Cystic fibrosis Flashcards
What is the gene prevalence of cystic fibrosis in Europe?
1:25
What is the disease prevalence of cystic fibrosis in Europe?
(1:25 x 1:25) x 4 = 1:2500 will have CF
Describe the inheritance of CF
Autosomal recessive
Describe the mutation associated with CF
Autosomal recessive mutation on q arm of chromosome 7 for the CF transmembrane conductance regulator (CFTR)
What is the most common deletion associate with CF
phe508del - codon deletion leads to improper folding of protein and it can not leave the ER to be presented on the surface and is instead recognised as faulty and destroyed
Seen in 70% of Northern European CF patients
How does CF affect the CFTR?
Can affect function or the levels of surface expression of the CFTR
What is the function of CFTR?
Active transport for chloride out into the mucus, regulating the liquid volume on epithelial surfaces/in the mucus
In CF, there is reduced Cl efflux and increased Na influx, leading to the development of thick mucus, hard to cough up
Describe neonatal screening for CF
Guthrie heel prick - day 5, CF and PKU
Immunoreactive trypsinogen levels in blood
Mutation analysis
Sweat test - Cl >60= positive for CF
What are the 2 cardinal features of cystic fibrosis?
Pancreatic insufficiency - abnormal stools, failure to thrive
Recurrent bronchopulmonary infections
How do you treat pancreatic insufficiency in CF?
Enteric coated enzyme pellets High energy diet - lots of fats Fat soluble vitamins and minerals H2 antagonist inhibitors Proton pump inhibitors
What are some complications of recurrent bronchopulmonary infections?
Pneumonitis Bronchiectasis Haemoptysis Scarring Abscesses Respiratory failure
How do you prevent infections in CF?
Segregation Airway clearance and adjuncts Mucolytics Prophylactic antibodies e.g. Staph Aureus Annual influenza jabs
How do you treat chronic infections in CF?
Continue Abx
Try and reduce bacterial load
Treat exacerbations
Reduce inflammation - ibuprofen, prednisalone and azithromycin
What is the predicted average life span of CF patients in the 21st century?
> 50yo
What are some other manifestations of CF that can lead to its identification?
GI dysmotility Hepatopathy Upper airway polyps and sinusitis Diabetes Osteopenia Heat exhaustion Bilateral absence of vas deferent Male infertility Vaginal candidiasis and stress incontinence
List some airway clearance techniques
Percussion and drainage
Autogenic drainage
Active cycle of breathing
List some airway clearance adjuncts
Positive expiratory pressure mask
Cornet/flutter
High frequency chest wall oscillation
List some mucolytics
DNase alfadornase
Hypertonic saline
How does undiagnosed CF in adults usually present?
Recurrent pulmonary infections Pancreatic insufficiency GI problems DM Liver disease Osteoporosis Infertility
What do abnormalities in CFTR lead to?
Decreased mucociliary clearance, increased bacterial adherence and decreased endocytosis of bacteria = infections
List some important infectious agents in CF
Pseudomonas aeruginosa
Burkholderia cepacia
Stenotrophomonas maltophilia
Mycobacterium abscessus
Describe Pseudomonas aeruginosa infections in CF
Colonisation increases with age Forms a protective biofilm Rapidly acquired multi drug resistance Reduces life expectancy by 10 years Rapid decline in lung function
Why does colonisation of Pseudomonas aeruginosa increase with age?
Repeat antibiotic use
Environment
Exposure from other CF patients
How do you treat Pseudomonas aeruginosa infections?
Oral ciplofloxacin and nebulised colomycin
If fails:
IV Ceftazidine and nebulised colomycin
