Cystic Fibrosis

Question 0

What gene is indicated in CF?

Answer 0

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene

Question 1

What is the inheritance pattern of CF?

Answer 1

Autosomal recessive

Question 2

What does CFTR gene code for?

Answer 2

A chloride ion channel

Question 3

Where is CFTR on the cell?

Answer 3

Apical luminal membrane

Question 4

What organ tissues is CFTR present?

Answer 4

Airways, pancreatic ducts, intestines, other tissues

Question 5

What is the mean survival age of a patient with CF?

Answer 5

37.4 years

Question 6

What is the prevalence of CF across ethnicities?

Answer 6

Caucasian: 1:2500
Hispanic: 1:9500
African American: 1:15000
Asian American: 1:32000

Question 7

How many caucasians are carriers?

Answer 7

1:32

Question 8

What are the five mutation classes for CF?

Answer 8

Class 1: No protein produced
Class 2: Defective protein folding
Class 3: Defective gating or regulation
Class 4: Defective ion transport
Class 5: Normal CFTR but decreased amounts

Question 9

What gene problem is indicated in Class 1 mutations?

Answer 9

G542X

Question 10

What gene problem is indicated in Class 2 CF?

Answer 10

F508del

Question 11

What gene problem is indicated in Class 3 mutations?

Answer 11

G551D

Question 12

What is the most common CF mutation?

Answer 12

F508del (70%)

Question 13

How much CFTR activity remains in classes 1, 2, 3? How about classes 4 and 5?

Answer 13

1-3: <5%

Question 14

What results from the F508del at the cellular level?

Answer 14

Misfolding, stays in ER for proteasome degradation

Some get to surface but do not function well

Question 15

Can outcome be predicted on an individual level when considering severity of mutation?

Answer 15

No

Question 16

What does the G551D mutation result in at the cellular level?

Answer 16

Inability for channel to respond to ATP, increases time in closed conformation

Question 17

What happens to water distribution when the CFTR gene is functioning properly?

Answer 17

Chloride goes to ECF

Water inside cell follows gradient, goes outside

Question 18

What happens to water flow when CFTR is functioning improperly?

Answer 18

Not enough water outside on cell surface

Question 19

What is the sequence of events that leads to CFTR regulation?

Answer 19

External stressors -> cAMP intracellular pathway -> Activation of PKA -> phosphorylation of R domain -> Activation of CFTR

Question 20

What is ASL and what is its function?

Answer 20

Airway surface liquid. Activates cilia and hydrates mucous

Question 21

What happens to ASL volume in CF?

Answer 21

ASL layer not maintained

Question 22

What bacteria infections are common in CF patients?

Answer 22

Staph aureus
Pseudomonas aeruginosa
Burkholderia sepacia
Haemophilus influenza
Aspirgillus fumigatus

Question 23

How many CF pediatric patients get Pseudomonas aeruginosa?

Answer 23

40-60%

Question 24

What are mainstays in treating lung dysfunction in CF?

Answer 24

Chest physiotherapy to remove drainage | Aggressive antibiotics to clear infection

Question 25

What other things are common to treat CF lung dysfunction?

Answer 25

Hypertonic saline flush and DNase aerosols to make mucous less viscous Anti-inflammatories

Question 26

What is the physiological function of CFTR in pancreatic cells?

Answer 26

Secrete HCO3 to recruit intracellular H2O | Prevent formation of protein plugs

Question 27

What is the pathophysiology of pancreatic CFTR dysfunction?

Answer 27

Protein plug blockage -> damage to cells -> proteolytic enzyme leakage -> destruction of tissue

Question 28

What is the function of CFTR in the intestine?

Answer 28

Hydration of intestinal epithelium

Question 29

What is the result of CFTR dysfunction in the intestine?

Answer 29

Obstruction Inability to absorb nutrients, fats Susceptibility to small and large bowel cancer

Question 30

What anatomical feature is absent in men with CF?

Answer 30

Vas deferens

Question 31

What is the definitive diagnostic test for CF?

Answer 31

Sweat test

Question 32

How does CFTR work in the skin?

Answer 32

Opposite of GI and lungs, reabsorbs Cl

Question 33

Why does CFTR dysfunction lead to salty sweat?

Answer 33

Decreased ability to reabsorb Cl and Na, salty sweat

Question 34

How can CF lead to diabetes?

Answer 34

Pancreatic destruction of Beta cells in pancreas | Insulin resistance as well

Question 35

What types of prenatal testing are available for CF?

Answer 35

Chorionic villous sampling Amniotic fluid Echogenic bowel on Ultrasound

Question 36

What are the major objectives for CF treatment?

Answer 36

Lung: Clear secretions, control infx Maintain nutrition Prevent intestinal obstruction

Question 37

What therapy has been used to target G551D mutations?

Answer 37

Ivacaftor: Keeps channel open longer

Question 38

What therapy has been tailored for F508del mutations?

Answer 38

Lumacaftor: promotes traffic of CFTR to the surface from ER | with Ivacaftor