Calcium

Calcium Principles

• Normal: 2.2-2.6 mmol/L
  • Ionic Ca2+: 1.1 - 1.3
  • Serum Ca2+ 50% bound to protein
  • Regulated by Vitamin D and PTH
  • Mg2+ is a cofactor for PTH secretion.  (i.e. see hypocalcemia, not corrected by dietary Ca2+.. probably has ↓ Mg2+ and is unable to secrete PTH
• NOTE:
  • PTH causes ↑Ca2+, ↓ PO4
  • Vitamin D3 (Calcitriol) causes ↑ Ca2+ and ↑ PO4

Hypocalcemia

• Total corrected calcium <2.2mmol/L
• Symptoms:
  • HYPERPOLARIZATION
  • Acute:
    • MSK:  tetany! parasthesia, laryngospasm,
    • Neuro: Tetany, parasthesia, laryngospasm, hyperreflexia
    • On Exam: Chvostek/Trousseau sign (very poor Sensitivity 25 and 30% respectively)
    • CVS: ECG changes,
    • Psych: delirium + Psych (emotional instability, anxiety, depression)
  • Chronic:
    • CNS: Lethargy, psychosis, basal ganglia calcification, Parkinson's, dystonia.
    • CVS: prolonged QT interval --> Torsades de pointes (V tach)
    • GI: steatorrhea
    • Endo: Impaired insulin release
    • SKIN: dry, scaling, alopecia, candidiasis.
    • Ocular: cataracts
    • MSK: generalized muscle weakness/wasting.
    • 
• APPROACH
  • Is the patient hypocalcemic (correct for albumin)?
  • PTH high or low?
  • If PTH high, is phosphate low or normal?
  • Is the Mg2+ level low? Hypomagnesemia can impair PTH secretion and action.
  • Other Causes:
    • Sepsis (unclear cause)
    • Magnesium Depletion (unable to secrete parathyroid hormone)
    • Alkalosis (reduces ionized fraction)
    • Blood transfusions (citrate chelates Ca++ in banked blood, short lived, resolves when citrate metabolized)
    • Drugs (heparin, theophylline, cimetidine, aminoglycosides)
    • Pancreatitis

• Treatment:
  • Correct underlying disorder
  • Mild/asymptomatic (Ca2+ ionized <0.8 mmol/L)
    • Increase dietary Ca by 1000 mg/d
    • Calcitriol 0.25 mcg/d
  • Symptomatic hypocalcemia (esp if ionized Ca2+ is <0.7mmol/L)  --> need IV
    • Two IV solutions:
      • 10% Calcium Gluconate [100mg/mL]
      • 10% Calcium Chloride [100mg/mL] (contains 3x elemental Ca++ than gluconate)
    • Can order as IV calcium gluconate 1-2g over 10-20min followed by slow infusion if needed. (i.e. 0.5-2 mg/kg/hr of elemental calcium for ≥ 6hrs.
    • Raise calcium to low normal >2.0-2.1mmol?L to prevent symptoms but keep PTH stimulation.
  • Do not correct if asymptomatic and suspected to be transient

Hypercalcemia

• Symptoms
• • Classically:
    • DEHYDRATION! (polyuria, renal failure)
    • Also:
      • Bones (bone pain), weakness.
      • Stones (Nephrolithiasis), Polyuria, Polydipsia-->Renal Failure/ Oliguria irrev.
      • Groans (vomiting, abdo pain, PUD)
      • Psychiatric overtones
      • CV: HTN, Arrhythmia, Short QT, Calcification of Arteries
        • With very high calcium can cause ST changes (do Ca++ in pts with ST changes)
        •  
        • 

  • Hypercalcemic crisis (>4mmol/L): Oliguria/anuria Mental status change (somnolence, coma) EMERGENCY!!

  •  
• Physiology
  • High calcium in the nephron interferes with re-absorption, causes Calcium diuresis, leading to dehydration and renal failure. 
  • Hydration is the #1 therapy  ---> Normal saline allows kidney re-perfusion, delivers sodium to the distal nephron, causing sodium diuresis and calcium follows. 

• Causes:
  • 90% - Hyperparathyroidism or malignancy
    • Can be local (osteolysis of local bone) or:
    • Humoral creating factor to activate bone resorption (i.e. PTHrP)
  • 10% - Others (thyrotoxicosis, immobilization, drugs (lithium, thiazides)
• Workup
  • Urine Ca (if low, then familial hypocalciuric hypocalcemia)
  • Electrolytes (Ca, Mg, PO4)
  • Albumin (correction 0.2:10 Calcium increase to 10 decrease)
  • CXR (Granuloma/malignancy)
  • PTHrP
    • Malignancies producing PTHrP: squamous cell carcinoma; lung, head, and neck cancer; lymphoma
• Treatment:
  • 1. IV NS!!! (most important!)
    • Calciuria usually causes dehydration = decreased Ca++ excretion.  Giving volume helps excretion.
  • 2. Loop Diuretics (not thiazides!)
    • Usually lasix 40-80mg IV q2h titrate to achieve hourly urine output of 100-200 mL/hr
    • Replace hourly urine output with Isotonic Saline
  • 3. Calcitonin
  • 4. Bisphosphonates
  • 5. Steroids (if Hypervitaminosis D secondary to malignancy [granulomatous disease etc..])
  • 6. Dialysis  (Last resort!)

• Increase Urinary Ca2+ excretion	Isonotic saline (4-5L) over 24hrs +/- loop diuretic (furosemide) but only if hypervolemic Calcitonin (2013: NOT USED DUE TO CANCER RISK) 4 IU/kg IM/SC q12h Only works for 48h, rapid onset within 4-6h Hydrocortisone  (adjunct to calcitonin)
  Diminish Bone Resorption	Bisphosphonates Acts rapidly, but transient (0.3-0.5mmol/L reduction) Esp for malignancy-induced (peak effect 2-4d, normalize Ca in 4-7d) IV pamidronate 90mg IV over 2 hours (reduce dose to 60mg for renal impairment) IV Zoledronate 4mg IV over 15min (equivalent to pamidronate in efficacy) Plicamycin 25 mcg/kg IV over 4hrs repeat q2h - HISTORIC (more rapid than pamidronate, toxic BM suppression) - antineoplastic agent that inhibits bone resorption) Mithramycin (rarely used) Hematotoxic and hepatotoxic
  Decrease GI Ca2+ Absorption	Corticosteroids in hypervitaminosis D and hematologic malignancies Slow onset: (5-10d), need high doses - i.e. Hydrocortisone 200mg IV daily in 2-3 divided doses
  Dialysis	LAST RESORT - Indication: severe malignancy-assd hypercalcemia renal insufficiency heart failure