HYPOCALCEMIA 

1. DEFINITION

Hypocalcemia = reduction in biologically active calcium.

Normal Ranges

Parameter	Normal
Total serum calcium	8.5–10.5 mg/dL
Ionized calcium	1.12–1.32 mmol/L (4.5–5.3 mg/dL)
Albumin	3.5–5 g/dL

Ionized calcium (iCa) is the physiologically active form and is preferred in ICU.

2. CALCIUM PHYSIOLOGY

Distribution

• 99% → bone
• 1% → extracellular
  
  • 45% ionized
  • 40% albumin-bound
  • 15% complexed (phosphate, citrate)

Key Regulators

Hormone	Action
PTH	↑ Ca reabsorption (kidney), ↑ bone resorption, ↑ 1α-hydroxylase
Vitamin D (1,25-OH₂D)	↑ gut Ca & phosphate absorption
Calcitonin	Minor role (↓ osteoclasts)
Magnesium	Required for PTH secretion + action

3. TYPES OF HYPOCALCEMIA

A. By Severity (Total Ca)

Severity	Ca level
Mild	7.5–8.5 mg/dL
Moderate	7.0–7.5 mg/dL
Severe	<7.0 mg/dL OR symptomatic

B. True vs Pseudohypocalcemia

• True → ↓ ionized Ca
• Pseudo → low albumin, normal iCa

4. CORRECTED CALCIUM (EXAM FAVORITE)

Formula

Corrected Ca=Measured Ca+0.8×(4−albumin)

BUT:
📌 ICU → always trust ionized calcium

5. ETIOLOGY 

A. ↓ PTH (Hypoparathyroidism)

Causes

• Post-thyroid/parathyroid surgery (most common in India)
• Autoimmune hypoparathyroidism
• DiGeorge syndrome
• Infiltration (hemochromatosis, Wilson)
• Radiation

Labs

• ↓ Ca
• ↑ phosphate
• ↓ PTH
• Normal Mg

B. PTH Resistance (Pseudohypoparathyroidism)

• Normal or ↑ PTH
• Target organ resistance

Albright hereditary osteodystrophy

• Short 4th metacarpal
• Short stature
• Obesity
• Intellectual disability

C. Vitamin D Deficiency / Resistance

Causes

• Nutritional deficiency
• Malabsorption
• CKD
• Liver disease
• Anticonvulsants
• Vitamin D–dependent rickets

Labs

• ↓ Ca
• ↓ phosphate
• ↑ PTH
• ↓ 25-OH vitamin D

D. Magnesium Disorders 

Mg State	Effect
↓ Mg	↓ PTH secretion + resistance
↑ Mg	Suppresses PTH

Hypocalcemia refractory to calcium → CHECK MAGNESIUM

E. Critical Illness–Related Hypocalcemia (ICU relevant)

Cause	Mechanism
Sepsis	Cytokine-mediated PTH resistance
Massive transfusion	Citrate chelation
Acute pancreatitis	Fat saponification
Rhabdomyolysis	Ca deposition in muscle
Tumor lysis syndrome	Hyperphosphatemia
AKI/CKD	↓ Vit D, ↑ phosphate
Burns	Ca sequestration

F. Drug-Induced

• Bisphosphonates
• Denosumab
• Cisplatin
• Foscarnet
• Loop diuretics
• Phenytoin
• PPIs (chronic)

6. CLINICAL FEATURES 

Neuromuscular

• Perioral numbness
• Paresthesias
• Muscle cramps
• Tetany
• Laryngospasm
• Seizures

Cardiovascular

• Prolonged QT
• Arrhythmias
• Hypotension
• ↓ myocardial contractility

Signs

• Chvostek sign
• Trousseau sign

7. ECG CHANGES (VERY HIGH-YIELD)

Finding	Mechanism
Prolonged QT	Prolonged ST
Torsades de pointes	Severe cases

8. DIAGNOSTIC APPROACH (STEP-WISE)

Step 1: Confirm

• Total Ca
• Ionized Ca

Step 2: Key Labs

Test	Purpose
PTH	Etiology
Mg	Refractory causes
Phosphate	Differentiation
25-OH Vit D	Deficiency
Creatinine	CKD

Step 3: Pattern Recognition

Ca	PTH	Phosphate	Diagnosis
↓	↓	↑	Hypoparathyroidism
↓	↑	↓	Vit D deficiency
↓	↑	↑	CKD
↓	N/↑	N	Critical illness

9. MANAGEMENT 

A. WHEN TO TREAT

Treat immediately if:

• Symptomatic
• Ca <7 mg/dL
• Ionized Ca <0.9 mmol/L
• Seizures, arrhythmia, laryngospasm

B. ACUTE SEVERE HYPOCALCEMIA (ICU PROTOCOL)

1️⃣ IV CALCIUM

Preparation	Elemental Ca
Calcium gluconate 10%	9 mg/mL
Calcium chloride 10%	27 mg/mL (central line only)

📌 Cardiac monitoring mandatory

C. CHRONIC / MILD HYPOCALCEMIA

Oral Calcium

• Calcium carbonate / citrate

Vitamin D

Condition	Therapy
Deficiency	Cholecalciferol
CKD / hypoparathyroid	Calcitriol

1️⃣ VITAMIN D DEFICIENCY

Cholecalciferol (Vitamin D₃)

📌 Requires functional kidneys for activation

📌 Not sufficient alone in hypoparathyroidism or advanced CKD

2️⃣ CHRONIC KIDNEY DISEASE (CKD)

Calcitriol (1,25-dihydroxyvitamin D₃)

Indications

• CKD stage 4–5
• Hypocalcemia with ↓ 1α-hydroxylase activity
• Secondary hyperparathyroidism

📌 Monitor:

• Calcium
• Phosphate
• Ca × PO₄ product (keep <55)

D. SPECIAL SITUATIONS

Hypomagnesemia

• MgSO₄ IV or oral first
• Calcium alone will fail

CKD

• Phosphate binders
• Active vitamin D
• Avoid hypercalcemia

Post-thyroidectomy

• Prophylactic Ca ± calcitriol

11. COMMON EXAM TRAPS

Trap	Reality
Low Ca in hypoalbuminemia	Ionized Ca normal
Giving Ca without Mg	No response
Calcium chloride peripherally	Tissue necrosis
Treating asymptomatic ICU hypocalcemia	Not recommended

13. REFERENCES

• Harrison’s Principles of Internal Medicine
• Endocrine Society Clinical Practice Guidelines
• UpToDate: Hypocalcemia
• NEJM reviews on electrolyte disorders
• ICU textbooks (Oh’s, Marino)