salt and water transport and their control

Question 1

electrolyte and water transport of the GI tract? 5

Answer 1

• 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

Question 2

describe how water and electrolyte transport is tightly regulated? 5

Answer 2

• 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

Question 3

describe the efficient conservation of water and salts? 3

Answer 3

• 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

Question 4

describe how the small intestine is the primary site for absorption? 2

Answer 4

• 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

Question 5

describe the small intestine adaptations? 5

Answer 5

• 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

Question 6

describe large intestine adaptations? 5

Answer 6

• 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

Question 7

what are electrolytes? 5

Answer 7

• 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

Question 8

describe osmolarity? 3

Answer 8

• 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

Question 9

describe the cell membrane transport mechanisms involved in electrolytes and water transport? 2

Answer 9

• 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

Question 10

describe primary active transport? 2

Answer 10

• Hydrolysis of ATP provides energy to move ions against their electrochemical gradient
• Na+/K+ ATPase pump

Question 11

describe the secondary active transport? 3

Answer 11

• 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

Question 12

describe the sodium potassium ATPase pump? 3

Answer 12

• 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

Question 13

describe symport and anti port transport mechanisms? 2

Answer 13

• 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

Question 14

what are the principles of enterocyte transport? 7

Answer 14

• 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

Question 15

describe different types of electrolyte transport? 3

Answer 15

• 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

Question 16

describe the variations in water and electrolyte transport in the small intestine? 4

Answer 16

• 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

Question 17

describe the variation in water and electrolyte transport in the large intestine? 4

Answer 17

• 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

Question 18

describe Na+ absorption in the small intestine? 5

Answer 18

• 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

Question 19

describe Cl- absorption in the small intestine? 5

Answer 19

• 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

Question 20

describe Na+ absorption in the large intestine? 3

Answer 20

• 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)

Question 21

describe Cl- absorption in the large intestine? 4

Answer 21

• 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

Question 22

describe how aldosterone regulates absorption? 3

Answer 22

• 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

Question 23

describe how glucocorticoids and somatostatin regulates absorption?

Answer 23

• Increase water and NaCl absorption by upregulation of NA+/K+ ATPase pump

Question 24

describe how the enteric nervous system regulates absorption? 2

Answer 24

• Parasympathetic promotes secretion

- Sympathetic promotes absorption

Question 25

describe the secretion of water and ions? 4

Answer 25

• 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

Question 26

describe what the secretion of water and NaCl is driven by? 7

Answer 26

• 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

Question 27

specifically describe the secretion of water? 4

Answer 27

• 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)

Question 28

describe how cystic fibrosis disrupts secretory mechanisms? 5

Answer 28

• 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

Question 29

what does the cholera toxin do to secretion? 8

Answer 29

• 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

Question 30

describe oral rehydration therapy? 4

Answer 30

• 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

Question 31

describe lactose intolerance? 3

Answer 31

• 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