Vitamin D Synthesis and Action

Vitamin D

• Vitamin D increases both plasma calcium (Ca²⁺) and phosphate levels.
• Vitamin D synthesis depends on calcium status, prolactin, parathyroid hormone, and estrogens.

Vitamin D Synthesis

• Synthesis starts with 7-dehydrocholesterol in the skin, processed by UV light.
• Diet or supplements can also provide Vitamin D.
• Cholecalciferol (Vitamin D3) is produced in the liver, converted to calcidiol (25-hydroxyvitamin D).
• Calcidiol is then processed in the kidneys to form calcitriol (1,25-dihydroxyvitamin D), which is the active form.
• An inactive metabolite (24,25-dihydroxyvitamin D) is also produced.

Vitamin D Action in the Intestine

• The primary function of vitamin D in the intestine is to increase calcium and phosphate absorption.
• The process is indirect; vitamin D stimulates the synthesis of calbindin D-28K, a protein that facilitates calcium transport across intestinal cells.
• A calcium channel, TRPV6, is involved in the lumen.

Vitamin D Action in the Kidney

• Vitamin D has a minor effect on kidney function, primarily in reabsorbing calcium and phosphate.

Vitamin D Action in the Bone

• Vitamin D, along with parathyroid hormone (PTH), affects osteoclast activity in bone.
• The combined effect results in bone resorption (breakdown of old bone).
• Vitamin D also stimulates bone mineralization (creation of new bone) due to high calcium levels.

Calcitonin

• Calcitonin is produced by parafollicular C cells of the thyroid gland (32 amino acids).
• It is a short-acting hormone (t_1/2 = 10 min) mainly impacting calcium levels.
• It decreases plasma [Ca²⁺] and inhibits osteoclast activity (bone resorption).
• It also decreases calcium and phosphate reabsorption in the kidneys.
• Calcitonin is not associated with significant pathophysiological conditions when deficient.
• It may have a role in infant, pregnancy, and lactation.

Other Hormones Affecting Bone Turnover

• Estrogens and androgens decrease bone reabsorption.
• Cortisol increases bone reabsorption.
• Thyroxine is necessary during fetal bone development and increases bone mass during growth.
• Local factors like IGF-1, TGF, PG's and BMP influence bone cell activity and formation.

Hypocalcemia

• Hypocalcemia is characterized by total serum calcium levels < 8.8 mg/dL (< 2.20 mmol/L) or ionized calcium levels < 4.7 mg/dL (< 1.17 mmol/L).
• Symptoms include hyperreflexia, spontaneous twitching, muscle cramps, tingling, numbness, muscle twitching, and signs like Trousseau and Chvostek signs.

Hypocalcaemia, Vit D Deficiency

• Dietary lack of Vitamin D, inability to absorb Vitamin D, or issues with Vitamin D metabolism (Kidney or Liver disease ) cause hypocalcaemia.
• Children: symptoms include rickets and abnormalities in growth and skeletal development.
• Adults: Symptoms include osteomalacia, leading to soft, bending bones.

Hypoparathyroidism

• Conditions like post-thyroid/parathyroid surgery, radioactive iodine ablation, and autoimmune disorders cause hypoparathyroidism.
• Low PTH, hypocalcaemia, and hyperphosphatemia are common symptoms.
• Replacement therapy, including oral calcium and vitamin D, is used for treatment.

Pseudohypoparathyroidism

• An inherited autosomal dominant disorder.
• Defects in the PTH receptor lead to this condition.

Hypercalcemia

• Hypercalcemia can be PTH-mediated (primary/tertiary hyperparathyroidism, familial hypocalciuric hypercalcemia, ectopic PTH secretion) or not PTH-mediated (vitamin D-mediated excess or malignant tumors that release PTH-related protein/Calcitriol-secreting tumors).

Primary Hyperparathyroidism

• High calcium levels, increased bone resorption, and increased calcium reabsorption in the kidneys are common symptoms.
• Kidney stones and surgical removal of parathyroid glands are possible treatments.

Secondary Hyperparathyroidism

• Hypocalcemia (caused by Vitamin D deficiency or chronic renal failure) usually triggers this condition.

Malignancy-Associated Hypercalcemia

• Cancer cells produce parathyroid hormone-related protein (PTHrP), leading to increased calcium levels.
• Bone, and cancer cells release calcium, along with increased intestinal absorption, triggering high calcium.
• Main cause of elevated serum calcium in hospitalized patients.

Osteoporosis

• A decrease in total bone mass.
• Long-term dietary calcium or vitamin D deficiency, vitamin C deficiency affecting collagen synthesis, immobilisation, stress, and menopause (reduced estrogen levels) are all possible causes.
• Certain medications, like anticonvulsants and glucocorticoids, also contribute to osteoporosis development.

Osteopenia

• A bone reduction condition signifying a 'poverty of bone.
• Osteoporosis, osteomalacia, and hyperparathyroidism are possible consequences.
• Deficient/normal matrix, normal/defecient mineralization, and increased/normal bone resorption differentiate stages.

This quiz covers the synthesis of Vitamin D, its dependence on various hormones, and its role in absorbing calcium and phosphate in the intestine. Test your knowledge on the biochemical processes and functions of Vitamin D in the body.