Does acidosis cause hyperkalemia or hypokalemia?

Acidosis and Potassium: The Type of Acidosis Determines the Effect

Acidosis causes hyperkalemia when it is due to mineral acids (respiratory acidosis, uremic acidosis, NH4Cl administration), but organic acidoses (diabetic ketoacidosis, lactic acidosis, alcoholic ketoacidosis) typically do NOT cause hyperkalemia unless complicated by other factors. 1

Understanding the Mechanism

The critical distinction lies in the type of acidosis:

Mineral Acid Acidosis → Hyperkalemia

• Respiratory acidosis, end-stage uremic acidosis, and NH4Cl-induced acidosis predictably increase serum potassium through hydrogen-potassium exchange across cell membranes 1
• The mineral acid anion cannot penetrate cells freely, creating a hydrogen ion gradient that drives potassium efflux from cells 1
• During acute ammonium chloride-induced metabolic acidosis, serum potassium correlates inversely with serum bicarbonate (r = -0.437; p < 0.001), though hyperkalemia rarely occurs when bicarbonate exceeds 16 mEq/L 2

Organic Acid Acidosis → Normal Potassium (Usually)

• Diabetic ketoacidosis, lactic acidosis, alcoholic ketoacidosis, and other organic acidemias do NOT produce hyperkalemia in uncomplicated cases 1
• The organic anion (beta-hydroxybutyrate, lactate) penetrates cells freely without creating a hydrogen gradient, thus preventing potassium efflux 1
• In diabetic ketoacidosis specifically, patients often present with elevated serum potassium despite total body potassium depletion, but this is not due to acidosis itself 3

What Actually Causes Hyperkalemia in Diabetic Ketoacidosis

When hyperkalemia occurs in DKA, the primary determinants are 4:

• Insulin deficiency (the major initiating cause)
• Hyperglycemia (osmotic effect pulling potassium from cells)
• Elevated anion gap (reflecting ketoacid accumulation)
• The equation: [K+]p = 25.4 - 3.02 pH + 0.001 glucose + 0.028 anion gap 4

Acidosis per se contributes minimally - pH accounts for only 8-15% of the variance in potassium levels 4

Complicating Factors That Cause Hyperkalemia in Organic Acidosis

When hyperkalemia does occur with organic acidosis, search for 1:

• Dehydration and renal hypoperfusion (reduced potassium excretion)
• Pre-existing renal disease
• Hypercatabolism (tissue breakdown releasing intracellular potassium)
• Hypoaldosteronism (common in diabetes, causing hyperkalemic renal tubular acidosis) 5
• Medications (RAAS inhibitors, potassium-sparing diuretics)

In primary adrenal insufficiency, hyperkalemia occurs in approximately half of patients due to aldosterone deficiency, impaired glomerular filtration, and acidosis 6

Clinical Management Implications

During DKA Treatment

• Correction of acidosis and volume expansion DECREASE serum potassium 6
• Initiate potassium replacement after serum levels fall below 5.5 mEq/L, assuming adequate urine output 6
• Add 20-30 mEq potassium to each liter of IV fluid once K+ < 5.5 mEq/L 7
• Patients typically have total body potassium deficits of 3-5 mEq/kg despite initially normal or elevated levels 7

In Chronic Kidney Disease

• Hyperkalemia becomes common when GFR decreases below 10-15 mL/min/1.73 m² 8
• The mechanism involves impaired renal potassium excretion, not acidosis 8
• Maintain target potassium 4.0-5.0 mEq/L to minimize mortality risk 8

Critical Pitfall to Avoid

The classical teaching that absence of hyperkalemia during severe acidosis indicates severe potassium deficiency is NOT universally valid in organic acidemias 1. In uncomplicated organic acidosis, normal potassium levels are expected even with severe acidemia.