Calcium and inorganic phosphate are crucial ions that serve numerous essential functions in the body. Calcium acts as a cofactor in enzymatic reactions, functions as a second messenger in signaling pathways, plays a vital role in neural transmission, blood clotting, and muscle contraction, and is a critical component of bone, teeth, cartilage, and the extracellular matrix. Inorganic phosphate is also important for bone composition and is necessary for various metabolic processes. At physiological pH, inorganic phosphate exists as HPO4− and H2PO4−, collectively referred to as Pi.

Recent research has shed light on the cellular mechanisms that regulate potassium (K+) secretion in the early segment of the ASDN in response to changes in dietary K+ content and acid-base balance. Increased K+ intake leads to elevated serum K+ levels, which in turn enhance K+ secretion through several mechanisms. Hyperkalemia, or high serum K+ levels, boosts the activity of ROMK channels in the apical plasma membrane of principal cells. It also inhibits the reabsorption of NaCl and water by the proximal tubule, increasing the flow rate in the ASDN, which further stimulates K+ secretion. Moreover, hyperkalemia increases the production of aldosterone, a hormone that facilitates K+ secretion through multiple mechanisms. Aldosterone increases the number of K+ channels in the apical plasma membrane, stimulates the uptake of K+ across the basolateral membrane, and enhances the movement of Na+ across the apical membrane, promoting the secretion of K+. Conversely, a low-K+ diet reduces K+ secretion by increasing the activity of protein tyrosine kinase, causing the endocytosis of ROMK channels and thereby reducing K+ secretion. Acidosis inhibits the activity of ROMK channels, leading to decreased K+ secretion, while alkalosis enhances ROMK channel activity, stimulating K+ secretion.

In addition to its role in metabolic processes and as a component of various molecules, inorganic phosphate is regulated by the kidneys in adults. The kidneys control the balance of total body calcium (Ca++) and phosphate (Pi) by excreting the absorbed amount from the intestines. When plasma levels of Ca++ and Pi decline significantly, the kidneys increase intestinal absorption, bone resorption (loss of Ca++ and Pi from bone), and renal tubular reabsorption to restore normal levels. During growth and pregnancy, intestinal absorption exceeds urinary excretion, leading to accumulation of Ca++ and Pi in developing fetal tissues and bones. Conversely, conditions such as bone disease or a decline in lean body mass result in increased urinary loss of Ca++ and Pi without affecting intestinal absorption, causing a net loss of these ions from the body. In chronic renal failure, Pi accumulates in the body as intestinal absorption surpasses urinary excretion, potentially leading to Pi buildup and bone changes. (Refer to the In The Clinic box discussion on chronic renal failure for further details).
Overview of Calcium and Inorganic Phosphate Homeostasis are multivalent ions that subserve many complex and vital functions. Ca++ is an important cofactor in many enzymatic reactions; it is a key second messenger in numerous signaling pathways; it plays an important role in neural transduction, blood clotting, and muscle contraction; and it is a critical component of the extracellular matrix, cartilage, teeth, and bone. Pi, like Ca++ , is a key component of bone. Pi is essential for metabolic aAt physiological pH, inorganic phosphate exists as HPO4 − and H2PO4 − (pK = 6.8). For simplicity, we collectively refer to these ion species as Pi.
Modified from Field MJ et al. In Narins R (ed). Textbook of Nephrology: Clinical Disorders of Fluid and Electrolyte Metabolism. 5th ed. New York: McGraw-Hill; 1994.
The cellular mechanisms whereby changes in the K+ content of the diet and acid-base balance regulate secretion of K+ by the early segment of the ASDN have recently been elucidated. Elevated K+ intake increases secretion of K+ by several mechanisms, all related to increased serum [K+]. Hyperkalemia increases the activity of the ROMK channel in the apical plasma membrane of principal cells. Moreover, hyperkalemia inhibits reabsorption of NaCl and water by the proximal tubule, thereby increasing the ASDN flow rate, a potent stimulus to secretion of K+ . Hyperkalemia also enhances [aldosterone], which increases K+ secretion by three mechanisms. First, aldosterone increases the number of K+ channels in the apical plasma membrane. Second, aldosterone stimulates uptake of K+ across the basolateral membrane by increasing the number of Na+,K+-ATPase pumps, thereby enhancing the electrochemical gradient driving secretion of K+ across the apical membrane. Third, aldosterone increases movement of Na+ across the apical membrane, which depolarizes the apical plasma membrane voltage and thus increases the electrochemical gradient, promoting secretion of K+ . A low-K+ diet dramatically reduces secretion of K+ by the ASDN by increasing the activity of protein tyrosine kinase, which causes ROMK channels to be endocytosed from the apical plasma membrane, thereby reducing K+ secretion. Acidosis decreases secretion of K+ by inhibiting the activity of ROMK channels, whereas alkalosis stimulates secretion of K+ by enhancing ROMK channel activity.
processes, including formation of adenosine triphosphate (ATP), and it is an important component of nucleotides, nucleosides, and phospholipids. Phosphorylation of proteins is an important mechanism of cellular signaling, and Pi is an important buffer in cells, plasma, and urine.
In adults the kidneys play important roles in regulating total body Ca++ and Pi by excreting the amount of Ca++ and Pi that is absorbed by the intestinal tract (normal bone remodeling results in no net addition of Ca++ and Pi to, or Ca++ and Pi release from, bone). If plasma concentrations of Ca++ and Pi decline substantially, intestinal absorption, bone resorption (i.e., loss of Ca++ and Pi from bone), and renal tubular reabsorption increase and return plasma concentrations of Ca++ and Pi to normal levels. During growth and pregnancy, intestinal absorption exceeds urinary excretion, and these ions accumulate in newly formed fetal tissue and bone. In contrast, bone disease (e.g., osteoporosis) or a decline in lean body mass increases urinary Ca++ and Pi loss without a change in intestinal absorption. These conditions produce a net loss of Ca++ and Pi from the body. Finally, during chronic renal failure, Pi accumulates in the body because absorption by the intestinal tract exceeds excretion in the urine. This can lead to accumulation of Pi in the body and changes in bone (see the In The Clinic box discussion of chronic renal failure).