Cystic Fibrosis

Question 1

What is the epidemiology of CF?

Answer 1

• Most common in Caucasian populations
• 1/2,500 births
• 1/25 people are carriers

Question 2

What are the symptoms of CF?

Answer 2

• Frequent lung infections (difficulty breathing and coughing up mucus)
• Poor growth
• Fatty stool
• Clubbing of fingers and toes
• Infertility in males

Question 3

What is the inheritance pattern of CF?

Answer 3

Autosomal recessive

Question 4

Which gene is affected in CF?

Answer 4

• Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene
• On chromosome 7

Question 5

What is the most common mutation of CFTR in CF?

Answer 5

• deltaF508: deletion of 3 nucleotides at 508th position

- results in loss of phenylalanine aa.

Question 6

What is the function of the CFTR protein?

Answer 6

• ATP-responsive chloride ion channel in apical membrane of epithelial cells.
• Also acts as inhibitor of ENaC (which allows Na+ entry into epithelial cells).

Question 7

Name 5 systems/organs that are affected in CF?

Answer 7

1. Respiratory tract
2. Skin (sweat glands)
3. Pancreas
4. GI tract
5. Genitals

Question 8

What is the effect of CF in the respiratory tract?

Answer 8

• Absence of CFTR in respiratory tract epithelium…
• no inhibition of ENaC…
• Na+ reabsorption from airway surface liquid to epithelial cells…
• water follows Na+ into cells…
• thick, dehydrated mucus…
• deficient mucociliary clearance and clogging of small airways…
• respiratory infections and lung damage.

Question 9

What is the effect of CF on sweat glands/skin?

Answer 9

• Absence of CFTR in epithelium lining sweat gland ducts…
• poor reabsorption of Cl- ions from duct lumen to epithelial cells…
• modified membrane potential (as Cl- has negative charge)…
• Na+ is not reabsorbed by epithelial Na+ channels…
• high Na+ and Cl- combine to create salt…
• moves to skin surface.

Sweat testing for abnormally salty sweat.

Question 10

What is the effect of CF in the pancreas?

Answer 10

Absence of CFTR in pancreas gland duct leads to:

1. Dehydrated pancreatic exocrine secretions - pancreas painfully inflamed (pancreatitis) and fibrotic.
2. Gut receives insufficient pancreatic digestive enzymes - malabsorption (e.g insufficient lipase production - faecal excretion of undigested fat, usually as diarrhoea).

Question 11

What is the effect of CF in the GI tract?

Answer 11

Absence of CF in GI tract epithelium - thick, dehydrated mucus:

• meconium ileus in some newborns
• constipation and invagination of parts of the GI tract in older CF sufferers

Question 12

What is the effect of CF in the genitals.

Answer 12

Absence of vas deferens - infertility in males