Mineral group

Calcium
(total and ionized)


Calcium-phosphate homeostasis involves interrelated actions of parathyroid hormone (PTH), vitamin D metabolites, and calcitonin on kidneys, bone, and intestines.

Parathyroid hormone

PTH is secreted by chief cells of the parathyroid gland and results in increased calcium and decreased phosphate in serum. Secretion is stimulated by decreased ionized calcium, decreased calcitriol, magnesium, dopamine, PGE2. Secretion is inhibited by increased ionized calcium and increased calcitriol.
Parathyroid hormone has 2 primary sites of action, the kidney and the bone. In the kidney, PTH enhances renal resorption of calcium in the distal tubules, collecting ducts and ascending limb of the loop of Henle and promotes excretion of phosphate in the proximal renal tubules. It also activates alpha1-hydroxylase in the kidney, which converts vitamin D to its active form, 1,25 (OH)2D. Parathyroid hormone acts on osteoblasts in bone, stimulating secretion of osteoclastogenic cytokines, IL-6, IL-11 and PGE2. These cytokines stimulate osteoclast formation and release of peptidases which lyse bone matrix (osteolysis), the end result being the release of calcium from bone stores.
Parathyroid hormone can be measured by immunoassay. Assays for detection of the intact molecule or amino-terminal end should be used, as assays for detection of the carboxy-terminal end of PTH are falsely elevated with decreased GFR. Interpretation of PTH levels should be done concurrently with knowledge of ionized calcium values, e.g. a normal PTH concentration in an animal with a high ionized calcium is inappropriate and compatible with a diagnosis of primary hyperparathyroidism.

Parathyroid hormone related protein (PTHrP)

Parathyroid hormone related protein is produced by several different cell types including lymphocytes, squamous epithelium, endocrine glands, bone, skeletal and smooth muscle and the kidney. The precise role of the protein is not known, but it is thought to be important for movement of calcium across membranes in the neonate and in the mammary gland. It is not involved in calcium homeostasis in physiologic states. PTHrP has a similar amino-terminal end to PTH and binds to PTH receptors. Therefore, PTHrP has a similar effect on calcium and phosphate as PTH. PTHrP is secreted by apocrine anal sac adenocarcinomas, some lymphomas and squamous cell carcinomas. It is responsible for the paraneoplastic hypercalcemia seen in these disorders. Specific assays for PTHrP are available.

Vitamin D

Vitamin D is ingested as vitamin D3 or produced in the skin under the influence of UV light. It is transported to the liver via vitamin D binding proteins where it is converted (with the enzyme 25 hydroxylase) to calcidiol or 25(OH)D. This is then transported to the kidney, where it is converted to its active form, calcitriol or 1,25 (OH)2D by the enzyme, alpha1-hydroxylase in the proximal renal tubules. This enzyme is stimulated by PTH, decreased calcium or phosphate. It is inhibited by calcitriol, increased calcium or phosphate.
Calcitriol acts on the intestines, kidneys and bone to increase calcium and phosphate values in serum. The main site of action is in the intestine, where calcitriol stimulates calcium and phosphate absorption. In the kidney, calcitriol promotes renal phosphate resorption in the proximal convoluted tubule and calcium resorption in the distal convoluted tubule. In bone, calcitriol facilitates the action of PTH on osteoblasts. Calcitriol can be produced by tumor macrophages and lymphoma cells, and is responsible for the hypercalcemia of malignancy seen in some dogs with lymphoma.
Assays for vitamin D3 and its metabolites are available.

Calcitonin

Calcitonin is produced by parafollicular cells in the thyroid gland (C cells). Production is stimulated by an increase in ionized calcium., beta-adrenergic stimulation, dopamine, estrogen, gastrin and glucagon.
Calcitonin counters the calcium- raising effects of vitamin D and PTH by inhibiting osteolysis and stimulation of renal excretion of calcium.

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