Episode 18: Why is thirst quenched so quickly?

This episode of the podcast was prompted by two questions. First, why do patients with primary polydipsia continues to drink despite a decrease in serum sodium and serum osmolarity. Second, why do we immediately become thirsty when we eat something salty. And, conversely, wondered why is our thirst immediately satiated after just a few sips of water. 

There is an even simpler query that helps answer some of these questions: “why do we drink”? There are, of course, lots of reasons why we drink the liquids we do. I generally drink coffee, water, carbonated water, and gin. The prompts for these ingestions are also different and include their mental and physiologic effects, social norms, because I think it is healthy, and anticipatory reasons. Anticipatory drinking refers to what we do with meals. More on this later. 

What is thirst?

Thirst is the conscious need for water for which there are two main drivers. The first one is familiar to most: increased osmolarity. Classically the onset of thirst was considered to have a threshold of approximately 295 mOsm/L. This is about 10-15 mOsm/L above that for ADH release (which is about 280 mOsm/L). More recent studies suggest that the osmotic threshold is closer to what leads to ADH release. As osmolarity increases, so does the intensity of thirst.

Increases in blood osmolarity are detected by two small structures in the forebrain known as the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT). Importantly, these two structures are located outside the blood–brain barrier and therefore have enhanced access to the circulation. Specialized neurons in the SFO and OVLT are activated by increases in blood osmolarity. When serum osmolarity increases, water leaves cells leading to intracellular dehydration. The SFO and OVLT neurons detect this change in cell volume via stretch-sensitive ion channels embedded in their plasma membranes. 

An increase in serum osmolarity results in intracellular volume depletion. So the thirst that results can be thought of as a mechanism to preserve and restore intracellular volume.

The other mechanism of thirst

It’s worth noting only about 2040% of patients with primary polydipsia offer “thirst” as the explanation for their excessive drinking. But, if such patients experience hyponatremia the first mechanism of thirst (increased osmolarity) must be completely shut off. If they are thirsty, it is likely related to the second mechanism. Although many assume antidiuretic hormone (ADH) leads to thirst, a different molecule is the cause. Interestingly, this molecule – and therefore the second mechanism of thirst – has a slightly different aim than the first: preserve extracellular volume. The molecule: angiotensin II (ATII). As with osmolarity, the SFO is the principal site in the brain where angiotensin II acts to make us thirsty. Some of the evidence supporting this comes from studies where angiotensin II was injected directly into the SFO of rats. They drink like mad after this.

Is angiotensin II to blame?

The obvious question that follows from this is: does angiotensin II lead to the excessive drinking seen in primary polydipsia? The short answer is maybe, though the data isn’t clear. To understand the possible link, three observations are worth noting:

  1. Though the mechanism of schizophrenia is clearly multifactorial, the “dopamine hypothesis” remains a leading explanatory model. 
  2. High levels of dopamine are associated with increased drinking. In fact, lesions of the dopaminergic nigrostriatal pathway cause rats to become adipsic. They stop drinking!
  3. When D2-antagonists like haloperidol are injected intracranially they block ATII-induced drinking.

These three observations suggest dopaminergic systems participate in ATII-induced thirst. Exactly how ATII and dopamine interconnect isn’t clear. But, one could imagine that conditions with excess dopamine – conditions such as schizophrenia – may also have excessive drinking.

There’s another theory offered in 1993 that proposed that chronic D2 blockade induced by typical neuroleptics may increase ATII levels, leading to increased thirst, and polydipsia.

Captopril to the rescue?

Based on the mechanisms described above it is unsurprising that ACE inhibitors have been used in high renin states associated with increased thirst and water consumption. One example is chronic kidney disease, where some patients have high renin, high ATII, and excessive thirst. Captopril blunts this.

The literature for the use of ACE inhibitors in the treatment of primary polydipsia are mostly case reports and showed mixed results. It’s complex!

Are you satiated?

Now to why we feel immediate relief after taking a sip of water. One explanation may be that there is an immediate change in osmolarity. If osmolarity drops within seconds of water ingestion then we might feel immediately less thirsty. But this can’t be it as it takes 10 or more minutes for ingested water to be fully absorbed into the bloodstream and decrease osmolarity.

But we know from personal experience that we don’t need to drink for 10 minutes in order for our thirst to go down. For skeptics, there is data showing that if you infusion 5% saline and increasing osmolarity, thirst shoots up. This same data shows that as soon as drinking is allowed, thirst plummets.

The answer relates back to the SFO. Not only does this structure react to serum osmolarity and angiotensin II, it also receives direct inputs about what we place in our mouth during eating and drinking. The SFO uses information about the composition of what we eat and drink to predict how they will change our future blood osmolarity. It then changes our behavior accordingly.

So if someone drinks water, the SFO receives inputs that say “Hey, you’re going to have a drop in serum osmolarity in just a bit… no need to drink so much!” Or, if someone eat something salty, the SFO receives this input and says: “Hey, your osmolarity is about to go up. Please, be thirsty! Drink something lest we become hyperosmolar!”

All of this happens well before our serum osmolarity changes. Our brain anticipates changes and preemptively modulates our behavior.

How cool is that?

Take Home Points

  1. There are two main drivers of thirst: increased osmolarity and angiotensin II. But, there is also anticipatory thirst that bypass either of these mechanisms, using information about the food we eat. 
  2. Information about osmolarity, angiotensin II levels, and the composition of what we eat are sensed by the subfornical organ, among other structures.
  3. In primary polydipsia there may be a complex interplay between dopamine, angiotensin II, and thirst.
  4. There may be a role for ACE II in some forms of thirst, but data for their use in primary polydipsia is conflicting.

Learning Objectives

  1. Review the two basic mechanisms leading to thirst and generate potential treatment options based on the two mechanisms of thirst.
  2. Critically analyze why patients with primary polydipsia may drink despite a suppressed serum osmolarity.
  3. Reflect on individual experience of thirst and how mechanisms inform these experiences.


Click here to obtain AMA PRA Category 1 Credits™ (1.00 hours), Non-Physician Attendance (1.00 hours), or ABIM MOC Part 2 (1.00 hours).

Listen to the episode

Credits & Citation

◾️Episode and show notes written by Tony Breu
◾️Audio edited by Clair Morgan of nodderly.com

Breu AC, Cooper AZ, Abrams HR. Why is thirst quenched so quickly? The Curious Clinicians Podcast. February 3, 2021. https://curiousclinicians.com/2021/01/20/episode-17-why-does-bilirubin-deposit-in-the-eyes/

Image credit: https://www.indiamart.com/proddetail/jaundice-treatment-18916823073.html

Published by Tony Breu

Tony Breu, MD is an internist/hospitalist who loves asking ‘why’?

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