What is the difference between ionized calcium and calcium

Here's what you need to know. Calcium supplements can help you build strong bones. However, they may also cause negative health effects for many people. A urine calcium test is done to measure how much calcium is passed out of the body through urine. Find information on why a serum albumin test is performed, how to prepare for the test, what to expect during the test, and how to interpret results.

Magnesium is vital to regulating blood pressure and maintaining bone strength. Learn about the serum test, which tells you how much of the element is…. Malabsorption syndrome refers to a number of disorders in which the small intestine is unable to absorb enough nutrients.

These nutrients may include…. Phosphorus is vital to bone growth and energy storage, among other things. Learn about the serum test, which tells you how much of the element is in…. Multiple tests can analyze metabolism. Most need blood drawn, but some can be ordered online and done at home. Here are 2. Health Conditions Discover Plan Connect. Ionized Calcium Test. Medically reviewed by Daniel Murrell, M. Why do I need an ionized calcium test?

How do I prepare for an ionized calcium test? How is an ionized calcium test performed? What are the risks of an ionized calcium test? What do the results mean?

To those situations, we could also add several case reports of pseudo-hypercalcemia total calcium related to multiple myeloma, which have led to misdiagnosis and injudicious care 90 , 91 , while ionized calcium levels were normal. The added value of ionized calcium has also been advanced in the context of hypocalcemia, a frequent and sometimes serious complication of thyroidectomy. Although ionized calcium measurement does not seem to bring any obvious benefit in the detection of postoperative hypocalcemia compared to total serum calcium levels 90 , its preoperative and early postoperative values may have predictive capacities regarding the occurrence of symptomatic post-operative hypocalcemia 91 , This could also apply to all other forms of primary or secondary hypocalcemia, but data are still lacking.

For the follow-up of patients with moderate or advanced chronic kidney disease including end-stage kidney disease , the monitoring of serum calcium levels is essential. Indeed, these patients are at high cardiovascular risk, mainly mediated by the chronic kidney disease—mineral bone disorder CKD-MBD 93 , This syndrome begins in the early stages of CKD and worsens as kidney function deteriorates.

This leads to specific abnormalities in the bone turnover, which can reach the stage of adynamic bone disease Clinically, we observe a renal osteodystrophy syndrome, responsible for increased bone fragility, as well as accelerated vessels and soft tissues calcification, thus explaining the high cardiovascular risk in the CKD population This explains the need to closely monitor the mineral metabolism parameters in CKD patients.

However, reports confirm the relevance of ionized calcium testing for this population. Indeed, there may be a significant risk of misdiagnosing a CKD patient as hypercalcemic with total calcium measurement although ionized calcium level is in the standard range 63 , 97 - These results may thus have a direct impact on these patients care, regarding the prescription of calcium or vitamin D supplementation or the use of calcimimetics.

Surprisingly, a study of more than CKD stage 3 to 5 patients demonstrated that albumin-adjusted serum calcium levels did not perform better than unadjusted total serum calcium for the detection of ionized calcium abnormalities Similarly, the study of Clase et al.

This phenomenon is most often related to persistent hyperparathyroidism. For these patients as well, the performance of total calcium dosage seems very limited, in the same way as for CKD patients. The extracellular calcium concentration has a direct impact on cells with calcium-sensing receptors on their surface parathyroid, renal tubule but also on excitable cells by influencing their membrane potential. This concerns particularly the heart, for which calcium homeostasis is directly involved in myocardial contraction.

There is a link between ionized calcium levels and electrocardiogram modifications - , illustrated by few case reports of severe arrhythmias caused by abrupt changes in ionized calcium levels , Calcium levels also interact with the smooth muscle fibers present in vessel walls, thus explaining the observed link between ionized calcium and blood pressure , Furthermore, in addition to enhancing calcium deposits in the soft tissues and vascular walls, chronic exposure to high levels of circulating calcium may increase the risk of cardiovascular events This may also be mediated by the association of calcium serum levels and some specific cardiovascular risk factors such as high blood pressure, carbohydrate intolerance and dyslipidemia - While several studies have shown a link between high levels of total calcium and the occurrence of cardiovascular complications 96 , - , the work of Ogard et al.

Although some studies have found a link between the depth of hypocalcemia and the risk of in-hospital or early mortality, the predictive value of ionized calcium levels at ICU admission is still debated , - The studies of Choi et al.

Nevertheless, ionized calcium assay appears to be more strongly associated with mortality risk in some specific ICU patients, such as those experiencing acute kidney injury , and those requiring renal replacement therapy , Moreover, the literature has highlighted some discrepancies between total and ionized calcium levels in patients admitted for acute pancreatitis , or for severe liver dysfunction requiring transplantation Finally, a recently conducted prospective study on patients hospitalized for hypertensive intracerebral hemorrhage showed that low ionized calcium was an independent risk factor for early expansion of intracerebral hematoma, as well as poor short-term prognosis The use of extracorporeal circulation, and more specifically plasmapheresis, justifies the close monitoring of ionized calcium level, given the risk of its sudden drop due to citrate anticoagulation and the common substitution by fresh plasma - The use of ionized calcium dosage has also been the subject of some other sparse studies, which may suggest a broader indication of its measurement.

Indeed, in a study involving 1, men with fertility disorders, a link was found between ionized calcium levels and semen quality, as well as sex steroid levels Some works have also reported a relationship between ionized calcium levels and the occurrence of preeclampsia , A study in elderly patients followed for depression also described a link between elevated levels of ionized calcium and white matter hemorrhages detected on brain MRI Finally, the use of the ionized calcium assay also seems useful when administering drugs and chemotherapies known to be associated with ionized calcium disturbances cisplatin, leucovorinfluorouracil, bisphosphonates for example - Some recent reports, however, have drawn attention to the risk of calcium status misinterpretation by ionized calcium testing in patients under Leflunomide treatment, due to analytical interferences , In conclusion, the current state of the art seems to insist on the added value of routine ionized calcium measurement for specific populations, such as patients suspected of hyperparathyroidism, suffering from cancer, admitted to intensive care units, or followed for CKD Figure 3.

For the other conditions mentioned above, we currently lack data to justify the broadening of ionized calcium monitoring indications. Although its routine use seems increasingly justified in many situations 15 , some authors have recently pointed out the risk of drifting to an inappropriate over-prescribing of ionized calcium testing 16 , 41 , In connection with these previous works concerning the overuse of ionized calcium, we may distinguish two main situations of interest: first, the specific cases previously detailed and the situations of moderate dyscalcemia.

Indeed, the discrepancies between total and ionized calcium almost never concern the situations of frank hyper- or hypocalcemia. This confirms the need for a thinking on precise clinical indications of ionized calcium testing and their integration into international guidelines 12 , The authors have no conflicts of interest to declare. The two most common causes of hypercalcemia are primary hyperparathyroidism and malignant disease cancer.

In a tiny minority, excessive PTH is due to abnormal increase in size hyperplasia of all parathyroid glands or parathyroid cancer. The condition can occur at any age and in both sexes, but postmenopausal women are the most commonly affected. Excessive PTH secretion leads to bone demineralization osteoporosis and chronic hypercalcemia that predisposes to urine-stone formation and renal damage. In rare cases, the hypercalcemia is of sufficient severity to threaten life [22].

Surgical removal of the offending adenoma is curative. Hypercalcemia can be a complication of soft-tissue cancer, most commonly cancers of breast, lung and esophagus. Hypercalcemia is also a common feature of multiple myeloma, a hematological malignancy of plasma cells in bone marrow.

Taken together, malignant disease is the second most common cause of hypercalcemia. One of the principal causes of hypercalcemia in these cases is uncontrolled excessive production by tumor cells of a protein called parathyroid hormone-related peptide PTHrP [23].

This is, as its name implies, similar to PTH in both structure and action. Like PTH, it increases plasma calcium by resorbing bone and decreasing calcium excretion.

The uncontrolled action of PTHrP inevitably results in abnormal loss of calcium from bone and consequent hypercalcemia. Direct destruction of bone tissue osteolysis by tumor cells that have metastasized to bone can also result in hypercalcemia; this is the principal mechanism of the hypercalcemia associated with multiple myeloma.

Generally speaking, hypercalcemia develops late in malignant disease and is a poor prognostic sign [24]. It is still important to detect because treatment aimed at normalizing calcium provides relief from symptoms of hypercalcemia, which in turn materially improves the quality of life of affected cancer patients [25].

Rare causes of hypercalcemia [26] include chronic renal failure, hyperthyroidism, sarcoidosis and tuberculosis. Some drugs, including thiazide diuretics and lithium, can precipitate hypercalcemia, as can ingestion of excessive vitamin D.

Hypocalcemia is much less common than hypercalcemia [27] except in two patient groups: the critically ill and neonates. The conditions most frequently associated with hypocalcemia in this patient group are sepsis, acute pancreatitis, acute renal failure, severe burns, trauma with rhabdomyolysis, alkalosis and massive blood transfusion.

Hypocalcemia is relatively common in the neonatal intensive care unit. The normal transition from an intrauterine environment to physiological independence at birth includes a rapid reduction in plasma calcium concentration. In some babies, most notably the premature, those with low birth weight and those born to diabetic mothers, this physiological reduction is exaggerated and transient hypocalcemia develops due to inadequate PTH response of immature parathyroid glands [29]. In general, the range and severity of symptoms associated with hypercalcemia reflect the severity of the increase.

Mild hypercalcemia, roughly defined as ionized calcium in the range 1. These may include gastrointestinal nausea, vomiting, constipation and neuropsychiatric lethargy, depression, confusion ; psychosis, seizures and coma may ensue. Cardiac arrest can occur if hypercalcemia is particularly severe. The effect of hypercalcemia on renal function is manifest acutely as polyuria and resulting polydipsia thirst.

Long-standing chronic hypercalcemia, even if mild, predisposes to urine-stone formation and calcium-induced damage to renal tubule cells that can progress to renal failure. Mild hypocalcemia, roughly defined as ionized calcium in the range 0.

Most common signs and symptoms associated with more severe hypocalcemia are manifestations of neuromuscular irritability, including paresthesia of peripheral extremities, muscle cramps, tetany and seizures. Laryngeal spasm may restrict normal respiration and the effect on cardiac contractility may be evident as arrhythmias; ECG changes include prolonged QT interval and T-wave inversion.

Markedly severe hypocalcemia can cause cardiac arrest. Long-standing hypocalcemia is associated with risk of cataracts. Measurement of ionized calcium is made using calcium ion-selective electrode ISE direct potentiometry. A reference method [30] has been described that is the basis of all routine methods available in blood gas and electrolyte analyzers.

All that is required of the operator is introduction of sample whole blood, serum or plasma into the analyzer; results are available within a minute or two. Despite the consensus that ionized calcium, rather than total calcium, is the preferred measure of calcium status and that ionized calcium measurement is simpler and faster, total calcium continues to be measured in clinical laboratories.

Ionized calcium measurement has in general been confined to point-of-care settings such as recovery room, intensive care, emergency rooms and operating theaters. One of the reasons for the slow adoption of ionized calcium is that blood collection and preservation requirements are far more exacting than those required for measurement of total calcium. It is vital that the pH of a blood sample for ionized calcium estimation is preserved because calcium binding and therefore ionized calcium concentration is pH dependant.

For this reason, blood must be collected anaerobically to minimize the in vitro decrease in pH that would result from aerobic metabolism. At this temperature whole-blood samples can be stored for up to 4 hours. For whole-blood estimation, the most suitable if results are required urgently, the sample must be collected into a syringe containing the anticoagulant heparin in a lyophilized dried state.

The use of standard lithium heparin is associated with significant potential error because heparin binds calcium, leading to artefactually reduced ionized calcium concentration. The magnitude of this error is dependant on heparin concentration. Whatever the heparin formulation used, it is essential for accurate results that the correct volume of blood is sampled to achieve correct heparin concentration and that blood and anticoagulant are well mixed immediately after sampling.

Blood collected for serum estimation must be processed anaerobically. Samples should ideally be centrifuged at low temperature and the cap should not be removed prior to analysis. Full recommendations for collection, transport and storage of specimens for ionized calcium are published [31]. The maintenance of plasma ionized calcium concentration within well-defined limits is essential for the many life-preserving physiological and cellular pathways that depend on ionized calcium.

The action of two hormones, parathyroid hormone and calcitriol, is of major importance in this regard. A range of clinical conditions — some very common — are associated with disturbance in calcium metabolism and resulting abnormality in ionized calcium concentration. If sufficiently severe, these changes in plasma ionized calcium concentration have profound adverse effect and may actually threaten survival.

Before the development of a reliable means of accurately measuring ionized calcium concentration in the mid-to-late s, the only means of assessing calcium status was to measure total calcium concentration in plasma. Because this does not accurately reflect ionized calcium concentration in some clinical situations, it is a less satisfactory alternative.

For a number of mainly logistical reasons, it continues to be used, but measurement of ionized calcium rather than total calcium is widely considered mandatory for some patient groups, most notably the critically ill.

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