salt and water transport and their control Flashcards
1
Q
electrolyte and water transport of the GI tract? 5
A
- Water and electrolytes provide medium for:
- Digestive processes within the GI tract
- Metabolic processes within the body on absorption
- Replace daily loss of body fluids in sweat, urine, lungs and faeces
- When regulatory processes fail it can lead to life threatening diarrhoea and electrolyte imbalance
2
Q
describe how water and electrolyte transport is tightly regulated? 5
A
- Net absorption and minimal loss of water and electrolytes in faeces occurs
- Secretion/ absorption regulation by:
- Gut luminal contents (osmolarity)- in absence of food electrolytes are primarily responsible for creation of osmotic pressure in gut lumen
- Enteric and automonic signals
- Endocrine hormones
- Immunogenic signals
3
Q
describe the efficient conservation of water and salts? 3
A
- Bidirectional secretion and absorption occur across GI epithelium daily
- Secretions dominate in upper GI tract: saliva, gastric and pancreatic juice, intestinal juice= facilitate movement along the GI tract, mixing with digestive enzymes, chemical reactions, nutrient absorption
- Absorption dominates overall: 98% of ingested and secreted water and electrolytes are absorbed
4
Q
describe how the small intestine is the primary site for absorption? 2
A
- Ingested and secreted water and electrolytes and predominantly absorbed in the small intestine (jejunum)
- Distinct secretion and absorptive profiles depend on variations in epithelial membrane transport proteins and permeability along the GI tract
5
Q
describe the small intestine adaptations? 5
A
- Surface area: folds, villi, microvilli
- Villi lymphatic blood vessels
- Enterocyte actin myofilaments 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), acidic (rapid increase in HCO3- rich secretions)
- Epithelium is more permeable than the large intestine
6
Q
describe large intestine adaptations? 5
A
- 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 (digestive enzyme activity is absent)
- Epithelium is les permeable than small intestine
- Has additional absorptive capacity for water and NaCl in exchange for K+ loss
7
Q
what are electrolytes? 5
A
- Dissociate in solution into ions- carry an electrical charge
- The concentration of different electrolytes differs in the cytosol and extracellular fluid
- BUT osmotic balance is maintained
- An electrochemical gradient occurs across the cell membrane
- Ions will diffuse down their electrochemical gradient if mechanisms are present to do so
8
Q
describe osmolarity? 3
A
- Electrolytes create an osmotic gradient across a semi-permeable membrane for the movement of water by osmosis
- An increase in osmotically active particles creates a hypertonic environment
- Water will move from a hypo-to hypertonic environment
9
Q
describe the cell membrane transport mechanisms involved in electrolytes and water transport? 2
A
- Permeable to non-polar hydrophobic molecules, some small, uncharged polar molecules diffusion down concentration gradient
- Non-permeable to movement of large and charged polar molecules- facilitated diffusion requires carriers or channels membrane proteins
10
Q
describe primary active transport? 2
A
- Hydrolysis of ATP provides energy to move ions against their electrochemical gradient
- Na+/K+ ATPase pump
11
Q
describe the secondary active transport? 3
A
- Uses gradient created by primary pump to move substance against is electrochemical gradient
- Symport=two molecules in same direction
- Antiport= two molecules in opposite direction
12
Q
describe the sodium potassium ATPase pump? 3
A
- 3 Na+ exported and 2 K+ imported against gradient using energy from ATP hydrolysis by ATPase
- Keeps Na+ cytosol concentration
- Important mechanism driving gut absorption
13
Q
describe symport and anti port transport mechanisms? 2
A
- Secondary active transport using the gradient supplied by Na+/K+ ATPase active transport of Na+ out of the cell
- Na+ is then transported down its concentration gradient into the cell with (symport) of in exchange for. (antiport) other molecules, moving them against concentration gradient
14
Q
what are the principles of enterocyte transport? 7
A
- Polarised with an apical and basolateral membrane
- 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 effects bidirectional fluid flux
- Occurs by transcellular and paracellular routes
- Transcellular absorption may be against concentration gradient and require ATP
- Paracellular routes (between cells) do not require energy
15
Q
describe different types of electrolyte transport? 3
A
- Passive= down the electrochemical gradient through ion channels or carriers or permeable tight junctions
- Solvent drag= water follows Na+ gradient via osmosis, taking other ions (upper intestine where tight junction more permeable)
- Active= requiring ATP, Na+/K+ ATPase pump depletes cellular Na+ and draws Na+ across apical membrane from gut lumen via channel or cotransporter
16
Q
describe the variations in water and electrolyte transport in the small intestine? 4
A
- Chyme contains water and key electrolytes Na=, K+, Cl- and HCO3- from ingested food and secretions of the GI tract
- Rapid osmotic equilibration in the duodenum to form isotonic chyme= secretion of H2O into hypertonic chyme, absorption of H2o from hypotonic chyme
- Jejunum absorbs N+, K+, Cl- and H2O and ileum secrete HCO3-
- Na+ and Cl- are conserved, HCO3- secretion
17
Q
describe the variation in water and electrolyte transport in the large intestine? 4
A
- Smaller volume of chyme enters large intestine, 100-200ml is excreted
- Water and electrolytes are absorbed in the proximal colon
- Tight junctions prevent back-diffusion of ions into lumen allowing more complete NaCl absorption, limited loss in faeces
- Secretion of HCO3- and K+ occurs
18
Q
describe Na+ absorption in the small intestine? 5
A
- Drives absorption of ions, organics, H20
- Driven by basolateral active transport of Na+ into the interstitial space via Na+/K+ ATPase pump
- Dominance of mechanisms vary along the small intestine:
- Via passive diffusions
- Via apical membrane carrier proteins= organic substrate Na/glucose and Na/amino acid transporters, Na/H antiport, Na/Cl symport
19
Q
describe Cl- absorption in the small intestine? 5
A
- Cl- absorption occurs down electrical gradient
- Na+ absorption with nutrients is electrogenic (leads to net negative change in the lumen and net positive charge in the paracellular spaces). This provides an electrochemical gradient for Cl- absorption
- Cotransport with Na+= dominant mechanism in proximal ileum
- Counter-transport in exchange for HCO3-= dominant in distal ileum as Na+ decreased, large intestine
- Carbonic anhydrase mediated production of HCO3- in the cell occurs for Cl- exchange
20
Q
describe Na+ absorption in the large intestine? 3
A
- Driven by Na+/K+ ATPase in the basolateral membrane
- Sodium entry by= Na+ channels, Na+/H+ transporter, no glucose/amino carrier activity
- K+ becomes concentrated in lumen as water is absorbed down a concentration gradient or secreted when lumen concentration low (net secretion)
21
Q
describe Cl- absorption in the large intestine? 4
A
- Cl- ions are exchanged for HCO3-
- Net secretion of HCO3- provides a buffer for acid produced by bacteria with absorption of Cl- ions
- Tight junctions ensure no ion backflow into lumen
- Na+ and CL- movement creates osmotic gradient for transcellular water movement
22
Q
describe how aldosterone regulates absorption? 3
A
- Dehydration causes aldosterone release from adrenal cortex
- Upregulates Na absorption by stimulations of Na+/K+ ATPase pump and Na channels
- Increased NaCl and water absorption occurs from lumen at expense of K+ secretion into the lumen
23
Q
describe how glucocorticoids and somatostatin regulates absorption?
A
- Increase water and NaCl absorption by upregulation of NA+/K+ ATPase pump
24
Q
describe how the enteric nervous system regulates absorption? 2
A
- Parasympathetic promotes secretion
- Sympathetic promotes absorption
25
Q
describe the secretion of water and ions? 4
A
- 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
26
Q
describe what the secretion of water and NaCl is driven by? 7
A
- 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 the CFTR into the intestinal lumen
- Cl- ions provide electronegativity in the intestinal lumen to draw Na+ into the luma
- Creates an osmotic gradient for water movement into the gut lumen via paracellular routes
27
Q
specifically describe the secretion of water? 4
A
- All water secretion is via osmosis down an osmotic gradient created by solutes or ions
- 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 chyme
- Factors that disrupt tonicity of gut lumen contents (osmotic) or increase enterocyte secretion (secretory) may cause diarrhoea (also principle by which laxatives work)
28
Q
describe how cystic fibrosis disrupts secretory mechanisms? 5
A
- Congenital autosomal recessive disease
- Deletion in the gene for the CFTR channel
- CFRT is the 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 new-borns
29
Q
what does the cholera toxin do to secretion? 8
A
- 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 channels
- Depends on Na+/K+ ATPase pump
- Leads to massive Cl- efflux, Na+ and water (via osmosis) into gut lumen, particularly in the jejunum
- Profuse, watery, secretory diarrhoea, circulatory shock caused by dehydration, life threatening
- Permanent: effects only reduced follow enterocyte turnover
- Treatment via oral rehydration therapy
30
Q
describe oral rehydration therapy? 4
A
- Promotes 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
31
Q
describe lactose intolerance? 3
A
- caused by a deficient in the enzyme lactase
- lactose (disaccharide in milk) is not digested and remains in the lumen
- creates an osmotic gradient to cause osmotic diarrhoea
