PARATHYROID GLANDS

Parathyroid anatomy and physiology and its pathologic states are discussed thoroughly in Chapter 115. The following discussion highlights the role of PTH in the regulation of calcium metabolism.

Calcium Metabolism

Calcium homeostasis depends on the release of PTH and on small amounts of vitamin D and calcitonin. The function of the parathyroid glands is to maintain calcium and phosphorus homeostasis. Calcium is important for the formation of intercellular ground substance, teeth, and bone. At the membrane level, it affects neuromuscular irritability, muscular contractility, and cardiac rhythmicity. Lack of extracellular calcium causes tetany and death if not corrected.

PTH is a peptide of 84 amino acids with an active amino-terminal end and an inactive carboxy-terminal end. Its secretion by the parathyroid glands is enhanced by a low ionized serum calcium and a high phosphate level.

Calcitonin, a peptide of 32 amino acids, is produced by the parafollicular C cells of the thyroid and contributes to calcium homeostasis by suppressing osteoclastic activity in bone and decreasing the amount of calcium available to the extracellular space. Calcium circulates in the extracellular compartment in three forms: 47% is ionized and is the free and active form that is readily used; 47% is bound to albumin and globulin and fluctuates with the serum protein level; and 6% is bound to anions such as bicarbonate, phosphate, and citrate.

Calcium is pumped from the extracellular compartment into the intracellular space. When serum calcium falls, the parathyroids release PTH, which increases osteoclastic activity, causing resorption of bone and release of calcium; increases resorption of calcium at the renal tubular cell; increases absorption of calcium from the gastrointestinal tract; stimulates renal-1-hydroxylase, which allows 1-hydroxylation of vitamin D in the kidney; and increases excretion of phosphorus in the urine, decreasing the serum phosphorus level.

Vitamin D is produced from exposure to sunlight or is obtained from the diet. Dietary calcium is provided by dairy products, green vegetables, nuts, fish, and calcium supplements. Approximately 1 g of calcium is ingested each day, and most of this is absorbed in the duodenum and upper jejunum. 1,25-Dihydroxyvitamin D increases the uptake of calcium at the brush border of the intestine by increasing cellular ATP and alkaline phosphatase content. At the other end of the cell, calcium is extruded into the extracellular fluid in exchange for sodium. The inactive vitamin D is transported by carrier protein to the liver, where it is 25-hydroxylated. It is then transported to the kidney, where 1-hydroxylation takes place, and it becomes activated to perform its function in maintaining calcium homeostasis by increasing calcium absorption and increasing calcium release from bone by osteoclastic activity.