Vitamin D Overview and Synthesis

Vitamin D

• Vitamin D (1,25-dihydroxycholecalciferol) increases plasma calcium and phosphate levels.
• Synthesis of Vitamin D depends on calcium status, prolactin, parathyroid hormone, and estrogens.

Vitamin D Synthesis

• Vitamin D3 (cholecalciferol) is synthesised in the skin from 7-dehydrocholesterol via UV light.
• Vitamin D2 (ergocalciferol) is obtained through diet or supplements.
• The liver converts vitamin D to calcidiol (25-hydroxyvitamin D).
• The kidney converts calcidiol to calcitriol (1,25-dihydroxyvitamin D), the active form of vitamin D.
• An inactive metabolite (24,25-dihydroxyvitamin D) is also produced in the kidney.

Vitamin D Action

• Intestine: Vitamin D increases calcium and phosphate absorption (indirectly). It does this by inducing the synthesis of calbindin D-28K, a protein that binds calcium, which then gets transported across the intestinal cell. The calcium channel in the gut lumen is TRPV6.
• Kidney: Vitamin D has a minor effect on calcium and phosphate reabsorption.
• Bone: Vitamin D has a minor role in bone resorption (in conjunction with PTH, on old bone), and in new bone mineralisation, which is driven by high calcium levels.

Calcitonin

• Calcitonin is a product of parafollicular C cells in the thyroid.
• It's a 32 amino acid peptide with a specific structure.
• Calcitonin's action is primarily short-term (T1/2 = 10 minutes), influencing calcium homeostasis.
• It lowers plasma calcium levels by inhibiting osteoclast activity in bone, preventing calcium release into the blood, and reducing calcium and phosphate reabsorption in the kidneys.
• There are no major pathological consequences from a lack of calcitonin. It might play a role in infancy, pregnancy, and lactation.

Other Hormones Affecting Bone Turnover

• Estrogen and androgens decrease bone reabsorption.
• Cortisol increases bone reabsorption.
• Thyroxine is crucial for fetal bone development and peak bone mass accrual during growth. In adults, it has a catabolic effect on bone turnover.
• Local factors such as IGF-1, TGFs (transforming growth factors), PGs (prostaglandins) and BMPs (bone morphogenetic proteins) play specific roles in osteoblast proliferation, activity, and bone formation.

Hypocalcemia

• Hypocalcemia is a condition marked by low total serum calcium (<8.8 mg/dL or <2.20 mmol/L) and serum ionized calcium (<4.7 mg/dL or <1.17 mmol/L) if normal plasma protein levels.
• Symptoms include hyperreflexia, twitching, muscle cramps, tingling, numbness, muscle weakness, and, potentially, Trousseau's and Chvostek's signs.
• Trousseau's sign is characterized by carpopedal spasms that result from occluding brachial artery blood flow.
• Chvostek's sign is a twitching in the facial muscles induced by a tap on the facial nerve.

Vitamin D Deficiency

• Causes can include dietary lack, inability to absorb vitamin D, or issues with metabolizing inactive vitamin D (e.g., kidney or liver disorders).
• Childhood deficiency manifests as rickets, skeletal deformities, and growth failure.
• Adult deficiency results in osteomalacia (soft bones) and difficulty bearing weight.

Vitamin D Resistance

• Kidney's inability to produce 1,25-hydroxycholecalciferol.
• Congenital absence or impairment of 1α-hydroxylase or chronic kidney disease.

Hypoparathyroidism

• Post-thyroid/parathyroid surgery, radioactive iodine (I₂), or autoimmune deficiency can cause this.
• Low parathyroid hormone (PTH), hypocalcemia and hyperphosphatemia are characteristic.
• Treatment includes hormone replacement therapy and calcium/vitamin D supplements.
• Pseudohypoparathyroidism is an inherited condition where PTH receptors don't work properly.

Hypercalcemia

• Hypercalcemia is a condition with elevated blood calcium levels.
• PTH-mediated causes include primary and tertiary hyperparathyroidism, familial hypocalciuric hypercalcemia, and ectopic PTH secretion.
• Vitamin D-mediated causes include excessive vitamin D ingestion or calcitriol excess.
• Not PTH/Vitamin D-mediated causes include tumors that secrete PTH-related protein (PTHrP), and those that affect calcium metabolism by bone metastases and destruction.

Hyperparathyroidism

• Primary hyperparathyroidism results in hypercalcemia, increased bone resorption and absorption of calcium (gut and kidney). Kidney stones are common. Treatment surgically removing the parathyroid glands.
• Secondary hyperparathyroidism occurs due to hypocalcemia from vitamin D deficiency or chronic kidney failure.

Malignancy-Associated Hypercalcemia

• Cancer can cause excessive calcium release from bones thus raising calcium levels in blood.
• The mechanism involves parathyroid hormone-related protein (PTHrP) increasing bone resorption of calcium.
• The PTH receptor family includes PTH1 and PTH2 receptors, and PTH, PTHrP, and TIP39 are the ligands that bind to these receptors.
• This condition is a common cause of hypercalcemia in hospitalized patients.

Osteoporosis

• Osteoporosis is a decrease in total bone mass.
• Causes include long-term dietary deficiencies of calcium and vitamin D, vitamin C deficiency (needed for collagen synthesis), immobilization, and menopause's reduced estrogen levels.
• Certain medications, such as anticonvulsants and corticosteroids, also contribute.

Osteopenia

• Osteopenia is a term for low bone density, representing a decrease in bone mass.
• May predispose someone to osteoporosis.

This quiz delves into the intricate details of Vitamin D, including its synthesis, action in the body, and factors influencing its production. Explore how Vitamin D affects plasma calcium and phosphate levels and its absorption processes in the intestine and kidney. Test your understanding of this essential nutrient and its biological significance.