U01.01.083 Vitamin D

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Learning Objectives

  • Trace the activation pathway of Vitamin D from skin/diet to the kidney.
  • Identify the roles of PTH, Calcium, and Phosphate in regulating 1\alpha-hydroxylase.
  • Differentiate between Rickets and Osteomalacia.
  • Explain the mechanism of Hypercalcemia in granulomatous diseases.

1. Synthesis and Activation

Vitamin D is unique because it can be synthesized endogenously via UV exposure or obtained through the diet. It requires two hydroxylation steps to become active.

  • Source:
    • D3 (Cholecalciferol): From sun exposure (stratum basale) and animal products (fish, milk).
    • D2 (Ergocalciferol): From plants, fungi, and yeasts.
  • Liver: Converts D2/D3 to 25-OH D3 (the primary storage form) via 25-hydroxylase.
  • Kidney: Converts 25-OH D3 to 1,25-(OH)2 D3 (Calcitriol), the active form, via 1\alpha-hydroxylase.

2. Physiological Functions & Regulation

Calcitriol acts primarily to increase serum calcium and phosphate levels to support bone mineralization.

Target Organ Action of 1,25-(OH)2 D3
Intestine ↑ absorption of dietary Ca^{2+} and PO_4^{3-}.
Bone ↑ mineralization (at low levels); ↑ resorption (at high levels).
Kidney ↑ Ca^{2+} and PO_4^{3-} reabsorption.

Regulation: 1\alpha-hydroxylase activity is stimulated by ↑ PTH, ↓ serum Ca^{2+}, and ↓ serum $LatexPO_4^{3-}$. Calcitriol also provides negative feedback on its own production.

3. Deficiency: Rickets and Osteomalacia

Deficiency leads to poor bone mineralization. Causes include CKD (loss of 1\alpha-hydroxylase), malabsorption, and lack of sun exposure.

  • Rickets (Children): Softening of bones leading to skeletal deformities like genu varum (bowlegs) and rachitic rosary.
  • Osteomalacia (Adults): Bone pain, muscle weakness, and increased risk of “pseudo-fractures.”
  • Hypocalcemic Tetany: Involuntary muscle contractions due to low serum calcium.

4. Toxicity & Granulomatous Disease

Excess Vitamin D causes Hypercalcemia and hypercalciuria (loss of appetite, stupor).

High-Yield Correlation: In granulomatous diseases (like Sarcoidosis), epithelioid macrophages contain 1$\alpha$-hydroxylase and activate Vitamin D independent of PTH, leading to hypercalcemia.

 

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