Cystic Fibrosis Flashcards
Parkinson’s is the commonest inherited genetic condition in the UK.
True or False?
False
Cystic Fibrosis
Cystic fibrosis is an ——– ——– condition.
Autosomal recessive
How many people are carriers
1 in 25
1 in 2500 births
97% of cystic fibrosis occurs in the
Caucasian population
How many individuals with CF in the UK?
9000 individuals (approx)
Cystic fibrosis is
the mutation of a gene located on chromosom 7q31, which codes for a protein called cystic fibrosis transmembrane regulator (CFTR)
What is the commonest mutation of CF?
Delta F5-8
Diagram inheritance of CF
CFTR protein
- CF occurs due to a mutation in a gene on the long arm of chromosome 7
- results in defect in the cystic fibrosis transmembrane conductance regulator protein
- CFTR sits in the membrane of epithelial cells and regulates the transport of Cl- through activation of cyclic AMP and through calcium activated chloride channels
- CFTR inhibits transport of sodium through the sodium channels in the epithelial cell membrane and regulates the movement of bicarbonate ions
process of CFTR
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Impact of abnormal CFTR:
- abnormal CFTR protein leads to decreased chloride reabsorption and increased sodium reabsorption
- secretions have high viscosity and reduced water content
- this impedes mucociliary clearance in the bronchi so respiratory secretions are stagnant
- decreased defence from respiratory infections
consequenc of recurring infections in the lungs
bronchiectasis
- recurring infections causes constant inflammation in the lungs, terminal and respiratory bronchioles not major airways
- causes destruction and dilation of the distal airways with mucous impaction, which predisposes to more infection which predisposes to worsening of the inflammation
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bronchiectasis
Common organs affected by CF?
- Respiratory System:
- bronchiectasis
- recurrent respiratory infections
- respiratory infections
- Gastrointestinal System:
- pancreatic insufficiency
- diabetic mellitus
- Skin:
- increased sweat, when exercising can lose a lot of sodium
- Reproductive system:
- infertile
CF process fill out
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Symptoms of upper respiratory tract in CF:
- chronic sinus disease
- nasal polyps
Symptoms of lower respiratory tract:
- chronic cough and sputum
- bronchiectasis (dilated and inflamed bronchi)
- chronic suppurative lung disease (pus)
- colonisation with bacteria
- frequent respiratory infections
- clubbing
Common bacteria causing disease in CF and consequence:
- Staphylococcus aureus
- Haemopilus influenzae
- pseudomonas aeruginosa (grram +)
- burholderia cepacia (gram -)
- colonisation
- difficult to eradicate
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CF: gastrointestinal tract flow chart:
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Impact of CF on gastrointestinal disease:
- defective CFTR leads to abnormal chloride transport in pancrease leads to destruction of pancreas and exocrine insufficiency
- decrease in lipase activity
- decreased absorption of fat in small intestine
- steatorrhoea (fat in tstool, pale and floats)
- decreased water content in intestines leads to thick faecal material leads to intestinal obstruction: “meconium ileus equivalent” in adults as it mimics meconium ileus in neonates”
- COMPLETE
CF presentations in newborn
- meconium ileus
- failure to thrive
- recurrent respiratory infections
Three types/times of screening for CF:
- antenatal
- prenatal
- neonatal
Antenatal screening for CF:
- after birth
- carrier testing
- genetic counselling
Prenatal screening for CF:
- DNA analysis on sample of chorionic villus
- amniocentesis
- allows reproductive decision making
Neonatal screening for CF:
- newborn screening
- Futhrie test
- sweat test
Why is screening for Cf useful?
- early diagnosis and treatment improves outcome
Diagnosis of CF:
- clinical presentation:
- recurrent respiratory infection
- meconium ileus
- Failure to thrive
- positive sweat test = chloride content > 60mmol/L = abnormal
- DNA analysis: genotyping for common mutations
- chest x ray usually abnormal
diagram
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Management of CF:
- specialist centre
- MDT:
- nurse specialists, dieticians, OT, psych, support for family, etc
- CF trust
Treatment of respiratory disease (CF):
- prompt antibiotics for respiratory infections
- intense chest physio to remove mucus; once or twice a day
- nebulised DNAse (breaks down DNA of secretions and bacteria) leads to a decrease in viscosity
- mucolytic drugs
- bronchodilators
- long term oxygen therapy
- lung or heart transplant
Management of pancreatic disease (CF):
- exocrine:
- creaon (pancreatic enzymes)
- multivitamins
- nutritional support (enteral feeding)
- endocrine (diabetes):
- insulin
median survival years diagram
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Potential new treatments for CF:
- gene therapy
- RNA correction
- CTFR modulation
Gene Therapy for CF improves
- Kaftrio: triple therapy
- Potentiator and corrector impact on production and function
- improves symptoms
- improves lung function
- improves survival
