CF Module- Scott Flashcards Preview

CRRAB II- FINAL > CF Module- Scott > Flashcards

Flashcards in CF Module- Scott Deck (31):
1

How is CF inherited?

Autosomal Recessive

2

What gene is mutated in CF?

CFTR gene = cystic fibrosis transmembrane conductance regulator gene

3

What does the CFTR gene code for?

It is a chloride and bicarb channel found on apical surface of epithelial cells lining airways, pancreatic ducts, intestines, and other tissues

4

What causes 90% of deaths in CF?

Respiratory Failure

5

How many transmembrane domains does the CFTR channel have?

12 transmembrane domains

6

What are the two regulatory sites to promote opening of the channel?

R domain: gets phosphorylated

Nucleotide binding domain (NBD): binds ATP

7

What is the function of CFTR channel?

-Controls luminal ion concentration and pH
-Controls movement of H20

8

Which way is Cl- moving through the CFTR channel?

It is moving DOWN its concentration gradient. Into the lumen (and it pulls water with it!)

9

What two regulatory signals are needed to open the CFTR channel?

-Cyclic AMP intercellular signaling pathway activates protein kinase A which phosphorylates the R domain

-ATP that are generated bind to the NBD domains

10

What chromosome is the CFTR gene found on?

Chromosome 7

11

Does incidence of CF vary with ethnic group?

YES!!! Mutation based diagnostic tests are tailored to different ethnic groups

12

Which classes of CFTR mutations are more severe?

Class 1-3

13

Which classes of CFTR mutations are less severe?

Class 4-5

14

Which mutation is seen in 70% of CF alleles/ most common?

Class 2! Defective protein folding activates ER quality control and degrades protein

F508del

15

G524X mutation

Class 1 = nonsense mutation and no protein is produced

16

F508del mutation

Class 2 = defective protein folding activates ER quality control and degrades protein

*seen in 70% of CF alleles

17

G551D mutation

Class 3 = defective gating or regulation of channel opening

18

Describe Class 4 and 5 mutaitons

Class 4 = defective ion transport

Class 5= normal CFTR produced but decreased amounts

**These mutations have less severe disease

19

How much CFTR activity is remaining in severe disease? (Class mutation 1-3) vs. Less Severe disease?

Less than 1% CFTR activity in class 1-3

Around 5% CFTR activity in class 3-4

20

What are the 4 bacterial infections characteristic of CF?

Staph Aureus
Pseudomonas aeruginosa
Burkholderia Cepacia
H. influenza

21

Describe the pathogenesis of CF

-Decreased ASL layer
-Build up of viscous mucous and failure to clear bacteria
-Persistent colonization and desicated mucous leads to inflammation (damaging agents)
-Infection + inflammation + mucus plugging = long term structural damage
-Ultimate outcome is respiratory failure

22

Which inflammatory pathway is activated in epithelial cells?

LPS
LTR4
MyD88
NFkB

23

What are the main inflammatory mediators in CF?

IL1B
TNF alpha
IL-8

*These recruit neutrophils!

24

What do neutrophils release that ultimately causes damage to CFTR itself and epithelial cells?

Neutrophils release elastase

25

What infections appears in 40-60% of pediatric patients with CF?

Pseudomonas Aurgenosa

26

What are 4 things that help prevent pulmonary damage in pts with CF?

-Chest physiotherapy to improve drainage
-Aggressive treatment of infections with antibiotics
-Hypertonic Saline w/ DNAase aerosols to make mucous less viscous
-Anti-inflammatories

27

When is associated liver disease considered clinically significant?

When it occurs with cirrhosis or portal hypertension

28

How is molecular genetic knowledge used for better testing and treatment?

-Widespread screening
-New treatments to correct specific mutation defects

29

What is the overall CF risk?

1/2500

30

What is the definitive test for diagnosising CF?

The sweat test

31

What is the difference in pancreatic involvement the severe (I, II, III) and less severe (IV, V) mutations?

The severe mutations cause a defect in pancreatic ducts. The less severe ones do not-the pancreas is sufficient!