RENAL NATRIURESIS, OXIDATIVE STRESS, AND DIABETIC NEPHROPATHY

Central role of the kidney in keeping electrolyte balance and osmolarity

Electrolytes are defined as minerals that carry an electric charge when dissolved in liquid such as blood. The major blood electrolytes—sodium, potassium, chloride, and bicarbonate—are involved in the regulation of nerve and muscle function and in the maintenance of acid-base balance and water balance. Electrolytes maintain normal fluid levels in various compartments because the amount of fluid that a compartment contains depends on the concentration of electrolytes in it. If the electrolyte concentration is high, fluid moves into that compartment by osmosis, while if the electrolyte concentration is low, fluid moves out of that compartment. To adjust fluid levels, the body can actively move electrolytes in or out of cells. Hence, having an electrolyte balance is very important in maintaining fluid balance among the compartments.

The kidneys play a critical role in keeping physiologically suitable electrolyte concentrations. This is done by filtering electrolytes and water from the blood, returning some to the blood and excreting any excess into the urine. Overall, the kidneys maintain a balance between the daily consumption and excretion of electrolytes and water. An electrolyte imbalance can result from dehydration or overhydration (e.g., intravenous fluid administration), effects of drugs, or certain heart, kidney, or liver disorders.

In addition to regulating the total fluid volume, the osmolarity (the amount of solute per unit volume) of bodily fluids must be tightly regulated. Extreme variations in osmolarity cause cells to shrink or swell, damaging or destroying cellular structures and disrupting normal cellular functions. The regulation of osmolarity is achieved by balancing the intake and excretion of sodium with that of water. Sodium is by far the major solute in the extracellular fluids and therefore it effectively determines the osmolarity of extracellular fluids.

An important concept is that the regulation of osmolarity must be integrated with the regulation of volume because changes in water volume alone will have either diluting or concentrating effects on bodily fluids (Table 7.1). For example, when a person becomes dehydrated, he or she loses proportionately more water than solute (sodium), resulting in increased osmolarity of bodily fluids. In this situation, the body must conserve water (e.g., by increased drinking or by antiduresis) but not sodium, to lower the rise in osmolarity. On the other hand, a loss of large amount of blood from trauma

Table 7.1 Changes in urine volume and osmolarity under various conditions

or surgery is associated with loses of sodium and water that are proportionate to the composition of bodily fluids. In this situation, the body should conserve both water and sodium (e.g., intravenous administration of saline).

As noted above, ADH plays a major role in lowering blood osmolarity by increasing water reabsorption in the kidneys, helping to dilute bodily fluids (Figure 7.5). To prevent osmolarity from decreasing below normal, the kidneys have other regulated mechanisms for reabsorbing sodium in the distal nephron. This is primarily done by aldosterone, which increases sodium reabsorption. The adrenal cortex directly senses plasma osmolarity. When osmolarity increases above normal, aldosterone secretion is inhibited. The lack of aldosterone causes less sodium to be reabsorbed in the distal tubule. At the same time, ADH secretion increases to conserve water, complementing the effects of low aldosterone levels to decrease the osmolarity of bodily fluids. The net effect is a decrease in the amount of urine excreted, with an increase in the osmolarity of the urine and the lowering of blood osmolarity.