Cystic Fibrosis

Question 1

Describe the molecular basis of cystic fibrosis

Answer 1

• CFTR transports Cl- and bicarbonate (+ regulates ENAC)
• Cl- is transported out of cells into airways + H2O follows
• critical role in the hydration of mucous in the airway tract
• defective CFTR function leads to reduced airway surface hydration > thick sticky mucous + impaired mucociliary clearance

Question 2

What is cystic fibrosis?

Answer 2

• Autosomoal recessive disorder | chromosome 7
• Mutation in the cystic fibrosis transmembrane conductance regulator

Question 3

What is the most common mutation in cystic fibrosis?

Answer 3

Phe508del CFTR protein

Question 4

What does a mutation in the Phe508del CFTR protein cause?

Answer 4

• defective intracellular processing + trafficking
• decreased stability > reduces quantity of CFTR protein at apical surface of epithelial cells
• exhibits defective channel gating

Question 5

How do you diagnose cystic fibrosis?

Answer 5

• One or more of the characteristic phenotypic features
• or history of CF in sibling
• or positive newborn screening test result

AND

• increased sweat chloride conc. sweat test
• or identification of 2 CF mutations by extended genotyping

Question 6

Classic clinical presentations of cystic fibrosis

Answer 6

Meconium ileus
Intestinal malabsoption + pancreatic insufficiency
Recurrent chest infections
Newborn screening

Question 7

What is meconium ileus?

Answer 7

Newborn baby’s first poo (meconium) is stuck due to sticky secretions in the bowel

Question 8

Lung complications of cystic fibrosis

Answer 8

Bronchiectasis
Pneumothorax
Haemoptysis
Respiratory failure

Question 9

What lifestyle advice is given to a patient with cystic fibrosis?

Answer 9

• no smoking
• avoid friends with colds/infections
• avoid jacuzzis
• clean + dry nebulisers thoroughly
• avoid stables, compost or rotting vegetation - risk of aspergillus fumigatus inhalation
• flu vaccine
• pneumococcal vaccine
• sodium chloride tablets in hot weather or after vigorous exercise

Question 10

Clinical management of cystic fibrosis

Answer 10

• holistic care
• up to date flu + pneumococcal vaccines
• chest physio + infection management to maintain lung health
• optimal nutritional state- BMI, vitamins etc.

Question 11

What is the only cure for cystic fibrosis?

Answer 11

Lung transplant

Question 12

What factors contribute to the impaired nutritional status in cystic fibrosis?

Answer 12

• pancreatic insufficiency
• chronic malabsorption
• chronic inflammation > increased energy expenditure
• increased energy requirements for breathing

Question 13

Liver complications of cystic fibrosis

Answer 13

Chronic liver disease
Portal hypertension

Question 14

Complications of cystic fibrosis

Answer 14

• bronchiectasis
• pneumothorax
• cardiac failure
• chronic liver disease
• oesophagitis
• distal intestinal obstruction syndrome
• low BMI
• chronic sinusitis
• male infertility
• gallstones
• pancreatic insufficiency
• osteoporosis
• arthritis

Question 15

Why should you advise a patient with cystic fibrosis to avoid jacuzzis?

Answer 15

Avoid risk of pseudomonas aeruginosa infection

Question 16

Why are patient with cystic fibrosis at higher risk of becoming underweight?

Answer 16

Due to malabsoprtion from GI tract: increased mucous prevents digestive enxyme from working > harder for patients to get correct nutrients

Question 17

What investigations are used for diagnosis of cystic fibrosis?

Answer 17

New born heel prick test
Sweat test

Question 18

Why should you advise patient with cystic fibrosis to avoid farms + compost?

Answer 18

Reduce risk of aspergillus fumigatus inhalation

Question 19

What is the inheritance pattern in cystic fibrosis?

Answer 19

Autosomal recessive