PHOSPHATE PHYSIOLOGY

About 1 g of phosphorus is ingested daily. In general, intake exceeds metabolic requirements. Approximately 70% (700 mg) is absorbed primarily from the small intestine, with the rest (300 mg) eliminated in the feces. In addition to 1,25-(OH)₂ D₃ (vitamin D), parathyroid hormone facilitates absorption of phosphate from the gut lumen. The gut secretes phosphate into the lumen and then reabsorbs it, unless it is bound there by calcium or antacids or it is lost by diarrhea or drainage through ostomies or fistulas. Under normal dietary conditions, absorption of phosphate occurs through paracellular diffusive pathways with little regulation. When luminal phosphate concentrations are low, an active sodium-dependent transport mechanism is activated, and additional phosphate is absorbed. ^[56] When dietary intake is normal, phosphate absorption is essentially an unregulated process. However, cations such as calcium, magnesium, and aluminum decrease phosphate absorption by directly binding with phosphate in the gut lumen. This is useful clinically in renal failure to limit the amount of phosphate reabsorbed by the gut. Because of the unregulated nature of phosphate absorption in the gut, the kidneys become the primary organ of excretion of excess phosphate. The kidneys normally excrete 700 mg/day by filtering 6 g and reabsorbing 5.3 g. Urinary phosphate elimination approximately equals intestinal absorption.

Phosphate stores and releases energy through high-energy phosphate bonds and is integral to the structure of proteins, lipids, and bone. Bone functions as the primary reservoir of phosphate and calcium in the body. When the body requires extra calcium, bone is broken down to release calcium for the body's use. In addition to calcium, significant amounts of phosphate are also liberated. This balance is controlled by the regulatory processes discussed in the previous section.

Factors favoring cellular uptake include glucose, fructose, alkalosis, insulin, β-adrenergic stimulation, and anabolism. Phosphate occurs in organic or inorganic forms. Most of the intracellular phosphate is organic. Plasma contains lipid phosphates, organic ester phosphates, and inorganic phosphates, including divalent (HPO₄ ^2- ) and monovalent (H₂ PO₄ ^- ) phosphate. At physiologic pH, 80% of the inorganic phosphate is divalent. Normally, plasma inorganic phosphate is maintained between 3.0 and 4.5 mg/100 mL in adults and 4.0 to 5.0 mg/100 mL in children. Parathyroid hormone inhibits proximal tubular inorganic phosphate reabsorption and increases inorganic phosphate excretion. In animals that are thyroparathyroidectomized, parathyroid hormone is absent, and reabsorption of inorganic phosphate increases significantly and ultimately increases plasma inorganic phosphate levels. In patients with primary hyperparathyroidism, parathyroid hormone secretion is elevated, and plasma levels of inorganic phosphate are low; however, steady-state urinary inorganic phosphate excretion is not markedly increased because it depends largely on intestinal inorganic phosphate absorption. Dietary restriction of inorganic phosphate leads to almost 100% reabsorption of filtered inorganic phosphate and to reduction of urinary phosphate to zero.^[57]

Hyperphosphatemia

Severe hyperphosphatemia occurs after tissue damage or cell death. A moderate to severe hyperphosphatemia may be caused by an impaired ability to excrete phosphorus because of renal failure. As renal failure worsens and the glomerular filtration rate falls below 25 mL/min, hyperphosphatemia may develop. Other causes include iatrogenic, hypothermia, massive liver failure, and certain hematologic malignancies associated with high cell turnover. The increased cell turnover can be part of the malignancy or may result from cell destruction when chemotherapy is instituted.

Hypoparathyroidism can cause hyperphosphatemia in the presence of normal renal function. Rapid increases in serum phosphate can lead to development of severe hypocalcemia. Hypocalcemia results from decreased calcitriol production, which causes significant decline in gastrointestinal tract absorption of calcium. There may be frank precipitation of calcium and phosphate, further decreasing serum calcium levels.^[58] When the calcium-phosphorus product exceeds 70, the risk of abnormal calcification is increased. Treatment involves administration of phosphate-binding antacids such as aluminum antacids and sucralfate, calcium citrate, or calcium carbonate and may include dialysis, especially in patients with renal failure^[59] ( Table 46-14 ).