Labs: Calcium

Summary

Calcium is a vital mineral in the body, playing a key role in bone health, muscle function, nerve signaling, and blood clotting. Laboratory analysis of serum calcium levels helps assess calcium homeostasis and detect conditions such as hypercalcemia or hypocalcemia. Total calcium includes both bound and free calcium, while ionized calcium measures the physiologically active form. Factors like albumin levels, pH, and parathyroid hormone influence calcium levels, making clinical context essential for interpretation.

Key Terms

Ionized Calcium: Ionized calcium is the physiologically active form of calcium in the blood, not bound to proteins or anions, and is crucial for various cellular functions, including muscle contraction, nerve transmission, and blood clotting.

Basic Science

Calcium (Ca2+) is an essential mineral vital for numerous physiological processes. About 99% of the body's calcium is stored in bones, providing structural support. The remaining 1% circulates in the blood and extracellular fluid and is critical for:

Muscle Contraction: Ca2+ influx into muscle cells initiates contraction.
Nerve Transmission: Ca2+ is crucial for neurotransmitter release at synapses.
Blood Clotting: Ca2+ is a cofactor in the coagulation cascade.
Cellular Signaling: Acts as a second messenger in various signaling pathways.
Bone Health: Necessary for bone formation and remodeling.

Calcium homeostasis is tightly regulated by:

Parathyroid Hormone (PTH): Increases blood calcium by promoting bone resorption, increasing renal reabsorption, and stimulating vitamin D activation.
Vitamin D: Increases intestinal calcium absorption.
Calcitonin: Decreases blood calcium (less important in humans).

Lab Analysis of Calcium

Calcium levels are typically measured in the serum. Normal range is approximately 8.5-10.5 mg/dL, but the specific reference range may vary by lab. In select patients, consider both total and ionized calcium:

Total Calcium: Measures all calcium in the blood (bound to proteins and free). Changes in albumin levels can affect total calcium, so it needs to be adjusted, especially for hypoalbuminemia.
Ionized Calcium: Measures the biologically active, free calcium. This is the most accurate measurement of calcium status.

Abnormal Calcium Levels

Hypercalcemia

Definition: Serum calcium > 10.5 mg/dL or ionized calcium above normal.

Etiologies:

Primary Hyperparathyroidism: Most common cause, typically due to a parathyroid adenoma. Increased PTH leads to increased bone resorption and renal calcium reabsorption.
Malignancy: Tumor lysis, bone metastases, and paraneoplastic syndrome with PTH-related peptide (PTHrP) release, such as in lung, breast, and myeloma cancers.
Thiazide Diuretics: Reduce calcium excretion in kidneys.
Vitamin D Toxicity: Can increase calcium absorption.
Immobilization: Prolonged bed rest can cause bone breakdown and hypercalcemia.
Familial hypocalciuric hypercalcemia (FHH): Rare, but important to recognize.

Patient History:

Often asymptomatic in mild cases.
“Stones, bones, groans, thrones, and psychiatric overtones”: Renal stones, bone pain, abdominal pain/constipation, polyuria, and depression/confusion.
History of malignancy or hyperparathyroidism
Family history of hypercalcemia
Recent thiazide diuretic use or vitamin D intake
Recent large calcium carbonate (commonly known as tums) intake

Physical Exam Findings:

Often non-specific, may be normal in mild cases.
Severe cases may show signs of dehydration, muscle weakness, confusion, and arrhythmias.

Labs to Consider:

Serum total calcium and albumin
Ionized calcium
PTH level
25-hydroxyvitamin D
Phosphorus
Creatinine
Urine calcium excretion
EKG ( looking for shortened QT interval )

Differential Diagnosis:

Primary hyperparathyroidism
Malignancy-associated hypercalcemia
Thiazide diuretic-induced hypercalcemia
Vitamin D toxicity
Familial Hypocalciuric Hypercalcemia (FHH)

Management:

IV Fluids: Normal saline to increase renal excretion.
Loop Diuretics: (e.g., furosemide) after rehydration to further increase calcium excretion.
Bisphosphonates: (e.g., zoledronic acid) Inhibit osteoclast-mediated bone resorption; slower onset but longer effect.
Calcitonin: Rapidly reduces calcium but short-acting. Used for acute management of severe hypercalcemia.
Cinacalcet: Calcimimetic drug, decreases PTH secretion in hyperparathyroidism.
Treatment of underlying cause: Parathyroidectomy for primary hyperparathyroidism. Treatment of cancer.

Hypocalcemia (Low Calcium)

Definition: Serum calcium < 8.5 mg/dL or ionized calcium below normal.