The kidneys, along with the GI tract and bone, are responsible for maintaining plasma Ca++ and Pi levels and balance. This section of the chapter focuses on the kidneys' role in handling Ca++ and Pi, with an emphasis on the hormones and factors that regulate urinary excretion.

Ca++ is involved in various cellular processes, such as bone formation, cell division and growth, blood coagulation, hormone-response coupling, and electrical stimulus-response coupling (e.g., muscle contraction, neurotransmitter release). The majority of Ca++ (99%) is stored in bone and teeth, while a small percentage is found in the intracellular fluid (ICF) and extracellular fluid (ECF). The concentration of Ca++ in plasma is normally maintained at 10 mg/dL (2.5 mM or 5 mEq/L). Approximately 50% of the Ca++ in plasma is ionized, 40% is bound to plasma proteins (mainly albumin), and 10% is complexed to several anions, including Pi, HCO3 − , citrate, and SO42−. The distribution of Ca++ in plasma is influenced by the pH of the plasma.

Acidemia increases the percentage of ionized Ca++ by decreasing the Ca++ bound to proteins, while alkalemia decreases the percentage of ionized Ca++ by altering the Ca++ bound to proteins. Individuals with alkalemia are more susceptible to tetany (tonic muscular spasms), while those with acidemia are less susceptible, even with reduced total plasma Ca++ levels. In patients with metabolic acidosis, the increase in [H+] causes more H+ to bind to plasma proteins, Pi, HCO3 − , citrate, and SO42−, displacing Ca++ and increasing the plasma concentration of ionized Ca++. In alkalemia, the decrease in [H+] causes some H+ ions to dissociate from plasma proteins, Pi, HCO3 − , citrate, and SO42−, in exchange for Ca++, thereby decreasing the plasma concentration of ionized Ca++. Additionally, the plasma albumin concentration also affects ionized plasma [Ca++]. Hypoalbuminemia increases ionized [Ca++], while hyperalbuminemia decreases it. The total measured plasma [Ca++] does not reflect the total ionized [Ca++], which is the physiologically relevant measure of plasma [Ca++]. Hypocalcemia (low ionized plasma [Ca++]) increases the excitability of nerve and muscle cells and can lead to hypocalcemic tetany. This occurs because hypocalcemia shifts the threshold potential to more negative values.
This brief introduction reveals that the kidneys, in conjunction with the GI tract and bone, play a major role in maintaining plasma Ca++ and Pi levels as well as Ca++ and Pi balance (see ). Accordingly this section of the chapter discusses Ca++ and Pi handling by the kidneys, with an emphasis on the hormones and factors that regulate urinary excretion.
Cellular processes in which Ca++ plays an important role include bone formation, cell division and growth, blood coagulation, hormone-response coupling, and electrical stimulus-response coupling (e.g., muscle contraction, neurotransmitter release). Nearly 99% of Ca++ is stored in bone and teeth, approximately 1% is found in ICF, and 0.1% in ECF. The total Ca++ concentration ([Ca++]) in plasma is 10 mg/dL (2.5 mM or 5 mEq/L), and its concentration is normally maintained within very narrow limits. Approximately 50% of the Ca++ in plasma is ionized, 40% is bound to plasma proteins (mainly albumin), and 10% is complexed to several anions, including Pi, HCO3 − , citrate, and SO42− (Fig. 36.11 ). The pH of plasma influences this distribution (
Fig. 36.12). Acidemia increases the
CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis 1.25 mmol/L E A S 0.25 mmol/L R 1.0 mmol/L D • Fig. 36.12 Effect of pH on plasma [Ca++]. (From Koeppen BM, Stanton BA. Renal Physiology. 5th ed. Philadelphia: Elsevier; 2013.) • Fig. 36.11 Distribution of Ca++ in plasma. (From Koeppen BM, Stanton BA. Renal Physiology. 5th ed. Philadelphia: Elsevier; 2013.) • Fig. 36.13 Effect of Ca++ on nerve and muscle excitability. (From Koeppen BM, Stanton BA. Renal
Physiology. 5th ed. Philadelphia: Elsevier; 2013.) percentage of ionized Ca++ at the expense of Ca++ bound to proteins, whereas alkalemia decreases the percentage of ionized Ca++, again by altering the Ca++ bound to proteins. Individuals with alkalemia are susceptible to tetany (tonic muscular spasms), whereas individuals with acidemia are less susceptible to tetany, even when total plasma Ca++ levels are reduced. The increase in [H+] in patients with metabolic acidosis causes more H+ to bind to plasma proteins, Pi, HCO3 − , citrate, and SO42− , thereby displacing Ca++ . This displacement increases the plasma concentration of ionized Ca++ . In alkalemia the [H+] of plasma decreases. Some H+ ions dissociate from plasma proteins, Pi, HCO3 − , citrate, and SO42− in exchange for Ca++ , thereby decreasing the plasma concentration of ionized Ca++ . In addition, the plasma albumin concentration also affects ionized plasma [Ca++].
Hypoalbuminemia increases the ionized [Ca++], whereas hyperalbuminemia decreases ionized plasma [Ca++]. The total measured plasma [Ca++] does not reflect the total ionized [Ca++], which is the physiologically relevant measure of plasma [Ca++]. A low ionized plasma [Ca++] (hypocalcemia) increases the excitability of nerve and muscle cells and can lead to hypocalcemic tetany. Tetany associated with hypocalcemia occurs because hypocalcemia causes the threshold potential to shift to more negative values (i.e., closer to the resting membrane voltage) (
Fig.