CYSTIC FIBROSIS Flashcards
Whats the epidemiology of CF?
1 in 25 are carriers
1 in 2500 have CF
Most common in white ethnicity (in the UK 93% are white)
What causes CF?
Mutations in the CFTR gene on the long arm of chromosome 7
Mutations may result in no functional CFTR, abnormal regulation o the channel, abnormal conduction of Cl- through the channel, defective protein processing etc,..
What does the CFTR gene code for?
Epithelial chloride channels which are regulated by cAMP
What’s the pathogenesis of CF?
Defects in CFTR channels = defects in normal Cl- transport = dehydration and depletion of airway surface liquid = mucociliary dysfunction = impaired mucus clearance, airway obstruction and predisposition to infection -> can lead to chronic bronchitis, damage to bronchi and even bronchiectasis
Similar issues are seen in other organs e.g. impaired biliary and pancreatic drainage due to vicious secretions = impaired digestion and malabsorption. This is why pancreatic insufficiency, diabetes and liver impairment is common in pt with CF
How is CF detected?
In the UK, CF is universally screened for as part of the newborn heel prick test conducted at day 5 after birth
The diagnosis may even be made prior to this based on USS findings and chorionic villus sampling and amniocentesis
5% of pt are diagnosed after 18
What are the clinical manifestations of CF?
neonatal period (around 20%): meconium ileus, less commonly prolonged jaundice. Parents may report their child tastes particularly salty when they kiss them
recurrent chest infections and thick sputum production (40%)
malabsorption (30%): steatorrhoea, failure to thrive
other features (10%): liver disease
Others: short stature, diabetes, delayed puberty, rectal prolapse, nasal polyps, male infertility, female sub fertility
What maliganncies are CF patients at risk of?
Small and large intestines
Pancreas
Biliary treee
Hepatocellular if they have cirrhosis
Which bacteria commonly colonise in patients with CF?
Staphylococcus aureus
Pseudomonas aeruginosa
Less common:
Burkholderia cepacia
Aspergillus
Klebsiella pneumonia
E.coli
Haemophilus influenza
What is the CFTR gene?
cystic fibrosis transmembrane conductance regulatory gene
Whats the most common variant of the CFTR gene mutation?
Delta-F508
Why can CF cause male infertility?
The mutation can lead to congenital bilateral absence of the vas deferens
Whats the inheritance pattern for CF?
Autosomal recessive
What is Meconium ileus?
Meconium is the black stool that should be passed within 24 hours of birth
In 20% of CF babies, the Meconium is thick and sticky so it can obstruct the bowel = Meconium ileus
Presents as not passing Meconium within 24 hours, abdominal distension and vomiting
How do you diagnose CF?
Gold standard - Sweat test - patients with CF will have abnormally high Cl- in their sweat i.e. >60mEq/L
What can cause a false negative sweat test?
Skin oedema e.g. due to hypoalbuminaemia from pancreatic exocrine insufficiency
