Hypokalemia refers to a pathological condition in which serum potassium levels are less than 3.5 mmol/L. The primary cause of hypokalemia is potassium depletion, a condition characterized by a loss of total body potassium. However, in clinical practice, serum potassium levels may also drop due to dilution or intracellular potassium shifts, even if total body potassium is not deficient. Conversely, potassium deficiency may still occur with normal or elevated serum potassium levels under certain circumstances, such as hemoconcentration or extracellular potassium shifts.
Etiology, Classification, and Pathogenesis
Potassium-Deficient Hypokalemia
This type of hypokalemia is characterized by reduced total body potassium, intracellular potassium levels, and serum potassium concentration.
Insufficient Potassium Intake
Examples include prolonged fasting, selective eating habits, or anorexia where daily potassium intake is less than 3 g for more than two weeks.
Excessive Potassium Loss
The primary routes of potassium loss are through the gastrointestinal tract or kidneys.
Gastrointestinal Potassium Loss
Potassium loss through digestive fluid is observed in conditions such as chronic and significant vomiting (e.g., caused by pyloric obstruction), diarrhea (e.g., vasoactive intestinal peptide tumors, laxative abuse, cholera), or after gastrointestinal, biliary, or ileostomy drainage.
Renal Potassium Loss
Examples include:
- Renal Diseases: Conditions such as the diuretic phase of acute renal failure, renal tubular acidosis, hypokalemic nephropathy, diuresis after relieving urinary obstruction, or Liddle syndrome.
- Endocrine Disorders: Such as primary or secondary hyperaldosteronism, Cushing’s syndrome, ectopic ACTH syndrome, and others.
- Diuretics: Potassium-wasting diuretics such as furosemide, ethacrynic acid, bumetanide, hydrochlorothiazide, metolazone, and acetazolamide, or osmotic diuretics such as mannitol, sorbitol, or hypertonic glucose solutions.
- Excessive Sodium Supplementation: This can enhance sodium-potassium exchange in renal tubules, leading to increased potassium excretion.
- Alkalosis or the recovery phase of acidosis.
- Certain Antibiotics: Examples include penicillin, gentamicin, carbenicillin, and polymyxin B.
Other Causes of Potassium Loss
Factors include extensive burns, abdominal paracentesis, peritoneal drainage, dialysis, or long-term exposure to high-temperature environments.
Translocation Hypokalemia
This type of hypokalemia results from the shift of extracellular potassium into cells. Total body potassium levels remain normal, intracellular potassium levels increase, and serum potassium concentration decreases. Examples include:
- Metabolic or Respiratory Alkalosis, or the Recovery Phase of Acidosis: In general, for every 0.1 increase in blood pH, serum potassium decreases by approximately 0.7 mmol/L.
- Administration of Large Quantities of Glucose Solution: Particularly in combination with insulin therapy.
- Periodic Paralysis: Such as familial hypokalemic periodic paralysis or paralysis associated with Graves' disease.
- Acute Stress: Leads to increased adrenaline secretion, which promotes potassium influx into cells.
- Poisoning: Resulting from substances like gossypol or barium chloride.
- Treatment for Anemia: Using folic acid or vitamin B12.
- Repeated Transfusions of Refrigerated and Washed Red Blood Cells: Stored red blood cells can lose up to 50% of their potassium during storage, which, upon entering the body, rapidly redistributes to intracellular compartments.
- Hypothermia Therapy: Causes potassium to shift into cells.
Dilutional Hypokalemia
This occurs during extracellular fluid retention, where serum potassium concentration is relatively decreased despite normal total body potassium and intracellular potassium levels. Situations include water overload, water intoxication, or rapid and excessive intravenous fluids without timely potassium supplementation.
Clinical Manifestations
The clinical features of hypokalemia depend on the speed, severity, and extent of abnormalities in potassium concentration inside and outside the cells. Chronic, mild hypokalemia may present with few or no symptoms, while symptoms in acute, severe cases can be pronounced and even life-threatening.
Potassium-Deficient Hypokalemia
Skeletal Muscle Manifestations
When serum potassium levels drop below 3.0 mmol/L, patients may experience fatigue, weakness, and lack of energy. Levels below 2.5 mmol/L often lead to generalized muscle weakness, flaccid paralysis of the limbs, and diminished or absent tendon reflexes. Severe cases may result in paralysis of the diaphragm or respiratory muscles, causing respiratory difficulties, swallowing impairment, or even suffocation. Sensory disturbances, such as numbness and pain, may occur. In prolonged cases, complications such as muscle fiber dissolution, necrosis, atrophy, or neural degeneration can develop.
Digestive System Manifestations
Symptoms include nausea, vomiting, anorexia, abdominal distension, constipation, and reduced or absent intestinal peristalsis. In severe cases, intestinal paralysis and submucosal edema may occur.
Central Nervous System Manifestations
Symptoms such as lethargy, slow responses, disorientation, drowsiness, or even coma may develop.
Circulatory System Manifestations
Enhanced myocardial excitability and tachycardia are observed in the early stages. Atrial or ventricular premature beats may occur. Severe hypokalemia may manifest as hypokalemic cardiomyopathy, myocardial necrosis, or fibrosis.
Electrocardiogram (ECG)
When serum potassium levels fall to 3.5 mmol/L, T waves become wide and flattened, QT interval prolongs, and U waves appear. In severe cases, T waves invert, the ST segment shows depression, and multifocal premature beats or ventricular tachycardia may occur. Extremely severe cases can result in ventricular flutter, ventricular fibrillation, cardiac arrest, or shock leading to sudden death.
Urinary System Manifestations
Long-term or severe potassium loss can lead to degeneration and necrosis of renal tubular epithelial cells, resulting in reduced urine-concentrating ability, excessive thirst and drinking, and increased nighttime urination. Potassium-depletion nephropathy may develop, presenting with proteinuria and cylinder-shaped urinary sediments.
Acid-Base Imbalance
During potassium deficiency, intracellular potassium is depleted, allowing extracellular sodium (Na+) and hydrogen ions (H+) to move into cells. In renal distal tubules, potassium-sodium exchange is reduced, while hydrogen-sodium exchange increases, leading to metabolic alkalosis, intracellular acidosis, and paradoxical acidic urine.
Translocation Hypokalemia
Also referred to as periodic paralysis, this condition often begins suddenly during the early hours of the morning or nighttime. The primary signs include episodic flaccid paralysis or limb weakness, typically involving the lower limbs more prominently, though in some cases, the upper limbs may also be affected. Severe cases may extend to areas above the neck or even involve the diaphragm. Symptoms peak within 1–2 hours and generally last for several hours, but in rare cases, episodes can persist for several days.
Dilutional Hypokalemia
This condition is most commonly associated with water overload or water intoxication.
Diagnosis
Diagnosis is generally based on the patient’s medical history and serum potassium measurements. Recurrent episodes of periodic paralysis serve as a key feature of translocation hypokalemia, while other types of hypokalemia lack specific symptoms or signs. Diagnostic contributions include characteristic ECG findings, such as low T waves, QT interval prolongation, and the presence of U waves.
Differential diagnosis should focus on distinguishing between renal (typically with urinary potassium levels greater than 20 mmol/L) and extrarenal potassium losses. Investigations for potential underlying causes, including plasma renin activity and aldosterone levels, may be necessary. In general, serum potassium levels provide a rough estimate of the degree of potassium deficit in potassium-deficient hypokalemia. A serum potassium level below 3.5 mmol/L suggests potassium loss exceeding 10% of the total potassium stores.
Prevention and Treatment
Management involves actively treating the underlying disease and providing potassium-rich foods. For patients with potassium-deficient hypokalemia, addressing the primary condition and supplementing potassium promptly are necessary.
In cases where hypovolemia, peripheral circulatory failure, or shock lead to renal dysfunction, potassium supplementation should generally wait until sufficient blood volume is restored and urinary output reaches 30–40 ml/h. Observation should continue for six hours after this baseline is achieved. When daily urine output exceeds 500 ml, potassium supplementation can be administered.
Potassium Supplementation Doses
The required potassium dose may be estimated as follows:
- Mild Potassium Deficiency: When serum potassium levels are between 3.0–3.5 mmol/L, approximately 100 mmol of potassium (equivalent to 8 g of potassium chloride) can be supplemented.
- Moderate Potassium Deficiency: When serum potassium levels are between 2.5–3.0 mmol/L, approximately 300 mmol of potassium (equivalent to 24 g of potassium chloride) can be supplemented.
- Severe Potassium Deficiency: When serum potassium levels are between 2.0–2.5 mmol/L, approximately 500 mmol of potassium (equivalent to 40 g of potassium chloride) can be supplemented.
In general, the daily potassium supplementation should not exceed 200 mmol (equivalent to 15 g of potassium chloride).
Types of Potassium Supplementation
Dietary Potassium Supplementation
Foods high in potassium include meat, vegetables, fruits, and legumes, containing approximately 0.2–0.4 g of potassium per 100 g. Grains, such as rice and flour, contain 0.09–0.14 g of potassium per 100 g, while eggs contain about 0.06–0.09 g of potassium per 100 g.
Pharmacological Potassium Supplementation
Potassium chloride contains approximately 13–14 mmol of potassium per gram and is the most commonly used source of potassium.
Potassium citrate contains approximately 9 mmol of potassium per gram and is suitable for patients with hyperchloremia (e.g., renal tubular acidosis).
Potassium acetate contains approximately 10 mmol of potassium per gram and is also suitable for patients with hyperchloremia.
Potassium glutamate contains approximately 4.5 mmol of potassium per gram and is appropriate for patients with hepatic failure combined with hypokalemia.
Potassium-Magnesium aspartate solution contains 3.0 mmol of potassium and 3.5 mmol of magnesium per 10 ml and is effective in promoting potassium entry into cells.
Methods of Potassium Supplementation
Administration Routes
In mild cases, potassium-rich foods may be given. For oral supplementation, potassium chloride is the preferred choice. To minimize gastrointestinal side effects, a 10% potassium chloride solution can be diluted in juice or milk and consumed after meals, or sustained-release potassium chloride tablets can be used. Alternatives include a 10% potassium citrate solution or nasogastric potassium supplementation. In severe cases, intravenous potassium supplementation is required.
Infusion Rate
The usual intravenous infusion rate for potassium is 20–40 mmol/h but should not exceed 50–60 mmol/h.
Infusion Concentration
For conventional intravenous potassium supplementation, a solution containing 20–40 mmol/L of potassium or 1.5–3.0 g/L of potassium chloride is generally used. For severe hypokalemia cases where fluid intake must be restricted or oral potassium supplementation is not possible, deep venous access and a precise micro-infusion pump may be required for controlled administration.
Precautions
Renal function and urine output should be monitored during potassium supplementation. Potassium supplementation is considered safe when daily urine output exceeds 500 ml or hourly output exceeds 30 ml.
For hypokalemic patients, potassium chloride should be administered intravenously in normal saline. For those whose serum potassium has returned to normal, potassium chloride may instead be administered in glucose solutions to prevent hyperkalemia and correct potassium deficiency. If serum potassium remains normal 24 hours after stopping intravenous potassium, oral potassium supplementation can be initiated.
Patients receiving higher concentrations of intravenous potassium solution should undergo continuous cardiac monitoring, with serum potassium levels measured hourly to avoid severe hyperkalemia or cardiac arrest.
Potassium uptake by cells is relatively slow, with intracellular and extracellular potassium equilibrium taking approximately 15 hours or more. Close monitoring is essential during and after infusion to prevent transient hyperkalemia.
Refractory hypokalemia may require correction of associated alkalosis and hypomagnesemia.
Potassium supplementation may exacerbate pre-existing hypocalcemia, leading to tetany. Calcium supplementation should be provided if this occurs.
Long-term use of potassium chloride enteric-coated tablets should be avoided to prevent complications such as intestinal narrowing, bleeding, or obstruction due to localized high potassium concentrations.