The Biomarker Handbook is a curated series that seeks to provide readers with insights on each biomarker we cover in our blood test packages and its relation to our body.
Strong bones, strong teeth, and a healthy heart depend upon a number of different bioelements amongst which calcium plays a pivotal role. This important element accounts for about 1-2% of the adult weight and is the most abundant mineral in the body.
Calcium exists mainly in its ionized, free form in the body which is metabolically active. An ionized calcium blood test is usually reserved for critical care in hospital settings.
Another form of calcium includes that bound to proteins (mainly albumin) and anions, which is the metabolically inactive form. The balance between ionized and bound calcium is called total calcium blood test and measures the amount of all of these forms of calcium in the serum.
The total calcium reference range in an adult is 8.9 – 10.1 mg/dL.
The normal ionized calcium range in an adult is 4.8 – 5.7 mg/dL.
The Role of Calcium in the Body
Although calcium is required for a number of different functions in the body, around 99% of calcium is found in bones and teeth alone. This percentage denotes the crucial role of calcium in the proper growth and maintenance of our bones and teeth.
Calcium also helps to keep skeletal muscles functioning properly, in nerve signal transmission, in the clotting of blood, and in the maintenance of a healthy heartbeat. Inside the cells, calcium makes an important constituent of enzymes and transport channels.
Disturbances in Calcium Levels:
High calcium levels: Hypercalcemia
When the level of calcium in the blood is elevated beyond the normal range, it is called hypercalcemia. Hypercalcemia can be caused by metabolic, drug-induced and genetic factors.
One of the most common causes of hypercalcemia is enlarged and overactive parathyroid glands. These glands produce the parathyroid hormone (PTH) which is essential in calcium absorption and homeostasis.
Hypercalcemia is also sometimes caused by an excess of calcium and/or Vitamin D intake through supplements, malignant conditions (of the breast, lung or bones), genetic disorders such as familial hypocalciuric hypercalcemia, certain drugs such as lithium (to treat bipolar disorder), severe dehydration and prolonged immobility (non-weigh bearing bones release calcium into the blood).
Hypercalcemia has clinical manifestation on the kidneys, bones, brain and muscles. Hypercalcemia can cause frequent urination and excessive thirst. Excess calcium can paradoxically weaken bones (osteoporosis) since there is more calcium in the blood than deposited in the bone, causing symptoms like bone pain, muscle weakness and depression. The heart function can also be affected by increased calcium levels. In severe hypercalcemia, irregular heartbeats can occur which is potentially life-threatening. Hypercalcemia can alter brain function to manifest as confusion, depression, lethargy and fatigue.
The gastrointestinal system may also be affected by hypercalcemia, causing nausea, vomiting, stomach cramps and constipation.
Clinical consequences of hypercalcemia
Hypercalcemia should be treated by your physician as early as possible. Clinical complications of hypercalcemia, if left untreated can include the following.
- Osteoporosis: conditions that cause excess release of calcium from bones to the blood will lead to bone thinning, or osteoporosis. This may lead to bone fractures, spinal column curvature, and loss of height.
- Kidney stones: hypercalcemia can lead to calcium crystals to deposit in the kidneys leading to calcium stones. This is extremely painful when stones are being passed into the bladder or out of the urethra.
- Kidney failure: if severe, the hypercalcemia may damage your kidneys and lead to organ failure to perform its usual duties of cleansing your blood and balancing fluid levels.
- Nervous system problems: hypercalcemia if severe can cause confusion, dementia and coma, which can be fatal.
- Abnormal heart rhythm: hypercalcemia can lead to a fast and/or irregular heart rate. This requires immediate medical attention.
Low calcium levels: Hypocalcemia
Hypocalcemia is the condition where serum calcium levels drop below the normal reference range. Hypoparathyroidism (underactive parathyroid glands) is the most common cause of hypocalcemia. These glands may accidentally be excised during a total thyroidectomy or they may be underactive due to an autoimmune disorder. Inadequate intake of calcium and Vitamin D in the diet and reduced magnesium levels in the blood can also cause hypocalcemia.
Secondary causes of hypocalcemia include kidney disease, pancreatitis, bone disease and cancer.
The signs and symptoms of reduced blood calcium levels depend on the chronicity of the condition. In chronic hypocalcemia, the disease may be asymptomatic and go unnoticed. In acute conditions, however, the clinical manifestation might be severe and potentially fatal.
Severe hypocalcemia can cause a painful spastic muscular condition, tetany, which is the most important clinical manifestation of decreased blood calcium levels. Neurological (dementia, seizures, depression), cardiovascular (heart failure, hypotension) and other symptoms such as cataracts and dermatitis may also result.
Hypocalcemia can lead to osteoporosis, osteopenia, and in children can lead to inadequate growth in bone (strength, length). The recommended daily intake of calcium is as follows:
|Age group||Daily recommended dietary allowance (RDA)|
|Children, 9-18 years||1,300 mg|
|Children, 4-8 years||1,000 mg|
|Children, 1-3 years||700 mg|
|Children, 7-12 months||260 mg|
|Children, 0-6 months||200 mg|
Testing for Serum Calcium Levels
The total blood calcium test usually forms part of a routine health screening or basic metabolic panel. This is by far the most common way of tracking your calcium biomarker in the outpatient setting. The ionized calcium test is more specific and requires more expertise to perform (usually in a hospital setting as it requires special handling of the specimen). A urine calcium test is also sometimes ordered for someone with symptoms of kidney stones, or kidney failure.
Your health professional may order calcium levels to be measured during a general physical examination. Other conditions that prompt serum calcium levels to be tested are:
- Before a major surgical procedure
- When your plasma protein levels are abnormal
- Before blood transfusions
- Renal disease
- Certain types of cancer
- When you experience symptoms of high (fatigue, anorexia, nausea, vomiting, excessive thirst) or low calcium levels (cramps, numbness, dementia)
Calcium therapy monitoring is usually done in cases of cancer, evaluating the effectiveness of vitamin D therapy, renal failure and/or a kidney transplant.
In some cases, your doctor may also order alternative tests to assess calcium level and its effect. These tests include testing for vitamin D levels, phosphate levels, albumin levels and performing renal function tests for any associated kidney diseases such as stone.
Treatment Approaches for Hypercalcemia
When you suffer from hypercalcemia, the management involves finding the cause, treating the cause, treat the abnormal biomarker itself if necessary, and find out if there are any health consequences associated with the disease and the biomarker abnormality. When hypercalcemia is mild, your doctor might choose to watch and wait (monitoring your bones and kidneys to ensure they remain healthy). If it is a concern, then your doctor will find the cause (ordering tests such as bone studies and parathyroid hormone levels in your blood, vitamin D, kidney function tests, protein and albumin levels).
Calcitonin, calcimimetic, bisphosphonates, prednisone and diuretics are some medications the doctor may prescribe if necessary to help reduce your calcium level. In cases of an overactive parathyroid gland, part or whole of the gland may be excised through surgery. Your doctor will also monitor the health of your bones and kidneys.
Treatment Approaches for Hypocalcemia
Proper management of hypocalcemia also depends on the severity. Commonly your doctor will try to find the cause for the low calcium, and decide if management of the underlying cause and also the low calcium itself are necessary. If the disease is long-standing, the doctor will also test for any possible complications arising from the underlying disease itself or the low calcium (bone health).
In most cases of hypocalcemia, symptoms are mild; calcium supplements (calcium carbonate, calcium citrate or calcium phosphate) and vitamin D treatment are needed to rectify blood calcium levels. Around 1-3 g/d of calcium is recommended.
In acute cases or more severe hypocalcemia, calcium and magnesium medications may be necessary. The patient may also be admitted if he/she requires IV therapy. In critical illness, low calcium is known to be a marker of disease severity, and whether these people need treatment of their low calcium should be decided by treating clinician.
Severe hypocalcemia with manifestations of painful muscle spasms and tetany require IV replacement. Around 100-300 mg of calcium is the recommended dose for these patients. Patients with severe hypocalcemia are monitored continuously, and oral calcium and vitamin D treatment is started as early as possible.
In every case of hypocalcemia, the underlying disease is investigated and treatment approaches in correcting the disease are considered. If the parathyroid glands or PTH is involved, the doctor may recommend recombinant human parathyroid hormone to be started.
Recognising the signs and symptoms of abnormal blood calcium levels is important. Talk to your health care professional immediately when you experience any of the symptoms.
Calcium is a vital mineral for proper body function, particularly in bone health, kidney health, and cell signalling (muscle contraction, nerve conduction, brain function). Any abnormality of calcium must be treated by your clinician with proper investigation of the underlying disease, treatment of the disease and the abnormal calcium itself if necessary, and investigation of any health consequences from the underlying disease and the calcium effect. Calcium abnormality can signal serious illness and have health consequences.
Many people with abnormal calcium levels do not have any symptoms or clinical signs, so in a routine metabolic screen, you can detect any abnormality early and investigate and treat it accordingly.
If you want to find out more about calcium and how to maintain healthy levels of it, take a look at our lifestyle article here!
Interested in other biomarkers? Check out the rest of The Biomarker Handbook.
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