Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5–5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. If minor in severity, hypokalemia is usually asymptomatic. However, acute reductions in K+ level or severe hypokalemia can lead to cardiac arrhythmias, muscle weakness, rhabdomyolysis, paralysis, and respiratory failure. Diagnosis is by clinical history and lab testing. Management is guided by severity and includes treating urgent symptoms, replacing the K+ deficit, and treating the underlying cause.

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Potassium (K+) is the main intracellular cation in all cells and is distributed unevenly between the intracellular fluid (98%) and extracellular fluid (2%). The large disparity is necessary for maintaining the resting membrane potential of cells.

  • The GI tract secretes 5%–10% of absorbed K+ daily.
  • Kidneys are responsible for 90%–95% of the overall K+ regulation and will severely limit the excretion of K+ if intake is low.


Hypokalemia is defined as plasma K+ concentration < 3.5 mEq/L.

Sites of action in the kidney

  • Glomerulus: K+ is freely filtered.
  • Proximal tubule: 65%–70% of filtered K+ is reabsorbed.
  • Thick ascending limb of the loop of Henle: 10%–25% of filtered K+ is reabsorbed.
  • Principal cell (cortical collecting duct): K+ is secreted.
  • 𝛼-intercalated cell (collecting duct): K+ is reabsorbed.


The etiologies of hypokalemia can be grouped by 4 distinct mechanisms: poor dietary K+ intake, transcellular shift, GI losses, and renal losses. 

  • Poor dietary K+ intake:
    • Western diet: approximately 70–150 mmol K+/day
    • Uncommon cause outside of chronic malnutrition states (e.g., alcoholism)
  • Transcellular shift:
    • Intracellular shifting of K+ results in hypokalemia
    • Factors increasing the intracellular shift:
      • Insulin 
      • β2 adrenergic agonists (e.g., albuterol)
      • Alkalosis: H+/K+ exchanger moves H+ out of the cell to help balance extracellular pH in exchange for K+ moving into the cell to maintain electroneutrality.
  • GI losses: hypokalemia develops due to downstream effects on the kidney:
    • Upper GI losses: HCl is also in gastric fluid → metabolic alkalosis → contributes to hypokalemia via transcellular shifting:
      • Vomiting
      • Nasogastric tube output
    • Lower GI losses: 
      • Diarrhea
      • Laxative abuse
      • Villous adenoma
  • Renal losses:
    • Metabolic alkalosis with high blood pressure:
      • ↑ Aldosterone due to primary hyperaldosteronism, adrenal tumor, bilateral adrenal hyperplasia, or renal artery stenosis
      • ↑ Cortisol due to excessive ingestion of black licorice
      • ↑ Cortisol due to genetic conditions (congenital adrenal hyperplasia)
      • Liddle syndrome 
    • Metabolic alkalosis with low or normal blood pressure:
      • Loop and thiazide diuretics: a significant cause of hypokalemia in outpatients and hospitalized patients
      • Salt-wasting nephropathy (Bartter syndrome, Gitelman syndrome)
    • Metabolic acidosis:
      • Type 1 (distal) or type 2 (proximal) renal tubular acidosis (RTA)
      • Nonreabsorbable anions (e.g., 𝛽-hydroxybutyrate (diabetic ketoacidosis) or toluene sniffing (drug of abuse))
    • Hypomagnesemia:
      • Can directly cause hypokalemia
      • Can be due to diarrhea or diuretics
      • Uncorrected hypomagnesemia can make hypokalemia correction due to any cause difficult.

Clinical Presentation

Presentation of hypokalemia may include nausea, vomiting, constipation, skeletal muscle manifestations, and cardiac manifestations, which are potentially very serious. Symptoms are more likely to appear as the severity of hypokalemia increases, but patients may be asymptomatic even with relatively severe hypokalemia.

  • Cardiac manifestations:
    • ECG changes:
      • Decreased amplitude of T wave
      • Prominent U waves
      • ST depression
      • Prolongation of QT intervals
    • Arrhythmias:
      • Premature atrial/ventricular contractions 
      • Atrioventricular block, sinus bradycardia
      • Ventricular tachycardia and/or ventricular fibrillation if severe
  • Muscular symptoms:
    • With mild-to-moderate hypokalemia:
      • Muscle cramps, myalgia, generalized weakness
      • Relatively common (especially muscle cramps), but also somewhat nonspecific
    • With severe hypokalemia (< 2–2.5 mEq/L): 
      • Patients may be asymptomatic even if severe hypokalemia is present.
      • Rhabdomyolysis with an elevated serum CK level
      • Ileus
      • Respiratory failure due to respiratory muscle weakness (may require intubation if severe)
ECG changes seen in hypokalemia

ECG changes seen in hypokalemia

Image by Lecturio. License: CC BY-NC-SA 4.0

Diagnosis and Management


  • Clinical history:
    • Identify the cause of hypokalemia (e.g., GI losses, diuretic use).
    • If the diagnosis is clear from history, no further testing is needed.
  • Lab testing: urine studies if the diagnosis is still unclear
  • Spot urine K+: frequently unreliable due to many possible confounding variables:
    • > 15 mEq/L: renal loss
    • < 15 mEq/L: extrarenal loss
  • Urine potassium-creatinine ratio (more reliable than spot urine K+):
    • Adjusts for urine volume
    • Correlates better with the 24-hour urine collection (impractical)
    • < 15 mEq/g = extrarenal loss or transcellular shift:
      • If concurrent metabolic acidosis → likely due to diarrhea (including villous adenoma or laxative abuse)
      • If concurrent metabolic alkalosis → likely due to vomiting or diuretic use
    • > 15 mEq/g = renal loss:
      • If concurrent metabolic acidosis → RTA or nonreabsorbable anion
      • If concurrent metabolic alkalosis, low/normal blood pressure, and hypovolemia → could be due to diuretics, salt-wasting nephropathy (Bartter or Gitelman syndrome), or vomiting 
      • If concurrent metabolic alkalosis, high blood pressure, and hypervolemia → may be due to mineralocorticoid excess, renal artery stenosis, or Liddle syndrome


  • Treat urgent complications if present:
    • Respiratory failure
    • Arrhythmia: increased risk occurs with:
      • Increasing severity of hypokalemia (particularly < 2.5 mEq/L)
      • Concurrent hypomagnesemia
      • Concurrent coronary artery disease
      • Concurrent digoxin or antiarrhythmic drug 
      • Older age
  • Replace K+:
    • Mild to moderately severe: oral KCl or potassium citrate
    • Severe (< 3 mEq/L, urgent symptoms, or if unable to take by mouth): IV K+
    • Maximal rate of infusion: 
      • 10 mEq/hr through peripheral IV
      • 20 mEq/hr through a central line
      • Fast rates of infusion can cause pain and irritation to the peripheral veins.
    • KCl should not be mixed in 5% dextrose in water (causes insulin release→ transcellular shift).
  • Replace magnesium if low
  • Monitoring is important at all levels of hypokalemia:
    • Cardiac monitoring:
      • Serial ECGs and/or continuous cardiac monitoring (i.e., telemetry)
      • Some patients will not have signs of arrhythmia or ECG changes even with severe hypokalemia.
    • Lab monitoring:
      • Repeat serum K+ frequently based on the severity of hypokalemia and the clinical situation.
      • Glucose monitoring for hypoglycemia
  • Treat the underlying disease (potassium-sparing diuretic may be required):
    • Bartter syndrome or Gitelman syndrome: amiloride
    • Primary aldosteronism: spironolactone
    • Chronic diuretic use

Clinical Relevance

  • Rhabdomyolysis: potassium may be normal or high on presentation due to the release of intracellular K+ as muscle cells die. Because many causes of rhabdomyolysis exist other than hypokalemia and the risk of hyperkalemia with overaggressive K+ replacement is significant, only replace K+ if and when plasma levels are low. Diagnosis is made by history and CK levels, and management of the underlying cause is needed.
  • Diabetic ketoacidosis (DKA): presents with K+ deficit of the total body (urinary losses from osmotic diuresis/polyuria); however, plasma K+ is normal or high due to severe transcellular shifting from insulin deficiency. Diagnosis is made by history and lab testing, which include glucose and serum ketones. Treatment includes starting an insulin drip and replacing K+ once the plasma level falls to 4.5 mEq/L since the intracellular shift will cause hypokalemia. 
  • Hypokalemic periodic paralysis: characterized by acute attacks of muscle weakness and/or paralysis precipitated by rest after exercise, stress, and/or a high-carbohydrate meal. Hypokalemic periodic paralysis can be genetic or acquired (associated with hyperthyroidism/thyrotoxicosis). Hypokalemic periodic paralysis is the prototypical disease due to severe transcellular shifting of K+. The presentation includes a plasma K+ decrease to 1.5–2.5 mEq/L. Supplemental K+ should only be replaced if symptomatic and done cautiously given the risk for rebound hyperkalemia once the transcellular shifting is corrected. 
  • Chronic hypokalemia: can have long-term adverse effects, including worsening hypertension, chronic kidney disease, and polyuria. Chronic hypokalemia may increase the risk of developing diabetes in conjunction with thiazide diuretics.
  • False-positive hypokalemia: a common occurrence in hospital settings, usually caused by blood drawn from an IV nearby a hypotonic fluid infusion. Cells in the blood can also have significant uptake of K+ if the blood sample is left in warm temperatures for a prolonged period of time, or if the WBC is very high (e.g., > 100,000/mL in leukemia).
  • Salt-wasting nephropathies: Bartter syndrome and Gitelman syndrome with a clinical presentation of metabolic alkalosis, low or normal blood pressure, and hypokalemia from renal losses. Both are rare, autosomal recessive syndromes; however, the mechanism of Bartter syndrome resembles a loop diuretic and the mechanism of Gitelman syndrome resembles a thiazide diuretic. Treatment includes a potassium-sparing diuretic (spironolactone or amiloride) and NSAIDs.
  • Liddle syndrome: a rare, autosomal dominant disease presenting clinically with metabolic alkalosis, high blood pressure, and hypokalemia from renal losses. Treatment includes a potassium-sparing diuretic (amiloride or triamterene).
  • Type 1 RTA (also known as distal RTA): the condition results in systemic metabolic acidosis due to impaired distal acidification in the kidney. Distal RTA can be genetic or acquired (due to drugs or autoimmune disease). Diagnosis is made on history and lab testing. Treatment is oral bicarbonate, usually in the form of sodium bicarbonate or potassium citrate.
  • Type 2 RTA (also known as proximal RTA): the condition results in systemic metabolic acidosis due to impaired reabsorption of filtered bicarbonate in the proximal tubule. Proximal RTA can be genetic or acquired (i.e. due to drugs or multiple myeloma). Diagnosis is made on history and lab testing. Treatment is more complicated than type 1 RTA and involves a combination of oral bicarbonate, oral K+ supplementation, hydrochlorothiazide, and a potassium-sparing diuretic (amiloride or spironolactone).
  • Nonreabsorbable anions: anions (e.g., 𝛽-hydroxybutyrate, hippurate) associated with metabolic acidosis cause hypokalemia from increased renal excretion of K+. Ketoacidosis can result from uncontrolled diabetes, starvation, or alcoholism and is associated with high 𝛽-hydroxybutyrate levels. Hippurate is a metabolite of toluene, which is found in paint thinner, and inhaled as a drug of abuse (“huffing”). 


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