Chloride Secretion Epithelial Cells Flashcards
Step 1 chloride secretion
Tight junction divide cells into apical and basolateral membrane domains
Step 2 chloride secretion
Na pump sets up ion gradients (x3Na+ out x2K+ in)
What step of chloride secretions does the “NaK2Cl symporter uses the energy of the Na gradient to actively accumulate chloride above its electrochemical gradient”
Step 3 chloride secretion
Step 4 chloride secretion
Cl leaves the cell by passive diffusion through an ion channel
What step of chloride secretion does “Na exit via the basolateral Na-pump and K+ via channel”
Step 5 chloride secretion
Step 6 chloride secretion
The transport of Cl across the epithelium induces paracellular Na and water fluxes
What has to be open for accumulation of Cl- above electrochemical equilibrium to leave the cell
Cl- channel is open
In the rate-limiting step what is strictly regulated (gated)
The opening of the Cl- channel
What is the rate-limiting step in Cl- secretion
The opening of the Cl- channel
What has Cl- channel been identified at the molecular level as…
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
The overstimulation of _____ has been implicated in ____ diarrhea and its _____ causes ____ fibrosis
The overstimulation of CFTR has been implicated in SECRETORY diarrhea and its DYSFUNCTION causes CYSTIC fibrosis
What is secretory diarrhea caused by
Excessive stimulation of the secretory cells in the crypts of the small intestine and colon
What is excessive stimulation of secretory cells caused by
- Abnormally high conc. of endogenous secretagogues produced by tumours or inflammation
- Secretion of enterotoxins from bacteria (Vibrio Cholerae)
_____ irreversibly activate ____ cyclase causing a ____ stimulation of CFTR lead to a ____ that overwhelms the absorptive capacity of the colon
ENTEROTOXINS irreversibly activate ADENYLATE cyclase causing a MAXIMAL stimulation of CFTR lead to a SECRETION that overwhelms the absorptive capacity of the colon
What can oral rehydration therapy be used to treat caused by cholera
Secretory diarrhea
What is inherited in an autosomal recessive fashion that affects children and young adults
Cystic fibrosis
What have no symptoms of cystic fibrosis but are carriers
Heterozygotes
List the organs affected by cystic fibrosis
- Airways
- Liver
- Pancreas
- Small intestine
- Reproductive tract
- Skin
In cystic fibrosis what are most cases mortality a result of
Respiratory failure
What is a common them of involvement in cystic fibrosis
Epithelial tissues
Clinical management of cystic fibrosis
- Chest percussion to improve clearance of infected secretions
- Antibiotics to treat infections
- Pancreatic enzyme replacement
- Attention to nutritional status
CFTR is a __ channel regulated by ___ kinase A dependent _____ of the R domain and binding of ___ to the NBD
CFTR is a Cl channel regulated by PROTEIN kinase A dependent PHOSPHORYLATION of the R domain and binding of ATP to the NBD
Do normal or CF lung epithelial cells “a balance between secretion and absorption keeps the lung surface moist but prevents excessive fluid build up”
Normal lung epithelial cells
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”
Lung epithelial cell in CF
Blocking Cl- secretion contribution to lung pathology flow pathway
- CFTR gene defect (gene therapy)
- Defective ion transport
- Airway surface liquid depletion
- Defective mucocillary clearance
- Mucus obstruction»_space;> infection»_space;> inflammation
What type of sweat do people with CF have
Very salty sweat
2 stage process of sweat formation
- Primary isotonic secretion of fluid by acinar cells
- Secondary reabsorption of NaCl but NOT H2O produces a hypotonic solution
The failure of epithelial cells in the ducts of sweat glands to reabsorb NaCl produces…
Salty sweat in CF patients
CF and sweat formation; in ___ cells the membrane potential is ____ and Cl- wants to enter the cell ___ its _____ gradient
CF and sweat formation; in DUCT cells the membrane potential is DEPOLARISED and Cl- wants to enter the cell DOWN its ELECTROCHEMICAL gradient
What produces a salty sweat
CF patient CFTR is defective and Cl- accumulates in the duct lumen
