Cystic Fibrosis

Question 1

Parkinson’s is the commonest inherited genetic condition in the UK.

True or False?

Answer 1

False

Cystic Fibrosis

Question 2

Cystic fibrosis is an ——– ——– condition.

Answer 2

Autosomal recessive

Question 3

How many people are carriers

Answer 3

1 in 25
1 in 2500 births

Question 4

97% of cystic fibrosis occurs in the

Answer 4

Caucasian population

Question 5

How many individuals with CF in the UK?

Answer 5

9000 individuals (approx)

Question 6

Cystic fibrosis is

Answer 6

the mutation of a gene located on chromosom 7q31, which codes for a protein called cystic fibrosis transmembrane regulator (CFTR)

Question 7

What is the commonest mutation of CF?

Answer 7

Delta F5-8

Question 8

Diagram inheritance of CF

Answer 8

Question 9

CFTR protein

Answer 9

• CF occurs due to a mutation in a gene on the long arm of chromosome 7
• results in defect in the cystic fibrosis transmembrane conductance regulator protein
• CFTR sits in the membrane of epithelial cells and regulates the transport of Cl- through activation of cyclic AMP and through calcium activated chloride channels
• CFTR inhibits transport of sodium through the sodium channels in the epithelial cell membrane and regulates the movement of bicarbonate ions

Question 10

process of CFTR

Answer 10

insert

Question 11

Answer 11

Question 12

Impact of abnormal CFTR:

Answer 12

• abnormal CFTR protein leads to decreased chloride reabsorption and increased sodium reabsorption
• secretions have high viscosity and reduced water content
• this impedes mucociliary clearance in the bronchi so respiratory secretions are stagnant
• decreased defence from respiratory infections

Question 13

consequenc of recurring infections in the lungs

Answer 13

bronchiectasis

• recurring infections causes constant inflammation in the lungs, terminal and respiratory bronchioles not major airways
• causes destruction and dilation of the distal airways with mucous impaction, which predisposes to more infection which predisposes to worsening of the inflammation

Question 14

insert chest x ray

Answer 14

bronchiectasis

Question 15

Common organs affected by CF?

Answer 15

• Respiratory System:
  
  • bronchiectasis
  • recurrent respiratory infections
  • respiratory infections
• Gastrointestinal System:
  
  • pancreatic insufficiency
  • diabetic mellitus
• Skin:
  
  • increased sweat, when exercising can lose a lot of sodium
• Reproductive system:
  
  • infertile

Question 16

CF process fill out

Answer 16

insert

Question 17

Symptoms of upper respiratory tract in CF:

Answer 17

• chronic sinus disease
• nasal polyps

Question 18

Symptoms of lower respiratory tract:

Answer 18

• chronic cough and sputum
• bronchiectasis (dilated and inflamed bronchi)
• chronic suppurative lung disease (pus)
• colonisation with bacteria
• frequent respiratory infections
• clubbing

Question 19

Common bacteria causing disease in CF and consequence:

Answer 19

• Staphylococcus aureus
• Haemopilus influenzae
• pseudomonas aeruginosa (grram +)
• burholderia cepacia (gram -)
• colonisation
• difficult to eradicate

Question 20

Insert chest x ray

Answer 20

insert

Question 21

insert CT scan

Answer 21

insert

Question 22

CF: gastrointestinal tract flow chart:

Answer 22

insert

Question 23

Impact of CF on gastrointestinal disease:

Answer 23

• defective CFTR leads to abnormal chloride transport in pancrease leads to destruction of pancreas and exocrine insufficiency
• decrease in lipase activity
• decreased absorption of fat in small intestine
• steatorrhoea (fat in tstool, pale and floats)
• decreased water content in intestines leads to thick faecal material leads to intestinal obstruction: “meconium ileus equivalent” in adults as it mimics meconium ileus in neonates”
• COMPLETE

Question 24

CF presentations in newborn

Answer 24

• meconium ileus
• failure to thrive
• recurrent respiratory infections

Question 25

Three types/times of screening for CF:

Answer 25

- antenatal - prenatal - neonatal

Question 26

Antenatal screening for CF:

Answer 26

- after birth - carrier testing - genetic counselling

Question 27

Prenatal screening for CF:

Answer 27

- DNA analysis on sample of chorionic villus - amniocentesis - allows reproductive decision making

Question 28

Neonatal screening for CF:

Answer 28

- newborn screening - Futhrie test - sweat test

Question 29

Why is screening for Cf useful?

Answer 29

- early diagnosis and treatment improves outcome

Question 30

Diagnosis of CF:

Answer 30

- clinical presentation: - recurrent respiratory infection - meconium ileus - Failure to thrive - positive sweat test = chloride content > 60mmol/L = abnormal - DNA analysis: genotyping for common mutations - chest x ray usually abnormal

Question 31

diagram

Answer 31

insert

Question 32

Management of CF:

Answer 32

- specialist centre - MDT: - nurse specialists, dieticians, OT, psych, support for family, etc - CF trust

Question 33

Treatment of respiratory disease (CF):

Answer 33

- prompt antibiotics for respiratory infections - intense chest physio to remove mucus; once or twice a day - nebulised DNAse (breaks down DNA of secretions and bacteria) leads to a decrease in viscosity - mucolytic drugs - bronchodilators - long term oxygen therapy - lung or heart transplant

Question 34

Management of pancreatic disease (CF):

Answer 34

- exocrine: - creaon (pancreatic enzymes) - multivitamins - nutritional support (enteral feeding) - endocrine (diabetes): - insulin

Question 35

median survival years diagram

Answer 35

insert

Question 36

Potential new treatments for CF:

Answer 36

- gene therapy - RNA correction - CTFR modulation

Question 37

Gene Therapy for CF improves

Answer 37

- Kaftrio: triple therapy - Potentiator and corrector impact on production and function - improves symptoms - improves lung function - improves survival