Cystic Fibrosis Flashcards
How many in Caucasian live births
1 in 2000-2500
Commonest mutation
DeltaF508 (70%, is also most severe)
Cause of death in 90%
Respiratory failure
What is the protein affected called and what chromosome is it on
Transmembrane conductance regulator protein (CFTR) on chromosome 7
What goes wrong with CFTR protein
It has reduced chlorine secretion from epithelium and reduce Na absorption from lumen causing reduced airway surface liquid and thick sticky mucus which can cause shearing. Also impaired bacterial killing by neutrophils
5 classes of mutations
1- No synthesis 2- block in processing (delta F508) 3- block in regulation 4- altered conductance 5- reduced synthesis
How is CF usually diagnosed
Antenatal testing by preimplantation genetic diagnosis, Chorionoic villus sampling or amniocentesis. After someone in family is identified or newborn Guthrie bloodspot
Postnatal testing for CF
Sweat testing measures Cl concentration in sweat. Abnormal is >60mm
Two cardinal features of CF
Pancreatic insufficiency and recurrent bronchopulmonary infection
Pancreatic insufficiency
Abnormal stools, failure to thrive, diabetes (classes 4-6 have some pancreatic function)
How much CFTR function do we need to be asymptomatic
5%
Consequences of recurrent bronchopulmonary infections
Pneumonia, bronchiectasis, scarring, abscesses
Why do CF patients have recurrent pulmonary infection
Decrease in mucociliary clearance and bacteria endocytosis, increase in bacterial adherence
Bronchiectasis in CXR
Tramlines and signet rings and mucous plugging and consolidation
Nail clubbing
Low O2
Who manages CF
MDT
Treatment of pancreatic insufficiency
Enteric coated enzyme pellets, high energy diet, fat soluble vitamin and mineral supplements
Treatment of respiratory features in CF
Physio for airway clearance, mucolytics and bronchodilators, antibiotics, azithromycin for inflammation, support
Extra things CF can cause
Diabetes, osteoporosis, pnuemothorax, haemoptysis
Issues with diabetes in CF
Diet compliance is difficult, but insulin helps.
Osteoporosis in CF
1/3 fall in bone mineral density, slower gain and faster loss. Occurs due to malnutrition and low bmi, and vitamin D/K deficiency and cytokines and delayed puberty. Treated with bone protection medication and weight bearing exercises
Pneumothorax in CF
Affects 3-4%, treated same as usual
Haemoptysis in CF
Destruction of bronchial wall, can get chest gurgling. Massive classes as 100mls an hour or over 240mls in 24 hours. Treated with bronchial angiogram and embolisation
Most common organisms in children
Staphylococcus aureus and haemophilus influenzae and Pseudonomas aerigunosa
Most common organisms in adults
Pseudonomas and staphylococcus aureus
Pseudonomas aerigunosa in CF
By 18 years old 80% have it, colonisation increases with age. Forms a biofiolm
New drugs for CF
Ivacaftor,
Ivacaftor/lumacaftor (orkambi)
Ivacaftor/tezacaftor (symkevi)
Help with CFTR production but don’t really benefit lung function
Double lung transplants
If rapid deterioration, FEV1<30%, life threatening exacerbations, survival <2y. 30-40% die on waiting list, survival 62% for 5 years
Contra-indications for lung transplants
organ failure, malignancy, drugs, systemic infection
Median survival of CF patients
40, over 50% in UK are now over 18.
