Calcium, Magnesium, and Phosphate Metabolism

Calcium, Magnesium, and Phosphate Metabolism

• Calcium, magnesium, and phosphate are essential for various bodily functions.
• The regulation of these minerals is crucial for maintaining overall health.

Why Learn About Calcium?

• Calcium salts play a vital role in providing structural integrity to the skeleton.
• Calcium ions are essential extracellularly and in cellular fluids for normal biochemical processes.
• Calcium ions are important for neuromuscular excitability, blood coagulation, hormonal secretion, and enzymatic regulation.

Regulation of Intracellular Calcium Concentration

• Intracellular calcium is stored in the mitochondria and endoplasmic reticulum (ER).
• "Pump-leak" transport systems maintain intracellular calcium levels.
• Calcium leaks into the cytosolic compartment and is actively pumped into storage organelles.

Extracellular Calcium

• Calcium in serum is found in three fractions.
• 50% is ionized calcium.
• 40% is protein-bound calcium
• 90% of the protein-bound calcium is bound to albumin
• The remainder of the protein bound calcium is bound to globulins
• 10% is calcium complexed to serum constituents such as citrate and phosphate.
• Citrate is used in blood transfusions.

Hormones Involved in Calcium Regulation

• Parathyroid hormone (PTH) is involved in calcium regulation
• Calcitriol [1,25(OH)2D] is involved in calcium regulation
• Calcitonin is involved in calcium regulation
• Calcitonin deficiency doesn't typically cause calcium abnormalities.

Parathyroid Hormone (PTH)

• PTH is a single-chain peptide hormone.
• PTH helps maintain extracellular fluid (ECF) calcium levels.
• PTH secretion is stimulated by calcium-sensing receptors.
• PTH acts directly on bone and kidneys.
• PTH acts indirectly on the gut via 1,25(OH)2D.
• PTH is produced when ionized calcium concentrations are low.
• PTH increases ionized serum calcium.
• PTH increases renal reabsorption of calcium.
• PTH decreases renal phosphate and bicarbonate (HCO3) reabsorption.
• PTH increases 1,25-(OH)2-D production.
• PTH increases osteoblast proliferation and osteoclastogenesis in bone.

Vitamin D

• Vitamin D is a steroid hormone.
• The body produces Vitamin D endogenously through exposure to sunlight.
• Vitamin D is absorbed from foods containing or supplemented with it.
• Vitamin D is metabolized to its active form (calcitriol) in the liver and kidneys.
• Vitamin D regulates calcium and phosphate metabolism.

1,25-(OH)2-Vitamin D (Calcitriol)

• Calcitriol increases calcium and phosphate absorption in the gut.
• Calcitriol potentiates the actions of PTH on osteoblasts, osteoclasts, and osteocytes in bone.
• Calcitriol stimulates osteoclastic resorption, especially at high concentrations.
• Calcitriol normalizes phosphate levels.
• Calcitriol acts via FGF23.

Measurement of Calcium

• Total calcium measurements include protein-bound, ionized, and complexed forms.
• Normal total calcium: 2.1 - 2.55 mmol/L.
• Total calcium measurements are unreliable in cases where protein is affects, like low albumin, elevated plasma proteins, alkalosis, acidosis, or venous stasis.
• Total calcium measurements are often sufficiently accurate for most clinical applications.
• Ionized calcium measurement employs a calcium-specific electrode on blood gas analyzers.
• Ionized calcium results are available immediately.
• Normal range of ionized calcium: 1.15 – 1.3 mmol/L.
• Ionized calcium levels aren't affected by plasma protein levels.
• Ionized calcium is recommended for patients with low albumin, elevated plasma proteins, alkalosis, acidosis, or rapidly changing ionized calcium levels.

Phosphorus Homeostasis

• Phosphorus is important for hydroxyapatite crystal formation in bones and teeth.
• It's a component of phosphoproteins, phospholipids, and nucleic acids.
• Phosphorus acts as a cofactor for enzymes like NADP and ADP.
• Phosphorus acts as a 2nd messenger like cAMP and ITP.
• It provides energy storage via phosphocreatine.
• Phosphorus contributes to oxygenation via 2,3-DPG.
• It plays a role in acid-base status by acting as a urine buffer.

Forms of Phosphorus

• Phosphorus is organic (phospholipids, phosphoproteins) and inorganic in the body.
• Inorganic phosphorus in the blood is ionized (53%), protein-bound (15%), or complexed (47%).
• Phosphorus measurement captures total inorganic phosphorus.
• Normal phosphorus: 0.8 – 1.35 mmol/L (adults), 1.2 – 1.9 mmol/L (children).

Fibroblast Growth Factor 23 (FGF23)

• FGF23 is secreted by osteoblasts and osteocytes in response to hyperphosphatemia, increased PTH, and increased 1,25-(OH)2-D.
• It binds to Klotho-FGFR1 receptors in the kidney and parathyroids.
• FGF23 decreases serum phosphate levels.
• FGF23 increases renal phosphate excretion.
• FGF23 increases phosphorus deposition in bone.

Magnesium Homeostasis

• Magnesium is an important cofactor in phosphate transfer reactions such as ATP formation, energy storage, and nucleic acid synthesis.
• Magnesium interacts with calcium to create resting potentials of excitable membranes in nerve and muscle cells.
• Magnesium impacts neuromuscular excitability, nerve conduction, and hormone secretion.
• Hypomagnesemia impairs PTH secretion and action and can affect other hormones.

Magnesium

• The body gets magnesium through dietary intake and GIT absorption.
• Magnesium is absorbed through active and passive transport in the small intestine.
• The kidneys reabsorb magnesium.
• 25% is reabsorbed in the PCT by passive paracellular diffusion.
• 60% is reabsorbed in the ascending loop of Henle (ALH) by passive diffusion.
• Filtered calcium and tubular ATPase activities also influence magnesium movement across tubular membranes.

Measurement of Magnesium

• Magnesium measurement captures total magnesium.
• Total magnesium is Free (60%), protein-bound (25%), complexed (15%).
• The free fraction of magnesium is biologically active.
• Magnesium measurements are unreliable if albumin is low or plasma proteins are elevated.
• Normal plasma magnesium: 0.7 – 0.95 mmol/L.
• Increased urine magnesium can be caused by diuretics or renal tubular dysfunction.

Questions and Answers

• PTH is important for minute-to-minute regulation of ionized calcium.
• Ionized calcium should be used to assess calcium status in patients post blood transfusion.
• Vitamin D deficiency is expected to lead to decreased calcium and decreased phosphate.
• High phosphate is a stimulatory factor for FGF 23 secretion.
• Magnesium is an important cofactor in the secretion and action of PTH.