CF Flashcards
CF stats
1/2000-1/2500 in Caucasian live births
1/25 carriers
>2000 possible mutations, different mutations causing different types of disease
most common CF mutation
delta F508 - CFTR (transmembrane conductance regulator protein) in chromosome 7
- this is also the most severe type and is associated with liver disease
what does CTFR protein do?
allows Cl- to flow out of the lung epithelium, letting Na+ flow in as a response. This will be followed by subsequent flow of H2O out of the cells, hydrating the mucous layer and on top and making it easy to clear by cilia.
without this, there would be abnormal transport of Cl-/Na+ and result in reduced airway liquid and sticky mucous –> shearing of epithelium, collapse of cilia layer and infection–>inflammation–>scar tissue, also reduces neutrophils activity due to reduced Cl- concentration.
but there is heterozygous advantage of increased resistance to salmonella and cholera
6 classes of CF mutations (class 6 not listed)
- 12%, G542X, no CTFR synthesis
- 87% (most common), delta F508, block in processing of CTFR protein
- 5%, G551Db, block in regulation
- 5%, R117H/D1152H, altered conductance
- 5%, 3849+10kbC–>T5T/A455E, reduced synthesis
3 stages of screening for CF
- antenatal
- neonatal
- postnatal
tests done in antenatal screening
(done after identification of CF in parents or sibling)
- preimplantation genetic diagnosis (from blastocyst)
- chorionic villus sampling (from placenta)
- amniocentesis (from amniotic fluid)
tests done in neonatal screening
- newborn blood spot day 5 (Guthrie test): if positive, refer to clinical assessment and sweat test
tests done for post natal screening
- sweat test: (if sweat chloride> 60mmol/L, high chance of CF 40-59, inconclusive <39 unlikely to be CF) - do faecal elastase test of confirm
10 systemic effects of CF
- pancreatic insufficiency effect
- recurrent bronchopulmonary infection
- type II diabetes
- osteoporosis
- pneumothorax
- haemoptysis
- finger clubbing
- arthropathy
- vasculitis
- bronchiectasis
effects of pancreatic insufficiency
might be useful to know that they normally secrete lipase which digests fat
- abnormal stool (pale, fatty, foul-smelling)
- failure to thrive (deficiency of fat soluble vitamins)
- diabetes
- classes 1-3 CF have pancreatic insufficiency while classes 4-6 have some pancreatic function (you actually only need 5% of the pancreas to be working to be asymptomatic)
recurrent bronchopulmonary infections effects
ex. pneumonia, bronchiectasis
- airways become stiff, dilated from chronic inflammation, would eventually result in obstruction, which leads to infection, scarring, abscesses.
(happens in a cycle)
causes of bronchopulmonary infections (side effects of nonfunctional CFTR protein)
- decreased mucociliary clearance from electrolyte and water transport problems, like with CGFR mutation (causes the cilia to become damaged)
- increased bacterial adherance to thick mucous
- shearing and infections caused by thick mucous against epithelium
- decreased encocytosis due to decreased neutrophil acitivity
progression of bronchopulmonary infections
progressive bronchietasis (this leads to infection) –> recurrent LRTI (begins to suffer from lung function) –> progressive airflow obstruction due to fibrosis and scarring (increasing exertional dyspnoea, survival related to FEV1)–> resp failure (nocturnal non invasive ventilation or even lung transplant needed)
4 CXR signs of bronchiectasis
- tramlines
- signet rings (cross section scans)
- mucous plugging
- consolidation
is finger clubbing present in CF?
YES
due to low O2 in the blood
this is also present in other diseases like CVS, liver, AIDS, inflammatory bowel disease
