Calcium metabolism

Calcium Metabolism Study Notes

Overview of Calcium Metabolism

  • Plasma Calcium Concentration: Calcium levels in the plasma are critical for various physiological processes and are tightly regulated by hormonal control.

  • Total Plasma Calcium: Normal total plasma calcium concentration is between 2.2 - 2.5 mM, made up of:

    • Free ionized calcium (~1.2 mM, ~45% biologically active)

    • Calcium bound to serum proteins (~45%)

    • Calcium complexed with anions (~10%, e.g., phosphate, lactate, bicarbonate)

Factors Affecting Plasma Calcium Concentration

  • Bound and Free Ionized [Ca²⁺]: Plasma calcium exists in three forms: free ionized, bound to proteins, and complexed with anions.

  • Albumin-Corrected Total Plasma [Ca²⁺]:

    • Calculated using:

    • Albumin-corrected Ca²⁺ (in mmol/L) = Measured Ca²⁺ + [40 - serum albumin (g/L)] × 0.02

    • Albumin-corrected Ca²⁺ (in mg/dL) = Measured Ca²⁺ + [4 - serum albumin (g/dL)] × 0.8

    • Corrects for changes in serum albumin concentration, as hypocalcemia can result from hypoalbuminemia.

General Functions of Calcium

  • Key Functions:

    • Membrane excitability of nerves and muscles: Calcium stabilizes membrane structure and plays a crucial role in neurotransmission and muscle contractions.

    • Cofactor for blood clotting.

    • Formation and growth of bones and teeth.

    • Cell adhesion and intracellular signaling.

  • Consequence of Calcium Imbalance:

    • Hypocalcemia: Increased neuromuscular excitability, tetany (muscle spasms), Chvostek’s and Trousseau’s signs.

    • Hypercalcemia: Decreased neuromuscular excitability, muscle weakness, CNS impairment (confusion, somnolence), hypercalcemia-induced ileus and renal issues (nephrolithiasis).

Hormonal Control of Plasma [Ca²⁺]

  • Key Hormones: Three main hormones regulate calcium homeostasis:

    • Parathyroid Hormone (PTH): Increases blood calcium levels through bone resorption, renal reabsorption, and intestinal absorption of calcium.

    • Calcitonin: Decreases blood calcium levels by inhibiting bone resorption and enhancing renal calcium excretion.

    • Calcitriol (1,25-dihydroxycholecalciferol): Increases blood calcium by enhancing intestinal absorption and promoting bone resorption.

  • Hormonal Responses:

    • Hypocalcemia: Increases PTH and calcitriol secretion, decreases calcitonin.

    • Hypercalcemia: Inhibits PTH release, stimulates calcitonin release.

Control of Hormone Secretion

  • Control of Calcitonin Secretion:

    • Secreted by C-cells of the thyroid gland in response to an increase in plasma ionized [Ca²⁺].

    • Inhibited by lower plasma ionized [Ca²⁺].

    • Affected by gastrointestinal hormones (e.g., gastrin, CCK).

  • Control of PTH Secretion:

    • Secreted by chief cells in the parathyroid glands, stimulated by a decrease in plasma [Ca²⁺] and an increase in phosphate levels.

    • Inhibited by an increase in plasma [Ca²⁺] and negative feedback from calcitriol.

Anabolic Effects of PTH

  • Mechanism: PTH can stimulate bone formation at low intermittent doses, promoting the differentiation and proliferation of osteoblasts and decreasing sclerostin production, leading to increased bone mass.

  • Treatment: teriparatide (recombinant hPTH1-34) is used to treat osteoporosis by stimulating new bone formation.

Physiology of Calcium Regulation in the Kidney

  • Renal Handling of Calcium: Calcium reabsorption occurs predominantly in:

    • Proximal Tubule: Affected by body fluid status.

    • Thick Ascending Limb (TAL): Influenced by loop diuretics.

    • Distal Convoluted Tubule: Affected by thiazide diuretics.

  • Calcium Sensing Receptor (CaSR): Detects serum calcium levels and modulates PTH secretion accordingly.

Calcium Homeostasis and Bone Development

  • Other Hormones Affecting Calcium Levels:

    • Sex Steroids: Promote bone formation and maintain calcium homeostasis.

    • Glucocorticoids: Inhibit calcium absorption and promote bone resorption, leading to osteoporosis.

    • Growth Hormone (GH)/IGF-1: Stimulate bone growth and mineralization.

    • Thyroid Hormones: Influence bone remodeling and calcium homeostasis.

Disorders of Calcium Metabolism

  • Primary Hyperparathyroidism: Characterized by elevated serum calcium and low serum phosphate due to parathyroid adenomas. Symptoms include renal stones and bone pain.

  • Secondary Hyperparathyroidism: Often seen in renal failure due to low calcium levels and high phosphate levels, leading to increased PTH secretion.

  • Tertiary Hyperparathyroidism: Continued high PTH levels after correction of the underlying cause of secondary hyperparathyroidism.

  • Humoral Hypercalcemia of Malignancy (HHM): Caused by PTHrP secreted by tumors, leading to increased calcium levels despite normal parathyroid function.

Clinical Testing and Management of Calcium Metabolism Disorders

  • Testing Protocols: Serum levels of calcium, phosphate, PTH, and renal function tests to assess calcium metabolism disorders.

  • Management Strategies: Include hydration, diuretics in case of hypercalcemia, calcitonin, and monitoring of bone density over time.

Case Studies and Examples

  • A case study may illustrate hypercalcemia due to squamous cell carcinoma, demonstrating elevated calcium levels alongside normal PTH levels indicating HHM.

  • Clinical signs like muscle weakness, polyuria, and confusion contribute to diagnosis and treatment strategies.