Illustration: Diagnostic Flowchart of hyponatremia, adapted from Workenehet al. 2023. „Hyponatremia Demystified: Integrating Physiology to Shape Clinical Practice“. Advances in Kidney Disease and Health 30 (2): 85–101. https://doi.org/10.1053/j.akdh.2022.11.004.

Is urgent treatment indicated?

Because of its clinical variability and potential for emergency, hyponatremia should always be considered early and managed promptly. This is done by assessing the rate of onset, the clinical presentation and biochemical severity.

What is the tonicity?

The first step in evaluating hyponatremia is to determine whether it is associated with hypotonicity (and therefore is "true hyponatremia". This is assessed by measuring serum osmolality (SOsm). A low SOsm (<275 mOsm/kg) confirms hypotonic hyponatremia.

Is the hyponatremia AVP-dependent?

In the case of Hypotonic Hyponatremia, the next step is to determine whether the hypotonic hyponatremia is mediated by arginine vasopressin (AVP). This can be assessed by evaluating urine osmolality (UOsm). If the urine is not maximally dilute (UOsm > 100 mOsm/kg), it suggests that AVP is active and contributes to water retention. Conversely, a maximally dilute urine (UOsm < 100 mOsm/kg) indicates AVP-independent hypotonic hyponatremia.

Is AVP secretion appropriate?

If hypotonic Hyponatremia is AVP dependent, the next step is to assess whether AVP secretion is appropriate in the context of hypotonic hyponatremia. Among the possible triggers, a reduction in effective arterial blood volume (EABV) is the only physiologically valid stimulus for AVP release under these conditions.

When EABV is decreased, as seen in hypovolemia, heart failure, or cirrhosis, the body activates the renin-angiotensin-aldosterone system (RAAS), which promotes sodium retention. In such cases, urinary sodium concentration (UNa) is typically low, often less than 20 mmol/L.

On the other hand, a UNa greater than 30 mmol/L generally suggests that RAAS is not fully activated, implying that EABV is normal, elevated, or at least does not play the main role in hyponatremia pathogenesis. In this setting, ongoing AVP secretion is not appropriate

You may observe that this flowchart (as well as the one in the original article) does not include volume status as part of the diagnostic approach to hyponatremia. I personally prefer the physiology-based strategy for diagnosing hyponatremia proposed by Workeneh et al rather than the traditional volume status–based algorithm, because clinical evaluation of extracellular fluid (ECF) volume often lacks sensitivity and specificity in this context, as already mentioned above. Nonetheless, I still recommend conducting a clinical assessment of volume status, ideally supported by point-of-care ultrasound, to help identify signs of cardiac decompensation, especially since this assessment is typically done before laboratory results are available.

Whether you use this exact flowchart or another, maintaining a systematic approach to hyponatremia not only clarifies the diagnostic process but also ensures accurate identification of the underlying cause and timely initiation of appropriate therapy. True diagnostic clarity comes from understanding the pathophysiological reasoning behind every test.

References

All Illustrations were created in https://BioRender.com

Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013 Oct;126(10 Suppl 1):S1-42. doi: 10.1016/j.amjmed.2013.07.006. PMID: 24074529.

Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout J. Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen, Evi Nagler, on behalf of the Hyponatraemia Guideline Development Group, Clinical practice guideline on diagnosis and treatment of hyponatraemia, Nephrology Dialysis Transplantation, Volume 29, Issue suppl_2, April 2014, Pages i1–i39, https://doi.org/10.1093/ndt/gfu040

Workenehet al. 2023. „Hyponatremia Demystified: Integrating Physiology to Shape Clinical Practice“. Advances in Kidney Disease and Health 30 (2): 85–101. https://doi.org/10.1053/j.akdh.2022.11.004.