1/9 🤔 Why doesn't an elevated BUN lead to extreme thirst? If increased serum osmolarity compels us to seek water, uremia should be a significant driver of this craving. And yet, it isn't. Let's examine why.
2/ We've known for nearly a century that an increase in serum urea is not a significant driver of thirst. In 1937, Alfred Gilman published an experiment in which dogs received an IV injection of either: ➤20% NaCl ➤40% urea Both are hypertonic solutions. t.ly/MIdqH
3/ After 30 minutes, the dogs were offered water, and had blood work drawn. Gilman made two key observations: 🔑 The increase in serum osmolarity with hypertonic NaCl and urea were nearly identical 🔑 Dogs drank significantly more water after hypertonic NaCl injection t.ly/MIdqH
4/ Gilman then made another crucial observation: 💡Only NaCl led to a reduction in serum specific gravity. This suggested a shift of water from the intracellular to the extracellular space. This only occurs with an effective osmole (e.g., sodium) and not an ineffective osmole (e.g., urea).
5/ Based on this experiment, Gilman concluded that it is INTRAcellular dehydration that leads to thirst. This results from a hypertonic extracellular space (e.g., hypernatremia) and the movement of water outside of cells. t.ly/It2oB
6/ What is the "sensor" for cellular dehydration? It appears that transient receptor potential vanilloid 1 (TRPV1) is key. TRPV1 is a non-selective cation channel that detects harmful stimuli like heat and capsaicin. 💡 It is also activated by cell shrinking! t.ly/lqhvy
7/ The explanation above leads to a beautiful symmetry of thirst promoters. Either... ➤EXTRAcellular volume depletion ...or... ➤INTRAcellular volume depletion... ...will make you seek water.
8/ The mechanism described above helps explain why other ineffective osmoles that increase serum osmolarity (e.g., glucose) are not independent drivers of thirst. t.ly/odecD
9/9 💧 An increase in effective osmoles (e.g., sodium) produces thirst via the movement of water out of cells (i.e., intracellular dehydration) 💧Urea and other ineffective osmoles don't produce the same shifts and, therefore, lead to less thirst
@tony_breu Thanks for that really interesting thread. A review that has just been published may be of interest to you and your audience: x.com/NeuroCellPress…
@tony_breu Thanks for that really interesting thread. A review that has just been published may be of interest to you and your audience: x.com/NeuroCellPress…
