PATHOPHYS: Cystic Fibrosis Flashcards
What portion of the population has CF?
Both children and adults (because treatment is allowing more CF patients to live into adulthood
What does the CF gene code for?
CFTR (cystic fibrosis transmembrane regulator)
Where is the CFTR gene located?
long arm of chromosome 7
How many mutations are found in CFTR?
over 1800
What is the most common mutaiton in CFTR in caucasians?
Delta F508
Where is CFTR located? What does it do?
located at the cell surface and acts as a regulated chloride channel
What does CFTR regulate?
increases airway surface liquid (ASL) via inhibiting Na+ absorption (along with water) and Cl- secretion
What does ASL do?
Forms periciliary liquid layer
Dilutes mucus—facilities entrapment of bacteria and clearance (helps clear airway secretions)
What does a mutant CFTR do to ASL?
Normal CFTR will cause Cl- ions to be secreted if the ASL fluid is low and in mutant CFTR, Cl- ions not secreted
Normal CFTR blocks an ENaC channel, mutant CFTR does not block this and sodium absorption is increased (water follows sodium and ASL volume decreases)
At what funcitonal level do mutations of the CFTR occur in the cell?
ALL OVER: membrane, vesicles, golgi, ER, and nucleus
this is why there are so many subtypes
What is the pathogenesis of CF?
Abnormal CFTR leads to defective ion and fluid transport which impairs mucociliary clearance. This leads to obstruction or mucus plugging that allows for CHRONIC infections, inflammation (with break-down of cartilage) and scarring of the lung.
What do people of CF die from?
end stage lung disease
What are the 5 classes of CFTR mutations?
NO CFTR I: No synthesis II: Block in processing (delta 508- CFTR does not reach surface!) SOME CFTR III: Block in regulation IV: Altered conductance V: Reduced synthesis
What is the clinical hallmark of CF?
chronic sinusitis
also see clubbing, airway obstruction, nasal polyps, etc.
If a CF patient has asthma symptoms with eosinophils, what should you think about?
ABPA (aspergillus)
