cystic fibrosis: Flashcards
cystic fibrosis:
epithelial cells produce excessive sticky mucus
affects lungs, gut, liver, reproductive tract and pancreas
leads to lung disease caused by bacterial infection in airways
symptoms of cystic fibrosis:
- Thick sticky mucus secretion in lungs
- Chronic cough
- Wheezing
- Bronchitis
- infertility
body can not absorb nutrients…
- Salty skin
- poor infant growth
- malnutrition
- diabetes
cause of cystic fibrosis:
autosomal recessive disease
mutations in CFTR: cystic fibrosis transmembrane protein
= type of ABC (ATP-binding cassette) regulator
△F508 mutation = deletion of phenylalanine at position 508
operation of CFTR
Control Cl- efflux and osmosis our of epithelial cells in lungs, liver, pancreas, reproductive tract, gut.
Stage 1 - Channel closed
Stage 2 - cAMP activates PKA, which then phosphorylates the regulatory domain of CFTR
Stage 3 - ATP is able to bind to nucleotide binding domains
aStage 4 - conformational change opens the pore of the channel allowing Cl- ions to leave cell
Stage 5 - ATP is hydrolysed to ADP causing channel to close.
Airway Surface Liquid (ASL) volume is determined by…
the action of pumps, transporters, and channels in both apical and basolateral membranes
consequences of CFTR loss of function:
= Mutation prevents channel from functioning properly
= Prevents chloride efflux and osmosis out of cell
= cells produce abnormally thick, sticky mucus
= inhibits cilia movement as mucus layer compresses cilia
= traps bacteria = chronic infection
Failure of clearance in CF airways results in…
- dehydrated mucus plaques blocking airways.
- bacteria colonize mucus
Macrophages and neutrophils try to attack bacteria but can’t penetrate concentrated mucus
treatments:
physiotherapy/ exercise
lung transplant
bovine pancreatic dornase to reduce mucus viscoelasticity
ASL volume restoration
gene therapy
medication:
bronchodilaters
antibiotics
steroids
nutritional supplements
