Cystic fibrosis Flashcards
What are the genetic problems associated with CF
- 1/25 carriers
- 1 in 2000-2500 live births
- Commonest mutation 𝚫F508
What type of genetic disorder is CF
Autosomal recessive disorder
Most common in Caucasian
Where is the mutation
transmembrane conductance regulator protein (CFTR) on Chr 7
What does this protein normally do
normal protein allows chloride to move out of cell
no mucus build up
What does a mutated protein cause
abnormal protein= chloride stuck in cell
Na+ and H2O stay with chloride
mucus build up outside of cell
What is the effect of mucus build up
Mucus collects bacteria
↓ mucociliary clearance
Mucus sticks to mucosa, causing inflammation + ↑ bacterial access which decreases bacterial killing
What are the 6 classification of mutaion in CTFR
1-3 severe disease
- Pancreatic insufficient
- 𝚫F508 class 2= severe disease
4-5 milder disease
- Some pancreatic function
What are the complications of CFTR
Pancreatic insufficency
Repeated Lung infection
Progressive bronchiectasis
Scarring
Abscesses
Type 2 DM
Osteoporosis
What is the effect of pancreatic insuffeciency
- Lack of pancreatic enzymes (trypsin, colistin)
- Fat Malabsorption
- Abnormal stool-steatorrhea
- Failure to thrive
What is the effect of repeated lung infection
- Pseudomonas aeruginosa
- Burkholderia cepacia (genomovar III)
- Non tuberculous mycobacteria
What is the effect of Osteoporosis
Decrease bone mineral densisty
Increased fracture risk
What are the other effects of these complications
Progressive resp decline
Chronic sputum production
Survival related to FEV1
Increasing SOB
What are some less common complications of CFTR
- Risk of pneumothorax
- Nail clubbing
- Male infertility (NO vas deferens)
- Meconium ileus
- Haemoptysis due to bronchial wall destruction
What does antenatal testing involve
- Pre-implantation genetic diagnosis
- Chorionic villus sampling
- Amniocentesis
What does neonatal testing involve
New-born bloodspot day 5 (Guthrie test)
- if +ve-> clinical assessment & sweat test
Sweat test- measure chloride concentration in sweat, >60 mmol/l= abnormal