Lecture 24: Traffic Across Epithelial Cells (Chloride Secretion)

Question 1

how does chloride secretion work?

Answer 1

1. tight junctions divide cells into apical and basolateral membrane domains
2. na pump sets up ion gradients in the basolateral membrane
3. entry step: nak2cl (secondary active transporter) accumulates chloride above its electrochemical gradient
4. cl- leaves cell through passive diffusion (ion channel in apical into lumen)
5. sodium pumped out –> gets more nakcl through the pump
6. potassium leaves as well through passive diffusion. makes inner cell more negative (which makes cl want to leave cell)
7. cl- gathered in the lumen of the cell will attract na+ and water through paracellular membrane.

**osmolarity is the same but volume has been moved across them. isotonic movement secretion.

Question 2

what is the rate limiting step in chloride secretion

Answer 2

cl- has to leave the cell, and can only do this when the cl- channel is open (its usually gated)

channel is called cystic fibrosis.

Question 3

what is CFTR?

Answer 3

cystic fibrosis transmembrane conductance regulator is a protein, can be defected

Question 4

how does diarrhoea occur?

Answer 4

caused by excessive stimulation of secretory cells in the crypts of the small intestine and the colon

2. due to abnormally high conc of endogenous secretagogues produced by tours or inflammation
3. more commonly due to secretion of enterotoxins from bacteria (vibro cholerae)

irreversibly activate adenylate cyclse causing maximal stimulation of cftr –> secretion overwhelms the absorptive capacity of the colon.

causes more poop to come out

Question 5

molecular mechanism of cholera

Answer 5

g protein coupled receptor –> adenlyate cyclase –> atp –> camp –> protein kinase a (phosphorylates CFTR) –> activates ion channel.

cholera toxin irreversibly activates adenylate cyclase causing activation of CFTR (inhibits it)

so, adenyl cyclase cannot be turned off, it will continuously phosphorylate the channel, and cl- will keep flowing through the channel to the lumen. –> dehydration.

Question 6

how to treat diarrhoea

Answer 6

glucose stimulated water flux (glucose absoroption increase)

through oral hydration therapy.

since they are all stem cells, you can fix this in 5-7 days.

Question 7

what exactly is cystic fibrosis?

Answer 7

cftr that has a genetic defect (inherited from your parents)
- affects children and young adults
- inherited in an autosomal recessive fasion (heterozygotes have no symptoms but are carriers disease freq caries among ethnic groups)

Question 8

what are the organs affected by cystic fibrosis?

Answer 8

airways, liver, pancreas, small intestine, reproducive tract, skin, sweat gland.

always involves epithelial tissues!!!!!

most cases of mortality are respiratory failure.

Question 9

clinical management of cystic fibrosis

Answer 9

chest percussions to improve clearance of infected secretions
antibiotics to treat infections
pancreatic enzyme replacement
attention to nutritional status.

Question 10

cystic fibrosis: a defect in cl- secretion: lungs

Answer 10

a balance between secretion and absorption keeps lung surface moist but prevents excessive fluid build up.

defect prevents cl- secretion + enhances na+ absorption to give a dry lung surface

also no mucous belt –> bacteria grows –> damaged tissue –> no gas exchange –> lung transplant –> death.

Question 11

sweat??

Answer 11

very salty sweat

1. primary isotonic secretion of fluid by acinar cells
2. secondary reabsorption of nacl but NOT water produces a hypotonic solution

salt comes from failure of epithelial cells to reabsorb nacl