Obstructive lung disease: cystic fibrosis (R3)

Question 1

Pathophysiology
- What is the name of the gene + protein?
- What is this protein’s normal function?

Answer 1

CFTR gene (cystic fibrosis transmembrane conductance regulator) which encodes the CFTR protein
Protein migrates from the ER to the plasma membrane

Question 2

Pathophysiology
- What mode of inheritance?
- What is the mutation?
- What is the effect of the mutation

Answer 2

Autosomal recessive
Deletion of 3 bases in DNA; leading to deletion of the 508th amino acid, phenylalanine (ΔF508)
Results in the CFTR protein being misfolded, so it can’t migrate from the ER to the plasma membrane.
Can’t pump out Cl- ions into secretions –> secretions become thick.

Question 3

Clinical features
- Main issue in newborns?

Answer 3

Question 4

Clinical features
- Main issue in early childhood?

Answer 4

Pancreatic secretions are thickened –> can block pancreatic ducts

Question 5

Clinical features
- Consequences of blocked pancreatic ducts?

Answer 5

• Pancreatic enzymes don’t reach the small intestines –> proteins and fat not absorbed. Can lead to poor weight gain, failure to thrive, and steatorrhea
• Acute and chronic pancreatitis
• Insulin dependent diabetes (from pancreatic damage)

Question 6

Clinical features
- Main issue in later childhood?

Answer 6

Affects the lungs.
Thickened mucus impairs mucociliary clearance

Question 7

Clinical features
- Consequences of this?

Answer 7

• Predisposed to bacterial infections –> CF exacerbation
• Chronic bacterial infection and inflammation can lead to bronchiectasis
• Repeated CF exacerbations can lead to respiratory failure, which is the leading cause of death

Question 8

Investigations
- 2 main diagnostic tests?

Answer 8

IRT - immunoreactive trypsinogen
Sweat test

Question 9

Investigation
- Why would IRT be found in the blood?
- How is the IRT test performed?
- If positive, next step?

Answer 9

IRT is released into the blood when the pancreas is damaged.
Heel prick
Sweat test

Question 10

Investigation
- When CFTR doesn’t work in the sweat glands, what happens to Cl-?
- In CF, what does a positive sweat test show?

Answer 10

• Cl- can’t be reabsorbed
• High Cl- in sweat