Integration of Pathology and Genetics - Cystic Fibrosis

Question 1

What is the inheritance pattern of cystic fibrosis?

Answer 1

Autosomal recessive

Question 2

What is the most common population of cystic fibrosis carriers in the US?

Answer 2

North American Caucasians

Question 3

What are the clinical features of CF?

Answer 3

• Pulmonary symptoms
• Malnutrition
• Steatorrhea

Question 4

What is the function of cystic fibrosis transmembrane regulator (CFTR)?

Answer 4

Has many functions - main function is as a Cl- channel but it is also a regulatory protein for other channels - its functions are TISSUE specific

Question 5

What is the most common mutation in CF?

Answer 5

F508 3 base deletion which removes a phenylalanine

Question 6

What are the most serious types of CF mutations?

Answer 6

Class I - decrease in severity as the class number increases

Question 7

What is the generally accepted theory for the pulmonary pathogenesis of CF?

Answer 7

ASL (airway surface liquid) has low volume due to lack of regulation of ENaC, Na is hyper- absorbed, Cl follows through other pathways, water follows passively, low volume of ASL leads to increased mucus concentrations, delayed transport, mucus adhesions, decreased ciliary beat and inhibited bacterial clearance.

Question 8

What can be seen on x-ray of CF?

Answer 8

• Upper lobe predominant bronchiectasis 
– Signet ring
– Tram tracking
• Peribronchial cuffing
• Nodules/mucous impaction 
• Blebs,cysts

Question 9

Why are CF patients more susceptible to Pseudomonas?

Answer 9

Generally unknown but thought to be due to the ASL milieu and the cell receptors

Question 10

What are the effects of CF on the sinuses?

Answer 10

• Hypertrophy/hyperplasia of secretory elements
• Inflammation and edema
• Polyps

Question 11

What are the effects of CF on the pancreas?

Answer 11

Obstruction of ducts with inspissated secretions leads to dilation, destruction and fibrosis - fat malabsorption

Question 12

How can fat absorption in CF patients be evaluated very easily?

Answer 12

Look at Vitamin D/E/K/A levels

Question 13

What is CF related diabetes?

Answer 13

• Pancreatic endocrine insufficiency

* Symptoms- polyuria, polydipsia, weight loss, unexplained drop in lung function

Question 14

How does CF lead to bone and joint disease?

Answer 14

Large majority due to Vitamin D deficiency and calcium malabsorption

Question 15

What is the effect of CF on the GU of females?

Answer 15

Endocervicitis, mucus distended cervical glands – Anovulatory with 1/5 infertile

Question 16

What is the effect of CF on the GU of males?

Answer 16

Failure in transport (vas deferens) with 98% infertile

Question 17

What is the effect of CF in the sweat glands?

Answer 17

Sweat becomes salty with increased sensitivity to dehydration

Question 18

What are some lab tests that can diagnose CF?

Answer 18

– Sweat test
– Genetic test
– Nasal potential

Question 19

How might hypertonic saline work in CF treatment?

Answer 19

Increased osmolality of ASL will draw more water out

Question 20

What is a potentiator?

Answer 20

Protein that binds to the dysfunctional CFTR protein and corrects its folding to regain function

Question 21

What is a corrector?

Answer 21

A therapeutic chaperone used to help the dysfunctional CFTR fold correctly