Parathyroid chief cell

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Parathyroid chief cell
Parathyroid oxyphil and chief cells - annotated.jpg
Micrograph of a parathyroid gland. H&E stain.
Details
Location Parathyroid gland
Identifiers
TH H3.08.02.5.00002
FMA 69078
Anatomical terms of microanatomy

Parathyroid chief cells (also called parathyroid principal cells or simply parathyroid cells) are one of the two cell types of the parathyroid glands, along with oxyphil cells. [1] The chief cells are much more prevalent in the parathyroid gland than the oxyphil cells. It is perceived that oxyphil cells may be derived from chief cells at puberty, [2] as they are not present at birth like chief cells. [3]

Contents

Most individuals display four parathyroid glands adjacent to the thyroid gland anterior in the neck.

Histology

The chief cells are organized as dense cords surrounding the capillaries in the parathyroid. [4]

Chief cells appear as a dark purple in an H&E stain, with the oxyphil cells staining as a lighter pink. [3]

They are polygonal in shape with a round nucleus. [2]

Chief cells spend most time inactive due to normal calcium level conditions. These inactive cells are classified as cuboidal. They have low levels of secretory granules, as opposed to active chief cells. These granules can contain acid phosphatase. Acid phosphatase is only found in larger secretory granules, 400 to 900 nm in diameter, and is less prevalent in smaller granules. This acid phosphatase is also present in the Golgi apparatus of the chief cell. However, the Golgi apparatus areas associated with parathyroid hormone packaging contained little or no acid phosphatase. [5] The chief cells become active in response to low calcium in the blood. The low level is sensed by the calcium- sensing receptor. These active cells have a greater electron density than the inactive chief cells. [6] The electron density is caused by the secretory granules. The chief cell is thought to have a clear cytoplasm. [7]

Function

The four parathyroid glands are embedded in the thyroid gland. Parathyroid.png
The four parathyroid glands are embedded in the thyroid gland.

The chief cells of the parathyroid glands sense the amount of calcium in the blood, and release the calcium-increasing hormone parathyroid hormone (PTH) accordingly to correct or maintain normal blood calcium levels. [8] It therefore regulates calcium metabolism as part of the endocrine system. PTH raises calcium levels by releasing calcium from bone storage, as well as retaining calcium from the urine, and alerts the intestines to absorb more calcium from ingested nutrients. [9] Too much of either hormone can be an indicator of disease.

Calcium-sensing receptor (CaR)

The secretion of parathyroid hormone (PTH) is regulated by the interaction of the calcium-sensing receptor with calcium in the blood. The calcium-sensing receptor is present on the plasma membrane of the chief cells. The CaR is a G protein-coupled receptor, as part of the C family. The CaR is divided into three general domains. These include an NH2- terminal extracellular end, a COOH-terminal intracellular end, and seven transmembrane domains. The CaR interacts positively with phospholipase C (PLC) and adenylyl cyclase. The CaR includes phosphorylation sites for protein kinase C (PKC) and protein kinase A (PKA). The phosphorylation of the PLC is seen to inhibit the secretion of PTH due to high calcium levels in the blood. The function of the PKA sites is currently unknown. [10]

Clinical significance

Hyperparathyroidism

Osteoporotic bone is largely decreased in strength and increased in porosity due to the loss in calcium. Bone Comparison of Healthy and Osteoporotic Vertibrae.png
Osteoporotic bone is largely decreased in strength and increased in porosity due to the loss in calcium.

Because the formation of PTH regulates the calcium level in the blood, it can affect all areas of the body. The overactivity of a parathyroid gland is known as hyperparathyroidism. It is unknown what directly causes hyperparathyroidism. However there are many factors that can cause over-secretion of PTH. The further consequence of this disorder can be osteopenia, or even osteoporosis, which is the loss of bone density. [11] This leaves bones more porous, fragile, and likely to experience fracture. This can be detected by usage of dual-energy X-ray absorptiometry (DEXA). Interesting enough, a derivative of synthetic PTH is often given to patients with osteoporosis to combat the disease. [12]

Vitamin D deficiency

Vitamin D in the kidney assists in the absorption of calcium in the blood. Some individuals may be vitamin D deficient, which prevents them from retaining calcium. [11] While their parathyroid gland is functional, it senses a very low level of calcium in the blood and constantly secretes hormone, increasing PTH levels.

Medications

There are many drugs that can affect calcium level in the blood, and therefore PTH secretion. For example, many individuals may take a calcium carbonate supplement, which increases the calcium level in the blood. PTH is decreased. Many medications may also increase urination, furthering loss of calcium.

Parathyroid adenoma

A parathyroid adenoma is the most common cause of hyperparathyroidism. [2] They are more commonly found in women than in men. In this form, the chief cells mutate to exhibit multiple nuclei. [2] Chief cells in parathyroid adenomas also display acid phosphatase activity. [5] It is a benign tumor of the gland that requires surgical removal. [13] These benign adenomas are typically affect only one or two of the parathyroid glands, known respectively as a single adenoma or double adenoma. Typically, no disease is linked to the cause. [14] A primary adenoma can only develop as a primary cause.

Chief cell hyperplasia

In many way, chief cell hyperplasia is similar to parathyroid adenoma. The hyperplasia is seen as an enlargement of all four of the parathyroid glands, as opposed to a parathyroid adenoma is viewed as an enlargement of one gland. [14] Chief cell hyperplasia is a common disorder in individuals with other endocrine abnormalities, though it may still occur sporadically. A chief cell hyperplasia can develop from either a primary or secondary cause.

Parathyroid carcinoma

In extremely rare cases, a malignant tumor may develop within the parathyroid gland. They can be detected intraoperatively, imaging, or through blood testing. A thick fibrous capsule is usually present around the gland, as opposed to the thin capsule present in benign adenomas. [7] Parathyroid hormone level is often greater in carcinomas than in benign disorders.

Hypoparathyroidism

There are very few cases of hypoparathyroidism. Most often, it is related with surgical removal of the parathyroid glands. It can also be due to a head or neck injury and further loss of function of the glands. Hypoparathyroidism can also be linked to a low serum magnesium level in the blood. Serum magnesium is necessary for full secretion of PTH. [15] Without the parathyroid glands, there is no trigger to release calcium into the blood. Another consequence of hypoparathyroidism is the lack of calcium in the blood to trigger muscle contraction. Without calcium present, muscles innervation is unable to take place. This is especially crucial in the function of the most important muscle of the body – the heart.

See also

Related Research Articles

<span class="mw-page-title-main">Endocrine system</span> Hormone-producing glands of a body

The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. In humans, the major endocrine glands are the thyroid gland, parathyroid gland, pituitary gland, pineal gland, the testes (male), ovaries (female), and the adrenal glands. The hypothalamus, pancreas, and thymus also function as endocrine glands, among other functions. Other organs, such as the kidneys, also have roles within the endocrine system by secreting certain hormones. The study of the endocrine system and its disorders is known as endocrinology. It is one of the most important systems of the human body.

<span class="mw-page-title-main">Parathyroid gland</span> Endocrine gland

Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to a low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones.

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in Homo sapiens

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

Calcium metabolism is the movement and regulation of calcium ions (Ca2+) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.

Disorders of calcium metabolism occur when the body has too little or too much calcium. The serum level of calcium is closely regulated within a fairly limited range in the human body. In a healthy physiology, extracellular calcium levels are maintained within a tight range through the actions of parathyroid hormone, vitamin D and the calcium sensing receptor. Disorders in calcium metabolism can lead to hypocalcemia, decreased plasma levels of calcium or hypercalcemia, elevated plasma calcium levels.

<span class="mw-page-title-main">Oxyphil cell (parathyroid)</span>

Parathyroid oxyphil cells are one out of the two types of cells found in the parathyroid gland, the other being parathyroid chief cell. Oxyphil cells are only found in a select few number of species and humans are one of them.

Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany, and several other symptoms. It is a very rare disease. The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The primary treatment of hypoparathyroidism is calcium and vitamin D supplementation. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease. Additionally, medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone.

<span class="mw-page-title-main">Hyperparathyroidism</span> Medical condition

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli. Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium leaving the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low. With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis.

<span class="mw-page-title-main">Parathyroidectomy</span> Surgical removal of one or more of the parathyroid glands

Parathyroidectomy is the surgical removal of one or more of the (usually) four parathyroid glands. This procedure is used to remove an adenoma or hyperplasia of these glands when they are producing excessive parathyroid hormone (PTH): hyperparathyroidism. The glands are usually four in number and located adjacent to the posterior surface of the thyroid gland, but their exact location is variable. When an elevated PTH level is found, a sestamibi scan or an ultrasound may be performed in order to confirm the presence and location of abnormal parathyroid tissue.

<span class="mw-page-title-main">Endocrine gland</span> Glands of the endocrine system that secrete hormones to blood

Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.

<span class="mw-page-title-main">Primary hyperparathyroidism</span> Medical condition

Primary hyperparathyroidism is a medical condition where the parathyroid gland produce excess amounts of parathyroid hormone (PTH). The symptoms of the condition relate to the resulting elevated serum calcium (hypercalcemia), which can cause digestive symptoms, kidney stones, psychiatric abnormalities, and bone disease.

<span class="mw-page-title-main">Multiple endocrine neoplasia type 1</span> Medical condition

Multiple endocrine neoplasia type 1 (MEN-1) is one of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas. Individuals suffering from this disorder are prone to developing multiple endocrine and nonendocrine tumors. It was first described by Paul Wermer in 1954.

<span class="mw-page-title-main">Osteitis fibrosa cystica</span> Medical condition

Osteitis fibrosa cystica is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue, and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica (OFC), also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone, is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss.

<span class="mw-page-title-main">Secondary hyperparathyroidism</span> Medical condition

Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia, with resultant hyperplasia of these glands. This disorder is primarily seen in patients with chronic kidney failure. It is sometimes abbreviated "SHPT" in medical literature.

<span class="mw-page-title-main">Tertiary hyperparathyroidism</span> Medical condition

Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone. Anatomically, these glands are located in the neck, para-lateral to the thyroid gland, which does not have any influence in the production of parathyroid hormone. Parathyroid hormone is released by the parathyroid glands in response to low blood calcium circulation. Persistent low levels of circulating calcium are thought to be the catalyst in the progressive development of adenoma, in the parathyroid glands resulting in primary hyperparathyroidism. While primary hyperparathyroidism is the most common form of this condition, secondary and tertiary are thought to result due to chronic kidney disease (CKD). Estimates of CKD prevalence in the global community range from 11 to 13% which translate to a large portion of the global population at risk of developing tertiary hyperparathyroidism. Tertiary hyperparathyroidism was first described in the late 1960s and had been misdiagnosed as primary prior to this. Unlike primary hyperparathyroidism, the tertiary form presents as a progressive stage of resolved secondary hyperparathyroidism with biochemical hallmarks that include elevated calcium ion levels in the blood, hypercalcemia, along with autonomous production of parathyroid hormone and adenoma in all four parathyroid glands. Upon diagnosis treatment of tertiary hyperparathyroidism usually leads to a surgical intervention.

<span class="mw-page-title-main">Endocrine disease</span> Medical condition

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.

<span class="mw-page-title-main">Parathyroid adenoma</span> Medical condition

A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.

<span class="mw-page-title-main">Parathyroid carcinoma</span> Medical condition

Parathyroid carcinoma is a rare cancer resulting in parathyroid adenoma to carcinoma progression. It forms in tissues of one or more of the parathyroid glands.

<span class="mw-page-title-main">Parathyroid disease</span> Medical condition

Many conditions are associated with disorders of the function of the parathyroid gland. Some disorders may be purely anatomical resulting in an enlarged gland which will raise concern. Such benign disorders, such as parathyroid cyst, are not discussed here. Parathyroid diseases can be divided into those causing hyperparathyroidism, and those causing hypoparathyroidism.

<span class="mw-page-title-main">Sestamibi parathyroid scan</span> Procedure in nuclear medicine

A sestamibi parathyroid scan is a procedure in nuclear medicine which is performed to localize parathyroid adenoma, which causes Hyperparathyroidism. Adequate localization of parathyroid adenoma allows the surgeon to use a minimally invasive surgical approach.

References

  1. ↑ "Dictionary - Normal: Parathyroid gland - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2015-11-18.
  2. 1 2 3 4 Bilezikian, John (2015). The Parathyroids: Basic and Clinical Concepts. San Diego: Academic Press. pp. 23–39. ISBN   978-0-12-397166-1.
  3. 1 2 Ritter, Cynthia S.; Haughey, Bruce H.; Miller, Brent; Brown, Alex J. (2012-08-01). "Differential Gene Expression by Oxyphil and Chief Cells of Human Parathyroid Glands". The Journal of Clinical Endocrinology and Metabolism. 97 (8): E1499–E1505. doi:10.1210/jc.2011-3366. ISSN   0021-972X. PMC   3591682 . PMID   22585091.
  4. ↑ Ritchie, Judith E.; Balasubramanian, Saba P. (2014). "Anatomy of the pituitary, thyroid, parathyroid and adrenal glands". Surgery (Oxford). 32 (10): 499–503. doi:10.1016/j.mpsur.2014.07.005.
  5. 1 2 Shannon, W. Allen; Roth, Sanford I. (1974-12-01). "An Ultrastructural Study of Acid Phosphatase Activity in Normal, Adenomatous and Hyperplastic (Chief Cell Type) Human Parathyroid Glands". The American Journal of Pathology. 77 (3): 493–506. ISSN   0002-9440. PMC   1910932 . PMID   4432915.
  6. ↑ Thomas, John (1997). Endocrine Toxicology. Washington DC: CRC Press. pp. 1–31. ISBN   1-56032-613-1.
  7. 1 2 Okpokam, Atuora; Johnson, Sarah J. (2014-10-01). "Pathology of the pituitary, parathyroid, thyroid and adrenal glands". Surgery (Oxford). Endocrine Surgery. 32 (10): 513–524. doi:10.1016/j.mpsur.2014.07.007.
  8. ↑ Ritter, Cynthia S.; Haughey, Bruce H.; Miller, Brent; Brown, Alex J. (2012). "Differential Gene Expression by Oxyphil and Chief Cells of Human Parathyroid Glands". The Journal of Clinical Endocrinology & Metabolism. 97 (8): E1499–E1505. doi: 10.1210/jc.2011-3366 . ISSN   0021-972X. PMC   3591682 . PMID   22585091.
  9. ↑ "Parathyroid Hormone". arbl.cvmbs.colostate.edu. Retrieved 2015-11-18.
  10. ↑ Naveh-Many, Tally (2005). Molecular Biology of the Parathyroid . New York: Plenum. pp.  44–51. ISBN   0-306-47847-1.
  11. 1 2 "Osteoporosis Caused by Parathyroid and Hyperparathyroidism with High Calcium". parathyroid.com. Retrieved 2015-11-18.
  12. ↑ Charest-Morin, Xavier; Fortin, Jean-Philippe; Lodge, Robert; Allaeys, Isabelle; Poubelle, Patrice E.; Marceau, François (2014-10-01). "A tagged parathyroid hormone derivative as a carrier of antibody cargoes transported by the G protein coupled PTH1 receptor" (PDF). Peptides. 60: 71–79. doi:10.1016/j.peptides.2014.08.001. hdl: 20.500.11794/15924 . PMID   25128082. S2CID   35111560.
  13. ↑ "Parathyroid adenoma: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-11-18.
  14. 1 2 Cope, Oliver; Keynes, W. Milo; Roth, Sanford I.; Castleman, Benjamin (1958-09-01). "Primary Chief-Cell Hyperplasia of the ParaThyroid Glands". Annals of Surgery. 148 (3): 375–387. doi:10.1097/00000658-195809000-00007. ISSN   0003-4932. PMC   1450806 . PMID   13571915.
  15. ↑ "Hypoparathyroidism Causes - Mayo Clinic". www.mayoclinic.org. Retrieved 2015-11-20.
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