salt & water transport & their control Flashcards
what does water & electrolytes provide medium for?
- digestive processes within the GI tract
- metabolic processes within the body absorption
- replace daily loss of body fluids on sweat, urine, lungs and faeces
what is secretion/absorption of water and electrolytes regulated by?
- gut luminal contents in absence of food electrolytes are primarily responsible for creation of osmotic in gut lumen
- enteric and autonomic signals
- endocrine hormones
- immunogenic signals
how is the conservation of water and salts efficient?
- bidirectional secretion and absorption occur across GI epithelium daily
- secretions dominate the upper GI tract: saliva, bile, gastric and pancreatic juice, intestinal juice
- facilitate movement along the GI tract, mixing with digestive enzymes, chemical reactions, nutrient absorption
- absorption dominates overall: 98% ingested and secreted water and electrolytes are absorbed
why is the small intestine the primary site for absorption?
- ingested and secreted water and electrolytes are predominantly absorbed in the small intestine
- distinct secretion and absorptive profiles depend on variations in epithelial membrane transport proteins and permeability along the GI tract
what are the adaptations of the small intestine?
- surface area: folds, villi, microvilli
- villi lymphatic and blood vessels
- enterocyte actin microfilaments rhythmically contract to move microvilli for maximum exposure to lumen contents
- rapid response to chyme: hypertonic (osmosis of water into lumen to form isotonic chyme) and acidic (rapid increase in HCO3- rich secretions)
- epithelium is more permeable than the large intestine
what are the adaptations of the large intestine?
- no villi but surface is covered with crypts/intestinal glands
- smaller role in transport of water and salts, bacterial microbiome role in protein digestion/vitamin synthesis
- smaller role in digestion: nutrient absorption is limited
- epithelium is less permeable than small intestine
- has additional absorptive capacity for water and NaCl in exchange for K+ loss
how do non-polar hydrophobic molecules move across membranes?
- molecules are small and uncharged polar molecules
- they diffuse down a concentration gradient
how do large and charged polar molecules move across membranes?
facilitated diffusion: required carrier or channel membrane proteins
how does primary active transport work?
- hydrolysis of ATP provides energy to move ions against their electrochemical gradient
- Na+/K+ ATPase pump
how does secondary active transport work?
- uses gradient created by primary pump to move substances against its electrochemical gradient
- symport
- antiport
what does symport mean?
2 molecules in same direction
what does antiport mean?
2 molecules in opposite direction
how does the sodium potassium ATPase pump work?
- 3 Na+ exported and 2 K+ imported against electrochemical gradient using energy from ATP hydrolysis by ATPase
- keeps Na+ cytosol concentration low
- important mechanism driving gut absorption
what are the principles of enterocyte transport?
- polarised with an apical and basolateral memrbane
- tight junctions provide a barrier to free flow of gut lumen contents
- tight junctions more permeable in proximal small intestine
- tonicity of chyme entering duodenum affects bidirectional fluid flux
- occurs by trans cellular and paracellular routes
- transcellular absorption may be against concentration gradient and require ATP
- paracellular routes do not require energy
what are the 3 types of electrolyte transport?
- passive
- solvent drag
- active
what is passive electrolyte transport?
down electrochemical gradient through ion channels or carriers or permeable tight junctions
what is solvent drag electrolyte transport?
water follows Na+ gradient via osmosis taking other ions
what is active electrolyte transport?
requires ATP, Na+/K+ ATPase pump depletes cellular Na+ and draws Na+ across apical membrane from gut lumen via channel or cotransporter
how are water and electrolytes transported in the small intestine?
- chyme contains water and key electrolytes Na+, K+, Cl0 and HCO3- from injected food and secretions of the GI tract
- rapid osmotic equilibrium in the duodenum to form isotonic chyme (secretion of H2O into hypotonic chyme and absorption of H2O from hypotonic chyme)
- jejunum absorbs Na+, K+, Cl- and H2O
- ileum secretes HCO3-
- Na+ and Cl- are considered, HCO3- secretion
how are water and electrolytes transported in the large intestine?
- smaller volume of chyme enters large intestine, 100-200ml is excreted
- water and electrolytes are absorbed in proximal colon
- tight junctions prevent back diffusion of ions into lumen allowing more compete NaCl absorption, limited loss in faeces
- secretion of HCO2- and K+ occurs
how is Na+ absorbed in the small intestine?
- drives absorption of ions, organics, H2O
- driven by basolateral active transport of Na+ into the interstitial space via Na+/K+ ATPase pump
- dominance of mechanisms vary along the small intestine
how doe mechanisms vary along the small intestine?
- via passive diffusion
- bia apical membrane carrier proteins
- organic substrate Na/glucose and Na/amino acid co-transporters
- Na/H antiport
- Na/Cl symport (ileum)
how is Cl- absorbed in the small intestine?
- Cl- absorption occurs from electrical gradient
- Na+ absorbed with nutrient is electrogenic (less to net negative charge in lumen and net positive charge in paracellular spaces) which drives an electrochemical gradient for Cl- absorption
- cotransport with Na+: dominant mechanism in proximal ileum
- counter transport in exchange for HCO3-: dominant in distal ilia as Na+ decreased, large intestine
- carbonic anhydrase mediated production of HCO3- in the cell occurs for Cl- exchange
how is Na+ absorbed in the large intestine?
- driven by Na+/K+ ATPase in the basolateral membrane
- sodium entry by: Na+ channels, Na+/H+ transporter and no glucose/amino acid carrier activity
- K+ becomes concentrated in lumen as water is absorbed from gut; may be absorbed down a concentration gradient or secreted when lumen concentration is low (net secretion)
how is Cl- absorbed in the large intestine?
- Cl- ions are exchanged for HCO3-
- net secretion of HCO3- provides buffer for acid produced by bacteria with absorption of Cl- ions
- tight junctions ensure no ion back flow into lumen
- Na+ and Cl- movement creates osmotic gradient for transcellular water movement
how does aldosterone help to regulate absorption?
- dehydration causes aldosterone release from adrenal cortex
- up regulates Na absorption by stimulation of Na+/K+ ATPase pump and Na channels
- increased NaCl and water absorption occurs from the lumen at the expense of K+ secretion into the lumen
how do glucocorticoids and somatostatin help to regulate absorption?
increase water and NaCl absorption by up regulation of Na+/K+ ATPase pump
how does the enteric nervous system help to regulate absorption?
parasympathetic promotes secretion; sympathetic promotes absorption
how is water absorbed in the GI tract?
- all water absorption in the GI tract is via osmosis from gut lumen via enterocytes into extracellular spaces and then into blood
- process is absolutely dependent on absorption of nutrients and electrolytes, particularly sodium which creates and osmotic gradient causing water movement from the gut epithelium
what are the paracellular and transcellular routes of water absorption?
- basolateral Na+/K+ ATPase pump lead to a build up of Na+ in the paracellular spaces between enterocytes and keeps cell Na+ concentration low
- Na+ moves into enterocytes and keeps cell Na+ concentration low
- Na+ moves into enterocytes down concentration gradient and is pumped out into interstitial fluid
- H2O follows by osmosis and enterocytes and the paracellular spaces
- hydrostatic pressure in interstitial fluid causes water and solute movement into blood vessels
how are water and ions secreted in the GI tract?
- enterocytes in crypts and villi express different combinations of transport proteins indicating different roles
- enterocytes on the SI villi are absorptive and dominate nutrient transport
- enterocytes in the crypt are secretory with minimal nutrient transport
- water and electrolyte secretion in the small and large intestine is via crypt enterocytes
how is the secretion of water and NaCl in the GI tract 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 is used to drive 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
how is water secreted in the GI tract?
- via osmosis down an osmotic gradient created by solutes of ions
- in the duodenum hypertonic chyme causes water to move into gut lumen via osmosis to form isotonic chyme (in addition to Cl- drive 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
what are the mechanisms in the body that cause cystic fibrosis?
- disruption of 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 stick mucus and high viscosity of luminal contents occurs
- present with intestinal obstruction and meconium ileum in newborns
how does the cholera toxin permanently switch on enterocyte secretion?
- cholera toxin secreted by bacteria vibrio cholera
- binds to cell receptor on apical membrane of crypt cells to irreversible up regulate adenylate cyclase generating excess cAMP which stimulate 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, water, secretory diarrhoea, circulatory shock caused by dehydration, life threatening
- permanent: effects only reduced following enterocyte turnover
- treatment via rehydration therapy
how does oral rehydration therapy work
- oral rehydration solutions (ORS) promote fluid reabsorption by coupling sodium with glucose in solution
- the membrane carrier protein specific for Na+ - glucose transport (SGLT-1) is preserved in most diarrhoea disease
- SFLT-1 binds 2 Na+ to one glucose, transporting them into cell, Cl- follows for electrochemical balance
- replaces salt and water loss from secretory diarrhoea
how does lactose intolerance work?
- caused by a deficiency in the enzyme lactase
- lactose is not digested and remains in the lumen
- creates and osmotic gradient to cause osmotic diarrhoea
