Electrolytes are positively and negatively charged molecules called ions, that are found within the body's cells and extracellular fluids, including blood plasma. A test for electrolytes includes the measurement of sodium, potassium, chloride, and bicarbonate. These ions are measured to assess renal (kidney), endocrine (glandular), and acid-base function, and are components of both renal function and comprehensive metabolic biochemistry profiles. Other important electrolytes routinely measured in serum or plasma include calcium and phosphorus. These are measured together because they are both affected by bone and parathyroid diseases, and often move in opposing directions. Magnesium is another electrolyte that is routinely measured. Like calcium, it will cause tetany (uncontrolled muscle contractions) when levels are too low in the extracellular fluids.
Tests that measure the concentration of electrolytes are needed for both the diagnosis and management of renal, endocrine, acid-base, water balance, and many other conditions. Their importance lies in part with the serious consequences that follow from the relatively small changes that diseases or abnormal conditions may cause. For example, the reference range for potassium is 3.6-5.0 mmol/l. Potassium is often a STAT (needed immediately) test because values below 3.0 mmol/l are associated with arrhythmia (irregular heartbeat), tachycardia (rapid heartbeat), and cardiac arrest, and values above 6.0 mmol/L are associated with bradycardia (slow heartbeat) and heart failure. Abnormal potassium cannot be treated without reference to bicarbonate, which is a measure of the buffering capacity of the plasma. Sodium bicarbonate and dissolved carbon dioxide act together to resist changes in blood pH. For example, an increased plasma bicarbonate indicates a condition called metabolic alkalosis, which results in blood pH that is too high. This may cause hydrogen ions to shift from the cells into the extracellular fluid in exchange for potassium. As potassium moves into the cells, the plasma concentration falls. The low plasma potassium, called hypokalemia, should not be treated by administration of potassium, but by identifying and eliminating the cause of the alkalosis. Administration of potassium would result in hyperkalemia when the acid-base disturbance is corrected. Sodium measurements are very useful in differentiating the cause of an abnormal potassium result. Conditions such as the overuse of diuretics (drugs that promote lower blood pressure) often result in low levels of both sodium and potassium. On the other hand, Cushing's disease (adrenocortical over-activity) and Addison's disease (adrenocortical under-activity) drive the sodium and potassium in opposing directions. Chloride levels will follow sodium levels except in the case of acid-base imbalances, in which chloride may move in the opposing direction of bicarbonate. In short, diagnosis and management of a patient with an electrolyte disturbance is best served by measuring all four electrolytes.
Sodium is the principal extracellular cation and potassium the principal intracellular cation. A cation is an ion with a positive charge. An anion is an ion with a negative charge. Sodium levels are directly related to the osmotic pressure of the plasma. In fact, since an anion is always associated with sodium (usually chloride or bicarbonate), the plasma osmolality (total dissolved solute concentration) can be estimated. Since water will often follow sodium by diffusion, loss of sodium leads to dehydration and retention of sodium leads to edema. Conditions that promote increased sodium, called hypernatremia, do so without promoting an equivalent gain in water. Such conditions include diabetes insipidus (water loss by the kidneys), Cushing's disease, and hyperaldosteronism (increased sodium reabsorption). Many other conditions, such as congestive heart failure, cirrhosis of the liver, and renal disease result in renal retention of sodium, but an equivalent amount of water is retained as well. This results in a condition called total body sodium excess, which causes hypertension and edema, but not an elevated serum sodium concentration. Low serum sodium, called hyponatremia, may result from Addison's disease, excessive diuretic therapy, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), burns, diarrhea, vomiting, and cystic fibrosis. In fact, the diagnosis of cystic fibrosis is made by demonstrating an elevated chloride concentration (greater than 60 mmol/l) in sweat.
Potassium is the electrolyte used as a hallmark sign of renal failure. Like sodium, potassium is freely filtered by the kidney. However, in the distal tubule sodium is reabsorbed and potassium is secreted. In renal failure, the combination of decreased filtration and decreased secretion combine to cause increased plasma potassium. Hyperkalemia is the most significant and life-threatening complication of renal failure. Hyperkalemia is also commonly caused by hemolytic anemia (release from hemolysed red blood cells), diabetes insipidus, Addison's disease, and digitalis toxicity. Frequent causes of low serum potassium include alkalosis, diarrhea and vomiting, excessive use of thiazide diuretics, Cushing's disease, intravenous fluid administration, and SIADH.
Calcium and phosphorus are measured together because they are both likely to be abnormal in bone and parathyroid disease states. Parathyroid hormone causes resorption of these minerals from bone. However, it promotes intestinal absorption and renal reabsorption of calcium and renal excretion of phosphorus. In hyperparathyroidism, serum calcium will be increased and phosphorus will be decreased. In hypoparathyroidism and renal disease, serum calcium will be low but phosphorus will be high. In vitamin D dependent rickets (VDDR), both calcium and phosphorus will be low; however, calcium is normal while phosphorus is low in vitamin D resistant rickets (VDRR). Differential diagnosis of an abnormal serum calcium is aided by the measurement of ionized calcium (i.e., calcium not bound by protein). Approximately 45% of the calcium in blood is bound to protein, 45% is ionized, and 10% is complexed to anions in the form of undissociated salts. Only the ionized calcium is physiologically active, and the level of ionized calcium is regulated by parathyroid hormone (PTH) via negative feedback (high ionized calcium inhibits secretion of PTH). While hypoparathyroidism, VDDR, renal failure, hypoalbuminemia, hypovitaminosis D, and other conditions may cause low total calcium, only hypoparathyroidism (and alkalosis) will result in low ionized calcium. Conversely, while hyperparathyroidism, malignancies (those that secrete parathyroid hormone-related protein), multiple myeloma, antacids, hyperproteinemia, dehydration, and hypervitaminosis D cause an elevated total calcium, only hyperparathyroidism, malignancy, and acidosis cause an elevated ionized calcium.
Serum magnesium levels may be increased by hemolytic anemia, renal failure, Addison's disease, hyperparathyroidism, and magnesium-based antacids. Chronic alcoholism is the most common cause of a low serum magnesium owing to poor nutrition. Serum magnesium is also decreased in diarrhea, hypoparathyroidism, pancreatitis, Cushing's disease, and with excessive diuretic use. Low magnesium can be caused by a number of antibiotics and other drugs and by administration of intravenous solutions. Magnesium is needed for secretion of parathyroid hormone, and therefore, a low serum magnesium can induce hypocalcemia. Magnesium deficiency is very common in regions where the water supply does not contain sufficient magnesium salts. Magnesium acts as a calcium channel blocker, and when cellular magnesium is low, high intracellular calcium results. This leads to hypertension, tachycardia, and tetany. Unfortunately serum total magnesium levels do not correlate well with intracellular magnesium levels, and serum measurement is not very sensitive for detecting chronic deficiency because of compensatory contributions from bone. Ionized magnesium levels are better correlated with intracellular levels because the ionized form can move freely between the cells and extracellular fluids.
Electrolytes are measured by a process known as potentiometry. This method measures the voltage that develops between the inner and outer surfaces of an ion selective electrode. The electrode (membrane) is made of a material that is selectively permeable to the ion being measured. This potential is measured by comparing it to the potential of a reference electrode. Since the potential of the reference electrode is held constant, the difference in voltage between the two electrodes is attributed to the concentration of ion in the sample.
Electrolyte tests are performed on whole blood, plasma, or serum, usually collected from a vein or capillary.
Special procedures are followed when collecting a sweat sample for electrolyte analysis. This procedure, called pilocarpine iontophoresis, uses electric current applied to the arm of the patient (usually an infant) in order to convey the pilocarpine to the sweat glands where it will stimulate sweating. Care must be taken to ensure that the collection device (macroduct tubing or gauze) does not become contaminated and that the patient's parent or guardian understands the need for the electrical equipment employed.
Usually no special preparation is necessary by the patient. Samples for calcium and phosphorus and for magnesium should be collected following an eight-hour fast.
Discomfort or bruising may occur at the puncture site, or the person may feel dizzy or faint. Pressure to the puncture site until the bleeding stops reduces bruising. Applying warm packs to the puncture site relieves discomfort.
Minor temporary discomfort may occur with any blood test, but there are no complications specific to electrolyte testing.
Electrolyte concentrations are similar whether measured in serum or plasma. Values are expressed as mmol/L for sodium, potassium, chloride, and bicarbonate. Magnesium results are often reported as milliequivalents per liter (meq/L) or in mg/dL. Total calcium is usually reported in mg/dL and ionized calcium in mmol/L. Since severe electrolyte disturbances can be associated with life-threatening consequences such as heart failure, shock, coma, or tetany, alert values are used to warn physicians of impending crisis. Typical reference ranges and alert values are cited below:
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MedLine Plus. "Electrolytes." October 18, 2001 [cited April 4, 2003]. http://www.nlm.nih.gov/medlineplus/ency/article/002350.htm .
National Institutes of Health. [cited April 5, 2003]. http://www.nlm.nih.gov/medlineplus/encyclopedia.html .
Erika J. Norris Mark A. Best, M.D.