Cystic Fibrosis Flashcards
What is cystic fibrosis?
https://www.youtube.com/watch?v=BhFpFiZumS0
In cystic fibrosis (CF) there is an alteration in the viscosity and tenacity of mucus produced at epithelial surfaces due to a genetic defect. The classical form of the syndrome includes bronchopulmonary infection and pancreatic insufficiency, with a high sweat sodium and chloride concentration
How is the mode of inheritence of the gene mutation inherited in cystic fibrosis?
Autosomal recessive inheritence
What gene is the mutation present on?
CFTR gene - Chromosome 7
What is the mutation that is most commonly present on the CFTR gene?
Specific deletion at position 508 in the amino acid sequence [ΔF508] – which results in a defect in a transmembrane regulator protein
What is the purpose of the CFTR gene?
Encodes the protein that forms the cystic fibrosis transmembrane conductance regulator.
What is the function of the CF transmembrane conductance regulator?
CFTR protein functions as a chloride channel pumping Cl- ions out of the cell. This regulates the liquid volume present on the epithelial surface by directly modulating Chloride efflux and indirectly modulating sodium influx via ENaC.
When normally functioning, the viscosity of the mucus allows cilia to function properly. It traps pathogens and debris to be transported via the mucociliary escalator, and allows leucocytes to move into the mucus
What occurs when the CFTR transmembrane protein becomes altered due to mutation in the CFTR gene?
Dysfunction in the CFTR gene creates an imbalance in the electrolyte concentrations across the cell membrane, resulting in an abnormally thick mucus (due to decreased Cl- efflux and increased Na+ influx).
Due to increased viscosity, the cilia become flattened, the gap of fluid between the mucus and the cell membrane becomes less, and the mucociliary escalator ceases to function appropriately. The reduction in distance between the mucus and the cell membrane allows pathogens a greater chance to adhere to the surface of the cell. It also traps extravasating neutrophils and prevents them from performing their normal immune function via phagocytosis.
What test is done on newborns to Screen for CF?
Guthrie test
What are features of CF in a neonate?
- Failure to thrive
- Meconium Ileus
- Rectal prolapse
- Gut atresia
- Obstructive jaundice
What are respiratory features of CF in infants and young children?
- Cough
- Wheeze
- Recurrent infections
- Haemoptysis
- Pneumothorax
- Bronchiectasis
- Resp. failure
- Cor pulmonale
What are gastrointestinal features of CF in infants and young children?
- Pancreatic insufficiency
- Distal intestinal obstruction syndrome
- Gallstones
- Cirrhosis
- GORD
- Constipation
- Can have Crohn’s or coeliac
What features suggest pancreatic insufficiency?
- Diabetes mellitus
- Steatorrhoea
What other features (besides respiratory and GI) can present in CF?
- Male infertility
- Osteoporosis
- Arthritis
- Vasculitis
- Nasal polyps
- HPOA
- Sinusitis
- Vaginal candidiasis
What are signs of CF?
- Clubbing
- Cyanosis
- Bilateral coarse crackles
What does the Guthrie test check for?
- Maple Syrup Urine Disease
- Cystic Fibrosis
- Congenital hypothyroidism
- Phenylketonuria
- MCADD
- Sickle Cell Disease
What investigations (apart from guthrie test) could you do if you suspected CF?
- Bloods - FBC, U+E’s, LFTs, Clotting, Vitamin A, D, E, glucose tolerance test
- Sweat test
- Chorionic villous sampling
- Faecal Elastase
- CXR
- Bacteriology - if infection present
- Abdo ultrasound
- Spirometry
What is the theory behind the sweat test for CF?
For normal salt reabsorption to occur, individual ions of sodium and chloride must be taken from the sweat and moved back into cells of the sweat duct. For sweat to be produced with the proper concentrations of sodium and chloride, sodium channels and chloride channels (CFTRs) must work properly to remove ions from the sweat.
In CF, the CFTR chloride channel is defective, and does not allow chloride to be reabsorbed into sweat duct cells. Consequently (by proxy), more sodium stays in the duct cells, and more chloride remains in the sweat. The concentration of chloride in sweat is therefore elevated in individuals with cystic fibrosis, and this can be used to screen for CF.
What is the pathophysiology behind recurrent respiratory infection in CF?
What is the most commonly implicated organism in chest infections in children with CF?
Staph aureus
What is the most common cause of bacterial lung infection in adults with CF?
P. Aeruginosa
What organisms can cause infection in CF patients?
- P. aeruginosa
- Staph aureus
- H. influenzae
- Burkkholderia cenocepacia
- Stenotrophomonas maltophila
- Mycobacterium Abscessus
