Comprehensive Physiology Wiley Online Library

Phosphate Homeostasis

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Phosphate Regulation
2 Plasma Phosphate Concentration
3 Renal Handling of Phosphate
3.1 Ulfrafilterability of Plasma Phosphate
3.2 Localization and Direction of Phosphate Transport
3.3 Heterogeneity of Phosphate Transport Rates
3.4 Secretion of Phosphate
4 Cellular Mechanisms of Phosphate Transport
4.1 Phosphate Entry
4.2 Phosphate Exit
4.3 Intracellular Conditions
4.4 Intracellular Mediators and Regulators of Phosphate Transport
4.5 Interactions between Phosphate Transport and Cellular Metabolism
4.6 Metabolic Requirement for Inorganic Phosphate
5 Regulation of Phosphate Excretion
5.1 Dietary Adaptation
5.2 Parathyroid Hormone
5.3 Vitamin D Metabolites
5.4 Thyroid Hormone
5.5 Calcitonin
5.6 Somatotropin (Growth Hormone)
5.7 Insulin
5.8 Catecholamines
5.9 Atrial Natriuretic Peptides
5.10 Vasopressin
5.11 Glucagon
5.12 Glucocorticoids
6 Nonhormonal Factors Affecting Phosphate
6.1 Metabolic Acidosis
6.2 Respiratory Alkalosis
6.3 Hypercapnea
6.4 Extracellular Volume Expansion
6.5 Influence of Calcium on Phosphate Excretion
Figure 1. Figure 1.

Effect of phosphate restriction on urinary phosphate excretion in men (triangles) and women (circles). During control and recovery periods, dietary phosphate averaged ∼46 mmol/day and was reduced to ∼1 mmol/day during phosphate restriction period. Variance is shown as SEM.

From Dominguez et al., J. Clin. Endocrinol. Metab. 76
Figure 2. Figure 2.

Relationship between dietary intake and gastrointestinal absorption of phosphate in 51 normal human subjects.

From Nordin, Calcium, Phosphate and Magnesium Metabolism 194
Figure 3. Figure 3.

Diurnal variation of serum phosphate concentrations in apparently healthy men.

From Markowitz et al., Science 177
Figure 4. Figure 4.

Renal reabsorption of phosphate as a function of filtered load during phosphate loading in rats after chronic thyroparathyroidectomy. Saturation of reabsorption is demonstrable in animals maintained on high phosphate diet (1%; closed circles) but not in animals on a low phosphate diet (0.02%; open circles).

From Steele and DeLuca, J. Clin. Invest. 232
Figure 5. Figure 5.

Changes in mineral and electrolyte concentrations along proximal tubule as measured by electron probe microanalysis of samples obtained from intact female Munich rats. Samples are grouped according to ratio of inulin concentration in the tubular fluid (TF) versus glomerular ultrafiltrate (GF).

Adapted from Le‐Gremillec, Pflugers Arch. 160
Figure 6. Figure 6.

Demonstration of sodium gradient–dependent phosphate uptake in brush border membrane vesicles derived from rabbit kidney. Phosphate uptake is stimulated by an inward‐directed sodium gradient (Nao>Nai) except in the presence of arsenate. Phosphate uptake is not stimulated by a potassium gradient (Ko>Ki) or when sodium is present without a gradient (Nai = Nao).

Adapted from Cheng and Sacktor, J. Biol. Chem. 55
Figure 7. Figure 7.

Effect of pH on sodium gradient–dependent phosphate uptake into rabbit brush border membrane vesicles. Effects of pH occur with sodium but not with potassium gradients.

Reprinted with permission from Cheng and Sacktor, J. Biol. Chem. 55
Figure 8. Figure 8.

Combined effects of sodium and pH on phosphate uptake into renal brush border membrane vesicles from rat kidney. Vertical bars compare events at 75 mM and 300 mM sodium.

Reprinted with permission from Amstutz et al., Am. J. Physiol. 5
Figure 9. Figure 9.

Schematic model of phosphate transport across proximal tubule. Major entry mechanism is sodium gradient–dependent uptake, which prefers divalent phosphate and has a sodium:phosphate stoichiometry of 2:1. Sodium site is inhibited by hydrogen ions. Number (or velocity) of phosphate transporters at luminal surface is variable by mechanisms that are rapid (insertion) or slow (synthesis). Cytosolic inorganic phosphate interacts with such metabolic processes as oxidative metabolism and glycolysis, which organify phosphate, and gluconeogenesis, which liberates phosphate. Ionic distribution of cytosolic phosphate is determined by cytosolic pH. Phosphate exit occurs mainly by electrodiffusion (bold arrow), but a number of facilitated transport mechanisms have also been proposed.

Figure 10. Figure 10.

Effects of phosphate on oxidative phosphorylation in rabbit cortical tubules that have been permeabilized with digitonin to allow entry of ADP. The ordinate displays the difference between oxygen consumption in the presence or absence of 0.375 mM ADP, which gives maximal stimulation.

Reprinted with permission from Brazy et al., Am. J. Physiol. 38
Figure 11. Figure 11.

Effect of dietary phosphate on maximal phosphate transport rates () in early and late proximal convoluted tubules from the rabbit kidney. Tubules were obtained from rabbits maintained for 5–7 days on diets containing 0.07% (low), 0.38% (normal), or 0.70% (high) phosphate. All tubules were studied in vitro under the same conditions.

Reprinted with permission from Brazy et al., Kidney Int. 30
Figure 12. Figure 12.

Effects of PTH infusion on the fractional excretion of phosphate (FEPl) and cyclic AMP excretion in acutely thyroparathy‐roidectomized rats maintained on either high (1%) or low (0.07%) phosphate diets for 25–35 days.

Reprinted with permission from Steele, J. Clin. Invest. 231


Figure 1.

Effect of phosphate restriction on urinary phosphate excretion in men (triangles) and women (circles). During control and recovery periods, dietary phosphate averaged ∼46 mmol/day and was reduced to ∼1 mmol/day during phosphate restriction period. Variance is shown as SEM.

From Dominguez et al., J. Clin. Endocrinol. Metab. 76


Figure 2.

Relationship between dietary intake and gastrointestinal absorption of phosphate in 51 normal human subjects.

From Nordin, Calcium, Phosphate and Magnesium Metabolism 194


Figure 3.

Diurnal variation of serum phosphate concentrations in apparently healthy men.

From Markowitz et al., Science 177


Figure 4.

Renal reabsorption of phosphate as a function of filtered load during phosphate loading in rats after chronic thyroparathyroidectomy. Saturation of reabsorption is demonstrable in animals maintained on high phosphate diet (1%; closed circles) but not in animals on a low phosphate diet (0.02%; open circles).

From Steele and DeLuca, J. Clin. Invest. 232


Figure 5.

Changes in mineral and electrolyte concentrations along proximal tubule as measured by electron probe microanalysis of samples obtained from intact female Munich rats. Samples are grouped according to ratio of inulin concentration in the tubular fluid (TF) versus glomerular ultrafiltrate (GF).

Adapted from Le‐Gremillec, Pflugers Arch. 160


Figure 6.

Demonstration of sodium gradient–dependent phosphate uptake in brush border membrane vesicles derived from rabbit kidney. Phosphate uptake is stimulated by an inward‐directed sodium gradient (Nao>Nai) except in the presence of arsenate. Phosphate uptake is not stimulated by a potassium gradient (Ko>Ki) or when sodium is present without a gradient (Nai = Nao).

Adapted from Cheng and Sacktor, J. Biol. Chem. 55


Figure 7.

Effect of pH on sodium gradient–dependent phosphate uptake into rabbit brush border membrane vesicles. Effects of pH occur with sodium but not with potassium gradients.

Reprinted with permission from Cheng and Sacktor, J. Biol. Chem. 55


Figure 8.

Combined effects of sodium and pH on phosphate uptake into renal brush border membrane vesicles from rat kidney. Vertical bars compare events at 75 mM and 300 mM sodium.

Reprinted with permission from Amstutz et al., Am. J. Physiol. 5


Figure 9.

Schematic model of phosphate transport across proximal tubule. Major entry mechanism is sodium gradient–dependent uptake, which prefers divalent phosphate and has a sodium:phosphate stoichiometry of 2:1. Sodium site is inhibited by hydrogen ions. Number (or velocity) of phosphate transporters at luminal surface is variable by mechanisms that are rapid (insertion) or slow (synthesis). Cytosolic inorganic phosphate interacts with such metabolic processes as oxidative metabolism and glycolysis, which organify phosphate, and gluconeogenesis, which liberates phosphate. Ionic distribution of cytosolic phosphate is determined by cytosolic pH. Phosphate exit occurs mainly by electrodiffusion (bold arrow), but a number of facilitated transport mechanisms have also been proposed.



Figure 10.

Effects of phosphate on oxidative phosphorylation in rabbit cortical tubules that have been permeabilized with digitonin to allow entry of ADP. The ordinate displays the difference between oxygen consumption in the presence or absence of 0.375 mM ADP, which gives maximal stimulation.

Reprinted with permission from Brazy et al., Am. J. Physiol. 38


Figure 11.

Effect of dietary phosphate on maximal phosphate transport rates () in early and late proximal convoluted tubules from the rabbit kidney. Tubules were obtained from rabbits maintained for 5–7 days on diets containing 0.07% (low), 0.38% (normal), or 0.70% (high) phosphate. All tubules were studied in vitro under the same conditions.

Reprinted with permission from Brazy et al., Kidney Int. 30


Figure 12.

Effects of PTH infusion on the fractional excretion of phosphate (FEPl) and cyclic AMP excretion in acutely thyroparathy‐roidectomized rats maintained on either high (1%) or low (0.07%) phosphate diets for 25–35 days.

Reprinted with permission from Steele, J. Clin. Invest. 231
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Vincent W. Dennis. Phosphate Homeostasis. Compr Physiol 2011, Supplement 25: Handbook of Physiology, Renal Physiology: 1785-1815. First published in print 1992. doi: 10.1002/cphy.cp080237