Tests that measure the concentration of electrolytes are useful in the emergency room and to obtain clues for the diagnosis of specific diseases. Electrolyte tests are used for diagnosing dietary deficiencies, excess loss of nutrients due to urination, vomiting, and diarrhea, or abnormal shifts in the location of an electrolyte within the body. When an abnormal electrolyte value is detected, the physician may either act to immediately correct the imbalance directly (in the case of an emergency) or run further tests to determine the underlying cause of the abnormal electrolyte value. Electrolyte disturbances can occur with malfunctioning of the kidney (renal failure), infections that produce severe and continual diarrhea or vomiting, drugs that cause loss of electrolytes in the urine (diuretics), poisoning due to accidental consumption of electrolytes, or diseases involving hormones that regulate electrolyte concentrations.

Electrolyte tests are performed from routine blood tests. The techniques are simple, automated, and fairly uniform throughout the United States. During the preparation of blood plasma or serum, health workers must take care not to break the red blood cells, especially when testing for serum potassium. Because the concentration of potassium within red blood cells is much higher than in the surrounding plasma or serum, broken cells would cause falsely elevated potassium levels.

Electrolyte tests are typically conducted on blood plasma or serum, urine, and diarrheal fluids. Electrolytes can be classified in at least five different ways. One way is that some electrolytes tend to exist mostly inside cells, or are intracellular, while others tend to be outside cells, or are extracellular. Potassium, phosphate, and magnesium occur at much greater levels inside the cell than outside, while sodium and chloride occur at much greater levels extracellularly. A second classification distinguishes those electrolytes that participate directly in the transmission of nerve impulses and those that do not. Sodium, potassium, and calcium are the important electrolytes involved in nerve impulses, and disorders affecting them are most closely associated with neurological disorders. A third classification focuses on electrolytes that are able to form a tight union, or complex, with one another. Calcium and phosphate have the greatest tendency to form complexes with each other. Disorders that cause an increase in either plasma calcium or phosphate can result in the deposit of calcium-phosphate crystals in the soft tissues of the body. A fourth classification concerns those electrolytes that influence the acidity or alkalinity of the bloodstream, also known as the pH. The pH of the bloodstream is normally in the range of 7.35–7.45. A decrease below this range is called acidosis, while a pH above this range is called alkalosis. The electrolytes most closely associated with the pH of the bloodstream are bicarbonate, chloride, and phosphate.

All electrolyte tests can be performed on plasma or serum. Plasma is prepared by withdrawing a blood sample and placing it in a test tube containing a chemical that prevents blood from clotting (an anticoagulant). Serum is prepared by withdrawing a blood sample, placing it in a test tube, and allowing it to clot. The blood spontaneously clots within a minute of withdrawing the blood from a vein. The serum or plasma is then rapidly spun with a centrifuge in order to remove the blood cells or clot.

Electrolyte concentrations are similar whether measured in serum or plasma. Values can be expressed in terms of weight per unit volume (mg/deciliter; mg/dL) or in the number of molecules in a volume, or molarity (moles or millimoles/liter; M or mM). The range of normal values sometimes varies slightly between different age groups, for males and females, and between different analytical laboratories.

The normal level of serum sodium is in the range of 136–145 mM. The normal levels of serum potassium are 3.5–5.0 mM. Note that sodium occurs at a much higher concentration than potassium. The normal concentration of total serum calcium (bound calcium plus free calcium) is in the range of 8.8–10.4 mg/dL. About 40% of the total calcium in the plasma is loosely bound to proteins; this calcium is referred to as bound calcium. The normal range of free calcium is 4.8–5.2 mg/dL. The normal concentration of serum magnesium is in the range of 2.0–3.0 mg/dL.

The normal concentration range of chloride is 350–375 mg/dL or 98–106 mM. The normal level of phosphate, as expressed as the concentration of phosphorus, is 2.0–4.3 mg/dL. Bicarbonate is an electrolyte that is freely and spontaneously interconvertable with carbonic acid and carbon dioxide. The normal concentration of carbonic acid (H2CO3) is about 1.35 mM. The normal concentration of bicarbonate (HCO3−) is about 27 mM. The concentration of total carbon dioxide is the sum of carbonic acid and bicarbonate; this sum is normally in the range of 26–28 mM. The ratio of bicarbonate/carbonic acid is more significant than the actual concentrations of these two forms of carbon dioxide. Its normal value is 27/1.35 (equivalent to 20/1).

High serum sodium levels (hypernatremia) occur at sodium concentrations over 145 mM, with severe hypernatremia over 152 mM. Hypernatremia is usually caused by diseases that cause excessive urination. In these cases, water is lost, but sodium is still retained in the body. The symptoms include confusion and can lead to convulsions and coma. Low serum sodium levels (hyponatremia) are below 130 mM, with severe hyponatremia at or below 125 mM. Hyponatremia often occurs with severe diarrhea, with losses of both water and sodium, but with sodium loss exceeding water loss. Hyponatremia provokes clinical problems only if serum sodium falls below 125 mM, especially if this has occurred rapidly. The symptoms can be as mild as tiredness but may lead to convulsions and coma.

High serum potassium (hyperkalemia) occurs at potassium levels above 5.0 mM; it is considered severe over 8.0 mM. Hyperkalemia is relatively uncommon, but sometimes occurs in patients with kidney failure who take potassium supplements. Hyperkalemia can result in abnormal beating of the heart (cardiac arrhythmias). Low serum potassium (hypokalemia) occurs when serum potassium falls below 3.0 mM. It can result from low dietary potassium, as during starvation or in patients with anorexia nervosa; from excessive losses via the kidneys, as caused by diuretic drugs; or by diseases of the adrenal or pituitary glands. Mild hypokalemia causes muscle weakness, while severe hypokalemia can cause paralysis, the inability to breathe, and cardiac arrhythmias.

High levels of calcium ions (hypercalcemia) occur at free calcium ion concentrations over 5.2 mg/dL or total serum calcium above 10.4 mg/dL. Hypercalcemia usually occurs when the body dissolves bone at an abnormally fast rate, increasing both serum calcium and serum phosphate. Sudden hypercalcemia can cause vomiting and coma, while prolonged and moderate hypercalcemia results in the deposit of calcium phosphate crystals in the kidneys and eye. Hypocalcemia occurs when serum free calcium ions fall below 4.4 mg/dL, or when total serum calcium falls below 8.8 mg/dL. Hypocalcemia can result from hypoparathyroidism (low parathyroid hormone), from failure to produce 1,25-dihydroxyvitamin D, from low levels of plasma magnesium, and from phosphate poisoning (the phosphate enters the bloodstream and forms a complex with the free serum calcium). Hypocalcemia can cause depression and muscle spasms.

Hypermagnesemia occurs at serum magnesium levels over 25 mM (60 mg/dL). Hypermagnesemia is rare but can occur with the excessive consumption of magnesium salts. Hypomagnesemia occurs when serum magnesium levels fall below 0.8 mM, and can result from poor nutrition. Chronic alcoholism is the most common cause of hypomagnesemia, in part because of poor diet. Magnesium levels below 0.5 mM (1.2 mg/dL) cause serum calcium levels to decline. Some of the symptoms of hypomagnesemia, including twitching and convulsions, actually result from the concurrent hypocalcemia. Hypomagnesemia can also result in hypokalemia and thereby cause cardiac arrhythmias.

Serum chloride levels sometimes increase to abnormal levels as an undesirable side effect of medical treatment with sodium chloride or ammonium chloride. The toxicity of chloride results not from the chloride itself, but from the fact that the chloride occurs as the acid, hydrogen chloride (more commonly known as hydrochloric acid, or HCl). An overdose of chloride may cause the accumulation of hydrochloric acid in the bloodstream, with consequent acidosis. Renal tubular acidosis, one of many kidney diseases, involves the failure to release acid into the urine. The acidosis produces weakness, headache, nausea, and cardiac arrest. Low plasma chloride leads to the opposite situation: a decline in the acid content of the bloodstream. This is known as alkalization of the bloodstream, or alkalosis. Hydrochloric acid, originally from extracellular fluids, can be lost by vomiting. At its most severe, alkalosis results in paralysis (tetany).

Hyperphosphatemia occurs at serum phosphate levels above 5 mg/dL. It can result from the failure of the kidneys to excrete phosphate into the urine, causing phosphate to accumulate in the bloodstream. Hyperphosphatemia can also be caused by the impaired action of parathyroid hormone and by phosphate poisoning. Severe hyperphosphatemia can cause paralysis, convulsions, and cardiac arrest. These symptoms result because the phosphate, occurring in elevated levels, complexes with free serum calcium, resulting in hypocalcemia. Tests for heart function (an electrocardiogram) and parathyroid hormone levels are used in the diagnosis of hyperphosphatemia. Hypophosphatemia occurs if serum phosphorus falls to 2.0 mg/dL or lower. It often results from a shift of inorganic phosphate from the bloodstream to various organs and tissues. This shift can be caused by a rise in pH (alkalization) of the bloodstream, which can occur during hyperventilation, a reaction in various disease states. A shift in phosphate to intracellular tissues may draw calcium away from the bloodstream via the formation of insoluble calcium phosphate crystals within cells, with consequent hypocalcemia. Thus, tests for abnormalities in phosphate metabolism also involve tests for serum calcium.

Bicarbonate metabolism involves several compounds. When dietary starches, sugars, and fats are broken down for energy production, carbon dioxide is created. Much of this carbon dioxide (CO2) spontaneously converts to carbonic acid (H2CO3), and some of the carbonic acid spontaneously converts to bicarbonate (HCO3−) plus a hydrogen ion (H+). Eventually, almost every molecule of carbon dioxide produced in the body, whether in the form of carbon dioxide, carbonic acid, or bicarbonate, must convert back to carbon dioxide in order to leave via the lungs during normal breathing.

If one holds one's breath, carbon dioxide cannot escape from the lungs, but continues to be generated within the body. This results in an increase in production of carbonic acid. A portion of the carbonic acid breaks apart (dissociates), causing an increase in hydrogen ions in the plasma, with a resulting acidosis. Tests for serum bicarbonate levels are accompanied by tests for acidosis (pH test). Conversely, when one breathes too rapidly (hyperventilation), the carbon dioxide is drawn off from the bloodstream and expelled in the breath at an increased rate. This results in an increase in the rate of combination of bicarbonate with hydrogen ions, resulting in alkalosis. Acidosis and alkalosis can be produced by means other than by altering the rate of breathing. The carbonic acid and bicarbonate in the bloodstream minimize (or buffer) any trend to acidosis or alkalosis. Tests for bicarbonate are generally accompanied by tests for blood pH and possibly tests for kidney malfunction, abnormal hormone function, or gastrointestinal disorders.