Phosphorus

Marker Name: Phosphorus

REFERENCE RANGES FOR SERUM PHOSPHORUS:

Laboratory reference range: 2.5–4.5 mg/dL

Functional reference range: 3.0–4.0 mg/dL

DESCRIPTION:

Phosphorus (P) is a primary constituent of bones and teeth, which contain about 85 percent of total body phosphorus as hydroxyapatite. Remaining phosphorus is found primarily inside cells as a crucial component of adenosine triphosphate (ATP), phospholipids in cell membranes, and the structural framework of DNA and RNA. Phosphorus also helps regulate use of certain vitamins and minerals such as vitamin D, iodine, magnesium, and zinc.^1,2 A relatively small amount of phosphorus is found in the plasma as phospholipids, ester phosphates, and inorganic phosphate anions.³

Regulation of phosphorus homeostasis involves intestinal absorption and secretion, renal excretion and reabsorption, and bone formation and resorption. These regulatory processes involve a complex interplay of parathyroid hormone (PTH), calcitonin, fibroblast growth factor 23 (FGF23) and its cofactor Klotho, and possibly estrogens. Dietary deficiency is rare, as intake and absorption of dietary phosphate in the small intestine are normally high and proceed with minimal regulation by calcitriol, while a relatively small amount of phosphate is excreted in the colon. Bone resorption can raise plasma phosphate concentration and is regulated by PTH, calcitriol, and possibly FGF23. The kidneys play the most important role in phosphorus balance, as renal phosphate reabsorption can vary widely and responds to dietary phosphate consumption, serum phosphate level, PTH, FGF23, other phosphatonins, and calcitriol.³

High serum phosphorus concentration (hyperphosphatemia) can be caused by tissue breakdown, movement of phosphate out of cells, vitamin D toxicity, decreased renal excretion, pseudohyperphosphatemia (due to a laboratory artifact), or certain drugs. A complete list of conditions and drugs that can cause hyperphosphatemia is provided below.²

Low serum phosphorus concentration (hypophosphatemia) can be caused by alcoholism, vitamin D deficiency or resistance, decreased intestinal absorption, redistribution of phosphate from extracellular fluid into cells (as seen in hungry bone syndrome), renal replacement therapies, increased urinary phosphate excretion, and certain drugs. A full list of conditions and drugs that can cause low serum phosphorus is below.^4,5

If the etiology of abnormal serum phosphorus is unclear from patient history, it can be useful to measure vitamin D.⁶

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:²

• Vitamin D toxicity
• Cell lysis
  • Tumor lysis syndrome
  • Rhabdomyolysis
• Cellular shift of phosphate out of cells
  • Lactic acidosis
  • Ketoacidosis
  • Severe hyperglycemia
• Decreased renal excretion
  • Reduced glomerular filtration rate
    • Acute kidney injury
    • Chronic kidney disease
  • Increased tubular reabsorption
    • Hypoparathyroidism
    • Pseudohypoparathyroidism (renal resistance to PTH)
    • Acromegaly
    • Familial tumoral calcinosis
  • Pseudohyperphosphatemia (laboratory artifact)
    • Hyperglobulinemia
      • Multiple myeloma
      • Waldenström’s macroglobulinemia
      • Monoclonal gammopathy
    • Hyperlipidemia
    • Hemolysis
    • Hyperbilirubinemia
    • Sample contamination with certain medications
      • High-dose liposomal amphotericin B
      • Heparin
      • Recombinant tissue plasminogen activator
    • Drugs
      • Bisphosphonates (e.g., etidronate)
      • Phosphate-containing laxatives
      • Fosphenytoin

Low in:^4,5

• Vitamin D deficiency or resistance
• Alcoholism
• Decreased intestinal absorption
  • Inadequate intake (rare)
  • Steatorrhea
  • Chronic diarrhea
  • Inflammatory bowel disease (e.g., Crohn’s disease, celiac disease)¹
• Redistribution of phosphate from extracellular fluid into cells
  • Increased insulin secretion
    • Treatment of diabetic ketoacidosis or nonketotic hyperglycemia
    • Refeeding of malnourished patients
    • Patients receiving hyperalimentation
  • Acute respiratory alkalosis
  • Hungry bone syndrome
    • Post-parathyroidectomy
    • Post-thyroidectomy in patients with preexisting osteopenia
  • Renal replacement therapies
  • Increased urinary phosphate excretion
    • Primary and secondary hyperparathyroidism
    • Osmotic diuresis
    • Intravenous iron administration (especially formulations containing carbohydrate moieties)
    • Post renal transplantation
    • Post partial hepatectomy
    • Hereditary hypophosphatemic rickets
    • Tumor-induced osteomalacia
    • Fibrous dysplasia (rare)
    • McCune-Albright syndrome (rare)
    • Fanconi syndrome, as seen in:
      • Multiple myeloma
      • Cystinosis
      • Wilson’s disease
      • Hereditary fructose intolerance
    • Drugs
      • Thiazide diuretics with carbonic anhydrase inhibitory activity (e.g., metolazone)
      • Antacids containing aluminum or magnesium
      • Cinacalcet treatment
      • Tenofovir
      • Acetazolamide
      • Imatinib mesylate

FUNCTIONAL RANGE INDICATIONS:

High in:

• Excessive vitamin D supplementation
• Impaired kidney function (check BUN, creatinine, and other markers of kidney function)
• Recent broken bone
• Many other disease states

Low in:

• Vitamin D deficiency
• Hypochlorhydria
• Fluid loss
• Many other disease states

References:

1. https://umm.edu/health/medical/altmed/supplement/phosphorus
2. http://www.uptodate.com/contents/overview-of-the-causes-and-treatment-of-hyperphosphatemia
3. http://www.uptodate.com/contents/regulation-of-calcium-and-phosphate-balance
4. http://www.uptodate.com/contents/causes-of-hypophosphatemia
5. http://www.uptodate.com/contents/hypophosphatemia-in-the-alcoholic-patient
6. http://www.uptodate.com/contents/evaluation-and-treatment-of-hypophosphatemia