L18 - Traffic acros epithelial cells: Chloride secretion Flashcards
(19 cards)
What are the steps of chloride secretion
Na/K ATPase sets up ion gradients
The NAK2Cl symporter uses energy of Na gradient to actively accumulate chloride above its concentration gradient
Cl leaves the cell by passive diffusion through ion channel (at apical membrane)
Na exits via the basolateral Na-pump and K+ via channel
The transport of Cl- across epithelium induces paracellular Na+ and water flux
What is the rate limiting step in chloride secretion
Opening of the CFTR (Cl-) channel
What is CFTR
Cystic Fibrosis Transmembrane conductance regulator
What is secretory diarrhoea
Caused by excessive stimulation of the secretory cells in the crypts of the small instestine and colon
What are secretagogoues
A substance (hormone or neutrotransmitter) that causes another substance to be secreted
What is a bacteria that can cause secretory diarrhoea
Secretion of enterotoxins from Vibrio cholerae
What do enterotoxins do
Irreversibly activate adenylate cyclase causing a maximal stimulation (continuous activation) of CFTR
How can secretory diarrhoea be treated
Oral rehydration therapy - this counteracts the overstimulation of secretion
What is cystic fibrosis
A complex inherited disorder that affects children and young aduts
Inherited in an autosomal recessive fashion
What organs are affected by cystic fibrosis
A wide range of organs, but a common theme is the involvement of epithelial tissues
What are clinical methods of cystic fibrosis management
Chest percussion
Antibiotics
Pancreatic enzyme replacement
Attention to nutritional status
Where does glucose absorption and chloride secretion occur in the intestine
Glucose absorption occurs in the villi, chloride secretion occurs in the crypts
What is the difference between osmotic and secretory diarrhoea
Osmotic diarrhea caused by pulling water out of small intestine
Secretory diarrhea caused by increased secretion in the small intestine and/or colon
What is the CFTR
A Cl- channel regulated by Protein Kinase A (PKA) dependent phosphorylation of the R domain, and binding of ATP to nucleotide binding domain (NBD)
What are the steps of CFTR activation
Phosphorylation of R domain, ATP binds to NBD, Channel opens and Cl- diffuses down electrochemical gradient
What happens to Na+ absorption in cystic fibrosis
More Na+ absorption
How does CFTR contribute to dry lungs
CFTR gene defect -> Defective ion transport -> Airway surface liquid depletion -> Defective mucociliary clearance -> Mucous obstruction -> Infection / inflammation
How does cystic fibrosis lead to salty sweat formation
In the duct cells the membrane potentiatl is depolarised and Cl- wants to re-enter the cell down its electrochemical gradient
However the CFTR is dysfunctional and Cl- accumulates in the duct lumen producing salty sweat
