Which of the following statement(s) is/are true concerning abnormalities in calcium concentration?

b. About 45% of total plasma calcium is in the ionized state and is responsible for most physiologic actions

c. Changes in plasma protein levels or pH can alter the proportion of calcium in the ionized state

d. Intravenous normal saline administration is the first step in treatment of hypercalcemia

e. Classic signs of hypocalcemia include hyperactive deep tendon refluxes, Cvostek’s sign and Trousseau’s sign

Calcium is a divalent cation found in abundance in the human body. About 99% of total body calcium is located in bone in the form of hydroxyapatite crystals. Calcium homeostasis depends on the exchange of calcium between bone and extracellular fluid, renal excretion, and intestinal absorption. These three processes are controlled to a great extent by parathyroid hormone. In extracellular fluid, calcium exists in three forms: ionized calcium, non-ionized calcium, and protein-bound calcium. Ionized calcium, which comprises about 45% of total calcium is responsible for most physiologic actions of calcium in the body, and its level is tightly controlled by a regulatory mechanisms. Some nonionized calcium is complexed with non-protein anions, including phosphate and citrate, and does not easily disassociate. These molecular forms make up only about 15% of total calcium present in plasma. About 40% of extracellular nonionized calcium is bound to proteins, with most being bound to albumin. Changes in either plasma protein levels or pH can alter the proportion of calcium in the ionized state. The most common cause of hypercalcemia is primary hyperparathyroidism. Hypercalcemia can also occur secondary to malignant disease, caused either by a metastasis to bone or by autonomous tumor secretion of hormone-like substances that alter calcium homeostasis. Neuromuscular effects may be the earliest manifestations and include muscle fatigue, weakness, personality disorders, psychosis, confusion, and coma. Elevation of total serum calcium concentrations to greater than 14mg/dL requires prompt treatment to prevent any serious and potentially lethal complications. Immediate measures are directed toward maximizing renal excretion of calcium. Vigorous hydration with 0.9% saline solution to prompt diuresis should be the initial step in treatment. The addition of potassium to the resuscitation fluid as well as the use of furosemide can also be used for treatment. Serum calcium levels below 8 mg/dL may be associated with symptoms and signs that are primary manifestations of neuromuscular abnormalities. These include muscle cramps, perioral tingling, parastesias, laryngeal stridor, tetany, seizures and psychotic behavior. Classic signs of hypocalcemia include hyperactive, deep tendon reflexes, Cvostek’s sign, and Trousseau’s sign. Symptomatic hypocalcemia is best treated with intravenous infusion of calcium in the form of calcium gluconate or calcium chloride.