Calcium Balance

The kidneys play an important role in the maintenance of Ca2+ balance. Ca2 + intake is about 1,000 mg/day and mainly comes from dairy products in the diet. About 300 mg/day are absorbed by the small intestine, a process controlled by 1,25(OH)2 vitamin D3. About 150 mg Ca2+/day are secreted into the gastrointestinal tract (via saliva, gastric juice, pancreatic juice, bile, and intestinal secretions), so that net absorption is only about 150 mg/day. Fecal Ca2+ excretion is about 850 mg/day and urinary excretion about 150 mg/day.

A normal plasma [Ca2+] is about 10 mg/dL, which is equal to 2.5 mmol/L (since the atomic weight of calcium is 40) or 5 mEq/L. About 40% of plasma Ca2+ is bound to plasma proteins (mainly serum albumin), 10% is bound to small diffusible anions (such as citrate, bicarbonate, phosphate, and sulfate) and 50% is free or ionized. It is the ionized Ca2+ in the blood that is physiologically important and closely regulated (see Chapter 36). Most of the Ca2+ in the body is in bone (99%), which constantly turns over. In a healthy adult, the rate of release of Ca2+ from old bone exactly matches the rate of deposition of Ca2+ in newly formed bone (500 mg/day).

Ca2+ that is not bound to plasma proteins (i.e., 60% of the plasma Ca2+) is freely filterable in the glomeruli. About 60% of the filtered Ca2+ is reabsorbed in the proximal convoluted tubule (Fig. 24.18). Two thirds is reabsorbed via a paracellular route in response to solvent drag and the small lumen positive potential ( + 3 mV) found in the late proximal convoluted tubule. One third is reabsorbed via a tran-scellular route that includes Ca2+ channels in the apical plasma membrane and a primary Ca2+-ATPase or 3 Na+/1 Ca2+ exchanger in the basolateral plasma membrane. About 30% of filtered Ca2+ is reabsorbed along the loop of Henle. Most of the Ca2+ reabsorbed in the thick ascending limb is by passive transport through the tight junctions, propelled by the lumen positive potential.

Reabsorption continues along the distal convoluted tubule. Reabsorption here is increased by thiazide diuretics, which may be prescribed in cases of excessive Ca2+ in the urine, hypercalciuria, and kidney stone disease (see Clinical Focus Box 24.2). Thiazides inhibit the luminal membrane Na-Cl cotransporter in distal convoluted tubule cells, which leads to a fall in intracellular [Na+]. This, in turn, promotes Na+-Ca2+ exchange and increased basolateral extrusion of Ca2+ and increased Ca2+ reabsorption.

The late distal tubule (connecting tubule and initial part of the cortical collecting duct) is an important site of control of Ca2+ excretion because this is where parathyroid hormone (PTH) increases Ca2+ reabsorption. Ca2+ diffuses into the cells, primarily through an epithelial Ca2+ channel (ECaC) in the apical membrane, is transported through the cytoplasm by a 1,25(OH)2 vitamin D3-dependent calcium-binding protein, called calbindin, and is extruded by a Na+/Ca2+ exchange or Ca2+-ATPase in the basolateral plasma membrane. Only about 0.5 to 2% of the filtered Ca2+

Proximal convoluted

Proximal convoluted

Proximal Convoluted Tubule Physiology
0.5-2% Urine

! The percentage of the filtered load of Ca2+ remaining in tubular fluid as it flows down the nephron. The kidneys filter about 10,800 mg/day (0.6 X 100 mg/L X 180 L/day) and excrete only about 0.5 to 2% of the filtered load, that is, about 50 to 200 mg/day. Thiazides increase Ca2+ reabsorption by the distal convoluted tubule, and PTH increases Ca2+ reabsorption by the connecting tubule and cortical collecting duct.

is usually excreted. (Chapter 34 discusses Ca2+ balance and its control by several hormones in more detail.)

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