Sodium Homeostasis, a Balance Necessary for Life

Abstract

Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this solute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin-angiotensin-aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis.

Keywords: excitatory and inhibitory circuits; hypernatremia; hyponatremia; kidney; natriuresis; posterior hypothalamus; salt intake; sodium homeostasis; taste.

Figure 1

Behavioral and physiological mechanisms to maintain the osmolality/natremia (upper) and volemia (lower) of extracellular fluid (ECF) (from Mahía and Bernal [7], with permission from Elsevier).

Figure 2

Schematic representation of cells in a taste bud, and transduction of NaCl taste in a taste receptor cell (yellow: taste receptor cells, red: support cells, pink: immature precursor cells). Taste receptor cells form synapses with afferent nerve fibers that penetrate the taste bud, crossing the basal membrane.

Figure 3

Main structures of the rat brain involved in Na homeostasis (AP: area postrema; BNST: bed nucleus of the stria terminalis; CeA: central amygdala; E3–E4: medial tuberomammillary nuclei; ME: median eminence; NST: nucleus of the solitary tract; PBN: parabrachial nucleus; pre-LC: pre-locus coeruleus; PVN: paraventricular nucleus; SFO: subfornical organ; SON: supraoptic nucleus) (adapted from [63]).

Figure 4

Afferent neural and humoral pathways involved in salt intake and main central excitatory (green) and inhibitory (red) circuits (AP: area postrema; BNST: bed nucleus of the stria terminalis; LPBN: lateral parabrachial nucleus; NST: nucleus of the solitary tract; pre-LC: pre-locus coeruleus; PVN: paraventricular nucleus; SFO: subfornical organ; VTA: ventral tegmental area).

Figure 5

Components of the nephron (From Holly Fischer, Wikipedia commons).