Embryologically, the inferior parathyroid glands (and the thymus) are derived from the third branchial pouch; the superior glands, from the fourth branchial pouch. Normally, the inferior parathyroids separate from the thymus and come to lie below the superior parathyroids. Failure of these structures to separate results in the atypical association of the parathyroids with the thymus in the adult. The principal (chief) cells differentiate during embryonic development and are functionally active in regulating fetal calcium metabolism. The oxyphil cells differentiate later at puberty.
Principal cells and oxyphil cells constitute the epithelial cells of the parathyroid gland.
 Principal (chief) cells, the more numerous of the parenchymal cells of the parathyroid (Fig. 21.17), are responsible for regulating the synthesis, storage, and secretion of large amounts of PTH. They are small, polygonal cells, with a diameter of 7 to 10 m and a centrally located nucleus. The pale-staining, slightly acidophilic cytoplasm contains lipofuscin-containing vesicles, large accumulations of glycogen, and lipid droplets. Small, dense, membrane-limited vesicles seen with the TEM or after using special stains with the light microscope are thought to be the storage form of PTH. Principal cells can replicate when they are chronically stimulated by changes in blood calcium levels.
 Oxyphil cells constitute a minor portion of the parenchymal cells and are not known to have a secretory role. They are found singly or in clusters; the cells are more rounded, considerably larger than the principal cells, and have a distinctly acidophilic cytoplasm (see Fig. 21.17). Mitochondria, often with bizarre shapes and sizes, almost fill the cytoplasm and are responsible for the strong acidophilia of these cells. No secretory vesicles and little if any rER are present. Cytoplasmic inclusion bodies consist of occasional lysosomes, lipid droplets, and glycogen distributed among the mitochondria.
Parathyroid hormone regulates calcium and phosphate levels in the blood.
The parathyroids function in the regulation of calcium and phosphate levels. Parathyroid hormone (PTH) is essential
FIGURE 21.17 • Photomicrograph of human parathyroid gland. This H&E–stained specimen shows the gland with part of its connective tissue capsule (Cap). The blood vessels (BV) are located in the connective tissue septum between lobes of the gland. The principal cells are arranged in two masses (top and bottom) and are separated by a large cluster of oxyphil cells (center). The oxyphil cells are the larger cell type with prominent eosinophilic cytoplasm. They may occur in small groups or in larger masses, as seen here. The principal cells are more numerous. They are smaller, having less cytoplasm, and consequently exhibit closer proximity of their nuclei. Adipose cells (AC) are present in variable, although limited, numbers. 175.
for life. Therefore, care must be taken during thyroidectomy to leave some functioning parathyroid tissue. If the glands are totally removed, death will ensue because muscles, including the laryngeal and other respiratory muscles, go into tetanic contraction as the blood calcium level falls.
PTH is an 84–amino acid linear peptide (Table 21.8). It binds to a specific PTH receptor on target cells that interacts with G protein to activate a second-messenger system. PTH release causes the level of calcium in the blood to increase. Simultaneously, it reduces the concentration of serum phosphate. Secretion of PTH is regulated by the serum calcium level through a simple feedback system. When parathyroid calcium-sensing receptors on principal cells detect low serum