Cystic Fibrosis Flashcards
what type of genetic disorder is CF
autosomal recessive
how many people are carriers
one in 25
describe CF trans-membrane conductance regulators
chloride channels ATP regulators
describe the role of trans-membrane conductance regulators
transport of chloride, sodium and water in and out of cell
what does a defect in the TMCR mean on a cellular level
sodium channels defective so suck in sodium and water back into the cells
what are the resulting consequences of a TMCR gene mutation
altered secretions, blocked ducts, impaired mucosal defence, infection, inflammation, cystic fibrosis
what are the clinical presentations of a defective CFTR
CYSTIC FIBROSIS OF THE PANCREAS salty sweaty, intestinal blockage, fibrotic pancreas, failure to thrive, recurrent bacterial lung infections, congenital bilateral absence of vas deferens, filled sinuses, gallbladder and liver disease
What are the reasons behind the clinical presentations of CF
infection/ inflammation because of blocked ducts
what class of CFTR defect is the most severe
class 1- many die in utero
what is the biochemical phenotype of a class 1 CFTR defect
no CFTR synthesis
what is the biochemical phenotype of a class 2 CFTR defect
CFTR trafficking defect (delta F508)
how can patients with class 2 defect survive
as golgi helps to stop some defect genes
what is the biochemical phenotype of a class 3 CFTR defect
dysregulation of CFTR- diminished ATP binding and hydrolysis, protiens cant get through membrane
how severe is a class three CFTR defect
mild forms
what is the biochemical phenotype of a class 4 CFTR defect
defective chloride conductance or channel gating, proteins embedded in membrane
how severe is a class 4 CFTR defect
milder than class three
what is the biochemical phenotype of a class 5 CFTR defect
reduced CFTR transcription and synthesis, dont make enough protein, normal function but at reduced level
what are the five types of mutations
missense, deletion, premature stop, deletion (frameshift)
name two mutations that affect the CF gene working correctly
delta F508, G551D
in a recessive disease, are the mutations on each gene the same
no can be different
patients with what conditions get tested for CF and sweat testing
bronchiectasis under 40, upper lobe bronchiectasis, colonisation with Staph, infertility, low weight
why do some people not get diagnosed until adulthood
don’t present, lack of continuity of care, present sporadically or out of hours, don’t think about it
what is upper lobe bronchiectasis
dilated bronchi and thickening of bronchi walls in upper lobes of the lung
what are the difficulties of CF
treatment burden and complications can be rapid in onset
what are many of the treatments for CF
preventative treatment
how is CF prophylactically managed
antibiotics, treatment for pancreas (excrine and endocrine), bowls and liver as well as regular clinic review
what happens during exocrine failure in the pancreas
ducts sludged up, failure of secretion of lipases, amylase; digestive failure
how is exocrine failure treated, how does it work and why is it not effective
creon- allows patient to absorb energy, patient avoid taking it to lose weight
describe endocrine failure in the pancreas
destruction of pancreatic islet cells, fatty replacement of pancreatic tisse, leads to diabetes
how is endocrine failure in the pancreas treated
annual oral glucose tolerance test, diabetes treated with CGMs and insulin
what is a common bowl problem in CF and what causes it and its symptoms
distal intestinal obstruction syndrome (DIOS) thick mucus blocks the large and small intestine, similar symptoms to constipation
how is dios treated
gastrograffin, laxido, fluids
how is dios prevented
laxido, hydration, keep moving
how is the liver usually affected in CF
sludging up of hepatic ducts (inta and extrahepatic), portal hypertension (anastamoses, variceal bleeding, hepatic encephalopathy)
what treatment is used to treat liver problems in CF
TIPPS
how are exacerbations managed
in hospital for two weeks antibiotics, physiotherapy (autogenic drainage), adequate hydration, increased dietary input
why are two antibiotics always used in CF
reduce resistance
what oral antibiotics are used in CF
augmentin, fluclox, minocycline, septrin, fusidin, ciprofloxacin
what IV antibiotics are used to treat pseudomonas infections in CF
tazocin, ceftazidime, tobramicin, meropenem, colistin
what IV antibiotics are used to treat staph. Aureus infections in CF
flucloxacillin, tigecycline
what IV antibiotics are used to treat cepacia infections in CF
temocillin
what severity of CF does the G551D lead to
moderatly severe
what class of mutation is the G551D gene
class III
what is the phenotype of the G551D mutation
normal CFTR, delivered to epithelium normally, non functioning channel
how is the G551D treated
open channel, Ivacaftor- improves chloride flow
what is the downside of ivacaftor
very expensve
in recessive disorders like CF do you need to treat both mutations or just one
just one
what are the methods in which a gene can be treated
direct effects on proteins, post-translational modification, increased transcription, gene replacement
how is a F508 delta mutation treated
lumacaftor- binds to CFTR changes its shape so it can pass through golgi- very expensive £200,000 per annum
