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FIGURE 2 Change in total body output of Na+ when Na+ intake is suddenly increased and then decreased. Note that the changes in output always lag behind the changes in intake, causing a net accumulation or loss of Na+ during a transient period. The increase in ECF volume is indicated by the increase in body weight with increased intake and by the decrease in the body weight with decreased intake. (Modified from Reineck HJ, Stein JH. Sodium metabolism. In Maxwell MH, Kleeman CR, Narins RG, eds. Clinical disorders of fluid and electrolyte metabolism, 4th ed. New York: McGraw-Hill, 1987, pp 33-59.)

volume manifested by an increase in body weight. When the Na+ intake rate is abruptly returned to 15 mmol/ day, Na+ output remains temporarily higher than Na+ intake until a new steady state is established. During this transient period, Na+ excretion by the kidneys exceeds Na+ intake, resulting in a negative Na+ balance and a loss of ECF volume that is manifested by a decrease in body weight. Just the opposite happens with the decrease in daily Na+ intake from the normal level of 150-250 mmol/day. There is a transient period of Na+ loss resulting in a contracted ECF volume and decreased body weight. This is reversed when Na+ intake is returned to normal.

The slower response of the Na+ excretory system can be contrasted with the relatively rapid response of the thirst and the vasopressin mechanisms to changes in plasma osmolality. As discussed in Chapter 28, an increase in water intake is rapidly followed by a diuresis that results in excretion of the excess water in 1-2 hr. In contrast, if one ingests or infuses the equivalent of 1 L of isotonic saline, it takes the body about 2-4 days to excrete this excess load of both salt and water. Because of this slower response of the Na+ regulatory mechanism, the regular daily intake of Na+ can be an important determinant of the basal ECF volume. Individuals who by habit have a higher daily Na+ intake may have a slightly expanded ECF volume, whereas those individuals on a low-salt diet have a lower ECF volume in proportion to their body size.

Because plasma volume is proportional to ECF volume and is an important determinant of the mean circulatory filling pressure, ECF volume plays a role in the maintenance of a normal blood pressure. A higher dietary Na+ intake disposes the individual to a higher ECF volume and a higher blood pressure, whereas a lower Na+ intake is associated with a decreased ECF volume and a lower blood pressure. Many individuals maintain a relatively constant blood pressure despite wide variations in daily Na+ intake. On the other hand, other individuals seem to be quite sensitive to changes in Na+ intake. Some patients with hypertension respond with a fall in blood pressure when they are placed on a low-salt diet with no drug therapy. Others may show a fall in blood pressure only when salt restriction is combined with diuretics. Individuals such as these are referred to as salt-sensitive hypertensive patients, and their hypertension can sometimes be controlled with Na+ restriction and diuretics. It would appear that these individuals have a greater propensity to retain Na+ in the presence of a high Na+ intake and, thus, expand their ECF volume and raise their basal blood pressure. Alternatively, in a salt-sensitive hypertensive patient the elevated blood pressure may be necessary to produce sufficient Na+ excretion via pressure natriuresis to maintain body Na+ balance (see later discussion). Therefore, daily Na+ intake and the efficiency with which the kidney excretes Na+ are important determinants of total ECF volume and blood pressure.

The next sections consider how Na+ excretion by the kidneys is regulated in response to changes in dietary intake. To understand this feedback regulation of body Na+ content, it is necessary to identify the receptors that sense changes in ECF volume, the effectors that mediate changes in Na+ reabsorption by the kidney, and the final effects on different nephron segments that reabsorb Na+.

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