Cystic Fibrosis Flashcards
What is the carrier rate and incidence of CF?
Carrier rate: 1 in 25. Incidence: 1 in 2,500 live births.
What are the complications of CF?
Bronchiectasis (cystic and saccular), tenacious sputum, biliary obstruction and obstructive hepatitis, pancreatic dysfunction (endocrine - CFRDM [cystic fibrosis related diabetes mellitus], exocrine [excess fat in faeces]), infertility for males, psychological issues.
Is CF autosomal recessive?
Yes.
Describe how the trans-membrane conductance regulator doesn’t work in CF.
Chloride channel does not work properly, less chloride is pumped out and more sodium is let in so more water gets in. Leads to dry secretions.
Describe the progression from CTFR DNA mutation to CF.
CTFR mutation -> altered protein -> ion transport -> altered secretions -> blocked ducts and impaired mucosal clearance -> infection, inflammation -> CF.
What does CF cause?
Salty sweat, intestinal blockage, fibrotic pancreas, failure to thrive, recurrent bacterial lung infections, congenital bilateral abscence of vas deferens, filled sinuses, gallbladder and liver disease.
Describe different types of defects in CFTR
Class I - no CFTR synthesis at all. II - CTFR trafficking defect, less CFTR gets to cell membrane. III - dysregulation of CTFR (diminished ATP binding and hydrolysis), IV - defective chloride conductance of channel gating. V - reduced CTFR transcription and synthesis.
What is the CFTR?
Cystic fibrosis transmembrane conductance regulator.
Give a common and uncommon mutation that causes CF.
Common - F508del. Uncommon - G551D.
For a recessive disease, can you have different mutations in each copy of the gene?
Yes.
Who gets tested for CF?
Anyone who had bronchiectasis under 40, upper lobe bronchiectasis, colonisation with staph, infertility or low weight gets a CF genetic test.
How do people with CF miss getting diagnosed?
Don’t present, present out of hours, present sporadically, failure to think about it, loss of continuity in primary care.
Describe some of the difficulties in treating CF.
Massive treatment burden (they take lots of medications), much treatment is preventative, complications can be rapid onset, when they feel sick they think it must be CF but it isn’t always.
What is managed prophylactically in CF?
Antibiotics, pancreas, bowels, liver. Have a regular clinic review.
What antibiotics are used in different CF infections?
Staph aureus - oral flucloxacillin and septrin. Pseudomonas - oral azithromysin; nebulised colomycin, tobramycin, aztreonam; inhaled tobramycin.
How does CF cause pancreas exocrine failure and how is it treated?
Sludged up ducts, failure of secretion of lipases and amylase, digestive failure. Take CREON.
How does CF cause pancreas endocrine failure and how is this managed?
Destruction of pancreatic islet cells, fatty replacement of pancreatic tissue. Have OGTT (oral glucose tolerance test) once a year and CGMS (continuous glucose monitoring), they usually need insulin as they have insulin production failure.
What is distal intestinal obstruction syndrome (DIOS)?
Thick mucus blocks up the intestines, symptoms similar to constipation.
What is the treatment for DIOS and how can you prevent it?
Treatment - gastrograffin, laxido and fluids. Prevention - laxido, hydration and keeping moving.
What are the effects of CF on the liver?
Sludging up of hepatic ducts (intra and extra hepatic), portal hypertension (porto-systemic anastomoses, variceal bleeding, hepatic encephalopathy [causes disturbances of conscioussness]).
What is the treatment of CF in the liver?
TIPSS (transjugular intrahepatic portosystemic shunt) (reduces anastomoses, reduction in bleeding risk, can increase encephalopathy risk).
How can you manage an exacerbation of CF?
Antibiotics, physiotherapy (autogenic drainage, ACBT [active cycle of breathing technique], with and without physiotherapist), adequate hydration, increased dietary input (dietician).
Why do you always give 2 antibiotics in CF?
To reduce resistance.
What antibiotics do you give in CF?
Orals: augmentin, flucloxacillin, minocycline, septrin, fusidin, ciprofloxacin. IVs: for pseudomonas - tazocin, ceftazidime, tobramycin, meropenem, colistin. for staph aureus - flucloxacillin, tigecycline. For cepacia - temocillin.
What are the benefits of giving the patient antibiotics at home?
Well tolerated, safe, saves money and keeps patients working.
What does the G551D mutation do?
Normal CFTR, delivered to epithelium normally, non-functioning channel.
What is ivacaftor and how does it work and what people will it benefit?
CFTR potentiator, improves chloride flow through the CFTR, people with G551D mutation.
What drugs can be used to treat CF with the F508del mutation?
Lumacaftor.
