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





    • Total corrected calcium <2.2mmol/L
    • Symptoms:
      • 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.
        • HypocalcemiaECG.png
      • 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


    • 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)
            • HypercalcemiaECG.png
      • 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. 

    Screen Shot 2017-08-20 at 1.33.16 PM.png

    • 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


      • 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



      - Indication:

      • severe malignancy-assd hypercalcemia
      • renal insufficiency
      • heart failure
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