Salt and water transport and its control Flashcards

1
Q

What do water and electrolytes provide medium for?

A
  • 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
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2
Q

What happens when salt and water regulatory processes fail?

A

•When regulatory processes fail it can lead to life threatening diarrhoea and electrolyte imbalance

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3
Q

What is the daily input and stool output of water?

A

Large daily fluid turnover in the GI tract (mL)

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4
Q

What is secretion and absorption regulated by?

A
  • 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
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5
Q

How are water and salts efficiently conserved?

A

Bidirectional secretion and absorption occurs across GI epithelium daily

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6
Q

Where do secretions dominate?

A
  • 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
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7
Q

Where does absorption dominate?

A

•Absorption dominates overall: 98% (~8.8 L) of ingested and secreted water and electrolytes are absorbed

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8
Q

What is the primary site of absorption?

A

Small intestine

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9
Q

How does absorption occur in the small intestine?

A

•Ingested and secreted water and electrolytes are predominantly absorbed in the small intestine (jejunum)

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10
Q

What do secretion and absorption profiles depend on in the small intestine?

A

•Distinct secretion and absorptive profiles depend on variations in epithelial membrane transport proteins and permeability along the GI tract

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11
Q

How is the small intestine adapted for absorption?

A
  • 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

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12
Q

Which part of the small intestine wall undergoes absorption?

A

Absorption by Villi epithelium

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13
Q

Which part of the small intestine wall undergoes secretion?

A

Water and electrolyte rich secretion by crypt / intestinal gland epithelium

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14
Q

How is the large intestine adapted for absorption?

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 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)
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15
Q

What is an electrochemical gradient?

A
  • an electrochemical gradient occurs across the cell membrane
  • Ions will diffuse down their electrochemical gradient if mechanisms are present to do so
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16
Q

How does the concentration of electrolytes differ throughout the body?

A
  • 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 ​
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17
Q

What is an osmotic gradient?

A

•Electrolytes (and other osmotically active particles) create an osmotic gradient across a semi-permeable membrane for the movement of water by osmosis

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18
Q

How does water move in an osmotic gradient?

A
  • Water will move from a hypo- to hypertonic environment
  • An increase in osmotically active particles creates a hypertonic environment
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19
Q

Which cell membrane transport mechanisms are involved in electrolytes and water transport?

A
  • 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
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20
Q

What is primary active transport?

A
  • Hydrolysis of ATP provides energy to move ions against their electrochemical gradient
  • Na+-K+ ATPase pump
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21
Q

What is secondary active transport?

A
  • 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
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22
Q

How does the Sodium potassium ATPase pump
work?

A

•3 Na+ exported and 2 K+ imported against electrochemical gradient using energy from ATP hydrolysis by ATPase

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23
Q

Why is the Sodium potassium ATPase pump important?

A
  • Keeps Na+ cytosol concentration low
  • Important mechanism driving gut absorption
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24
Q

How do Symport and antiport transport mechanisms work?

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 it’s concentration gradient into the cell with (symport) or in exchange for (antiport) other molecules, moving them against their concentration gradient
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25
Q

What are the principles of enterocyte transport?

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 affects bidirectional fluid flux
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26
Q

Complete the diagram of the enterocyte

A
27
Q

What are the 2 routes of enterocyte transport?

A
  • Occurs by transcellular and paracellular routes
  • Transcellular absorption may be against concentration gradient and require ATP
  • Paracellular routes (between cells) do not require energy
28
Q

Complete the diagram on enterocyte transport

A
29
Q

How does transcellular electrolyte transport occur?

A

Transcellular electrolyte transport is via transport proteins

30
Q

What are the different transport proteins in intestinal cells?

A
31
Q

What are the 3 types of electrolyte transport?

A
  • 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
32
Q

What water and electrolyte transport happens in the small intestine?

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
  • Jejunum absorbs Na+, K+, Cl- and H2O and Ileum secretes HCO3- (~6.5 L absorbed)
  • Na+ and Cl- are conserved, HCO3- secretion
33
Q

What does rapid osmotic equilibriation in the small intestine involve?

A
  • secretion of H2O into hypertonic chyme
  • absorption of H2O from hypotonic chyme
34
Q

What water and electrolyte transport occurs in the large intestine?

A
  • 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

35
Q

How does Na+ absorption occur in the small intestine?

A
  • 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
36
Q

What is Na+ absorption in the small intestine important for?

A

•Drives absorption of ions, organics, H2O

37
Q

What apical membrane carrier proteins absorb Na+ in the small intestine?

A
  • Organic substrate Na/glucose and Na/amino acid co-transporters
  • Na/H antiport
  • Na/Cl symport (ileum)
38
Q

How does Cl- transport occur in the small intestine?

A

§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

39
Q

What are the 3 mechanisms for Cl- transport in the small intestine?

A

§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

40
Q

How is Na+ absorbed in the large intestine?

A
  • 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
41
Q

What happens to K+ in the large intestine as a result of Na+ absorption?

A

•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)

42
Q

How is Cl- absorbed in the large intestine?

A
  • 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
43
Q

How does aldosterone regulate absorption?

A
  • 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
44
Q

How is absorption regulated?

A
  • 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
45
Q

How is water absorbed?

A
  • 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
46
Q

What are the 2 routes of water absorption and how do they work?

A
  • 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
47
Q

Complete the diagram

A
48
Q

Which part of the enterocytes are absorptive and secretory?

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
49
Q

Where are water and ions secreted from?

A

•Water and electrolyte secretion in the small and large intestine is via crypt enterocytes

50
Q

Which small intestine feature of water and electrolyte absorption are absent in the large intestine?

A

Note: villus structure absent in large intestine

51
Q

How are water and electrolytes secreted?

A
  • 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
52
Q

What is CFTR?

A

CFTR - Cystic fibrosis transmembrane conductance regulator (CFTR) channel

53
Q

How is water secreted?

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 isotonic chyme
54
Q

What causes diarrhoea?

A

•Factors that disrupt tonicity of gut lumen contents (osmotic) or increase enterocyte secretion (secretory) may cause diarrhoea (also principle by which laxatives work)

55
Q

What is the effect of cystic fibrosis?

A
  • 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
56
Q

What is cystic fibrosis?

A
  • Congenital autosomal recessive disease
  • Deletion in gene for CFTR channel
57
Q

What causes cholera?

A

•Cholera toxin secreted by bacteria vibrio cholera

58
Q

What are the effects of cholera toxin?

A
  • 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
59
Q

How is cholera treated?

A
  • Permanent: effects only reduced following enterocyte turnover
  • Treatment via oral rehydration therapy
60
Q

What is oral rehydration therapy?

A

•oral rehydration solutions (ORS) promote fluid absorption by coupling sodium with glucose in solution

61
Q

How does oral rehydration therapy work?

A
  • 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
62
Q

What is oral rehdration therapy for?

A

•Replaces salt and water loss from secretory diarrhoea

63
Q

What is lactose intolerance?

A
  • 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