Anatomy and PhysiologyAnatomy

Source: Guyton: Textbook of Medical Physiology 11th EditionDiscovery of the human parathyroid glands was said to be accidental. It was years ago when surgeons were puzzled by their patients who have undergone partial or even total thyroid gland removal that some of them recovered but some suffered muscle spasms, severe pain, and eventually died. It was only then that a distinction was made between the separate hormonal functions of the thyroid and parathyroid gland. [1]

The parathyroid glands are tiny, grayish tan to yellow-gray in colour each weighing 30-40 mg [1]. They are nearly hidden in the posterior view of the thyroid gland. [2] A normal adult normally has four glands which averages a total parathyroid tissue mass of 120-160 mg. Although, the precise number of parathyroid glands vary in different individuals from six, eight or more. [1] It is said that 10% of people have extra number of parathyroid gland.[3] The inconsistency of the location and number of parathyroid gland in every individual sometimes causes problems in searching the neck to locate diseases in the gland during surgical operations. [4]There are two parathyroid glands located on each side one positioned on a higher area called the superior parathyroid glands, while the ones on the lower two are called the inferior parathyroid glands. On opposite sides of the neck is a branch of superior thyroidal artery that supplies the upper parathyroid gland, while the lower parathyroid gland is supplied by the inferior thyroidal artery. [1]The superior parathyroid glands are located at the fourth branchial pouches of the embryo. And because they are closely related to the thyroid gland, they are positioned along the dorsal portion of the upper thyroid. [4] Anatomically, the upper parathyroid glands are located in the posterior to the middle one third of the thyroid gland. They are near the point of junction between the middle thyroid artery and the regular laryngeal nerve. Different locations of the parathyroid gland may be in the tracheoesophageal groove and the retroesophageal space. The inferior thyroid artery generally supplies the upper parathyroid gland its sufficient needed blood. [3]The lower or inferior parathyroid glands are situated from the lateral to the lower pole of the thyroid gland. It is third in the branchial pouch, and in contrast to the upper parathyroid gland, it descends in a distance with the thymic anlage. As a result, its position is more variable than that of the superior parathyroid glands. Inferior thyroid arteries supplies blood to the inferior parathyroid glands. Common ectopic glands can be found in the thymic remnants, anterior the mediastinum. [4]

Source: Marieb,Hoehn: Human Anatomy and Physiology 7th EditionThe PTG consist mostly of chief cells and oxyphil cells embedded with a fibrous capsule intermixed with adipose tissue which increases with age and may reach 60-70% of the gland volume. [1] The chief cells are 12-20m in diameter, central, round, and uniform in nuclei. They vary in colour depending on the stain that is used and its glycogen content, from light to dark pink with hematoxylin and eosin stains. These cells sometimes appear water-clear due to lack of glycogen. They secrete granules that contain parathyroid hormone (PTH). On the other hand, Oxyphil cells can be found in single or small clusters throughout the parathyroid. What differs them from chief cells is that they are slightly larger in size, acidophilic cytoplasm, and mitochondria are tightly packed. Glycogen is present but unlike Chief cells, secretory granules are sparse or absent. [5]The Parathyroid hormone or parathormone, is the most important protein hormone that is produced by the parathyroid gland. Base on structure, it is an 84-amino-acid single-chain peptide. [2] Its release is triggered by decreased Ca2+ levels in the bloodstream. [5] Further functions of the PTH will be described on the physiology of the parathyroid gland.

source: Marieb,Hoehn: Human Anatomy and Physiology 7th EditionPhysiology The parathyroid gland possesses specialized calcium-sensing receptors that respond to rising or falling ambient calcium by increasing or decreasing PTH secretion, respectively. The parathyroid glands are not controlled by the hormones secreted by the hypothalamus and the pituitary rather it is controlled by the amount of free calcium that is contained in the bloodstream. [5] The gland secrets a polypeptide hormone called the parathyroid hormone (PTH) that is needed to regulate Ca2+ homeostasis. [6] It stimulates three main organs: the skeleton, the kidneys, and the intestine. [1]Normally, when a decrease in the levels of free calcium in the body is detected, stimulation of the parathyroid gland is made to secrete and synthesize PTH. PTH has its metabolic functions to regulate calcium as well: (these action increases calcium level in the body therefore inhibiting further PTH secretion) [1] To increase calcium reabsorption in the renal tubules to conserve calcium To increase vitamin D conversion to dihydroxy (active form) in the kidneys To increase phosphate excretion through urine excretion to lower serum phosphate levels To enhance gastrointestinal calcium absorption [5] PTH increases renal Ca2+ reabsorption in the distal tubule,PTH may have direct and some indirect actions in bones than is evident within minutes. [2] This is considered to be a slow process than can go on for days. PTH increases Ca2+ released by the bones to the bloodstream through the increase of osteoclasts in bones leading to bone breakdown. The red bone marrow is stimulated by stem cells to differentiate into osteoclasts to increase osteoclast number. Continuous elevated PTH leads to osteoclast bone resorption. [6]Secretion of PTH Controlled by the serum [Ca2+] by negative feedback. Decreased serum [Ca2+] increases PTH secretion. Mild decreases in serum [Mg2+] also stimulate PTH secretion. Severe decreases in serum [Mg2+] inhibit PTH secretion and produce symptoms of hypoparathyroidism. The second messenger for PTH secretion by the parathyroid gland is cyclic AMP.

Secretion of parathyroid hormone is controlled chiefly byserum[Ca2+] throughnegative feedback.Calcium-sensing receptorslocated on parathyroid cells are activated when [Ca2+] is low.[12]The G-protein coupled calcium receptors (CaR) sense extracellular calcium and may be found on the surface on a wide variety cells distributed in the brain, heart, skin, stomach, C cells, and other tissues. In the parathyroid gland, sensation of high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C. This hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to liberate intracellular messengers IP3 and diacylglycerol (DAG). Ultimately, these two messengers result in a release of calcium from intracellular stores and a subsequent flux of extracellular calcium into the cytoplasmic space. The effect of this signaling of high extracellular calcium results in an intracellular calcium concentration that inhibits the secretion of preformed PTH from storage granules in the parathyroid gland. In contrast to the mechanism that most secretory cells use, calciuminhibitsvesicle fusion and release of PTH. [7]The kidneys initial response from increased PTH is to increase renal calcium resorption and phosphate excretion. As the secretion of PTH is increased Ca2+ is reabsorbed from the urine, goes back to the bloodstream therefore decreasing calcium level urine excretion. [2] Blocking of phosphate resorption happens in the proximal tubule of the kidney while calcium reabsorption happens in the ascending loop of Henle, distal tubule, and collecting tubule. [4]The final and most important function of the PTH is to convert 25-hydroxyvitamin D to its active form , 1,25-dihydroxyvitamin D-3 [1,25-(OH)2 D3] through activation in the proximal tubules of the kidney by an enzyme called enzyme 1-hydroxylase. The vitamin D in the kidneys is transported by the blood to the epithelial cells of small intestine promoting Ca2+ transport protein synthesis. Vitamin D formation results from the increase of blood Ca2+ levels by the PTH which in return increases Ca2+ absorption in urine. [6] Vitamin D also promotes intestinal absorption of phosphate ion although its mechanism is not yet clearly defined. But as compared with PTH, vitamin D exerts slower regulatory effect on calcium levels. Calcium levels in the body is critical mainly because it controls calcium ion homeostasis essential for body functions such as nerve impulse transmission, muscle contraction, muscle contraction, and blood clotting. [1] Same with the other endocrine glands of the body, abnormalities related with the parathyroid glands may include both hyperfunction and hypofunction. [5]Ca2+ metabolism/homeostasis

Serum [Ca2+] is determined by the interplay of intestinal absorption, renal excretion and bone remodeling (bone resorption and formation). Each component is hormonally regulated. To maintain Ca2+ balance, net intestinal absorption must be exactly balanced by urinary excretion:1. Positive Ca2+ balance is seen in growing children, where intestinal Ca2+ absorption exceeds urinary excretion and the difference is deposited in the growing bones.2. Negative Ca2+ balance is seen in women during pregnancy or lactation, where intestinal Ca2+ absorption is less than urinary excretion and the difference comes from the maternal bones. [9]

Phosphate metabolismPhosphates are absorbed from foodstuff. Specialized channel proteins called sodium-phosphate transporters 2b (or NaPi2b) located at the surface of the epithelial cells of the small intestine are performing the task. About 1.5 g of phosphate are captured daily by this process by a normal adult.

Once in the bloodstream, phosphates can be absorbed byorgans and tissues. A part of it is stored in bones. Then, phosphates reach the kidneys where most of it is filtered out of the blood. But before being eliminated in the urine, another channel protein (NaPi2a) similar to the one that capture phosphate from foodstuff bring it back to bloodstream in a process called 'reabsorption'. This steps of filtration and reabsorption taking place in the kidney are crucial for the maintenance of phosphate levels. [8]

By: Genesis Adrianne V. Ege & Rouselle John[7] http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch6/s5ch6_9.htm[8] http://www.xlhresearch.net/Phosphatemetabolism.htm[9] www.the-ainet.com/rom-med/files/.../Calcium_metabolism.pdf