Block 2 Lecture 26 Flashcards
(18 cards)
explain the CFTR gene
it is an autosomal recessive gene, not sex linked and individual must have 2 copies of recessive gene
what are the odds of being a carrier
1 in 815
what are the odds of white people having CF
1 in 3,300
what are the odds of African Americans have CF
1 in 15,000
what are the odds of asian Americans having CF
1 in 32,000
what are the odds of a child in the United States being born with CF
1 in 4,000
what is the clinical presentation of CF
- some degree of malnourishment
- chronic pulmonary disease
- high concentrations of NaCl in sweat
what are gastrointestinal problems due to
pancreatic insufficiency
what are respiratory problems due to
airways being plugged with thick secretions from chronic bacterial infections
what kind of protein is CFTR
an ATP dependent, 2nd messenger regulated Cl- channel,
it hydrolyzes ATP but used ATP as a ligand for the channel to open
what is the most common mutation of CFTR and what happens
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
what is pleiotropy
when one gene influences multiple phenotypic traits
what are the pleiotropic actions of CFTR a result of
CFTR interacting with other proteins and with the cytoskeleton through interactions with PDZ containing proteins at apical pole of the cell
what should happen in cephalic/gastric phases of digestion?
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
what should happen in the intestinal phase of digestion?
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
what is the acinar impact of a lesion in CFTR?
- 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
what is the ductal impact of a lesion in CFTR?
- 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
what does inadequate secretion of NaHCO3 and water result in
- insufficient volume flow to move digestive enzymes into the small intestine
- 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
