Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth
The physiology of calcium and phosphate metabolism, formation of bone and teeth, and regulation of vitamin D, parathyroid hormone (PTH), and calcitonin are all closely intertwined. Extracellular calcium ion concentration, for example, is determined by the interplay of calcium absorption from the intestine, renal excretion of calcium, and bone uptake and release of calcium, each of which is regulated by the hormones just noted. Because phosphate homeostasis and calcium homeostasis are closely associated, they are discussed together in this chapter.
Overview of Calcium and Phosphate Regulation in the Extracellular Fluid and Plasma
Extracellular fluid calcium concentration normally is regulated very precisely, seldom rising or falling more than a few per cent from the normal value of about 9.4 mg/dl, which is equivalent to 2.4 mmol calcium per liter. This precise control is essential, because calcium plays a key role in many physiologic processes, including contraction of skeletal, cardiac, and smooth muscles; blood clotting; and transmission of nerve impulses, to name just a few. Excitable cells, such as neurons, are very sensitive to changes in calcium ion concentrations, and increases in calcium ion concentration above normal (hypercalcemia) cause progressive depression of the nervous system; conversely, decreases in calcium concentration (hypocalcemia) cause the nervous system to become more excited.
An important feature of extracellular calcium regulation is that only about 0.1 per cent of the total body calcium is in the extracellular fluid, about 1 per cent is in the cells, and the rest is stored in bones. Therefore, the bones can serve as large reservoirs, releasing calcium when extracellular fluid concentration decreases and storing excess calcium.
Approximately 85 per cent of the body's phosphate is stored in bones, 14 to 15 per cent is in the cells, and less than 1 per cent is in the extracellular fluid. Although extracellular fluid phosphate concentration is not nearly as well regulated as calcium concentration, phosphate serves several important functions and is controlled by many of the same factors that regulate calcium.
Calcium in the Plasma and Interstitial Fluid
The calcium in the plasma is present in three forms, as shown in Figure 79-1.
(1) About 41 per cent (1 mmol/L) of the calcium is combined with the plasma proteins and in this form is nondiffusible through the capillary membrane.
(2) About 9 per cent of the calcium (0.2 mmol/L) is diffusible through the capillary membrane but is combined with anionic substances of the plasma and interstitial fluids (citrate and phosphate, for instance) in such a manner that it
Distribution of ionized calcium (Ca++), diffusible but un-ionized calcium complexed to anions, and nondiffusible protein-bound calcium in blood plasma.
is not ionized. (3) The remaining 50 per cent of the calcium in the plasma is both diffusible through the capillary membrane and ionized.
Thus, the plasma and interstitial fluids have a normal calcium ion concentration of about 1.2 mmol/L (or 2.4 mEq/L, because it is a divalent ion), a level only one half the total plasma calcium concentration. This ionic calcium is the form that is important for most functions of calcium in the body, including the effect of calcium on the heart, the nervous system, and bone formation.
Inorganic phosphate in the plasma is mainly in two forms: HPO4- and H2PO4-. The concentration of HPO4- is about 1.05 mmol/L, and the concentration of H2PO4- is about 0.26 mmol/L. When the total quantity of phosphate in the extracellular fluid rises, so does the quantity of each of these two types of phosphate ions. Furthermore, when the pH of the extracellular fluid becomes more acidic, there is a relative increase in H2PO4_ and a decrease in HPO4-, whereas the opposite occurs when the extracellular fluid becomes alkaline. These relations were presented in the discussion of acid-base balance in Chapter 30.
Because it is difficult to determine chemically the exact quantities of HPO4- and H2PO4- in the blood, ordinarily the total quantity of phosphate is expressed in terms of milligrams of phosphorus per deciliter (100 ml) of blood. The average total quantity of inorganic phosphorus represented by both phosphate ions is about 4 mg/dl, varying between normal limits of 3 to 4 mg/dl in adults and 4 to 5 mg/dl in children.
Hypocalcemic tetany in the hand, called carpopedal spasm.
Hypocalcemic tetany in the hand, called carpopedal spasm.
Non-Bone Physiologic Effects of Altered Calcium and Phosphate Concentrations in the Body Fluids
Changing the level of phosphate in the extracellular fluid from far below normal to two to three times normal does not cause major immediate effects on the body. In contrast, even slight increases or decreases of calcium ion in the extracellular fluid can cause extreme immediate physiologic effects. In addition, chronic hypocalcemia or hypophosphatemia greatly decreases bone mineralization, as explained later in the chapter.
Hypocalcemia Causes Nervous System Excitement and Tetany. When the extracellular fluid concentration of calcium ions falls below normal, the nervous system becomes progressively more excitable, because this causes increased neuronal membrane permeability to sodium ions, allowing easy initiation of action potentials. At plasma calcium ion concentrations about 50 per cent below normal, the peripheral nerve fibers become so excitable that they begin to discharge spontaneously, initiating trains of nerve impulses that pass to the peripheral skeletal muscles to elicit tetanic muscle contraction. Consequently, hypocalcemia causes tetany. It also occasionally causes seizures because of its action of increasing excitability in the brain.
Figure 79-2 shows tetany in the hand, which usually occurs before tetany develops in most other parts of the body. This is called "carpopedal spasm."
Tetany ordinarily occurs when the blood concentration of calcium falls from its normal level of 9.4 mg/dl to about 6 mg/dl, which is only 35 per cent below the normal calcium concentration, and it is usually lethal at about 4 mg/dl.
In laboratory animals, in which calcium can gradually be reduced beyond the usual lethal levels, very extreme hypocalcemia can cause other effects that are seldom evident in patients, such as marked dilatation
Calcium intake (350 mg/day)
Absorption (350 mg/day)
Secretion (250 mg/day)
Feces (900 mg/day)
Urine (100 mg/day)
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