Flashcards in Cystic Fibrosis Deck (39)
What is the inheritance pattern of CF?
What gene is indicated in CF?
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene
What does CFTR gene code for?
A chloride ion channel
Where is CFTR on the cell?
Apical luminal membrane
What organ tissues is CFTR present?
Airways, pancreatic ducts, intestines, other tissues
What is the mean survival age of a patient with CF?
What is the prevalence of CF across ethnicities?
African American: 1:15000
Asian American: 1:32000
How many caucasians are carriers?
What are the five mutation classes for CF?
Class 1: No protein produced
Class 2: Defective protein folding
Class 3: Defective gating or regulation
Class 4: Defective ion transport
Class 5: Normal CFTR but decreased amounts
What gene problem is indicated in Class 1 mutations?
What gene problem is indicated in Class 2 CF?
What gene problem is indicated in Class 3 mutations?
What is the most common CF mutation?
How much CFTR activity remains in classes 1, 2, 3? How about classes 4 and 5?
What results from the F508del at the cellular level?
Misfolding, stays in ER for proteasome degradation
Some get to surface but do not function well
Can outcome be predicted on an individual level when considering severity of mutation?
What does the G551D mutation result in at the cellular level?
Inability for channel to respond to ATP, increases time in closed conformation
What happens to water distribution when the CFTR gene is functioning properly?
Chloride goes to ECF
Water inside cell follows gradient, goes outside
What happens to water flow when CFTR is functioning improperly?
Not enough water outside on cell surface
What is the sequence of events that leads to CFTR regulation?
External stressors -> cAMP intracellular pathway -> Activation of PKA -> phosphorylation of R domain -> Activation of CFTR
What is ASL and what is its function?
Airway surface liquid. Activates cilia and hydrates mucous
What happens to ASL volume in CF?
ASL layer not maintained
What bacteria infections are common in CF patients?
How many CF pediatric patients get Pseudomonas aeruginosa?
What are mainstays in treating lung dysfunction in CF?
Chest physiotherapy to remove drainage
Aggressive antibiotics to clear infection
What other things are common to treat CF lung dysfunction?
Hypertonic saline flush and DNase aerosols to make mucous less viscous
What is the physiological function of CFTR in pancreatic cells?
Secrete HCO3 to recruit intracellular H2O
Prevent formation of protein plugs
What is the pathophysiology of pancreatic CFTR dysfunction?
Protein plug blockage -> damage to cells -> proteolytic enzyme leakage -> destruction of tissue
What is the function of CFTR in the intestine?
Hydration of intestinal epithelium