MW L6 Cystic Fibrosis

Question 1

1 in …. people are carriers

Answer 1

25

Question 2

Most common mutation?

Answer 2

Δf508 ( Δ- deletion f-phenylalanine)

Question 3

Mutation is thought to be a survival advantage in…

Answer 3

cholera

Question 4

Most common cause of morbidity? (2)

Answer 4

lung dysfunction and infection

Question 5

Characterised by build up of…

Answer 5

neutrophils

Question 6

CF is a defect in

Answer 6

ion transport

Question 7

Secretory organs are affected, for example: (5)

Answer 7

• eccrine sweat glands
• digestive system (pancreas, meconium ileus)
• males usually infertile
• nasal polyps
• LUNG DISEASE

Question 8

What is meconium?

Answer 8

The earliest stool of the infant, should be passed within the few days of birth but may not be in CF

Question 9

What receptor is missing in CF

Answer 9

CFTR (cystic fibrosis transmembrane conductance receptor)

Question 10

How is air-surface liquid formed?

Answer 10

CFTR pumps out Cl-, Na+ follows (paracellular), water follows (aquaporins).
ENaC pumps Na+ back out.
= balance

Question 11

What happens to air-surface liquid in CF?

Answer 11

No CFTR so salt is no longer dragged through, lose water and airway surface is low volume.

Question 12

Low volume of air-surface liquid results in…

Answer 12

sticky viscous mucus
difficult for cilia to clear
growth of bacteria

Question 13

What can be used to partially correct the air-surface liquid?

Answer 13

Hypertonic saline

Question 14

Why are lung infections harder to treat in CF?

Answer 14

Biofilms

Question 15

Common lung infections: (4)

Answer 15

p aeruginosa
s aureus
h influenza
burkoholderia cepacia (rarer but harder to treat)

Question 16

Early treatment (2)?

Answer 16

Proper nutrition and enzyme suppliments

Question 17

Mucolysis therapy e.g.

Answer 17

DNAase (Dornase alpha)

N-acetyl cysteine is not effective

Question 18

What does DNAase do?

Answer 18

breaks down viscous mucus containing large amounts of DNA from inflammatory cells and bacteria

Question 19

Inhaled antibiotics are used e.g.

Answer 19

Tobramycin

Question 20

Beta agonists are used to….

Answer 20

activate residual CFTR if they are present

Question 21

3 types of defect causing CF

Answer 21

Premature stop codon - no CFTR
In-frame deletion - defective processing
Substitution - defective regulation

Question 22

Potential therapy for class 1 CF

Answer 22

Ataluren - fires readthrough (ignore) of premature stop

Question 23

What is class 1 CF caused by?

Answer 23

Premature stop codon (5% of pop)

Question 24

What is class 2 CF caused by?

Answer 24

Defective channel processing

Question 25

What is class 3 CF caused by?

Answer 25

Defective channel regualtion

Question 26

Therapy for class 3 CF?

Answer 26

Ivacaftor - turns on channels that don’t work as well

Question 27

Potential therapies for class 2? (2)

Answer 27

Lumacraftor and N6022 - stabilise CFTR on the membrane

Question 28

Alternative approach to treating CF? (2)

Answer 28

ENAC antagonism

Actiativing Cl channels

Question 29

What does ENAC transport?

Answer 29

Cl-

Question 30

What does CFTR transport?

Answer 30

Na+

Question 31

What are the risks of activating alternative Cl channels?

Answer 31

CaCC increase amount of mucus by activating goblet cells

Question 32

What does CaCC stand for?

What does it transport?

Answer 32

Calcium activated chloride channel

Question 33

e.g. of CaCC activator?

Answer 33

Denufosol (p2y2 agonist but not effective at maintain lung function)

Question 34

e.g. of blocking ENAC

Answer 34

amiloride

Question 35

risk of blocking the ENAC

Answer 35

hyperkalemia

Question 36

Substantial improvement in life expectancy due to (4)

Answer 36

Early recognition
Nutrition
Aggressive antibiotics
Transplant

Question 37

What anti-inflammatory therapies are used (2)?

Answer 37

High dose ibuprofen

Glucocorticoids