Cystic Fibrosis

Question 1

Where is the CF gene located?

Answer 1

long arm of chromosome 7

Question 2

What is the most common defect in CF patients?

Answer 2

Delta 508 (3 nucleotide deletion, loss of phenylalanine)

Question 3

Which genetic mutation do we have medication for?

Answer 3

G551 D

Question 4

Where is CFTR protein located?

Answer 4

plasma membrane of epithelial cells lining: lung, panc, intestines, GB, liver, kidney, salivary/sweat glands, epidydmis

Question 5

Class I CFTR mutation is?

Answer 5

premature stop codon! defective protein production so decreased quantity

Question 6

Class II CFTR mutation is in processing and trafficking… explain

Answer 6

deletion of aa causes improper folding of the polypeptide. Leads to abnormal interactions with chaperone proteins in ER and degradation in ER so the protein does not arrive at the apical membrane!

Question 7

Which CFTR mutation is there medication that can modify function?

Answer 7

Class III defective cAMP regulation of the CFTR… gating abnormality! So, meds attach and enhance the channel activity! potentiator!

Question 8

What three processes contribute to mechanical clearance of the lung?

Answer 8

ion transport systems (in airway epithelium), secreted products (mucins), ciliary beating

Question 9

What are the three ion transport systems located in the apical airway epithelium?

Answer 9

ENaC, CFTR, CACC (Ca activated CL- channel)

Question 10

What is one of the CFTR modifying genes that cause wide spectrum of phenotypes?

Answer 10

Transforming Growth Factor-Beta 1

Question 11

What are the most important bacterial infections with CF lung disease?

Answer 11

staph aureus and pseudomonas aeruginosa

Question 12

What are some characteristic radiologic features of CF?

Answer 12

Tram Tracks (thick dilated airway and mucus block), pleural line separating lung from air

Question 13

What agents work to change the viscosity of mucous?

Answer 13

Dornase Alfa (rhDNase, pulmozyne) lyse dead inflamm cells so it's easier to cough out the mucus!
hypertopic saline to hydrate the mucus

Question 14

What role does azythromycin play in CF therapy?

Answer 14

Improves lung function and decreases exacerbations by working as anti-inflammatory agent. not for antibiotics!

Question 15

How successful are lung transplants in CF patients?

Answer 15

VERY!!! best!! because patients are younger and have fewer comorbidities

Question 16

Why are CF patients predisposed to diabetes?

Answer 16

Their digestive enzymes cannot get out of the pancreas because ducts are clogged. SO, the enzymes digest the pancreas! leads to diabetes

Question 17

What are a CF patient’s clinical manifestations of Pancreatic/GI disease?

Answer 17

Large, fatty, greasy stools! poor weight gain!

Question 18

Diet advice for CF?

Answer 18

High caloric, high fat diet because they need to gain wait! also malabsoprtion of fat soluble vitamins so give supplements. nutritional support!

Question 19

How can we treat CF pancreatic disease?

Answer 19

enzyme replacement therapy, suppress gastric acid secretion (helps enzymes work better)

Question 20

How do we diagnose CF?

Answer 20

Sweat chloride measurement- pilocarpine iontophoresis method- IRT test or genetic test

Question 21

What are the criteria for diagnosing CF?

Answer 21

2 known CF causing mutations OR any of the following plus 2 sweat chloride levels great than 60 : family history, positive newborn screening test, typical symptoms