Calcium and phosphate

Calcium normal serum 8.5 - 10.5 mg/dL

• Role -bone health, muscle contractility, nerve tissue excitability, secretion from exocrine and endocrine glands, cofactor for enzyme systems and coagulation cascade

• Total Body- 1400g with 99% in bones and 1% in plasma/extravascular fluid

  • dietary intake of 1000 -1200 mg in natural and fortified foods

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• Normal Plasma range 8.5-10.5 mg/dL with 40% protein bound and rest free ionized

• Normal Ionized range 4.6-5.2 mg/dL

• Corrected Ca in mg/dL

  $0.8\left(4\frac{g}{dl}-A\operatorname{lb}_{obs}\frac{g}{dl}\right)+Ca_{obs}\frac{mg}{dl}$

• Parathyroid glands - secrete 15-65 pg/mL of parathyroid hormone (PTH)

  • increases bone and kidney Ca reabsorption and GI absorption and stimulate kidney to make Calcitriol (negative feedback regulated)

Hypocalcemia Ca < 8.5 mg/dL

• Manifestations - Convulsions, Arrhythmias, Tetany, Spasms CATS

  • seizures, bradycardia, prolonged QT interval, laryngospasm, paresthesias, latent tetany (trousseau’s and chvostek’s signs)

• Etiology- Vitamin D deficiency (< 30 ng/mL ), hypoparathyroidism, hyperphosphatemia, drugs like cinacalcet (sensipar) and bone resorption inhibitors (bisphosphonates, denosumab)

  • hypoparathyroidism - less Ca and less or normal PTH

  • Vitamin D deficiency or hyperphosphatemia - less Ca and more PTH with renal insufficiency

• Treatment - address underlying cause and Ca supplement

• 2g of eCa/day or 500-600 mg per dose of eCa

Vitamin D

• Metabolism - skin absorbs precursor → liver hydroxylates to 25(OH)D → 1-a-hydroxylase in kidney turns it into Calcitriol

  • Ergocalciferol (plants D₂)and Cholecalciferol (animals D₃)

    • dietary inactive forms of Vitamin D that increase Ca and Phos GI absorption

    • dosed 50,000 IU PO weekly or 6,000 daily over 8 weeks

      • maintenance 1000 to 2000 IU PO daily

  • Calcitriol (Rocaltrol or 1,25(OH)₂D)

    • active form of Vitamin D

    • decreases PTH and increases Ca and Phos absorption in GI

    • PO 0.25 - 1 mcg/day or IV 0.5 - 4 mcg 3x/wk

Hypercalcemia Ca > 10.5 mg/dL

• Manifestations: bones (osteopenia), groans (anorexia, N/V,abdominal pain, constipation), stones (nephrolithiasis), thrones (dehydration as poly/nocturia), psychiatric overtones (lethargy/fatigue, headache, confusion/memory impairment, depression,acute psychosis)

• Etiologies - hyperparathyroidism increasing PTH , malignancy PTH related protein tumor causing more absorption in kidney and bones, medications

  • thiazides renal reabsorption, lithium bone reabsorption, Ca-containing antacids, Vitamin D overdose, immobilization

• Regulation - body wants to reduce PTH to reduce Ca inhibiting reabsorption methods and Calcitriol

• Treatment: depends on underlying cause, severity, s/sx, and duration

• Hydration and Diuresis - increase urinary excretion and stop renal reabsorption onset of 1-2 days

  • 1-2 L of NS bolus then maintenance at 250 to 300 mL/h to maintain UoP of 100-150

  • furosemide 40-80 mg Q1-4H

• Bisphosphonates - inhibit bone resorption with onset of 2 days repeated in 7 days

  • Zoledronic acid 4-8 mg IV over 15 min

  • Pamidronate 30-90 mg IV over 2 - 24 hr

  • ADR- fever, myalgias/arthralgias, N/V, nephrotoxicity, jaw osteonecrosis

• Calcitonin/Miacalcin - inhibit bone resorption and renal reabsorption onset 1-2hr

  • 4 IU/ kg SQ or IM Q12H max 8 IU/kg Q6H

  • ADR - N/V, facial flushing, hypersensitivity skin test, tachyphylaxis (drug response drops once admin)

• Denosumab (Xgeva) - inhibits bone resorption for bisphosphonates malignancy

  • 120 mg SQ Q4W

  • ADR - Jaw osteonecrosis, severe hypoglycemia for renal insufficiency

• Dialysis for renal insufficiency or Ca concentrations are life-threatening

Hyperparathyroidism

• Vitamin D analogs - calcitriol, paricalcitol, doxercalciferol

  • suppress PTH circulation to decrease bone and kidney reabsorption and GI absorption

• Calcimimetics - cinacalcet, etelcalcetide

  • increase Ca sensing receptor sensitivity to decrease PTH and serum Ca

Phosphate serum 2.5-4.5 mg/dL

• Role - bone health, energy (ATP), cell membrane structure, cell signaling, oxygen delivery

• Total Body- 85% bone, 14% soft tissue, <1% extracellular fluid

  • average adult diet 800-1600 mg/day with 60-80% absorbed reduced without vit D

Hypophosphatemia <2.5 mg/dL

• Manifestations

• Etiologies- dietary deficiency, refeeding syndrome, impaired GI absorption (malabsorptive conditions, vitamin D deficiency, phosphate-binding drugs), increased renal elimination from diuresis or hyperparathyroidism

• Treatment - severity based

Hyperphosphatemia serum phosphate > 4.5 mg/dL

• Phosphate Regulation - Phos levels high FGF23 activated

  • Fibroblast growth hormone (FGF23) - increases to increase renal excretion and inhibit vitamin D kills active to lessen GI absorption of Ca and Phos

  • Increases PTH - decreases serum Ca

    • increase bone resorption, intestinal absorption, renal reabsorption

    • decreases Phos by increasing bone resorption and intestinal absorption, decreased renal reabsorption

• Manifestations - hypocalcemia, bone pain, fractures, Calcification (Ca x Phos > 55)

• Etiologies - more intake from diet/supplements/vitamin D, renal dysfunction, increased tissue release due to tumor lysis syndrome, rhabdomyolysis, hemolysis

• Treatment - dietary restriction of 800-1000 mg/day, phosphate binding agents, dialysis

  • Phosphate Binders - bind dietary phosphorus, thus given with meals