Can hyperkalemia cause acidosis?

Hyperkalemia Does Not Cause Acidosis—It's the Reverse

Hyperkalemia causes metabolic acidosis, not the other way around. This is a critical distinction in clinical practice, as the traditional teaching that acidosis causes hyperkalemia is only true for mineral acid-induced acidosis (respiratory acidosis, uremic acidosis, NH4Cl administration), not for organic acidoses 1, 2.

The Mechanism: How Hyperkalemia Induces Acidosis

Hyperkalemia directly suppresses renal ammonia metabolism and excretion, which is the primary mechanism by which it causes metabolic acidosis 3, 4. This occurs through several pathways:

Proximal Tubule Effects

• Hyperkalemia decreases ammonia production in the proximal tubule by suppressing the ammonia-generating enzymes phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase 4
• It simultaneously increases expression of glutamine synthetase, an ammonia-recycling enzyme that further reduces net ammonia production 4

Collecting Duct Effects

• Hyperkalemia reduces medullary interstitial concentrations of NH4+ and NH3 by inhibiting NH4+ absorption in the thick ascending limb of Henle 3
• It decreases expression of the ammonia transporter Rhcg and impairs apical polarization of H+-ATPase in the inner stripe of the outer medullary collecting duct 4
• These changes collectively decrease ammonia entry into the collecting duct and reduce urinary ammonia excretion 3, 4

Clinical Evidence

• In experimental models, correcting hyperkalemia with hydrochlorothiazide or potassium-binding resins completely resolves the metabolic acidosis and normalizes ammonia excretion 5, 4
• In isolated hypoaldosteronism, hyperkalemia itself—rather than mineralocorticoid deficiency—is the primary cause of acidosis, as demonstrated by resolution of acidosis with potassium-lowering therapy alone 5

The Reverse Relationship: When Does Acidosis Cause Hyperkalemia?

Only mineral acid-induced acidosis causes hyperkalemia through transcellular potassium shifts 1, 2. This includes:

• Respiratory acidosis
• End-stage uremic acidosis
• NH4Cl or CaCl2-induced acidosis

Organic acidoses (diabetic ketoacidosis, lactic acidosis, alcoholic ketoacidosis) do NOT cause hyperkalemia in uncomplicated cases 1. The organic anions penetrate cells freely without creating a hydrogen ion gradient, thus preventing potassium efflux from cells 1.

Common Pitfall

• During treatment of diabetic ketoacidosis, correction of acidosis and volume expansion actually decrease serum potassium, and potassium replacement should be initiated when levels fall below 5.5 mEq/L 6
• The classical teaching that absence of hyperkalemia during severe acidosis indicates severe potassium deficiency is not valid in patients with uncomplicated organic acidemias 1

Clinical Implications for Hyperkalemia Management

When hyperkalemia and metabolic acidosis coexist, sodium bicarbonate should ONLY be used if metabolic acidosis is present (pH <7.35, bicarbonate <22 mEq/L) 7, 8. The bicarbonate:

• Promotes potassium excretion through increased distal sodium delivery 7
• Counters the release of potassium into blood caused by metabolic acidosis 7
• Takes 30-60 minutes to manifest effects on potassium levels 7, 8

When NOT to Use Bicarbonate

• Do not use sodium bicarbonate in patients without metabolic acidosis—it is ineffective and wastes time 7, 8
• In organic acidoses without complications, bicarbonate administration is unnecessary as these conditions do not inherently cause hyperkalemia 1

Type 4 Renal Tubular Acidosis

Hyperkalemia in association with metabolic acidosis that is out of proportion to changes in GFR defines type 4 RTA, the most common RTA observed 4. This syndrome is characterized by:

• Hyperchloremic metabolic acidosis 3
• Suppressed urinary ammonium excretion despite systemic acidosis 5, 4
• Normal or near-normal urine pH (typically around 4.9) 5
• Blunted titratable acid excretion 4

The potential for type 4 RTA is greatly augmented when renal insufficiency coexists with hyperkalemia, or in the presence of aldosterone deficiency or resistance 3.

Special Populations

Preterm Infants

• Non-oliguric hyperkalemia can develop after birth even without potassium intake, with risk factors including lack of antenatal corticosteroids, systemic acidosis, birth asphyxia, and catabolic states 6
• Early hyperkalemia in this population requires checking for systemic acidosis as a contributing factor 9

Primary Adrenal Insufficiency

• Hyperkalemia is present in approximately half of patients at diagnosis due to aldosterone deficiency, impaired glomerular filtration, and acidosis 6
• All three factors contribute synergistically to the electrolyte disturbance 6