Calcium, Total

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Subject: Calcium, Total

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Definition

  • Ninety-nine percent of the body's calcium is in bone. Of the remainder (of 1%) in blood, about 50% is ionized (free), about 10% is bound to anions (e.g., phosphate, bicarbonate), and about 40% (of 1%) in blood is bound to plasma proteins, (80–40%) of that to albumin.

  • Normal range: 8.7–10.7 mg/dL.

  • Critical values: <6.6 or >12.9 mg/dL.

Use

  • Diagnosis and monitoring of a wide range of disorders, including disorders of protein and vitamin D, and diseases of the bone, kidney, parathyroid gland, or GI tract.

Interpretation

Increased In

  • Hyperparathyroidism, primary and secondary

  • Acute and chronic renal failure

  • Following renal transplantation

  • Osteomalacia with malabsorption

  • Aluminum-associated osteomalacia

  • Malignant tumors (especially breast, lung, kidney; 2% of patients with Hodgkin or non-Hodgkin lymphoma)

    • Direct bone metastases (up to 30% of these patients) (e.g., breast cancer, Hodgkin and non-Hodgkin lymphoma, leukemia, pancreatic cancer, lung cancer)

    • Osteoclastic activating factor (e.g., multiple myeloma, Burkitt lymphoma; may be markedly increased in human T-cell leukemia virus-I–associated lymphoma

    • Humoral hypercalcemia of malignancy

    • Ectopic production of 1,25-dihydroxyvitamin D3 (e.g., Hodgkin and non-Hodgkin lymphoma)

  • Granulomatous disease (e.g., uncommon in sarcoidosis, TB, leprosy; more uncommon in mycoses, berylliosis, silicone granulomas, Crohn disease, eosinophilic granuloma, catscratch fever)

  • Effect of drugs

    • Vitamin D and A intoxication

    • Milk-alkali (Burnett) syndrome (rare)

    • Diuretics (e.g., thiazides)

    • Others (estrogens, androgens, progestins, tamoxifen, lithium, thyroid hormone, parenteral nutrition)

  • Renal failure, acute or chronic

  • Other endocrine conditions

    • Thyrotoxicosis (in 20–40% of patients; usually <14 mg/dL)

    • More uncommon: Some patients with hypothyroidism, Cushing syndrome, adrenal insufficiency, acromegaly, pheochromocytoma (rare), VIPoma syndrome

    • Multiple endocrine neoplasia

  • Acute osteoporosis (e.g., immobilization of young patients or in Paget disease)

  • Miscellaneous

    • Familial hypocalciuric hypercalcemia

    • Rhabdomyolysis causing acute renal failure

    • Porphyria

    • Dehydration with hyperproteinemia

    • Hypophosphatasia

    • Idiopathic hypercalcemia of infancy

  • Concomitant hypokalemia is not infrequent in hypercalcemia. Concomitant dehydration is almost always present because hypercalcemia causes nephrogenic diabetes insipidus.

Decreased In (Tables 16.13 and 16.14)

 
TABLE 16–13
Serum Phosphate, PTH, and Vitamin D Levels in Various Hypocalcemic Disorders
 
TABLE 16–14
Variations of Various Serum and Urine Analytes in Association with Hypocalcemic Disorders
  • Hypoparathyroidism

    • Surgical

    • Idiopathic infiltration of parathyroids (e.g., sarcoid, amyloid, hemochromatosis, tumor)

    • Hereditary (e.g., DiGeorge syndrome)

    • Pseudohypoparathyroidism

    • Chronic renal disease with uremia and phosphate retention, Fanconi syndromes, renal tubular acidosis

    • Malabsorption of calcium and vitamin D, obstructive jaundice

    • Insufficient calcium, phosphorus, and vitamin D ingestion

    • Bone disease (osteomalacia, rickets)

    • Starvation

    • Late pregnancy

  • Altered bound calcium citrate

    • Multiple citrated blood transfusions

    • Dialysis with citrate anticoagulation

  • Hyperphosphatemia (e.g., phosphate enema/infusion)

  • Rhabdomyolysis

  • Tumor lysis syndrome

  • Acute severe illness (e.g., pancreatitis with extensive fat necrosis, sepsis, burns)

  • Respiratory alkalosis

  • Certain drugs

  • Osteoblastic tumor metastases

  • Neonates born of complicated pregnancies

    • Hyperbilirubinemia

    • Respiratory distress, asphyxia

    • Cerebral injuries

    • Infants of diabetic mothers

    • Prematurity

    • Maternal hypoparathyroidism

  • Hypermagnesemia (e.g., magnesium for treatment of toxemia of pregnancy)

  • Magnesium deficiency

  • Toxic shock syndrome

Temporary hypocalcemia after subtotal thyroidectomy in >40% of patients; >20% are symptomatic. 

Limitations

  • Total serum protein and albumin should always be measured simultaneously for proper interpretation of serum calcium levels, since 0.8 mg of calcium is bound to 1.0 g of albumin in serum; to correct, add 0.8 mg/dL for every 1.0 g/dL that serum albumin falls below 4.0 g/dL; binding to globulin only affects total calcium if globulin >6 g/dL.

  • Serum levels increased by

    • Hyperalbuminemia (e.g., multiple myeloma, Waldenström macroglobulinemia)

    • Dehydration

    • Venous stasis during blood collection by prolonged application of tourniquet

    • Use of cork-stoppered test tubes

    • Hyponatremia (<120 mEq/L), which increases the protein-bound fraction of calcium, thereby slightly increasing the total calcium (opposite effect in hypernatremia)

  • Serum levels decreased by

    • Hypomagnesemia (e.g., due to cisplatin chemotherapy)

    • Hyperphosphatemia (e.g., laxatives, phosphate enemas, chemotherapy of leukemia or lymphoma, rhabdomyolysis)

    • Hypoalbuminemia

    • Hemodilution

 
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