Cystic fibrosis Flashcards
Pathophysiology of CF?
Cystic fibrosis (CF) is an autosomal recessive disorder causing increased viscosity of secretions (e.g. lungs and pancreas). It is due to a defect in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which codes a cAMP-regulated chloride channel
Organisms which may colonise CF patients?
- Staphylococcus aureus
- Pseudomonas aeruginosa
- Burkholderia cepacia
- Aspergillus
The key consequences of the cystic fibrosis mutation are?
Thick pancreatic and biliary secretions that cause blockage of the ducts, resulting in a lack of digestive enzymes such as pancreatic lipase in the digestive tract
Low volume thick airway secretions that reduce airway clearance, resulting in bacterial colonisation and susceptibility to airway infections
Congenital bilateral absence of the vas deferens in males. Patients generally have healthy sperm, but the sperm have no way of getting from the testes to the ejaculate, resulting in male infertility
Cystic fibrosis is a common exam topic and is a favourite of examiners for testing your knowledge of genetic inheritance. Remember that cystic fibrosis is autosomal recessive. A popular scenario is: both parents are healthy, one sibling has cystic fibrosis and a second child does not have the disease, what is the likelihood of the second child being a carrier? We know the child doesn’t have the condition, so the answer is two in three.
TOM TIP
How does CF normally present?
Screened for at birth with the newborn bloodspot test
Meconium ileus is often the first sign of CG, 20% of babies with CF the meconium is thick and sticky, causing it to get stuck and obstruct the bowel. Presents as not passing meconium within 24 hours, abdominal distention and vomiting.
If cystic fibrosis is not diagnosed shortly after birth it can present later in childhood with typical signs and symptoms, recurrent lower respiratory tract infections, failure to thrive or pancreatitis.
Symptoms of CF?
Chronic cough
Thick sputum production
Recurrent respiratory tract infections
Loose, greasy stools (steatorrhoea) due to a lack of fat digesting lipase enzymes
Abdominal pain and bloating
Parents may report the child tastes particularly salty when they kiss them, due to the concentrated salt in the sweat
Poor weight and height gain (failure to thrive)
Signs of CF?
Low weight or height on growth charts
Nasal polyps
Finger clubbing
Crackles and wheezes on auscultation
Abdominal distention
Causes of clubbing in children?
Hereditary clubbing
Cyanotic heart disease
Infective endocarditis
Cystic fibrosis
Tuberculosis
Inflammatory bowel disease
Liver cirrhosis
There are three key methods for establishing a diagnosis:
Newborn blood spot testing is performed on all children shortly after birth and picks up most cases
The sweat test is the gold standard for diagnosis
Genetic testing for CFTR gene can be performed during pregnancy by amniocentesis or chorionic villous sampling, or as a blood test after birth
What is the Sweat test?
The sweat test is the key investigation to remember for cystic fibrosis. It is the gold standard for confirming the diagnosis.
A patch of skin is chosen for the test, typically on the arm or leg. Pilocarpine is applied to the skin on this patch. Electrodes are placed either side of the patch and a small current is passed between the electrodes.
This causes the skin to sweat. The sweat is absorbed with lab issued gauze or filter paper and sent to the lab for testing for the chloride concentration.
The diagnostic chloride concentration for cystic fibrosis is more than 60mmol/l.
Common microbial colonisers in CF?
Patients with cystic fibrosis struggle to clear the secretions in their airways. This creates a perfect environment with plenty of moisture and oxygen for colonies of bacteria to live and replicate. Examples of common colonisers are:
Staphylococcus aureus
Haemophilus influenza
Klebsiella pneumoniae
Escherichia coli
Burkhodheria cepacia
Pseudomonas aeruginosa
TOM TIPs:
The key colonisers to remember for your exams are staph aureus and pseudomonas aeruginosa
Patients with CF take long term prophylactic flucloxacilin to prevent staph aureus infection
Pseudomonas should be remembered as a particularly troublesome coloniser that is hard to treat and worsens the prognosis of patients with CF
About Pseudomonas Aeruginosa infections?
Once patients become colonised with pseudomonas, it can be very difficult to get rid of
Often they can become resistant to multiple antibiotics
Colonisation with pseudomonas leads to a significant increase in morbidity and mortality in patients with CF
The general advice is now to avoid contact with other children with cystic fibrosis. Cystic fibrosis clinics have separate clinic rooms for children with pseudomonas to minimise the risk of transmission.
Pseudomonas colonisation can be treated with long term nebulised antibiotics such as tobramycin. Oral ciprofloxacin is also used.
Cystic fibrosis will be managed by the specialist MDT. There are many aspects to management:
Chest physiotherapy several times a day is essential to clear mucus and reduce the risk of infection and colonisation
Exercise improves respiratory function and reserve, and helps clear sputum
High calorie diet is required for malabsorption, increased respiratory effort, coughing, infections and physiotherapy
CREON tablets to digest fats in patients with pancreatic insufficiency (these replace the missing lipase enzymes)
Prophylactic flucloxacillin tablets to reduce the risk of bacterial infections (particularly staph aureus)
Treat chest infections when they occur
Bronchodilators such as salbutamol inhalers can help treat bronchoconstriction
Nebulised DNase (dornase alfa) is an enzyme that can break down DNA material in respiratory secretions, making secretions less viscous and easier to clear
Nebulised hypertonic saline
Vaccinations including pneumococcal, influenza and varicella
Other Treatment Options: CF:
Lung transplantation is an option in end stage respiratory failure
Liver transplant in liver failure
Fertility treatment involving testicular sperm extraction for infertile males
Genetic counselling
