Electrolyte Tests
Definition
Electrolytes are positively and negatively charged ions that are found within the cells and extracellular fluids, including blood plasma. A test for electrolytes includes the measurement of sodium, potassium, chloride, and bicarbonate. These ions are needed to assess renal, endocrine, 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.
Purpose
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 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 test because values below 3.0 mmol/L are associated with arrhythmia, tachycardia, and cardiac arrest, and values above 6.0 mmol/L are associated with bradycardia 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 too high a blood pH. 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. 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 hyperfunction) and Addison's disease (adrenocortical insufficiency) drive the sodium and potassium in opposing directions. Chloride levels will follow sodium levels with the exception of acid-base imbalances, in which chloride may move in the opposing direction of bicarbonate. In essence, diagnosis and management of a patient with an electrolyte disturbance is best served by measuring all four electrolytes.
Description
Sodium is the principal extracellular cation and potassium the principal intracellular cation. 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 using the following formula: Osmolality in milliosmoles per killigram water = serum sodium x 2 + Glucose/18 + BUN/2.8 where BUN is the blood urea nitrogen concentration. 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 conditons 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.
Measurement of electrolytes
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. For example, sodium electrodes are made from a special glass formula that selectively binds sodium ions. The inside of the electrode is filled with a fluid containing sodium ions, and the outside of the glass membrane is immersed in the sample. A potential difference develops across the glass membrane that is dependent upon the difference in sodium concentration (activity) on the inside and outside of the glass membrane. 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 sodium in the sample. Ion selective membranes can be made from materials other than glass. For example, the antibiotic valinomycin is used to make potassium-measuring electrodes. Neutral carrier ionophores selective for lithium, calcium, and magnesium are also used for measurement of these substances in laboratory medicine. Ion selective electrodes can be used to measure whole blood, serum, or plasma since they respond to the electrolyte activity in the water phase of the sample only. One important aspect of electrolyte measurement is an artifact (erroneous result) called pseudohyponatremia that may occur when sodium is measured using a diluted blood sample. This happens when the plasma contains excessively high lipids or protein. These solids displace plasma water from the specimen, resulting in a low measurement of sodium that does not occur with an undiluted sample.
Total calcium and magnesium are usually measured by colorimetric procedures called dye binding assays. Calcium is displaced from protein by dilute acid or alkali and reacts with a dye (arsenazo III or cresolphthalein complexone) to form a colored product. When crosolphthalein complexone is used, 8-hydroxyquinoline is added to bind magnesium which also reacts with this dye. Magnesium is commonly measured by its reaction with a dye called Calmagite. A calcium chelator such as EGTA is added to prevent interference from calcium. Both calcium and magnesium may be measured by atomic absorption spectrophotometry. This procedure is more complex than colorimetric methods, but is also more accurate. Phosphorus is measured by reacting it with ammonium molybdate at an acid pH. The rate of ammonium phosphomolybdate formation is measured at 340 nm and is proportional to the inorganic phosphorus concentration (mono-and dihydrogen phosphate) of the sample.
Precautions
Electrolyte tests are performed on heparinized whole blood, heparinized plasma, or serum, usually collected from a vein or capillary. Venipuncture is performed observing universal precautions for the prevention of transmission of bloodborne pathogens. In order to prevent hemoconcentration, the tourniquet must be removed from the arm as soon as the blood starts to flow. The needle gauge must be sufficient in width to prevent mechanical damage to the red blood cells that will result in hemolysis (rupture of the membrane of the red blood cells). Because the concentration of potassium, magnesium, and phosphorus within red blood cells is much higher than in the plasma, hemolysis will cause falsely elevated results for these analytes. Plasma is often preferred over serum for measuring potassium, as the process of blood clotting can release potassium from platelets. Heparin is the only anticoagulant acceptable for electrolyte testing, as all other anticoagulants act by chelating calcium. Samples for ionized calcium should be collected using balanced (low) heparin which has a concentration of 20 U/mL. Higher concentrations bind calcium. Ionized calcium samples should be transported and stored on ice under anaerobic conditions and measured within 30 minutes of sample collection as pH changes in the blood will affect the ionized calcium.
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.
Preparation
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.
Aftercare
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.
Complications
Minor temporary discomfort may occur with any blood test, but there are no complications specific to electrolyte testing.
Results
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.
- Serum or plasma sodium: 135-145 mmol/L Alert levels: less than 120 mmol/L and greater than 160 mmol/L.
- Serum potassium: 3.6-5.4 mmol/L (plasma, 3.6-5.0mmol/L); Alert levels: less than 3.0 mmol/L and greater than 6.0 mmol/L.
- Serum or plasma chloride: 98 - 108 mmol/L.
- Sweat chloride: 4-60 mmol/L.
- Serum or plasma bicarbonate: 18-24 mmol/L (as total carbon dioxide, 22-26 mmol/L); Alert levels: less than 10 mmol/L and greater than 40 mmol/L.
- Serum calcium: 8.5-10.5 mg/dL (2.0-2.5 mmol/L); Alert levels: less than 6.0 mg/dL and greater than 13.0 mg/dL.
- Ionized calcium: 1.0-1.3 mmol/L.
- Serum inorganic phosphorus: 2.3-4.7 mg/dL (children, 4.0 - 7.0 mg/dL); Alert level: less than 1.0 mg/dL.
- Serum magnesium: 1.8-3.0 mg/dL (1.2-2.0 meq/L or0.5-1.0 mmol/L).
- Iionized magnesium: 0.53-0.67 mmol/L.
- Osmolality (calculated) 280-300 mosm/Kg.
Health care team roles
A physician orders electrolyte tests and interprets the results. A nurse or phlebotomist usually collects the blood sample by venipuncture. In some instances the nurse performs the electrolyte test using a point-of-care instrument consisting of a single use cartridge of ionselective electrodes and a battery operated analyzer. In the laboratory setting electrolyte tests are performed by clinical laboratory scientists/medical technologists or clinical laboratory technicians/medical laboratory technicians. Nurses, nurse practitioners, and physician assistants may find themselves involved in explaining results to patients and advising them regarding treatment or dietary correction of any problems identified.
KEY TERMS
Tetany—Inappropriately sustained muscle spasms.
Resources
BOOKS
Fishbach, Frances Talaska. A Manual of Laboratory and Diagnostic Tests, 6th ed. Philadelphia: Lippincott, 2000 pp. 338-355.
Tierney, Lawrence M., Stephen J. McPhee, and Maxine A. Papadakis. Current Medical Diagnosis and Treatment 2001. 40th ed. New York: Lange Medical Books/McGraw-Hill, 2001. pp.869-884.
OTHER
MedLine Plus. "Electrolytes." 2001. <http://www.nlm.nih.gov/medlineplus/ency/article/002350.htm>.
Erika J. Norris
