Cystic fibrosis Flashcards
What is CF?
Cystic fibrosis (CF) is an autosomal recessive genetic condition affecting mucus glands. It is caused by a genetic mutation of the cystic fibrosis transmembrane conductance regulatory gene on chromosome 7. There are many variants of this mutation, the most common is the delta-F508 mutation. This gene codes for cellular channels, particularly a type of chloride channel. Around 1 in 25 are carriers of the mutation and 1 in 2500 children have CF.
What are the consequences of the mutation?
-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
How does CF present?
ystic fibrosis is screened for at birth with the newborn bloodspot test.
Meconium ileus is often the first sign of cystic fibrosis. The first stool that a baby passes is called meconium. This is usually black and should be passed within 24 hours of birth. In about 20% of babies with CF, the meconium is thick and sticky, causing it to get stuck and obstruct the bowel. This is called meconium ileus, and is practically pathognomonic for cystic fibrosis. This 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?
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
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
How does the sweat test work?
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 diagnostic chloride concentration for cystic fibrosis is more than 60mmol/l.
What are the common microbial colonisers in CF?
Staphylococcus aureus
Haemophilus influenza
Klebsiella pneumoniae
Escherichia coli
Burkhodheria cepacia
Pseudomonas aeruginosa
Pseudomonas Aeruginosa treatment?
Once patients become colonised with pseudomonas, it can be very difficult to get rid of. Often, these bacteria can become resistant to multiple antibiotics. Colonisation with pseudomonas leads to a significant increase in morbidity and mortality in patients with CF. Pseudomonas colonisation can be treated with long term nebulised antibiotics such as tobramycin. Oral ciprofloxacin is also used.
Management of CF?
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
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
monitoring?
Patients with cystic fibrosis are managed and followed up in specialist clinics, typically every 6 months. They require regular monitoring of their sputum for colonisation of bacteria like pseudomonas. They also need monitoring and screening for diabetes, osteoporosis, vitamin D deficiency and liver failure.
Prognosis?
Life expectancy is improving and currently the cystic fibrosis trust gives a median life expectancy of 47 years.
90% of patients with CF develop pancreatic insufficiency
50% of adults with CF develop cystic fibrosis-related diabetes and require treatment with insulin
30% of adults with CF develop liver disease
Most males are infertile due to absent vas deferens
