What are the causes, effects, and treatments of hypokalemia (low potassium levels), hypomagnesemia (low magnesium levels), and hypophosphatemia (low phosphate levels), including clinical symptoms, EKG changes, and recommended repletion agents?

Electrolyte Imbalances: Comprehensive Management Guide

HYPOKALEMIA (Serum K+ <3.5 mEq/L)

Classification and Severity

Hypokalemia is classified as mild (3.0-3.5 mEq/L), moderate (2.5-2.9 mEq/L), or severe (<2.5 mEq/L), with increasing arrhythmia risk at lower levels. 1

Major Causes

Medication-Induced:

• Loop diuretics (furosemide) inhibit sodium/chloride reabsorption in the ascending limb of Henle, causing significant hypokalemia and metabolic alkalosis 2
• Thiazide diuretics inhibit sodium/chloride reabsorption in the distal tubule, leading to potassium wasting 2
• Beta-agonists cause transcellular potassium shifts and can worsen existing hypokalemia 3
• Insulin excess drives potassium intracellularly 3

Gastrointestinal Losses:

• Vomiting, diarrhea, and high-output fistulas cause direct potassium loss 2
• High-output enterocutaneous fistulas can trigger secondary hyperaldosteronism, further increasing renal potassium losses 2

Renal Losses:

• Primary hyperaldosteronism, Bartter syndrome, and Gitelman syndrome cause inappropriate renal potassium wasting 2
• Hypomagnesemia causes renal potassium wasting and makes hypokalemia resistant to correction 2, 3

Clinical Manifestations

Cardiac:

• Ventricular arrhythmias, including PVCs, ventricular tachycardia, torsades de pointes, and ventricular fibrillation 2
• First or second-degree AV block, atrial fibrillation 2
• Risk of progression to ventricular fibrillation, PEA, or asystole if untreated 2
• Increased digitalis toxicity risk in patients on digoxin 2

Neuromuscular:

• Muscle weakness, fatigue, and constipation in mild cases 4
• Flaccid paralysis, paresthesias, and depressed deep tendon reflexes in severe cases 2
• Respiratory muscle weakness causing respiratory difficulties 2
• Muscle necrosis at very low levels (≤2.5 mEq/L) 4

ECG Changes in Hypokalemia

Progressive ECG abnormalities include T-wave flattening and broadening, ST-segment depression, prominent U waves (>1 mm in V2-V3), and QT interval prolongation. 5, 1 U waves >0.5 mm in lead II or >1.0 mm in lead V3 are considered abnormal 1. Hypokalemia with concurrent hypomagnesemia prolongs the QT interval and increases risk of torsades de pointes. 5

Treatment Approach

Severe Hypokalemia (K+ <2.5 mEq/L or with ECG changes/symptoms):

• Requires immediate IV potassium replacement with continuous cardiac monitoring 2, 3
• Establish large-bore IV access for administration 3
• Standard rate: maximum 10 mEq/hour or 200 mEq per 24 hours when K+ >2.5 mEq/L 6
• Urgent cases (K+ <2 mEq/L with ECG changes or muscle paralysis): rates up to 40 mEq/hour or 400 mEq per 24 hours with continuous ECG monitoring 6
• Central venous administration preferred for concentrations >200 mEq/L to avoid peripheral vein irritation and ensure thorough dilution 6
• Recheck serum potassium within 1-2 hours after IV correction to avoid overcorrection 3

Moderate Hypokalemia (K+ 2.5-2.9 mEq/L):

• Oral potassium chloride 20-60 mEq/day to maintain serum K+ in 4.5-5.0 mEq/L range 3
• Dietary supplementation alone is rarely sufficient 3

Mild Hypokalemia (K+ 3.0-3.5 mEq/L):

• Oral potassium chloride supplementation 3
• Dietary modifications to increase potassium-rich foods may suffice in milder cases 3

Critical Concurrent Treatment:

• Always correct hypomagnesemia concurrently, as it makes hypokalemia resistant to correction regardless of potassium replacement route 3, 7
• For gastrointestinal losses with high-output stomas/fistulas, correct sodium/water depletion first to address secondary hyperaldosteronism 3

Monitoring Protocol

• Check potassium and renal function within 2-3 days and again at 7 days after initiating supplementation 3
• Monitor at least monthly for first 3 months, then every 3 months thereafter 3
• For patients on potassium-sparing diuretics, check every 5-7 days until values stabilize 3

Special Populations

Heart Failure Patients:

• Target serum potassium 4.0-5.0 mEq/L to prevent arrhythmias and sudden death 3
• Potassium levels outside this range show U-shaped correlation with increased mortality 3

Diuretic-Induced Hypokalemia:

• For persistent hypokalemia despite oral supplementation, add potassium-sparing diuretics: spironolactone 25-100 mg daily, amiloride 5-10 mg daily, or triamterene 50-100 mg daily 3
• Check serum potassium and creatinine 5-7 days after initiating potassium-sparing diuretic 3
• Avoid potassium-sparing diuretics when GFR <45 mL/min 3
• Use caution combining with ACE inhibitors or ARBs due to hyperkalemia risk 3

Diabetic Ketoacidosis:

• Include potassium in IV fluids once serum K+ falls below 5.5 mEq/L with adequate urine output 3
• Delay insulin treatment until K+ ≥3.3 mEq/L to avoid arrhythmias or cardiac arrest 2

Medications to Avoid in Severe Hypokalemia

• Digoxin should not be administered until hypokalemia is corrected, as it significantly increases risk of life-threatening arrhythmias 3
• Thiazide and loop diuretics should be questioned until correction achieved 3

Common Pitfalls

• Failing to monitor magnesium levels and correct hypomagnesemia makes potassium repletion ineffective 3
• Too-rapid IV potassium administration (>20 mEq/hour without extreme circumstances) can cause cardiac arrhythmias and arrest 3
• Not discontinuing potassium supplements when initiating aldosterone receptor antagonists leads to hyperkalemia 3
• Waiting too long to recheck potassium after IV administration risks undetected hyperkalemia 3

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HYPOMAGNESEMIA (Serum Mg <1.5 mEq/L)

Causes

Hypomagnesemia develops from inadequate intake, gastrointestinal losses, renal wasting, or medications including proton-pump inhibitors, macrolides, fluoroquinolones, gentamicin, and antiviral drugs. 5 Early symptoms may develop within 3-4 days or weeks of deficiency 7.

Clinical Manifestations

Predominant effects are neurological: muscle irritability, clonic twitching, tremors, and convulsions. 7 Hypocalcemia and hypokalemia frequently follow low serum magnesium 7. Deep tendon reflexes decrease as plasma magnesium rises above 4 mEq/L and disappear approaching 10 mEq/L 7.

ECG Changes in Hypomagnesemia

Hypomagnesemia contributes to QT prolongation and increases risk of torsades de pointes, even when magnesium levels appear normal. 1

Treatment

Magnesium sulfate IV is the primary repletion agent, with onset of anticonvulsant action immediate via IV (lasting ~30 minutes) and within 1 hour via IM (lasting 3-4 hours). 7 Effective anticonvulsant serum levels range from 2.5-7.5 mEq/L 7. Magnesium prevents convulsions by blocking neuromuscular transmission and decreasing acetylcholine release at the motor end-plate. 7

For torsades de pointes, administer magnesium bolus or infusion regardless of baseline magnesium level. 1 Parenteral magnesium therapy repairs plasma deficit and causes deficiency symptoms to cease 7.

Monitoring

Normal plasma magnesium levels range from 1.5-2.5 mEq/L 7. Magnesium is excreted solely by kidneys at a rate proportional to plasma concentration and glomerular filtration 7.

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HYPOPHOSPHATEMIA (Low Serum Phosphate)

Causes

Hypophosphatemia results from decreased intake, increased renal losses, gastrointestinal losses, or transcellular shifts (similar mechanisms to potassium). Refeeding syndrome is a critical cause where rapid carbohydrate administration drives phosphate intracellularly.

Clinical Manifestations

• Muscle weakness and respiratory failure in severe cases
• Rhabdomyolysis with very low levels
• Hemolytic anemia and impaired oxygen delivery
• Neurological symptoms including confusion, seizures, and coma
• Cardiac dysfunction

Treatment

Oral phosphate supplementation for mild cases; IV sodium phosphate or potassium phosphate for severe symptomatic hypophosphatemia with careful monitoring to avoid hyperphosphatemia.

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HYPERKALEMIA (Serum K+ >5.0 mEq/L)

Clinical Manifestations

Muscle weakness, paralysis, and cardiac conduction disturbances are the primary manifestations. 8 Symptoms may not correlate directly with serum levels 8.

ECG Changes in Hyperkalemia

Progressive ECG changes include peaked T waves (earliest sign at 5.5-6.5 mmol/L), flattened or absent P waves, prolonged PR interval, widened QRS complex, deepened S waves, and merging of S and T waves (6.5-7.5 mmol/L). 1 At severely elevated levels (>7.0-8.0 mmol/L), sine-wave pattern, idioventricular rhythms, and progression to asystolic cardiac arrest occur. 1

Treatment

Emergent treatment is required for clinical symptoms (muscle weakness, paralysis) or ECG abnormalities regardless of potassium level. 8, 9

Immediate Management:

1. IV calcium chloride or calcium gluconate to stabilize myocardial cell membrane (onset 1-3 minutes) 1, 3
2. Shift potassium intracellularly: insulin/glucose, sodium bicarbonate, or nebulized albuterol (onset 30-60 minutes) 1, 3
3. Promote excretion: diuresis, potassium binders (patiromer, sodium zirconium cyclosilicate), or dialysis 3, 8

Continuous cardiac monitoring required during treatment. 1 If no effect within 5-10 minutes of calcium administration, repeat dose 3.

Monitoring

For patients on mineralocorticoid receptor antagonists: if K+ >5.5 mmol/L, halve MRA dose; if K+ >6.0 mmol/L, discontinue MRA 3.

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HYPERMAGNESEMIA (Serum Mg >2.5 mEq/L)

Clinical Manifestations

Respiratory paralysis may occur as plasma magnesium approaches 10 mEq/L. 7 Heart block can occur at this or lower levels 7. Serum magnesium concentrations exceeding 12 mEq/L may be fatal. 7 Magnesium produces peripheral vasodilation, causing flushing and sweating at low doses and hypotension at larger doses 7.

ECG Changes in Hypermagnesemia

Hypermagnesemia causes prolonged PR and QRS intervals, prolonged QT interval, and in severe cases, atrioventricular nodal conduction block, bradycardia, and cardiac arrest. 1

Treatment

IV calcium administration antagonizes the central and peripheral effects of magnesium poisoning. 7 Discontinue magnesium sources, promote renal excretion with IV fluids and diuretics, and consider dialysis in severe cases with renal impairment.

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HYPERPHOSPHATEMIA: Long-Term Adverse Effects

Chronic Complications

Chronic hyperphosphatemia leads to vascular calcification, secondary hyperparathyroidism, renal osteodystrophy, and increased cardiovascular mortality. Calcium-phosphate product elevation causes metastatic calcification in soft tissues, blood vessels, heart valves, and joints. This accelerates atherosclerosis and increases risk of cardiovascular events and death, particularly in chronic kidney disease patients. Persistent hyperphosphatemia also suppresses calcitriol production, worsening bone disease and mineral metabolism abnormalities.