What are the causes and treatment of hypokalemia (low potassium levels)?

Causes of Hypokalemia

Medication-Induced Causes

Diuretics are the most common cause of hypokalemia in clinical practice, accounting for up to 40% of cases in patients taking these medications 1, 2.

Diuretic-Related Mechanisms

• Loop diuretics (furosemide, bumetanide, torsemide) inhibit sodium and chloride reabsorption in the ascending limb of the loop of Henle, causing significant potassium wasting and metabolic alkalosis 3
• Thiazide diuretics (hydrochlorothiazide) inhibit sodium and chloride reabsorption in the distal tubule, leading to hypokalemia 3
• Both classes produce metabolic alkalosis that perpetuates renal potassium losses 3

Other Medications Causing Hypokalemia

• Beta-agonists cause transcellular shifts of potassium into cells 4
• Insulin drives potassium intracellularly, particularly problematic in diabetic ketoacidosis management 4
• Corticosteroids (prednisolone, hydrocortisone) cause hypokalemia through mineralocorticoid effects, with hydrocortisone causing more severe potassium wasting than methylprednisolone at equivalent doses 4

Gastrointestinal Losses

Vomiting causes hypokalemia primarily through renal potassium losses driven by metabolic alkalosis and secondary hyperaldosteronism, not through direct loss of potassium in gastric fluid 3.

Mechanism of Vomiting-Induced Hypokalemia

• Loss of gastric acid creates metabolic alkalosis, leaving bicarbonate in circulation 3
• Metabolic alkalosis directly increases renal potassium excretion through enhanced sodium epithelial channel (ENaC) activity in the cortical collecting duct 3
• Volume depletion activates the renin-angiotensin-aldosterone system, promoting sodium retention and potassium excretion 3
• Increased sodium-bicarbonate delivery to the collecting duct enhances potassium excretion to maintain electroneutrality 3

Other GI Causes

• Diarrhea causes direct potassium losses 2, 5
• High-output fistulas or stomas can cause severe hypokalemia with secondary hyperaldosteronism 4, 3
• Constipation can paradoxically increase colonic potassium losses 4

Renal Losses

Primary Renal Disorders

• Primary hyperaldosteronism causes excessive renal potassium excretion 3
• Bartter syndrome and Gitelman syndrome are genetic tubular disorders causing renal potassium wasting 3
• Magnesium deficiency causes renal potassium wasting through dysfunction of potassium transport systems 4, 3

Secondary Hyperaldosteronism

• Volume depletion from any cause activates the renin-angiotensin-aldosterone system 3
• Sodium/water depletion paradoxically increases renal potassium losses 4

Transcellular Shifts

Transcellular shifts move potassium from extracellular to intracellular compartments without true body potassium depletion 2.

Causes of Transcellular Shifts

• Insulin excess drives potassium into cells 4, 2
• Beta-agonist therapy (albuterol, terbutaline) causes intracellular potassium shift 4, 2
• Thyrotoxicosis can cause periodic paralysis with severe hypokalemia 4
• Metabolic alkalosis promotes intracellular potassium movement 3

Inadequate Intake

• Dietary insufficiency is rarely the sole cause but contributes to hypokalemia when combined with other factors 3, 2
• Total parenteral nutrition without adequate potassium supplementation 5
• The World Health Organization recommends potassium intake of at least 3,510 mg per day for optimal cardiovascular health 6

Special Clinical Contexts

Diabetic Ketoacidosis

• Patients typically have total body potassium deficits of 3-5 mEq/kg body weight despite initially normal or elevated serum levels 4
• Osmotic diuresis causes massive urinary potassium losses 4

Tissue Destruction

• Catabolism, infection, surgery, or chemotherapy can cause potassium redistribution and losses 4

Concurrent Magnesium Depletion

Hypomagnesemia is the most common reason for refractory hypokalemia and must be corrected before potassium levels will normalize 4, 3.

• Magnesium depletion causes dysfunction of potassium transport systems 4
• Target magnesium level should be >0.6 mmol/L 4
• Use organic magnesium salts (aspartate, citrate, lactate) rather than oxide or hydroxide for superior bioavailability 4

Common Pitfalls in Diagnosis

• Failing to check magnesium levels is the most common reason for treatment failure 4
• Overlooking secondary hyperaldosteronism in volume-depleted patients 3
• Not correcting sodium/water depletion first in patients with GI losses, as hypoaldosteronism from volume depletion increases renal potassium losses 4
• Missing concealed diuretic use or herbal supplements containing licorice (which has mineralocorticoid effects) 3