Calcium and Phosphate Homeostasis

Integrated Regulatory Mechanisms
Calcium & Phosphate Homeostasis: Regulatory Pathways Parathyroid Glands PTH Secretion KIDNEYS Functions: • Ca²⁺ reabsorption ↑ • PO₄³⁻ excretion ↑ • 1α-hydroxylase ↑ • Calcitriol synthesis • FGF23 response BONES Functions: • Ca²⁺ storage (99%) • PO₄³⁻ storage (85%) • Resorption/Formation • FGF23 production GI TRACT Absorption: • Ca²⁺ (30-40%) • PO₄³⁻ (60-70%) • Vit D enhanced SERUM POOL Ca²⁺: 8.5-10.5 mg/dL PO₄³⁻: 2.5-4.5 mg/dL Vitamin D System Skin: 7-DHC → D₃ ↓ Liver: 25(OH)D ↓ Kidney: 1,25(OH)₂D (Calcitriol) FGF23 (from osteocytes) • ↓ PO₄ reabsorption • ↓ 1α-hydroxylase KLOTHO Essential Co-Receptor • Expressed in kidney • Enables FGF23 signaling • Anti-aging protein • ↓ in CKD → resistance ⚠️ Rate-limiting factor FGFR KL FGF23 FGF23-Klotho-FGFR Complex (Required for signaling) 🔑 KLOTHO: Critical Roles 1. Permits FGF23 binding 2. Regulates phosphate excretion 3. Suppresses 1,25(OH)₂D 4. Protects against calcification Deficiency → FGF23 resistance PTH → ↑Ca reabsorption ↓PO₄ reabsorption PTH → ↑Bone resorption 1α-hydroxylase Calcitriol → ↑Ca/PO₄ absorption Requires Klotho Low Ca²⁺ → ↑PTH KEY REGULATORY MECHANISMS PTH: ↑Ca, ↓PO₄ Calcitriol: ↑Ca, ↑PO₄ FGF23: ↓PO₄, ↓Calcitriol CaSR: Ca sensing KLOTHO: Essential co-receptor (Rate-limiting for FGF23 action)
PTH System
Renal Function
Intestinal Absorption
Bone Metabolism
Vitamin D Pathway
FGF23 System
Klotho Co-Receptor
Serum Pool & Feedback

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