Although hyperkalemia may be observed in a variety of conditions associated with metabolic acidosis, it is less likely to be seen in conditions associated with excess organic acids (eg, in lactic acidosis or diabetic ketoacidosis). A likely explanation for this finding revolves around the amazing organic anion transporter (OAT) and its attendant role in counteracting hyperkalemia by bringing potassium (K+) back into the cells.^1-5 See details of impact of extracellular and intracellular pH on K+ homeostasis in Figure.¹ 

Recall that in metabolic acidosis the increased concentration of hydrogen ion (H+) outside the cell reduces sodium (Na+) influx into cells through the Na+-H+ exchange channel resulting in a drop in the intracellular Na+.  Since the Na+K+ATPase ion channel depends on the intracellular Na+ for bringing K+ into the cells, the end-result is higher K+ concentrations in the extracellular space, potentially resulting in hyperkalemia.  This is what is often seen in conditions of mineral (non-organic) acid excess (eg, in respiratory acidosis or poor renal function).

In the case of organic acidosis, however, the OAT also plays an important factor in K+ homeostasis (Figure)¹.  As the name suggests, this transporter allows  organic acids such as lactic acid or ketones to enter the cell. As the H+ concentration increases intracellularly, there is more Na+-H+ exchange and more influx of Na+ into the cell.  More available Na+ intracellularly means more Na+ is pumped out by Na+K+ATPase, and more K+ is brought into the cell,^1-5 mitigating the impact of metabolic acidosis on K+ efflux into the  extracellular space and potentially even causing hypokalemia! 

Concurrent hyperkalemia and lactic acidosis or diabetic ketoacidosis may of course still occur.  However, in such cases, hyperkalemia is often due to an epiphenomenon related to complicating factors.  In the case of lactic acidosis, this may be related to concurrent renal dysfunction,³ while in diabetic ketoacidosis it may be related to hyperosmolarity or insulin deficiency.¹

So next time you see a patient who has hyperkalemia and lactic acidosis, ask yourself  “What else am I missing that can explain the hyperkalemia?“.

Bonus Pearl

Did you know that lactic acid in human blood was first discovered by the German physician–chemist, Johann Joseph Sherer, who sampled post-mortem blood from 2 women who died of puerperal fever in 1843? ⁶

Contributed by Nabi Chaudhri-Martinez MD, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

1. Aronson PS, Giebisch G. Effects of pH on potassium: new explanations for old observations. J Am Soc Nephrol. 2011 Nov;22(11):1981-9. doi: 10.1681/ASN.2011040414. Epub 2011 Oct 6. PMID: 21980112; PMCID: PMC3231780. https://jasn.asnjournals.org/content/22/11/1981.long
2. Orringer CE, Eustace JC, Wunsch CD, Gardner LB. Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia. N Engl J Med. 1977 Oct 13;297(15):796-9. doi: 10.1056/NEJM197710132971502. PMID: 19702. https://www.nejm.org/doi/10.1056/NEJM197710132971502?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
3. Fulop M. Serum potassium in lactic acidosis and ketoacidosis. N Engl J Med. 1979 May 10;300(19):1087-9. doi: 10.1056/NEJM197905103001905. PMID: 34793. https://www.nejm.org/doi/10.1056/NEJM197905103001905?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed
4. Adrogué HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med. 1981 Sep;71(3):456-67. doi: 10.1016/0002-9343(81)90182-0. PMID: 7025622. https://www.amjmed.com/article/0002-9343(81)90182-0/pdf
5. Nigam SK, Bush KT, Martovetsky G, et al. The organic anion transporter (OAT) family: A systems biology perspective. Physiol Rev 2015;95:83:123. The Organic Anion Transporter (OAT) Family: A Systems Biology Perspective (physiology.org)
6. Kompanje EJ, Jansen TC, van der Hoven B, Bakker J. The first demonstration of lactic acid in human blood in shock by Johann Joseph Scherer (1814-1869) in January 1843. Intensive Care Med. 2007;33(11):1967-1971. doi:10.1007/s00134-007-0788-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040486/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!