Fluids, Electrolytes & Nutrition: Calcium (Ca)

General Calcium Physiology

Vitamin D

  • Cholecalciferol (Vitamin D3) Source
    • Ultraviolet (UV) Light Converts 7-Dehydrocholesterol to Pre-Vitamin D3
      • By Photolysis
      • Pre-Vitamin D3 Spontaneously Isomerizes to Cholecalciferol (Vitamin D3)
    • Cholecalciferol Can Also Be Ingested
  • Vitamin D Activation
    • Liver Converts Cholecalciferol (Vitamin D3) to 25-Hydroxycholecalciferol (Calcifediol)
      • By Hydroxylation
    • Kidney Converts 25-Hydroxycholecalciferol (Calcifediol) to 1,25-Hydroxycholecalciferol (Calcitriol)
      • By Hydroxylation
  • Calcitriol (1,25-Hydroxycholecalciferol)
    • The Active Form of Vitamin D
    • Increases Calcium & Phosphate
      • Increases Intestinal Calcium & Phosphate Absorption (Primary Method)
      • Increases Renal Reabsorption of Calcium
      • Stimulates Calcium Release from Bone (Acts on Osteoblasts to Release RANKL which Activates Osteoclasts)

Parathyroid Hormone (PTH)

Calcitonin

Hypercalcemia

Causes

  • Most Common Causes (90%):
    • Hyperparathyroidism – Most Common Benign/Outpatient Cause
    • Malignancy
      • Breast Cancer – Most Common Malignant Cause
      • Squamous Cell Carcinoma of the Lung
      • Lytic Bone Lesions
  • Less Common Causes:
    • Vitamin D Intoxication
    • Thiazide Diuretics
    • Lithium
    • Familial Hypercalcemic Hypocalciuria (FHH)
    • Milk-Alkali Syndrome

Presentation Mn

  • Stones:
    • Kidney Stones
    • Gallstones
  • Bones:
    • Osteoporosis
    • Bone Pain
  • Groans:
    • Abdominal Pain
    • Peptic Ulcer Disease (PUD)
    • Pancreatitis
    • Constipation
    • Anorexia
    • Nausea & Vomiting
  • Thrones:
    • Polyuria (Urinary Frequency)
    • Polydipsia
  • Psychiatric Overtones:
    • Fatigue
    • Delirium
    • Coma
  • EKG Changes:
    • Shortened QT Interval
    • Bradycardia

Severity

  • Mild ≥ 10.5 mg/dL
  • Moderate ≥ 12.0 mg/dL
  • Severe/Crisis ≥ 14.0 mg/dL

Treatment

  • Mild: Nothing
  • Moderate-Severe: IV Normal Saline & Furosemide
    • Also Consider:
      • Bisphosphonates
      • Calcitonin
      • Dialysis

Related Pathology

  • Familial Hypercalcemic Hypocalciuria (FHH)
    • Cause: CaSR (Calcium-Sensing Receptor) Inactivating Mutations
      • Autosomal Dominant Inheritance
    • Effect: Parathyroid Gland Less Sensitive to Calcium
      • Higher than Normal Calcium Levels are Required to Inhibit PTH Release
    • Labs:
      • PTH Normal-Elevated
      • Calcium High
      • Urine Calcium Low (Ca/Cr Clearance Ratio < 0.01)
        • Ca/Cr Clearance Ratio = (24-Hour Urine Ca/Serum Ca) / 24-Hour Urine Cr/Serum Cr)
    • Treatment: Treat Hypercalcemia, No Surgical Treatment Required
  • Milk-Alkali Syndrome
    • Cause: Excessive Ingestion of Calcium with Absorbable Alkali (Vitamins/Milk)
    • Most Common in Older Women Taking Calcium Carbonate to Treat Osteoporosis
    • Most Often Asymptomatic
    • Labs:
      • High Calcium
      • Alkalosis
      • Acute Kidney Injury (AKI)
    • Diagnosis Based on History
    • Treatment: Stop Offending Agent & Treat Hypercalcemia
  • Malignancy
    • PTH-Related Protein (PTHrP)
      • Released in Malignancy with Rapid Onset Hyperparathyroidism
      • The Most Common (80%) Cause of Hypercalcemia in Malignancy
      • Most Common Causes:
        • Breast Cancer
        • Squamous Cell Carcinoma (Lung, Head or Neck)
        • Ovarian Cancer
    • Lytic Bone Lesions
      • Increases Calcium from Bone Breakdown
      • Less Common (80%) Cause of Hypercalcemia in Malignancy
      • Most Common Causes:
        • Multiple Myeloma
        • Breast Cancer Metastases
    • Other Causes of Hypercalcemia in Malignancy:
      • Ectopic PTH Secretion
      • Increased 1,25-Hydroxycholecalciferol (Calcitriol) Production – Lymphoma

Hypocalcemia

Causes

  • Parathyroid Injury During Thyroidectomy – Most Common Cause
  • Parathyroidectomy
  • Autoimmune Parathyroid Destruction
  • Blood Transfusion (Chelation)
  • Hypomagnesemia
  • Vitamin D Deficiency
  • Chronic Kidney Disease (CKD) Induced Vitamin D Deficiency
  • Medications:
    • Lactate
    • Foscarnet
    • Bisphosphonates
    • Denosumab
    • Cinacalcet
    • Chemotherapy
  • Acute Pancreatitis
  • Surgery
  • Sepsis or Severe Illness

Presentation

  • Perioral Tingling/Numbness – First Sign
  • Tetany
    • Chvostek Sign (Cheek Tap > Spasm)
    • Trousseau Sign (BP Cuff Inflation > Carpopedal Spasm)
  • Seizures
  • Anxiety & Depression
  • Prolonged QT Interval

Treatment

Pseudohypocalcemia

  • Definition: Falsely Low Calcium from Low Protein Levels (Particularly Albumin)
    • Total Calcium Low from Decreased Protein-Bound Calcium
    • Ionized Calcium Remains Stable
  • Corrected Calcium = Calcium + [0.8 x (4 – Albumin)]
  • Normal Ionized Calcium: 4.5-5.5 mg/dL

Mnemonic

Symptoms of Hypercalcemia

  • “Stones, Bones, Groans, Thrones & Psychiatric Overtones”