Week 3: Water flow in the intestines Flashcards
CFTR AKA
Cystic fibrosis transport regulator
How much water moves through the intestine on a daily basis?
~9 L
How much intestinal water comes from dietary sources?
~1-2 L out of the 9 L
How much intestinal water comes from the small intestine?
~1.5L out of 9L
Describe the mechanism of water movement in small intestines
- Na+K+ ATPase -> K+ into cell and Na+ out of cell into interstitial space
- K+ leak channels allow K+ to avoid gradient
- Tripartite transport symporter (Na+, K+ and Cl- into the cell)
- Cl- travels through CFTR which is activated by cAMP to allow Cl- to flow into the intestinal lumen
- There will be an electrochemical gradient formed by the Cl- ions in the lumen and the Na+ will flow through the interstitial space into the lumen of the intestine and water will follow
Describe regulation of small intestine CFTR
adenylate cyclase generates cAMP from ATP
Adenylate cyclase is activated by heterotrimeric G protein 7 transmembrane which binds VIP (Vasoactive intestinal peptide)
VIP activates heterotrimeric G protein which activates adenylate cyclase to create cAMP which activate the CFTR channel to let Cl- flow out into the lumen
VIP AKA
Vasoactive intestinal peptide
Vasoactive intestinal peptide functions
- activates heterotrimeric G protein to activate adenylate cyclase to activate CFTR in small intestine enterocytes to let Cl- out and for Na+ and water to follow to introduce water into the lumen to aid in digestion
- stimulates buffer secretion (pancreas) stimulates HCO3- to neutralize acid (main hormone that does this is secretin)
- Inhibits gastric secretions (once chyme is in small intestine there shouldn’t be food in the stomach
- Dilates intestinal capillaries (digestive material in intestine want to absorb and deliver to the rest of the body)
Where does VIP come from?
secreted by enteroendocrine cells in response to chyme in order to introduce water into the lumen to aid digestion
How much water is lost in the feces?
only ~100 mL of H20
How does the GI tract absorb the 9L of H2O
SGLT-1 Na+glucose symporter into the cell, Basal surface Na+K+ ATPase K+ into cell, Na+ to the body
GLUT2 uses concentration gradient of glucose to transport into the blood
Water follows the osmotically active glucose and Na+ into cells
Water flow of the large intestine
Na+K+ ATPase Na+ out, K+in
HCO3-Cl- antiporter HCO3- lumen, Cl- into cell coupled to Na+H+ antiporter Na+ in, H+ out
Na+ and Cl- from diet, CO2 from metabolism combined with water by Carbonic Anhydrase to form HCO3-
So now we have Na+ and Cl- being transported into the cell
Overall Na+ and Cl- transported to body and water follows
Fiber in the large intestine water absorption
fiber associates with water in the lumen making it less available to be absorbed back into the body keeping more water in the stools
Too much fiber loose stools
Too little water constipation
Large intestine H2O absorption in Cholera
- Na+K+ ATPase Na+ out, K+in
- Tripartite transporter Na+ in, K+ in, Cl- in to cell
- if an excess of chloride in a cell the chloride can go back out into the lumen by CFTR (CFTR will be constitutively active by ADP Ribosylation)
- Na+ will then move to neutralize the charge of the Cl- in the lumen
- Water will then move back into the lumen
Describe ADP Ribosylation
Ribose with Adenine nucleotide to covalently modify the heterotrimeric G protein and continuous production of cAMP and stimulates CFTR transporter into the constitutively active state causing diarrhea