What are the steps in chloride secretion? (5)
- Na pump sets up ion gradients
- NaK2Cl symporter (SAT) uses energy of gradient to accumulate Cl above electrochemical gradient
- Cl leaves cell by passive diffusion DOWN gradient through CHANNEL
- Na removed by PUMP (to maintain gradient), K via CHANNEL
- Induces paracellular Na and water fluxes
Why is the opening of the chloride channel the rate limiting step in chloride secretion? (2)
- Cl cannot leave the cell until the channel opens
- Opening of the channel is strictly regulated
What is the CFTR?
What regulates this?
Cystic Fibrosis Transmembrane conductance Regulator (the chloride channel)
- Defective in cystic fibrosis
- Regulated by ‘protein kinase A dependent phosphorylation of ‘R domain’’ and binding of ATP
What causes secretory diarrhea? (3)
- Excessive stimulation of the secretory cells in the small intestine and colon
- Could be due to high conc of endogenous SECRETAGOGUES produced by tumours or inflammation
- More commonly due to enteroxins in bacteria (stimulates CFTR)
What is the molecular mechanism of cholera?
Cholera toxin irreversibly binds to adenylate cyclase, this skips the GPCR (RLS) which controls this process
What are crypt cells? (2)
- Epithelial cells involved in secretion
- Can convert to villus
How do we treat secretory diarrhea?
Oral rehydration therapy
What is cystic fibrosis? (5)
- Complex inherited disorder affecting children and young adults
- Autosomal recessive inheritance (child has 1/4 chance)
- Heterozygotes have no symptoms but are carriers
- Freq varies among ethnicities
- Mean survival: 38yrs
What are the symptoms of CF? (6)
- Clogging of airways
- Infections
- Affects organs (liver, pancreas)
- Affects male glands
- Salty sweat
- Common death: lung disease
How do you clinically manage CF? (4)
- Chest percussion (clear mucous)
- Treat lung infections
- Pancreatic enzyme replacement
- Healthy eating
What causes CF? (2)
- Defect in CFTR/chloride secretion
- The defective CFTR prevents isotonic fluid secretion and enhances Na absorption
= Dry lung surface
What is the result of CFTR defect? (4)
- Defective ion transport
- Airway surface lipid depletion
- Defective mucocillary clearance
- Mucous obstruction, inflammation, infection
Why do people with CF have salty sweat?
- Primary isotonic secretion of fluid by acinar cells
- Secondary reabsorption of NaCl but NOT water = hypotonic solution
