Question

(a) Life-threatening diarrhea is a shockingly common problem in the developing world. People with life-threatening diarrhea are often \(\mathrm{Na}^{+}\)-depleted, and to save their lives, replacing \(\mathrm{Na}^{+}\)is essential. However, "raw" \(\mathrm{Na}^{+}\)in the intestines is not absorbed. Drinking a solution of \(\mathrm{NaCl}\) does not, therefore, replenish body \(\mathrm{Na}^{+}\). In fact, drinking such a solution can actually worsen a person's situation by osmotically dehydrating the blood and other body fluids. Explain how the drinking of a \(\mathrm{NaCl}\) solution could have this effect. (b) One of the greatest physiological discoveries of the twentieth century was that drinking a solution of mixed glucose and \(\mathrm{NaCl}\) can promote restoration of the body's \(\mathrm{Na}^{+}\). With the glucose concentration high enough in the solution, glucose "drives" the glucose-Na+ cotransporter in the apical membranes of intestinal epithelial cells, promoting \(\mathrm{Na}^{+}\)uptake in sick people. Explain the concept behind this manipulation of the cotransporter for therapeutic ends. The approach has saved millions of lives.

Short answer

Drinking NaCl solution worsens dehydration due to osmosis, where water moves from blood and cells to intestines, trying to balance the high solute concentration. However, glucose can stimulate the glucose-Na co-transporter in the intestines to intake more Na into cells, thus preventing dehydration. This principle has been applied in life-saving Oral Rehydration Therapy.

Step-by-step solution

Understanding the effect of NaCl solution

When a person drinks a NaCl solution, the intestines, where absorption of digested food and most of water occur, are filled with a high concentration of salt. Because of osmosis, water in cells and blood tends to move to the intestines where the concentration of solutes (NaCl here) is higher, hence, resulting in the dehydration of blood and body fluids.

Understanding the role of glucose in sodium absorption

Intestinal epithelial cells have glucose-Na cotransporter proteins which transport glucose and Na from the intestines into cells. These proteins use the glucose concentration gradient to drive the uptake of Na. When a person drinks a solution with high glucose concentration, it helps increase the concentration gradient between the intestines and cells, hence 'drives' the cotransporter to take up more Na along with glucose.

Application of the concept in rehydration therapy

Knowing that glucose can 'drive' the absorption of sodium in the intestines, a solution with high glucose concentration can be given to the patients. As a result, despite the high salt concentration in the intestines, the body can absorb sodium (and water) back, thus rehydrating the blood and body fluids. This is the basis of the Oral Rehydration Therapy (ORT), a simple, cheap and effective treatment for dehydration due to diarrhea, widely used in many countries.

Key concepts

Osmosis and Dehydration

Osmosis is a critical process in biology, where water moves across a semipermeable membrane from an area of low solute concentration to one of high solute concentration. It attempts to equalize the solute levels on both sides of the membrane. In the context of life-threatening diarrhea, where individuals can be depleted of sodium (a{^+}a{^+}), drinking a simple saline solution (a{Cl}) paradoxically exacerbates the problem.

When a a{Cl} solution is consumed, the concentration of a{Cl} in the intestines can become higher than that in the cells and bloodstream. Osmosis then causes water to be drawn from the bloodstream into the intestines in an attempt to balance the solute concentration. This movement of water reduces the fluid volume in the bloodstream—effectively dehydrating the individual rather than hydrating them. This counterintuitive phenomenon underlies the reason why saline solutions are inadequate for treating severe dehydration caused by diarrhea.

Glucose-Na+ Cotransporter

The glucose-Na cotransporter (often called the SGLT1 transporter) is a protein found in the apical membranes of intestinal epithelial cells. This transporter has the fascinating ability to move glucose and Na together from the intestinal lumen into the cells. Crucially, the SGLT1 transporter uses the gradient of high glucose concentration outside the cell (in the intestines) to facilitate the intake of a{^+}a{^+}, which otherwise would not move into the cells as readily.

The cotransporter allows glucose to 'piggyback' a{^+}a{^+} into the cells, effectively promoting the absorption of sodium without direct intake of saline solutions. Understanding how these transporters work has had significant implications for addressing dehydration, especially where diarrhea is involved.

Intestinal Sodium Absorption

Sodium absorption in the intestines is a delicate process that must be carefully managed, particularly during spells of acute diarrhea. The process is largely governed by cotransporters that allow a{^+}a{^+} to enter the intestinal cells. However, for these cotransporters to function efficiently, a driving force is needed — in this case, the presence of glucose.

When a high-glucose solution is drunk, it promotes a strong concentration gradient with low glucose inside the intestinal cells and high glucose in the intestine. This gradient powers the SGLT1 cotransporter, which in turn promotes both glucose and a{^+}a{^+} absorption. The glucose serves as both fuel for the cells and as a means to facilitate the vital absorption of sodium, which helps maintain fluid balance and prevent further dehydration.

Rehydration Solutions

Rehydration solutions are the cornerstone of effective treatment for dehydration caused by illnesses like diarrhea. The most efficient rehydration solutions contain a precise mixture of salts (including sodium) and glucose. The inclusion of glucose is not merely a source of energy but an essential component that stimulates the absorption of sodium through the SGLT1 transporter.

Oral Rehydration Therapy (ORT) capitalizes on this principle by using such balanced solutions to rehydrate individuals effectively. ORT is simple, cost-effective, and has been a lifesaving intervention for millions across the globe. These solutions are carefully formulated to ensure that they are isotonic, meaning they match the body's own osmolality, to prevent further osmotic imbalance and promote efficient water and electrolyte uptake.