*CF Flashcards
How many people carry the CF gene?
What type of gene condition is it?
1 in 25
Autosomal recessive
What is the cystic fibrosis trans-membrane conductance regulator gene?
The CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. This protein is activated by ATP and functions as a chloride channel (pumps chloride out of the cell) across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes.
What happens at a biological level if the CFTR gene is faulty?
Due to the fault with CFTR, chloride can’t be pumped out effectively and there is also a negative effect on its coupled channel, the Epithelial Na+ channel (ENAC), causing an increase in Na+ movement into the cell
Water follows sodium causing secretions to be dried out
it also stops sodium being pumped in
What are the consequences in a fault with CFTR? (8)
Salty sweat Intestinal blockage fibrotic pancreas failure to thrive recurrent bacterial lung infections congenital bilateral absence of vas deferens filled sinuses gallbladder anad liver disease
How does a mutation in the CFTR DNA cause cystic fibrosis?
CFTR DNA mutation = abnormal CFTR protein = ion transport abnormalities = abnormal secretions = blocked ducts and impaired mucosal defence = infection and inflammation = cystic fibrosis
How many classes of defects in CFTR are there?
5
Class I defect in CFTR?
No CFTR synthesis
Class II defect in CFTR?
CFTR trafficking defect (most common type)
Class III defect in CFTR?
The CFTR protein makes it to the cell membrane but does not open properly due to binding of ATP meaning chlorine cannot be conducted through it
Class IV defect in CFTR?
CFTR protein reaches the membrane and does partly work but channel is narrowed and therefore does work effectively
Class V defect in CFTR?
Reduced CFTR transcription and synthesis meaning some proteins are made and work effectively but not enough of them are made
Are all mutations equal?
No
What are the basic steps to forming a protein? (5)
DNA is transcribed and spliced
mRNA is translated and modified before being transported
What is a point mutation?
a mutation affecting only one or very few nucleotides in a gene sequence.
What is a missense mutation?
a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid.
What is a frameshift mutation?
Deletion or insertion of a number of bases that is not a multiple of 3.
What mutation do 1 in 25 people have that makes them a carrier of CF and causes 70% of CF cases (Class II)?
What does this do?
F508Del
Causes a deletion of the three nucleotides that comprise the codon for phenylalanine (F) at position 508 on chromosome 7.
What is the mutation that leads to 4-6% of CF cases (class III)? What does this cause? Other name for this gene
G551D
A “missense” mutation: instead of a glycine amino acid (G), aspartate (D) is added
(*for a recessive disease you can have different mutations in each copy of the gene)
“Celtic gene”
When is CF usually diagnosed?
Usually at birth although all babies have only been screened for CF since 2003 (blood test now done) meaning some cases may not have been screened or there may have been a false test result especially in some of the rarer mutations meaning some patients are diagnosed into adulthood
What signs in an adult should make you consider CF? (5)
Bronchiectasis under 40 Upper lobe bronchiectasis Colonisation with staph Infertility Lower weight
What 2 bacteria can CF patients commonly become colonised with?
Staph aureus
Pseudomonas
What treatment is given for staph aureus colonisation? (2)
Oral flucloxacillin or
Oral co-tramoxazole (septrin)
What treatment is given for pseudomonas colonisation? (5)
Oral Azinthromycin 1 of: Nebulised colomycin nebulised tobramycin nebulised aztreonam inhaled tobramycin
What drug do CF patients take for exocrine failure?
CREON - Digestive enzymes
Why do patients with CF get exocrine failure?
Due to their sludged up ducts = failure of secretion of lipase and amylase
Why do patients with CF have endocrine failure?
Destruction of pancreatic islet cells
fatty replacement of pancreatic tissue
How are patients monitored for endocrine failure?
Patients get annual oral glucose tolerance testing
Usually patients require insulin as they have insulin production failure and they therefore continually monitor their glucose
What is distal intestinal obstruction syndrome?
obstruction of the distal part of the small intestines by thickened intestinal content (symptoms similar to constipation)
Treatment of distal intestinal obstruction syndrome? (DIOS) (3)
Gastrograffin
Laxido
Fluids
Prevention of DIOS? (3)
Laxido
Hydration
Keep moving
What can develop in CF patients do to sludging up of hepatic ducts?
How does this present?
Portal hypetension
Porto-systemic anastamoses
variceal bleeding
hepatic encephalopathy
How is portal hypertension treated?
Problem with this?
TIPSS
Can increase encephalopathy risk
What type of physiotherapy do patients with CF carry out?
Autogenic drainage (controlled breathing to love mucus)
active cycle of breathing techniques (ACBT)
(without and without a physiotherapist)
How are exacerbations of CF managed?
Antibiotics
Physiotherapy
Adequate hydration
Increased dietary input (dietician and fridge in room)
Why are patients with CF always given 2 antibiotics?
to reduce resistance
What antibiotics can CF patients be given for exacerbations due to pseudomonas? (5)
Tazocin Caftazidime Tobramicin Metropenem Colistin
What antibiotics are patients given for exacerbations due to Staph Aureus?
Flucloxacillin
Tigecyline
What antibiotic is given for exacerbations due to cepacia?
Temocillin
What oral antibiotics can be given during exacerbations? (6)
Augmentin Flucloxacillin Minocycline Seprfin Fusidin Ciprofloxacin (antibiotics are also given IV)
How often do patients with CF come into hospital planned for antibiotics?
2 weeks of the year
What is OHPAT?
Outpatient and home parenteral antibiotic therapy - patients can get IV antibiotics at home
Life expectancy for a patient with CF?
41
What is the drug that is a CFTR potentiator for class III CF?
Ivacaftor
How is Ivacaftor taken?
Tablet twice a day
What must you not consume whilst on Ivacaftor?
Why?
Grapefruit
It increases its concentration in the blood
If a patient inheritance 2 different types of CF genes, do you need to treat both?
No - only one copy needs treated
therefore Ivacaftor can be used if one of the mutations is G551D and the other is not
What is a drug currently on phase II trial for the treatment of F508del CF?
Lumacaftor - showing promising results
