Cystic Fibrosis Flashcards
what does the CF gene code for?
a protein called cystic fibrosis transmembrane regulator
Where is the CFTR largely expressed? (5)
epithelial cells of the airways, pancreas, biliary system, GU system, sweat glands (All organs that involve mucus)
How does genotype help to predict the severity of lung disease and liver disease in CF?
genotype cannot predict severity
what is the most common mutation in CF?
deltaF508
Compare the prevalence of CF disease (how many in US) vs the number of Americans that are unknowing carriers
CF rare disease, only 30,000 US ppl have it
but 10 mil unknowing carriers
just know there is a diff here
what race is CF a disease of
whites
What is the inheritance pattern of CF?
Auto Recessive - 2 carrier parents - 25% chance of having affected child (full blown cf)
where is the CFTR gene located? chromosome and arm
CFTR is on long arm of chromosome 7 (this will be on exam)
what is the function of the CFTR protein? where is it located?
CFTR is located at the cell surface and acts as a regulated chloride channel
what percentage of CF patients have at least one copy of F508 del? i.e. either homozygous for F508 or heterozygous for it
87% (common things are common, so impt to remember F508)
48% homozygous for df508 mutation. NEED TO KNOW THIS
under normal conditions, what does CFTR inhibit
it inhibits the ENaC sodium channels (that would bring sodium into epithelial cells)
what happens regarding ENaC and the airway surface liquid when the CFTR is mutated/non functional
ENaC is not inhibited
sodium absorption is inc
Water follows sodium
ASL volume decreases - mucus is dehydrated and thick
Molecular consequences of CFTR mutations fall into 5 classes. what are they (briefly)? which one is deltaF508?
Class I - no synthesis (hardest to treat)
Class II - block in processing, cannot get to membrane (F508)
Class III - V - CFTR at surface cell membrane, but either non functional or reduced function
of the exocrine glandular ducts where CFTR is present (pancreas, lungs, sweat glands, glands of uterine cervix), which ducts are not obstructed in CF
uterine cervix glands
not obstructed
this is a shitty question - but the shit below explains the salty sweat
in the sweat gland, both the Cl and Na channel face the same direction, inward. If the CFTR is mutated, then you cannot reabsorb Cl or Na - leads to salty sweat
Oppo of lung and all the other epithelial tissues, where CFTR and ENaC are facing opposite directions
What is the symptom/condition that can be seen in infants w/ CF that help w/ diagnosis of an infant (probably the most common presenting condition of CF in kids)
meconium ileus - present as abdominal pain - due to pancreatic insufficiencies associated with CF
what are some general symptoms of CF seen in infancy
stools that are pale, foul or float
wheezing, pneumonia
salty-tasting skin
chronic cough
in classic CF
1) what is the activity of CFTR?
2) what upper respiratory symptoms will you see?
3) what other symptoms?
4) what test do you do?
5) what is generally age at diagnosis?
1) no CFTR at all
2) chronic sinusitis, severe bacterial infection of lungs
3) hepatobiliary disease, pancreatic exocrine insufficiency* - leads to malabsorption, meconium ileus at birth*
4) sweat chloride test
5) usually dx young
In non classic CF
1) most common symptoms
2) other variable chronic symptoms
3) pancreatic status
4) sweat chloride
5) age at dx
1) asthma-like sinopulmonary symptoms - also nasal polyps
2) chronic bacterial infxn of lungs - variable, later onset
3) Pancreas is still sufficient
4) sweat chloride - less elevated, but still up
5) dx later in life 25-30 ish - b/c they retain pancreatic function
what PFT pattern is seen w/ CF pts, obstructive or restrictive?
obstructive
w/ regards to the sinuses, what is a universal finding in CF?
pansinusitis - may also include nasal polyps
what finding on PVD exam may be associated with CF? (can also be associated with pulmonary dz, cardiac dz, etc)
digital clubbing - shamroth sign
what is the most common COD in CF pts?
most CF pts die of pulmonary complications
What will be the earlier diagnostic predictor of lung damage in CF, a CT scan or a PFT
CT scans detect damage before lung function decline - i.e. before PFT shows obstructive pattern
What is the correlation between CFTR function and the results of the sweat chloride test?
sweat chloride is inversely related to CFTR function - the higher the level of chloride, the more severe the disease
what is the correlation between sweat test results and pancreatic function?
CF pts w/ lower sweat chloride levels tend to retain pancreatic sufficiency
do CXR always detect early lung damage?
no - even though imaging may precede PFTs in picking up lung damage, the earliest damage may still not be detectable on CXR
what will a bronchography of a CF pt show? what disease process does this indicate
can visualize the saccular dilatations associated with the bronchiectasis seen in cystic fibrosis
what bacteria is commonly cultured from the sputum of adult pts w/ CF?
pseudomonas
(need to remember)
(it rhymes w/ cystic fibrosis)
what is predictive of survival in pts w/ CF?
What are the hard numbers of this?
the degree of pulmonary impairment
and FEV1 less than 30% predicted is associated with a 2-year survival less than 50%
CF affects function of pancreas - what is the pathophys of this and the clinical manifestations
dysfunction of pancreas leads to fat malabsorption - leads to greasy bulky stools**
CF pancreatic insufficiency - what vitmains will be malabsorbed
fat soluble vitmains - A, D, E, K
can lead to deficiency and coagulopathy
we see meconium ileus in children with CF - as a result of pancreatic insufficiency - what is the name of the adult counterpart of this problem?
distal intestinal obstruction syndrome (DIOS) - due to inspissated mucus in GI tract - chronic constipation
CF in pregnancy - what obstetric emergency are CF pts at increased risk for
premature delivery
what is the maternal and fetal outcome for most CF pts, better or worse?
better - maternal and fetal outcome is good for most pts
what is the fertility status of males in CF and why?
95% of males are sterile due to congenital bilateral absence of the vas deferens - sperm production is still there, but no communication for sperm to travel along the SS REDV
so going back to whether female CF patients are fertile or not, technically they are fertile. but they have difficulty conceiving for two reasons. what are they?
1) thick cervical mucus
2) Anovulatory cycles resulting from poor nutritional status
does maternal function deteriorate after pregnancy?
no
what number cutoff constitutes a positive sweat chloride test?
above 60 meq/L
what is the percentage of pts w/ homozygous F508/F508 del for CF?
48%
what are the names of the 2 common drugs used for CF?
inhaled Tobramycin and Pulmozyme
dsecribe the mechanism of Tobramycin and the effect it has on pulmonary function
it inhibits the steep decline in FEV1 over time by reducing pulmonary infections
what is the MOA of pulmozyme?
it hydrolyzes DNA in mucus, makes the mucus thinner so it can be easily expectorated
what is the important, common method of airway clearance for CF
postural drainage
what are the other methods of airway clearance in CF
hypertonic saline
Acapella, flutter valve
VEST - high frequncy chest wall oscillation
Pulmozyme
Class III CF is what type of mutation? What new medication has been targeted for it? MOA?
Class III = Missense mutation in G551D. New drug Ivacaftor [Kalydeco] developed, drops sweat Cl. Almost reversing CF in these patients.
What new drug was developed in 2013 for CF? What mutation does it target? MOA?
Lumacaftor/Ivacaftor [Orkambi] for df508 mutation. CFTR corrector/potientator
