Cystic fibrosis Flashcards
What is the inheritance of cystic fibrosis (CF)?
Autosomal recessive condition
What mutation causes CF and how does it affect the body?
- Causative mutation = mutation (delta-F508) in the CF transmembrane conductase regulator (CFTR) gene on chromosome 7
- This mutation leads to a combination of defective cholride secretion & increased Na absorption which affects cellular activities. Resulting in increased viscocity of secretions e.g. lungs & pancreas. This also affects antibacterial defences predisposing to infection & bronchiectasis
What are the consequences of CF?
- Salty sweat (high Na)
- Pancreatic insufficiency (fibrotic pancreas) - due to increased viscocity of secretions causing stagnation or secretions in the pancreas
- Biliary disease - due to bile becoming concentrated, causing plugging & local damage
- GI disease (intestinal blockage) - due to intraluminal water deficiency because of low volume secretions of increased viscocity from biliary system & pancreas
- Respiratory disease (recurrent bacterial lung infections, filled sinuses) - due to dehydration of airway surfaces reducing mucociliary clearance & favouring bacterial colonisation, local bacterial defences are also impaired by local salt concentrations
- Infertility - due to congenital bilateral absence of vas deferens
- Failure to thrive
What are the typical presenting features of CF ?
Neonatal:
- Meconium ileus
- Failure to thrive
- & less commonly prolonged jaundice
Children & young adults:
- Resp - cough, wheeze, recurrent infections, bronchiectasis (chronic sputum production)
- GI - pancreatic insufficiency (DM, steatorrhoea, failure to thrive), distal intestional obstruction (meconium ileus equivalent), gallstones, liver disease (cirrhosis)
- Additional features - short stature, male infertility (& female subfertility), delayed puberty, nasal polyps, sinusitis, rectal prolapse (due to bulky stools)
When are most patients diagnosed with CF?
Most are picked up during newborn screening programmes or early childhood, but around 5% are diagnosed after 18 y/o
What are the signs of CF ?
- Finger clubbing
- Cough or purulent sputum
- Bilateral coarse crackles
- Wheeze
- FEV1 showing obstructive pattern
How is CF diagnosed ?
- 1st line = sweat test (for children & young adults) - a Cl- conc. >60 indicates CF)
- OR a CF gene test (for adults)
What is the general management of CF ?
If evdience of lung disease offer mucoactive agent:
1st line = rhDNase OR 1st line for children & young people who cannot tolerate rhDNase & hypertonic NaCl = mannitol dry powder
2nd line = rhDNase + hypertonic NaCl or hypertonic NaCl alone
- Regular (at least twice daily) chest physiotherapy and postural drainage. Deep breathing exercises are also useful
- Prophylactic Abx’s with flucloxacillin used to prevent Staph.A infections in children & to prevent secondary infections when patient has an acute viral resp infection
- High calorie diet, including high fat intake*
- Patients with CF should try to minimise contact with each other to prevent cross infection with Burkholderia cepacia complex and Pseudomonas aeruginosa
- Vitamin supplementation
- Pancreatic enzyme supplements taken with meals
- Heart and lung transplant
What is used to treat cystic fibrosis patients who are homozygous for the delta F508 mutation?
Orkambi = lumacaftor + ivacaftor
Think harambi but different
If a patient with CF has evidence of lung disease what treatment is provided ?
If evdience of lung disease offer mucoactive agent:
- 1st line = rhDNase OR 1st line for children & young people who cannot tolerate rhDNase & hypertonic NaCl = mannitol dry powder
- 2nd line = rhDNase + hypertonic NaCl or hypertonic NaCl alone
When are prophylactic Abx’s used in patients with CF and what antibiotics are used ?
- Prophylactic Abx’s with flucloxacillin used to prevent Staph.A infections in children & to prevent secondary infections when patient has an acute viral resp infection
- Abx’s also used for infective exacerbations but the Abx will depend on the organism
If a CF patient has chronic pseudomonas aerginosa colonisation what treated is provided ?
Nebulised colistemethate sodium or tobramycin
If a patient with CF develops respiratory failure what should be done ?
They should be listed for heart & lung transplantation
What is the treatment of nasal polyps in patients with CF ?
- 1st line = nasal steroids
- 2nd line = polypectomy
What is the treatment of distal intestinal obstruction syndrome in someone with CF ?
Tx = Hydration + gastrograffin + laxido
