Cystic Fibrosis Flashcards
What is the significance of the chloride channel in CF?
In normal people, Cl - passes chloride form the cell into the membrane, it is an ATP regulator. Water will follow sodium so if the cell pushes out chloride, then less sodium will be pumped into the cell and then the lumen outside of the cell will stay hydrated
In CF, less chloride is pumped out and so more sodium is pumped into the cell and so more water goes into the cell and is not in the extrcellular membrane, creating dry secretions, thick mucus all over the body
What are the consequences of the chloride channel not working in CF?
Salty sweat Intentistal blockage Fibrotic pancreas Failure to thrive Recurrent bacterial lung infections Congenital bilateral absence of vas deferens Filled sinuses Gallbladder and liver disease
What is the mechanism of disease in CF?
CFTR DNA mutated Altered CFTR protein Altered ion transport Altered secretions Blocked ducts and impaired mucosal defence Infection and inflammation CF
Where is CFTR synthesised?
In the nucelus where is moves to the golgi apparatus where it is packaged up and then moves to the membrane where it acts as a chloride and sodium ion channel
What is class 1 CFTR mutation?
There is a nonesense, large frameshift or deletion that causes a premature stop codon meaning no CFTR protein is synthesized. Foetuses with this mutation generally do not survive pregnancy and die in utero
What is class 2 CFTR mutation?
Some missence and in-frame deletions disrupt the CFTR folding and trafficking to the surface of the cell. This results in either none or very little CFTR being transported to the surface of the cell. This is a severe form of CF
What is class 3 CFTR mutations?
Some missense mutations alter the sequence of amino acids, disrupting the regulation of CFTR, which means it will no longer open to channel agonists. This results in a reduced or lack of CTFR channel opening.
What is class 4 CFTR mutations?
Some missence mutations i.e. the substitution of an amino acid result in changes to the structure of the CFTR protein that forms the channel. A misshaped CFTR pore can restrict the movement of Cl- ions through the channel. This is known as conductance defect
What is a class 5 CFTR mutation?
Some missense mutations result in alternative RNA splicing disrupting the mRNA processing. This results in extremely reduced CFTR being produced in the cell, resulting in less CTFR protein at the surface of the cell
How can you work out how serious a CF mutation is?
If you sequence the gene, then you can work out which class the mutation belongs to and therefore how serious the mutation is
What is the commonest mutation that causes CF?
F508del
What patients in the bronchiectasis clinic will get a CF test?
Those with bronchiectasis under 40 Those with upper love bronchiectasis Those with a colonisation with staph Those who are infertile Those with a low weight
What is the prophylactic management of CF?
Antibiotics Pancreas - exocrine and endocrine Bowels Liver Regular clinic review
What antibiotics are given prophylactically in CF?
Staph aureus colonisation: oral fluclox and oral septrin
Pseudomonas colonisation: oral azithromycin, nebuliased colomycin, nebulisd tobramycin, nebuliased aztreonam, inhaled tobramycin
What is the prophylactic treatment of pancreas related problems in patients with CF?
Exocrine failure - blocked ducts, failure of secretion of lipases and amyase, digestive failure. Patients are prescribed creon but don't like taking it as it will make them put on weight Endocrine failure - destruction of pancreatic islet cells and the fatty replacement of pancreatic tissue. Annual OGTT (oral glucose tolerance test) and CGMS (continous glucose monitoring). They will usually need insulin as they have insulin production failure
