Calcium is a vital macronutrient that performs many functions in the human body (providing muscle contraction, blood clotting, conducting nerve impulses). Calcium is also a major component of bone tissue. Calcitriol (vitamin D) and parathyroid hormone take the most important part in the regulation of its metabolism. Hypercalcemia is a fairly common electrolyte disorder, occurring in approximately 0.17 to 3.9 cases per 100 people. Gender differences vary among people of different ages. Young men and women over 45 are more susceptible to this condition.
Causes of hypercalcemia
Hypercalcemia almost always indicates some disease or pathological process. However, sometimes it develops due to physiological reasons (in newborns on the 4th day of life, in adults after eating). The pathological causes of this condition are as follows:
- Hyperparathyroidism.
This is an endocrine disease characterized by hypersecretion of parathyroid hormone (PTH). It is the most common cause of hypercalcemia. Hyperparathyroidism is caused by adenoma, hyperplasia of the parathyroid glands, and renal failure. Sometimes hyperparathyroidism occurs as part of autoimmune polylinglandular syndrome or multiple endocrine neoplasia. - Oncological diseases.
Recognized as the second most common cause of this electrolyte disorder. In cancer, it occurs through two mechanisms. The first is bone destruction by metastases or primary focus (leukemia, lymphoma, myeloma). The second mechanism is the synthesis of PTH-like peptide by cancer cells (lung, breast, bladder cancer). - Granulomatous processes.
Chronic diseases characterized by the formation of cellular granulomas in tissues (primarily in the lungs) can also cause hypercalcemia. These include tuberculosis, sarcoidosis, histoplasmosis. Mononuclear phagocytes that are part of granulomas, due to the expression of 1-alpha hydroxylase, are able to convert vitamin D into the active form (calcitrirol, 1,25OH-D3), which enhances the absorption of calcium ions by the small intestine. - Prolonged immobilization.
As a result of prolonged inactivity, osteoclasts (cells that destroy bone tissue by dissolving mineral compounds) are activated. This leads to the release of calcium ions from the bones. This phenomenon occurs during forced immobilization after injuries, being in conditions of weightlessness (during space flights). - Taking medications.
This primarily applies to vitamin D and calcium supplements. Other medications (thiazide diuretics, theophylline, lithium) can also cause calcium imbalance by increasing osteodestruction or reabsorption processes in the tubules of the nephrons of the kidneys. - Other endocrine disorders.
In addition to the pathology of the parathyroid glands, other endocrine diseases are sometimes the cause of hypercalcemia. For example, an excess of thyroid hormones in hyperthyroidism increases the destruction of bone tissue. With adrenal insufficiency, the inhibitory effect of glucocorticoids on calcium metabolism is reduced.
Signs that the body does not have enough calcium
Lack of calcium in the body is a fairly significant problem, its name is hypocalcemia. Typically, signs of the disease are almost invisible to the sick person. Significant consequences may take several months or years to become apparent.
Most often, preschoolers and children of primary school age - from 4 to 8 years old, women in an interesting situation and elderly women suffer from the pathology.
The following general signs of the formation of the disease are distinguished:
- A decrease in the volume of bone tissue, which is accompanied by frequent fractures with a small degree of injury.
- Dry skin, brittleness and fragility of hair and nail plates are observed. This is due to changes in their internal structure.
- Blood does not clot well after a minor injury.
- There are problems with the functioning of the thyroid gland.
- Malfunctions in the functioning of the heart muscle and circulatory system are detected.
- There are periodic painful sensations in the lumbar region, which indicate the development of kidney pathology.
- The occurrence of muscle excitability, the manifestation, especially during night rest, of cramps, pain in the muscles and joints.
- An increased number of developing dental problems, rapidly developing caries, a clear process of demineralization, which indicates the leaching of a large amount of minerals from the dental tissue.
- The nervous system reacts sharply to a decrease in the amount of nutrients: a person becomes overly irritable, he often has an anxious feeling, and fatigue manifests itself quickly.
- Due to weakened immunity, the patient often begins to be exposed to viral infections and other pathogenic bacteria that stimulate the development of diseases.
For young children, calcium intake is especially necessary. Hypocalcemia in preschoolers and primary schoolchildren inhibits the growth process and provokes a lag behind the physical development of their peers.
Pathogenesis
An increase in calcium content in the blood changes the membrane potential of cells, which leads to inhibition of neuromuscular conduction in skeletal muscles, myocardium, and the gastrointestinal tract. The pathogenesis of neuropsychiatric symptoms is not completely clear. The role of slowing down the conduction of nerve impulses is assumed. Calcification of blood vessels, internal organs, dystrophy, and tissue shrinkage develops.
Due to hypercalciuria (increased filtration of calcium in the nephron tubules), the risk of nephrolithiasis increases. Calcium inhibits adenylate cyclase, which suppresses the renal effect of antidiuretic hormone. Also, due to the high extracellular concentration of this cation, the secretion of hydrochloric acid by the lining cells of the stomach increases, which leads to the development of peptic ulcers.
Classification
According to the current, chronic and acute hypercalcemia (hypercalcemic crisis) are distinguished. Based on the level of cation (in mmol/l), the following degrees of severity of hypercalcemia are distinguished:
- Easy.
The content of total Ca is less than 3, ionized Ca is less than 1.5. - Moderate.
The level of total Ca is up to 3.5, ionized - up to 1.8. - Heavy.
Total Ca is above 3.5, ionized Ca is more than 1.8.
Pseudohypercalcemia is considered separately. Part of the calcium binds to plasma proteins, therefore diseases such as paraproteinemic hemoblastoses (multiple myeloma), characterized by a high protein content in the blood, are accompanied by an increase in the level of total calcium. Determination of ionized calcium helps to exclude false hypercalcemia.
Hypocalcemic crisis
An exacerbation of calcium deficiency is characterized by a decrease in plasma minerals to less than 2.25 mmol/l. A hypocalcemic crisis is also dangerous.
The attack can occur suddenly, but, as a rule, it is preceded by a number of symptoms:
- feeling of "goosebumps";
- tingling feeling throughout the body;
- limbs and part of the face go numb;
- severe muscle weakness;
- sudden muscle pain;
- depression;
- change in skin color.
Gradually, loss of sensitivity and other signs are replaced by muscle twitching. Initially, the patient feels only mild and isolated spasms, but quickly enough the condition develops into attacks of severe convulsions.
Muscle tone is expressed by characteristic manifestations:
- “the hand of the obstetrician”;
- "horse foot";
- "fish mouth";
- and others.
The danger arises when spasms affect the muscle tissue of internal organs: renal/liver colic, laryngospasm or bronchospasm. Impaired breathing can cause asphyxia.
At the moment of crisis, the patient feels unbearable pain, from which he loses consciousness and the ability to rationally perceive what is happening.
Symptoms of hypercalcemia
With a mild degree of pathology, there may be no symptoms at all. In moderate to severe cases, muscle weakness appears, sometimes reaching such severity that it is difficult for the patient to get out of bed. Symptoms from the gastrointestinal tract are typical - nausea, vomiting and abdominal pain. Appetite decreases significantly and constipation occurs. Cardiac symptoms (increased blood pressure, tachycardia) are often observed.
Even with hypercalcemia of non-oncological origin due to anorexia and muscular dystrophy, the patient loses a lot of weight, acquires a cachectic appearance, which may give a false impression that he has a malignant neoplasm. The weakening of the effect of antidiuretic hormone on the kidneys causes the appearance of symptoms such as severe thirst, an increase in urine output to 5-6 liters per day.
Neuropsychological symptoms are especially clearly presented. First, emotional instability, impaired concentration, and slight drowsiness occur. In severe cases of pathology, confusion, delirium, and psychosis develop. Hallucinations are possible. With long-term high levels of calcium, it begins to be deposited in the tissues of the joints (chondrocalcinosis), which causes arthralgia.
A little more about the symptoms
The clinical picture in both cases is pronounced. The main area of damage is the skeletal system, which contains more than 90% of the total calcium content in the body.
Symptoms of hypercalcemia, regarding bone tissue:
- pseudo- and simple form of gout;
- deformation;
- pain;
- muscle weakness and atrophy;
- fractures even with simple bruises;
- cystic bone formations.
In the severe stage, there is a sensation of “pins and needles”, numbness and burning in certain parts of the body, and temporary paralysis of the pelvic muscles may occur.
Hypocalcemia is characterized by seizures that can affect not only the limbs, but also the muscles of the chest. The danger comes from a hypocalcemic crisis, which causes serious complications.
Complications
Hypercalcemia has a wide range of adverse effects. The most common complications are osteoporosis (due to increased release of calcium ions from bones), pathological fractures, and urolithiasis. Acute pancreatitis and intestinal obstruction occur less frequently. The most life-threatening condition is considered to be hypercalcemic crisis, in which mortality reaches 60%. The cause of death is heart or kidney failure.
Another severe but rare complication is calciphylaxis (calcifying uremic arteriolopathy), characterized by ischemic necrosis of the skin and subcutaneous fat. It develops in patients with end-stage renal failure. A prolonged increase in calcium in the blood can also lead to band keratopathy, calcification of the aorta and heart valves with the formation of heart defects.
Diagnostics
The profile of a medical specialist supervising a patient with this pathology is determined by the cause that caused this condition. Most often, such patients are seen by endocrinologists, nephrologists, and oncologists. When interviewing the patient, it is necessary to clarify what medications he is taking. During the examination, the doctor pays attention to symptoms such as decreased muscle tone and suppressed tendon reflexes. An additional examination is prescribed, including:
- Laboratory research.
A biochemical blood test measures the level of albumin, urea, and creatinine. Of the electrolytes, in addition to total and ionized Ca, the concentration of phosphorus and chlorides is determined. The content of vitamin D (25OH-D) is studied. PTH, PTH-like peptides. Daily urinary Ca excretion is checked. If thyrotoxicosis or hypocortisolism is suspected, a blood test for hormones (TSH, free T4, cortisol) is performed. - Functional tests.
Special provoking tests provide invaluable assistance for differential diagnosis of the causes of this disorder. These include tests with native vitamin D, thiazide diuretics, and calcitonin. A steroid suppression test with prednisolone can be used to exclude a process not associated with increased PTH secretion. - Instrumental research.
To search for adenoma or hyperplasia of the parathyroid glands, ultrasound, computed tomography, and scintigraphy are performed. Densitometry is performed to determine bone mineral density, and renal ultrasound is performed to diagnose nephrolithiasis. If there are symptoms that raise suspicion of an inflammatory process in the lungs or a malignant neoplasm, radiography, CT scan of the lungs, abdominal organs, and mammography should be prescribed to identify them.
Differential diagnosis must be made based on the predominant symptoms. Insipidal syndrome must be differentiated from diabetes mellitus and diabetes insipidus. Muscle weakness and hypotension should be distinguished from that with muscular dystrophies, myasthenia gravis, and polymyositis. Neuropsychiatric symptoms require the exclusion of psychiatric diseases.
Scintigraphy. Parathyroid adenoma
Blood Ca levels
The daily intake of macronutrients depends on age and gender.
Adults:
- men and women under 65 years of age – 800–1000 mg;
- from 65 years – 1200 mg;
- lactating and pregnant women – 1500–2000 mg.
Children:
- up to 6 months – 400 mg;
- up to 3 years – 600 mg;
- from 3 to 10 years – 800 mg;
- from 10 to 14 years – 1000 mg;
- up to 18 years – 1200 mg.
Increased amounts of calcium are required by athletes and people engaged in heavy physical labor. Also, its consumption should be increased in the presence of injuries and bone fractures. The exact daily dose is determined by the attending physician.
Treatment of hypercalcemia
Conservative therapy
Patients with any degree of severity should be hospitalized in a hospital (endocrinology, nephrology department) for treatment. Patients with severe neurological symptoms and hypercalcemic crisis should be transferred to the intensive care unit. It is necessary to discontinue all medications that can cause an increase in calcium levels. Treatment of hypercalcemia has the following directions:
- Increased excretion of calcium in urine.
First, it is necessary to ensure adequate rehydration with physiological NaCl solution (0.9%). This will improve renal perfusion and increase the filtration of calcium ions by the renal glomeruli. Additionally, forced diuresis is performed using loop diuretics (furosemide). It is necessary to constantly monitor blood electrolyte levels. - Decreased absorption of Ca in the intestine.
Sodium or potassium phosphate salts are well suited for this purpose. Phosphates are strictly contraindicated for the treatment of secondary hyperparathyroidism caused by renal failure. Also, glucocorticosteroids (prednisolone, hydrocortisone) and synthetic antimalarial drugs (hydroxychloroquine, chloroquine) are used to suppress Ca absorption in the gastrointestinal tract. - Suppression of bone resorption.
An important stage in the treatment of hypercalcemia caused by hyperparathyroidism or cancer. The most effective drugs for preventing the progression of osteoporosis are bisphosphonates (pamidronic acid, zoledronic acid), which inhibit the activity of osteoclasts. The peptide hormone calcitonin and the cytotoxic antibiotic mithramycin have a similar mechanism of action, but a faster effect. - Suppression of the production of PTH and PTH-like protein.
For the pathogenetic treatment of primary and secondary hyperparathyroidism, calcimimetics (cinacalcet) are used, which increase the sensitivity of PTG cell receptors, thereby reducing PTH production. Gallium nitrate is used to treat hypercalcemia caused by a malignant tumor, which inhibits the secretion of PTH-like protein by tumor cells. - Intensive therapy.
For the treatment of severe life-threatening conditions (hypercalcemic crisis, calciphylaxis), as well as when other conservative methods of therapy are ineffective, hemodialysis using a low-calcium dialysate solution is an emergency measure to reduce Ca in the serum.
Surgery
Surgical removal of the parathyroid glands is the main treatment for primary hyperparathyroidism. The main indication for surgical intervention is a Ca level above 2.75 mmol/l. To prevent postoperative hypocalcemia (“hungry bone syndrome”), the patient is prescribed vitamin D and calcium supplements. Malignant tumors also need to be removed. To treat oncohematological pathologies, bone marrow transplantation is performed.
Experimental treatment
New drugs are currently being developed to treat this condition. The drug osteoprotegerin, which is a cytokine from the family of tumor necrosis factors, is at the stage of clinical trials. It inhibits the differentiation of osteoclasts and stimulates their apoptosis. In in vitro experiments, the calcitriol analogue EB 1089 suppressed the expression of the PTH peptide gene.
Prognosis and prevention
Hypercalcemia is a severe and in some cases (especially in acute cases) a life-threatening pathological condition. In hypercalcemic crisis, the mortality rate is very high (60%). The frequency of deaths in chronic cases averages 20-25%. However, the prognosis is largely determined by the cause of the increase in Ca levels.
Prevention of this pathology consists in timely diagnosis and proper treatment of the diseases against which it develops. Before starting to take vitamin D or other medications that may increase Ca levels in the blood, a blood test should be performed to assess Ca levels.
