Serum calcium concentration

The parathyroid glands in FHH are reset to maintain a higher than normal serum calcium concentration owing to impaired suppression of PTH release in the face of hypercalcemia (e.g., resistance to CaQ+) (Fig. 2). Similarly the kidneys show a reduced calciuric response to hypercalcemia, which contributes to the hypercalcemia by promoting inappropriately reabsorption of calcium. Mouse models of FHH and NSHPT result from targeted inactivation of one or both CaR alleles, respectively [1,3]. These animals have provided valuable insights into the alterations in tissue function resulting from loss of the receptor. 

More than 99% of total body calcium is found in bone the remaining less than 1% is in the ECF and ICE Calcium plays a critical role in the transmission of nerve impulses, skeletal muscle contraction, myocardial contractions, maintenance of normal cellular permeability, and the formation of bones and teeth. There is a reciprocal relationship between the serum calcium concentration (normally 8.6 to 10.2 mg/dL [2.15 to 2.55 mmol/L]) and the serum phosphate concentration that is regulated by a complex interaction between parathyroid hormone, vitamin D, and calcitonin. About one-half of the serum calcium is bound to plasma proteins the other half is free ionized calcium. Given that the serum calcium has significant protein binding, the serum calcium concentration must be corrected in patients who have low albumin concentrations (the major serum protein). The most commonly used formula adds 0.8 mg/dL (0.2 mmol/L) of calcium for each gram of albumin deficiency as follows ... 

Agent Dosage Onset Duration Reduction in Serum Calcium Concentration Comments... 

Transient hypercalcemia rarely occurs. A trough serum calcium concentration is recommended 1 month after initiation of therapy. 

Each 1 g/dL drop in serum albumin concentration below 4 g/dL decreases total serum calcium concentration by 0.8 mg/dL. 

Distribution - Calcium is rapidly incorporated into skeletal tissue. Normal serum calcium concentrations range from 9 to 10.4 mg/dL (4.5 to 5.2 mEq/L), but only ionized calcium is active. Calcium crosses the placenta and reaches higher concentrations in fetal blood than maternal blood. Calcium also is distributed in milk. 

Mithramycin (also known as MIT and plicamy-cin) is an antibiotic that binds to DNA to regulate transcription. It attaches to specific regions of DNA that are rich in guanine and cytosine. It appears to lower serum calcium concentrations by blocking the hypercalcemic action of Vitamin D. After IV administration about 25% of the drug is excreted in the urine after 2 hours, and 40% after 15 hours. The main indications are treatment of testicular tumors and control of hypercalcemia and hypercalciuria. 

Mecfianism of Action A synthetic hormone that decreases osteoclast activity in bones, decreases tubular reabsorption of sodium and calcium in the kidneys, and increases absorption of calcium in the GI tract. Therapeutic Effect Regulates serum calcium concentrations. 

Mechanism of Action A bisphosphate that binds to bone and inhibits osteoclast-mediated calcium resorption. Therapeutic Effect Lowers serum calcium concentrations. 

Diltiazem is a calcium ion influx inhibitor which inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentration. 

The secondary mineralocorticoid activity of glucocorticoids can lead to salt and water retention, which can cause hypertension. Although the detailed mechanisms are as yet uncertain, glucocorticoid-induced hypertension often occurs in elderly patients and is more common in patients with total serum calcium concentrations below the reference range and/or in those with a family history of essential hypertension (SEDA-20, 368 19). 

The time of year and the point during the menstrual cycle during which vitamin D derivatives are measured may be important. In seven women there was a two-fold rise in the serum concentration of 1,25-dihydroxycolecalci-ferol on day 15 of the menstrual cycle compared with days 1 and 8, without a detectable change in the serum calcium concentration (187). This increase did not occur in five women taking oral contraceptives, and there was a small but significant fall in the serum calcium concentration. 

In a randomized study in premenopausal women also treated with nafarelin, four of 23 women randomized to PTIF, 34 500 IU/day had a serum calcium concentration over 2.67 mmol/1 4 hours after the injection the concentration normalized after the dose of parathyroid hormone was reduced and other treatment was continued (10). 

In another study, two of 10 men who were randomized to receive subcutaneous PTHi 34 400 IU/day for 18 months had serum calcium concentrations over 2.6 mmol/1 after 1 or 3 months the concentrations normalized after reduction of the dose of parathyroid hormone (11). 

When 15 euthymic bipolar patients who had taken lithium for a mean of 49 months were compared with 10 nonlithium euthymic bipolar controls, the former had significantly higher total serum calcium concentrations and intact PTH (iPTH) concentrations (656). The authors advised baseline and periodic serum calcium and iPTH concentrations and bone density measurements in all lithium patients, although whether the benefit outweighs cost is open to question. 

Ten patients who had taken lithium for less than 1 year and 13 who had taken it for more than 3 years were assessed for alterations in bone metabolism and parathyroid function (654). There were no differences in bone mineral density, serum calcium concentration, or PTH concentration, but both groups had increased bone turnover and the longterm group had nonsignificantly higher calcium and PTH concentrations (including one hyperparathyroid patient who had an adenoma excised). The authors conclusion that lithium therapy is not a risk factor for osteoporosis needs to be tempered by the small sample size, the case of adenoma, and the blood concentration trends. 

In 53 patients studied prospectively at 1, 6, 12, and 24 months, lithium increased serum PTH concentrations (apparent by 6 months) and increased renal reabsorption of calcium in the absence of a significant change in serum calcium (660). A prospective study of 101 lithium maintenance patients and 82 healthy controls showed higher serum calcium concentrations during lithium treatment than at baseline or in the controls, and higher calcium serum concentrations in those lithium patients over 60 years of age (633). 

A 64-year-old woman who had taken lithium for over 10 years was admitted with altered consciousness, agitation, and disorientation. The serum calcium was 3.35 mmol/1 (reference range 2.1-2.6 mmol/1) and the PTH concentration was raised. With hydration and conversion from lithium to valproate, the serum calcium concentration normalized, but 2 years later disorientation and hypercalcemia recurred and a 150 mg parathyroid adenoma was removed surgically (665). 

A patient with psoriasis developed hypercalcemia and hypercalciuria after 28 days of treatment with tacalcitol (1208). He had been taking long-term thiazide therapy for his hypertension. When he used topical tacalcitol ointment his serum calcium concentration and urinary calcium excretion gradually increased to 3.55 mmol/1 and 0.475 g/day respectively. Within 7 days of withdrawal of tacalcitol, the serum calcium concentration had normalized. 

The human organism contains 1-1.4 kg calcium, and about 1% of this is in the extracellular fluid. The rest is largely in bone. The serum calcium concentration is 9-11.5 mg/dL, of which 4.5-5.0 mg/dL is in the free, ionized, biologically active form. The rest is protein bound or complexed with a variety of chelators, such as citrate. The daily dietary calcium requirement is 400-500 mg, and each day, 300-400 mg calcium is lost in the urine and an additional 150 mg in the feces. Inorganic phosphorus (largely as HP042 ) amounts to 2.7-4.5 mg/dL in adult serum. 

The biochemical features of calcium-deficiency and vitamin D deficiency are very similar. Both disorders result in a low-to-normal serum calcium concentration, an elevated PTH level, a decreased or normal phosphorus concentration, and increased alkaline phosphatase activity. The serum concentration of 25-hydroxyvitamin D is normal or slightly decreased in calcium-deficiency rickets but is markedly decreased in vitamin D deficiency. On the other hand, the serum concentration of 1,25-dihydroxyvitamin D is greatly elevated in calcium-deficiency rickets but is normal or even slightly decreased in vitamin D-deficiency rickets. 

Vitamin D that is taken up by the fiver is converted to 25-hydroxyvitamin D by a microsomal hydroxylase (Fig. 30-3). 25-Hydroxyvitamin D is the main circulating form of vitamin D in the serum and the best indicator of vitamin D status. Normal serum levels are 14-60 ng/mL (35-150 nmol/L). When serum calcium concentrations decline, 25-hydroxyvitamin D is converted to 1,25-dihydroxyvitmin D by la-hydroxylase, a mixed-function oxidase that is located in the inner mitochondrial membrane in kidney tissue and whose expression is regulated by parathyroid hormone (PTH). The main function of 1,25-dihydroxyvitamin D is to increase the intestinal absorption of dietary calcium and phosphorus. When serum concentrations of calcium and phosphorus are normal or when large doses of vitamin D are administered, 25-hydroxyvitamin D is metabolized to 24,25-dihydroxyvitamin D in the renal... 

Phosphate An intracellular shift of phosphate occurs along with potassium as fluid rehydration commences.The phosphate deficit can also be worsened with correction of the metabolic acidosis. Controlled, randomized studies have shown that routine phosphate repletion is not necessary, but some practitioners think it prudent to provide supplemental phosphate if serum phosphate levels are less than 1 mEq/L, potentially reducing the risk of seizure or tissue ischemia. During intravenous phosphate administration, serum calcium concentrations should be monitored carefully to avoid hypocalcemia and tetany (Fisher and Kitabchi, 1983). 

In this in vivo model, stimulation of bone resorption was induced in thyroparathyroidectomized rats by the infusion of parathyroid hormone. The changes in bone resorption were monitored by measuring the serum calcium concentration, which is directly related to the extent of bone resorption. 

Q7 The total serum calcium concentration is normally about 9.5 mg dl 1. Approximately half of this is bound to plasma protein, mostly to albumin. Most of the remainder is unbound or ionized calcium, which is the physiologically and clinically important form. Hypercalcaemia, normally defined as a serum concentration of >12 mgdl-1, may sometimes be caused by excessive consumption of calcium in the diet. More important pathologically is malignant disease. Hypercalcaemia occurs when there are bone metastases associated with breast or prostate cancer. However, many tumours can produce a PTH-like protein causing elevated serum calcium levels. Furthermore, intoxication and immobilization of vitamin D or excess vitamin D may also cause hypercalcaemia. 

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