Cystic Fibrosis Flashcards
What is cystic fibrosis (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.
What is the pattern of inheritance of CF?
CF is an autosomal recessive genetic condition.
Briefly describe the pathophysiology of CF
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.
How common is CF?
Around 1 in 25 are carriers of the mutation and 1 in 2500 children have CF.
What are the consequences of the mutation in CF?
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
If 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?
The child doesn’t have the condition, so the answer is two in three.
Is CF screened for at birth?
Yes, CF is screened for at birth with the newborn bloodspot test.
What is often the first sign of CF?
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 CF is not diagnosed at birth how does it present later in life?
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.
What are the 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)
What are the signs of CF?
- Low weight or height on growth charts
- Nasal polyps
- Finger clubbing
- Crackles and wheezes on auscultation
- Abdominal distention
What are the causes of clubbing in children?
- Hereditary clubbing
- Cyanotic heart disease
- Infective endocarditis
- Cystic fibrosis
- Tuberculosis
- Inflammatory bowel disease
- Liver cirrhosis
Briefly describe the diagnosis of CF
There are three key methods for establishing a diagnosis that you should remember for your exams:
- 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 gold standard investigation for diagnosing CF?
Sweat test.
Briefly describe 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.
