Cystic Fibrosis Flashcards
What causes Cystic Fibrosis?
It is an autosomal recessive disorder.
It is caused by mutations in genes. Different mutations cause different types of disease.
There are over 2000 mutations that can cause cystic fibrosis. More are being discovered.
What is the most common mutation that causes CF?
delta (triangle) F508
What type of mutations cause Cystic fibrosis and how?
Mutations in the transmembrane conductance regulator protein (CFTR) which is coded on chromosome 7 occur.
This causes a reduced chloride secretion from the epithelium and a reduced Na absorption from the lumen.
What does the abnormal transport of chloride and sodium cause?
Reduced airway surface liquid, so the mucous layer, no longer sits on a layer of water, so it will sticky to the mucosa.
Thick sticky mucous
Cilia can be sheared
It impairs the killing of bacteria, done by neutrophils, as neutrophils require a normal chloride concentration to work properly.
How many classes of mutation are there and what does the classification depend on?
There are 6 classes of classification.
The classification depends on the amount of the protein produced, whether it is processed/moved to the membrane properly and whether the protein functions correctly.
What does a Class I mutation mean?
No synthesis of the protein
What does a Class II mutation mean?
There is a block in the processing of the mutation.
What does a Class III mutation mean?
There is a block in the regulation of the protein.
What does a Class IV mutation mean?
Altered conductance of the protein.
What does a Class V mutation mean?
Reduced synthesis
What kind of mutation is the most common mutation, the Delta F508 mutation?
It is a Class II mutation, so is a block in the processing of the protein.
What percentage of CF is caused by the Delta F508?
87%
How is Cystic fibrosis tested for?
Antenatal testing;
Pre-implantation genetic diagnosis
Chronic villous sampling (removal of a small sample of cells from the placenta)
Amniocentesis (amniotic fluid is removed from the uterus for testing)
Neonatal screening;
Newborn bloodspot day 5 (Guthrie test)- if positive will be referred for clinical assessment and sweat test.
What is a sweat test?
It measures the concentration of chloride that is excreted in sweat. In CF this will be elevated.
(this test is less reliable in adults, as CF sweat ranges can be normal once you are older)
What is abnormal result for chloride level?
> 60 millimoles per litre
40-59 is inconclusive
