Salt and Water transport and its control part 2 Flashcards
Regulation of absorption
Aldosterone: dehydration causes aldosterone release from adrenal cortex; upregulates Na absorption by stimulation of Na+/K+ ATPase pump and Na channels; increased NaCl and water absorption occurs from lumen at expense of K+ secretion into the lumen.
Glucocorticoids and somatostatin: increase water and NaCl absorption by upregulation of Na+/K+ ATPase pump.
Enteric nervous system: parasympathetic promotes secretion; sympathetic promotes absorption
Absorption of water
All water absorption in the GI tract is via osmosis from gut lumen via enterocytes into extracellular spaces and then into blood
Process dependent on absorption of nutrients and electrolytes, particularly Na which creates an osmotic gradient
Paracellular and transcellular routes
Basolateral Na+/K+ ATPase pumps leads to a build-up of Na+ in the paracellular spaces between enterocytes and keeps cell Na+concentration low
Na+ moves into enterocytes down conc gradient and is pumped out into interstitial fluid & H2O follows by osmosis into enterocytes and the paracellular spaces
Hydrostatic pressure in interstitial fluid causes water and solute movement into blood vessels
Secretion of water and ions
Enterocytes in crypts and villi express different combinations of transport proteins indicating differing role
Enterocytes on the SI villi are absorptive and dominate nutrient transport
Enterocytes in the crypts are secretory with minimal nutrient transport
Water and electrolyte secretion in the small and large intestine is via crypt enterocytes
Secretion of water and NaCl is driven by Cl-
Via crypt enterocytes to maintain lumen liquid content.
Na+/K+ ATPase pumps establish a Na+ electrochemical gradient across the basolateral membrane
This drives Na+, Cl- and K+ ions through Na+/K+/2Cl- cotransporters into crypt cells.
Cl- ions leave the cells via apical Cl- channels including CFTR into the intestinal lumen.
Cl- ions provide electronegativity in the intestinal lumen to draw Na+ into lumen - Creates an osmotic gradient for water movement into the gut lumen via paracellular routes
Secretion of water
All water secretion is via osmosis
In the duodenum hypertonic chyme causes water to move into the gut lumen by osmosis to form isotonic chyme (in addition to Cl- driven mechanism)
In the distal small intestine solutes are absorbed and water follows by osmosis maintaining a smaller volume of isotonic chyme
Factors that disrupt tonicity of gut lumen contents (osmotic) or increase enterocyte secretion (secretory) may cause diarrhoea (also principle by which laxatives work)
Cystic fibrosis disrupts secretory mechanisms
Congenital autosomal recessive disease
Deletion in gene for CFTR channel
CFTR is main Cl- channel in apical membrane of gut, pancreatic and airway epithelium
Secretion of sticky mucus and high viscosity of luminal contents occurs
Presents with intestinal obstruction and meconium ileus in newborns
Cholera toxin permanently switches on enterocyte secretion via cAMP
Cholera toxin secreted by bacteria vibrio cholera
Binds to cell receptor on apical membrane of crypt cells to irreversibly upregulate adenylate cyclase generating excess cAMP which stimulates Cl- secretion via CFTR Cl- channels
Depends on Na+/K+ ATPase pump
Leads to massive Cl- efflux, Na+ and water (via osmosis) into gut lumen particularly in jejunum
Profuse, watery, secretory diarrhoea, circulatory shock caused by dehydration, life threatening
Permanent: effects reduced following enterocyte turnover
Treatment via oral rehydration therapy
Oral rehydration therapy
Oral rehydration solutions (ORS) promote fluid absorption by coupling sodium with glucose in solution
The membrane carrier protein specific for Na+-glucose cotransport(SGLT-1) is preserved in most diarrhoeal diseases
SGLT-1 binds two Na+ to one glucose, transporting them into the cell, Cl- follows for electrochemical balance
Replaces salt and water loss from secretory diarrhoea
Lactose Intolerance
Caused by deficiency in enzyme lactase
Lactose is not digested and remains in lumen
Creates an osmotic gradient to cause osmotic diarrhoea