Endocrine System: Calcium and Phosphate Metabolism

Calcium and Phosphate Metabolism

• Production of 1,25-dihydroxycholecalciferol is increased by low plasma PO4 (3-) levels and inhibited by high plasma PO4 (3-) levels
• 1,25-Dihydroxycholecalciferol formation is also controlled by a direct negative feedback effect on 1α-hydroxylase, a positive feedback action on the formation of 24,25-dihydroxycholecalciferol, and a direct action on the parathyroid gland to inhibit PTH expression

Parathyroid Glands

• Humans usually have four parathyroid glands, two embedded in the superior poles of the thyroid and two in its inferior poles
• Each parathyroid gland is a richly vascularized disk, about 3 × 6 × 2 mm, containing two distinct types of cells: chief cells and oxyphil cells
• Chief cells synthesize and secrete PTH, contain a prominent Golgi apparatus, endoplasmic reticulum, and secretory granules
• Oxyphil cells contain oxyphil granules and large numbers of mitochondria in their cytoplasm, increase in number with age

Synthesis and Metabolism of PTH

• Human PTH is a linear polypeptide with a molecular weight of 9500, containing 84 amino acid residues
• PTH is synthesized as part of a larger molecule containing 115 amino acid residues (preproPTH)
• 1,25-Dihydroxycholecalciferol acts directly on the parathyroid glands to decrease preproPTH mRNA

Calcitonin

• Calcitonin is a Ca2+-lowering hormone produced by the parafollicular cells of the thyroid gland
• Calcitonin secretion is increased when the thyroid gland is exposed to a plasma calcium level of approximately 9.5 mg/dL
• β-Adrenergic agonists, dopamine, and estrogens also stimulate calcitonin secretion
• Gastrin, cholecystokinin (CCK), glucagon, and secretin have been reported to stimulate calcitonin secretion, with gastrin being the most potent stimulus

Bone Physiology

• Bone is a special form of connective tissue with a collagen framework impregnated with Ca2+ and PO4(3-) salts, particularly hydroxyapatites
• Bone is involved in overall Ca2+ and PO4(3-) homeostasis, protecting vital organs, and providing rigidity for locomotion and support against gravity
• Old bone is constantly being resorbed and new bone formed, permitting remodeling that allows it to respond to stresses and strains
• Bone is a living tissue that is well vascularized and has a total blood flow of 200–400 mL/min in adult humans

Bone Structure

• There are two types of bone: compact (cortical) bone and trabecular (spongy) bone
• Compact bone makes up the outer layer of most bones and accounts for 80% of the bone in the body
• Trabecular bone makes up the remaining 20% of bone in the body, is made up of spicules or plates, and has a high surface-to-volume ratio
• Nutrients diffuse from bone extracellular fluid (ECF) into the trabeculae, but in compact bone, nutrients are provided via haversian canals, which contain blood vessels

Bone Growth

• During fetal development, most bones are modeled in cartilage and then transformed into bone by ossification (enchondral bone formation)
• Exceptions include the clavicles, mandibles, and certain bones of the skull, which form bone directly (intramembranous bone formation)
• During growth, specialized areas at the ends of each long bone (epiphyses) are separated from the shaft of the bone by a plate of actively proliferating cartilage, the epiphysial plate