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KEY POINTS
■ The etiology of hyperphosphatemia includes excessive phosphate intake or renal reabsorption, diminished phosphate excretion, and transcellular shifting. Hyperphosphatemia is most often the culmination of several maladies rather than resulting from a single contributory cause. However, the most common cause of hyperphosphatemia is renal failure.
■ Most patients with hyperphosphatemia are asymptomatic. Clinically, manifestations common to hypocalcemia evolve and represent sequelae of hyperphosphatemia. CNS and cardiovascular system changes predominate the clinical presentation of hyperphosphatemia.
■ Efficacious treatment of hyperphosphatemia, where applicable, consists of successful treatment of the underlying pathologies. Otherwise, treatment centers on lowering phosphate intake and increasing renal excretion.
The incidence of hyperphosphatemia is relatively low, up to 3% of the general hospital population;1,2 however, this electrolyte imbalance often indicates significant comorbidity. Recognition of hyperphosphatemia is paramount to successful management of the at-risk patient and provides clinical insight into underlying metabolic function.
PHOSPHATE: A VITAL ANION
Body stores of phosphorus range from 700 to 1,000 g and are primarily coupled to oxygen as an anion phosphate (PO4). Approximately 85% of phosphate is an inorganic component of the crystalline hydroxyapatite contained in phosphate reservoirs in bone and teeth.3 The hydroxyapatites have a general structural formula of Ca10(PO4)6(OH)2 and provide the rigid architectural framework characteristic of osseous tissue.
Fourteen percent of phosphate is an organic intracellular anion that is essential for aerobic and anaerobic energy metabolism within RBCs. Via RBC 2,3-diphosphoglycerate, phosphate preferentially transfers oxygen from hemoglobin to cells exhibiting greatest hypoxia. In the cell membrane, phosphate provides for scaffolding as a phospholipid and serves as a major constituent of DNA and RNA nucleic acids and phosphoprotein macromolecules. In addition, phosphate is essential for carbohydrate, lipid, and protein metabolism; it functions as a cofactor in numerous enzyme systems and as an integral component in serum or intracellular acid-base metabolism. Finally, as adenosine triphosphate, phosphate undergoes hydrolysis to form adenosine diphosphate, yielding essential energy for all metabolic activity.1,4,5
The remaining 1% of inorganic phosphorus is found in the extracellular compartment, which is measurable within the serum. This phosphate contributes to electrical and acid-base homeostasis,5 with up to 90% in the free, unbound form; the other 10% remains bound to protein. A normal serum level, reflecting this extracellular phosphate, is 3.0 to 4.5 mg/dL.3
PHOSPHATE METABOLISM
Intake of elemental phosphorus ranges from 800 to 1,500 mg. Two-thirds of dietary phosphorus is absorbed in the duodenum and jejunum through both active and passive
diffusion. Absorption of phosphate is enhanced by 1,25-
dihydroxycholecalciferol. However, absorption is most efficient at lower dietary intake levels and diminishes with increased ingestion. Nonabsorbed phosphate is excreted
in the feces.5,6
Phosphate metabolism is rigorously regulated by sodium-coupled phosphate transporters located in the nephron, bones, and intestines7 in the body's concerted effort to maintain homeostasis. Phosphate excretion through the kidneys roughly equals absorption in the GI tract. Phosphate is principally absorbed via active transport at the proximal tubule, and the distal convoluted tubule provides an additional 10% to 15% of absorption. Reabsorption in the intestines and the kidneys is greater with dietary deficiencies and higher 1,25-dihydroxycholecalciferol levels and is lower with increased phosphorus intake. Additional mechanisms also facilitate phosphorus homeostasis; the presence of parathyroid hormone (PTH) is the most important. PTH inhibits phosphate reabsorption at the proximal and distal convoluted tubules, thereby promoting phosphaturia. In the intestines, PTH and 1,25-dihydroxycholecalciferol prompt phosphate absorption.8 PTH also determines plasma phosphate levels in conjunction with volume status. Volume expansion with an absence of PTH results in minimal phosphaturia; a volume expanded state with increased PTH elevates urinary phosphate levels.1
Similar homeostatic mechanisms in bony metabolism also help to achieve phosphate equilibrium. Approximately 3 mg/kg/d of phosphate enters bone, with an equal amount leaving the osseous reservoir through bony resorption. Important regulatory factors that determine bone formation and destruction, and thus phosphate levels, include PTH, vitamin D, sex hormones, acid-base balance, and the presence of generalized inflammation.1,5,6