Flashcards in Water Balance in the GI tract Deck (59):
What is a passive process driven by the transport of solutes (particularly Na+) from the lumen of the intestines to the bloodstream?
Absorption of water
How much water enters the tract per day?
How much water is absorbed by the small intestine?
How much water enters the large intestine, and of that what percentage is absorbed?
1 litre, 90% absorbed
What has 100ml in faeces and what has 50ml, along with, bilirubin and bacteria?
What is defined as a loss of fluid and solutes from the GI tract in excess of 500ml per day?
What is intestinal fluid movement always coupled to?
What two ways may water move?
What two prinicple mechanisms of Na absorption occurs throughout the small intestine and is most omportant in the post-prandial period (also occurs in the colon in the new born)?
What prinicple mechanism of Na movement occurs in the duodenum and jejunum and is stimulated by HCO3?
Where does Na+/H+ exchange occur?
In duodenum and jejunum
What stimulates Na+/H+ exchange?
Where and at what time does the parallel Na+/H+ and Cl-/HCO3 exchange occur?
In the ileum and colon, most important in the interdigestive period
What principle mechanism for Na exchange occurs in the colon (distal) and is regulated by aldosterone?
Epithelial Na+ channels (ENaC)
What to mechanisms of postprandial Na+ absorption are examples of secondary active transport and are electrogenic?
Na+/glucose and Na+/amino acid co-transport
Collectively, what does the overall transport of Na+ generate?
A transpepithelial potential (Vte) in which the lumen is negative
Due to the transepithelial potential in which the lumen is negative, what does this drive?
Parallel absorption of Cl-
Where does Na+/H+ exchange in the jejunum occur at?
Both the apical and baseolateral membranes (via different isoforms of the exchanger)
During Na+/H+ exchange in the jejunum, what two things contribute to transepithelial movement of Na+ and the regulation of intracellular pH?
NHE2 and NHE3
What is exchange at the apical membrane, in the jejunum stimulated by?
The alkaline environment of the lumen due to presence of bicarbonate from the pancreas
In the jejunum, what is absent?
A parallel Cl--HCO3 exchanger
What is the primary mechanism of Na+ absorption in the interdigestive period?
Na+/H+ and Cl-/HCO3- exchange in parallel
In Na+/H+ and Cl-/HCO3-, what is absorption like?
In Na+/H+ and Cl-/HCO3-, what is it regulated by?
Intracellular cAMP, cGMP and Ca2+, all of which reduce NaCl absorption
What is reduction in NaCl absorption a cause of?
Explain how secretory diarrhoea is caused due to infection with E. coli?
Enterotoxin from which activates adenylate cyclase and increases intracellular cAMP, reducing NaCl absorption
What mediates electrogenic Na+ absorption in the distal colon?
Epithelial Na+ channels (ENaC)
What is ENaC increased by?
What are the three actions of aldosterone on ENaC?
1. opens ENaC
2. Inserts more ENaC into membrane from intracellular vesicle pool
3. Increases synthesis of ENaC and Na+/K+-ATPase
What two routes can Cl absorption occur passively on?
Transcellular and paracellular
In the small intestine, what is the driving force for Cl- absorption provided by?
Lumen negative potential due to electrogenic transport of Na+ in Na+/glucose and Na+/amino-acid co-transporty]
In the large intestine, what is the driving force provided by for the absorption of Cl-?
Lumen negative potential due to electrogenic movement of Na+ through ENaC.
What is another mechanism for Cl- absorption that occurs in the ileum, proximal and distal colon?
What is another mechanism for Cl- absorption that occurs in the ileum and proximal colon?
parallel Na+/H+ and Cl-/HCO3 exchange
What occurs at a basal rate but is usually overshadowed by a higher rate of absorption?
What cells does Cl- secretion occur from?
What membrane does Cl- absorption into cell before secretion occur at?
What are the three processes involed on the basolateral membrane in Cl- secretion?
2. Na+/K+/2Cl-co-transporter (NKCC1)
3. K+ channels (IK1 and BK)
In Cl- secretion, what does low intracellular Na+ drive?
Inward movement of Na+, K+ and Cl- via NKCC1
In Cl- secretion, once low intracellular Na+ drives inward movement of Na+, K+ and Cl- via NKCC1, what occurs next?
K+ recycles via K+ channels, but intracellular concentration of Cl- increases providing an electrical chemical gradient for Cl- to exit cell via CFTR on teh apical membrane.
In Cl- secretion, once Cl- has exited the cell via CFTR on the apical membrane, what happens?
Lumen negative potential develops providing voltage-dependent secretion of Na+ through paracellular pathway
What has to be active for Cl- secretion to occur?
What 4 substances activate CFTR?
1. bacterial enterotoxins
2. Hormones and neurotransmitters
3. Immune cells products
4. Some laxatives
Activation of CFTR also occurs indirectly as a result of the generation of what three second messengers?
What two things does the Cl- conductance mediated by CFTR result from?
1. Opening of channels at the apical membrane
2. Insertion of channels from intracellular vesicles into the membrane
What causes metabolic acidosis, due to loss of HCO3 and hypokalaemia?
What 4 factors can lead to impaired absorption of NaCl and so lead to dairrhoea?
1. Congenital defects - congenital chloridorrhoea absence of Cl--HCO3 exchanger
4. Excess bile acid in colon
What is a cause of non-absorbable solutes in intestinal lumen - leading to diarrhoea?
What provides a classic example of excessive secretion to lead to diarrhoea?
Once cholera toxin has entered the enterocyte, what does it enzymatically inhibit?
GTPase activity of the Gsalpha subunit.
What does enzymatically inhibited GTPase increase the activity of?
Adenylate cyclase leading to increased cAMP
What does cAMP stimulate and what does it lead to?
CFTR - hypersecretion of Cl- with Na+ and water following
What does this describe: 2Na+ binds to SGLT1, affinity for glucose increases so glucose binds, Na+ and glucose translocate from extracellular to intracellular, 2Na+ dissociates, affinity for glucose falls so glucose dissociates and the cycle repeats?
Rehydration therapy exploting SGLT1
What types of drugs have anti-diarrhoeal activity/
Morphine and opiate drugs
What do opiates do to enteric neurones?
Inhibit them causing hyperpolarisation via activation of u-opoid receptors
What do opiates do to peristalsis and segmentation?
Decreased peristalsis and increased segmentation (i.e. constipating)
What do opiates do to fluid absorptin?
What drugs cause constriction of pyloric, ileocaecal and anal sphincters?