cystic fibrosis

Question 1

what type of mutation is cystic fibrosis?

Answer 1

CFTR gene mutation (chromosome 7)
- this is a chloride channel mutation (energy dependant channel)

Question 2

describe the normal action of the chloride channel?

Answer 2

• when the Cl channel open on the lung epithelial membrane, chloride moves out into the lumen of the airway
• this pulls Na with it. (maintaining neutrality)

This creates a salt of Na+Cl = osmotic pressure that pulls water out into the lumen.

Question 3

goblet cells in the airway?

how does the moisten the airway?

how do cilia act here?

Answer 3

produce mucopolysaccharide material.
- this will combine with water

this is what moisten the airways= airway surface liquid that traps bacteria.

cilia will move anything away that gets stuck here.

Question 4

how does all of this change in cystic fibrosis?

Answer 4

not enough water gets pulled out due to a defect in the chloride channel.

• this makes heavy mucus that will not move very well.

But we still want to get rid of the bacteria

Question 5

how does the body get rid of the bacteria in cystic fibrosis?

Answer 5

neutrophils will try to breakdown the bacteria = secretion of inflammatory molecules. THIS WILL DAMAGE LUNG TISSUE.

Question 6

where does this also happen in the body?

Answer 6

pancreas
liver
sweat glands
reproductive tract

Question 7

what is the main diagnostic technique for TB?

what genes are they looking for?

Answer 7

newborn screening for genes.

IRT (immunoreactive trypsinogen)
- this enzyme is produced by the pancreas (it should not be found in the blood, it is a sign that the pancreas is being destructed.

Question 8

what are some symptoms of cystic fibrosis?

Answer 8

recurrent chest infections
- infertility
- dibetes type 3
- pancreatitis
- liver dysfunction

Question 9

how does the sweat test work for screening for TB?

Answer 9

• uses the Pilocarpine ionotoporesis tenchnique (electrical current is applied)
• measure the minimum sweat volume and the chloride concentration of the sweat will be analysed.
• sweat chloride concentration >60 = CF
  40-60mmol/l Is borderline high
  <40 mmol/l is normal

Question 10

what are other tests that can be done to look for CF?

Answer 10

• stool elastase
• genetics

Question 11

what kind of doctors would be on the team for CF?

Answer 11

• respiratory
• GI/Liver
• Endocrine - diabetes

Question 12

what is CF exacerbation?

Answer 12

an exacerbation is defined as the need for. additional antibiotic treatment based on the presence of 2 or more of:
- change in sputum volume
- increased cough
- anorexia
- X-ray changes

Question 13

what are examples of:
viruses
bacteria
fungi
that we are concerned about in cystic fibrosis?

Answer 13

viruses = flu, rhinovirus

bacteria = s.aureus, pseudomonas

fungi = aspergillus

Question 14

what are 3 mechanisms of new CF therapies?

Answer 14

1) suppressors of premature stop codons
2) CFTR correctors
3) CFTR potentiators

Question 15

what are 5 things will make up treatment in the early years of CF?

Answer 15

1) airway clearance (mucolytic therapy delivery through nebulisers)

2) nutritional management (calories, vitamins, salt)

3) management of chest exacerbations

4) regular MDT clinic

5) Ad-hoc reviews