Calcium and phosphorus metabolism in the body and its disorders

Disruption of calcium metabolism due to deviations in the functionality of the endocrine glands can lead to serious complications. Calcium is a mineral necessary for the body to form and maintain healthy bone tissue. The body contains 1.5 kg of this mineral.

Calcium enters the body with food and is also produced by the parathyroid glands. The endocrine system regulates the metabolic processes between calcium and phosphorus. With hormonal deficiency, there is an increase in phosphate in the blood with a concomitant decrease in calcium levels. Dysfunction of the gland can also lead to the reverse process, when calcium levels are increased. Both types of deviations are not considered normal and cause the development of pathological processes.

Characteristics

In the human body, a violation of calcium metabolism provokes the development of various diseases. Calcium is considered an important element in the process of regulating the nervous excitability of muscle tissue, the process of hemostasis, in the stabilization of cell tissue membranes, and in the transduction of intracellular signals.

In medicine, there are two forms of disturbance of mineral metabolism in the endocrine system:

• hypocalcemia (hypoparathyroidism);
• hypercalcemia (hyperparathyroidism).

The second type of disease is more dangerous and requires more complex treatment. In most cases, if the pathology is advanced, doctors resort to surgery.

In order to understand what could provoke a change in the production of calcium by the parathyroid glands into the blood, how to deal with this disorder and what the consequences may be, each pathology should be considered separately.

Metabolism of calcium and phosphorus in early life

During the first year of life, the risk of metabolic disorders is highest, which is associated with the rapid growth and pace of development of the baby. Normally, in the first 12 months, a child triples the body weight given at birth, and from 50 average centimeters at birth, a one-year-old toddler grows to 75. In children, phosphorus-calcium metabolism is manifested by a relative or absolute deficiency of useful minerals and substances in the body.

Numerous factors lead to the emergence of such problems:

• lack of vitamin D;
• disruption of its metabolism due to immaturity of enzyme systems;
• deterioration of intestinal absorption and renal reabsorption of phosphorus and calcium;
• diseases of the endocrine system.

Hypercalcemic conditions, which represent an excess of calcium and phosphorus, are much less commonly diagnosed. Excessive amounts of chemicals in the body are no less dangerous for the child’s health and require medication correction. However, achieving this state with a normal diet is almost impossible. So the daily requirement for calcium in infants is equal to 50 mg per 1 kg of body weight. Therefore, a child who weighs about 10 kg should receive about 500 mg of Ca daily. 100 ml of mother's milk, which is the only source of nutrients, contains about 30 ml of Ca, and cow's milk contains more than 100 mg.

Causes of hypocalcemia

Endocrine organs are sensitive to effects on them, so calcium metabolism can be disrupted for various reasons.

A decrease in plasma Ca may occur for the following reasons:

• neck trauma with bleeding;
• complication after surgery on the thyroid gland;
• inflammatory processes;
• ionizing radiation;
• metastasis in endocrine organs;
• adrenal insufficiency;
• autoimmune diseases;
• systemic diseases.

Identifying the causes is considered the basis of treatment, since if the influence of negative factors continues, therapy will not be effective.

How to treat such diseases

Metabolic disorders require complex complex treatment. Phosphorus-calcium metabolism, brought back to normal, will eliminate most pathological consequences without any intervention. Therapy for osteoporosis, rickets and other metabolic disorders occurs in stages. First of all, specialists try to stop the resorption processes in order to prevent fractures, eliminate pain and return the patient to a working condition.

Drugs for calcium-phosphorus metabolism are selected based on the symptoms of the secondary disease (most often osteoporosis, rickets) and the pathogenesis of bone resorption. Equally important for recovery is following a diet based on the principle of balancing proteins, calcium salts and phosphorus. Massage and therapeutic exercises are recommended for patients as auxiliary methods of therapy.

Causes of hypercalcemia

Excess Ca in plasma can be caused by several factors. It is not uncommon for calcium metabolism disorders to occur due to the development of malignant tumors or benign tumors.

In 80% of patients, hypercalcemia develops due to disorders resulting from the formation of a solitary adenoma on the pituitary gland. Adenoma, in turn, is formed due to stress, low blood pressure, hormone intake, etc.

In 12% of cases, the cause is the primary form of hyperplasia. 2% of patients are diagnosed with parathyroid cancer. About 6% of patients have multiple adenoma.

Reasons can also include:

• deficiency in the diet of foods containing calcium;
• violation of malabsorption functions of the intestine;
• chronic renal failure.

Treatment in this case involves eliminating the cause. If after this the indicators do not change, targeted therapy or even surgery is performed.

Literature

1. VC. Bauman, “Biochemistry and physiology of vitamin D” Riga, Zinatye, 1989, 480 p.
2. Fleisch, Bisphosphonates in bone disease, 1997, London, 184p.
3. Feldman, D., and Mallon, P. J. and Gross, C. (1996). Vitamin D: metabolism and action.In Marcus, R., Feldman, D. and Kelsey, J. (eds) Osteoporosis, pp.205-35. (San Diego: Academic Press).
4. Bushinsky, D. A. and Krieger, N. S. (1992). Integration of calcium metabolism in the adult. In Coe, FL and Favus, MJ (eds.) Disorders of Bone and Mineral Metabolism, pp.417-32. (New York: Raven Press).
5. O.G.Arkhipova, E.A. Yuryeva, N.M. Dyatlova, “Prospects for the use of xydiphone”, J. Vses. chem. total them. DI. Mendeleeva, 1984, XXIX, 3, pp. 76-80.
6. T.A. Matkovskaya, N.P. Tatarnikova, etc. Pat. RF RU 2124881 C1.
7. E.A. Yuryeva, I.P. Dunaeva, G.I. Kulakova “The effectiveness of xydiphone depending on the method of its use”, In: New chelating agent xydiphone. Pharmacology, toxicology and therapy. Moscow, 1990, pp. 62-70.

(The article is abbreviated. The full text was published in the journal: Cosmetics and Medicine, 1999, No. 5/6, p. 71.)

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.

Biochemistry of phosphorus-calcium metabolism

After these chemicals enter the body, they are absorbed in the intestine, then exchanged between the blood and bone tissue, followed by the release of calcium and phosphorus from the body in the urine. This stage is called reabsorption, which occurs in the renal tubules.

The main indicator of a successful Ca exchange is its concentration in the blood, which normally varies between 2.3–2.8 mmol/l. The optimal level of phosphorus in the blood is considered to be 1.3–2.3 mmol/l. Important regulators of calcium-phosphorus metabolism are vitamin D, parathyroid hormone and calcitonin produced by the thyroid gland.

Half of the calcium contained in the blood is directly bound to plasma proteins, in particular albumin. The rest is ionized calcium, which seeps through the capillary walls into the lymphatic fluid. Ionized calcium serves as a regulator of many intracellular processes, including the transmission of impulses through the membrane into the cell. Thanks to this substance, a certain level of neuromuscular excitability is maintained in the body. Calcium bound to plasma proteins represents a kind of reserve reserve to maintain a minimum level of ionized calcium.

Hypercalcemic crisis

A rare but dangerous complication is hypercalcemic crisis. In an acute condition, the patient’s entire nervous system is disrupted and blood clotting accelerates. Increased blood density implies increased risks for the patient’s life, as this can lead to the formation of blood clots or complete cardiac arrest.

Hypercalcemic crisis has symptoms:

• maintaining temperature above 40°C;
• internal bleeding;
• signs of fever;
• severe itching of the skin.

Disturbances of the central nervous system lead to the occurrence of psychosis, and subsequently shock. The patient's condition leads to the fact that he does not understand what is happening. If medical assistance is not provided in a timely manner, respiratory paralysis begins, followed by cardiac arrest and death.

Physiological effects of calcium[edit | edit code]

Nerves and muscles[edit | edit code]

A moderate increase in calcium concentration in the extracellular fluid may not be accompanied by clinical signs of dysfunction of the nervous and muscular systems. However, with severe hypercalcemia, the excitability of nerves and muscles decreases, which leads to the development of muscle weakness, drowsiness, and even coma. On the contrary, a moderate decrease in calcium concentration increases excitability, leading to the appearance of Chvostek and Trousseau symptoms, tetanic convulsions and laryngospasm. It is believed that the entry of Ca into cells occurs: 1) through facilitated diffusion (using a carrier), 2) due to Na+/CaJ+-o6MeHa, 3) through channels. The permeability of the latter is regulated by hormones and mediators, and in many cells these channels are voltage-dependent. In the liver and skeletal muscle, intracellular calcium is reversibly taken up by the endoplasmic and sarcoplasmic reticulum, respectively.

Calcium ions play an important role in electromechanical coupling. The action potential causes the release of calcium from the sarcoplasmic reticulum of the muscle cell. The released calcium binds to troponin, removing the blocking effect of tropomyosin on the interaction of actin with myosin, and thereby activating the contraction process. When calcium is reabsorbed by the sarcoplasmic reticulum, the blocking action of tropomyosin is restored and the muscle relaxes.

Calcium ions are also necessary for exocytosis, so they play an important role in coupling stimulation with secretion in most exocrine and endocrine glands. The secretion of catecholamines by the adrenal medulla, the release of neurotransmitters at synapses, and the release of certain other biologically active substances (eg, histamine by mast cells) all require the presence of calcium. The cardiovascular system. Calcium ions play a critical role in electromechanical coupling in the heart muscle, as well as in conducting electrical impulses through certain areas of the heart, in particular in the AV node. Depolarization of cardiac muscle fibers opens voltage-gated calcium channels (so-called slow calcium channels), through which calcium enters the cell during the plateau of the action potential. A local increase in calcium concentration causes the opening of calcium channels in the sarcoplasmic reticulum, which further increases the calcium concentration in the cytoplasm and leads to contraction. In some cells, such as the AV node cells, the action potential is driven almost entirely by calcium influx through slow calcium channels.

In smooth muscle, including vascular smooth muscle, calcium mediates contraction and often generates a significant portion of the depolarizing current. Therefore, calcium antagonists have a strong effect on the contractility of the myocardium and vascular smooth muscle, as well as on the conduction of impulses in the heart. These drugs occupy an important place among antianginal, antiarrhythmic and antihypertensive drugs. Other effects. Calcium ions maintain the integrity of mucous membranes, participate in cell adhesion and ensure the functions of cell membranes. Calcium plays an important role in blood clotting mechanisms, although it is not used as a therapeutic agent for clotting disorders. Calcium chloride has an acidifying effect on urine (although ammonium salts are much more effective in this regard) and promotes diuresis.

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.

Rickets in children

This disease is a direct consequence of disruptions in phosphorus-calcium metabolism. Rickets usually develops in early childhood (up to three years) with a lack of vitamin D and disturbances in the absorption of microelements in the small intestine and kidneys, which leads to a change in the proportion of calcium and phosphorus in the blood. It is worth noting that adults living in northern latitudes often experience problems with phosphorus-calcium metabolism due to a lack of ultraviolet radiation and short stay in the fresh air throughout the year.

At the initial stage of the disease, hypocalcemia is diagnosed, which triggers the functioning of the parathyroid glands and causes hypersecretion of parathyroid hormone. Further, as in a chain: osteoclasts are activated, the synthesis of the protein base of bone is disrupted, mineral salts are deposited in insufficient quantities, leaching of calcium and phosphorus leads to hypercalcemia and hypophosphatemia. As a result, the child experiences delayed physical development.

Characteristic manifestations of rickets are:

• anemia;
• increased excitability and irritability;
• limb cramps and development of muscle hypotonicity;
• increased sweating;
• digestive system disorders;
• frequent urination;
• X-shaped or O-shaped shins;

• delayed teething and a tendency to rapid progression of oral caries infection.

Diagnostics

Calcium metabolism disorders are determined by laboratory tests. To determine the cause of the pathology, more extensive research is required, so specialists prescribe hardware studies. Additionally, differential diagnosis can be carried out.

Examination methods:

• urine test (general) - with elevated Ca levels, a mineral will be present in the biomaterial and the alkaline reaction will be pronounced;
• blood test (biochemical) - a significant increase/decrease in ionized and total calcium is detected in the plasma;
• ultrasound examination - the entire endocrine system is examined for the presence of tumors, tissue enlargement and other abnormalities;
• radiography - used to examine bones to determine the possible development of osteoporosis, fractures, cystic formations and other pathological processes;
• densitometry - used to accurately determine the density of bone tissue;
• radiography (with contrast agent) - helps to identify ulcerative lesions of the gastrointestinal tract and parathyroid adenoma in the retrosternal space;
• computed tomography - examines the urinary system and kidneys for the presence of stones;
• magnetic resonance imaging - allows you to obtain the most accurate data about tumor formations of the thyroid glands;
• spintigraphy is a study using radioactive isotopes, with the help of which it is possible to visualize the area under study.

Diagnostics allows you to obtain the maximum amount of information to identify provoking factors, characteristics of the disease and possible complications. Treatment can begin only after receiving the examination results.

Study of the clinical effectiveness of cosmetic creams containing xidifon

The use of creams containing bisphosphonate has a therapeutic and preventive effect, preventing calcium deposits in skin cells, which, in combination with the preventive effect of the nourishing base of the cream, suggests an increase in the anti-aging effect of cosmetics. In this regard, this part of the work is devoted to an experimental and clinical study of the biological activity of creams produced by the REPHARM Institute of Pharmaceutical Reagents. In the experiment, the following was carried out:

1. Histological examination of skin biopsies of white rats after 30 applications.
2. Studying the effect of creams on the state of the protective function of the skin of laboratory animals using the method of determining the time of alkali neutralization according to the Burghart method.
3. Clinical assessment of the state of functional indicators of the skin under the influence of the presented creams included:
   Study of the moisture-holding capacity of the skin;
4. Study of the state of lipid metabolism of the skin;
5. Study of skin elasticity;
6. Study of skin profile (width and depth of wrinkles).

The following results were obtained:

1. A histological study of animal skin preparations treated with REPHARM creams revealed their effect on water-electrolyte and protein metabolism in the skin, manifested in an increase in the hydration properties of the skin.
2. A study of the effect of creams on the state of the protective function of the skin showed that in group 1 of animals, i.e. in rats that received the cream, restoration of the initial time of neutralization of alkali by the skin (6 minutes) occurred after 2 days. After 3 days, this indicator decreased and amounted to 4 minutes, i.e. a prolonging effect of the drug was noted. In group 2 of animals, i.e. in rats on whose skin the cream was not applied, restoration of the initial time of alkali neutralization occurred only on the 7th day after cessation of exposure to alkali, i.e. almost 2.5 times slower than in rats of group 2. Thus, the results obtained indicated a pronounced positive effect of the cream on the condition of one of the main functions of the skin - protective.
3. The clinical trials involved 20 volunteers - clinically healthy women without a significant allergic history, aged 35 to 50 years. 11 patients were diagnosed with combination facial skin, 9 with dry skin complicated by hyperkeratosis. Clinically, this manifested itself in dry skin and the presence of a network of fine wrinkles. The cream was applied to previously cleansed skin of the face and body every day, 2 times a day for 3 weeks.

The study of the effect of creams on the moisture-holding capacity of the skin was carried out using the Moisture Meter device, Russia. 20 minutes after the first application of the cream, the moisture content in the skin increased by an average of 67.3% compared to the initial level, after 2 hours this figure was 51.5%, after 4 hours - 36.6%, after a course of use by 15 .6%.

The data obtained indicated a positive effect of the cream on water-electrolyte metabolism in the skin and a pronounced hydration effect of the drug.

When studying the effect of creams on the elastic properties of the skin, it was found that the stretching indicator as a result of a course of cream use increased by an average of 10.9% compared to the initial one.

When studying the skin profile (width and depth of wrinkles) using the Tester T-2000 device, it was found that as a result of 3 weeks of use of the cream, there was a decrease in the Rt tooth by 5.09%, Rmax by 6.7%, Rz-d by 6.3% compared to the initial level, i.e. a positive effect of the cream on indicators characterizing the skin profile was stated.

Based on the analysis of the formulation and the results of the research, we can conclude that REFARM cosmetic creams, which include a calcium metabolism regulator, are effective cosmetics, the use of which has a pronounced hydrating effect, improves the elasticity and tone of the skin, smoothes out a network of fine wrinkles, improves the protective function of the skin.

These cosmetics can be recommended for use in broad cosmetology practice to care for the body's skin as an effective means of preventing and correcting skin aging processes.