Step by Step
Act
Activation pathway — three steps
Vitamin D3 (cholecalciferol) is made in skin from 7-dehydrocholesterol + UV light (or obtained from diet — fatty fish, fortified foods). Step 1: liver → 25-hydroxylase → 25-OH-D3 (calcidiol) — the storage and serum form. Step 2: kidney → 1α-hydroxylase → 1,25-(OH)₂D3 (calcitriol) — the active form. PTH stimulates step 2; low phosphate also activates it.
Memory trick: Sun → skin → liver → kidney → calcitriol. Three stops on the vitamin D train.
Act2
Actions of calcitriol
Calcitriol (1,25-(OH)₂D3) binds nuclear vitamin D receptor (VDR) → gene expression changes: Intestine: ↑ Ca²⁺ and phosphate absorption (main effect). Kidney: ↑ Ca²⁺ and phosphate reabsorption. Bone: ↑ mineralization (at normal levels); at high levels supports osteoclast activity. Net result: raises serum Ca²⁺ and phosphate.
Ric
Rickets — deficiency in children
Rickets: vitamin D deficiency in growing children → inadequate bone mineralization → soft, pliable bones → bowing of weight-bearing legs, rachitic rosary (costochondral junction enlargement), Harrison's groove, craniotabes (soft skull). Lab: low Ca²⁺, low phosphate, HIGH ALP (alkaline phosphatase), HIGH PTH (secondary hyperparathyroidism).
Memory trick: Rickets = 'Rickety bones' in children. Low Ca²⁺ → PTH rises → tries to fix it.
Ost
Osteomalacia — deficiency in adults
Osteomalacia: same pathophysiology as rickets but in adults (epiphyses closed). Presents as bone pain, muscle weakness, fractures (especially pseudofractures/Looser zones on X-ray). Causes: low sunlight exposure, fat malabsorption, chronic kidney disease, anticonvulsants (induce hepatic enzymes that degrade vitamin D).
Applied Walkthrough
1
A breastfed infant in a northern city (low sunlight) with dark skin (melanin reduces UV penetration) develops rickets — breastmilk is low in vitamin D, and sun exposure is minimal.
2
Bowing of the legs, rachitic rosary, and elevated ALP confirm the diagnosis. Oral vitamin D3 supplementation corrects the deficiency over weeks.
3
A patient with chronic kidney disease (stage 4) develops osteomalacia — the kidney cannot perform 1α-hydroxylation → calcitriol deficiency → low Ca²⁺ → secondary hyperparathyroidism → bone loss.
4
Treatment: calcitriol (active form) directly — bypassing the defective kidney step. Calcium supplementation also given.
Exam Application
Exams test the three-step activation pathway (skin → liver → kidney), the active form (calcitriol/1,25-OH₂D3), which serum form is measured (25-OH-D3 for assessing stores), the difference between rickets (children) and osteomalacia (adults), and lab findings in deficiency (low Ca²⁺, low PO4, high ALP, high PTH). Causes of deficiency and the kidney disease connection are also high yield.
⚠ Common Trap
Students confuse 25-OH-D (calcidiol, the storage/serum form measured to assess vitamin D status) with 1,25-(OH)₂D (calcitriol, the active form). Also: vitamin D toxicity causes HYPERCALCEMIA (not just excess vitamin D in blood) — symptoms include kidney stones, polyuria, confusion, and calcification of soft tissues.
✓ Quick Self-Check
1. What is the active form of vitamin D?
1,25-dihydroxycholecalciferol (calcitriol) — produced by 1α-hydroxylation in the kidney.
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2. Which form of vitamin D is measured to assess vitamin D status?
25-hydroxycholecalciferol (25-OH-D3 / calcidiol) — the storage form in serum.
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3. What are the lab findings in vitamin D deficiency?
Low serum Ca²⁺, low phosphate, elevated ALP, elevated PTH (secondary hyperparathyroidism).
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4. Why do patients with chronic kidney disease develop osteomalacia?
The kidney cannot perform 1α-hydroxylation → calcitriol cannot be produced → calcium absorption falls → bone mineralization fails.
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5. What is the difference between rickets and osteomalacia?
Same pathophysiology (vitamin D deficiency → soft bones) but rickets affects growing children (epiphyses open); osteomalacia affects adults (epiphyses closed).
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