Pi homeostasis depends on two factors: the amount of Pi in the body and the distribution of Pi between the intracellular fluid (ICF) and extracellular fluid (ECF) compartments. The total body Pi levels are determined by the balance between Pi absorption by the intestines and Pi excretion by the kidneys. Pi absorption by the intestines can occur through active and passive mechanisms, and it is influenced by dietary Pi levels and calcitriol. In adults, the kidneys maintain a steady state by excreting an amount of Pi in the urine equal to the amount absorbed by the intestines. However, during growth, Pi accumulates in the body. Renal Pi excretion is the primary mechanism for regulating Pi balance and maintaining Pi homeostasis.

The second factor in maintaining Pi homeostasis is the distribution of Pi among bone and the ICF and ECF compartments. The regulation of plasma Pi levels is controlled by parathyroid hormone (PTH) and calcitriol, along with the kidneys. PTH and calcitriol stimulate the release of Pi from bone, and this release is always accompanied by the release of calcium (Ca++). The kidneys also play a significant role in maintaining plasma Pi levels within a narrow range. PTH increases Pi excretion, while calcitriol inhibits Pi excretion. Plasma Pi levels are determined by intestinal absorption, storage in bone, and Pi excretion by the kidneys. Maintaining plasma Pi levels is crucial for proper formation of the Ca++-Pi complex required for bone mineralization without deposition of Ca++-Pi in soft tissues.

An increase in plasma Pi levels directly stimulates the synthesis and release of PTH and decreases the ionized calcium levels, which further stimulates PTH release. PTH enhances urinary Pi excretion by inhibiting Pi reabsorption in the proximal tubule. Hyperphosphatemia also reduces calcitriol production by the proximal tubule, leading to a decrease in Pi absorption by the intestine. Both the increase in PTH and the decrease in calcitriol contribute to reducing plasma Pi levels.

The transport of phosphate along the nephron can be summarized as follows: the proximal tubule reabsorbs 80% of the filtered Pi, while the loop of Henle, distal tubule, and collecting duct reabsorb negligible amounts of Pi. Therefore, approximately 20% of the filtered Pi is excreted in urine.

In the proximal tubule, Pi reabsorption occurs through a transcellular route. There are two types of Na+/Pi symporters involved: type IIa transports 3Na+ with one divalent Pi (HPO42−) and carries a positive charge into the cell, while type IIc transports 2Na+ with one monovalent Pi (H2PO4−) and is electrically neutral. Pi is then transported across the basolateral membrane through a Pi-inorganic anion antiporter, which has not yet been characterized.
Fig. 36.17 . Maintenance of Pi homeostasis depends on two factors: (1) the amount of Pi in the body and (2) the distribution of Pi between the ICF and ECF compartments. Total body Pi levels are determined by the relative amount of Pi absorbed by the intestinal tract versus the amount excreted by the kidneys. Pi absorption by the intestinal tract occurs via active and passive mechanisms; Pi absorption increases as dietary Pi rises, and it is stimulated by calcitriol. Despite variations in Pi intake between 800 and 1500 mg/day, in adults (i.e., the steady state) the kidneys maintain total body Pi balance constant by excreting an amount of Pi in the urine equal to the amount absorbed by the intestinal tract (normal bone remodeling results in no net addition of Pi to, or Pi release from, bone). By contrast, during growth, Pi is accumulated in the body. Renal Pi excretion is the primary mechanism by which the body regulates Pi balance and thereby Pi homeostasis.
The second factor that maintains Pi homeostasis is distribution of Pi among bone and the ICF and ECF compartments. Regulation of plasma [Pi] is controlled by two hormones, PTH and calcitriol, in concert with the kidneys (see
Fig. 36.17 ). Release of Pi from bone is stimulated by the same hormones (i.e., PTH and calcitriol) that release Ca++ from this pool. Thus release of Pi from bone is always accompanied by release of Ca++ .
The kidneys also make an important contribution to maintaining plasma [Pi] within a narrow range (1–1.5 mM).
Pi excretion by the kidneys is regulated by PTH and calcitriol (see
Fig. 36.17 ). PTH increases Pi excretion, whereas calcitriol inhibits Pi excretion. Plasma [Pi] is determined by: (1) intestinal absorption, (2) storage in bone, and (3) Pi excretion by the kidneys. Maintenance of plasma [Pi] is essential for optimal Ca++-Pi complex formation required for bone mineralization without deposition of Ca++-Pi in vascular and other soft tissues.
A rise in plasma [Pi] directly stimulates PTH synthesis and release and also decreases the ionized [Ca++], which stimulates PTH release by its interaction with the CaSR. PTH enhances urinary Pi excretion by inhibiting proximal tubule Pi reabsorption. Hyperphosphatemia also decreases calcitriol production by the proximal tubule, which leads to a reduction in Pi absorption by the intestine. Both the increase in PTH and the decrease in calcitriol reduce  plasma [Pi].
Phosphate Transport Along the Nephron
Fig. 36.18 summarizes Pi transport by the various portions of the nephron. The proximal tubule reabsorbs 80% of the Pi filtered by the glomerulus; the loop of Henle, distal tubule, and collecting duct reabsorb negligible amounts of Pi. Therefore approximately 20% of the Pi filtered across the glomerular capillaries is excreted in urine.
Pi reabsorption by the proximal tubule occurs by a transcellular route (
Fig. 36.19 ). Pi uptake across the apical membrane of the proximal tubule occurs via two Na+/Pi symporters (IIa and IIc). Type IIa transports 3Na+ with one divalent Pi (HPO42−), and carries positive charge into the cell. Type IIc transports 2Na+ with one monovalent Pi (H2PO4 −) and is electrically neutral. Pi exits across the basolateral membrane by a Pi-inorganic anion antiporter that has not been characterized.