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Calcium and Its Disorders in Pediatrics

A Simple, Complete Guide for MBBS Final Year

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1. Why Calcium Matters

• Builds and strengthens bones and teeth (stored as hydroxyapatite)
• Triggers muscle contraction (cardiac and skeletal)
• Enables nerve signal transmission
• Drives hormone secretion and intracellular signaling
• Supports immune function

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2. Normal Calcium Values (Know These!)

Exam tip: In blood, calcium exists in 3 forms:

• ~45% bound to albumin (inactive)
• ~10% bound to anions like phosphate (inactive)
• ~45% ionized = the biologically active form

Corrected Ca = Measured Ca + 0.8 × (4 - serum albumin in g/dL)

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3. How the Body Regulates Calcium

1. Parathyroid glands sense low Ca via the Calcium-Sensing Receptor (CaSR) → secrete PTH
2. PTH acts on:
   • Bone → increases osteoclast activity → releases Ca and phosphate
   • Kidney → increases Ca reabsorption in distal tubule; increases phosphate excretion; activates vitamin D
   • Kidney → converts 25(OH)D to 1,25(OH)₂D (calcitriol) via 1α-hydroxylase
3. Calcitriol acts on the intestine → increases dietary calcium absorption
4. All three effects together raise serum calcium back to normal
5. High calcium → shuts off PTH secretion (negative feedback)

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4. HYPOCALCEMIA

Definition

• Total serum Ca < 8.5 mg/dL (or ionized Ca < 4.5 mg/dL)
• In neonates: Ca < 7.0 mg/dL (term) or < 7.5 mg/dL (preterm)

Classification - Very Important for Exams

IDM hypocalcemia mechanism: Maternal hyperglycemia → fetal hyperinsulinism → calcitonin release → calcium falls. Also maternal hyperparathyroidism suppresses fetal PTH glands.

• Vitamin D deficiency rickets - most common cause in India
• Celiac disease / malabsorption
• Hypoparathyroidism (genetic, autoimmune)
• Pseudohypoparathyroidism (PTH resistance, Albright's hereditary osteodystrophy)
• Chronic kidney disease
• Alkalosis - hyperventilation increases calcium binding to albumin → ionized Ca falls → tetany

Clinical Features - "Think CATS"

• Neuromuscular irritability - tingling, numbness of hands/feet/lips
• Tetany - sustained painful muscle spasm
• Trousseau's sign - inflate BP cuff above systolic for 3 min → carpopedal spasm (carpal tunnel squeezing - thumb adduction, finger flexion) → positive
• Chvostek's sign - tap facial nerve anterior to ear → ipsilateral facial muscle twitch → positive (less specific)
• Laryngospasm - "crowing" breathing, can be life-threatening in infants
• Seizures - a major cause of neonatal seizures
• Prolonged QTc on ECG → risk of arrhythmia
• Papilledema in chronic cases (raised ICP)
• Cataracts in long-standing hypoparathyroidism
• Dental hypoplasia, dry skin, brittle nails in chronic cases

Investigations

• Low Ca + High PO4 + Low PTH = Hypoparathyroidism
• Low Ca + High PO4 + High PTH = Pseudohypoparathyroidism or CKD
• Low Ca + Low PO4 + High PTH = Vitamin D deficiency (rickets)

Treatment

• IV Calcium gluconate 10%: 1-2 mL/kg (max 10 mL) slow IV over 10-20 min
• ECG monitoring during infusion (can cause arrhythmia if given too fast)
• Followed by calcium gluconate infusion: 2-4 mg/kg/hr

• Oral calcium carbonate or calcium gluconate supplements
• Vitamin D (cholecalciferol / calcitriol) depending on cause
• In hypoparathyroidism: calcitriol (active form) because cannot activate vitamin D
• Treat underlying cause (e.g., correct Mg, treat rickets, DiGeorge management)

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5. HYPERCALCEMIA

Definition

• Total serum Ca > 10.5 mg/dL
• Severe: > 14 mg/dL (hypercalcemic crisis)
• Less common than hypocalcemia in pediatrics

Causes in Children (PTH-based classification)

• Primary hyperparathyroidism - parathyroid adenoma (rare in children), MEN syndromes
• Familial Hypocalciuric Hypercalcemia (FHH) - CaSR mutation → PTH inappropriately normal/high with mild hypercalcemia; benign, urine calcium LOW
• Tertiary hyperparathyroidism - chronic CKD with autonomous PTH secretion

• Malignancy (second most common cause with hyperparathyroidism together = 80-90% of cases)
  • Solid tumors: PTHrP (PTH-related peptide) mimics PTH
  • Leukemia/lymphoma: osteolytic lesions or excess 1,25(OH)₂D production
• Vitamin D intoxication - excessive supplementation (common in India now with over-supplementation)
• Granulomatous diseases - TB, sarcoidosis - macrophages make excess 1,25(OH)₂D
• Williams syndrome - hypersensitivity to vitamin D (deletion 7q11)
• Subcutaneous fat necrosis of newborn - ectopic calcitriol production
• Immobilization - increased bone resorption
• Ketogenic diet for epilepsy in children

Clinical Features - "Bones, Stones, Groans, Moans, Thrones"

Investigations

• Both have high (or normal) PTH + high calcium
• FHH: urine calcium/creatinine ratio < 0.01 (kidneys retain calcium due to CaSR mutation)
• Primary HPT: urine calcium HIGH

Treatment

• Treat underlying cause
• Adequate hydration, avoid thiazides and vitamin D supplements
• FHH: no treatment needed (benign)

1. IV Normal Saline hydration - first and most important step
   • Expands volume, promotes renal calcium excretion
   • Rate: 10-20 mL/kg bolus, then maintenance + replacement
2. Loop diuretics (furosemide) - after adequate hydration
   • Blocks Ca reabsorption in loop of Henle → calciuresis
   • Never give before hydration (worsens hypercalcemia)
3. Bisphosphonates (pamidronate, zoledronate)
   • Inhibit osteoclast-mediated bone resorption
   • Drug of choice for malignancy-associated hypercalcemia
4. Calcitonin - rapid onset (hours), short duration
   • Inhibits bone resorption + increases renal Ca excretion
   • Useful as a bridge while awaiting bisphosphonate effect
5. Corticosteroids - for granulomatous disease, lymphoma, vitamin D toxicity
   • Inhibit macrophage CYP27B1, reduce 1,25(OH)₂D production
6. Cinacalcet (calcimimetic) - for primary HPT or tertiary HPT
   • Activates CaSR, suppresses PTH
   • Used in some pediatric cases with HPT
7. Dialysis - for renal failure + severe refractory hypercalcemia
8. Surgery (parathyroidectomy) - for confirmed primary HPT

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6. Quick Comparison Table (Exam Favorite)

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7. Pediatric High-Yield Points for Exams

1. DiGeorge syndrome (22q11 deletion) - absent thymus + absent parathyroids → immunodeficiency + hypocalcemia. Features: Conotruncal heart defects, dysmorphic face, hypocalcemia, T-cell deficiency.
2. Pseudohypoparathyroidism (PHP) - PTH is high but organs don't respond (PTH resistance). Look for Albright's hereditary osteodystrophy: short stature, short 4th metacarpal, obesity, round face, subcutaneous calcifications. Calcium low, phosphate high, PTH very high.
3. Hypomagnesemia causes hypocalcemia by suppressing PTH release - always check Mg in resistant hypocalcemia. Treat Mg first.
4. Williams syndrome - "elfin facies," supravalvular aortic stenosis, hypercalcemia, intellectual disability. Caused by chromosome 7q11 deletion.
5. Subcutaneous fat necrosis of newborn - large neonate, traumatic delivery → hard plaques on back/buttocks in first weeks → hypercalcemia due to ectopic 1,25(OH)₂D production. Can cause severe hypercalcemia - restrict dietary calcium and vitamin D.
6. Vitamin D deficiency rickets - most common metabolic bone disease in children in India.
   • Cause: poor sunlight, dark skin, exclusively breastfed without supplementation, maternal deficiency
   • Lab: low Ca, low PO4, high PTH, high ALP, low 25(OH)D
   • X-ray: cupping and fraying of metaphysis (especially distal radius), Looser zones
   • Treatment: Vitamin D 2000-4000 IU/day (Stoss therapy: single 600,000 IU dose)
7. Neonatal Trousseau / Chvostek - less reliable in neonates; seizures and apnea are the typical presentation.
8. ECG monitoring is mandatory during IV calcium infusion due to risk of bradycardia and cardiac arrest if pushed too fast.

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8. Summary Flowchart

Low Calcium (Hypocalcemia)
        ↓
   Check PTH
    /       \
Low PTH    High PTH
   ↓             ↓
Hypoparathyroidism   Check Phosphate & Vit D
(DiGeorge,          /              \
autoimmune,    High PO4          Low PO4
post-op,       Low Vit D         Low Vit D
genetic)        ↓                   ↓
             CKD/PHP            Vitamin D
                              Deficiency/Rickets

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