CF

Question 1

Syndrome of

Answer 1

chronic sinopulmonary infections, malabsorption and nutritional abnormalities

Question 2

CF gene encodes for the _______ protein

Answer 2

cystic fibrosis transmembrane conductance regulator (CFTR)

Question 3

CFTR functions as _______ and controls

Answer 3

• an ion channel

- the movement of salt and water into and out of cells

Question 4

Mutations in the CFTR gene impair

Answer 4

this movement, critically altering host defense in the lung

Question 5

_______ inheritance. CF gene is a large gene on chromosome _. _______ is the most common mutation

Answer 5

• Autosomal recessive
• 7
• deltaF508

Question 6

CFTR protein is a member of the _______ superfamily and expressed in the _______.

Answer 6

• ATP-binding cassette

- epithelial cells lining the exocrine glands

Question 7

CFR protein has ________ membrane spanning domains, __ nucleotide-binding domains and a unique, highly charged _______ domain.

Answer 7

• 2 six-span
• 2
• regulatory

Question 8

Diagnosing

Answer 8

• newborn screen

- sweat test (>60 mmol/L)

Question 9

CF tx

Answer 9

potentiator: Ivacaftor

Question 10

Mutations in CF tend to cause either:

Answer 10

(1) no protein synthesis
(2) misfolding of protein leading to degradation before reaching apical cell surface
(3) altered conductance such that the protein can’t be conveyed to the apical surface, or
(4) partial loss-of-function such that the CFTR proteins don’t work as well as normal.

Question 11

_______ and _______ are the most common pathogens found in CF lungs (since the mucus is an ideal breeding ground for bacteria).

Answer 11

• Pseudomonas

- Staphylococcus aureus

Question 12

In lung: CFTR normally excretes _______ to move _______ into the mucus layer overlaying the lung epithelium (like in the intestine). With defective CFTR, _______

Answer 12

• Cl-
• water
• this water secretion doesn’t happen

Question 13

normal CFTR also downregulates _______. Without CFTR, have elevated levels of _______, which further removes water from the lumen (and the mucus) into the epithelial cells, exacerbating the _______.

Answer 13

• epithelial sodium channels
• import of Na+ into epithelial cell
• thickness of the mucus

Question 14

in sweat glands, the CFTR defect causes a problem in _______, as opposed to in the lung and intestine, where the defect causes a problem in _______

Answer 14

• getting chloride into the epithelial cells

- getting them out

Question 15

Treat (lungs) with

Answer 15

airway clearance therapy, antibiotics to keep lungs clear, inhaled mucolytics (break up the mucus), brochodilators, enzyme replacement, vitamin A/D/E/K replacement, azithromycin used chronically

Question 16

Therapeutic approaches:

Answer 16

eventually need lung transplant. Gene therapy not working yet, but “protein rescue” seems promising: in principle, could correct misfolding or get nonconducted CFTR proteins to the cell membrane to work properly