Cell Processes: Traffic across epithelial cells: chloride secretion

Question 1

What is a NaK2Cl symporter

Answer 1

Transporter that uses the energy of the Na gradient to actively accumulate chloride above its electrochemical gradient (in chloride secretion)

Question 2

How does Cl leave cell in chloride secretion?

Answer 2

Cl leaves the cell by passive diffusion through an ion channel (exit step = secretion) it is selective for Cl- and gated (regulated)

Question 3

Why and how does Na and K leave cell in chloride secretion

Answer 3

Na exits via the basolateral Na-pump and K + via channel (K leaving makes cell more negative, so Cl- will want to leave negative environment)

Question 4

What does the transport of Cl across the epithlium do?

Answer 4

induces paracellular Na and water fluxes (creates negative environment which attracts positive ions)

Question 5

What is the rate limiting step of chloride secretion

Answer 5

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) (channel shut = no Cl- movement, no isotonic secretion)

Question 6

What causes secretory diarrhoea?

Answer 6

Caused by excessive stimulation of the secretory cells in the crypts of the small intestine and colon
Cells become over stimulated pump out a lot of Cl- so a lot of Na and water (exceeding capacity to reabsorb fluid in gut)

Question 7

One possible cause of excessive stimulation of the secretory cells. These molecules are produced by tumours and inflammation.

Answer 7

abnormally high concentrations of endogenous secretagogues

Question 8

What are the crypts

Answer 8

Location of secretory cells in the small intestine and colon

Question 9

A cause of excessive stimulation of the secretory cells due contaminated water

Answer 9

secretion of enterotoxins from bacteria such as Vibrio cholerae

Question 10

What are enterotoxins

Answer 10

toxins that irreversibly activate adenylyl cyclase causing a maximal stimulation of CFTR lead to a secretion that overwhelms the absorptive capacity of the colon

Question 11

What does oral therapy treat?

Answer 11

secretory diarrhoea caused by cholera

Question 12

5 step cholera toxin mechanism

Answer 12

cholera toxin irreversibly acts on adenylyl cyclase -> excess cAMP produced -> protein kinase A phosphorylates R region of CFTR -> ATP binds to nucleotide binding domain -> CFTR channel stays open

Question 13

What are villus cells involved in?

Answer 13

Absorption

Question 14

What is cystic fibrosis

Answer 14

A genetic disorder affecting children and young adults, usually ending in death from respiratory issues.

Question 15

How is cystic fibrosis inherited

Answer 15

It is inherited in an autosomal recessive fashion (Heterozygotes have no symptoms but are carriers)

Question 16

Likelihood of a child from two carriers getting cystic fibrosis

Answer 16

1/4

Question 17

Proportion of Northern European newborns affected by CF

Answer 17

1 in 2500

Question 18

Proportion of Northern Europeans who are carriers of CF

Answer 18

1 in 25

Question 19

6 organs commonly affected by CF

Answer 19

Airways, liver, pancreas, small intestine, reproductive tract, skin

Question 20

4 treatments to manage CF and increase survival time

Answer 20

chest percussion, antibiotics, enzyme replacement, attention to nutrition

Question 21

Most common way cystic fibrosis kills people

Answer 21

respiratory failure

Question 22

Median survival of patients with CF

Answer 22

38 years

Question 23

What does CFTR stand for

Answer 23

Cystic fibrosis transmembrane conductance regulator

Question 24

What is CFTR

Answer 24

Cl channel regulated by protein kinase A dependent phosphorylation of the R domain and binding of ATP to the NBD (nucleotide-binding domain)

Question 25

What causes R domain to leave CFTR pore

Answer 25

Binding of ATP to cause R domain to leave pore

Question 26

The absence of functional CFTR receptors in the lungs creates a

Answer 26

dry lung surface

Question 27

CFTR lung pathology (7)

Answer 27

CFTR gene defect -> defective ion transport -> airway surface liquid depletion -> defective mucociliary clearance -> mucus obstruction, infection, inflammation

Question 28

What does a normal lung epithelial cell do in Cl secretion

Answer 28

it has a balance between secretion and absorption keeping the lung surface moist and prevents excessive fluid build up

Question 29

What does a lung epithelial cell do in CF

Answer 29

the defective Cl- channel prevents isotonic fluid secretion and enhances Na+ absorption to give a dry lung surface

Question 30

Two stages of sweat formation

Answer 30

Primary isotonic secretion of fluid (by acinar cells), secondary reabsorption of NaCl to produce a hypotonic solution (by duct cells)

Question 31

What does failure to reabsorb NaCl in ducts of sweat glands do?

Answer 31

produce salty sweat in CF patients

Question 32

Neurotransmitters that stimulate sweat production

Answer 32

ACh (Acetylcholine), NA (Noradrenaline)

Question 33

Parasympathetic stimulation of sweat production uses...

Answer 33

ACh

Question 34

Sympathetic stimulation of sweat production uses...

Answer 34

NA

Question 35

What is CLCA

Answer 35

Chloride channel accessory, controlled by calcium - in Acini, controls secretion of Cl-

Question 36

What is ACh

Answer 36

Neurotransmitter that activates CLCA

Question 37

What is NA

Answer 37

Neurotransmitter that activates CFTR

Question 38

What is ENaC

Answer 38

Epithelial sodium channel, responsible for reabsorbing sodium out of the sweat.

Question 39

What special about CFTR

Answer 39

It is the only chloride channel responsible for reabsorbing chloride from sweat

Question 40

in sweat formation, why do Cl want to enter cell down electrochemical gradient

Answer 40

duct cells the membrane potential is depolarised

Question 41

Where does Cl- accumulate in CF patients

Answer 41

Cl- accumulates in the duct lumen producing salty sweat