L11&12 - Respiratory Channelopathies 1

Question 1

What is Cystic Fibrosis?

Answer 1

An Automosmal recessive disorder, known as a disease of electrolyte transport.

Question 2

What are some inpacted areas in Cysitic Fibrosis?

Answer 2

• Airways - Clogging and infection
• Liver - Blockage of small bile ducts and problems
  with liver function.
• Pancreas - Blockage of the ducts and prevents
  secretion of the digesive enzymes.
• Small intestine - Obstructions due to thick content
• Reproductive tract - absense of vas deferens, 95%
  of males are infertile, small
  number of women are also.

Question 3

What is CFTR?

Answer 3

• A gene that codes for the CFTR (cystic fibrosis transmembrane conductive regulator) protein.
• Mutations in this gene cause cystic fibrosis.

Question 4

What kind of channel is the CFTR protein?

Answer 4

cAMP activated Cl- Channel

Question 5

What is Variable penetrance?

Answer 5

When 2 individuals with the same mutation have different severity of symptoms.

Question 6

What are some common mutations of CF?

Answer 6

F508 del - up to 90% allelic frequency
G551D - 1-3% allecic frequency

Question 7

Why do CF patients have recurrent bacterial infections in the lungs?

Answer 7

The viscous mucus in the lungs prevent the cilia from moving the mucus and acting as a first line of defence against bacteria.

Question 8

How does Na+/Cl- handling affect the upper airways?

Answer 8

• Cl- secretion is limited and Na+ dominates, causing a decrease in the height of the liquid layer.
• This causes the cioar to bend over, not beating to move the mucus.

Question 9

How does Na+/Cl- handling affect the alveoli?

Answer 9

Can cause oedema

Question 10

How does Na+/Cl- handling affect the distal sweat glands?

Answer 10

Sodium and chloride secreted into the duct, the absorption of sodium and chloride on the apical membrane is imapcted causing salty sweat.

Question 11

What are some current treatments of CF?

Answer 11

Physiotherapy
Bronchodilator drugs
Antibiotic steriods
Mucolytics (eg DNAse) - to break down muscus

Question 12

How does gene therapy help CF?

Answer 12

CFTR DNA is delivered to target cells, The DNA is transcribed to mRNAand the protein is produced.

Question 12

How does gene therapy help CF?

Answer 12

CFTR DNA is delivered to target cells, The DNA is transcribed to mRNAand the protein is produced.
(Poor success rate & expensive)

Question 13

What are correctors?

Answer 13

eg Lumacaftor (F508 del)
They force mutant CFTR protein to the cell membraneis the mutant is functional then Cl- secretion is restored.

Question 14

What are Potentiators?

Answer 14

eg Ivacaftor - VX-770
They increase the Po of the CFTR channels, whcih must be trafficked the G55ID mutation is the target.