Water Balance in the G.I. tract Flashcards
describe the absorption of water in the GI tract
a passive process driven by the transport of solutes (especially Na+0 from the lumen of the intestines into the bloodstream
what is faeces made of
100ml water, 50ml cellulose, bilirubin, bacteria
what is diarrhoea in terms of fluids
loss of fluid and solutes from GI tract in excess of 500ml per da
what is interstitial fluid movement always coupled to
solute movement
what are the two routes water can travel via
transcellular- move across membranes via aquaporins
paracellular- through tight cell junctions between enterocytes
how does the re-absorption of Na+ allow the re-absorption of water
creates as osmotic pressure
what stimulates proton excretion
Na+/H+ exchange in the duodenum and jejunum stimulated by bicarbonate
what is the most important mechanism in the fasting state
Na+ co transport in the small intestine- inward movement of Na+ coupled to the movement of a monosaccharide (glucose of individual amino acid)
what is the post prandial period
time after eating
what is the most effective mechanism in the fasting state
parallel exchangers: Na+/H+ and Cl-/HCO3-
occurs in the ileum and colon
what epithelial channels are regulated by aldosterone
epithelial Na+ channels (ENaC)
what type of transport is the Na+ co transporters
secondary active transport
how are the Na+ co transporters electrogenic
as overall transport generates a transepithelial potential in which the lumen is negative (drives the parallel absorption of Cl-
how many Na for each glucose or amino acid
2
where does Na+/H+ exchange happen
in jejunum and proximal colon at apical membrane via NHE2 and NHE3
does the parallel exchange of Na+/H+ and Cl-/HCO3- create a a potential across the membrane
no is electroneutral
what regulates the parallel absorption of Na+ and Cl-
intracellular cAMP, cGMP and Ca2+ = all reduce NaCl absorbtion
in parallel absorption what goes out when Na+ and Cl- comes in
Na+/H+
Cl-/HCO3-
what does a reduction in NaCl absorption do
causes diarrhoea- secretory diarrhoea
what causes secretory diarrhoea
infection (e.coli) can increase intraceluular cAMP
what do ENaC channels do
mediate electrogenic Na+ absorption in the distal colon
what are ENaC channels regulated by
increased by aldosterone, not mediated by cAMP/GMP (the cyclic nucleotides)
how does aldosterone increase ENaC activity
opens then, puts more of them into the membrane, increases synthesis of them and Na+/K+-ATPase
why are ENaC ion channels not transporters
as the sodium travels down its electrical gradient
what happens if the ENaC channels are defective
lot of sodium in the colon which holds onto water= diarrhoea
how is Cl- absorbed in the colon
passively via trans-cellular or para-cellular routes
or
Cl–HCO3- exchange (ileum, proximal and distal colon) and (ii) parallel Na+-H+ and Cl–HCO3- exchange (ileum and proximal colon)
how is Cl- passively absorbed in the small intestine
driving force= lumen negative potential due to electrogenic transport of Na+ (Na+/glucose and Na+/amino acid) – negative lumen pushing cl out
how is Cl- passively absorbed in the large intestine
driving force= lumen negative potential due to electrogenic movement of Na+ through ENaC
when healthy, is there net Cl- absorption or secretion
absorption
where does Cl- secretion occur and at what rate
from crypt cells at a basal rate
how does Cl- leave the cell
via CFTR (cystic fibrosis) on the apical membrane down an electrochemical gradient
what does the secretion of Cl- lead to
creates negative lumen potential which leads to secretion of Na+ paracelullarly and K+ vis K+ channels (ions that came in with Cl_ via the NKCC1 channel)
what increases the activity of CFTR
bacterial endotoxins, calcium, cGMP and cAMP, hormones and neurotransmitters, immune cell products (prostaglandins, histamine), some laxatives
what is the overall effect of the opening of CFTR channels
secretory diarrhoea
what metabolic ion problems can diarrhoea cause
dehydration (Na+ and H2O loss)
metabolic acidosis (HCOs- loss)
hypokalaemia
what can cause impaired absoprtion of NaCl which results in diarrhoea
congenital defects, inflammation, infection, excess bile acid in colon
what are the biochemical causes of diarrhoea
impaired absorption of NaCl, non absorbable or poorly absorbable solutes in intestinal lumen (sugar substitutes,
hypermoblity, excessive secretion, lactase deficiency
why does hypermotility cause diarrhoea
not enough time to finish absorption
how does the cholera toxin cause diarrhoea
inhibits GTPase which increases cAMP which stimulates CFTR which causes secretory diarrhoea
how does lactase deficiency cause diarrhoea
as un-absorbed lactose acts osmotically and retains water in the lumen
how do rehydration therapies work
Absorption of Na+ and glucose by SGLT1 cause accompanying absorption of H2O
SGLT1 on apical membrane of enterocyte
what drugs are used as anti motility agents to treat diarrhoea
opoid drugs e.g. codeine, diphenoxylate and loperamide(last two low CNS penetration so less change of abuse),
how do opioids cause reduced motility
inhibit enteric neurones, decrease peristalsis, increased segmentation, increased fluid absorption, constriction of pyloric, ileocaecal and anal sphincters, increase tone of large intestine
