UW Division of Gastroenterology - Gut Course Syllabus (HuBio 551)

	Updated: 03/13/08 12:05 PM

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Authors: D.R. Saunders, C.E. Rubin, and J.D. Ostrow
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G. Normal Water & Electrolyte Absorption

Overall balance

Physicians need to have a basic knowledge of transport mechanisms to care for patients with diarrhea.

First, approximately 9 liters of electrolyte solution enter the small bowel daily as food and gastrointestinal secretions. Of this, no more than 2% of the water, 2% of the sodium, and 10% of the potassium appears in the feces, because 50% of water and electrolyte is absorbed in the jejunum, 30% in the ileum and most of the remaining 20% in the colon.

Upper Gastrointestinal Fluids
Fluid	L/day	Composition
Diet	2	Variable
Saliva	1	Hypotonic, alkaline
Gastric Juice	2	Isotonic, acid
Bile	1	Isotonic
Pancreatic Juice	2	Isotonic, alkaline
Intestinal juice	1	Isotonic, neutral
Total	9

Excretion of Gastointestinal Fluids
Component	Delivered to Colon*	Excreted
Water	600 ml	100 ml
Sodium	75 meq	4 meq
Potassium	5 meq	9 meq
Chloride	36 meq	2 meq
Bicarbonate	44 meq	3 meq
*Data from patients with ileostomies.

Bidirectional movement

Jejunal pores are larger than ileal pores

Second, there is bidirectional movement of molecules both in and out of the intestinal mucosa at all times. Net absorption means that more molecules pass through the mucosa into the body than leave it to enter the lumen; net secretion means the opposite. Jejunal mucosa is a moderately "leaky" epithelium which means that water and small solutes such as Na⁺ can cross it rapidly from blood to lumen and from lumen to blood. Solutions in the duodenum and upper jejunum come rapidly into osmotic equilibrium with plasma. A major function of the duodenum and upper jejunum is to render hypotonic and hypertonic meals isotonic with plasma. Ileal mucosa is less "leaky" while colonic mucosa is the least "leaky" of the three. The gut, unlike the kidney's loop of Henle, cannot create "free" water devoid of Na⁺. NaC1 is always present in the intestinal lumen, and the intercellular spaces.

Third, the engine that drives absorption is the Na⁺/K⁺ -ATPase pump at the basolateral membrane of intestinal epithelial cells. It is estimated that each jejunal epithelial cell employs over a million such pumps, and that one-quarter of all the ATP consumed by resting humans is utilized by Na⁺/K⁺ pumps. These pumps transfer one positive charge out of the cell per cycle (3 Na⁺ out; 2 K⁺ in) so that the interior of the epithelial cell is electrically negative, and has a Na+ concentration of about 20 mM (compared with 140 mM in plasma). This Na⁺ gradient drives many transport processes. Luminal Na+ can diffuse through Na⁺- channels down electrical and chemical gradients. Cl^- can enter the cells via a basolateral membrane carrier which couples the absorption of 2 Cl^- with 1 Na⁺ and 1 K⁺. Na⁺/H⁺ exchangers in the luminal membrane mediate the entry of 1 Na⁺ in exchange for the exit of 1 H⁺. This exchanger is also driven by the gradient for Na⁺, and by the higher concentration of H⁺ in the cytosol compared with H⁺ in the lumen.

Cl^- secretion

Fourth, throughout the small and large intestines Cl^- is secreted through selective Cl^- channels in the apical membrane. Na⁺ follows passively through paracellular pores.

Figure 5
Intestinal Secretion

The cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a CI^- channel which is activated by increases in intracellular cAMP.

Figure 6
Duodenal Transport

A carrier in the duodenum exchanges luminal Na⁺ for intracellular H⁺. The H⁺, delivered into the lumen, reacts with luminal bicarbonate yielding CO₂ and H₂O. CO₂ and H₂O are freely diffusible across the mucosa so that luminal osmolality is reduced. Because the “tight” junctions here are leaky, NaCl in the intercellular space can diffuse readily back in to the intestinal lumen (there is no net absorption of 140 mM NaCl).

SGLT at brush border membrane; 2 Na+ are carried with one glucose

Therefore a most important process for Na⁺ absorption in the proximal small intestine is carrier-mediated transport with nutrients (glucose, or galactose, or amino acids). A membrane carrier (Sodium-Glucose Linked Transporter) delivers glucose and Na⁺ into the absorptive cell; a glucose carrier (Glut-2) delivers glucose across the basolateral membrane into the intercellular space. Glucose is too large a molecule to diffuse through the “tight” junction back into the intestinal lumen. Rather, the glucose, with its medium of water and electrolytes, diffuses down a concentration gradient into plasma thereby “dragging” salt and water with it.

The human jejunum lacks the duodenal Na⁺/H⁺ exchanger. Instead, it couples Na⁺/H⁺ with CI^-/HCO3^- exchange.

Figure 7
Ileal Transport

Chief mechanism for Na⁺ absorption in ileum is coupled exchangers

Glucose, galactose, and amino acids can also be transported with Na+ by ileal absorptive cells, but most of these nutrients have been absorbed in the proximal half of the small intestine. Much water and NaCl remains to be absorbed by the ileum which relies on coupled exchangers Na⁺/H⁺, Cl^-/HCO₃^-. The ileum can also maintain a gradient for Na⁺ of ~15 mM (lumen, 125 mM; blood, 140 mM) because its pore size is tighter than the pores in the jejunum (Fig. 7). K⁺ (10-15 mM) replaces Na⁺ in the ileal lumen so that isotonicity with plasma (290 mosmols/kg) is maintained.

Diarrhea can result in hypokalemia

The upper small intestinal paracellular junctions are permeable to K⁺ so that luminal K⁺ is nearly in equilibrium with K⁺ in the intercellular spaces. The absorption of water, which is driven by osmotic forces, produces a small concentration gradient for K⁺ which favors that cation’s absorption. Large losses of K+ can occur when water absorption is impaired in diarrheal disease.

Notice how lumen contents influence the mechanisms of Na⁺ and H₂O absorption. In the upper half of the small intestine, Na⁺ absorption is primarily coupled with nutrient molecules such as glucose, galactose, amino acids. The ileum relies much less on nutrient-coupled transport because most of the nutrients have already been extracted from ileal chyme.

Remark on the efficiency of Na⁺/H⁺ and Cl^-/HCO₃^- exchangers. The reaction, H⁺ + HCO₃→H₂O + CO₂, on the luminal surface of absorption cells serves to lower luminal osmotic strength, and the H₂O and CO₂ can diffuse down concentration gradients into plasma.

Next Section (H): Water & Electrolyte Malabsorption »