Fluid balance Flashcards
what drives absorption of water?
transport of solutes (mainly sodium) from the intestine lumen into the bloodstream
provides a local osmotic force for reabsorption of water
intestinal fluid movement is always coupled to solute movement, true or false?
true
via what 2 routes can water move across the membrane?
transcellular and paracellular
what are the principle mechanisms through which sodium is reabsorbed?
Na+/H+ exchange = in duodenum and jejunum, stimulated by HCO3
Na/glucose or Na/amino acid co-transport = in small intestine in postprandial period
parallel Na/H+ and Cl-/HCO3 exchange = in colon and ileum in interdigestive period
Epithelial Na channels (ENAC) = in colon, regulated by aldosterone
how does Na/glucose and Na/amino acid exchange work?
secondary active transport
electrogenic
Na+ transport out of the cell via ATPase reduces cell conc of Na so lumen Na flows in and brings glucose
High glucose conc in the cell so it flows out via GLUT2 into bloodstream
Na movement generates transepithelial potential (VTE) where lumen is negative so Cl- also absorbed
Mediated by ATPase
how does Na/H+ exchange work?
happens at apical membrane and basolateral membrane
inward movement of 1 sodium = outward movement of 1 proton = electroneutral
happens via Na/H+ exchanger (NHE2 and NHE3)
exchange at apical membrane in jejunum stimulated by alkaline pH from presence of bicarbonate
what does NHE1 do?
cellular pH housekeeper
how does NA+/H+ and Cl/HCO3 parallel exchange work?
both happen in parallel in ileum and colon Na+/H+ same as before both are electroneutral more important in fasting state regulated by cAMP, cGMP and Ca2+ which all reduce NaCl absorption
what can a reduction in NaCl absorption cause?
diarrhoea
what can cause a reduction in NaCl absorption?
E. coli infection
how do epithelial Na+ channels (ENaC) work?
when open the channel allows sodium to flow into cell along electrochemical gradient and then out via sodium potassium pump
efficient and important for Na conservation
mediated by aldosterone
what are the 3 actions of aldosterone?
opens ENaC channels
inserts more ENaC into membrane from intracellular vescicle pool
increases synthesis of ENaC and Na+/K+ ATPase
how can chloride be absorbed?
passively either transcellular or paracellular
what is the driving force for chloride absorption in the small intestine?
lumen negative potential due to electrogenic transport of Na+ (Na/glucose and Na/amino acid)
what is the driving force behind chloride absorption in the large intestine?
lumen negaytive potential due to electrogenic movement of Na through ENaC
what other 2 methods can chloride be absorbed via?
Cl-/HCO3- exchange
parallel Na+/H+ and Cl-/HCO3- exchange
which is greater, chloride secretion or absorption?
absorption
at basal rate
where does chloride secretion occur?
crypt cells
what processes on the basolateral membrane are involved in chloride secretion?
Na+/K+ ATPase
Na+/K+/2Cl co-transporter (NKCC1)
K+ channels
= triple transporter - increases conc of chloride inducing secretion of Cl at the apical membrane
what mediates chloride secretion?
Calcium
cAMP
increase causes increased secretion via CFTR
what is the role of CFTR?
usually closed or not present so little Cl secretion
activated by:
- bacteria enterotoxins
-hormones/neurotransmitters (VIP, guanylin, ACh, bradykinin, serotonin)
- immune cells products (proastaglandins, hisamine)
- some laxatives (bile acids)
- generation of second messengers (cAMP, cGMP, Ca2+)
what does the opening and activation of CFTR cause?
secretory diarrhoea
what electrolyte loss can diarrhoea cause?
dehydration - Na+ and H2O loss
metabolic acidosis - HCO3 loss
hypokalaemia - K+ loss
what is the treatment for dairrhoea?
usually none as mostly viral so just sit and wait
maintain fluid and electrolyte balance first
use of anti-infective agents if appropriate
use of non-antimicrobial anti-diarrhoeal agents for symptoms
what can cause diarrhoea?
impaired NaCl absorption (congenital, infection, excess bile)
non/poorly absorbable solutes in the lumen (eg. lactase deficiency)
Hypermotility
Excessive secretion (eg. cholera)
describe rehydration therapy (SGLT1)
1) 2 sodium bind to SGLT1
2) affinity for glucose increases, glucose binds
3) sodium and glucose translocate from extracellular to intracellular
4) 2 sodium dissociate, glucose affinity falls
5) glucose dissociates
6) cycle is repeated
what anti-motility agents are used in diarrhoea?
many morphine-like drugs
- codeine
- diphenoxylate
- loperamide = most common, safest, non-addictive
how do opioids affect the alimentary tract?
Inhibit enteric neurones
Decrease peristalsis, increased segmentation
Increase fluid absorption
Constriction of pyloric, ileocaecal and anal sphincters
Increased tone of large intestine
what is the definition of diarrhoea in terms of fluid loss?
loss of fluids in excess of 500ml per day
what is the composition of faeces?
100ml water + 50ml cellulose, bilirubin and bacteria
what results from low intracellular sodium?
inward movement of sodium, potassium and chloride via NKCC1
how does chloride exit the cell?
potassium channels recycle potassium while Cl- concentration increases providing an electrochemical gradient for Cl- to exit the cell via CFTR on apical membrane
Describe the mechanism of excessive secretion in cholera
cholera toxin (CTX) enters enterocyte
enzymatically inhibits GTPase activity of the alpha subunit on G protein
Alpha subunit keeps signalling adenylate cyclase increasing its activity
Increased concentration of cAMP
cAMP stimulates CFTR
Hypersecretion of Cl- with Na and water following
what is the overall water balance in the GI tract?
9.3L enter tract per day
8.3L absorbed per day
1L enters large intestine of which 90% is absorbed
what effect does absorption of sodium and glucose by SGLT1 have on water absorption?
increases it
