Regulation of Extracellular Fluid Volume and NaCl Balance

Whole-Body Na ⁺ Balance

As described in Chapter 1 , steady-state balance describes the process by which the addition of substances to the body is matched by their equivalent loss from the body. Decades of research has established that the kidneys are the major route for the excretion of ingested Na ⁺ (primarily as NaCl). Normally, approximately 90% of ingested Na ⁺ is excreted in the urine, with the remaining 10% excreted in feces and in sweat. Although the amount of Na ⁺ lost from the body in sweat and feces can vary, it is not regulated to maintain steady-state whole-body Na ⁺ balance. In contrast the renal excretion of Na ⁺ is regulated so that steady-state balance is achieved.

The classical explanation for how whole-body Na ⁺ balance is maintained in the face of changing dietary NaCl intake is depicted in Fig. 6.2 , which for simplicity assumes 100% of ingested Na ⁺ is excreted in the urine. In response to an increase in dietary NaCl, the kidneys increase NaCl excretion. However, it takes several days before a new steady state is achieved. This results in a transient period of positive Na ⁺ balance (intake > excretion), with an increase in ECF volume (because of concomitant water retention to maintain ECF osmolality constant). This increase in ECF volume manifests itself as an increase in body weight (1 L = 1 kg). When dietary NaCl is reduced, a new steady state is again achieved after several days, with the intervening period of negative Na ⁺ balance (intake < excretion) causing ECF volume and body weight to decrease.

It is important to note that the kidneys can vary the excretion of Na ⁺ over a very wide range of intake (10 to 1000 mEq/day) with only modest or no long-term change in ECF volume.

In the Clinic

Long-term balance studies under carefully controlled conditions suggest that with a transition from ingesting a low-salt diet to ingesting a high-salt diet, there is an increase in ECF volume, which manifests itself as an increase in body weight ( Fig. 6.3 ). However, after 2 weeks on the high-salt diet, ECF volume, body Na ⁺ content, and body weight return to their previous values. These changes are associated with a suppression of aldosterone levels. Additional studies are required to confirm these observations and to determine their clinical significance.

Concept of Effective Circulating Volume

As described in Chapter 1 , the ECF is subdivided into two compartments: blood plasma and interstitial fluid. Plasma volume is a determinant of vascular volume and thus blood pressure and cardiac output. The maintenance of Na ⁺ balance, and thus ECF volume, involves a complex system of sensors and effector signals that act primarily on the kidneys to regulate the excretion of NaCl. As can be appreciated from the dependence of vascular volume, blood pressure, and cardiac output on ECF volume, this complex system is designed to ensure adequate tissue perfusion. Because the primary sensors of this system are located in the large vessels of the vascular system, changes in vascular volume, blood pressure, and cardiac output are the principal factors regulating renal NaCl excretion (described later in this chapter).

In a healthy person, changes in ECF volume result in parallel changes in vascular volume, blood pressure, and cardiac output. Thus a decrease in ECF volume, a situation termed volume contraction , results in reduced vascular volume, blood pressure, and cardiac output. Conversely an increase in ECF volume, a situation termed volume expansion , results in increased vascular volume, blood pressure, and cardiac output. The degree to which these cardiovascular parameters change depends on the degree of volume contraction or expansion and the effectiveness of cardiovascular reflex mechanisms. When a person is volume contracted, renal NaCl excretion is reduced. Conversely with volume expansion, renal NaCl excretion is enhanced (i.e., natriuresis ).

However, in some pathologic conditions (e.g., congestive heart failure and hepatic cirrhosis), the renal excretion of NaCl is not reflective of the ECF volume. In both these situations the volume of the ECF is increased. However, instead of increased renal NaCl excretion, as would be expected, a reduction in the renal excretion of NaCl occurs. To explain renal Na ⁺ handling in these situations, it is necessary to understand the concept of effective circulating volume (ECV) . Unlike the ECF, the ECV is not a measurable and distinct body fluid compartment. The ECV is the portion of the ECF that is contained within the vascular system and is “effectively” perfusing the tissues ( effective arterial blood volume is another commonly used term). More specifically the ECV reflects the perfusion of those portions of the vascular system that contain the volume sensors (described later in this chapter).

In healthy persons, ECV varies directly with the volume of the ECF and in particular the volume of the vascular system (arterial and venous), arterial blood pressure, and cardiac output. However, as noted, this is not the case in certain pathologic conditions. In the remaining sections of this chapter, the relationship between ECF volume and renal NaCl excretion in healthy adults, where changes in ECV and ECF volume occur in parallel, is examined.

Volume-Sensing Systems

The ECF volume (or ECV) is monitored by multiple sensors ( Box 6.1 ). A number of the sensors are located in the vascular system, and they monitor its fullness and pressure. These receptors typically are called volume receptors; because they respond to pressure-induced stretch of the walls of the receptor (e.g., blood vessels or cardiac atria), they also are referred to as baroreceptors (see Chapter 5 ). Evidence exists for Na ⁺ sensors within the central nervous system (CNS), as well as in the gastrointestinal tract and liver. The extent to which these sensors contribute to regulating Na ⁺ balance and thus ECF volume is not well understood. Therefore they are not considered further, and only the role of the vascular receptors in monitoring ECF volume (or ECV) is described.