51 The Parathyroid Glands and Vitamin D

Eugene J. Barrett Paula Barrett

The Gut, Kidneys, and Bone Regulate Calcium and Phosphate Balance

Calcium plays a critical role in many cellular processes, including hormone secretion, muscle contraction, nerve conduction, exocytosis, and the activation and inactivation of many enzymes. As described in Chapter 4 and elsewhere, Ca2+ also serves as an intracellular second messenger by carrying information from the cell membrane into the interior of the cell. It is therefore not surprising that the body very carefully regulates the plasma concentration of free ionized calcium ([Ca2+]), the physiologically active form of the ion, and maintains plasma [Ca2+] within a narrow range (between 1.0 and 1.3 mM, or 4.0 and 5.2 mg/dl). Phosphate is no less important. Because it is part of the adenosine triphosphate molecule, phosphate plays a critical role in cellular energy metabolism. It also plays crucial roles in the activation and deactivation of enzymes. However, unlike calcium, the plasma phosphate concentration is not very strictly regulated, and its levels fluctuate throughout the day, particularly after meals. Calcium homeostasis and phosphate homeostasis are intimately tied to each other for two reasons. First, calcium and phosphate are the principal components of hydroxyapatite crystals [Ca10(PO4)6(OH)2)], which by far constitute the major portion of the mineral phase of bone. Second, they are regulated by the same hormones, primarily parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol) and, to a lesser extent, the hormone calcitonin. These hormones act on three organ systems-the bone, the kidneys, and the gastrointestinal (GI) tract-to control the levels of these two ions in plasma. However, the actions of these hormones on calcium and phosphate are typically opposed in that a particular hormone may elevate the level of one ion while lowering that of the other. Figure 51-1 and Figure 51-2 depict the overall daily balance of calcium and phosphate for a subject in a steady state. CALCIUM BALANCE.
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Figure 51-1 Calcium distribution and balance. Note that all values are for a 70-kg human, expressed in terms of elemental calcium. ECF, extracellular fluid.

Figure 51-2 Phosphate distribution and balance. Note that all values are for a 70-kg human, expressed in elemental phosphorus. ECF, extracellular fluid.
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Most calcium is located within bone, approximately 1 kg (see Fig. 51-1). The total amount of calcium in the extracellular pool is only a fraction of this amount, about 1 g or 1000 mg. The typical daily dietary intake of calcium is approximately 800 to 1200 mg. Dairy products are the major dietary source of calcium. Although the intestines absorb approximately one half the dietary calcium (500 mg/day), they also secrete calcium for removal from the body (325 mg/day), and, therefore, the net intestinal uptake of calcium is only approximately 175 mg/day. The second major organ governing calcium homeostasis is bone, where calcium deposition of about 280 mg/day is matched by an equal amount of calcium resorption in the steady state. The third organ system involved, the kidneys, filter about 10 times the total extracellular pool of

calcium per day, about 10,000 mg/day. More than 98% of this Ca2+ is reabsorbed, and, therefore, the net renal excretion of Ca2+ is less than 2% of the filtered load (p. 807). In a person in Ca2+ balance, urinary excretion (175 mg/day) is the same as net absorption by the GI tract. In plasma, calcium exists in three physicochemical forms: (1) as a free ionized species, (2) bound to (more accurately, associated with) anionic sites on serum proteins (especially albumin), and (3) complexed with low-molecular-weight organic anions (e.g., citrate and oxalate). The total concentration of all three forms in the plasma is normally 2.2 to 2.7 mM (8.8 to 10.6 mg/dl). In healthy individuals, approximately 45% of calcium is free, 45% is bound to protein, and 10% is bound to small organic anions. The ionized form is the most important with regard to regulating the secretion of PTH and is involved in most of the biologic actions of calcium. PHOSPHATE BALANCE. Most phosphate is also present in bone, approximately 0.6 kg of elemental phosphorus (see Fig. 51-2). A smaller amount of phosphorus (0.1 kg) exists in the soft tissues, mainly as organic phosphates such as phospholipids, phosphoproteins, nucleic acids, and nucleotides. An even smaller amount (500 mg) is present in the extracellular fluid as inorganic phosphate. The daily dietary intake of phosphorus is typically 1400 mg, mostly as inorganic phosphate. Again, dairy products are the major source. The net absorption of phosphate by the intestines is approximately 900 mg/day. In the steady state, bone has relatively small phosphate turnover, about 210 mg/day. The kidneys filter approximately 14 times the total extracellular pool of phosphate per day (7000 mg/day) and reabsorb about 6100 mg/day. Hence, the net renal excretion of phosphorus is around 900 mg/day, the same as the net absorption by the GI tract. The concentration of total phosphate in plasma ranges from 0.8 to 1.5 mM (or 2.5 to 4.5 mg/dl of elemental phosphorus), a variation of 80%. Between 85% and 90% of the circulating phosphate is filterable by the kidneys, either ionized (50%) or complexed (40%), and only a small proportion (10% to 15%) is protein bound.
Printed from STUDENT CONSULT: Medical Physiology (on 28 August 2006) 2006 Elsevier