PHOSPHORUS METABOLISM

Phosphorus in more widely distributed than calcium and also serves a variety of biological functions (Table 2) (3,4). While most of phosphorus is skeletal as hydroxyapatite, 15 % is distributed among extraskeletal sites like phosphoproteins, phospholipids, and nucleic acids (Table 13). In blood, phosphorus exists as the phosphates, H2PO4G and HPO4=, but its concentration is measured as phosphorus, with a normal range of 2.5 - 4.5 mg/100 ml. The regulation is not as tight as it is for calcium, with substantial perturbations due to diet and alimentation.

Table 13. Phosphorus Metabolism

  • General

    • Widely distributed

    • Multiple biological functions Distribution

    • Skeletal - Hydroxyapatite:

    • 3 Ca(PO4)2 o Ca(OH)2

    • 15% extraskeletal

      • Phosphoproteins

      • Phospholipids

      • Nucleic acids

  • Blood Phosphate:

  • H2PO4- and HPO4=

  • Concentration measured as phosphorus: 2.5 - 4.5 mg/100 ml

  • Regulation

    • Not as closely as calcium

    • Diet

    • Alimentation

    • Growth

    • Diurnal rhythm

    • Hormones

    • Other factors

Table 14. Dietary Phosphorus

  • Most foods

  • 1 gm per day - variable

  • Absorption

    • Site - distal to duodenum

    • Mechanism

      • Calcium dependent

      • Calcium independent

  • Regulation

    • Diet - 70% absorbed

    • Calcitropic hormones

      • Vitamin D - increases

      • PTH - increases

    • CT - decreases

  • Other factors

    • GH - increases

    • Phosphate binders (Ca, Al) decrease

    • Calcium - decreases

    • Fecal - non-absorbed and secreted

Table 15. Urinary Phosphate

  • Major route of regulation

  • Related to diet 90% filtered (? protein binding)

  • Proximal tubule - 90% reabsorbed

    • H2PO4- - active

    • HPO4= - passive

  • Distal tubule - 10% reabsorbed

  • Regulation

    • Diet

    • Calcitropic hormones

      • PTH - increases excretion

      • CT - increases excretion

      • Vitamin D - decreases excretion

Dietary phosphorus comes from most foods, averaging about 1 gm per day (Table 14), with the most important sources being dairy products, grains, meats, and food additives (2,4). Absorption takes place at a site distal to duodenum and utilizes both calcium dependent and calcium independent mechanisms that can be active or passive. The most significant quantitatively is post-prandial passive absorption. Approximately 60-80% is absorbed primarily by a diffusional process without a significant saturable component; however, there is regulation by the calcitropic hormones, especially Vitamin D, whose active metabolites increases absorption, while PTH and CT have only minor direct effects (Tables 13 and 14). Calcium- and aluminum-containing phosphate binders can inhibit absorption and are used to do so in the treatment of renal disease. Fecal phosphate comprises non-absorbed and secreted components (Table 14).

Renal phosphate reabsorption controls the concentration of phosphate in serum, and it is usually quantified as the tubular resorption of phosphorus and expressed as the renal phosphate threshold (TmP/GFR), which closely mirrors the normal range of serum phosphorus (5). Although the TmP/GFR can be measured, it is usually estimated by a nomogram from measurements of serum and urinary phosphorus and creatinine. The proximal convoluted tubule reabsorbs about 75 percent of filtered phosphate, and most of the remainder is reabsorbed in the proximal straight tubule; the distal tubule segments may have a limited capacity for reabsorption, about 5 percent of filtered load (1,5).

Urinary phosphate is the major route of homeostatic regulation (5). About 90% is filtered, with reabsorption being the major regulatory step, primarily at the proximal tubule, where 80% is reabsorbed, mostly in the convoluted segment. PTH and CT increase phosphorus excretion, and Vitamin D decreases its excretion (Table 15). The most important factors regulating proximal phosphate reabsorption are PTH and the dietary phosphate intake. By resetting the renal phosphate threshold, PTH allows the kidney to prevent increases in serum phosphate with calcium. This protective mechanism is compromised in renal failure. Other factors that regulate phosphate reabsorption include growth hormone and insulin which increase proximal phosphate reabsorption. Glucocorticoids and calcitonin have a phosphaturic effect; and acidosis, both acute and chronic, causes phosphaturia. At all three sites of phosphate reabsorption, the proximal convoluted tubule, proximal straight tubule, and distal tubule, PTH decreases phosphate reabsorption. Calcitonin inhibits phosphate reabsorption in the proximal convoluted and proximal straight tubule; an action of calcitonin on the distal tubule is uncertain.