Cystic Fibrosis Flashcards
How many people does cystic fibrosis affect?
It is an autosomal recessive disorder that affects 1 in 2000-2500 people
What is the carrier frequency for CF?
1 in 25
How many different mutations can cause cystic fibrosis?
more than 2,000 different mutations can cause cystic fibrosis
What is the most common mutation which causes CF?
Phe508del (DF508 mutation)
the deletion of 3 nucleotides spanning positions 507 and 508 of the CFTR gene
results in the loss of a single codon for the amino acid phenylalanine
Where does the Phe508del occur?
Long arm of chromosome 7
What is meant by cystic fibrosis being “multisystem”?
It affects many different regions of the body
What is the mutation that causes CF and what does the mutation do?
Mutation in the CFTR gene which codes for the cystic fibrosis transmembrane regulator (CFTR) protein
Abnormal CFTR protein leads to disruption of chloride channels on cell surfaces
How does the production of abnormal mucous cause symptoms in the lungs?
Mucous is excessively thick and sticky
It will block the airways and the lungs
It can lead to repeated serious lung infections that can damage the lungs
How does the production of abnormal mucous cause symptoms in the pancreas?
The abnormal mucous blocks ducts/tubes in the pancreas
Digestive enzymes from the pancreas cannot reach the small intestine
What are the problems caused by digestive enzymes not reaching the small intestine?
Impaired absorption of fats and proteins
Leads to vitamin deficiency, weight loss and malnutrition
It leads to steatorrhea - fatty stools
How does the sweat composition of someone with CF vary?
High Na+ and Cl- content
Due to the defect of the Cl- channels
The sweat duct is impermeable to water absorption
How is a sweat chloride test used to diagnose CF?
The Cl- concentration of their sweat is greater than 60 mmol/L
More milder cases may be 30-60 mmol/L
What is mucociliary clearance?
A primary innate defence mechanism to protect the lungs from the effects of inhaled pollutants, allergens and pathogens
What is the effect of reduced mucociliary clearance in CF patients?
Increased infections
What causes airway dehydration in CF?
Increased amounts of Na+ and decreased amounts of Cl- in the airway
Why is there increased airway inflammation and infection in CF?
High levels of extracellular DNA are released from degenerating neutrophils
This accumulates in the airways in response to chronic infection
What % of patients develop CF related diabetes?
30%
What are the underlying lung abnormalities caused by CF?
pulmonary disease
bronchiectasis
pulmonary exacerbation
How do lung diseases caused by CF affect the airways?
They may affect the large and/or small airways
They usually show airway reversibility
What is bronchiectasis?
Permanent dilatation and obstruction of the airway wall
Involves permanent dilatation of the bronchi
What are pulmonary exacerbations?
CF lung disease involves chronic progression with intermittent episodes of acute worsening symptoms
What are the common symptoms of pulmonary exacerbations?
- increased cough
- increased sputum production
- change in sputum colour
- fever/malaise
What are the 6 main treatments for CF?
- nebulised antibiotics
- oral/IV antibiotics
- DNase
- Vitamins A, D, E, K
- Pancreatic enzymes
- Insulin
Why are antibiotics given to CF patients?
to treat bacterial colonisation
What does DNase do?
it breaks down thick sputum to allow clearance
What are the clinical signs of CF?
- Clubbing
2. Coarse crackles, wheeze or no sounds heard at all
What are the 5 main symptoms of CF?
- weight loss
- increased cough with production of large amounts of thick sputum
- haemoptysis
- fatty stools
- reduced vision
