Salt and water transport and its control Flashcards
What do 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
What happens when salt and water regulatory processes fail?
•When regulatory processes fail it can lead to life threatening diarrhoea and electrolyte imbalance
What is the daily input and stool output of water?
Large daily fluid turnover in the GI tract (mL)
What is secretion and absorption regulated by?
- gut luminal contents (osmolarity)- in absence of food electrolytes are primarily responsible for creation of osmotic pressure in gut lumen
- enteric and autonomic signals
- endocrine hormones
- immunogenic signals
How are water and salts efficiently conserved?
Bidirectional secretion and absorption occurs across GI epithelium daily
Where do secretions dominate?
- secretions dominate in upper GI tract (~7L): saliva, bile, gastric and pancreatic juice, intestinal juice
- Facilitate movement along the GI tract, mixing with digestive enzymes, chemical reactions, nutrient absorption
Where does absorption dominate?
•Absorption dominates overall: 98% (~8.8 L) of ingested and secreted water and electrolytes are absorbed
What is the primary site of absorption?
Small intestine
How does absorption occur in the small intestine?
•Ingested and secreted water and electrolytes are predominantly absorbed in the small intestine (jejunum)
What do secretion and absorption profiles depend on in the small intestine?
•Distinct secretion and absorptive profiles depend on variations in epithelial membrane transport proteins and permeability along the GI tract
How is the small intestine adapted for absorption?
- 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
- •Acidic: rapid increase in HCO3- rich secretions
Epithelium is more permeable than the large intestine
Which part of the small intestine wall undergoes absorption?
Absorption by Villi epithelium
Which part of the small intestine wall undergoes secretion?
Water and electrolyte rich secretion by crypt / intestinal gland epithelium
How is the large intestine adapted for absorption?
- 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 adsorption is limited (digestive enzyme activity absent)
- Epithelium is less permeable than small intestine
- Has additional absorptive capacity for water and NaCl in exchange for K+ loss (4-6 L)
What is an electrochemical gradient?
- an electrochemical gradient occurs across the cell membrane
- Ions will diffuse down their electrochemical gradient if mechanisms are present to do so
How does the concentration of electrolytes differ throughout the body?
- Electrolytes 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
What is an osmotic gradient?
•Electrolytes (and other osmotically active particles) create an osmotic gradient across a semi-permeable membrane for the movement of water by osmosis
How does water move in an osmotic gradient?
- Water will move from a hypo- to hypertonic environment
- An increase in osmotically active particles creates a hypertonic environment
Which cell membrane transport mechanisms are involved in electrolytes and water transport?
- Permeable to non-polar, hydrophobic molecules (O2, CO2), some small, uncharged polar molecules (e.g water, urea, ethanol)
- Diffusion down concentration gradient
- Non-permeable to movement of large and charged polar molecules (e.g ions, glucose)
- Facilitated diffusion: requires carrier (transporter) or channel membrane proteins
What is primary active transport?
- Hydrolysis of ATP provides energy to move ions against their electrochemical gradient
- Na+-K+ ATPase pump
What is secondary active transport?
- Uses gradient created by primary pump to move substance against it’s electrochemical gradient
- Symport: two molecules in same direction
- Antiport: two 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
Why is the Sodium potassium ATPase pump important?
- Keeps Na+ cytosol concentration low
- Important mechanism driving gut absorption
How do Symport and antiport transport mechanisms work?
- Secondary active transport using the gradient supplied by Na+-K+ ATPase active transport of Na+ out of the cell
- Na+ is then transported down it’s concentration gradient into the cell with (symport) or in exchange for (antiport) other molecules, moving them against their concentration gradient
What are the principles of enterocyte transport?
- 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 affects bidirectional fluid flux
Complete the diagram of the enterocyte
What are the 2 routes of enterocyte transport?
- Occurs by transcellular and paracellular routes
- Transcellular absorption may be against concentration gradient and require ATP
- Paracellular routes (between cells) do not require energy
Complete the diagram on enterocyte transport
How does transcellular electrolyte transport occur?
Transcellular electrolyte transport is via transport proteins
What are the different transport proteins in intestinal cells?
What are the 3 types of electrolyte transport?
- Passive: down electrochemical gradient through ion channels or carriers or permeable tight junctions
- Solvent drag: water follows Na+ gradient via osmosis, taking other ions (eg upper intestine where tight junctions 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
What water and electrolyte transport happens in the small intestine?
- 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
- Jejunum absorbs Na+, K+, Cl- and H2O and Ileum secretes HCO3- (~6.5 L absorbed)
- Na+ and Cl- are conserved, HCO3- secretion
What does rapid osmotic equilibriation in the small intestine involve?
- secretion of H2O into hypertonic chyme
- absorption of H2O from hypotonic chyme
What water and electrolyte transport occurs in the large intestine?
- Smaller volume of chyme (~2 L) enters large intestine, 100-200 ml is excreted
- water and electrolytes are absorbed in 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
How does Na+ absorption occur in the small intestine?
- 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 diffusion
- Via apical membrane carrier proteins
What is Na+ absorption in the small intestine important for?
•Drives absorption of ions, organics, H2O
What apical membrane carrier proteins absorb Na+ in the small intestine?
- Organic substrate Na/glucose and Na/amino acid co-transporters
- Na/H antiport
- Na/Cl symport (ileum)
How does Cl- transport occur in the small intestine?
§Cl- absorption occurs down electrical gradient
§Na+ absorption with nutrients is electrogenic (leads to net negative charge in the lumen and net positive charge in the paracellular spaces)
§This provides an electrochemical gradient for Cl- absorption
What are the 3 mechanisms for Cl- transport in the small intestine?
§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
How is Na+ absorbed in the large intestine?
- Driven by Na+/K+ ATPase in the basolateral membrane
- Sodium entry by
- Na+ channels (facilitated diffusion)
- Na+/H+ transporter
- No glucose/amino acid carrier activity
What happens to K+ in the large intestine as a result of Na+ absorption?
•K+ becomes concentrated in lumen as water is absorbed from gut; may be absorbed down a concentration gradient or secreted when lumen concentration 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 backflow into lumen
- Na+ and Cl- movement creates osmotic gradient for transcellular water movement
How does aldosterone regulate absorption?
- 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
How is absorption regulated?
- Aldosterone:
- Glucocorticoids and somatostatin: increase water and NaCl absorption by upregulation of Na+/K+ ATPase pump
- Enteric nervous system: parasympathetic promotes secretion; sympathetic promotes absorption
How is water absorbed?
- 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 an osmotic gradient causing water movement across the gut epithelium
What are the 2 routes of water absorption and how do they work?
- 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 concentration 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
Complete the diagram
Which part of the enterocytes are absorptive and secretory?
- 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
Where are water and ions secreted from?
•Water and electrolyte secretion in the small and large intestine is via crypt enterocytes
Which small intestine feature of water and electrolyte absorption are absent in the large intestine?
Note: villus structure absent in large intestine
How are water and electrolytes secreted?
- 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
What is CFTR?
CFTR - Cystic fibrosis transmembrane conductance regulator (CFTR) channel
How is water secreted?
- 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 isotonic chyme
What causes diarrhoea?
•Factors that disrupt tonicity of gut lumen contents (osmotic) or increase enterocyte secretion (secretory) may cause diarrhoea (also principle by which laxatives work)
What is the effect of cystic fibrosis?
- 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
What is cystic fibrosis?
- Congenital autosomal recessive disease
- Deletion in gene for CFTR channel
What causes cholera?
•Cholera toxin secreted by bacteria vibrio cholera
What are the effects of cholera toxin?
- 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 diarrhea, circulatory shock caused by dehydration, life threatening
How is cholera treated?
- Permanent: effects only reduced following enterocyte turnover
- Treatment via oral rehydration therapy
What is oral rehydration therapy?
•oral rehydration solutions (ORS) promote fluid absorption by coupling sodium with glucose in solution
How does oral rehydration therapy work?
- 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
What is oral rehdration therapy for?
•Replaces salt and water loss from secretory diarrhoea
What is lactose intolerance?
- Lactose intolerance caused by a deficiency in the enzyme lactase
- Lactose (disaccharide in milk) is not digested and remains in the lumen
- Creates an osmotic gradient to cause osmotic diarrhoea
