Effect of Blood pH on Ionized Calcium
As the pH of a blood sample decreases (becomes more acidic), the portion of calcium that is ionized increases.
Physiological Relationship Between pH and Ionized Calcium
The relationship between blood pH and ionized calcium is well-established in clinical guidelines and research. According to the European guideline on management of major bleeding and coagulopathy following trauma, ionized calcium (Ca²⁺) is pH-dependent, with a 0.1 unit increase in pH decreasing ionized calcium concentration by approximately 0.05 mmol/L 1. This inverse relationship means that when pH decreases (becomes more acidic), the ionized calcium concentration increases.
This relationship occurs because:
Calcium in blood exists in two primary forms:
- Ionized (free) calcium (approximately 45%)
- Protein-bound calcium (approximately 55%)
When blood becomes more acidic (lower pH):
- Hydrogen ions compete with calcium for protein binding sites
- More calcium is displaced from proteins
- The proportion of ionized calcium increases
Clinical Significance
The normal range of ionized calcium is 1.1–1.3 mmol/L (4.6-5.4 mg/dL) 1, 2. This ionized form is physiologically active and essential for:
- Formation and stabilization of fibrin polymerization sites
- Multiple platelet-related functions
- Cardiac contractility
- Systemic vascular resistance
In clinical settings, this relationship has important implications:
- Acidosis: Will increase ionized calcium levels, even when total calcium remains unchanged
- Alkalosis: Will decrease ionized calcium levels, potentially causing symptoms of hypocalcemia even with normal total calcium
Research studies have quantified this relationship. A study examining the effects of pH on ionized calcium and magnesium found that ionized calcium changes by approximately 0.36 mmol/L per pH unit 3. Another study determined that the mean slope of regression for log ionized calcium/pH was -0.39, confirming the inverse relationship 4.
Clinical Applications
Understanding this relationship is crucial in:
Interpreting calcium levels: When evaluating calcium status, pH must be considered
- Low pH (acidosis) may mask hypocalcemia by increasing the ionized fraction
- High pH (alkalosis) may mask hypercalcemia by decreasing the ionized fraction
Massive transfusion scenarios: Guidelines recommend monitoring ionized calcium levels during massive transfusion, as citrate in blood products can bind calcium and cause hypocalcemia 1
Laboratory measurements: When measuring ionized calcium, pH adjustment may be necessary for accurate interpretation
Conclusion
The answer is B: increases. As blood pH decreases, the portion of calcium that is ionized increases due to the displacement of calcium from protein binding sites by hydrogen ions.