Key Points continued

distal nephron and a corresponding increase or decrease in salt and water excretion. An increase in blood pressure can also produce a significant increase in Na+ excretion without changes in GFR or renal blood flow. This phenomenon is referred to as pressure natriuresis.

Aldosterone stimulates Na+ reabsorption in the connecting tubule and collecting duct (called the aldosterone-responsive distal nephron, ARDN), thereby regulating the excretion of ~2% of the filtered Na+.

The primary response to true or functional hypovolemia is to increase the plasma levels of the three hypovolemic hormones: vasopressin, renin, and norepinephrine. These hormones act to decrease the GFR, decrease Na+ reabsorption, and retain water.

In hypervolemia, the three hypovolemic hormones are suppressed and natriuretic hormones increase both GFR and Na+ reabsorption. Peritubular factors and locally released auta-coids also act to decrease the fractional reabsorption of salt and water by the proximal tubule.

The volume of extracellular fluid (ECF) volume is kept constant by a variety of homeostatic mechanisms. This multiplicity of regulation is essential for survival because the ECF volume determines the circulating plasma volume and, thus, mean circulatory filling pressure and cardiac output. ECF volume is determined directly by Na+ balance, which maintains a constant total body content of Na+. Thus, the total amount of Na+ in the body is the important regulated parameter, and not the Na+ concentration.

The relative unimportance of the concentration of Na+ in the plasma as an indicator of ECF volume is often confusing. However, as shown by Eq. [1] in Chapter 28, the plasma Na+ concentration is kept constant by the regulation of free water excretion by the kidneys via alterations in vasopressin secretion. The vasopressin mechanism maintains a constant plasma osmolality, and thus a constant plasma Na+ concentration. Therefore, changes in this concentration reflect a loss or gain of body water but not necessarily a loss or gain in the total amount of Na+ in the body. Changes in the Na+ concentration in the plasma occur only when fluid losses or gains have exceeded the capacity of the thirst mechanism and the renal concentrating and diluting mechanism to regulate water balance. This may occur with extreme loss or intake of water, or when the thirst or vasopressin mechanisms are impaired (see Chapter 28).

Why is the ECF volume so dependent on body Na+ balance? Equation [1] illustrates the determinants of the plasma Na+ concentration (PNa). As with any solute concentration, it can be calculated as the total amount of solute divided by the volume of distribution. Because Na+ is actively pumped out of most cells in the body, the volume of distribution of Na+ is approximately the ECF volume.

amount of Na+ in ECF

ECF volume

As discussed earlier and in Chapter 28, vasopressin and thirst maintain a constant plasma osmolality, but because the primary determinant of the plasma osmol-ality is the concentration of Na+ and its associated anions, a constant osmolality also requires a constant Na+ concentration. However, the body could maintain a constant PNa despite an increase of the total amount of Na+ if extracellular fluid volume were increased. Conversely, Na+ loss accompanied by an equivalent decrease in extracellular fluid volume would also lead to a constant PNa.

The primary parameter of concern is the ECF volume, which can be expressed in terms of the other two parameters in Eq. [1] as follows:

ECF volume =

amount of Na+ in ECF

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