Water Balance in the G.I. tract

Question 1

describe the absorption of water in the GI tract

Answer 1

a passive process driven by the transport of solutes (especially Na+0 from the lumen of the intestines into the bloodstream

Question 2

what is faeces made of

Answer 2

100ml water, 50ml cellulose, bilirubin, bacteria

Question 3

what is diarrhoea in terms of fluids

Answer 3

loss of fluid and solutes from GI tract in excess of 500ml per da

Question 4

what is interstitial fluid movement always coupled to

Answer 4

solute movement

Question 5

what are the two routes water can travel via

Answer 5

transcellular- move across membranes via aquaporins

paracellular- through tight cell junctions between enterocytes

Question 6

how does the re-absorption of Na+ allow the re-absorption of water

Answer 6

creates as osmotic pressure

Question 7

what stimulates proton excretion

Answer 7

Na+/H+ exchange in the duodenum and jejunum stimulated by bicarbonate

Question 8

what is the most important mechanism in the fasting state

Answer 8

Na+ co transport in the small intestine- inward movement of Na+ coupled to the movement of a monosaccharide (glucose of individual amino acid)

Question 9

what is the post prandial period

Answer 9

time after eating

Question 10

what is the most effective mechanism in the fasting state

Answer 10

parallel exchangers: Na+/H+ and Cl-/HCO3-

occurs in the ileum and colon

Question 11

what epithelial channels are regulated by aldosterone

Answer 11

epithelial Na+ channels (ENaC)

Question 12

what type of transport is the Na+ co transporters

Answer 12

secondary active transport

Question 13

how are the Na+ co transporters electrogenic

Answer 13

as overall transport generates a transepithelial potential in which the lumen is negative (drives the parallel absorption of Cl-

Question 14

how many Na for each glucose or amino acid

Answer 14

2

Question 15

where does Na+/H+ exchange happen

Answer 15

in jejunum and proximal colon at apical membrane via NHE2 and NHE3

Question 16

does the parallel exchange of Na+/H+ and Cl-/HCO3- create a a potential across the membrane

Answer 16

no is electroneutral

Question 17

what regulates the parallel absorption of Na+ and Cl-

Answer 17

intracellular cAMP, cGMP and Ca2+ = all reduce NaCl absorbtion

Question 18

in parallel absorption what goes out when Na+ and Cl- comes in

Answer 18

Na+/H+

Cl-/HCO3-

Question 19

what does a reduction in NaCl absorption do

Answer 19

causes diarrhoea- secretory diarrhoea

Question 20

what causes secretory diarrhoea

Answer 20

infection (e.coli) can increase intraceluular cAMP

Question 21

what do ENaC channels do

Answer 21

mediate electrogenic Na+ absorption in the distal colon

Question 22

what are ENaC channels regulated by

Answer 22

increased by aldosterone, not mediated by cAMP/GMP (the cyclic nucleotides)

Question 23

how does aldosterone increase ENaC activity

Answer 23

opens then, puts more of them into the membrane, increases synthesis of them and Na+/K+-ATPase

Question 24

why are ENaC ion channels not transporters

Answer 24

as the sodium travels down its electrical gradient

Question 25

what happens if the ENaC channels are defective

Answer 25

lot of sodium in the colon which holds onto water= diarrhoea

Question 26

how is Cl- absorbed in the colon

Answer 26

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)

Question 27

how is Cl- passively absorbed in the small intestine

Answer 27

driving force= lumen negative potential due to electrogenic transport of Na+ (Na+/glucose and Na+/amino acid) – negative lumen pushing cl out

Question 28

how is Cl- passively absorbed in the large intestine

Answer 28

driving force= lumen negative potential due to electrogenic movement of Na+ through ENaC

Question 29

when healthy, is there net Cl- absorption or secretion

Answer 29

absorption

Question 30

where does Cl- secretion occur and at what rate

Answer 30

from crypt cells at a basal rate

Question 31

how does Cl- leave the cell

Answer 31

via CFTR (cystic fibrosis) on the apical membrane down an electrochemical gradient

Question 32

what does the secretion of Cl- lead to

Answer 32

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)

Question 33

what increases the activity of CFTR

Answer 33

``` bacterial endotoxins, calcium, cGMP and cAMP, hormones and neurotransmitters, immune cell products (prostaglandins, histamine), some laxatives ```

Question 34

what is the overall effect of the opening of CFTR channels

Answer 34

secretory diarrhoea

Question 35

what metabolic ion problems can diarrhoea cause

Answer 35

dehydration (Na+ and H2O loss) metabolic acidosis (HCOs- loss) hypokalaemia

Question 36

what can cause impaired absoprtion of NaCl which results in diarrhoea

Answer 36

congenital defects, inflammation, infection, excess bile acid in colon

Question 37

what are the biochemical causes of diarrhoea

Answer 37

impaired absorption of NaCl, non absorbable or poorly absorbable solutes in intestinal lumen (sugar substitutes, hypermoblity, excessive secretion, lactase deficiency

Question 38

why does hypermotility cause diarrhoea

Answer 38

not enough time to finish absorption

Question 39

how does the cholera toxin cause diarrhoea

Answer 39

inhibits GTPase which increases cAMP which stimulates CFTR which causes secretory diarrhoea

Question 40

how does lactase deficiency cause diarrhoea

Answer 40

as un-absorbed lactose acts osmotically and retains water in the lumen

Question 41

how do rehydration therapies work

Answer 41

Absorption of Na+ and glucose by SGLT1 cause accompanying absorption of H2O SGLT1 on apical membrane of enterocyte

Question 42

what drugs are used as anti motility agents to treat diarrhoea

Answer 42

opoid drugs e.g. codeine, diphenoxylate and loperamide(last two low CNS penetration so less change of abuse),

Question 43

how do opioids cause reduced motility

Answer 43

inhibit enteric neurones, decrease peristalsis, increased segmentation, increased fluid absorption, constriction of pyloric, ileocaecal and anal sphincters, increase tone of large intestine