Dr. Pruthvi, I can certainly provide a detailed guide on vitamin D physiology.
While I can't
generate a PDF file directly, the following information is structured for easy use as a study
guide for medical students, similar to the one on vitamin B12.
Vitamin D: General Physiology
Vitamin D is a fat-soluble vitamin that acts more like a steroid hormone than a vitamin. It is
essential for calcium and phosphate homeostasis and plays a crucial role in bone health. It
exists in two main forms:
• Vitamin D3 (cholecalciferol): Synthesized in the skin upon exposure to ultraviolet B
(UVB) radiation from sunlight. It is also found in some animal-based foods like oily
fish.
• Vitamin D2 (ergocalciferol): Derived from plant sources and found in fortified foods
and supplements.
Both forms are biologically inactive and must be metabolized to become active.
Synthesis and Metabolism
The activation of vitamin D is a two-step hydroxylation process that occurs in the liver and
kidneys.
• Skin Synthesis: The process begins in the skin where 7-dehydrocholesterol, a
precursor molecule, is converted to pre-vitamin D3 by UVB radiation. This pre-
vitamin D3 then spontaneously isomerizes into vitamin D3 (cholecalciferol). This
process is self-regulating, as prolonged sun exposure leads to the breakdown of pre-
vitamin D3 into inactive byproducts, preventing vitamin D toxicity from sunlight
alone.
• Liver Hydroxylation: Both dietary vitamin D (D2 and D3) and that synthesized in the
skin are transported to the liver. Here, the enzyme 25-hydroxylase (CYP2R1) adds a
hydroxyl group at the C-25 position, converting it to 25-hydroxyvitamin D [25(OH)D],
also known as calcidiol. This is the main circulating form of vitamin D and the best
indicator of a person's vitamin D status.
• Kidney Hydroxylation (Activation): The 25(OH)D is then transported to the kidneys.
The enzyme 1-alpha-hydroxylase (CYP27B1), primarily located in the proximal
convoluted tubules of the kidney, adds another hydroxyl group at the C-1 position.
This final step converts 25(OH)D into 1,25-dihydroxyvitamin D [1,25(OH)2D], the
biologically active form of vitamin D, also known as calcitriol. The activity of 1-alpha-
hydroxylase is tightly regulated by hormones like parathyroid hormone (PTH) and
fibroblast growth factor 23 (FGF23).
Key Physiological Functions
The primary function of active vitamin D (calcitriol) is to maintain serum calcium and
phosphorus levels within a narrow range.
• Intestinal Absorption: Calcitriol acts on the small intestine to increase the absorption
of dietary calcium and phosphorus. It does this by stimulating the synthesis of
calcium-binding proteins, such as calbindin, which facilitate the movement of these
minerals across the intestinal wall.
• Bone Regulation: When serum calcium levels are low, calcitriol, along with PTH,
promotes the mobilization of calcium from bone. This process, involving osteoclasts,
helps to maintain calcium homeostasis, but prolonged mobilization can weaken
bones. Calcitriol also facilitates bone mineralization by ensuring sufficient calcium
and phosphate are available for deposition.
• Kidney Reabsorption: Calcitriol increases calcium and phosphorus reabsorption from
the renal tubules in the kidneys, reducing their excretion in urine.
Clinical Significance: Deficiency
A deficiency in vitamin D can have severe consequences, particularly on bone health.
• Rickets: In children, a lack of vitamin D leads to inadequate bone mineralization,
causing the bones to become soft and deformed. This condition is known as rickets,
which can result in bowed legs and other skeletal deformities.
• Osteomalacia: In adults, vitamin D deficiency leads to osteomalacia, a condition
characterized by soft bones and an accumulation of unmineralized osteoid.
Symptoms include bone pain and muscle weakness.
• Secondary Hyperparathyroidism: Chronic vitamin D deficiency leads to low serum
calcium, which triggers an increase in PTH secretion (secondary
hyperparathyroidism). This elevated PTH mobilizes calcium from the bone, increasing
the risk of osteoporosis and fractures.
Risk Factors for Deficiency:
• Insufficient sunlight exposure: This is the most common cause, especially in
northern latitudes or for individuals who are housebound, use sunscreen, or have
darker skin pigmentation.
• Inadequate dietary intake: Particularly relevant for individuals who are vegan or
vegetarian without proper supplementation.
• Malabsorption syndromes: Conditions like Crohn's disease, celiac disease, or cystic
fibrosis can impair fat-soluble vitamin absorption.
• Renal or liver disease: These conditions can interfere with the metabolic activation
of vitamin D.
