cystic fibrosis Flashcards
what the main symptoms of CF?
production of sticky mucus that can occlude lung and pancreaus
> repeated lung infection
> poor food absorption
very salty sweat
coughing
poor growth
how is sweat generated?
sweat gland produces NaCl rich fluid in the secretory coil which is then modified in the duct
so the final sweat excreted is hypotoic as salt is actively pumped out
how does sweat change in CF?
why?
becomes very salty
because of reduced ductal salt absorption
as the electric potential across duct wall is increased so harder to pump out salt
final sweat conc is very high
what is the defect in CF?
the cystic fibrosis gene encodes for the
cystic fibrosis transmembrane regulator (CFTR)
why are CF therapies difficult?
gene-correction therapies for CFTR have been unsuccessful as the defects are in epithelial cells
they have a high turnover so the defective protein would persist
what is the consequence of a mutated CFTR?
can be reduced chloride transport across cell
as difficult to insert channel into membrane
higher degredation of the channel
how is mucocicilary clearance affected in CF?
the rate of mucus clearance is reduced in CF
as there is a collapse in the fluid layer reducing cillia beat frequency
why is the CFTR/ chloride channel important in pancreaus?
it enables exchange of bicarbonate and allows fluid secretion
in CF the secreted digestive fluid clogs the small ducts
what is the consequence of a occuluded pancreaus?
digestive secretion blocks small ducts and destroys pancreatic unit
digestive enzymes like trypsin become activated within acinar cells
what is the main mutation in CF?
a deletion of F508
Phenylalanine
responsible for 60-70% CF cases and affects protein folding and channel function
name a current therapy for CF?
Orkambi
how does the current CF therapy work?
Uses a CFTR potentiator and CFTR corrector
this dual therapy makes it more likely for CFTR to be inserted in membrane and prevents use of antibiotics or physiotherapy
effectively overcomes issue of mucus accumulation
