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Maintenance of the tonicity of extracellular fluids within a very narrow range is crucial for proper cell function. Normal blood tonicity is maintained over a 10-fold variation in water intake by a coordinated interaction among the vasopressin, thirst, and renal systems. Dysfunction in any of these systems can result in abnormal regulation of blood osmolality, which if not properly recognized and treated, may cause life-threatening hyperosmolality or hypoosmolality.1

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Vasopressin Synthesis

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Plasma osmolality is regulated principally via vasopressin (also termed anti-diuretic hormone, ADH) release from the posterior pituitary, or neurohypophysis, whereas volume homeostasis is determined largely through the action of the renin-angiotensin-aldosterone system, with contributions from both vasopressin and the natriuretic peptide family. The nine amino acid peptide vasopressin is synthesized in hypothalamic paraventricular and supraoptic magnocellular neurons, whose axons travel caudally and converge at the infundibulum before terminating in the posterior pituitary, transporting the hormone to its primary site of storage and release into the systemic circulation (see Fig. 521-2).

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Osmotic Regulation

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Water balance is regulated in two ways: vasopressin secretion stimulates water reabsorption by the kidney, thereby reducing future water losses; and thirst stimulates water ingestion, which restores past water losses. The two systems work in parallel to efficiently regulate extracellular fluid tonicity (Fig. 525-1). However, when both vasopressin secretion and thirst are compromised, life-threatening abnormalities in plasma osmolality can occur.

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Figure 525-1.
Graphic Jump Location

Regulation of vasopressin secretion and serum osmolality. Hyperosmolality, hypovolemia, or hypotension is sensed by osmosensors, volume sensors, or barosensors, respectively. These stimulate both vasopressin (VP) secretion and thirst. VP, acting on the kidney, causes increased reabsorption of water (antidiuresis). Thirst causes increased water ingestion. The results of these dual negative feedback loops cause a reduction in hyperosmolality or hypotension/hypovolemia.

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Normal blood osmolality ranges between 280 and 290 milliosmoles/kg H2O (mosm/kg). An osmosensor located outside the blood-brain barrier near the anterior hypothalamus can detect as little as 1% to 2% change in blood osmolality. When osmolality increases above a threshold of 283 mosm/kg, it signals the posterior pituitary to secrete vasopressin. Hypothalamic neurons distinct from those that control vasopressin secretion stimulate thirst sensation at a threshold (~293 mosm/kg) slightly higher than that for vasopressin release.

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Nonosmotic Regulation

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Vasopressin is also secreted in response to a decrease in intravascular volume or pressure. Vasopressin concentration rises exponentially after a reduction in intravascular volume that exceeds 8%. When blood volume or blood pressure decreases by 25%, vasopressin levels rise to 20- to 30-fold above normal, high enough to cause vasoconstriction and vastly exceeding those required for maximal antidiuresis (~5 pg/mL). Nausea, pain, hypoglycemia, psychologic stress, ethanol, and chlorpropamide are also clinically important triggers for vasopressin release. Vasopressin secretion is inhibited by glucocorticoids.

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Vasopressin Metabolism and Action

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