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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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!

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

Why is my relatively healthy elderly patient so prone to hyperkalemia?

Hyporeninemic hypoaldosteronism (HH)—without impairment of cortisol synthesis— is associated with hyperkalemic (type IV) renal tubular acidosis (RTA) and is not uncommon among older patients despite glomerular filtration rates (GFRs) >20 ml/min, and absence of diabetes mellitus or chronic tubulointerstitial disease (1-7).  

Hyperkalemia due to HH in the elderly should come as no surprise because the renin-angiotensin-aldosterone system (RAAS) function declines with age, reaching its lowest level by age 60. 1-4   In fact, older people have comparatively lower mean levels of plasma renin and aldosterone at baseline and have an impaired ability to mount appropriate responses to RAAS stimuli, such as upright posture, volume depletion, catecholamines, or potassium administration (3-5).

The impaired RAAS capacity in the elderly often becomes more obvious when they are prescribed medications that further suppress RAAS (3). These include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-channel blockers, nonsteroidal anti-inflammatory agents and heparin (3,7). 

Drugs that increase aldosterone resistance, including potassium-sparing diuretics (eg, spironolactone, amiloride, triamterene, eplerenone) and certain antibiotics (eg, trimethoprim, pentamidine) may also aggravate hyperkalemia associated with HH (7). 

A variety of mechanisms leading to HH with aging have been proposed. These include impaired conversion of prorenin to renin, prostaglandin deficiency, sympathetic nervous system dysfunction and increased plasma levels of atrial natriuretic factors as found in congestive heart failure (1,7). 

Bonus pearl: Did you know that the first case of “pure hypoaldosteronism” was described in 1957 in a 71 year old non-diabetic patient with hyperkalemia in the setting of congestive heart failure? (8)

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References

  1. Bauer JH. Age-related changes in the renin-aldosterone system. Physiological effects and clinical implications. Drugs & Aging 1993;3:238-45. https://www.ncbi.nlm.nih.gov/pubmed/8324299
  2. Musso CG, Jauregui JR. Renin-angiotensin-aldosterone system and the aging kidney. Expert Rev Endocrinol Metab 2014;9:543-46. https://www.tandfonline.com/doi/full/10.1586/17446651.2014.956723
  3. Yoon HE, Choi BS. The renin-angiotensin system and aging in the kidney. Korean J Intern Med 2014;29:291-95. https://www.researchgate.net/publication/262530577_The_renin-angiotensin_system_and_aging_in_the_kidney
  4. Nadler JL, Lee FO, Hsueh W, et al. Evidence of prostacyclin deficiency in the syndrome of hyporeninemic hypoaldosteronism. N Engl J Med 1986;314:1015-20. https://www.ncbi.nlm.nih.gov/pubmed/3515183
  5. Williams GH. Hyporeninemic hypoaldosteronism. N Engl J Med 1986;314:1041-42. https://www.ncbi.nlm.nih.gov/pubmed/3515186
  6.  Block BL, Bernard S, Schwartzstein RM. Hypo-hypo: a complex metabolic disorder. Ann Am Thorac Soc 2016;13:127-133. https://www.ncbi.nlm.nih.gov/pubmed/26730868
  7. Michelis MF. Hyperkalemia in the elderly. Am J Kid Dis 1990;16:296-99.https://www.ajkd.org/article/S0272-6386(12)80005-9/pdf
  8. Hudson JB, Chobanian AV, Relman AS. Hypoaldosteronism. A clinical study of a patient with an isolated adrenal mineralocorticoid deficiency, resulting in hyperkaliemia and Stokes-Adams attack. N Engl J Med 1957;257:529-36. https://www.ncbi.nlm.nih.gov/pubmed/13464977

 

Why is my relatively healthy elderly patient so prone to hyperkalemia?

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?

Any respiratory rate (RR) greater than 20/min in an adult patient may be cause for concern, particularly in the setting of potentially serious disease and absence of an obvious cause such as pain or fever.

Our patient’s RR is outside the commonly cited normal range of 12-20/min. It indicates increased alveolar ventilation which may in turn be caused by hypoxia, hypercapnea, or metabolic acidosis, all portending possibly poor outcome, if left untreated.It’s no surprise that an abnormal RR is often the first sign of clinical deterioration.2 RR is also the least likely of the vital signs to be affected by polypharmacy (eg, NSAIDs affecting temperature, beta-blockers affecting heart rate and blood pressure). 

Another reason for not dismissing an RR of 22 in our patient is the common practice of guessing rather than measuring the RR by healthcare providers in part likely due to the  more “labor-intensive” nature of measuring RRs compared to other vital signs and lack of appreciation for its importance in assessing severity of disease. 1 Of note, in an experimental study of doctors viewing videos of mock patients, over 50% failed to detect abnormal RR when using the “spot” technique of estimating without a timer.3 Even when presented with a RR of 30/min, over 20% of doctors reported it as normal (12-20/min)!

Final tidbit: Do you want to know what a RR of 20/min really feels like? Take a breath every 3 seconds.  If you are like most, it doesn’t feel “normal”!

References
1. Cretikos MA, Bellomo R, Hillman K. Respiratory rate: the neglected vital sign. MJA 2008;188:657-59. https://www.ncbi.nlm.nih.gov/pubmed/18513176
2. Flenady T, Dwer T, Applegarth J. Accurate respiratory rates count: So should you! Australas Emerg Nurs J 2017; 20:45-47. https://www.ncbi.nlm.nih.gov/pubmed/28073649
3. Philip KEJ, Pack E, Cambiano V et al. The accuracy of respiratory rate assessment by doctors in a London teaching hospital: a cross-sectional study. J Clin Monit Comput2015;29:455-60. https://www.ncbi.nlm.nih.gov/pubmed/25273624

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?