Plasma free calcium

Plasma membrane channels. The most common mechanism for the movement of into smooth muscle cells Ifom the extracellular space is the electrodiffusion of Ca " ions through highly selective channels. This movement can be significant in two quite different ways. First, Ca ions carry two positive charges and, in fact, most of the inward charge movement across the plasma membrane of smooth muscle myocytes is carried by Ca. Most smooth muscle action potentials are known to be Ca " action potentials. And second, the concentration of intracellular free calcium, the second messenger, is increased by inward calcium movement. 

In regards to necrosis, it is clear that the old adage an ounce of prevention is worth a pound of cure applies. Agents that stabilize ion homeostasis have proved to be effective in preventing necrosis in cell culture studies. For example, drugs that activate plasma membrane potassium ion channels or chloride ion channels can prevent membrane depolarization and so inhibit sodium and calcium ion influx. Agents that prevent large sustained increases in intracellular free calcium levels can also prevent neuronal... 

CalcitrioPs action primary function is in regulating plasma calcium concentration. In health, the plasma total calcium concentration is tightly controlled at 2.35-2.55 mmol/1. Only the ionized or free fraction, amounting to about 50% of the total, is physiologically active in for example, maintenance of membrane electrical potential and bone formation. The hormone causes increased bone resorption via activation of osteoclasts (see Section 9.4) and increased intestinal absorption of calcium following the synthesis of a specific binding protein in mucosal cells. As described in Section 4.7, some... 

PTH is secreted from the parathyroid glands in response to a low plasma concentration of ionized (free) calcium. PTH immediately causes the transfer of labile calcium stores from bone into the bloodstream. PTH increases rates of dietary calcium absorption by the intestine indirectly via the vitamin D3 system activation of enterocyte activity. Within the kidney, PTH directly stimulates calcium reabsorption and a phosphate diuresis. 

Calcium is present in three forms e.g., as free calcium ion, bound to plasma protein albumin and in diffusable complexes. The endocrine system, through parathyroid hormone and calcitonin, helps in keeping the concentration of ionized plasma calcium in normal level. Decrease in plasma levels of ionized calcium leads to increased parathyroid hormone secretion. Parathyroid hormone tends to increase plasma calcium level by increasing bone resorption, increasing intestinal absorption and increasing reabsorption of calcium in kidney. Vitamin D acts by stimulating... 

Damage to the plasma membrane allows increased influx of Ca2+. The result of this will be the same as inhibition of the efflux, a rise in cytosolic free calcium. Paracetamol and carbon tetrachloride cause this increased influx. 

More recently, Bortolotti et al. (2008) provided evidence to refute this calcium-mediated mechanism of weight loss, presenting results from a placebo-controlled crossover study of 10 obese adults with habitually low calcium intakes (<800 mg/day). Results indicated that dietary supplementation of 800 mg of calcium/day had no effect on circulating plasma free fatty acid concentrations or glycerol turnover. Theoretically, a calcium-mediated stimulation of lipolysis would have resulted in an increase in plasma free fatty acid concentrations and glycerol turnover, thus indicating a need for further research. 

The mobilization of calcium results not only in the observed transient rise in intracellular free calcium and enhanced cellular efflux, but also in a net loss of calcium from the cell (Fig. 1). Thus, total cell calcium declines with All stimulation of adrenal and vascular smooth muscle cells [44]. Furthermore, total cell calcium remains low throughout the duration of exposure to All, suggesting that the continued formation of small amounts of 1,4,5-IP3 prevents refilling of the ER pool. Upon the removal of All and the immediate reduction in IP3 concentration, total cell calcium rapidly recovers to prestimulation levels without a detectable change in cytosolic free calcium, as measured by calcium-sensitive dyes. This observation has been taken as evidence that the IP3-releasable ER pool is in direct communication with the plasma membrane and that extracellular calcium refills the pool without entering the bulk cytosol (see Ref. 45). The location of this pool within the cell (cytosolic vs. adjacent to the plasma membrane) remains a matter of controversy (see Rasmussen arid Barrett, Chapter 4). 

Calcium ions (Ca ) are important for the mediation of hepatic injury. Cytosolic free calcium is maintained at relatively low concentrations compared to the extracellular levels. The majority of intracellular calcium is sequestered within the mitochondria and endoplasmic reticulum. Membrane associated calcium and magnesium ATPases are responsible for maintaining the calcium gradient (Farrell et ah, 1990). Significant and persistent increases in the intracellular calcium result from nonspecific increases in permeability of the plasma membrane, mitochondrial membranes, and membranes of the smooth endoplasmic reticulum. Calcium pumps in the mitochondrial membrane require NADPH, thus depletion of available NADPH can cause calcium release from mitochondria (Cullen, 2005). 

Vitamin D is used in the maintenance of plasma calcium ion concentrations. The normal level of free calcium ions in the plasma ranges from 1,0 to 1.5 mM. This concentration is needed to support a rxormal rate of deposit of calcium In bone during growth and during bone turnover. Apparently, vitamin D has no direct effect on the deposit of calcium ions in bone. It seems to act only indirectly and in maintaining plasma calcium at a level required to support bone mineralization. Note, however, that there remains interest in the possibility that vitamin D does have a direct effect on the cells that synthesize bone. A few details on bone formation and structure and on the vitamin D-dependent process of bone resorption are presented here. 

Many sick persons have low serum albumin levels. The hypocalcemia occurring with low serum albumin results in a decrease in the total concentration of plasma calcium, but not in a decrease in that of free calcium ions. This type of hypocalcemia, which can occur with cirrhosis of the liver, does not result in the clinical signs of hypocalcemia, because free plasma Ca levels are maintained. 

Hypocalcemia commonly occurs during the first I or 2 days of life in premature, low-birth-weight infants. The exact mccKaiusm is not clear. Hypocalcemia can also present in newborns fed cow milk, because cow milk contains calcium and phosphorus in a ratio of about 1.34/1.0, by weight. Mother s milk contains relatively less phosphate the calcium/phosphorus ratio is 2.25/1,0. The excess phosphate in cow milk promotes hyperphosphatemia in the newborn. It is thought that plasma phosphate, in elevated concentrations, fonns a complex with plasma calcium. Formation of this complex reduces the levels of free calcium, resulting in symptoms of hypocalcemia. The newborn is not as able to make hormonal adjustments to maintain plasma calcium levels as is the older infant (Mizrachi et al., 1968). 

The free calcium fraction is the biologically active form. Its concentration in plasma is tightly regulated by the calcium-regulating hormones PTH and 1,25-dihydroxyvitamin D. 

Calcium can be redistributed among the three plasma pools, acutely or chronically, by alterations in the concentration of protein and small anions, changes in pH, or changes in the quantities of free calcium and total calcium in the serum (Figure 49-2). 

ExtraceHuiar calcium provides calcium ion for the maintenance of intracellular calcium, bone mineralization, blood coagulation, and plasma membrane potential. Calcium stabilizes the plasma membranes and influences permeability and excitability. A decrease in the serum free calcium concentration causes increased neuromuscular excitability and tetany an increased concentration reduces neuromuscular excitability. 

Reference intervals for Total and Free Calcium IN Serum and Plasma Total Calcium... 

Whole blood specimens develop a fiquid-junction potential different from that of serum or plasma because of the presence of erythrocytes. A positive bias that is directly proportional to the hematocrit has been reported. In addition, free calcium values have been reported to differ among capillary blood, venous blood, and serum samples because of differences in pH. Therefore, reference intervals... 

Instruments for the measurement of free magnesium in whole blood, plasma, or serum are available commercially. These instruments use ISEs with neutral carrier ionophores, including ETH 5220, ETH 7025, or a proprietary ionophore. Current ionophores or electrodes have insufficient selectivity for magnesium over calcium. Free calcium is simultaneously determined and used chemometrically with the signal from the magnesium electrode to calculate free magnesium concentrations. 

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