**Standard formula**: Corrected Ca (mg/dL) = Measured Total Ca + 0.8 × (4.0 - Albumin g/dL). **Example**: Measured Ca 7.5, Albumin 2.0 → Corrected Ca = 7.5 + 0.8 × (4.0 - 2.0) = **9.1 mg/dL** (normal, not hypocalcemia). **Alternative formula** (Payne formula, UK): Corrected Ca = Measured Ca + 0.02 × (40 - Albumin g/L). **Why correct?**: 40-45% of total calcium is bound to albumin, 50-55% is ionized (active form), 5-10% bound to anions.

Low albumin → less protein-bound calcium → measured total calcium drops, but **ionized calcium stays normal**. **Clinical scenario**: ICU patient, albumin 2.5, total Ca 8.0 (appears low).

Corrected Ca = 8.0 + 0.8 × 1.5 = **9.2 mg/dL** (normal)—no calcium replacement needed. **When NOT to correct**: If ionized calcium directly measured (gold standard 4.5-5.5 mg/dL), severe acidosis/alkalosis (pH affects ionized fraction), heparin therapy (interferes with binding).

**Ionized calcium (iCa) is preferred in**: **Critically ill patients** (ICU, sepsis, post-surgery)—acid-base imbalances change ionized fraction independent of albumin. **Severe hypo/hyperalbuminemia** (albumin <2.0 or >5.0)—correction formula less accurate outside 2.5-4.5 range. **Massive transfusions** (>4 units blood)—citrate binds calcium, total Ca normal but iCa drops. **Chronic kidney disease Stage 4-5** (secondary hyperparathyroidism alters Ca-albumin binding). **Hyperparathyroidism workup** (elevated iCa confirms true hypercalcemia vs artifact). **Pancreatitis** (calcium-soap formation, rapid Ca changes). **pH extremes** (acidosis <7.2 increases iCa by 5-10%, alkalosis >7.6 decreases iCa). **When correction is OK**: Stable outpatient, normal pH, albumin 2.5-4.5, no critical illness. **Example discrepancy**: Total Ca 10.5 (high-normal), albumin 2.0 → Corrected 12.1 (high), but **iCa 5.0** (normal)—overestimated by formula due to uremia affecting binding. **Gold standard**: Arterial/venous iCa with simultaneous pH measurement—most accurate, but requires blood gas analyzer.

**Hypocalcemia causes**: **Hypoparathyroidism** (post-thyroidectomy, autoimmune, genetic—PTH <10 pg/mL with low Ca). **Vitamin D deficiency** (<20 ng/mL 25-OH vitamin D, malabsorption, CKD). **Hypomagnesemia** (<1.5 mg/dL—Mg required for PTH secretion and action, alcoholism, diuretics). **CKD Stage 4-5** (hyperphosphatemia binds Ca, Vit D deficiency). **Acute pancreatitis** (calcium-soap formation, fat necrosis). **Tumor lysis syndrome** (phosphate release binds Ca). **Medications**: Loop diuretics, bisphosphonates, denosumab, calcitonin, chemotherapy. **Symptoms by severity**: **Mild** (7.5-8.4 mg/dL): Perioral numbness, muscle cramps. **Moderate** (6.5-7.4): Chvostek/Trousseau signs (facial twitch, carpal spasm), tetany, paresthesias. **Severe** (<6.5): Laryngospasm, bronchospasm, seizures, QT prolongation (risk Torsades de Pointes), heart failure. **Emergency threshold**: iCa <3.0 mg/dL or total Ca <6.0—IV calcium gluconate 1-2g over 10 min, then continuous infusion. **Chronic management**: Oral calcium 1-2g/day + calcitriol 0.25-1 mcg/day (active Vit D).

**Hypercalcemia causes**: **Primary hyperparathyroidism** (90% outpatient hypercalcemia—PTH >65 pg/mL with high Ca, adenoma/hyperplasia). **Malignancy** (90% inpatient hypercalcemia—PTHrP from lung/breast/renal cancer, or bone mets). **Granulomatous disease** (sarcoidosis, TB—macrophages convert Vit D to active form). **Medications**: Thiazide diuretics, lithium, excessive Vit D/A, calcium-alkali syndrome (Tums abuse). **Immobilization** (bone resorption), **hyperthyroidism**, **milk-alkali syndrome**. **Symptoms by severity**: **Mild** (10.5-11.9 mg/dL): Fatigue, constipation, polyuria ("stones, bones, groans, psychiatric overtones"). **Moderate** (12-13.9): Nausea, vomiting, confusion, muscle weakness, nephrolithiasis. **Severe** (>14 or iCa >7.0): Stupor, coma, pancreatitis, short QT interval, bradycardia, cardiac arrest. **Hypercalcemic crisis** (Ca >14): **Medical emergency**—IV saline 200-300 mL/hr (rehydrate first), calcitonin 4 IU/kg IM q12h (rapid onset), bisphosphonates (zoledronic acid 4mg IV, works in 2-4 days), treat underlying cause (parathyroidectomy, chemotherapy). **Dialysis** if Ca >18 or renal failure.

Cirrhosis/liver disease causes **profound hypoalbuminemia** (often 1.5-2.5 g/dL), drastically lowering measured total calcium. **Example**: Cirrhotic patient, albumin 1.8, total Ca 6.8 (very low), corrected Ca = 6.8 + 0.8 × (4.0 - 1.8) = **8.56 mg/dL** (low-normal). **Common scenario**: 70% of cirrhotic patients have total Ca <8.5, but only 10-20% have true hypocalcemia (low iCa). **Why correction underestimates in cirrhosis**: Altered calcium-albumin binding affinity (uremia, acidosis, bilirubin competition). **Gold standard**: Measure **ionized calcium directly**—often normal (4.5-5.0) despite corrected Ca suggesting low. **PTH response**: Usually appropriate (elevated PTH if truly low Ca, suppressed if normal). **Clinical impact**: Avoid unnecessary calcium supplementation (risks hypercalcemia when albumin improves post-transplant). **Hepatorenal syndrome**: Combined with CKD → true hypocalcemia more common (Vit D deficiency, secondary hyperparathyroidism). **Best practice**: Cirrhosis + total Ca <8.0 → always measure iCa before treating, check 25-OH Vit D (<20 ng/mL in 80% cirrhotics), Mg (<1.5 in 50%), PTH.

**pH-calcium relationship**: Acidosis **increases** ionized calcium, alkalosis **decreases** it—total calcium stays constant. **Mechanism**: H⁺ competes with Ca²⁺ for albumin binding sites. **Acidosis** (pH <7.35): More H⁺ → displaces Ca²⁺ from albumin → higher free iCa. **Alkalosis** (pH >7.45): Less H⁺ → more Ca²⁺ binds albumin → lower free iCa. **Magnitude**: For every 0.1 pH unit change, iCa changes **0.05-0.1 mg/dL** (5-10%). **Example 1** (hyperventilation alkalosis): pH 7.6, total Ca 9.5 (normal), iCa 3.8 (low, symptomatic tetany)—treat alkalosis with rebreathing, not calcium. **Example 2** (DKA acidosis): pH 7.1, total Ca 8.0 (low-normal), iCa 5.5 (high-normal)—correcting acidosis will drop iCa, may need calcium after pH normalized. **Clinical significance**: **Respiratory alkalosis** (anxiety, pain, mechanical ventilation) → iCa drops → perioral numbness, carpopedal spasm (common in ICU). **Metabolic acidosis** (sepsis, renal failure) → iCa rises → may mask true hypocalcemia until pH corrected. **Lab reporting**: Most blood gas analyzers report iCa at pH 7.4 (pH-corrected value)—closer to true physiologic iCa.