Transport Across Epithelia Flashcards
What is chloride secretion
- A two step process where a cotransporter located in the basolateral membrane accumulates chloride above its electrochemical gradient.
- This enables chloride to leave the cell via a chloride channel located in the apical membrane.
- Sodium moves via the paracellular pathway to preserve electoneutrality.
What are the key features of chloride secretion across an epithelial cell
- tight junctions divide into apical and basolateral membrane
- Na pump sets up ion gradients
- The NaK2Cl symporter uses the energy of the Na gradient to actively accumulate chloride above its electrochemical gradient
- Cl leaves the cell by passive diffusion through an ion chennl.
- Na exits via the basolateral Na pump and K+ via channel
- The transport of Cl across the epithelium induces paracellular Na and water fluxes.
What is the rate limiting step in chloride secretion
The opening of the Cl- channel
Describing the rate limiting step
- Although Cl- is accumulated above electrochemical equilibrium is can not leave the cell unless the Cl- channel is open.
- The opening of the Cl- channel is strictly regulated (gated).
- Thus the opening of the Cl- channel is the rate limiting step in Cl- secretion.
What is one cause (least common) of secretory diarrhoea?
- Excessive stimulation of the secretory cells in the crypts of the small intestine and colon.
- This could be due to abnormally high concentrations of endogenous secretagogues produced by tumours or inflammation.
Two causes of secretory diarrhoea
Excessive stimulation of the secretory cells in the crypts of the small intestine and colon and more commonly, the secretion of enterotixins from bacteria such as Vibrio cholerae.
What is the second cause of secretory diarrhoea (most common)?
- Due to secretion of enterotoxins from bacteria such as Vibrio cholerae.
- Enterotoxins irreversibly activate andeylate cyclase causing a maximal stimulation of CFTR lead to secretion that overwhelms the absorptive capacity of the colon.
What is the molecular mechanism of cholera
Cholera toxin irreversibly activates adenlylate cyclase causing activation of CFTR. This catalyses the production of ATP to cAMP which activates protein kinase A which phosphorylates CFTR.
How do we treat secretory diarrhoea caused by cholera?
Through oral rehydration therapy.
What is cystic fibrosis
A complex inherited disorder that affects children and young adults.
Organs affected by cystic fibrosis
Patients infected have a wide range of symptoms. A common theme is the involvement of epithelial tissues. Most cases of mortality are due to respiratory failure.
How does cystic fibrosis affect the liver
Plugging of small bile ducts impedes digestion and disrupts liver function in perhaps five percent of patients.
How does cystic fibrosis affect the airways
Clogging anf infection of bronchial passages impeded breathing. The infections progressively destroy the lungs. Lung disease accounts for most deaths from cystic fibrosis.
How does cystic fibrosis affect the pancreas
Occlusion of ducts prevents the pancreas from delivering critical digestive enzymes to the bowel in 85% of patients. Diabetes can result as well.
How does cystic fibrosis affect the reproductive tract
Absence of fine ducts, such as the vas deferens, renders 95% of males infertile. Occasionally, women are made infertile by a dense plug of mucus that blocks sperm from entering the uterus.
How does cystic fibrosis affect the skin?
Malfunctioning of sweat glands causes perspiration to contain excessive salt (NACl). Measurement of chlride in seat is a mainstay of diagnosis.
What does clinical managemtn of cystic fibrosis include?
- chest percussion to imporove clearance of infected secretions
- antibiotics to treat infections
- pancreatic enzyme replacement
- attention to nutritional status
What is CFTR (cystic fibrosis transmembrane conductance regulator?
- CFTR is a Cl- channel that mediates the passive diffusion of Cl- doewn its electrochemical gradient.
- It is regulated by protein kinase A, and dependent on the phosphorylation of the regular domain and binding of ATP to the NBD (nucleotide binding domain)
In a patient with cystic fibrosis, what does a defect in Cl- secretion look like.
- The defective Cl- channel prevents isotonic fluid secretion and enhances Na+ absorption to give a dry lung surface. The mucus becomes thick and difficult to remove.
- Bacteria proliferate and attract immune cells, which can damage healthy tissue. DNA released from bacteria and lung cells added to the stickiness.
- Airways become plugged and begin to deteriorate.
What do epithelial cells of a normal lung look like
- There is a balance between secretion and absorption keeps the lung surface moist but prevents excessive fluid build up.
- The thin, wet mucus traps inhaled particles, allows clilia to push mucus up to the throat for removal and keeps the airways clear for breathing.
Blocking Cl- secretion contributes to lung patholog
- CFTR gene defect
- defective ion transport
- airway surface liquid depletion
- defective mucocillary clearance
- mucus obstruction - infection - inflammation
Formation of sweat.
Formatin of sweat is a two stage process
* primary isotonic secretion of fluid by acinar cells
* a secondary reabsorption of NaCl but not water. produces a hypotonic solution.
How is the salty sweat produced in CF patients
Failure of epithelial cells in the ducts of sweat glands to reabsorb NaCl produces the salty sweat in CF patients.
Sweat formation in CF patients
In the duct cells, the membrane potential is depolarised and Cl- wants to enter the cell down its electrochemical gradient.
In CF patients, CFTR is defective and Cl- accumulates in the duct lumen producing salty sweat.
