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
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