Osmoregulation versus volume regulation

A common misconception is that regulation of the plasma Na+ concentration is closely correlated with the regulation of Na+ excretion. However, it is related to volume regulation, which has different sensors and effectors (volume receptors) from those involved in water balance and osmoregulation (osmoreceptors).

• A water load is rapidly excreted (in 4-6 hours) by inhibition of ADH release. This process is normally so efficient that volume regulation is not affected and there is no change in ANP release or in the activity of the renin-angiotensin-aldosterone system. Thus, a
  dilute urine is excreted, and there is little alteration in the excretion of Na⁺.
• Isotonic saline administration, in contrast, causes an increase in volume but no change in plasma osmolality. In this setting, ANP secretion is increased, aldosterone secretion is reduced, and ADH secretion does not change. The net effect is the appropriate excretion of the excess Na⁺ in a relatively iso-osmotic urine.

In some cases, both volume and osmolality are altered and both pathways are activated. For example, if a person with normal renal function eats salted potato chips and peanuts without drinking any water, the excess Na+ will increase the plasma osmolality, leading to osmotic water movement out of the cells and increased extracellular volume. The rise in osmolality will stimulate both ADH release and thirst (the main reason why many restaurants and bars supply free salted foods), whereas the hypervolaemia will enhance the secretion of ANP and suppress that of aldosterone. The net effect is increased excretion of Na+ without water.

This principle of separate volume and osmoregulatory pathways is also evident in the syndrome of inappropriate ADH secretion (SIADH). Patients with SIADH have impaired water excretion and hyponatraemia caused by the persistent presence of ADH. However, the release of ANP and aldosterone is not impaired and, thus, Na+ handling remains intact. These findings have implications for the correction of the hyponatraemia in this setting and require restriction of water intake.

ADH is also secreted by nonosmotic stimuli such as stress (e.g. surgery, trauma), markedly reduced effective circulatory volume (cardiac failure, hepatic cirrhosis), psychiatric disturbance, and nausea, irrespective of plasma osmolality. This is mediated by the effects of sympathetic overactivity on supraoptic and paraventricular nuclei. In addition to water retention, ADH release in these conditions promotes vasoconstriction owing to the activation of V1 (vasopressin) receptors distributed in the vascular tissue.

Regulation of cell volume

Maintenance of a constant volume in the face of extracellular and intracellular osmotic alterations is a critical problem faced by all cells. Most cells respond to swelling or shrinkage by activating specific metabolic or membrane-transport processes that return cell volume to its normal resting state. Within minutes after exposure to hypotonic solutions and resulting cell swelling, a common feature of many cells is the increase in plasma membrane potassium and chloride conductance. Although extrusion of intracellular potassium certainly contributes to a regulatory volume decrease, the role of chloride efflux itself is modest, given the relatively low intracellular chloride concentration. Indeed other intracellular osmolytes, such as taurine and other amino acids, are transported out of the cell to achieve a regulatory volume decrease. In contrast, these regulatory mechanisms are operative in reverse to protect cell volume under hyper-tonic conditions, as is the case in the renal medulla. The tubular cells at the tip of renal papillae, which are constantly exposed to a hypertonic extracellular milieu, maintain their cell volume on a long-term basis by actively taking up smaller molecules, such as betaine, taurine and myoinositol, and by synthesizing more sorbitol and glycerophosphocholine.

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