Cystic Fibrosis

Question 1

What is cystic fibrosis?

Answer 1

It is a multi system autosomal recessive disorder which results in abnormal ion transport across epithelial cells.

Question 2

Which protein is affected in CF, where is the mutation and what is the most common mutation?

Answer 2

CFTR protein is affected, which is a chloride dependant channel on the membrane of cells.

The mutation is on chromosome 7.

~1000 mutations have been shown to cause CF but the most common is F508

Question 3

What systems are affected in CF?

Answer 3

Respiratory system:
Thick mucous which leads to repeated respiratory infections and bronchiectasis. Often ends with Pseundomonas colonisation. They may develop progressive air flow obstruction which can eventually cause cor pulmonale.

Pancreatic:
Ducts get blocked by thick secretions therefore digestive enzymes cannot be released causing absorption issues, streatorrhoea, poor growth and weight gain.

May also eventually develop pancreatitis, diabetes and gallstones sue to issues with the pancreas.

Hepatic:
Liver failure due to chronic blockage of ducts

Reproductive:
Men are infertile as they are born without a vas deferens

Question 4

Describe the pathological changes which occur in the lung?

Answer 4

Abnormal Cl channels which lead to there being thick mucous in the lung.

This is difficult to cough up and therefore patients get repeated LRTI which predispose to bronchiectasis. (abnormal dilatation of bronchioles)

Question 5

How does CF present?

Answer 5

Usually it is found via screening.

The heel-prick test for immunoreactive trypsinogen is used to screen for CF shortly after birth.

If not picked up via screening patient would present with failure to thrive/poor growth, pale diahorea and repeated respiratory infections.

Question 6

How is CF treated?

Answer 6

Respiratory:

• Physiotherapy twice weekly
• Prophylactic abx (flucloxacillin + rescue abx for exacerbations)
• Mucolytics (hypertonic saline, nebulised DNAse)

Pancreatic:

• Creon (oral enteric coated pancreatic replacement)
• High calorie diet
• Fat soluble vitamin replacement

Note respiratory infections are treated with 14 days intensive IV abx.

Question 7

Discuss transplantation as a treatment for CF?

Answer 7

Lung transplant.

In certain patients heart lung transplant.

Patients may get referred when respiratory function is less than 30%.

Increases mortality and morbidity however has significant risks as it is a major operation and with transplantation there is always a risk of rejection.

Donor must have a compatible cell type as well as being a similar size to the patient.

Some patients may also need liver transplants.

Question 8

What are the main organisms which cause infection in cystic fibrosis?

Answer 8

Can become infected by normal organisms but we particularly worry about the following as they are very difficult to eradicate:

• Pseudomonas aeruginosa
• Stenotrophomonas maltophilia
• Achromobacter xylosoxidans
• Non tuberculous mycobacteria
• MRSA