Calcium is both filtered and reabsorbed in the kidneys but not secreted. Therefore, the rate of renal calcium excretion is calculated as
Renal calcium excretion = Calcium filtered – Calcium reabsorbed
Only about 60 percent of the plasma calcium is ionized, with 40 percent being bound to the plasma proteins and 10 percent complexed with anions such as phosphate. Therefore, only about 60 percent of the plasma calcium can be filtered at the glomerulus. Normally, about 99 percent of the filtered calcium is reabsorbed by the tubules, with only about 1 percent of the filtered calcium being excreted. About 65 percent of the filtered calcium is reabsorbed in the proximal tubule, 25 to 30 percent is reabsorbed in the loop of Henle, and 4 to 9 percent is reabsorbed in the distal and collecting tubules. This pattern of reabsorption is similar to that for sodium.
As is true with the other ions, calcium excretion is adjusted to meet the body’s needs. With an increase in calcium intake, there is also increased renal calcium excretion, although much of the increase of calcium intake is eliminated in the feces. With calcium depletion, calcium excretion by the kidneys decreases as a result of enhanced tubular reabsorption.
Proximal Tubular Calcium Reabsorption. Most of the calcium reabsorption in the proximal tubule occurs through the paracellular pathway; it is dissolved in water and carried with the reabsorbed fluid as it flows between the cells. Only about 20% of proximal tubular calcium reabsorption occurs through the transcellular pathway in two steps. (1) Calcium diffuses from the tubular lumen into the cell down an electrochemical gradient due to the much higher concentration of calcium in the tubular lumen, compared with the epithelial cell cytoplasm, and because the cell interior has a negative charge relative to the tubular lumen. (2) Calcium exits the cell across the basolateral membrane by a calcium-ATPase pump and by sodium-calcium counter-transporter (Figure 1).
Fig1. Mechanisms of calcium reabsorption by paracellular and transcellular pathways in the proximal tubular cells.
Loop of Henle and Distal Tubule Calcium Reabsorption. In the loop of Henle, calcium reabsorption is restricted to the thick ascending limb. Approximately 50% of calcium reabsorption in the thick ascending limb occurs through the paracellular route by passive diffusion due to the slight positive charge of the tubular lumen relative to the interstitial fluid. The remaining 50% of calcium reabsorption in the thick ascending limb occurs through the transcellular pathway, a process that is stimulated by PTH.
In the distal tubule, calcium reabsorption occurs almost entirely by active transport through the cell mem brane. The mechanism for this active transport is similar to that in the proximal tubule and thick ascending limb and involves diffusion across the luminal membrane through calcium channels and exit across the basolateral membrane by a calcium-ATPase pump, as well as a sodium-calcium counter-transport mechanism. In this segment, as well as in the loops of Henle, PTH stimulates calcium reabsorption. Vitamin D (calcitriol) and calcitonin also stimulate calcium reabsorption in the thick ascending limb of Henle’s loop and in the distal tubule, although these hormones are not as important quantitatively as PTH in reducing renal calcium excretion.
Factors That Regulate Tubular Calcium Reabsorption. One of the primary controllers of renal tubular calcium reabsorption is PTH. Increased levels of PTH stimulate calcium reabsorption in the thick ascending loops of Henle and distal tubules, which reduces urinary excretion of calcium. Conversely, reduction of PTH pro motes calcium excretion by decreasing reabsorption in the loops of Henle and distal tubules.
In the proximal tubule, calcium reabsorption usually parallels sodium and water reabsorption and is independent of PTH. Therefore, in instances of extracellular volume expansion or increased arterial pressure— both of which decrease proximal sodium and water reabsorption—there is also reduction in calcium reabsorption and, consequently, increased urinary excretion of calcium. Conversely, with extracellular volume con traction or decreased blood pressure, calcium excretion decreases primarily because of increased proximal tubular reabsorption.
Another factor that influences calcium reabsorption is the plasma concentration of phosphate. Increased plasma phosphate stimulates PTH, which increases calcium reabsorption by the renal tubules, thereby reducing calcium excretion. The opposite occurs with reduction in plasma phosphate concentration.
Calcium reabsorption is also stimulated by metabolic alkalosis and inhibited by metabolic acidosis. Thus, acidosis tends to increase calcium excretion, whereas alkalosis tends to reduce calcium excretion. Most of the effect of hydrogen ion concentration on calcium excretion results from changes in calcium reabsorption in the distal tubule.
A summary of the factors that are known to influence calcium excretion by the renal tubules is shown in Table 1.
Table1. Factors That Alter Renal Calcium Excretion
