Chloride Secretion Epithelial Cells

Question 1

Step 1 chloride secretion

Answer 1

Tight junction divide cells into apical and basolateral membrane domains

Question 2

Step 2 chloride secretion

Answer 2

Na pump sets up ion gradients (x3Na+ out x2K+ in)

Question 3

What step of chloride secretions does the “NaK2Cl symporter uses the energy of the Na gradient to actively accumulate chloride above its electrochemical gradient”

Answer 3

Step 3 chloride secretion

Question 4

Step 4 chloride secretion

Answer 4

Cl leaves the cell by passive diffusion through an ion channel

Question 5

What step of chloride secretion does “Na exit via the basolateral Na-pump and K+ via channel”

Answer 5

Step 5 chloride secretion

Question 6

Step 6 chloride secretion

Answer 6

The transport of Cl across the epithelium induces paracellular Na and water fluxes

Question 7

What has to be open for accumulation of Cl- above electrochemical equilibrium to leave the cell

Answer 7

Cl- channel is open

Question 8

In the rate-limiting step what is strictly regulated (gated)

Answer 8

The opening of the Cl- channel

Question 9

What is the rate-limiting step in Cl- secretion

Answer 9

The opening of the Cl- channel

Question 10

What has Cl- channel been identified at the molecular level as…

Answer 10

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

Question 11

The overstimulation of _____ has been implicated in ____ diarrhea and its _____ causes ____ fibrosis

Answer 11

The overstimulation of CFTR has been implicated in SECRETORY diarrhea and its DYSFUNCTION causes CYSTIC fibrosis

Question 12

What is secretory diarrhea caused by

Answer 12

Excessive stimulation of the secretory cells in the crypts of the small intestine and colon

Question 13

What is excessive stimulation of secretory cells caused by

Answer 13

• Abnormally high conc. of endogenous secretagogues produced by tumours or inflammation
• Secretion of enterotoxins from bacteria (Vibrio Cholerae)

Question 14

_____ irreversibly activate ____ cyclase causing a ____ stimulation of CFTR lead to a ____ that overwhelms the absorptive capacity of the colon

Answer 14

ENTEROTOXINS irreversibly activate ADENYLATE cyclase causing a MAXIMAL stimulation of CFTR lead to a SECRETION that overwhelms the absorptive capacity of the colon

Question 15

What can oral rehydration therapy be used to treat caused by cholera

Answer 15

Secretory diarrhea

Question 16

What is inherited in an autosomal recessive fashion that affects children and young adults

Answer 16

Cystic fibrosis

Question 17

What have no symptoms of cystic fibrosis but are carriers

Answer 17

Heterozygotes

Question 18

List the organs affected by cystic fibrosis

Answer 18

• Airways
• Liver
• Pancreas
• Small intestine
• Reproductive tract
• Skin

Question 19

In cystic fibrosis what are most cases mortality a result of

Answer 19

Respiratory failure

Question 20

What is a common them of involvement in cystic fibrosis

Answer 20

Epithelial tissues

Question 21

Clinical management of cystic fibrosis

Answer 21

• Chest percussion to improve clearance of infected secretions
• Antibiotics to treat infections
• Pancreatic enzyme replacement
• Attention to nutritional status

Question 22

CFTR is a __ channel regulated by ___ kinase A dependent _____ of the R domain and binding of ___ to the NBD

Answer 22

CFTR is a Cl channel regulated by PROTEIN kinase A dependent PHOSPHORYLATION of the R domain and binding of ATP to the NBD

Question 23

Do normal or CF lung epithelial cells “a balance between secretion and absorption keeps the lung surface moist but prevents excessive fluid build up”

Answer 23

Normal lung epithelial cells

Question 24

Do normal or CF lung epithelial cells “the defective Cl- channel prevents isotonic fluid secretion and enhances Na+ absorption to give a dry lung surface - enviro grows bacteria”

Answer 24

Lung epithelial cell in CF

Question 25

Blocking Cl- secretion contribution to lung pathology flow pathway

Answer 25

1. CFTR gene defect (gene therapy)
2. Defective ion transport
3. Airway surface liquid depletion
4. Defective mucocillary clearance
5. Mucus obstruction&raquo_space;> infection&raquo_space;> inflammation

Question 26

What type of sweat do people with CF have

Answer 26

Very salty sweat

Question 27

2 stage process of sweat formation

Answer 27

• Primary isotonic secretion of fluid by acinar cells
• Secondary reabsorption of NaCl but NOT H2O produces a hypotonic solution

Question 28

The failure of epithelial cells in the ducts of sweat glands to reabsorb NaCl produces…

Answer 28

Salty sweat in CF patients

Question 29

CF and sweat formation; in ___ cells the membrane potential is ____ and Cl- wants to enter the cell ___ its _____ gradient

Answer 29

CF and sweat formation; in DUCT cells the membrane potential is DEPOLARISED and Cl- wants to enter the cell DOWN its ELECTROCHEMICAL gradient

Question 30

What produces a salty sweat

Answer 30

CF patient CFTR is defective and Cl- accumulates in the duct lumen