Disorders of Calcium and Phosphate Metabolism

Ca/P Homeostasis - Bone Builders' Blueprint

• PTH (Parathyroid Hormone): ↑ Serum $Ca^{2+}$, ↓ Serum $PO_4^{3-}$.
  • Bone: ↑ Resorption (↑ $Ca^{2+}$, ↑ $PO_4^{3-}$ release).
  • Kidney: ↑ $Ca^{2+}$ reabsorption, ↓ $PO_4^{3-}$ reabsorption, ↑ Vit D activation.
  • Intestine (indirectly via Vit D): ↑ $Ca^{2+}$ & $PO_4^{3-}$ absorption.
• Vitamin D (Calcitriol): ↑ Serum $Ca^{2+}$, ↑ Serum $PO_4^{3-}$.
  • Intestine: ↑ $Ca^{2+}$ & $PO_4^{3-}$ absorption.
  • Bone: ↑ Mineralization (indirect), ↑ Resorption (high doses).
  • Kidney: ↑ $Ca^{2+}$ & $PO_4^{3-}$ reabsorption.
• Calcitonin: ↓ Serum $Ca^{2+}$, ↓ Serum $PO_4^{3-}$. (Minor role in humans)
  • Bone: ↓ Resorption.
  • Kidney: ↑ $Ca^{2+}$ & $PO_4^{3-}$ excretion.

Normal Serum Levels:

• Total $Ca^{2+}$: 8.5‑10.5 mg/dL
• Ionized $Ca^{2+}$: 4.65‑5.25 mg/dL
• $PO_4^{3-}$: 2.5‑4.5 mg/dL
• ALP: 30‑120 U/L
• PTH: 10‑65 pg/mL
• 25(OH)Vit D: 30‑100 ng/mL

⭐ Ionized calcium ($Ca^{2+}$) is the physiologically active form and its level is affected by pH (acidosis ↑ $Ca^{2+}$, alkalosis ↓ $Ca^{2+}$).

Hypocalcemia - Calcium Crash Course

• Causes: Vitamin D deficiency, hypoparathyroidism (e.g., DiGeorge syndrome), pseudohypoparathyroidism, chronic renal failure, acute pancreatitis, massive blood transfusion (citrate toxicity).
• Clinical Features: 📌 CATS go numb:
  • Convulsions
  • Arrhythmias
  • Tetany (Chvostek's sign, Trousseau's sign)
  • Spasms, paresthesias (numbness, tingling)
  • Symptomatic if Ionized Ca < 4.4 mg/dL or Total Ca < 7.5 mg/dL.
• ECG: Prolonged QT interval.
• Acute Management:

• Chronic Management: Oral Calcium supplements + Vitamin D.

⭐ DiGeorge syndrome (22q11.2 deletion) is a significant cause of neonatal hypocalcemia due to parathyroid hypoplasia.

Hypercalcemia - Calcium Overload Ops

• Causes: Hyperparathyroidism, Malignancy (rare peds), Vitamin D intoxication, Immobilization, Williams Syndrome, Granulomatous diseases (e.g., Sarcoidosis).
• Clinical Features: 📌 'Bones (pain), Stones (renal), Groans (abdominal pain), Psychiatric Overtones (confusion)'. Severe if Ca > 14 mg/dL.
• ECG: Short QT interval.
• Management:
  • Hydration (IV Normal Saline), Furosemide (post-hydration).
  • Bisphosphonates (e.g., Pamidronate), Calcitonin.
  • Dialysis for severe/refractory cases.

⭐ Williams syndrome is associated with idiopathic infantile hypercalcemia.

Rickets & Osteomalacia - Bendy Bones Brigade

Defective bone mineralization: rickets (growing), osteomalacia (mature).

• Types:
  • Nutritional: Vit D deficiency (commonest).
  • Vit D Dependent: Type 1 ($1\alpha$-hydroxylase $\downarrow$), Type 2 (receptor defect).
  • Hypophosphatemic: X-linked dominant.
  • Renal osteodystrophy.
• CF: Delayed fontanelles, craniotabes, rachitic rosary, Harrison's sulcus, wide wrists/ankles, bowing.
• X-ray: Metaphyseal cupping, fraying, splaying. Widened physis.
• Labs: $\downarrow$Ca, $\downarrow$P (not hypophosphatemic), $\uparrow$ALP, $\uparrow$PTH. 25(OH)D$\downarrow$ (nutritional), 1,25(OH)2D varies.
• Rx: Vit D (Stoss: 300,000-600,000 IU), Ca, P as needed.

⭐ Serum ALP is often elevated before X-ray changes in rickets.

Phosphate Imbalances - Phosphorus Patrol

• Hypophosphatemia (↓$PO_4^{3-}$):
  • Causes: ↓Intake/absorption (malnutrition, antacids), ↑renal excretion (Fanconi syndrome), intracellular shift (refeeding syndrome, DKA).
  • Features: Muscle weakness, rhabdomyolysis, respiratory failure, altered mental status. Severe < 1 mg/dL.
  • Mgmt: Oral/IV phosphate replacement; treat underlying cause.
• Hyperphosphatemia (↑$PO_4^{3-}$):
  • Causes: CKD (most common), hypoparathyroidism, tumor lysis syndrome, Vit D intoxication, ↑phosphate intake.
  • Features: Often asymptomatic; symptoms of hypocalcemia (tetany), soft tissue/vascular calcification.
  • Mgmt: Dietary phosphate restriction, phosphate binders, dialysis if severe.

⭐ Refeeding syndrome is a potentially fatal condition characterized by severe hypophosphatemia following re-introduction of nutrition in malnourished individuals, leading to cardiac, pulmonary, and neurological complications.

High‑Yield Points - ⚡ Biggest Takeaways

• Rickets: Vitamin D deficiency causes ↓Ca, ↓PO4, ↑ALP, ↑PTH; features craniotabes, rachitic rosary.
• Hypoparathyroidism: Presents with ↓Ca, ↑PO4, ↓PTH; Chvostek's/Trousseau's signs, DiGeorge association.
• Pseudohypoparathyroidism: PTH resistance leads to ↓Ca, ↑PO4, ↑PTH; Albright's osteodystrophy.
• Hypercalcemia causes: Consider immobilization, malignancy, hyperparathyroidism (MEN syndromes), or FHH (CaSR mutation, low urine Ca).
• VDDR: Type 1 (1α-hydroxylase defect), Type 2 (Vitamin D receptor defect).