Cystic Fibrosis

Question 1

What is Cystic Fibrosis (CF)?

Answer 1

An autosomal recessive genetic disorder associated with defective ion transport that affects fluid secretion in exocrine glands and epithelial linings.

Thick, sticky secretions are produced that plug up airways and ducts.

Question 2

CF is a multi-system disease. Which other systems are affected?

Answer 2

Affects the function of:
- airways
- pancreas = blocks ducts
- sweat glands = salty sweat
- intestines = cannot fully absorb nutrients
- liver = blocks ducts
- reproductive tracts = complications

Question 3

What is the etiology of CF?

Answer 3

• An autosomal recessive genetic disorder
• affected gene is the cystic fibrosis transmembrane conductance regulator (CFTR) gene
• > 2000 different mutations of the CFTR exist = type of mutation determines the severity of symptoms

Question 4

Which is the most common mutation of the CFTR gene resulting in CF?

Answer 4

Delta F508 mutation
- 87.5% of Canadians with CF
- 3 nucloetide deletion at position 508 = loss of phenylalanine in the amino acid sequence

Question 5

What is the CFTR protein?

Answer 5

A chloride channel found on the apical surface of epithelial cells of airways, pancreatic ducts, sweat glands, bile ducts and reproductive tracts.

Question 6

Describe the link between CFTR channels and epithelial hydration.

Answer 6

1. CFTR channels open = Cl- enters lumen (becomes more negative)
2. Na+ moves towards the neg charge through leaky junctions between cells
3. Water follows by osmosis

If the CFTR channel is absent or defective, Cl- cannot leave the cell and water secretion is impaired.

Question 7

How does impaired CFTR channels lead to respiratory dysfunction.

Answer 7

• A water layer is needed for cilia movement
• when airway hydration is impaired = mucus becomes thick and viscous and cannot be cleared

Question 8

As a result of bacterial retention and recurrent infections, 70-75% of patients are infected with?

Answer 8

Pseudomonas aeruginosa

Question 9

What happens with recurrent infections for patients with CF?

Answer 9

1. cause airway inflammation (bronchitis) and mucus production = increased airway obstruction
2. neutrophils infiltrate airways
   - release elastase = breakdown of airway elastic fibres
   - release DNA when they die = increases viscosity of mucus

Question 10

Describe 3 progressive lung changes with CF.

Answer 10

1. Bronchiectasis = destruction of elastic fibres and wall weakening cause irreversible dilation of bronchi
2. Lung abscesses form (pus-filled cavities)
3. Pulmonary fibrosis develops (scar tissue) which decreases lung compliance = restrictive lung disease.

Question 11

Describe the effects of CF on the digestive function.

Answer 11

Thick mucus blocks:
- pancreatic duct = impairs the release of digestive enzymes (called pancreatic insufficiency)
- bile ducts = impairs the release of bile needed for fat emulsification

= impairs digestion and absorption

Question 12

What is meconium ileus?

Answer 12

Meconium Ileus = passage of the meconium at birth is restricted, normally passes first 12-72 hours

Causes distention behind the ileum (abdominal distension, vomiting)

Question 13

What is steatorrhea?

Answer 13

Sign of CF - frequent, bulky, foul-smelling, fatty stools (impaired fat digestion & absorption)

Question 14

What vitamin deficiencies are associated with CF?

Answer 14

Fat-soluble vitamins.
- bleeding tendencies (vit K deficiency)
- bone weakening and risk of fracture (Vit D deficiency)

Question 15

How is CF diagnosed?

Answer 15

1. Routine screening of newborns in BC - check blood for immunoreactive trypsinogen (IRT) a protein produced by the pancreas
2. Presence of clinical features of CF
3. Genetic testing
4. Sweat test
5. Stool analysis (low fecal elastase)
6. Sputum culture (for any infections)
7. Diagnostic studies to assess lung involvement (chest x-ray, CT scan, pulmonary function testing)

Question 16

What does the sweat test measure for?

Answer 16

Cl- concentrations. In CF, Na+ and Cl- reabsorption are impaired (d/t CFTR channel dysfunction)

Question 17

How do Oscillating Positive Expiratory Pressure (OPEP) devices work?

Answer 17

1) create positive pressure air pulses during exhalation that help open airways
2) create high frequency oscillations (vibrations) that help loosen secretions that can be coughed out

Question 18

How is CF managed in children under 6?

Answer 18

Postural drainage and percussion are used to loosen mucus.

Question 19

Why should all CF patients undergo genotyping?

Answer 19

There are new therapies (CFTR modulators) designed to correct malfunctioning protein made by the CFTR gene but only with specific mutations.