Calcium-Phosphate Homeostasis System
Interactive diagram showing the integrated regulation system with kidneys, parathyroid glands, bones, and intestines
🔑 Key Concept: This system demonstrates the intricate feedback loops between PTH, FGF23, calcitriol, and calcitonin. Note how kidneys (shown in red) serve dual roles as both target organs and hormone producers in calcium-phosphate homeostasis.
🎯 Calcium Quick Reference
Normal Range: 8.5-10.5 mg/dL (2.12-2.62 mmol/L)
Ionized Calcium: 1.12-1.32 mmol/L (4.5-5.3 mg/dL)
📊 Calcium Distribution & Physiology
Total Body Calcium
~1,000g
Adult human body
Skeletal System
99%
Stored as hydroxyapatite
Extracellular
0.1%
Physiologically active
Intracellular
0.9%
Signaling & metabolism
Serum Calcium Forms
Ionized (45%) + Protein-bound (40%) + Complexed (15%)
Critical Concept: Only ionized calcium is physiologically active. Protein-bound calcium (primarily to albumin) is inactive but measured in total calcium assays.
🔄 Calcium Regulation System
Primary Regulators
| Hormone | Stimulus | Bone Effect | Kidney Effect | GI Effect | Net Result |
|---|---|---|---|---|---|
| PTH | ↓ Ionized Ca²⁺ | ↑ Resorption | ↑ Ca reabsorption ↓ PO₄ reabsorption ↑ Calcitriol |
Indirect (via calcitriol) | ↑ Serum Ca²⁺ |
| Calcitriol (1,25-Vit D) |
↑ PTH ↓ PO₄ |
↑ Resorption | ↑ Ca reabsorption | ↑ Ca & PO₄ absorption | ↑ Ca²⁺ & PO₄ |
| Calcitonin | ↑ Serum Ca²⁺ | ↓ Resorption | ↑ Ca excretion | None | ↓ Serum Ca²⁺ |
| FGF23 | ↑ PO₄ ↑ Calcitriol |
None | ↑ PO₄ excretion ↓ Calcitriol |
↓ PO₄ absorption | ↓ PO₄, indirect ↓ Ca²⁺ |
Corrected Calcium Formula
Corrected Ca = Measured Ca + 0.8 × (4.0 - Albumin)
For every 1 g/dL decrease in albumin below 4.0, add 0.8 mg/dL to measured calcium
📉 Hypocalcemia Overview
Corrected Ca < 8.5 mg/dL
Key Causes
- Hypoparathyroidism: Post-surgical, autoimmune
- Vitamin D Deficiency: Most common worldwide
- Hypomagnesemia: Must correct first!
- CKD: ↓ Calcitriol synthesis
- Pancreatitis: Saponification
- Medications: Bisphosphonates, denosumab
Clinical Manifestations
- Perioral numbness, paresthesias
- Tetany, carpopedal spasm
- Chvostek's sign (facial twitching)
- Trousseau's sign (carpal spasm)
- Seizures (severe cases)
- QT prolongation on ECG
Emergency Treatment
Calcium gluconate 10%: 1-2 amps (90-180 mg elemental Ca) IV over 10 min
Then: 50-100 mL/hr continuous infusion
📈 Hypercalcemia Overview
Corrected Ca > 10.5 mg/dL
Key Causes (90% = "2 Ps")
- Primary hyperPTH: 90% outpatient
- Malignancy (PTHrP): 90% inpatient
- Other: Vitamin D excess, thiazides
- Granulomas: Sarcoid, TB
- Immobilization: Paget's, adolescents
- Milk-alkali syndrome: CaCO₃ excess
Clinical Manifestations
- "Stones" - Nephrolithiasis
- "Bones" - Bone pain, osteoporosis
- "Groans" - Abdominal pain
- "Psychiatric overtones" - Confusion
- Polyuria, dehydration
- Short QT on ECG
Emergency Treatment
IV Fluids: NS 200-300 mL/hr
Bisphosphonates: Zoledronic acid 4mg IV
📚 VITAMINS TRAP Mnemonic
PTH-Independent Causes of Hypercalcemia:
- V - Vitamin D intoxication
- I - Immobilization
- T - Thyrotoxicosis, Thiazides
- A - Adrenal insufficiency, Vitamin A
- M - Milk-alkali syndrome, Medications
- I - Inflammatory disorders (granulomas)
- N - Neoplasm (PTHrP or lytic lesions)
- S - Sarcoidosis
- T - Teriparatide, Tertiary hyperparathyroidism
- R - Rhabdomyolysis (recovery phase)
- A - AIDS (MAC, PCP with treatment)
- P - Pheochromocytoma, Parenteral nutrition
⚠️ Critical Drug-Calcium Interactions
Drugs Affecting Calcium Levels
↑ Increase Calcium
- Thiazide diuretics (↑ reabsorption)
- Lithium (↑ PTH setpoint)
- Vitamin D supplements
- Calcium supplements
- Teriparatide (PTH analog)
- Vitamin A excess
↓ Decrease Calcium
- Loop diuretics (↑ excretion)
- Bisphosphonates
- Denosumab
- Calcitonin
- Phosphate supplements
- Cinacalcet (calcimimetic)
Calcium Effects on Drug Absorption
Reduced absorption when taken with calcium:
- Tetracyclines, Fluoroquinolones (chelation)
- Levothyroxine (30-40% reduction)
- Bisphosphonates (<2% absorption with calcium)
- Iron supplements
Clinical Pearl: Separate calcium from these medications by ≥2 hours
🔬 Laboratory Evaluation Algorithm
Initial Workup for Any Calcium Disorder:
- Confirm finding: Repeat calcium, check albumin
- Calculate corrected calcium or get ionized calcium
- Essential labs:
- PTH (intact) - KEY discriminator
- Phosphate - Inverse relationship
- Magnesium - Must be >1.7 mg/dL
- Creatinine - Assess kidney function
- 25-OH Vitamin D - Deficiency common
PTH Interpretation Guide:
| Calcium Level | PTH Level | Interpretation | Next Steps |
|---|---|---|---|
| ↑ High | ↑ High/Normal | Primary hyperparathyroidism | 24hr urine Ca, imaging |
| ↑ High | ↓ Low | PTH-independent (VITAMINS TRAP) | PTHrP, SPEP, Vit D levels |
| ↓ Low | ↑ High | Secondary hyperparathyroidism | Vit D, Mg, Cr, phosphate |
| ↓ Low | ↓ Low/Normal | Hypoparathyroidism | Mg (must correct first!) |
💡 High-Yield Clinical Pearls
- ✓ Always check magnesium - Hypocalcemia won't correct without Mg >1.7 mg/dL
- ✓ Albumin matters - Use corrected calcium or ionized calcium for accuracy
- ✓ "Inappropriately normal" PTH with hypercalcemia = hyperparathyroidism
- ✓ Hungry bone syndrome - Post-parathyroidectomy severe hypocalcemia
- ✓ Calcium × Phosphate product >55 = Risk of metastatic calcification
- ✓ IV calcium + digoxin = Risk of fatal arrhythmias (give slowly!)
- ✓ Pseudohypocalcemia - EDTA tube contamination (purple top)
- ✓ FHH vs primary hyperPTH - Check Ca/Cr clearance ratio (<0.01 = FHH)
- ✓ Bisphosphonates take 2-4 days - Use calcitonin as bridge
- ✓ Vitamin D deficiency - Most common cause of hypocalcemia worldwide
📋 Quick Reference Values
| Parameter | Normal Range | Critical Values |
|---|---|---|
| Total Calcium | 8.5-10.5 mg/dL | <7.0 or >14.0 mg/dL |
| Ionized Calcium | 4.5-5.3 mg/dL | <3.5 or >7.0 mg/dL |
| PTH (intact) | 15-65 pg/mL | Context dependent |
| 25-OH Vitamin D | 30-80 ng/mL | <20 ng/mL (deficient) |
| 1,25-OH₂ Vitamin D | 25-65 pg/mL | Elevated in granulomas |
| Phosphate | 2.5-4.5 mg/dL | Inversely related to Ca |
| Magnesium | 1.7-2.2 mg/dL | <1.2 affects Ca/PTH |