become dangerous:
- Bacteria stop growing and lesions calcify
- Immunosuppression allows reactivation of infection
- TB can now spread throughout lung and to other parts of body
Describe how Primary TB infection works and how they are dangerous:
- Lesion forms and liquifies
- Bacteria coughed up in sputum and spreads systemically when swallowed
- Patients die from systemic TB infection
In which part of the lung does reactivated TB like to reside?
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.
What cytokines are released by the TB infected MQs?
Which cytokines do the TH1 helper cells release in response?
What is the result?
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
Describe the morphology of a granuloma (3 layers from outside in):
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!
Mycobacterium TB (MTB): Describe the cell wall; how does it protect MTB? Describe the growth requirements/ growth pattern
- 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!!!!
How do we stain MTB
- 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.)
How is TB transmitted? What is a vital factor determining whether or not patient becomes infected?
- Aerosol transmission via prolonged contact between susceptible person and person with active disease
- Infectious dose is very important here!
Inside what cells does TB grow?
How is this possible (3)?
How does TB cause lung damage?
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
