Why doesn’t my patient with lactic acidosis have hyperkalemia?

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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  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!

Why doesn’t my patient with lactic acidosis have hyperkalemia?

My hospitalized patient with sepsis has persistently elevated lactic acid despite volume resuscitation, source control, and adequate oxygenation. What could I be missing?

Although the causes of lactic acidosis are legion (eg, sepsis, tissue hypoperfusion, ischemic bowel, malignancy, medications, liver dysfunction), thiamine deficiency (TD) is an often-overlooked cause of persistently elevated serum lactic acid (LA) in critically ill hospitalized patients,1 reported in 20-70% of septic patients.2  Septic shock patients may be particularly at risk of TD because of increased mitochondrial oxidative stress, decreased nutritional intake and presence of comorbid conditions (eg,  alcoholism, persistent vomiting).3

Early recognition of TD in hospitalized patients may be particularly difficult because of the frequent absence of the “classic” signs and symptoms of Wernicke’s encephalopathy (eg, ataxia, cranial nerve palsies and confusion) and lack of readily available confirmatory laboratory tests.4

TD-related lactic acidosis should be suspected when an elevated LA persists despite adequate treatment of its putative cause(s) (4,5). Administration of IV thiamine in this setting may result in rapid clearance of LA.3-5

TD causes lactic acidosis type B which is due to the generation of excess LA, not impairment in tissue oxygenation, as is the case for lactic acidosis type A. Thiamine is an essential co-factor in aerobic metabolism, facilitating the conversion of pyruvate to acetyl-CoA which enters the citric acid (Krebs) cycle within the mitochondria. In TD, pyruvate does not undergo aerobic metabolism and is converted to LA instead, leading to lactic acidosis.

Bonus pearl: Did you know that because of its limited tissue storage, thiamine stores may be depleted within only 3 weeks of reduced oral intake!


  1. O’Donnell K. Lactic acidosis: a lesser known side effect of thiamine deficiency. Practical Gastroenterol March 2017:24.   https://www.practicalgastro.com/article/176921/Lactic-Acidosis-Lesser-Known-Side-Effect-of-Thiamine-Deficiency
  2. Marik PE. Thiamine: an essential component of the metabolic resuscitation protocol. Crit Care Med 2018;46:1869-70. https://journals.lww.com/ccmjournal/Fulltext/2018/11000/Thiamine___An_Essential_Component_of_the_Metabolic.23.aspx
  3. Woolum JA, Abner EL, Kelly A, et al. Effect of thiamine administration on lactate clearance and mortality in patients with septic shock. Crit Care Med 2018;46:1747-52. https://journals.lww.com/ccmjournal/Fulltext/2018/11000/Effect_of_Thiamine_Administration_on_Lactate.5.aspx
  4. Kourouni I, Pirrotta S, Mathew J, et al. Thiamine: an underutilized agent in refractory lactic acidosis. Chest 2016; 150:247A. https://journal.chestnet.org/article/S0012-3692(16)56459-9/pdf
  5. Shah S, Wald E. Type B lactic acidosis secondary to thiamine deficiency in a child with malignancy. Pediatrics 2015; 135:e221-e224. http://pediatrics.aappublications.org/content/135/1/e221

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My hospitalized patient with sepsis has persistently elevated lactic acid despite volume resuscitation, source control, and adequate oxygenation. What could I be missing?