A Quick Reference on Phosphorus PDF 2017 Veterinary Clinics

A Q u i c k R e f e ren c e o n Phosphorus Ashley E. Allen-Durrance, DVM KEYWORDS  Phosphorus  Phosphate  Anion  Hypophosphatemia  Hyperphosphatemia KEY POINTS  Phosphorus, or phosphate, is the body’s major intracellular anion involved in cellular en- ergy, membrane integrity, a...

A Q u i c k R e f e ren c e o n Phosphorus Ashley E. Allen-Durrance, DVM KEYWORDS  Phosphorus  Phosphate  Anion  Hypophosphatemia  Hyperphosphatemia KEY POINTS  Phosphorus, or phosphate, is the body’s major intracellular anion involved in cellular en- ergy, membrane integrity, and metabolism.  Technically, phosphorus is an element and phosphate is a molecular anion; however, the terms are often used interchangeably. For simplicity, phosphate will be used throughout the text to refer to either.  Phosphate is vital to normal dentition and osseous matrix, tissue oxygenation, and enzy- matic processes.  Distribution of phosphate is primarily intracellular; thus, measuring serum phosphate is not necessarily reflective of total body stores.  Numerous causes of hypophosphatemia and hyperphosphatemia exist in dogs and cats, and the underlying cause should be treated in addition to managing the phosphate derangement.  Phosphorus, or phosphate, is the body’s major intracellular anion and is required to produce ATP, guanosine triphosphate, cyclic adenosine monophosphate, and phosphocreatine, which function to maintain cellular membrane integrity, energy stores, metabolic processes (muscle contraction, nerve impulse conduction, cell transport), and biochemical messenger sys- tems.1–3 In addition, phosphorus is vital in maintaining normal bone and dental matrix, regulating tissue oxygenation (2,3-diphosphoglycerate [2,3-DPG]), buffering acidotic conditions in the body, and regulating many en- zymes (eg, 1a-hydroxylase and glutaminase).  Phosphate distribution  80% to 85% stored as hydroxyapatite in bone matrix  14% to 15% stored in soft tissues, such as muscle  Less than 1% stored in the extracellular space The author has nothing to disclose. Small Animal Clinical Sciences, University of Florida, 2015 Southwest 16th Avenue, Gainesville, FL 32608, USA E-mail address: [email protected] Vet Clin Small Anim 47 (2017) 257–262 http://dx.doi.org/10.1016/j.cvsm.2016.09.003 vetsmall.theclinics.com 0195-5616/17/ª 2016 Elsevier Inc. All rights reserved. 258 Allen-Durrance  Phosphate regulation  Parathyroid hormone ([ release of phosphate from bone, [ renal phosphate excretion), calcitriol ([ intestinal phosphate absorption), and calcitonin ([ renal phosphate excretion) regulate phosphate.  Phosphatonins, such as fibroblast growth factor-23 (FGF-23), are phosphate regulatory substances with autocrine, paracrine, or endocrine mechanisms of action. FGF-23 has primarily a phosphaturic action.  Gastrointestinal absorption of phosphorus is linearly related to intake and 60% to 70% of ingested phosphorus is absorbed in the small intestine.  In the kidneys, 60% to 100% (depending on bodily needs) of filtered phosphate is reabsorbed in the proximal convoluted tubule. Growth hormone, insulin, insulin-like growth factor 1, and thyroxine increase renal tubular phosphate reabsorption. ANALYSIS  Indications  Serum phosphate is commonly measured during systemic disease and is included in many chemistry panels. It should be measured and monitored regularly in patients with acute kidney injury or chronic kidney disease, in those taking oral phosphate binders, in those undergoing chemotherapy with a high tumor burden, after refeeding if severely malnourished, in those being treated for diabetes melli- tus or hyperosmolar conditions, in patients with concurrent hypercalcemic condi- tions, and in those with acute or chronic anorexia, vomiting, or diarrhea.  Reference range  Serum concentrations of phosphate measured by blood chemistry analyzers do not necessarily reflect whole-body phosphate balance because it is the pre- dominant intracellular anion and rapid transcellular shifts can occur.  Phosphate concentration is typically expressed as phosphate mass (mg/dL). Normal range of serum phosphate concentration in dogs and cats is 2.5 mg/ dL to 6 mg/dL (0.8–1.9 mmol/L), with variation expected based on patient age and chemistry analyzer used. Serum phosphate concentrations up to 10 mg/dL have been reported in normal healthy puppies.  Conversion: normal serum phosphate concentration of 3.1 mg/dL 5 1 mmol/L phosphate 5 1.8 mEq/L phosphate  Transient peaks in serum phosphate occur 6 to 8 hours after a meal; therefore, ideally collect blood samples after a 12-hour fast.  Danger values  Severe hypophosphatemia (below 1 mg/dL or 0.31 mmol/L) is generally asso- ciated with whole-body phosphate depletion and can result in hemolysis or rhabdomyolysis.  Severe hyperphosphatemia can result in tetany (due to hypocalcemia), soft tis- sue mineralization (especially if calcium  phosphate product is >60–70), and metabolic acidosis (for each 1-mg/dL increase in phosphate expect a 0.55- mEq/L decrease in bicarbonate). Severe acute hyperphosphatemia without coexisting hypercalcemia (eg, phosphate enema toxicity) can result in acute kidney injury.  Artifacts  Mannitol (25 mmol/L) can interfere with DuPont Automatic Clinical Analyzer colorimetric tests, leading to spurious hypophosphatemia.  Hemolysis, hypertriglyceridemia, hyperbilirubinemia, and presence of a mono- clonal gammopathy can lead to spurious hyperphosphatemia.  Phosphorus 259  Drug effects  Phosphate-binding antacids interfere with gastrointestinal absorption of phosphate.  Mannitol can cause phosphate wasting due to its diuretic effects.  Insulin, dextrose, and bicarbonate cause phosphate to shift intracellularly and may result in hypophosphatemia. HYPOPHOSPHATEMIA  Causes (Box 1)  Hypophosphatemia can occur secondary to decreased gastrointestinal ab- sorption (anorexia, diarrhea, vomiting, and malabsorptive conditions), trans- cellular shifts (metabolic or iatrogenic alkalosis, refeeding syndrome, and insulin therapy), increased renal excretion (conditions associated with diuresis, such as diabetic ketoacidosis, diuretic administration, overzealous fluid administration, and postobstructive diuresis), or some combination of these.  Signs  Depletion of ATP and 2,3-DPG affects most cells in the body and is responsible for the severe clinical signs of hypophosphatemia.  Clinical signs of mild hypophosphatemia (1–2.5 mg/dL) can be vague and include generalized weakness, tremors, muscle pain, ataxia, anorexia, nausea, functional ileus, and vomiting.  Hemolysis, rhabdomyolysis, acute respiratory failure, seizures, and coma can occur with severe hypophosphatemia (