Calcitriol

Calcitriol synthesis

Active form of vitamin D, normally made in the kidney.

- Calcitriol

85 related topics

Relevance

Vitamin D receptor

Member of the nuclear receptor family of transcription factors.

Crystallographic structure of a heterodimer of the nuclear receptors PPAR-γ (green) and RXR-α (cyan) bound to double stranded DNA (magenta) and two molecules of the NCOA2 coactivator (red). The PPAR-γ antagonist GW9662 and RXR-α agonist retinoic acid are depicted as space-filling models (carbon = white, oxygen = red, nitrogen = blue, chlorine = green).

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.

Kidney

The kidneys are two reddish-brown bean-shaped organs found in vertebrates.

The kidneys lie in the retroperitoneal space behind the abdomen, and act to filter blood to create urine.
Images showing the human trunk, with positions of the organs show, and kidneys seen at the vertebral level of T12 to L3.
1. Renal pyramid •
2. Interlobular artery •
3. Renal artery •
4. Renal vein
5. Renal hilum •
6. Renal pelvis •
7. Ureter •
8. Minor calyx •
9. Renal capsule •
10. Inferior renal capsule •
11. Superior renal capsule •
12. Interlobular vein •
13. Nephron •
14. Renal sinus •
15. Major calyx •
16. Renal papilla •
17. Renal column
The nephron, shown here, is the functional unit of the kidneys. Its parts are labelled except the (gray) connecting tubule located after the (dark red) distal convoluted tubule and before the large (gray) collecting duct (mislabeled collection duct).
Four main processes are involved in the creation of urine.
Secretion and reabsorption of various substances throughout the nephron
A depiction of peritoneal dialysis.
Hökarpanna, Swedish pork and kidney stew
thumb|Normal adult right kidney as seen on abdominal ultrasound with a pole to pole measurement of 9.34 cm.
A CT scan of the abdomen showing the position of the kidneys. The left cross-section in the upper abdomen shows the liver on the left side of scan (right side of body). Center: cross-section showing the kidneys below the liver and spleen. Right: further cross-section through the left kidney.
Image showing the structures that the kidney lies near.
Left kidney
Right Kidney
Kidney
Right Kidney
Right kidney
Left kidney
Kidneys

For example, they convert a precursor of vitamin D to its active form, calcitriol; and synthesize the hormones erythropoietin and renin.

Calcium in biology

Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells.

Calcium regulation in the human body
Reference ranges for blood tests, showing calcium levels in purple at right

Parathyroid hormone secreted by the parathyroid gland regulates the resorption of Ca2+ from bone, reabsorption in the kidney back into circulation, and increases in the activation of vitamin D3 to calcitriol.

Hypocalcemia

Low calcium levels in the blood serum.

Purpura
An ECG of a person with hypocalcemia

However, in either circumstance, maintenance doses of both calcium and vitamin-D (often as 1,25-(OH)2-D3, i.e. calcitriol) are often necessary to prevent further decline

Hyperparathyroidism

Increase in parathyroid hormone levels in the blood.

Thyroid and parathyroid
Calcification in the brain due to hyperparathyroidism
Pepper & Salt, classical X-Ray appearance of hyperparathyroidisim
Parathyroid adenoma.

This typically occurs when the 1,25 dihydroxyvitamin D3 levels in the blood are low and hypocalcemia is present.

Chronic kidney disease

Type of kidney disease in which there is gradual loss of kidney function over a period of months to years.

Uremic frost on the head in someone with chronic kidney disease
A 12-lead ECG of a person with CKD and a severe electrolyte imbalance: hyperkalemia (7.4 mmol/l) with hypocalcemia (1.6 mmol/l). The T-waves are peaked and the QT interval is prolonged.
Chronic renal disease caused by glomerulonephritis with increased echogenicity and reduced cortical thickness. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.
Nephrotic syndrome. Hyperechoic kidney without demarcation of cortex and medulla.
Chronic pyelonephritis with reduced kidney size and focal cortical thinning. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.
End-stage chronic kidney disease with increased echogenicity, homogenous architecture without visible differentiation between parenchyma and renal sinus and reduced kidney size. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.

Hypocalcemia results from 1,25 dihydroxyvitamin D3 deficiency (caused by high FGF-23 and reduced kidney mass) and resistance to the action of parathyroid hormone. Osteocytes are responsible for the increased production of FGF-23, which is a potent inhibitor of the enzyme 1-alpha-hydroxylase (responsible for the conversion of 25-hydroxycholecalciferol into 1,25 dihydroxyvitamin D3). Later, this progresses to secondary hyperparathyroidism, kidney osteodystrophy, and vascular calcification that further impairs cardiac function. An extreme consequence is the occurrence of the rare condition named calciphylaxis.

Osteoporosis

Systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk.

Elderly woman with osteoporosis showing a curved back from compression fractures of her back bones.
Illustration depicting normal standing posture and osteoporosis
Progression of the shape of vertebral column with age in osteoporosis
Bone density peaks at about 30 years of age. Women lose bone mass more rapidly than men.
The body regulates calcium homeostasis with two pathways; one is signaled to turn on when blood calcium levels drop below normal and one is the pathway that is signaled to turn on when blood calcium levels are elevated.
Osteoporosis locations
Multiple osteoporotic wedge fractures demonstrated on a lateral thoraco-lumbar spine X-ray
Age-standardised hip fracture rates in 2012.
Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.
Light micrograph of osteoblasts, several displaying a prominent Golgi apparatus, actively synthesizing osteoid containing two osteocytes.
Collapse of vertebra on the right, normal on the left

Vitamin D deficiency: Low circulating Vitamin D is common among the elderly worldwide. Mild vitamin D insufficiency is associated with increased parathyroid hormone (PTH) production. PTH increases bone resorption, leading to bone loss. A positive association exists between serum 1,25-dihydroxycholecalciferol levels and bone mineral density, while PTH is negatively associated with bone mineral density.

Cholecalciferol

Type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement.

500px

It is converted in the liver to calcifediol (25-hydroxyvitamin D) which is then converted in the kidney to calcitriol (1,25-dihydroxyvitamin D).

Vitamin D

Group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects.

Cholecalciferol (D3)
Calcium regulation in the human body. The role of active vitamin D (1,25-dihydroxyvitamin D, calcitriol) is shown in orange.
Global vitamin D serum levels among adults (nmol/L).
The photochemistry of vitamin D biosynthesis in animal and fungi
Thermal isomerization of previtaminD3 to vitamin D3
In the epidermal strata of the skin, vitamin D production is greatest in the stratum basale (colored red in the illustration) and stratum spinosum (colored light brown).
Liver hydroxylation of cholecalciferol to calcifediol
Kidney hydroxylation of calcifediol to calcitriol

Instead it can be considered a hormone, with activation of the vitamin D pro-hormone resulting in the active form, calcitriol, which then produces effects via a nuclear receptor in multiple locations.

Hypercalcaemia

High calcium level in the blood serum.

Calcium within the periodic table
Micrograph of ovarian small cell carcinoma of the hypercalcemic type. H&E stain.
An Osborn wave, an abnormal EKG tracing that can be associated with hypercalcemia.
Trisetum flavescens (yellow oat grass)

Elevated 1,25(OH)2D (see calcitriol under Vitamin D) levels (e.g. sarcoidosis and other granulomatous diseases such as tuberculosis, berylliosis, histoplasmosis, Crohn's disease, and granulomatosis with polyangiitis)