Cystic Fibrosis Flashcards
How many live births does cystic fibrosis affect
1 in 2500
How is cystic fibrosis inherited
in an autosomal recessive manner
How much of the population are carriers for the disease
1 in 25
Where is the mutational defect that causes cystic fibrosis
On the long arm of chromosome 7 that codes for (CFTR)
What does CFTR stand for
Cystic Fibrosis Transmembrane conductance regulator
What is the most common mutation
Deletion of three base pairs of the gene results in the loss of phenylalanine at position 508
What is the primary physiological defect in cystic fibrosis
Reduced chloride conductance at epthelial embranes
What is a characteristic of the disease
Chloride and sodium in the sweat (salty sweat)
How many classes of mutations of the CFTR gene are there
5
Mutations in classes 1-3 result in what
No CFTR function at the cell membrane
What is more severe? classes 1-3 or classes 4-5
Classes 1-3
What does reduced chloride secretion and increased sodium reabsorption result in in the bronchial mucosa
Secretions of abnormal viscosity with reduced water content of the airway surface liquid and reduced depth of the periciliary fluid
What inactivates defensins
The high salt content of the airway surface
What inactivates defensins
The high salt content of the airway surface
What are defensins
Naturally occurring antimicrobial peptides on the epithelial surface
Why does bacteria adhere to the mucosa and proliferate in patients with cystic fibrosis
These patients have abnormal mucus glycoproteins that act as binding sites for the bacteria
In what organ is there abdnormal ion transport resulting in plugging and obstruction of ductules with pregressive destruction of the gland
Pancreas
Why does malabsorption occur in patients with cystic fibrosis
Pancreatic enzymes fail to reach the small intestine which results in malabsorption off fats with steathorrhoea and failure to gain weight
What might cause diabetes in a patient with cystic fibrosis
Progressive destruciton of the endocrine pancreas
Why do patients with cystic fibrosis have an increased incidence of fallstones and biliary cirrhosis
Abnormalities of bile secretion and absorption
10% of children with cystic fibrosis present with what at birth
Meconium ileus
What is meconium ileus
A form of intestinal obstruction caused by inspissated viscid faecal material resulting from lack of pancreatic enzymes and from reduced intestinal water secretion
What are other symptoms of cystic fibrosis
obvious malabsorption by the age of 6 month (50%0
failure to thrive
abdominal distension
copious offensive stools from steatorrhoea
Rectal prolapse occasionally occurs
What is the most prominent feature of cystic fibrosis
Recurrent respiratory infections with cough, sputum production and wheeze
What is the most prominent feature of cystic fibrosis
Recurrent respiratory infections with cough, sputum production and wheeze
What are the typical organisms isolated in sputum cultures
Staph Aureus
Haemophilus influenzae
Streptococcus pneumoniae
By the teenage years, many patients will have become infected with what?
Mucoid strains of pseudomonas aerginosa
What organism causes onion rot
Burkholderia cepacia complex
How can burkholderia cepacia complex spread
From person to person in close social contact (those with CF)
What type of Burkholderia cepacia is associated with the worst prognosis
Type 3
Why is social contact between patients with CF discouraged
Because of the potential for transmission of infection between patients
What happens as the cycle of infection and inflammation progress
Lung damage worsens with deteriorating airways obstruction, destruction of lung parenchyma, impairment of gas exchange and the development of hypoxaemia, hypercapnia and cor pulmonale
What provokes hypertrophy of the bronchial arteries and what does this result in
Persistent pulmonary inflammation
Haemoptysis
What are some of the GI complications that patients with CF can develop
Fatty liver gallstones focal biliary fibrosis multinodular cirrhosis and hepatosplenomegaly portal hypertension oesophageal varices liver failure
What is the equivalent of meconium ileus
Distal intestinal obstruction syndrome
Where is there often a palpable mass (GI) in patients with CF
Right ileac fossa
What is the treatment to prevent recurrence of GI symptoms
Pancreatic enzyme supplements, avoidance of dehydration and possible use of laxatives
What specifically causes almost all male CF patients to be infertile
The congenital bilateral absence of the vas deferens
What are CF patients at risk of developing in hot weather and why
Heat prostration
As a result of excess loss of salt in sweat
How is the diagnosis of CF based upon
The demonstration of elevated sweat chloride concentrations on a sweat test in association with characteristic clinical features such as recurrent respiratory infections or pancreatic insufficiency
What are the two known cystic fibrosis mutations on DNA analysis
Delta F508 and G542X
What is sweating induced by
Pilocarpine iontophoresis
How is the sweat test carried out
Pilocarpine is placed on the skin of the forearm and a small electrical current is passed across it to enhance its penetration of the skin and stimulation of the sweat ducts.
What have the sweat chloride levels got to be above for a high suspicion of CF
over 60mmol/L
What is used to detect carrier status
Genotyping
What do infants with CF have
Elevated serum immunoreactive trypsin activity
How is newborn screening for CF carried out
Measured on a single dried blood spot obtained on a Guthrie card as part of the newborn screening programme for diseases such as PKU and hypothyroidism
What are the 4 basic elements to treatment for CF
Chest physio - to clear the bronchial secretions
Antibiotics to treat the pulmonary infection
Pancreatic enzyme supplements to correct the nutritional deficits
Dietary support
At what stage of the disease is chest physiotherapy important
All stages
What 3 techniques are used during chest physio
Postural drainage
Chest percussion
Positive expiratory pressure devices
What is given long term from early childhood?
Flucloxacillin
What is the usual antibiotic used to treat exacerbations
Amoxicillin
Some patients have a reversible component to their airways obstruction and benefit from what
Bronchodilator drugs (salbutamol) and inhaled steroids (beclametasone)
How is mucolytic medication administered
By nebulisation and improves the lung function and reduces the number of exacerbations in some patients
How is mannitol administered
A dry powder inhalor
How does mannitol work
It is an osmotic agent that also increases the warter content of the airway surface liquid with improved mucociliary clearance
What might be useful in reducing lung injury by inhibiting the migration and activation of neutrophils
High dose ibuprofen
When are pancreatic enzyme supplements taken
With each meal and with snacks containing fat
Patients with CF required how much of the recommended daily calorie intake for individuals without CF
120-150%
An FEV1 of less than 30% of the predicted value is associated with what kind of mortality rate
50% 2 year mortality rate
What is the main option to be considered in patients with advanced disease
Lung transplantation
What is the median survival for CF patients nowadays
38 years
What social factors are also affected through the illness
Reduced life expectancy Insurance choice of career relationships marriage pregnancy fertility
