1- physiology of fluid + gastric secretion

Question 1

what is absorption of water driven by?

Answer 1

it’s a passive process driven by transport of solutes (particularly Na+) from lumen of intestines to blood stream

Question 2

what is balance of how much water is ingested/secreted to how much is absorbed?

Answer 2

usually equally balanced - same amount ingested and secreted is normally absorbed

Question 3

what happens in diarrhoea?

Answer 3

you get loss of fluid + solutes = which leads to loss of electrolytes

defined as loss in excess of 500 ml per day

Question 4

how much liquid does faeces normally have?

Answer 4

100ml of water along with 50ml cellulose, bilirubin + bacteria

Question 5

what are the 5 different transporters that can drive movement of water?

Answer 5

1. Na+/glucose co-transport
2. Na+/amino acid co-transport
3. Na+/H+ exchange
4. parallel Na+/H+ and Cl-/HCO3- exchange
5. epithelial Na+ channels (ENaC)

Question 6

what transporters for movement if water occur in small intestine?

Answer 6

1. Na+/glucose co-transport
2. Na+/amino acid co-transport
   = most important in post prandial period (period after digestion)

Question 7

what transporter for movement of water occurs in duodenum + jejunum?

Answer 7

Na+/H+ exchange
= stimulated by luminal HCO3-

Question 8

what transporter for movement of water occurs in ileum + colon?

Answer 8

parallel Na+/H+ and CL-/HCO3- exchange
= important in interdigestive period (after upper Gi tract cleared of food)

Question 9

what transporter for movement of water occurs in colon? (particularly distal)

Answer 9

epithelial Na+ channels, ENaC (regulated by aldosterone)

Question 10

what is mechanism for absorption by sodium and glucose/amino acid tranpsorters?

Answer 10

will be active in duodenum and a bit lesser degree in ileum:

• these transporters use sodium gradient across apical membrane (side facing lumen) to transport glucose + amino acids into enterocytes
• this sodium gradient is maintained by Na/K ATPase pump on basolateral membrane of enterocytes (SOPI)
• collectively the overall transport of Na+ generates a transepithelial potential (VTE) in which the lumen is negative – this drives the parallel absorption of Cl- (which helps for lots of things like electrolyte balance)

Question 11

what is cellular mechanism for sodium/ hydrogen ion pump?

Answer 11

in jejunum and exchange at apical membrane is stimulated by alkaline (high pH, low H+) due to bicarbonate presence from pancreas
- the exchange of Na+/H+ and CI-/HCO3- occurs in parallel
- it’s regulated by cAMP, cGMP and Ca2+ which all reduce NaCl absorption

Question 12

what are the different isoforms of Na+/H+ pump?

Answer 12

NHE2+NHE3 which are on apical membrane and NHE1 which is on basolateral membrane

NHE2 + NHE3 contribute to transepithelial movement of Na+ (and the regulation of intracellular pH).
NHE1 is a ‘cellular pH housekeeper’

Question 13

where is electroneutral?

Answer 13

intestine = no electrical charge gradient

Question 14

what is effect of reduction in NaCl absorption?

Answer 14

cause of diarrhoea (e.g. secretory diarrhoea due to infection with E. coli – heat stable enterotoxin from which activates adenylate cyclase and increases intracellular cAMP)

Question 15

what is ENaC pump and what regulates it?

Answer 15

ENaC pump = mediate electrogenic Na+ absorption in distal colon

• increased by aldosterone but not regulated by cAMP or cGMP

Question 16

what are 3 functions of aldosterone in ENaC pump?

Answer 16

opens ENaC (seconds), inserts more ENaC into membrane from intracellular vesicle pool (mins) and increases synthesis of ENaC and NA/K ATPase (hours)

Question 17

what is driving force for chloride absorption in small + large intestine?

Answer 17

in small intestine - driven by lumen negative potential due to electrogenic transport of Na+ (Na+/glucose and Na+/amino acid)

in large intestine - driven by lumen negative potential due to electrogenic movement of Na+ through ENaC

Question 18

what is cellular mechanism for chloride secretion?

Answer 18

• usually down to cystic fibrosis transmembrane receptor (CFTR)
• occurs at basal rate but is usually overshadowed by a higher rate of absorption
• occurs from crypt cells rather than villus cells
• is important in many diarrhoeas

Question 19

what are the 3 processes involved in chloride secretion?

Answer 19

1. Na+/K+ ATPAse
2. Na+/K+/2Cl cotransporter (NKCC1)
3. K+ channels

Question 20

what role does Na+/K+/2Cl cotransporter have in chloride secretion?

Answer 20

low intracellular Na+ drives inward movement of Na+, K+ and Cl- via NKCC1

Question 21

what role does CFTR channel have in chloride secretion

Answer 21

normally, only little bit of Cl- secretion as CFTR channel closed or not present

• secretion occurs when indirectly activated by bacterial endotoxins, several hormones + neurotransmitters, immune cell products, some laxatives e.g. bile acids
• activation of CFTR can occur because of second messengers like cAMP, cGMP

Question 22

what happens when CFTR channel activated?

Answer 22

This activation results in the opening of CFTR channels at the apical membrane or the insertion of channels from intracellular vesicles into the membrane, ultimately causing secretory diarrhea

Question 23

what is mechanism of chloride secretion?

Answer 23

• Low intracellular Na+ drives inward movement of Na+, K+ and Cl- via NKCC1
• K+ recycles out via K+ channels, leaves intracellular concentration of Cl- increases providing an electrochemical gradient (negative inside) for Cl- to exit cell via CFTR on the apical membrane
• movement of ions (Cl- ions particularly) makes electrical potential difference across epithelial layer with negative potential in lumen, this means Na+ secreted into lumen along with Cl-

Question 24

what causes diarrhoea? (things not a problem with body)

Answer 24

• infectious agents - viruses, bacteria
• chronic disease
• toxins
• drugs
• psychological factors

Question 25

what is effects of diarrhoae?

Answer 25

• may involve small or large intestine
• can result in dehydration (Na+ and H2O loss), metabolic acidosis (HCO3- loss) and hypokalaemia (K+ loss)
• may be fatal if severe e.g. cholera

Question 26

what is treatment of severe acute diarrhoea?

Answer 26

• maintenance of fluid + electrolyte balance (1st priority)
• use of anti-infective agents
• use of non-antimicrobial antidiarrheal agents (symptomatic

Question 27

what are causes of diarrhoea? (things because of body)

Answer 27

• impaired absorption of NaCl
• congenital defects
• inflammation
• excess bile acid in colon
• non-absorbable or poorly absorbable solutes in intestinal lumen
• lactase deficiency
• hypermotility

Question 28

how is diarrhoea caused in cholera for example?

Answer 28

bacterial toxin secreted in cholera inhibits GTPase which increase activity of adenyl cyclase (activate adenylyl cyclase converting ATP →cAMP) cAMP stimulates CFTR - hypersecretion of Cl- with Na+ and water following

Question 29

what is mechanism of rehydration therapy using SGLT2?

Answer 29

1. 2 Na+ bind
2. Affinity for glucose increases, glucose binds
3. Na+ and glucose translocate from extracellular to intracellular
4. 2 Na+ dissociate, affinity for glucose falls
5. Glucose dissociates
6. Cycle is repeated

(moves glucose in using Na+)