Cystic Fibrosis

Question 1

What is the genetic abnormality in CF?

Answer 1

• CFTR (cystic fibrosis transmembrane conductance regulator) abnormality
• Autosomal recessive (homo/heterozygous)

Question 2

What is CFTR, and what is its physiological role?

Answer 2

• chloride channel found in the apical membrane of epithelial cells - lungs, intestines, pancreatic ducts, sweat glands, and reproductive organs
• CFTR has two functions:
1. Inhibits ENaC -> dec sodium abs into cell -> water doesn’t follow into cell
2. Secretes Cl- -> reduces water absorption

Question 3

In CF, what does the CFTR not do?

Answer 3

• -> ENaC not inhibited and Cl- ions not secreted

* abnormal salt transport by epithelial cells -> thick, sticky secretions

Question 4

Complications of CF

Answer 4

○ Pancreas: blockage ducts -> early activation of pancreatic enzymes -> autodestruction

○ Intestine: bulky stools -> obstruction (esp. ileum)

○ Respiratory: cycle of mucus retention -> chronic infection and inflammation -> chronic pulmonary disease inc. cor pulmonale -> resp failure

• Cor pulmonale
• DM (onset usually between 18-21 years of age)
• Osteoporosis
• Chronic sinusitis
• Failure to thrive
• Advanced liver disease

Question 5

How does CF lead to chronic lung infections?

Answer 5

1. thick mucous -> obstruction -> infection -> inflammation -> thickened mucous
2. ASL (airway surface liquid) volume hyperabsorption has important consequences for both the PC (periciliary) and the mucus layer:
   □ Volume depletion of PCL →failure of ciliary beating
   □ Absence of lubrication → adherent mucus plaque

-> promotes chronic infection

Question 6

What might be one of the first symptoms of CF?

Answer 6

Failure to pass meconium

Question 7

What features might CF present with?

Answer 7

• Bowel obstruction with meconium (meconium ileus)
• Failure to thrive
• Insatiable appetite
• Wet cough
• Recurrent infection
• Chronic sinusitis
• Haemoptysis
• Steatorrhoea
• GORD
• Pancreatitis
• Hepatosplenomegaly (rare)
• Genital abnormalities in males (bilateral absence of vas deferens)

Question 8

Ix for CF

Answer 8

(Newborn screening = immunoreactive trypsinogen test)

1. Chloride sweat test: positive (> 60 mmol/L)in homozygote: Dx confirmed
2. If <60mmol/L (but clinically suspect) -> genetic testing:
   □ 2 mutations = Dx

3. If 1 mutation - further tests:
	□ panc enczymes in faeces
	□ sinus radiography 
	□ sputum/throat swaps 
	□ PFTs, CXR (hyperinflated, increased pulmonary markings (especially in upper lobes))

Question 9

Classic presentation of CF

Answer 9

Infant with FTT

Question 10

Most common lung infection in CF

Answer 10

Pseudomonas

Question 11

Mx of CF

Answer 11

• General: chest physio, postural drainage
• Nutrition: high energy + protein diet, fat-soluble vit supp

Rx:
• Bronchodilators (salbutamol +/- ipratropium bromide)
• Inhaled mucolytic (dornase alfa and hypertonic saline)
• IV Abx for exacerbations(tobramycin and ticarcillin/clavulanic acid)
• Pancreatic enzyme replacement, bile acids for liver disease