Cystic Fibrosis Flashcards
Define cystic fibrosis.
Autosomal recessive condition characterised by recurrent lung infections, malabsorption and failure to thrive.
Explain the aetiology/risk factors for cystic fibrosis.
Common genotype (70–80%): Phenylalanine deletion at position 508 (DF508) results in a defective gene on chromosome 7 q.
There are more than 900 known mutations of this gene.
Defective gene codes for abnormal transport protein (CFTR) in the cell membrane.
Associations: Obstructive azoospermia.
What is the pathophysiology of cystic fibrosis?
Genetic: Defective CFTR acts as cAMP chloride channel blocker. Reduced chloride transport accompanied by reduced Na and H2O transport across epithelial cells results in dehydrated viscous secretions causing luminal obstruction, destruction and scarring of exocrine glands.
Respiratory: Lung is normal at birth but as it matures, mucous gland hyperplasia occurs, and thick viscid mucus is formed in the small airways. Patients are predisposed to chronic infection with Staphylococcus aureus, Haemophilus influenzae and Pseudomonas which leads to areas of fibrosis, consolidation and bronchiectasis.
Pancreatic: Exocrine enzyme insufficiency causes malabsorption and steatorrhoea.
Summarise the epidemiology of cystic fibrosis.
1/2500 live births.
More common in Caucasians.
What are the presenting symptoms of cystic fibrosis?
Neonatal: Meconium ileus (bowel obstruction by thick meconium).
Infancy: Recurrent chest infections, steatorrhea, failure to thrive, developmental delay.
Older children: Asthma, ABPA, recurrent chest infections.
What are the signs of cystic fibrosis?
Signs of malnutrition: Muscle mass decreased, protuberant abdomen.
Respiratory: Hyperinflation, coarse crepitations, expiratory wheeze, wet cough.
Others: Clubbing, bilateral absence of the vas deferens
What are investigations for cystic fibrosis?
Sweat test (gold standard): Sweat Cl- of >50 mmol/L and Na2+ of >60 mmol/L by pilocarpine iontophoresis, weight of sweat >100 mg on 2 occasions.
Lung function: Obstructive picture with air trapping and hyperinflation (Decreased FEV1, Increased Total lung capacity).
Guthrie’s test: Increased serum immunoreactive trypsin (all UK newborns are now screened).
Antenatal tests: First trimester CVS (95% sensitivity). Second trimester decrease intestinal ALP in amniotic fluid (90% sensitivity).
What is the long-term management for the respiratory symptoms of cystic fibrosis?
Specialist physiotherapy sessions to mobilise secretions. This can include a high-frequency oscillatory vest device (VEST therapy).
Inhaled bronchodilator (salbutamol)
Inhaled mucolytic (Hypertonic saline or dornase alfa)
Inhaled tobramycin for chronic Pseudomonas infection.
Inhaled corticosteroid
Ivacaftor – CFTR potentiator (only useful in G551D gene mutations).
Last line would be to consider lung transplant .
What is the long-term management for the GI symptoms of cystic fibrosis?
Specialist dietician
In pancreatic insufficiency give pancreatin.
Can also give PPIs and fat-soluble vitamin supplementation.
In Liver disease give urosdeoxycholic acid to prevent gallstone development.
In GORD give PPIs
Consider Ivacaftor in specific CFTR mutations.
What is the long-term management for non-specific symptoms of cystic fibrosis?
Psychological support and counselling for carer and patient.
Specialist nurses.
Specialist pharmacists.
Regular follow-ups and monitoring for complications.
Immunizations especially for influenza and pneumococcus.
What is the acute management for meconium intestinal obstruction?
Lactulose or any water-soluble contrast enema + osmotic agent.
NG decompression if still obstructed
Surgery if peritonitc
What is the mangement for acute respiratory distress in cystic fibrosis?
Oral antibiotic if mild exacerbation, IV if not.
Increased chest physiotherapy
Bronchodilator, mucolytic.
What are the possible complications of cystic fibrosis?
Respiratory: Bronchiectasis, cor pulmonale, pneumothorax, hemoptysis.
GI: Cirrhosis, portal hypertension, distal intestinal obstruction syndrome; viscid mucofaeculent material obstructs the bowel.
Endocrine: DM, decreased fertility. 99% of males are infertile due to obstruction and abnormal development of vas deferens. Females are often sub fertile but there have been many successful pregnancies.
Psychological
What is the prognosis of cystic fibrosis?
Most sufferers now survive into adult life (median survival 40 years). Children with Pseudomonas colonization have a 2–3-fold increased mortality over 8 years.
