Medical Physiology, 3rd Edition

CHAPTER 40. Integration of Salt and Water Balance

Gerhard Giebisch, Erich E. Windhager, Peter S. Aronson

Two separate but closely interrelated control systems regulate the volume and osmolality of the extracellular fluid (ECF). It is important to regulate the ECF volume to maintain blood pressure, which is essential for adequate tissue perfusion and function. The body regulates ECF volume by adjusting the total-body content of NaCl. It is important to regulate the extracellular osmolality because hypotonic (see pp. 131–132) or hypertonic (see p. 131) osmolalities cause changes in cell volume that seriously compromise cell function, especially in the central nervous system (CNS). The body regulates extracellular osmolality by adjusting total-body water content. These two homeostatic mechanisms—for ECF volume and osmolality—use different sensors, different hormonal transducers, and different effectors (Table 40-1). However, they have one thing in common: some of their effectors, although different, are located in the kidney. In the case of the ECF volume, the control system modulates the urinary excretion of Na+. In the case of osmolality, the control system modulates the urinary excretion of solute-free water or simply free water (see pp. 806–807).

TABLE 40-1

Comparison of the Systems Controlling ECF Volume and Osmolality




What is sensed?

Effective circulating volume

Plasma osmolality


Carotid sinus, aortic arch, renal afferent arteriole, atria

Hypothalamic osmoreceptors

Efferent pathways

Renin-angiotensin-aldosterone axis, sympathetic nervous system, AVP, ANP




Short term: Heart, blood vessels
Long term: Kidney


Brain: drinking behavior

What is affected?

Short term: Blood pressure
Long term: Na+ excretion

Renal water excretion

Water intake

Sodium Balance

The maintenance of the ECF volume, or Na+ balance, depends on signals that reflect the adequacy of the circulation—the so-called effective circulating volume, discussed below. Low- and high-pressure baroreceptors send afferent signals to the brain (see pp. 536–537), which translates this “volume signal” into several responses that can affect ECF volume or blood pressure over either the short or the long term. The short-term effects (over a period of seconds to minutes) occur as the autonomic nervous system and humoral mechanisms modulate the activity of the heart and blood vessels to control blood pressure. The long-term effects (over a period of hours to days) consist of nervous, humoral, and hemodynamic mechanisms that modulate renal Na+ excretion (see pp. 763–769). In the first part of this chapter, we discuss the entire feedback loop, of which Na+ excretion is the effector.

Why is the Na+ content of the body the main determinant of the ECF volume? Na+, with its associated anions, Cl and image, is the main osmotic constituent of the ECF volume; when Na salts move, water must follow. Because the body generally maintains ECF osmolality within narrow limits (e.g., ~290 milliosmoles/kg, or 290 mOsm), it follows that whole-body Na+ content—which the kidneys control—must be the major determinant of the ECF volume. A simple example illustrates the point. If the kidney were to enhance the excretion of Na+ and its accompanying anions by 145 milliequivalents (meq) each—the amount of solute normally present in 1 L of ECF—the kidneys would have to excrete an additional liter of urine to prevent a serious fall in osmolality. Alternatively, the addition of 145 mmol of “dry” NaCl to the ECF obligates the addition of 1 L of water to the ECF; this addition can be accomplished by ingestion of water or reduction of renal excretion of free water. Relatively small changes in Na+ excretion lead to marked alterations in the ECF volume. Thus, precise and sensitive control mechanisms are needed to safeguard and regulate the body's content of Na+.

Water Balance

The maintenance of osmolality, or water balance, depends on receptors in the hypothalamus that detect changes in the plasma osmolality. These receptors send signals to areas of the brain that (1) control thirst and thus regulate free-water intake and (2) control the production of arginine vasopressin (AVP)—also known as antidiuretic hormone (ADH)—and thus regulate free-water excretion by the kidneys. We discuss renal water excretion beginning on page 806. In the second part of this chapter, we discuss the entire feedback loop, of which water excretion is merely the end point.

Why is the water content of the body the main determinant of osmolality? Total-body osmolality is defined as the ratio of total-body osmoles to total-body water (see p. 102). Although the ECF volume control system can regulate the amount of extracellular osmoles, it has little effect on total-body osmoles. Total-body osmoles are largely a function of the intracellular milieu because the intracellular compartment is larger than the ECF and its solute composition is highly regulated. Total-body osmoles do not change substantially except during growth or during certain disease states, such as diabetes mellitus (in which excess glucose increases total-body osmolality). Only by controlling water independent of Na+ control can the body control osmolality.

Control of Extracellular Fluid Volume

Control of Water Content (Extracellular Osmolality)