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Calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Calcitriol increases blood calcium (Ca2+) mainly by increasing the uptake of calcium from the intestines. It can be given as a medication for the treatment of low blood calcium and hyperparathyroidism due to kidney disease, low blood calcium due to hypoparathyroidism, osteoporosis, osteomalacia, and familial hypophosphatemia, and can be taken by mouth or by injection into a vein. Excessive amounts or intake can result in weakness, headache, nausea, constipation, urinary tract infections, and abdominal pain. Serious side effects may include high blood calcium and anaphylaxis. Regular blood tests are recommended after the medication is started and when the dose is changed. Calcitriol was identified as the active ...
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Vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). The major natural source of the vitamin is synthesis of cholecalciferol in the lower layers of epidermis of the skin through a chemical reaction that is dependent on sun exposure (specifically UVB radiation). Cholecalciferol and ergocalciferol can be ingested from the diet and supplements. Only a few foods, such as the flesh of fatty fish, naturally contain significant amounts of vitamin D. In the U.S. and other countries, cow's milk and plant-derived milk substitutes are fortified with vitamin D, as are many breakfast cereals. Mushrooms exposed to ultraviolet light contribute useful amounts of vitamin D2. Dietary recommendations typically assume that all of a person's vitamin D is taken ...
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Calcipotriol
Calcipotriol, also known as calcipotriene, is a synthetic derivative of calcitriol, a form of vitamin D. It is used in the treatment of psoriasis. It is safe for long-term application in psoriatic skin conditions. It was patented in 1985 and approved for medical use in 1991. It is marketed under the trade name "Dovonex" in the United States, "Daivonex" outside North America, and "Psorcutan" in Germany. It is on the World Health Organization's List of Essential Medicines. Calcipotriol is also available as Calcipotriol/betamethasone dipropionate, a fixed-dose combination medication with the synthetic corticosteroid betamethasone dipropionate for the treatment of plaque psoriasis. Medical uses Chronic plaque psoriasis is the chief medical use of calcipotriol. It has also been used successfully in the treatment of alopecia areata. Contraindications Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only contraindications for calcipotriol ...
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Renal Osteodystrophy
Renal osteodystrophy/adynamic bone disease is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure. The traditional types of renal osteodystrophy have been defined on the basis of turnover and mineralization as follows: 1) mild, slight increase in turnover and normal mineralization; 2) osteitis fibrosa, increased turnover and abnormal mineralization; 3) osteomalacia, decreased turnover and abnormal mineralization; 4) adynamic, decreased turnover and acellularity; and, 5) mixed, increased turnover with abnormal mineralization. A Kidney Disease: Improving Global Outcomes report has suggested that bone biopsies in patients with CKD should be characterized by determining bo ...
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Familial Hypophosphatemia
X-linked hypophosphatemia (XLH) is an X-linked dominant form of rickets (or osteomalacia) that differs from most cases of dietary deficiency rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short stature and genu varum (bow-leggedness). It is associated with a mutation in the ''PHEX'' gene sequence (Xp.22) and subsequent inactivity of the PHEX protein. ''PHEX'' mutations lead to an elevated circulating (systemic) level of the hormone FGF23 which results in renal phosphate wasting, and locally in the extracellular matrix of bones and teeth an elevated level of the mineralization/calcification-inhibiting protein osteopontin. An inactivating mutation in the PHEX gene results in an increase in systemic circulating FGF23, and a decrease in the enzymatic activity of the PHEX enzyme which normally removes (degrades) mineralization-inhibiting osteopontin protein; in XLH, the decreased PHEX enzyme activity leads to an accumulation of inhibito ...
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Vitamin D Analogue
The active natural hormonal form of vitamin D is 1,25-dihydroxyvitamin D (1,25(OH)2D). This molecule and other naturally occurring forms of vitamin D, including its precursors and metabolites, have been modified to synthesize pharmaceuticals with potentially greater, or selective, therapeutic actions. Types These include: * Alfacalcidol * Calcipotriol (calcipotriene) * Doxercalciferol * Falecalcitriol * Paricalcitol * Tacalcitol Mechanisms These modified vitamin D analogues have side chain or other modifications. They aim to reduce the classical renal and intestinal effects of calcitriol on calcium and phosphate homeostasis, from its effects on other biologic processes. They target cell proliferation and differentiation, especially in skin, or other effects in the parathyroid gland (secondary hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparat ...
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High Blood Calcium
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest. Most outpatient cases are due to primary hyperparathyroidism and inpatient cases due to cancer. Other causes of hypercalcemia include sarcoidosis, tuberculosis, Paget disease, multiple endocrine neoplasia (MEN), vitamin D toxicity, familial hypocalciuric hypercalcaemia and certain medications such as lithium and hydrochlorothiazide. Diagnosis should generally include either a corrected calcium or ionized calcium level and be confirmed after a week. Specific chang ...
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Hypercalcemia
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest. Most outpatient cases are due to primary hyperparathyroidism and inpatient cases due to cancer. Other causes of hypercalcemia include sarcoidosis, tuberculosis, Paget disease, multiple endocrine neoplasia (MEN), vitamin D toxicity, familial hypocalciuric hypercalcaemia and certain medications such as lithium and hydrochlorothiazide. Diagnosis should generally include either a corrected calcium or ionized calcium level and be confirmed after a week. Specific chang ...
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Vitamin D Receptor
The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. VDR binding results in expression or transrepression of many specific gene products. VDR is also involved in microRNA-directed post transcriptional mechanisms. In humans, the vitamin D receptor is encoded by the ''VDR'' gene located on chromosome 12q13.11. VDR is expressed in most tissues of the body, and regulates transcription of genes involved in intestinal and renal transport of calcium and other minerals. Glucocorticoids decrease VDR expression. Many types of immune cells also express VDR. Function The VDR gene encodes the nuclear hormone receptor for vitamin D. The most potent natural ag ...
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Kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder. The kidney participates in the control of the volume of various body fluids, fluid osmolality, acid–base balance, various electrolyte concentrations, and removal of toxins. Filtration occurs in the glomerulus: one-fifth of the blood volume that enters the kidneys is filtered. Examples of substances reabsorbed are solute-free water, sodium, bicarbonate, glucose, and amino acids. Examples of substances secreted are hydrogen, ammonium, potassium and uric acid. The nephron is the structural and functional unit of the kidney. Each adult human kidney contains around 1 million nephrons, while a mouse kidney contains on ...
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Kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder. The kidney participates in the control of the volume of various body fluids, fluid osmolality, acid–base balance, various electrolyte concentrations, and removal of toxins. Filtration occurs in the glomerulus: one-fifth of the blood volume that enters the kidneys is filtered. Examples of substances reabsorbed are solute-free water, sodium, bicarbonate, glucose, and amino acids. Examples of substances secreted are hydrogen, ammonium, potassium and uric acid. The nephron is the structural and functional unit of the kidney. Each adult human kidney contains around 1 million nephrons, while a mouse kidney contains on ...
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Rickets
Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications may include bone deformities, bone pseudofractures and fractures, muscle spasms, or an abnormally curved spine. The most common cause of rickets is a vitamin D deficiency, although hereditary genetic forms also exist. This can result from eating a diet without enough vitamin D, dark skin, too little sun exposure, exclusive breastfeeding without vitamin D supplementation, celiac disease, and certain genetic conditions. Other factors may include not enough calcium or phosphorus. The underlying mechanism involves insufficient calcification of the growth plate. Diagnosis is generally based on blood tests finding a low calcium, low phosphorus, and a high alkaline phosphatase together with X-rays. Prevention for exclusively breastfed babies ...
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Calcium In Biology
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cell (biology), cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a Cofactor (biochemistry), cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell cell membrane, membranes, as well as proper bone formation. Plasma calcium levels in mammals are tightly regulated, electronic-book electronic- with bone acting as the major mineral storage site. Calcium ions, Ca2+, are released from bone into the bloodstream under controlled conditions. Calcium is transported through the bloodstream as dissolved ions or bound to proteins such as serum albumin. Parathyroid hormone secreted by the parathyroid gland regulates ...
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