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
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.
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.
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.
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.
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.