CF Flashcards
What is CF?
Chronic, progressive & life limiting autosomal recessive genetic dz characterized by chronic resp dz, pancreatic insufficiency, elevation of sweat electrolytes, & male infertility
What’s the clinical presentaiton of CF?
Cl channel defect in exocrine glands
Thick secretions
Recurrent pneumonia
Pancreatic insufficiency
High salt content in sweat
Male infertility
Malnourishment
Which protein/gene is defective in CF?
CFTR: a cAMP regulated Cl channel located in apical membrane of glandular epithelium
Located on long arm of chromosome #7
Leads to defective ion transport
What’s the defect in ion transport in CF?
Cl channel is normally bidirectional so it can maintain a good gradient but in CF it’s nonfunctional/closed
In CF, Cl stays in the cell, Na follows, and water follows, leaving a really thick secretion outside the cell because everything else has gone inside
What’s the pathway from genes –> dz in CF?
CFTR gene defect –>
Defective ion transport –>
Airway surface liquid depletion (thick & dehydrated) –>
Defective mucociliary clearnance –>
Cycle of mucus obstruction, finlammation, and infection
How does the cycle of infect/inflam/airway obstruction propagate in CF?
Abnromality in Cl transport –> airway surface fluid becomes thick & you get surface plugging –> bacteria get stuck in it so neutrophils come in to try to clean it up
What are the five classes of CFTR mutations?
I: no synthesis
II: block in processing
III: block in regulation
IV: altered conductance
V: reduced conductance
(I&II=”garden variety dz, no Cl channel is functional; the rest have more function in Cl transporter)
What’s the relationship between phenotype and genotype in CF?
No clear relationship/correlation
But we know that variation exists & accounts for the variation in presentation of CF
Why is sweat salty in CF patients?
CFTR also exists on sweat glands in order to reabsorb swat (normally)
In CF patients, CFTR isn’t functional so your body can’t reabsorb the sweat–> very salty sweat!
What is the sweat test in CF? What is it used for?
Used to diagnose CF
Give pt pilocarpene (induces sweat), soak sweat in gauze, and measure amount of Cl
The degree of Cl in sweat mostly matches the class of the defect: class I/II have the most Cl in salt (>60 mEq/L) versus normal is <40
Which bug is particularly concerning in CF patients, particularly older ones?
Pseudomonas aeruginosa
Goal is to prevent colonization/infection from a young age
Why is pseudomonas particularly bothersome?
Because later/chronic infections become more resistant to drug treatment
It develops a sheath & a biofilm, making it impermeable to antibiotics
Treat early bc early infections are susceptible to drugs!
Is inflammation in CF only due to infection?
No, there seems to be a separate process in which inflammation is high in CF- not sure why
What type of pulm dz is CF - obstructive, restrictive, parenchymal, interstitial?
Obstructive!!
Difficult to move air in/out of lungs
Almost exclusively affects the airway
What do the pulm function tests in CF look like?
Low FEV
In moderate/severe dz, low FEV1
You progressively lose more and more lung function over time
You get air trapping
You breathe closer to max exp flow rates every day
What does a CF chx look like?
Small heart, low diaphragm= squished by lung due to hyperinflation
Increased markings
Big lung fields
You can get scarring in advanced dz due to bronchiectasis
