Serum Calcium Testing

Serum calcium testing is primarily used to evaluate the function of the parathyroid glands and to assess calcium metabolism.
Total calcium is the measurement most frequently reported on laboratory results. It comprises several forms:
- Ionized Calcium: This is the physiologically active form of calcium. Direct testing for ionized calcium is significantly more expensive and difficult to perform.
- Protein-bound Calcium: Approximately $40\%$ of serum calcium is bound to proteins, predominantly albumin.
- Complexed Calcium: Calcium that is bound to other components, including citrate and bicarbonate ( $HCO_{3}^{-}$ ).

The biological system maintains serum calcium levels within a very tight window, typically between $8.5\,\text{mg/dL}$ and $10.5\,\text{mg/dL}$ .
Due to the sensitivity of these tests to outside factors, even small deviations from this specified range warrant clinical consideration for retesting.
Hypercalcemia is formally identified when serum calcium levels are found to be elevated on $3$ separate occasions.
Critical threshold levels include:
- High Levels: Associated with a risk for coma.
- Low Levels: Values less than $4\,\text{mg/dL}$ are considered within the deadly range.

Renal Failure and Renal Transplantation: The kidneys are essential for the excretion and reabsorption of calcium. They are also responsible for the final activation of Vitamin D3.
Parathyroid Disorders: Conditions causing increased output of parathyroid hormone ( $\text{PTH}$ ) lead to significant metabolic issues.
Malignancies: Various forms of cancer result in observable alterations to serum calcium.

Primary Hyperparathyroidism: This is the leading cause of hypercalcemia.
- The inciting incident is an overproduction of parathyroid hormone ( $\text{PTH}$ ) by the parathyroid glands.
- Effects include decreased urinary excretion of calcium, increased bone resorption, and increased gastrointestinal (GI) absorption via Vitamin D mechanisms.
- Despite these mechanisms, it is noted that these factors lead to a hypocalcemia due to that hypoparathyroidism primary hypoparathyroidism.
Malignancy: This is the second most common cause of hypercalcemia, occurring via two distinct mechanisms:
- Tumor Metastasis to the Bone: Destruction and resorption of the bone tissue push calcium directly into the bloodstream.
- Ectopic Hormone Production: Certain cancers secrete a hormone or hormone-like substance that mimics the actions of $\text{PTH}$ , thereby driving up serum calcium levels.
Excessive Vitamin D Ingestion: This up-regulates calcium absorption in the gut and affects renal tubules in a manner similar to $\text{PTH}$ , leading to elevated serum levels.

Malabsorption Conditions: Because Vitamin D is a fat-soluble vitamin, malabsorption leads to Vitamin D deficiency, which down-regulates the GI absorption of calcium.
Renal Failure: Diseased kidneys cannot perform the final activation of Vitamin D, which halts the regulated GI absorption of calcium.

Plasma Albumin and Calcium Relationship: These levels typically move in parallel because roughly $40\%$ of calcium is bound to albumin.
- In clinical presentations, patients with hypoalbuminemia (decreased albumin) will also present with hypercalcemia.
- It is standard clinical practice to monitor plasma albumin alongside calcium to determine if calcium abnormalities are attributable to protein level alterations.
Plasma pH and Ionized Calcium Relationship: These factors share an inverse relationship.
- Acidosis (Decreased pH): Leads to an increase in free, ionized calcium.
- Alkalosis (Increased pH): Leads to a decrease in ionized calcium.
Vitamin D Toxicity: Excessive Vitamin D levels directly increase serum calcium by increasing absorption from the gut.
Venous Stasis: This occurs during blood collection if the tourniquet is applied for too long, impacting the pH of the blood and altering the calcium reading.
- To ensure accuracy, the tourniquet must be applied for no longer than $1\,\text{minute}$ .