Cystic fibrosis Flashcards
What is cystic fibrosis?
CF is an autosomal recessive disorder causing increased viscosity of secretions (e.g. lungs and pancreas).
*one of the most commonest autosomal recessive diseases
What is the pathophysiology of CF?
Mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) on chromosome 7 => codes for cyclic AMP-regulated NA+/Cl- channel.
This increases sodium absorption and causes abnormal chloride secretion in the epithelial cells lining the airways => thicker mucus impairing the function of cilia
Broad range of severity of exocrine gland function leading to:
=> 10% with meconium ileus in neonates
=> prolonged jaundice
=> recurrent chest infection (pneumonia) ± clubbing
=> failure to thrive / slow growth
=> malabsorption (30%): steatorrhoea, failure to thrive
=> Other features (10%): liver disease
Other features of CF:
=> short stature
=> diabetes mellitus
=> delayed puberty
=> rectal prolapse (due to bulky stools)
=> nasal polyps
=> male infertility, female sub fertility
Most patients picked up during newborn screening programmes (heel prick test) but ~5% are missed and diagnosed after 18 years of age.
Antenatal carrier status testing and preimplantation genetic diagnosis after in vitro fertilisation are both possible
How is CF in children diagnosed?
- UK: all newborns are screened for an abnormally raised immunoreactive trypsinogen and 29 CFTR mutations on the Guthrie card (85% coverage)
=> neonatal heel prick test between 5-9 days of age - Sweat test
- Faecal elastase: evidence of abnormal pancreatic exocrine function
- Immunoreactive trypsinogen raised / DNA
- CXR
- Sputum culture (mycobacterium colonisation affects unto 20%)
- Malabsorption screen
- Random glucose
- Spirometry (obstructive pattern with decreased FVC and increased lung volumes)
- Genetic screening: identify CF mutation
Why is a sweat test carried out in children with CF?
What is the diagnostic value?
Why are there so many false positive / negative cases?
- Sweat test: Sweat Cl-
=> <40mmol/L is normal (CF probability low)
=> >60mmol/L diagnostic of CF
*patients with CF have abnormally high Cl- sweat content
2. False positive tests seen in: => atopic eczema, => adrenal insufficiency, => ectodermal dysplasia, => glycogen storage diseases, => hypothyroidism, => dehydration, => malnutrition
*on the first day of life 25% of healthy newborns show a sweat sodium concentration of >65mmol/L but this rapidly decreases the next day
- False negative sweat test seen in:
=> oedema
=> poor test technique
What does CXR show in a child with CF?
=> Hyperinflation
=> Increased anteroposterior diameter
=> Bronchial dilation
=> Cysts
=> Linear shadows
=> Infiltrates
What does spirometry show in a child with CF?
=> Obstructive pattern
=> Decreased FVC
=> Increased lung volumes
How do you manage respiratory symptoms (neutrophilic airway inflammation) in children with CF?
- Start chest physiotherapy x3/day at diagnosis => helps clear mucus and prevent pneumonias
=> Teach parents percussion + postural drainage
=> older children learn forced expiration technique - Infection:
i) Staph aureus, strep. pneumoniae and H. influenza in younger children
ii) Eventually >90% chronically infected with Pseudomonas aeruginosa
iii) Aspergillosis can occur in adolescents
iv) Burkholderia cepacia assoc. with rapid progression of lung disease
=> Treat acute infection after sputum culture using higher than or double standard doses and for weeks in needed.
=> Treat with ticarcillin 80mg/kg (max 3.2kg)/6-8h IV (if aged >1month) + gentamicin or ceftazidime (50mg/kg/8h IV) alone
=> Prophylaxis antibiotics, bronchodilators and medicine to thin secretions (e.g. dornase alpha)
*if very ill, need respiratory support urgently
=> Last resort: bilateral lung transplant in end-stage pulmonary disease in CF
How do you manage gastrointestinal problems and nutrition in CF?
Energy needs rise by 130% in CF due to malabsorption and chronic lung inflammation.
=> steatorrhoea due to pancreatic malabsorption which needs enzymes
i) Pancrex powder for infants and older children
ii) Creon (pancreatic enzymes inc. amylase, lipase, protease) for older children
iii) Omeprazole (or cimetidine or ranitidine) help increase absorption by increasing duodenal pH
=> If the above controls steatorrhoea then a low fat diet is not needed
=> Vitamins still given
- Fine bore nasogastric feeding is required if weight is not maintained
- GI obstruction due to Creon being omitted/inadequate or child dehydrated => meconium ileum equivalent - admit urgently to specialists
Risk of impaired glucose tolerance rises with age and higher for homozygous 508 gene.
Screen early for with oral glucose tolerance test from age 12
=> may need insulin
=> optimise diet, then optimise dose => only try oral hypoglycaemics if diet is satisfactory
How does meconium ileus present in CF?
Failure to pass stool or vomit in the first 2 days of life.
=> distended loops of bowl seen through abdominal wall
=> a plug of meconium may show as a firm mass in one loop
=> tiny bubbles may be seen in the meconium (inspissated)
Management:
=> Nasogastric tube drainage
=> Washout enemas (gastrograffin)
=> Excision of gut containing most meconium
What are the complications of CF?
Haemoptysis
Pneumonia
Pneumothorax
Pulmonary osteoarthropathy
Diabetes mellitus
Cirrhosis
Cholesterol gallstones
Fibrosing colonopathy
Male infertility
What is the prognosis for CF?
=> Death from pneumonia / cor pulmonale
=> most survive to adulthood (median age 31-51 years)
What are the newer management options for CF?
- Recombinant human deoxyribonuclease (rhDNAse)
=> shown to improve lung function
=> reduce number of pulmonary exacerbations - Ivacaftor (CFTR potentiator):
=> improve lung function in g551D mutation - Lung transplantation (heart + lung or double lung):
=> safer
=> consider in deteriorating (FEV1 <30% of expected) despite maximum therapy, good nutrition and no TB / aspergillus - Gene therapy:
=> insert normal copies of CFTR gene into patients, producing CFTR protein (still in research)
