The Physiological Regulation of Thirst and Fluid

hirst is a subjective perception that provides the urge for humans and animals to drink fluids. It is a component of the regulatory mechanisms that maintain body fluid homeostasis and ultimately is essential for survival. This urge to ingest fluids may arise for several reasons that include habitual, cultural, and psychogenic drives as well as the regulatory response to reductions in the fluid content of various bodily compartments, hypertonicity of the extracellular fluid, or increases in the circulating concentration of some dipsogenic hormones. Such regulatory thirst, and the cerebral mechanisms generating it, are the subjects of this review. When the body loses water, it is usually depleted from both the extracellular and intracellular compartments, but it may not necessarily be lost equally from each of the fluid spaces. Loss of NaCl (the major solute of the extracellular fluid) together with water results in proportionately more extracellular fluid being depleted than if water alone is lost. This may occur, for example, with fluid loss from the alimentary tract that occurs in conditions of vomiting or diarrhea, and when this fluid loss takes the form of an isotonic fluid, then the depletion will be entirely from the extracellular fluid. However, if hypertonic fluid is added to the extracellular compartment, there will be an osmotic depletion of water from the intracellular compartment into the extracellular fluid, and this latter compartment will be expanded. A range of compensatory responses are engaged when depletion of either the intra- or extracellular compartment occurs. These responses (e.g., vasopressin secretion, stimulation of the renin-angiotensin-aldosterone system, sympathetic activation, and reduced renal solute and water excretion) have the effect of minimizing changes in body fluid volume and composition. However, such mechanisms, although of undoubted benefit to the animal, do not restore body fluids to the original state. For this to occur, fluid losses must be replenished. Therefore, thirst, which provides the motivation to drink, is an important component of the coordinated sequence of physiological responses that maintain the volume and composition of body fluids. In the following paragraphs, we outline the cerebral mechanisms that subserve the water-drinking responses that are associated with 1) hypertonicity, cellular dehydration, and osmoreceptor stimulation; 2) hypovolemia and extracellular dehydration, including the role of circulating angiotensin (ANG) II as a dipsogenic hormone and the afferent neural inflow that also provides stimuli to the thirst mechanism; and 3) other hormonal signals that may stimulate (e.g., relaxin) or inhibit [e.g., atrial natriuretic peptide (ANP)] thirst.