Parathyroid Gland Function in Human Physiology.
The Parathyroid Gland Function in Human Physiology
?
Introduction:
The parathyroid glands are made up of four small glands. They are found near the thyroid gland in the neck or chest, also known as the upper mediastinum. They function as part of the endocrine system. The parathyroid glands, like all other parts of the endocrine system, play an important role in hormone regulation in the body. These glands make parathyroid hormone (PTH), which regulates the levels of calcium and phosphorus in the blood. Moreover, it Release of calcium by bones into the bloodstream, Absorption of calcium from food by the intestines and Conservation of calcium by the kidneys Stimulates cells in the kidney to transforms weaker forms of vitamin D into the form that is strongest at absorbing calcium from the intestines.
?
1.1 Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth.
The physiology of calcium and phosphate metabolism, bone and dental formation, and vitamin D, parathyroid hormone (PTH), and calcitonin regulation are all interconnected. Extracellular calcium ion concentration, for example, is determined by the interaction of absorption of calcium from the intestine, renal calcium excretion, and bone calcium uptake and release, all of which are regulated by the aforementioned hormones. Because phosphate and calcium homeostasis are so closely related. Extracellular fluid calcium concentration is normally tightly regulated, rarely deviating more than a few percent from the normal value of about 9.4 mg/dl (2.4 mmol calcium per liter). This precise control is required because calcium is involved in a variety of physiologic processes, including skeletal, cardiac, and smooth muscle contraction, blood clotting, and nerve impulse transmission, to name a few. Excitable cells, such as neurons, are sensitive to changes in calcium ion concentrations, and calcium ion concentrations above normal (hypercalcemia) cause progressive nervous system depression; conversely, calcium concentrations below normal (hypocalcemia) cause the nervous system to become more excited. The fact that only about 0.1 percent of extracellular calcium is regulated is an important feature. One percent of total body calcium is in extracellular fluid, one percent is in cells and organelles, and the rest is stored in bones. As a result, the bones can act as large reservoirs, releasing calcium when the concentration of extracellular fluid decreases and storing excess calcium.
?
1.2 Effects of PTH in the Bones:
PTH stimulates release of calcium ions in the bones in an indirect manner via osteoclasts, which inevitably results to bone resorption. PTH, on the other hand, directly stimulates osteoblasts, increasing their expression of RANKL, a receptor activator for nuclear factor Kappa-B ligand, allowing osteoblasts to differentiate into osteocytes. PTH also inhibits osteoprotegerin secretion, allowing for preferential differentiation into osteoclasts. Osteoprotegerin normally competes with RANKL for binding, reducing the ability to form osteoclasts. Osteoclasts can remodel bones (resorb) by dissolving and degrading hydroxyapatite and other organic materials, releasing calcium into the blood.
?
1.3 Effects of PTH on the Kidneys:
In increasing serum calcium levels, parathyroid hormone serves three main functions in the kidneys. The large percentage of physiologic calcium reabsorption in the nephron takes place in the proximal convoluted tubule and the ascending loop of Henle. Circulating parathyroid hormone stimulates calcium reabsorption by targeting the distal convoluted tubule and collecting duct. Phosphate reabsorption in the proximal convoluted tubule is reduced by parathyroid hormone. Phosphate ions in the serum form insoluble salts with calcium, resulting in lower plasma calcium. As a result of the phosphate ion reduction, there is more ionized calcium in the blood.
?
1.4 TH Indirect Effects on the Small Intestines and Reabsorption of Calcium:
PTH stimulates the production of 1alpha-hydroxylase in the proximal convoluted tubule beginning in the kidneys. This enzyme, 1alpha-hydroxylase, is necessary for the synthesis of active vitamin D - 1,25-dihydroxycholecalciferol - from the inactive form 25-hydroxycholecalciferol. Calcium reabsorption in the distal convoluted tubule is mediated by active vitamin D via calbindin-D, a cytosolic vitamin D-dependent calcium-binding protein. Vitamin D promotes calcium absorption in the small intestine via an active transcellular pathway and a passive paracellular pathway. The transcellular pathway necessitates energy, whereas the paracellular pathway allows calcium to pass through tight junctions.
?
PTH in the Context of Hypercalcemia and Hypocalcaemia
2.1 PTH in the Context of Hypercalcemia
If you have high calcium levels in your blood, you should have suppressed PTH levels in circulation, which are lower than the normal range of 10 to 65 ng/L. If serum PTH levels are found to be elevated in the context of hypercalcemia, further investigation of the parathyroid gland is warranted, and imaging will be performed.
?
2.2 PTH in the Context of Hypocalcaemia
If the clinical scenario includes hypocalcaemia and low PTH levels, the concern is that the parathyroid glands are not producing enough PTH. Hypoparathyroidism can be caused by a variety of conditions and manifest in a variety of ways. Depending on the cause, PTH underproduction can be chronic or transient. The most common causes of hypoparathyroidism are autoimmune destruction of the gland, thyroid resection damage, or severe illnesses. Each of those conditions would necessitate further investigation.
?
Hypoparathyroidism and Hyperparathyroidism
3.1 Hyperparathyroidism
Hyperparathyroidism is classified as primary, secondary, or tertiary dysfunction. Primary hyperparathyroidism is caused by a parathyroid gland abnormality, such as an adenoma or hyperplasia, which causes the gland to over secrete. This is characterized by elevated PTH levels, hypercalcemia, and hypophosphatemia in lab results. ?Primary hyperparathyroidism is typically caused by an adenoma, hyperplasia, or, in rare cases, a carcinoma. Adenomas are extremely rare and can be surgically removed. Multiple endocrine neoplasia (MEN) types I and II, as well as an autosomal dominant condition known as familial hypocalciuric hypercalcemia, can all be associated with hyperplasia. Patients with MEN type I frequently have tumours in the pituitary gland, parathyroid gland, and pancreas. The presence of medullary thyroid is a feature of MEN type II. The presence of medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia distinguishes this condition. A mutation of the calcium-sensing receptor in the parathyroid gland and kidney causes familial hypocalciuric hypercalcemia, resulting in a higher-than-normal set point. This results in a lack of inhibition of PTH secretion until serum calcium levels rise, resulting in increased bone resorption and hypercalcemia. Hypercalcemia is exacerbated further by increased renal calcium absorption, resulting in hypocalciuria. These conditions are uncommon and are not always amenable to surgical resection. Hyperparathyroidism is associated with hypercalcemia, which can cause symptoms such as excessive thirst and urination, constipation, bone pain, fatigue, depression, and possibly kidney stones. This is often remembered as "stones, bones, groans, thrones, and psychiatric overtones."
?
Secondary hyperparathyroidism is defined as PTH over secretion as a compensatory response to abnormally low calcium levels in the blood caused by other pathological processes such as renal failure, gastrointestinal malabsorption, or simply a vitamin D deficiency. The lab values vary depending on the underlying pathology. PTH will be elevated in chronic renal failure, but calcium and phosphate will be decreased. PTH will be elevated in the presence of malabsorption and vitamin D deficiency, but calcium and phosphate will be decreased.
?
Tertiary hyperparathyroidism is extremely rare, but it can occur in the context of ongoing PTH secretion even after a secondary hyperparathyroidism precipitating condition has been resolved. PTH levels will be moderately elevated, calcium levels will be normal or elevated, and phosphate levels will be low.
领英推荐
?
?
3.2 Hypoparathyroidism
Hypoparathyroidism does not occur as frequently as an overactive gland and has a variable duration. Hypoparathyroidism can be either chronic or transient. The most common cause of hypothyroidism is when a person's parathyroid gland is removed during elective surgery, or when it is damaged iatrogenically during a thyroid resection procedure due to the close anatomical proximity. The next most common cause of PTH underproduction is autoimmune disorders, which cause the destruction or damage of the glands individually or collectively. This is seen in Type I Autoimmune Polyendocrine Syndrome. The autoimmune regulatory (AIRE) gene mutation causes autoimmune polyendocrine syndrome type I, which is characterized by the triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. Another reason for hypothyroidism is caused by the failure in the embryological development of the parathyroid glands. DiGeorge syndrome is caused by a chromosomal 22q11 deletion and is characterized by the failure of the third and fourth pharyngeal pouches to form, which are responsible for the embryological formation of the thymus and parathyroid gland. Chronic infections (due to a lack of mature T lymphocyte proliferation in an absent thymus), hypoparathyroidism, cleft lip/palate, congenital cardiac defects (i.e., persistent truncus arteriosus, tetralogy of Fallot, or ventricular septal defect), and craniofacial abnormalities are all manifestations of DiGeorge syndrome.)
Hypocalcaemia, which can cause abdominal pain, muscle cramping, and paresthesias, is also linked to hypoparathyroidism. Chvostek and Trousseau signs are two clinical tests used to assess hypocalcaemia. When the cheek is lightly tapped and the face contracts on the same side, the Chvostek sign is positive. Because of the hypocalcaemia, the facial nerve is hyper excitable. When a blood pressure cuff is placed on an arm and inflated higher than the systolic blood pressure for three minutes, it causes muscle spasms in the ipsilateral hand and forearm. This happens after the brachial artery is occluded, which allows hypocalcaemia to cause nerve excitability.
?
Refreneces:
?
Hans SK, Levine SN. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): May 15, 2022. Hypoparathyroidism. [PubMed]
6.
Goyal A, Anastasopoulou C, Ngu M, Singh S. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): May 8, 2022. Hypocalcemia. [PubMed]
7.
Silva BC, Cusano NE, Bilezikian JP. Primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab. 2018 Sep 28;:101247. [PubMed]
8.
Prades JM, Asanau A, Timoshenko AP, Gavid M, Martin C. Endoscopic parathyroidectomy in primary hyperparathyroidism. Eur Arch Otorhinolaryngol. 2011 Jun;268(6):893-7. [PubMed]
9.
Endo I, Matsumoto T, Fukumoto S. [Pathophysiology and classitication of parathyroidism]. Clin Calcium. 2007 Aug;17(8):1175-81. [PubMed]
10.
Sugarman JA, Douglass AM, Say EA, Shields CL. Stones, bones, groans, thrones, and psychiatric overtones: Systemic associations of sclerochoroidal calcification. Oman J Ophthalmol. 2017 Jan-Apr;10(1):47-49. [PMC free article] [PubMed]
11.
Pitt SC, Sippel RS, Chen H. Secondary and tertiary hyperparathyroidism, state of the art surgical management. Surg Clin North Am. 2009 Oct;89(5):1227-39. [PMC free article] [PubMed]
12.
Husebye ES, Perheentupa J, Rautemaa R, K?mpe O. Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J Intern Med. 2009 May;265(5):514-29. [PubMed]
13.
Kraus C, Vanicek T, Weidenauer A, Khanaqa T, Stamenkovic M, Lanzenberger R, Willeit M, Kasper S. DiGeorge syndrome : Relevance of psychiatric symptoms in undiagnosed adult patients. Wien Klin Wochenschr. 2018 Apr;130(7-8):283-287. [PMC free article] [PubMed]
14.
Vakiti A, Mewawalla P. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 25, 2021. Malignancy-Related Hypercalcemia. [PubMed]
15.
Afzal M, Kathuria P. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 23, 2021. Familial Hypocalciuric Hypercalcemia. [PubMed]
16.
Sadiq NM, Naganathan S, Badireddy M. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Nov 26, 2021. Hypercalcemia. [PubMed]
17) Guyton