An elevated plasma concentration of ionized calcium (Ca++) can lead to arrhythmias, lethargy, disorientation, and even death. This is because hypercalcemia causes the threshold potential to shift to less negative values, making it farther from the resting membrane voltage. The regulation of plasma Ca++ is primarily controlled by parathyroid hormone (PTH), calcitriol (the active form of vitamin D3), and plasma Ca++. Within cells, Ca++ is either sequestered in the endoplasmic reticulum and mitochondria or bound to proteins, resulting in a very low free intracellular concentration of Ca++. The concentration gradient of Ca++ across cell membranes is maintained by a Ca++-ATPase pump (PMCa1b) in all cells and a 3Na+/Ca++ exchanger (NCX1) in some cells.

Calcium homeostasis depends on two factors: the total amount of Ca++ in the body and the distribution of Ca++ between bone and extracellular fluid (ECF). The total body Ca++ level is determined by the balance between Ca++ absorption by the intestinal tract and Ca++ excretion by the kidneys. The intestinal absorption of Ca++ is facilitated by a carrier-mediated transport mechanism that is stimulated by calcitriol. Normally, the intestine absorbs 200 mg/day of Ca++, but this can increase to 600 mg/day when calcitriol levels rise. In adults, the amount of Ca++ excreted by the kidneys matches the amount absorbed by the gastrointestinal tract (200 mg/day), resulting in Ca++ balance. The distribution of Ca++ between bone and ECF also plays a role in Ca++ homeostasis.
36.13). An elevated ionized plasma [Ca • Fig. 36.14 Overview of Ca++ homeostasis. PTH, parathyroid hormone. (From Koeppen BM, Stanton BA. Renal Physiology. 5th ed. Philadelphia: Elsevier; 2013.) arrhythmias, lethargy, disorientation, and even death.
This effect of hypercalcemia occurs because an elevated plasma [Ca++] causes the threshold potential to shift to less negative values (i.e., farther from the resting membrane voltage). Plasma [Ca++] is regulated within a very narrow range, primarily by parathyroid hormone (PTH), calcitriol (1,25-dihydroxyvitamin D), the active metabolite of vitamin D3, and plasma Ca++ , and this regulation will be discussed next.
Within cells, Ca++ is sequestered in the endoplasmic reticulum and mitochondria, or it is bound to proteins. Thus the free intracellular [Ca++] is very low (≈100 nM). The large concentration gradient for [Ca++] across cell membranes is maintained by a Ca++-ATPase pump (PMCa1b) in all cells and by a 3Na+/Ca++ exchanger (NCX1) in some cells.
Overview of Calcium Homeostasis
Ca++ homeostasis depends on two factors: (1) the total amount of Ca++ in the body and (2) the distribution of Ca++ between bone and ECF. The total body Ca++ level is determined by the relative amounts of Ca++ absorbed by the intestinal tract and excreted by the kidneys (Fig.
36.14 ). The intestinal tract absorbs Ca++ through an active carrier-mediated transport mechanism that is stimulated by calcitriol, the active metabolite of vitamin D3 that is produced in the proximal tubule of the kidneys. Net Ca++ absorption by the intestine is normally 200 mg/day, but it can increase to 600 mg/day when calcitriol levels rise. In adults, Ca++ excretion by the kidneys equals the amount absorbed by the GI tract (200 mg/day), and it changes in bIn clinical practice the terms hypercalcemia and hypocalcemia are often used to describe a high or low total plasma [Ca++], respectively, even though this usage is not the physiologically correct usage of hypercalcemia and hypocalcemia.
parallel with intestinal absorption. Thus in adults, Ca++ balance is maintained because the amount of Ca++ ingested in an average diet (1000 mg/day) equals the amount lost in feces (800 mg/day, the amount that escapes absorption by the intestinal tract) plus the amount excreted in urine (200 mg/day).
The second factor that controls Ca++ homeostasis is the distribution of Ca++ between bone and ECF (see