CF Flashcards
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Chloride ion channel
Apical membrane of epithelial cells
Chromosome for CF
CFTR gene on chromosome 7 long arm
How do you diagnose CF?
Need 1+ typical phenotypic features of CF, sibling with CF, or positive newborn screening
THEN… you need lab confirmation
2 + sweat chloride tests, 2 known disease causing CFTR mutations, abnormal nasal potential different.
What is the median age at diagnosis?
5.3 months Meconium ileus: 0.2 month newborn screening: 0.5 month Symptoms: 14.5 months Increased risk of complications in patients diagnosed by symptoms vs NBS.
Respiratory Disease in CF
Lung infection & inflammation cycle damage the lungs and decrease lung function (FEV1)
Incidence of pulmonary exacerbations increase with age.
Progressive lung disease is the leading cause of death in CF patients.
Pulmonary Manifestations of CF
Chronic cough, sputum production, recurrent infections, bronchiectasis, hemoptysis, pneumothorax, allergic bronchopulmonary aspergillosis (we breath this fungus in every day) pulmonary arterial hypertension, respiratory insufficiency/failure
Pathogenesis of Lung Disease in CF
Abnormal CFTR gene, abnormal CFTR protein, abnormal salt transport, abnormal mucus, impaired clearance, infection, inflammatory response, bronchiectasis… (diagram in lecture slides)
Most common respiratory infections in CF?
Staph and then Pseudomonas later in life
Therapeutic Approaches to CF
Depends on the stage:
Genetic mutation -> Protein rescue/activation -> proper ion transport -> anti infective anti inflammatory -> transplanation.
A lot of research is being done with genetic replacement therapy but not much success.
Positive Sweat Test Result
> 60 mmol/L -> Consistent with CF
40-60 mmol/L -> borderline-further investigation warranted
Nasal Potential Difference
Measures chloride ion secretion of CFTR protein after isoproterenol challenge
Absent in CF nasal epithelium
Technically challenging! -> lab must do regularly to be good at it.
Newborn Screen
Immunoreactive trypsinogen (IRT): cutoff varies by state second test: IRT, DNA numerous false positives and also picks up carriers.
IRT/DNA approach
immunoreactive trypsinogen (pancreative enzyme precursor, elevated in CF patients) -> mutant analysis (F508del or a panel of mutations) -> sweat test
Staph aureus in CF patients
Gram + cocci
Most commonly found isolate in CF
Now have to worry about Methicillin Resistant Staph Aureus (MRSA)
Treatment: MSSA: naficillin, cefazolin, oxacillin
MRSA: vancomycin, septra, clindamycin, linezolid
MRSA is associated with decreased survival
CF and Burkholderia cepacia Complex
Formerly classified as pseudomonas, but now a complex (BCC) of different genomovars.
usually far in progression of CF
may be colonization or active infection
Usually highly resistant to many antiobiotics
What is Cepacia Syndrome?
End stage lung function with fevers, weight loss, feeling bad
Pseudomonas aeruginosa
Infection occurs as early as first year of life
Prevalence increases with age -> more than 73% of adult are chronically infected.
Chronic infection with P. aer. is an independent risk factor for accelerated …. (slide)
What is the mucoid phenotype associated with CF patients?
With prolonged infection, P. aeruginosa converts to a mucoid phenotype by the production of alginate. Mucoid phenotype is seen infrequently in pop without CF.
Conversion of P. aeruginosa to the mucoid phenotype worsens prognosis.
Pseudomonas aeruginosa
Gram negative rod
Catalase positive, oxidase positive
aerobic
flagella provide motility
antibiotic resistance ranges from sensitive to pan-resistant
Questions on boards often say it “smells like grapes or blue tortilla chips in the lab”
How do we treat CF patients with pseudomonas infection? What is meant by “double covering”
Generally in CF, will “double cover”
Pseudomonas to help prevent resistance
One antibiotic from two different classes with differing MOA
ex. one cell wall active agent, one ribosome directed agent
Using two drugs that work in the same manner is NOT double covering!
Why do CF patients require very high doses of antibiotics?
Lung pathology
CF patients are HYPER metabolic and often very thin
All anti-pseudomonal drugs are IV expect for which ones?
flouroquinolones
How do you test for Pancreatic insufficiency? (PI)
Fecal elastase levels < 200 mcg/gm
72 hr stool sample with dietary inventory
Fat excretion > 7% of intake is abnormal
Secretin stimulation test
PERT for pancreatic insufficiency
varying amt of lipase, protease and amylase
granules/microspheres coated with pH sensitive material
improves fecal fat absorption in pts with PI
Acid suppression increases efficacy of enzymes
