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After studying this chapter, you should be able to:

  • Describe how the tonicity (osmolality) of the extracellular fluid is maintained by alterations in water intake and vasopressin secretion.

  • Discuss the effects of vasopressin, the receptors on which it acts, and how its secretion is regulated.

  • Describe how the volume of the extracellular fluid is maintained by alterations in renin and aldosterone secretion.

  • Define the stimuli and the reactions that lead to the formation of angiotensin II

  • List the functions of angiotensin II, and the receptors on which it acts.

  • Describe the function of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and detail the receptors on which they act.

  • Describe the site and mechanism of action of erythropoietin, and the feedback regulation of its secretion.


This chapter is a review of the major homeostatic mechanisms that operate, primarily through the kidneys and the lungs, to maintain the tonicity, the volume, and the specific ionic composition of the extracellular fluid (ECF). The interstitial portion of this fluid is the fluid environment of the cells, and life depends on the constancy of this “internal sea” (see Chapter 1).


The defense of the tonicity of the ECF is primarily the function of the vasopressin-secreting and thirst mechanisms. The total body osmolality is directly proportional to the total body sodium plus the total body potassium divided by the total body water, so that changes in the osmolality of the body fluids occur when a mismatch exists between the amount of these electrolytes and the amount of water ingested or lost from the body. When the effective osmotic pressure of the plasma rises, vasopressin secretion is increased and the thirst mechanism is stimulated; water is retained in the body, diluting the hypertonic plasma; and water intake is increased (Figure 38–1). Conversely, when the plasma becomes hypotonic, vasopressin secretion is decreased and “solute-free water” (water in excess of solute) is excreted. In this way, the tonicity of the body fluids is maintained within a narrow normal range. In health, plasma osmolality ranges from 280 mOsm/kg of H2O to 295 mOsm/kg of H2O, with vasopressin secretion maximally inhibited at 285 mOsm/kg and stimulated at higher values (Figure 38–2).


Mechanisms for defending extracellular fluid (ECF) tonicity. The dashed arrow indicates inhibition. (Used with permission of J Fitzsimmons.)


Relation between plasma osmolality and plasma vasopressin in healthy adult humans during infusion of hypertonic saline. LD, limit of detection. (Reproduced with permission from Thompson CJ, et al: The osmotic thresholds for thirst and vasopressin are similar in healthy humans. Clin Sci [Colch] 1986; Dec; 71:(6):651–656.)

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