11.6: Triggering Drinking Behavior - Osmometric and Volumetric Thirst

Learning Objectives

1. Discuss the role of solutes in determining the movement of water in the body.
2. Distinguish between intracellular and extracellular fluid.
3. Compare and contrast osmotic and volumetric (hypovolemic) thirst.

Overview

When talking about thirst, we are talking not just about water in the body, but also the major solute (dissolved substance) we find in this water, salt or sodium chloride (NaCl). Regulating the body's water is necessarily impacted by the substances that are dissolved in that water. Thirst is a signal to the body that there has been a loss of fluid or, more specifically, that there is a fluid imbalance. About two-thirds of the body's water is intracellular, meaning within cells. The other third, the extracellular fluid, consists of interstitial fluid (the fluid bathing cells), cerebrospinal fluid (fluid in the ventricular system), and blood plasma (intravascular).

Because we effectively have two places where water is found (intracellular and extracellular), we have two systems for monitoring the body's fluid levels - and a variety of ways of inducing thirst, as well as different types of thirst. In addition, salt appetite is necessarily associated with one form of thirst as the need created by the fluid loss requires both salt and water to restore homeostasis. One system focuses on the levels of intracellular fluid and triggers osmotic thirst. The other monitors extracellular levels - more specifically, plasma or blood volume - and triggers volumetric thirst. Volumetric thirst is associated with a need for both salt and water.

Intracellular Fluid Volume

Intracellular fluid volume is controlled by the concentration of solutes in the interstitial fluid (the fluid outside of cells). Under normal circumstances, the fluid outside and inside the cell is isotonic (the concentration of solutes is equal). If, however, the solute concentration is increased in the interstitial fluid (due to ingestion of solutes or loss of water), water will leave the cell by the process of osmosis. Osmosis is simply movement of water from an area of low solute concentration to an area of high concentration, water will move as needed to even out the solute concentration (Figure \(\PageIndex{1}\)). If the interstitial fluid (the fluid outside of the cell) is hypertonic (if it has a higher solute concentration), water will leave the cell. If the interstitial fluid is hypotonic, water will enter the cell. Both conditions may be dangerous - disrupting normal neuronal function. When there is a difference between the solute concentration of the interstitial fluid and the intracellular fluid, the movement of water by osmosis causes changes in intracellular volume.

Figure \(\PageIndex{1}\): Water movement in hypertonic, isotonic and hypotonic solutions. (Images from Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436., CC BY 3.0 , via Wikimedia Commons)

Generally, there is no need to regulate the volume of the interstitial fluid, although we do regulate its tonicity (solute concentration) through its effects on the intracellular fluid volume. More specifically, we monitor the movement of water.

Plasma Volume (Extracellular)

The other important and closely regulated fluid compartment is the blood plasma. If there is a loss of plasma volume (hypovolemia), this can impair the functioning of the heart. If increased, there may be a dangerous increase in blood pressure. If hypovolemia is severe enough the heart can no longer pump effectively. The vascular system can correct for loss of volume, but only within a limited range.

Two Variables, Two Regulatory Mechanisms

In order to maintain optimal fluid balance, the two variables are monitored:

• Movement of water (intracellular)
• Plasma volume (extracellular)

As there are two variables being monitored, there will be two different regulatory mechanisms that underlie thirst. The monitoring of fluid levels is tied to the monitoring of sodium levels. There are two mechanisms for dealing with a need for fluid and salt or sodium - we see both physiological and behavioral mechanisms for dealing with a need for water and salt:

• Physiologically - At the kidney, the excretion (loss) of water and salt can be modified. And alterations in heart rate and blood pressure can also compensate for losses.
• Behaviorally - ingest water and salt

What is the role of the kidneys and how is kidney activity regulated? Typically, we ingest much more salt and water than we need and what we don't need is excreted. Blood is essentially filtered by the kidneys. The functional units of the kidneys, the nephrons, extract fluid from the blood and carry it (collect it into) the ureter. From the ureter, urine passes to the urinary bladder where urine is stored.

As discussed in the prior section, two hormones are involved in the excretion of sodium and water by the kidney - both hormonal signals increase retention:

• Aldosterone is secreted by the adrenal cortex.
• Vasopressin (Anti Diuretic Hormone or ADH) is secreted by the posterior pituitary, but produced by the hypothalamus. The two names by which this hormone is known reflect two aspects of its effects, "vasopressin" is a reference to its ability to cause contraction of blood vessels while ADH reflects its role in preventing excretion.

What happens without vasopressin? No water is retained. Without vasopressin, diabetes insipidus develops, leading to excessive water loss and increased thirst. Incidentally, the term diabetes insipidus literally means "a tasteless passing through". The urine is so dilute, it has little taste. It is, as you might expect, treated with vasopressin - in the form of a nasal spray. The diabetes you more commonly hear of (due to a lack of or insensitivity to insulin) is technically diabetes mellitus. Diabetes, again, means "passing through". Mellitus means "sweet" as the urine of the diabetic would be sweet with unused glucose.

Osmometric (Osmotic) Thirst - Detecting Water Movement Out of Cells

So, we can drink to replenish lost fluid and the kidney's function can conserve or allow fluids to be lost. As we have two variables that we are monitoring, we have two different types of thirst. Osmotic thirst derives its name from the word osmosis. Osmotic thirst is triggered by loss of volume from the intracellular fluid stores. This form of thirst is produced when the solute concentration or tonicity of the fluid outside of the cell is increased, causing water to move out of the cell. If the concentration of intracellular solutes is increased with something that passes into the cell - so the extracellular and intracellular solute concentrations remain isotonic and there's no net movement of water - drinking will not be triggered. In other words, it isn't just changes in the solute concentration that are detected, it is the loss of water from the intracellular compartment that matters (cellular dehydration).

Recall from the previous section, that antidiuretic hormone (ADH), otherwise known as vasopressin will be released by the pituitary gland in situations of cellular dehydration. Thus, the next question is what area of the brain responds to these osmotic change and the rise in hormones like vasopressin?

Osmoreceptors can be classified as central or peripheral osmoreceptors based on their location. The central receptors are primarily present in the lamina terminalis region of the anterior hypothalamus, including the organum vasculosum laminae terminalis (OVLT) and the subfornical organ (SFO) (Danziger & Zeidel, 2015; Xu et al., 2000; Muhsin & Mount, 2016). The OVLT has been shown to be sensitive to vasopressin (McKinley, et al., 2004) and, thus can influence both the physiological and behavioral response during osmotic thirst. Since the there is an excess of extracellular salt in this situation, the thirst would be for pure water without solutes.

The receptor cells in both of the OVLT and SFO are also sensitive to angiotensin II (abbreviated as AII; Bichet, 2012; Benarroch, 2011), which is important in the control of volumetric thirst (see below). Some SFO/OVLT neurons also receive signals from peripheral arterial baroreceptors. Thus, SFO/OVLT neurons sense plasma osmolality, volume, and pressure to control thirst. These cells depolarize due to increased Na+ concentration, cell shrinkage, angiotensin II or negative suction pressure, and discharge neuronal spikes, which later initiate the sensation of thirst or vasopressin release or both (Muhsin & Mount, 2016; Gizowski & Bourque, 2018).

Volumetric (Hypovolemic) Thirst - Detecting Blood Loss

Volumetric thirst is triggered when there is a loss of volume from the extracellular fluid stores. Volumetric thirst is triggered by a decrease in blood volume referred to as hypovolemia. Hypovolemia is usually accompanied by a drop in blood pressure (hypotension). Hypovolemia and hypotension then ultimately lead to the production of angiotensin II. As discussed in the last section, a cascade of events is triggered when the kidneys detect a decrease in blood pressure and release the enzyme renin. This activates the renin-angiotensin-aldosterone system. Angiotensinogen, produced by the liver, is acted on by renin to produce angiotensin I, which is then converted into angiotensin II. Angiotensin II functions as a hormone and then causes the release of the hormone aldosterone by the adrenal cortex, resulting in increased sodium reabsorption, water retention, and an increase in blood pressure.

Following extracellular fluid loss - loss of plasma volume - there is a need for both salt and water. A rat will now drink a saline solution that it normally rejects. This indicates that there is a mechanism for monitoring the body's sodium concentration, so that needs are detected and then mechanisms are employed to satisfy them. Unlike osmotic thirst, volumetric thirst is accompanied by a salt appetite.

Angiotensin II, the 3rd "step" when the renin-angiotensin-aldosterone system is activated, travels through the blood stream and exerts multiple effects.

• Angiotensin II acts at the adrenal cortex to stimulate aldosterone secretion.
• Angiotensin II acts at the posterior pituitary to stimulate vasopressin (ADH) secretion.
• Angiotensin II acts at the muscles of the the small arteries to cause contraction (increasing blood pressure).
• Angiotensin II triggers drinking and salt ingestion.

Although angiotensin II is thought to produce thirst and act on other brain sites, it does not cross the blood-brain barrier. Thus, in order to cause thirst and other effects, angiotensin II must act at a part of the brain that lacks this barrier. The subfornical organ (SFO) appears to be the site at which angiotensin II acts to cause volumetric thirst.

Evidence for the role of the SFO in water ingestion:

• Very low doses of angiotensin II at the SFO cause drinking.
• Angiotensin II-induced drinking is blocked by blocking angiotensin II receptors at the SFO.
• Electrical stimulation of the SFO produces drinking.

Furthermore, neurons in the SFO increase their activity in response to angiotensin II, even when neural connections are cut - demonstrating that the neurons are responding to the AII.

The SFO has outputs to several brain regions. And these connections mediate the endocrine, autonomic, and behavioral responses associated with thirst. It is involved in a number of the effects of AII.

Normal Drinking

Just as we typically eat long before a physiological need for fuel would trigger hunger, we drink before change in the body's fluid stores would be detected. As with eating, we have learned elements of our drinking behavior. When do we habitually drink? Normally, we drink with meals. While eating does produce a need for fluid, we typically drink before that need would normally be detected. Food in the digestive system causes water to be diverted to these areas and absorbed food increases the solute concentration of the plasma and produces osmometric thirst.

Why do animals drink before a need is detected? Animals will actually learn to drink more if their diet is changed such that they need to drink more. With a high protein diet, more water is needed. Animals will learn to drink more with a meal in anticipation of the need.

What signals or causes drinking with a meal? The movement of water into the digestive system produces hypovolemia. The hypovolemia causes the kidneys to secrete renin and AII levels are increased. During a normal meal the levels of renin actually double. If we then block AII production, we'll see a decrease in drinking with a meal.

Summary

In order to maintain an appropriate fluid balance, intracellular and extracellular fluid levels are monitored. Intracellular or osmometric thirst is triggered when water moves out of cells. In contrast, hypovolemic thirst and an appetite for salt is triggered when the loss of blood volume creates a need for salt and water.

References

Leib, D. E., Zimmerman, C. A., & Knight, Z. A. (2016). Thirst. Current biology : CB, 26(24), R1260–R1265. https://doi.org/10.1016/j.cub.2016.11.019

Stricker E. M. (1981). Thirst and sodium appetite after colloid treatment in rats. Journal of comparative and physiological psychology, 95(1), 1–25. https://doi.org/10.1037/h0077764

McKinley, M. J., Mathai, M. L., McAllen, R. M., McClear, R. C., Miselis, R. R., Pennington, G. L., Vivas, L., Wade, J. D., & Oldfield, B. J. (2004). Vasopressin secretion: osmotic and hormonal regulation by the lamina terminalis. Journal of neuroendocrinology, 16(4), 340–347. https://doi.org/10.1111/j.0953-8194.2004.01184.x

Attributions

"Osmometric Thirst - Detecting Water Movement Out of Cells" adapted from Koshy, R. & Jamil, R. (2021). Physiology, Osmoreceptors. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557510/ (CC BY)