cystic fibrosis Flashcards
Gene and types of mutations for CF
CFTR gene
may be nonsense mutation, delat F508 or other mutation that prevents proper localization; loss of function mutations, decreased conductance or decreased gene expression
CFTR function
cAMP activated channel that conducts ATP and Cl. regulates CaACC and ENaC. key role in ion transport across membranes and maintenance of airway surface liquid layer
CFTR complex function
Takes Cl and ATP out of cells and into lungs. Also activates CaACC, which also takes out Cl. Meanwhile, it inhibits ENaC, which is trying to bring Na into the cell and out of the lung. together, this puts NaCl in lung, water flows to where the salt is to make mucus
What happens when CFTR is broken?
less Cl and ATP transport by CFTR less Cl transport by CaACC more Na transport by ENaC decreased airway surface liquid layre and increased mucus viscosity. leads to chronic airway infection
diagnosis of CF (best)
sweat test best. in sweat test, CFTR channels are oriented opposite to how they are in the lung- function to reclaim salt from sweat duct. too much salt in sweat suggests CF. less than 40 mmol/L is normal; more than 60 is abnormal
Nasal potential differences
another screen for CF. measures electrical potential across nasal mucosa acter acteviating CFTR by isoproteronol. in vivo assessment of CFTR function in resp. tract but must be done at a CFTR research center
Pathogenesis of lung disease in CF (up to chronic inflammatory response)
CFTR mutation –> loss of function –> altered ion transport. this has widespread effects in pancreas, sinuses, liver, vas deferens, and skin. it als leads to decreased airway surface liquid, thick mucus secretions, and impaired mucociliary clearance. these factors lead to chronic infection and then a chronic inflammatory response.
How the inflammatory response contributes to pathology in CF (PMNs)
PMNs are part of the inflammatory response to chronic bacterial infection. PMNs release elastase and reactive oxygen species, both of which promote bronchiectasis. Elastase also increases the inflammatory response. PMNs also release DNA-actin, which exacerbate mucociliary clearance
What kinds of infections are seen in CF?
First, S. aureus. later, pseudomonas aeruginosa is important. once established, infection is never eradicated, so we are just trying to control infection in CF therapies.
Approaches to CF treatment
airway clearance, infection management, and medications that reduce inflammation.
What meds are used to help with airway clearance in CF?
mannitol, hypertonic saline
How do we control infection in CF
chronic antibiotics- cipro, amikacin
How do we control chronic inflammation in CF
azithromycin, simvastatin, anti-cytokines, anti-proteinases
what are some causes of increased bacterial load in CF
viral infection, medication non-compliance, build up over time
treatment for pulmonary exacerbations of CF
antibiotics, oral steroids, increased airway clearance treatments
