Block 2 Lecture 26

Question 1

explain the CFTR gene

Answer 1

it is an autosomal recessive gene, not sex linked and individual must have 2 copies of recessive gene

Question 2

what are the odds of being a carrier

Answer 2

1 in 815

Question 3

what are the odds of white people having CF

Answer 3

1 in 3,300

Question 4

what are the odds of African Americans have CF

Answer 4

1 in 15,000

Question 5

what are the odds of asian Americans having CF

Answer 5

1 in 32,000

Question 6

what are the odds of a child in the United States being born with CF

Answer 6

1 in 4,000

Question 7

what is the clinical presentation of CF

Answer 7

1. some degree of malnourishment
2. chronic pulmonary disease
3. high concentrations of NaCl in sweat

Question 8

what are gastrointestinal problems due to

Answer 8

pancreatic insufficiency

Question 9

what are respiratory problems due to

Answer 9

airways being plugged with thick secretions from chronic bacterial infections

Question 10

what kind of protein is CFTR

Answer 10

an ATP dependent, 2nd messenger regulated Cl- channel,

it hydrolyzes ATP but used ATP as a ligand for the channel to open

Question 11

what is the most common mutation of CFTR and what happens

Answer 11

deltaF508 referring to the deletion of phenylalanine at position 508 of the amino acid sequence, results in protein that does not traffic properly so it gets degraded rather than inserted in the plasma membrnae

Question 12

what is pleiotropy

Answer 12

when one gene influences multiple phenotypic traits

Question 13

what are the pleiotropic actions of CFTR a result of

Answer 13

CFTR interacting with other proteins and with the cytoskeleton through interactions with PDZ containing proteins at apical pole of the cell

Question 14

what should happen in cephalic/gastric phases of digestion?

Answer 14

2 principle hormones are ACh and gastrin. ACh receptors in acinar cells interact with ACh released in response to vagus nerve. CCK receptors interact with gastrin. zymogens and fluid from acinar cells are released in response to these stimuli

Question 15

what should happen in the intestinal phase of digestion?

Answer 15

CCK is the major stimulator of acinar secretion of zymogen granules. CCK is released from I cells found in the wall of the duodenum in response to lipids in chyme. CCK binds to the CCk receptor on basolateral membrane of acinar cells and activates pathways that release zymogen granules and secretion of Cl- Na+ and water.
-secretin is the major stimulator of ductal secretion of NaHCO3 and water. secretin is released by S-cells found in walls of the duodenum in response to H+ in chyme. secretin binds to the secretin receptor in basolateral membrane of ductal cells and leads to secretion of HCO3- Na+ and water

Question 16

what is the acinar impact of a lesion in CFTR?

Answer 16

• acinar cells rely on a Ca2+ activated Cl- channel so CFTR has no direct impact on acinar cell function
• because of duct cells being affected and acidifying the lumen, endocytosis at the apical membrane is inhibited at acidic pH

Question 17

what is the ductal impact of a lesion in CFTR?

Answer 17

• apical Cl- channels are CFTR mediated
• secretion of HCO3- into lumen depends on cycling of Cl-
• with CFTR being compromised this cycling breaks down and once Cl- secreted by acinar cells is depleted, the Cl-/HCO3- exchanger can’t function so no HCO3- is secreted

Question 18

what does inadequate secretion of NaHCO3 and water result in

Answer 18

1. insufficient volume flow to move digestive enzymes into the small intestine
2. acidification of lumen results in failure of zymogen secretion by acinar cells resulting in premature activated of the digestive enzymes that digest the pancreatic cells they’re made in