Cystic Fibrosis

Question 1

How many people does cystic fibrosis affect?

Answer 1

It is an autosomal recessive disorder that affects 1 in 2000-2500 people

Question 2

What is the carrier frequency for CF?

Answer 2

1 in 25

Question 3

How many different mutations can cause cystic fibrosis?

Answer 3

more than 2,000 different mutations can cause cystic fibrosis

Question 4

What is the most common mutation which causes CF?

Answer 4

Phe508del (DF508 mutation)

the deletion of 3 nucleotides spanning positions 507 and 508 of the CFTR gene

results in the loss of a single codon for the amino acid phenylalanine

Question 5

Where does the Phe508del occur?

Answer 5

Long arm of chromosome 7

Question 6

What is meant by cystic fibrosis being “multisystem”?

Answer 6

It affects many different regions of the body

Question 7

What is the mutation that causes CF and what does the mutation do?

Answer 7

Mutation in the CFTR gene which codes for the cystic fibrosis transmembrane regulator (CFTR) protein

Abnormal CFTR protein leads to disruption of chloride channels on cell surfaces

Question 8

How does the production of abnormal mucous cause symptoms in the lungs?

Answer 8

Mucous is excessively thick and sticky

It will block the airways and the lungs

It can lead to repeated serious lung infections that can damage the lungs

Question 9

How does the production of abnormal mucous cause symptoms in the pancreas?

Answer 9

The abnormal mucous blocks ducts/tubes in the pancreas

Digestive enzymes from the pancreas cannot reach the small intestine

Question 10

What are the problems caused by digestive enzymes not reaching the small intestine?

Answer 10

Impaired absorption of fats and proteins

Leads to vitamin deficiency, weight loss and malnutrition

It leads to steatorrhea - fatty stools

Question 11

How does the sweat composition of someone with CF vary?

Answer 11

High Na+ and Cl- content

Due to the defect of the Cl- channels

The sweat duct is impermeable to water absorption

Question 12

How is a sweat chloride test used to diagnose CF?

Answer 12

The Cl- concentration of their sweat is greater than 60 mmol/L

More milder cases may be 30-60 mmol/L

Question 13

What is mucociliary clearance?

Answer 13

A primary innate defence mechanism to protect the lungs from the effects of inhaled pollutants, allergens and pathogens

Question 14

What is the effect of reduced mucociliary clearance in CF patients?

Answer 14

Increased infections

Question 15

What causes airway dehydration in CF?

Answer 15

Increased amounts of Na+ and decreased amounts of Cl- in the airway

Question 16

Why is there increased airway inflammation and infection in CF?

Answer 16

High levels of extracellular DNA are released from degenerating neutrophils

This accumulates in the airways in response to chronic infection

Question 17

What % of patients develop CF related diabetes?

Answer 17

30%

Question 18

What are the underlying lung abnormalities caused by CF?

Answer 18

pulmonary disease
bronchiectasis
pulmonary exacerbation

Question 19

How do lung diseases caused by CF affect the airways?

Answer 19

They may affect the large and/or small airways

They usually show airway reversibility

Question 20

What is bronchiectasis?

Answer 20

Permanent dilatation and obstruction of the airway wall

Involves permanent dilatation of the bronchi

Question 21

What are pulmonary exacerbations?

Answer 21

CF lung disease involves chronic progression with intermittent episodes of acute worsening symptoms

Question 22

What are the common symptoms of pulmonary exacerbations?

Answer 22

1. increased cough
2. increased sputum production
3. change in sputum colour
4. fever/malaise

Question 23

What are the 6 main treatments for CF?

Answer 23

1. nebulised antibiotics
2. oral/IV antibiotics
3. DNase
4. Vitamins A, D, E, K
5. Pancreatic enzymes
6. Insulin

Question 24

Why are antibiotics given to CF patients?

Answer 24

to treat bacterial colonisation

Question 25

What does DNase do?

Answer 25

it breaks down thick sputum to allow clearance

Question 26

What are the clinical signs of CF?

Answer 26

1. Clubbing

2. Coarse crackles, wheeze or no sounds heard at all

Question 27

What are the 5 main symptoms of CF?

Answer 27

1. weight loss
2. increased cough with production of large amounts of thick sputum
3. haemoptysis
4. fatty stools
5. reduced vision