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Subject: Calcium, Total
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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.
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.
Hyperparathyroidism, primary and secondary
Acute and chronic renal failure
Following renal transplantation
Osteomalacia with malabsorption
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)
Familial hypocalciuric hypercalcemia
Rhabdomyolysis causing acute renal failure
Dehydration with hyperproteinemia
Idiopathic hypercalcemia of infancy
Concomitant hypokalemia is not infrequent in hypercalcemia. Concomitant dehydration is almost always present because hypercalcemia causes nephrogenic diabetes insipidus.
PO4, phosphate; N, normal; I, increased; D, decreased.
Idiopathic infiltration of parathyroids (e.g., sarcoid, amyloid, hemochromatosis, tumor)
Hereditary (e.g., DiGeorge syndrome)
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)
Altered bound calcium citrate
Multiple citrated blood transfusions
Dialysis with citrate anticoagulation
Hyperphosphatemia (e.g., phosphate enema/infusion)
Tumor lysis syndrome
Acute severe illness (e.g., pancreatitis with extensive fat necrosis, sepsis, burns)
Cancer chemotherapy drugs (e.g., cisplatin, mithramycin, cytosine arabinoside)
Antibiotics (e.g., gentamicin, pentamidine, ketoconazole)
Chronic therapeutic use of anticonvulsant drugs (e.g., phenobarbital, phenytoin)
Gadolinium-based magnetic resonance (MR) imaging contrast agents.
Osteoblastic tumor metastases
Neonates born of complicated pregnancies
Respiratory distress, asphyxia
Infants of diabetic mothers
Hypermagnesemia (e.g., magnesium for treatment of toxemia of pregnancy)
Toxic shock syndrome
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)
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)