Calcium Homeostasis Mechanism
Calcium homeostasis is maintained through a complex regulatory system involving parathyroid hormone (PTH), vitamin D, and calcium-sensing receptors that coordinate calcium transport at the gut, kidney, and bone to maintain serum calcium levels within a narrow range. 1
Key Regulators of Calcium Homeostasis
- Parathyroid hormone (PTH) is a central regulator that responds to low serum calcium by increasing bone resorption, enhancing renal calcium reabsorption, and stimulating vitamin D activation 2, 1
- Vitamin D (specifically 1,25-dihydroxyvitamin D) enhances intestinal calcium absorption and works with PTH to maintain normal serum calcium levels 2, 1
- Calcium-sensing receptors (CaSRs) on parathyroid cells detect changes in serum ionized calcium and regulate PTH secretion through negative feedback 3
- Fibroblast growth factor-23 (FGF-23) and Klotho are additional regulators that interact with the PTH-vitamin D axis 3, 1
Organ Systems Involved in Calcium Regulation
Bone
- Serves as the primary calcium reservoir, containing 99% of total body calcium 4
- PTH stimulates bone resorption, releasing calcium into the bloodstream during hypocalcemia 1
- During periods of growth, calcium balance is positive (200-300 mg/day), becoming neutral in mature adults and negative with advancing age 5
Kidneys
- PTH increases calcium reabsorption in the distal tubule while decreasing phosphate reabsorption in the proximal tubule 2
- PTH stimulates the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in the kidneys 2
- The phosphaturic effect of PTH is crucial for maintaining normal serum phosphate levels, especially as kidney function declines 2
Intestine
- Vitamin D enhances intestinal calcium absorption in the duodenum and jejunum 5
- Passive intestinal calcium absorption (gradient-dependent) can be augmented by increasing calcium intake 5
- Dietary calcium requirements vary by age, with "adequate intakes" established rather than RDAs due to lack of direct biochemical measurements reflecting calcium nutritional status 5
Pathophysiology of Calcium Disorders
Hypocalcemia
- Defined as serum calcium levels below 8.4 mg/dL (2.10 mmol/L) 6
- Clinical manifestations include neuromuscular irritability, tetany, seizures, and cardiac dysrhythmias 6, 7
- Treatment involves calcium supplementation (oral or IV) and addressing the underlying cause 6
Hypercalcemia
- Defined as serum calcium concentration >10.5 mg/dL 8
- Most commonly caused by primary hyperparathyroidism and malignancies 8, 3
- Can lead to renal impairment, bone disease, and cardiovascular damage 3
Clinical Considerations
- Total daily intake of elemental calcium in patients with chronic kidney disease (CKD) should not exceed 2,000 mg per day 5, 6
- In CKD, calcium homeostasis becomes progressively disrupted as kidney function declines, requiring careful monitoring and management 2, 9
- Calcium supplementation may enhance soft tissue calcification and cardiovascular disease in patients with CKD-mineral bone disorders 9
- Dialysate calcium concentration of 2.5 mEq/L is generally recommended for patients on dialysis, allowing flexible use of other therapies directed at treating bone and parathyroid abnormalities 5
Pharmacological Interventions
- Cinacalcet acts as a calcimimetic agent that increases the sensitivity of calcium-sensing receptors, directly lowering PTH levels and decreasing serum calcium 10
- Calcium gluconate is used for acute symptomatic hypocalcemia, providing 9.3 mg (0.465 mEq) of elemental calcium per mL 4
- Active vitamin D sterols (calcitriol, alfacalcidol, or doxercalciferol) may be indicated for patients with CKD and persistent PTH elevation 6