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Potassium balance in acid-base disorders

Potassium balance in acid-base disorders
Literature review current through: Jan 2024.
This topic last updated: Jan 29, 2024.

INTRODUCTION — There are important interactions between potassium and acid-base balance that involve both transcellular cation exchanges and alterations in kidney function [1]. These changes are most pronounced with metabolic acidosis but can also occur with metabolic alkalosis and, to a lesser degree, respiratory acid-base disorders.

INTERNAL POTASSIUM BALANCE — Acid-base disturbances cause potassium to shift into and out of cells, a phenomenon called "internal potassium balance" [2]. An often-quoted study found that the plasma potassium concentration will rise by 0.6 mEq/L for every 0.1 unit reduction of the extracellular pH [3]. However, this estimate was based upon only five patients with a variety of disturbances, and the range was very broad (0.2 to 1.7 mEq/L). This variability in the rise or fall of the plasma potassium in response to changes in extracellular pH was confirmed in subsequent studies [2,4].

Metabolic acidosis — In metabolic acidosis, more than one-half of the excess hydrogen ions are buffered in the cells. In this setting, electroneutrality is maintained in part by the movement of intracellular potassium into the extracellular fluid (figure 1). Thus, metabolic acidosis results in a plasma potassium concentration that is elevated in relation to total body stores. The net effect in some cases is overt hyperkalemia; in other patients who are potassium depleted due to urinary or gastrointestinal losses, the plasma potassium concentration is normal or even reduced [5,6]. There is still a relative increase in the plasma potassium concentration, however, as evidenced by a further fall in the plasma potassium concentration if the acidemia is corrected.

A fall in pH is much less likely to raise the plasma potassium concentration in patients with lactic acidosis or ketoacidosis [7,8]. The hyperkalemia that is commonly seen in diabetic ketoacidosis (DKA), for example, is more closely related to the insulin deficiency and hyperosmolality than to the degree of acidemia. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis".)

Why this occurs is not well understood. Two factors that may contribute are the ability of the organic anion to accompany the hydrogen ion into the cell, perhaps as the lipid-soluble, intact acid [9], and differential effects on insulin and glucagon secretion [4,10].

Just as metabolic acidosis can cause hyperkalemia, a rise in the plasma potassium concentration can induce a mild metabolic acidosis. In patients with hypoaldosteronism, for example, the mild metabolic acidosis is primarily due to the associated hyperkalemia [11]. Two factors contribute to this phenomenon:

A transcellular exchange occurs as the entry of most of the excess potassium into the cells is balanced in part by intracellular hydrogen ions moving into the extracellular fluid [12]. The net effect is an extracellular acidosis and an intracellular alkalosis.

Normally, the kidney increases ammonium excretion after an acid load, an effect that is stimulated in part by a fall in intracellular pH [13]. In hyperkalemia, the associated intracellular alkalosis diminishes ammonium generation by the proximal tubule [14]. Hyperkalemia reduces the expression of ammonia-generating enzymes in the proximal tubule and upregulates expression of the ammonia-recycling enzyme glutamine synthetase [15]. Normally, ammonium exiting the proximal tubule is reabsorbed in the thick ascending limb via the apical Na+-K+/NH4+-2Cl- cotransporter (NKCC2), after which it crosses the interstitium and is excreted into the urine by the collecting duct [16-18]. However, potassium competes with ammonium for reabsorption by NKCC2, and therefore, elevated tubular potassium concentrations can impair normal renal ammonium handling, resulting in acidosis [19]. In addition, hyperkalemia reduces expression of the ammonia transporter family member Rhcg and decreases apical expression of H-ATPase in the inner stripe of the outer medullary collecting duct, further compromising urinary ammonium excretion [15].

The net effect of these changes in cation distribution and kidney function is that metabolic acidosis and relative hyperkalemia are often seen together.

Metabolic alkalosis — For similar reasons in which the above ionic changes are reversed, metabolic alkalosis and hypokalemia are commonly associated. Metabolic alkalosis causes potassium movement into the cells, and hypokalemia causes hydrogen movement into the cells [20,21]. With metabolic alkalosis, the plasma potassium concentration falls, although the change in potassium is smaller in magnitude than is observed in metabolic acidosis [7].

Respiratory acid-base disorders — Respiratory acidosis and alkalosis induce relatively small changes in potassium balance [7]. The reason for this minor effect is not well understood.

CONCURRENT DISORDERS OF POTASSIUM BALANCE — The preceding discussion has emphasized the effect of pH on potassium distribution between the cells and extracellular fluid. However, patients with acid-base disturbances commonly have concurrent disorders of external potassium balance that can affect this relationship.

Concurrent metabolic acidosis — In metabolic acidosis caused by diarrhea, fecal loss of alkali is accompanied by gastrointestinal loss of potassium. The net result is a normal anion gap metabolic acidosis with potassium depletion and hypokalemia. (See "Causes of hypokalemia in adults", section on 'Lower gastrointestinal losses'.)

In several organic acidoses, the acid anion is excreted in the urine with sodium or potassium as the accompanying cation. Hypokalemia may result despite the concurrent shift of potassium out of cells in response to acidemia. The metabolic acidosis caused by glue sniffing is the most dramatic example of this phenomenon. Inhaled toluene is metabolized to hippuric acid, and the acid anion (hippurate) is eliminated in the urine by both filtration and secretion, commonly resulting in hypokalemia [22]. (See "The delta anion gap/delta HCO3 ratio in patients with a high anion gap metabolic acidosis".)

Renal potassium wasting also occurs in diabetic ketoacidosis (DKA) and occasionally may lead to hypokalemia (6 percent of patients with DKA in one study) [23]. However, in contrast to toluene inhalation, many patients with DKA may develop hyperkalemia. Hyperkalemia in such patients results from profound potassium shift out of cells caused by hyperosmolality and insulin deficiency, and not, as noted above, by the metabolic acidosis. The administration of insulin typically leads to hypokalemia, unmasking the true state of potassium balance. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment".)

Renal potassium wasting can result in severe hypokalemia in untreated distal renal tubular acidosis (RTA) and in patients with proximal RTA who are treated with sodium bicarbonate. On the other hand, true hyperkalemia (ie, increased body potassium stores) is present in patients with hypoaldosteronism (type 4 RTA) due to impaired urinary potassium excretion. (See "Overview and pathophysiology of renal tubular acidosis and the effect on potassium balance".)

Concurrent metabolic alkalosis — Renal potassium wasting resulting in potassium depletion and hypokalemia is a feature of most causes of metabolic alkalosis (eg, vomiting, diuretics, Bartter and Gitelman syndromes).

SUMMARY

Potassium balance in metabolic acidosis – In metabolic acidosis, more than one-half of the excess hydrogen ions are buffered in the cells. In this setting, electroneutrality is maintained in part by the movement of intracellular potassium into the extracellular fluid (figure 1). Thus, metabolic acidosis results in a plasma potassium concentration that is elevated in relation to total body stores. The net effect in some cases is overt hyperkalemia. (See 'Metabolic acidosis' above.)

Just as metabolic acidosis can cause hyperkalemia, a rise in the plasma potassium concentration can induce a mild metabolic acidosis. This is due to transcellular exchange as most of the excess potassium enters the cells with intracellular hydrogen ions moving into the extracellular fluid. The net effect is an extracellular acidosis and an intracellular alkalosis. In the kidney, hyperkalemia diminishes ammonium excretion, thereby preventing excretion of the daily acid load and contributing to the metabolic acidosis. (See 'Metabolic acidosis' above.)

Potassium balance in metabolic alkalosis – For reasons that are similar but reciprocal, metabolic alkalosis and hypokalemia are commonly associated. Metabolic alkalosis causes potassium movement into the cells, and hypokalemia causes hydrogen movement into the cells. (See 'Metabolic alkalosis' above.)

Disorders leading to both potassium and acid-base abnormalities – Some patients with metabolic acid-base disorder have concurrent disorders of potassium balance which can produce hypokalemia or hyperkalemia through mechanisms other than those dependent upon cellular exchange. Examples include diarrhea, renal tubular acidosis, and diabetic ketoacidosis (DKA). (See 'Concurrent disorders of potassium balance' above.)

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Topic 2353 Version 20.0

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