Calcium and Bone Metabolism

Calcium & Phosphate - Mineral Harmony

• Normal Serum Calcium: 8.5-10.5 mg/dL (Total); 4.5-5.5 mg/dL (Ionized - active form).
• Normal Serum Phosphate: 2.5-4.5 mg/dL.
• Key Hormonal Regulators:
  • Parathyroid Hormone (PTH): ↑ Ca, ↓ PO₄ (acts on bone, kidney).
  • Vitamin D (Calcitriol): ↑ Ca, ↑ PO₄ (acts on gut, bone, kidney).
  • Calcitonin: ↓ Ca, ↓ PO₄ (minor role in humans).
• Calcium-Phosphate Product: $Ca \times PO_4$ normally < 55 mg²/dL².
  • 📌 Mnemonic: "PTH Pushes The High (Ca), Flushes The Low (PO₄)".

⭐ Ionized calcium is the physiologically active form and is affected by pH (acidosis ↑ ionized Ca, alkalosis ↓ ionized Ca).

Calcium's Captains - PTH & Vit D

Parathyroid Hormone (PTH):

• Secreted by: Parathyroid chief cells (stimulus: ↓ Serum $Ca^{2+}$).
• Key Actions:
  • Bone: ↑ Osteoclast activity → ↑ $Ca^{2+}$ & ↑ $PO_4^{3-}$ release.
  • Kidney: ↑ $Ca^{2+}$ reabsorption (DCT); ↓ $PO_4^{3-}$ reabsorption (PCT) → phosphaturia. 📌 PTH = Phosphate Trashing Hormone.
  • Kidney: Stimulates 1α-hydroxylase → ↑ active Vit D ($1,25(OH)_2D$).
• Overall: ↑ Serum $Ca^{2+}$, ↓ Serum $PO_4^{3-}$.

Vitamin D (Calcitriol - $1,25(OH)_2D$):

• Activation: Diet/Skin → Liver ($25(OH)D$) → Kidney ($1,25(OH)_2D$ by 1α-hydroxylase; stim: PTH, ↓$Ca^{2+}$, ↓$PO_4^{3-}$).
• Key Actions:
  • Intestine: ↑ $Ca^{2+}$ & ↑ $PO_4^{3-}$ absorption (primary effect).
  • Bone: Promotes mineralization; high doses → resorption.
  • Kidney: ↑ $Ca^{2+}$ & ↑ $PO_4^{3-}$ reabsorption.
  • Parathyroid: ↓ PTH synthesis (feedback).
• Overall: ↑ Serum $Ca^{2+}$, ↑ Serum $PO_4^{3-}$.

⭐ PTH primarily increases serum calcium and decreases serum phosphate (via phosphaturia), while active Vitamin D (calcitriol) increases both serum calcium and serum phosphate (via gut/kidney absorption).

Calcium Chaos - Ups & Downs Drama

Hypocalcemia (↓$Ca^{2+}$)

• Causes: Hypoparathyroidism, Vit D deficiency, CKD, ↓Mg.
• S/S: Tetany (Chvostek's, Trousseau's signs), paresthesia. 📌 CATS Go Numb (Convulsions, Arrhythmias, Tetany, Spasms). ECG: ↑QT interval.
• Rx: Acute: IV $Ca^{2+}$ gluconate. Chronic: Oral $Ca^{2+}$ + Vit D.

Hypercalcemia (↑$Ca^{2+}$)

• Causes:
  • PTH-dependent: Primary hyperparathyroidism.
  • PTH-independent: Malignancy (PTHrP), Vit D toxicity, Sarcoidosis. 📌 CHIMPANZEES.
• S/S: "Stones (renal), Bones (pain), Groans (abd pain), Thrones (polyuria), Psych". ECG: ↓QT interval.
• Rx: IV Saline, Furosemide (post-hydration), Bisphosphonates.

⭐ Malignancy & primary hyperparathyroidism: most common causes of hypercalcemia in adults.

Bone Structure Blues - When Bones Weaken

• Osteoporosis: Reduced bone mass & microarchitectural deterioration, ↑fracture risk.
  • Risk Factors: Age, post-menopause, low Ca/Vit D, corticosteroids, smoking. 📌 ACCESS: Alcohol, Corticosteroid, Calcium low, Estrogen low, Smoking, Sedentary.
  • Diagnosis: DEXA scan T-score ≤ -2.5.
  • Clinical: Fragility fractures (vertebral, hip, Colles'). Often silent.
  • Management: Calcium, Vit D, bisphosphonates, exercise.
• Osteomalacia & Rickets: Defective bone mineralization; soft bones.
  • Rickets (children): Epiphyseal plate widening, bowing legs, rachitic rosary.
  • Osteomalacia (adults): Bone pain, muscle weakness, waddling gait.
  • Causes: Severe Vit D deficiency (common), renal phosphate wasting, malabsorption.
  • Labs: ↓Ca²⁺, ↓PO₄³⁻ (or normal Ca²⁺ due to ↑PTH), ↑ALP, ↑PTH. $25(OH)D$ levels low.

  ⭐ Looser's zones (pseudofractures) on X-ray are characteristic of osteomalacia.

High-Yield Points - ⚡ Biggest Takeaways

• Primary hyperparathyroidism: Commonest outpatient hypercalcemia; stones, bones, groans.
• Vitamin D deficiency: Causes rickets/osteomalacia; ↓Ca, ↓PO4, ↑PTH, ↑ALP.
• Paget's disease of bone: ↑ALP, normal Ca/PO4; risk of osteosarcoma, deafness.
• Osteoporosis: Diagnosed by DEXA (T-score ≤ -2.5); bisphosphonates are first-line.
• Hypercalcemia of malignancy: Often due to PTHrP or lytic bone metastases.
• Hypoparathyroidism: Presents with ↓Ca, ↑PO4, ↓PTH; Chvostek's & Trousseau's signs.