Kalsiyum
Özet
Kalsiyum (Ca) minerali, nöromüsküler ve sinyal yolaklarının düzenlenmesi, kemik gelişimi, büyümesi ve bakımı ile hücre iskeletinin stabilitesi için gereklidir. Birçok önemli işlevi olan kalsiyumun plazma düzeyini normal aralıklarda tutmak önemlidir. Plazma kalsiyum düzeylerinin kontrolü, bağırsaktan emilim, renal tübüllerden emilim ve gerektiğinde kemik depolarından dengelemenin birleşimiyle sağlanır. Bazı hastalıklar durumunda bu denge bozulur ve hipokalsemi veya hiperkalsemi meydana gelebilir. Hipokalseminin başlıca semptomları arasında kas seyirmeleri ve spazmları, karpopedal spazm, huzursuzluk, fokal veya jeneralize nöbetler, kişilik bozuklukları, ekstrapiramidal bulgular, apne, stridor, bronkospazm, laringospazm, kilo alamama, beslenme güçlüğü, kuru cilt, kırılgan tırnaklar, atopik egzema, diş çürüğü, karın ağrısı, kusma, kabızlık ve biliyer kolik alır. Hiperkalsemisi olan hastalarda böbrek tutulumuna bağlı poliüri, polidipsi, nefrolitiyazis, nefrokalsinoz, distal renal tübüler asidoz, nefrojenik diyabetes insipidus, akut ve kronik böbrek yetmezliği görülebilir. Gastrointestinal sistemde anoreksi, bulantı, kusma, kabızlık, pankreatit ve peptik ülser görülürken, kas iskelet sisteminde kas güçsüzlüğü, kemik ağrısı, osteopeni/osteoporoz görülebilir. Depresyon, tükenmişlik sendromu, konsantrasyon bozukluğu, bilinç bulanıklığı, konfüzyon ve koma gibi nörokognitif değişiklikler izlenebilir. Hiperkalseminin en ciddi bulgusu ise bradikardi ve QT aralığının kısalması sonucu meydana gelen kardiyak arresttir. Bu bölümde kalsiyumun, profilaksi gerektiren durumları, diyetteki kalsiyum içeren ürünleri, hipokalsemi/hiperkalsemi etiyolojisi, klinik durumu ve tedavisi anlatılacaktır.
Calcium (Ca) mineral is necessary for the regulation of neuromuscular and signaling pathways, bone development, growth and maintenance, and stability of the cytoskeleton. It is important to keep the plasma levels of calcium, which has many important functions, within normal ranges. Control of plasma calcium levels is achieved by a combination of absorption from the intestine, absorption from the renal tubules, and, when necessary, balancing from bone stores. In some diseases, this balance is disrupted and hypocalcemia or hypercalcemia may occur. The main symptoms of hypocalcemia include muscle twitching and spasms, carpopedal spasm, restlessness, focal or generalized seizures, personality disorders, extrapyramidal findings, apnea, stridor, bronchospasm, laryngospasm, failure to gain weight, feeding difficulties, dry skin, brittle nails, atopic eczema, tooth decay, abdominal pain, vomiting, constipation, and biliary colic. In patients with hypercalcemia, polyuria, polydipsia, nephrolithiasis, nephrocalcinosis, distal renal tubular acidosis, nephrogenic diabetes insipidus, acute and chronic renal failure due to renal involvement may be observed. Anorexia, nausea, vomiting, constipation, pancreatitis and peptic ulcer are observed in the gastrointestinal system, while muscle weakness, bone pain, osteopenia/osteoporosis may be observed in the musculoskeletal system. Neurocognitive changes such as depression, burnout syndrome, impaired concentration, clouding of consciousness, confusion and coma may be observed. The most serious finding of hypercalcemia is cardiac arrest resulting from bradycardia and shortening of the QT interval. This section will discuss calcium, conditions requiring prophylaxis, calcium-containing products in the diet, etiology, clinical status and treatment of hypocalcemia/hypercalcemia.
Referanslar
Battafarano G, Chiellini G, Saponaro, et al. Calcium Metabolism: Hormonal Crosstalk, Pathophysiology and Disease. Frontiers in Medicine; 2022;9. doi: 10.3389/fmed.2022.899416.
Hall J E. Guyton ve Hall Tıbbi Fizyoloji. 13nd ed. (Çev. Berrak Çağlayan YEĞEN, Çev. Ed.). Ankara: Güneş Tıp Kitabevleri; 2017, p 1002-3.
Fujita H, Sugimoto K, Inatomi S. et al. Tight junction proteins claudin‐2 and ‐12 are critical for vitamin D‐dependent Ca2+ absorption between enterocytes. Mol. Biol. Cell. 2008;19 (5): 1912–21.
Hoenderop JG, Nilius B, Bindels RJ. Calcium absorption across epithelia. Physiol Rev. 2005;85 (1): 373–422.
Diaz de Barboza G, Guizzardi S, Tolosa de Talamoni N. Molecular aspects of intestinal calcium absorption. World J. Gastroenterol. 2015;2219–2840.
Yu AS. Claudins and the kidney. J. Am. Soc. Nephrol. 2015;26(1):11–9.
Dattani M. T. & Brook C. G. D. Brook's clinical pediatric endocrinology (Seventh). Wiley-Blackwell;2020. Available at: https://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=2240097. Accessed: October 10 2023
Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol. Rev. 2001;81 (1): 239–297.
Conlin PR, Fajtova VT, Mortensen RM, et al. Hysteresis in the relationship between serum ionized calcium and intact parathyroid hormone during recovery from induced hyper‐ and hypocalcemia in normal humans. J. Clin. Endocrinol. Metab. 1989;69 (3): 593–599.
Cheloha RW, Gellman SH, Vilardaga JP, et al. PTH receptor‐1 signalling‐mechanistic insights and therapeutic prospects. Nat. Rev. Endocrinol. 2015;11 (12): 712–24.
Allgrove J. Physiology of Calcium, Phosphate, Magnesium and Vitamin D. Endocr Dev. 2015;28:7-32. doi: 10.1159/000380990.
Okuda K, Usui E, Ohyama Y. Recent progress in enzymology and molecular biology of enzymes involved in vitamin D metabolism. J. Lipid Res. 1995;36 (8): 1641–1652.
St‐Arnaud R, Messerlian S, Moir JM, et al. The 25‐hydroxyvitamin D 1‐alpha‐hydroxylase gene maps to the pseudovitamin D‐deficiency rickets (PDDR) disease locus. J. Bone Miner. Res.1997;12 (10): 1552–1559.
McLaughlin MB, Jialal I. Calcitonin. In: StatPearls. StatPearls Publishing, Treasure Island (FL); 2022. PMID: 30725954.
15.Librizzi M, Naselli F, Abruscato G, et al. Parathyroid Hormone Related Protein (PTHrP)-Associated Molecular Signatures in Tissue Differentiation and Non-Tumoral Diseases. Biology, 2023;12(7), 950.
Campbell, A. K. Intracellular calcium. John Wiley & Sons.2014; 2(1):23-29.
US Department of Agriculture, Agriculture Research Service. US Department of Agriculture Nutrient Data Laboratory. Available at: www.ars.usda.gov/main/site.main.htm?modecode.12354500. Accessed December 21, 2023.
Nutrition, Calcium-rich foods 2022. Available at: https://health.clevelandclinic.org/calcium-rich-foods/. Accessed: October 10 2023
National Instutites of Health, Calcium, 2023. Available at: https://ods.od.nih.gov/factsheets/Calcium-Consumer/ Accessed: October 10 2023
Namgung R, Tsang RC. Perinatal calcium and phosphorus metabolism. In: Oh W, Guignard JP, Baumgart S (eds) Polin RA (consulting ed). Nephrology and fluid/electrolyte physiology, neonatology questions and controversies (3rd ed). Philadelphia, Elsevier 2019: 65-84.
Shoback DM, Bilezikian JP, Costa AG, et al. Presentation of hypoparathyroidism: etiologies and clinical features. J. Clin. Endocrinol. Metab. 2016. jc20153909.
Allen W. Root, Michael A. Levine.Disorders of Mineral Metabolism II. Abnormalities of Mineral Homeostasis in the Newborn, Infant, Child, and Adolescent. Sperling M. A(eds). Sperling Pediatric Endocrinology (Fifth Edition), Philadelphia, Elsevier 2021: 705-813. doi: 10.1016/B978-0-323-62520-3.00020-8.
Maiya S, Sullivan I, Allgrove J, et al. Hypocalcaemia and vitamin D deficiency: an important, but preventable, cause of life‐threatening infant heart failure. Heart. 2018;94 (5): 581–4.
Egbuna OI, Brown EM. Hypercalcemic and hypocalcemic conditions due to calcium- sensing receptor mutations. Best Practice & Research Clin Rheumatol 2008; 22: 129- 148.
Ildiko H, Koves Kathryn D, Ness A, et al. Disorders of Calcium and Phosphorus Metabolism. Christine A. Gleason, Sandra E.(eds.). Avery's Diseases of the Newborn (Tenth Edition), Philadelphia, Elsevier, 2018, 1333-1350. doi:10.1016/B978-0-323-40139-5.00095-4.
Loughead JL, Mimouni F, Tsang RC, et al. A role for Mg in neonatal parathyroid gland function. Am J Coll Nutr 1991; 10: 123-126.
Korkmaz HA, Ozka, B. Hypoparathyroidism in children and adolescents. Annals of Pediatric Endocrinology & Metabolism, 2023; 28(3), 159.
Ding C, Buckingham B, Levine MA. Familial isolated hypoparathyroidism caused by a mutation in the gene for the transcription factor GCMB. J. Clin. Invest. 2001;108 (8): 1215–1220.
Bowl MR, Nesbit MA, Harding B, et al. An interstitial deletion‐insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X‐linked recessive hypoparathyroidism. J. Clin. Invest. 2005;115 (10): 2822–2831.
Habel A, Herriot R, Kumararatne D, et al. Towards a safety net for management of 22q11.2 deletion syndrome: guidelines for our times. Eur. J. Pediatr. 2014;173 (6): 757–765.
Grigalionienė K, Burnytė B, Ambrozaitytė L, Utkus A. Wide diagnostic and genotypic spectrum in patients with suspected mitochondrial disease. Orphanet journal of rare diseases, 2023;18(1), 307.
Dinoi E, Pierotti L, Mazoni L, et al. Clinical and molecular characteristics of two Italian kindreds with hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome. Journal of Endocrinological Investigation, 2023;1-10.
Paldino G, Faienza MF, Cappa, et al. Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies. Frontiers in Immunology, 2023;14.
Zung A, Barash G, Banne E, et al. Novel Calcium-Sensing Receptor (CASR) Mutation in a Family with Autosomal Dominant Hypocalcemia Type 1 (ADH1): Genetic Study over Three Generations and Clinical Characteristics. Hormone Research in Paediatrics, 2023;1-10.
Del Sindaco G, Berkenou J, Pagnano A, et al. Neonatal and early infancy features of patients with inactivating PTH/PTHrP Signaling Disorders/Pseudohypoparathyroidism. The Journal of Clinical Endocrinology & Metabolism, 2023;236.
Rubin MR, Levine MA. Hypoparathyroidism and pseudohypoparathyroidism. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 8th ed, Rosen CJ (Ed), American Society of Bone and Mineral Research, Ames, Iowa 2013;579.
Renaghan, Amanda DeMauro, and Mitchell H. Rosner. "Hypercalcemia: etiology and management." Oxford University. (2018): 549-551.
Walker MD, & Shane E. Hypercalcemia: a rewiev. JAMA. 2022; 328(16), 1624-1636.
Abrams SA, Tiosano D. Disorders of calcium, phosphorus, and magnesium metabolism in the neonate. In: Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin’s neonatal perinatal medicine- diseases of the fetus and infant.(11th ed). Philadelphia: Elsevier 2020:1611-1642.
Sawhney S, Vaish R., Jain S, et al. Parathyroid carcinoma: a review. Indian journal of surgical oncology, 2022;13(1), 133-142.
Pieterman CR, & Valk, G. D. Update on the clinical management of multiple endocrine neoplasia type 1. Clinical Endocrinology, 2022;97(4), 409-423.
Mathiesen, JS, Effraimidis G, Rossing, M, et al. Multiple endocrine neoplasia type 2: A review. In Seminars in Cancer Biology 2022;(79), 163-179.
de Herder WW, & Hofland J. Multiple endocrine neoplasia type 4. Endotext, 2022.
Boro H, Khatiwada S, Alam S, et al. The spectrum of manifestations of primary hyperparathyroidism in children and adolescents. Pediatric Endocrinology Diabetes and Metabolism, 2022; 28(1).
Lasbleiz A, Paladino NC, Romanet P, et al. Familial hypocalciuric hypercalcemia: the challenge of diagnosis. Endocrine, 2022;1-4.
Clines GA, Guise TA. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. Endocr Relat Cancer 2005; 12:549.
Tebben PJ, Singh RJ, Kumar R. Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment. Endocr Rev 2016; 37:521.
Mifsud S, Mifsud EL, Agius SM, et al. Immobilisation hypercalcaemia. British Journal of Hospital Medicine, 2022;83(6), 1-7.
