Intestinal H20 And Electrolyte Transport

Front 1

Describe the volumes of oral fluid intake and total fluid secretion that daily enter the GI tract and name sources of the fluid secretions

Back 1

Secretions: ≈ 7.0 L
Salivary Secretion, Gastric Secretion, Pancreatic Secretion, Bile Secretion, Intestinal Secretion
Oral Intake: ≈ 2.0 L
Total: ≈ 9.0 L

Front 2

Describe the fundamental process that causes H2O movement across the intestinal epithelium

Back 2

-set-up of osmotic gradients determines direction of water movement (passive and paracellular through tight junctions) -- Some H2O movement in upper duodenum bc gastric contents entering there not usually isosmotic with body fluids -- BUT Most H2O movement is solute-coupled - due to osmotic gradients across the epith
set up by transport of Na+, Cl-, HCO3 and digested nutrients -- carrier mediated transp of Na+ by 2nd active IMPORTANT and set up by Na gradient from ATPase -- in SI, H2O absorbed by villi and secreted by crypts -- In LI, absorbed by surface epith and secr by crypts

Front 3

Identify the various types of Na+ transport mechanisms in the small intestine and colon and explain each one’s essential role in the absorption and secretion of H2O across the intestinal epithelia

Back 3

*Na+ transport through apical is done using by Na+ channels using gradient set up by ATPase -- (Na/H co-trsport in SI AND Na/H plus ENAC channel in colon) --subsequent movement across BL is due to ATPase and accompanied by transepith mvmt of Cl, bicarb, and nutrients

Front 4

Identify the transepithelial solute movements that lead to the absorption of H2O in the small intestine and colon and describe the cellular mechanisms that produce these solute movements

Back 4

--In ileum and proximal colon, Cl goes into cell by cl/bicarb exchanger and out BL side through membrane transporters
--Butyric acid exchanged in colon by But-/Bicarb exchangers in both Apical (But- in) and BL (But- out)
--ENaC channels (stim by aldo) in apical membrane of distal colon cause more Na to be absorbed through BL, and this, coupled with paracellular Cl- movement (it is repelled) causes H2O to follow!

Front 5

Explain the roles of Cl-, the basolateral Na/K/2Cl cotransporter, and the apical CFTR channel in the normal intestinal secretion of water and in secretory diarrhea

Back 5

**The ATPase provides energy to run the Na/K/Cl tri-transporter in the BL membrane, which bring Cl into cytosol to power the gradient needed for Cl to go into lumen though CFTR channel in Apical membrane -- Na follows out Apical paracellularly and net transport of NaCl causes H20 to follow osmotically paracellularly **Rate of H2O secretion is controlled through control of the Cl- conductance of CFTR channel: conductance and total number *** Cl- conductance is controlled by a Gs-type GPCR - adenylyl cyclase - cAMP - protein kinase A pathway. Receptors respond to VIP (from neural reflexes) and histamine and PGs (local factors) *** also controlled by cytosolic cGMP, elevated by stim of apical guanylin receptors

Front 6

Net Na+ movement by time GI contents have reached the colon

Back 6

Absorption via apical Na-nutrient cotransporters in small intestine, Na-H exchanger in small intestine and colon, and ENaC channels in colon -- Some passive paracellular secretion associated with H2O secretion.
***Net movement: Absorption

Front 7

Explain the general causes of these types of diarrhea: transport mismatch, osmotic and secretory

Back 7

*Transport mismatch -- chyme propelled to rapidly for existing rate of absorption -- hyper motility --> reduced absorptive surface area
*Osmotic -- elevated Amt of non-absorbed electrolytes due to digestive enzyme deficiency, inhibition of colonic digestion by anaerobic bacteria, or ingestion of undigestible/unabsorbable substances
*Secretory -- upset in balance btw NaCl-related H20 absorption and secretion -- excessive stimulation of water secretion (Cl secretion): *Cholera - sustained activation of Gs-protein *E. coli (traveler’s diarrhea) - releases toxins that activate the guanylin receptor in the apical membrane cGMP. *Reduced rate of H2O absorption: Inhibition of apical Na+ and Cl transporters in jejunem, ileum, and colon.

Front 8

Explain the physiological reason why oral rehydration therapy (ORT) can help ameliorate the effect of secretory diarrhea

Back 8

-sugars in an electrolyte solution -- can be absorbed because Na-Glucose co-transporters in Villi are normal!!!

Front 9

Net K+ movement by time GI contents have reached the colon

Back 9

1. As H2O is absorbed in jejunem and ileum, the [K+] in
chyme increases paracellular diffusion of K+ across epithelial layer.
2. All ingested K+ has been absorbed from chyme by
the time it enters the colon.
3. In the distal colon, some K+ is secreted into lumen
as a result of Na+ uptake through ENaC. Increases
in Na+ influx through ENaC increases the [K+]
gradient increases K+ secretion through channel in apical -- Colonic secretion of K+ is flow-dependent.
4. Because of the abundance of K+ in food, much more K+ is absorbed than secreted.
***Net movement: Absorption

Front 10

Net Cl- movement by time GI contents have reached the colon

Back 10

Absorption via apical Cl-HCO3 exchangers in small intestine and colon + paracellular diffusion -- Some secretion through CFTR channel associated with H2O secretion
***Net movement: Absorption

Front 11

Net HCO3- movement by time GI contents have reached the colon

Back 11

1. Secreted into duodenum in pancreatic juice and bile - neutralizes acidic chyme from stomach.
2. Absorbed in large quantities in the jejunem.
Accomplished by combined action of the apical Na-H exchanger and the basolateral HCO3- transporter -- Virtually all of secreted HCO3- is absorbed in jejunem.
3. Secreted by apical Cl-HCO3 exchanger in ileum and
colon.
***Net movement: Secretion

Front 12

Consequences of Diarrhea

Back 12

1. Excessive fluid loss from the circulation --> reduction in cardiac output --> drop in MAP.
2. Reduction in K+ absorption in small intestine (failure to absorb all K+) and an increase in colonic K+ secretion --> net reduction in K+ absorption --> hypokalemia.
3. Reduction in HCO3- absorption--> increase in net HCO3- loss from the body --> metabolic acidosis.