PATHOPHYSIOLOGY OF WATER ELECTROLYTE METABOLISM. PATHOPHYSIOLOGY OF MINERAL METABOLISM.

I. PLAN OF STUDY OF THE TOPIC. 1. Changes in water distribution and water volume. 2. Types of dehydration, causes and mechanisms of development. 3. Effect of dehydration on the body. 4. Edema and dropsy: definition, classification. 5. Mechanisms of edema development: pathogenic factors and pathogenesis of different types of edema. 6. Significance of edema for organism. 7. Etiological and pathogenetic principles of edema and dehydration treatment. 8. Disturbance of trace elements metabolism. 9. Disturbance of macronutrients metabolism.

II. QUATIONS FOR SELFCONTROL. 1. Types of water balance disturbances. 2. Extracellular water sector. 3. Basic mechanisms of volume water sectors changes. 4. Types of dehydration according to mechanisms of development. 5. Mechanisms of dehydration caused by primary absolute lack of water. 6. Types of dehydration according to speed of water losing. 7. Types of dehydration according to degree of water or electrolyte lack. 8. Pathological conditions when develops " water deficiency due to of limited water supply." 9. Manifestations of intracellular dehydration. 10. Main mechanisms of dehydration from due to a lack of electrolytes. 11. Main causes of hyperosmolar dehydration in the loss of electrolytes through the gastrointestinal tract. 12. Phenomena arising from the violation of the blood supply to the nervous tissue during dehydration. 13. Definition of edema. 14. Classification of edema according to prevalence. 15. Classification of edema according to speed of development. 16. Classification of edema according to pathogenesis. 17. Classification of edema according to etiology. 18. Definition of dropsy. 19. Types of dropsy. 20. Types of lymphatic insufficiency. 21. Pathogenic factors in the development of cardiac edema. 22. Pathogenic factors in the development of nephrotic edema. 23. Pathogenic factors in the development of nephritic edema. 24. Basic principles of therapy in cases of water-electrolyte disorders. 25. Biological role of sodium. Types of hyponatremia depending on the osmolality of the extracellular fluid. 26. Types and causes of hypotonic hyponatremia. 27. Causes and main clinical manifestations of hypernatremia. 28. Biological role of potassium. Causes and main clinical manifestations of hypo - and hyperkalemia. 29. Biological role of calcium and phosphorus in the human body. 30. Causes, mechanisms and main clinical manifestations of hypocalcemia. 31. Causes and main symptoms of hypercalcemia. 32. Causes and main clinical manifestations of hypo-and hyperphosphatemia. 33. Biological role of magnesium, causes and main symptoms of hypo - and hypermagnesemia. 34. Biological role of iron, causes and main symptoms of decrease and increase of iron. 35. Biological role of copper, causes and main symptoms of hypo - and hypercupremia. 36. Biological role of zinc, causes and main symptoms of zinc deficiency and excess in the body. 37. Biological role of manganese, causes and main symptoms of manganese deficiency and excess in the body. 38. Biological role of chromium, causes and main symptoms of chromium deficiency and excess in the body. 39. Biological role of selenium, causes and main symptoms of selenium deficiency and excess in the body. 40. Biological role of molybdenum, causes and main symptoms of molybdenum deficiency and excess in the body. 41. Biological role of iodine, causes and main symptoms of iodine deficiency in the body. 42. Biological role of cobalt, causes and main symptoms of cobalt deficiency and excess in the body. 43. Biological role of fluorine, causes and main symptoms of fluorine deficiency and excess in the body.

12.8. DISORDERS OF WATER-ELECTROLYTE EXCHANGE (DISHYDRIA). DEHYDRATION. EDEMA Water is a universal environment and an indispensable structural component of any living system. It is a unique solvent of biopolymers and the necessary environment for the passage of all biochemical reactions of the body. In liquid water, at the temperature of a human body, its free molecules and structured “crystalline” aggregates, which are in a state of mobile equilibrium, are chaotically distributed. The degree of structuring of water in cells reflects their functional activity under the action of a wide variety of external and internal environment factors, even in ultra-low-intensive doses. The structure of the water in cells determines the ability of tissues to saturate and give away water (hydration ability of tissues). The high frequency of disorders of water and electrolyte metabolism and the severity of the processes caused by this disorder, especially in childhood, make the problem important and actual. 12.8.1. Changes in the distribution and volume of water in the human body The following violations of the water balance disorders are known: negative, accompanied by the development of dehydration of the body with all the consequences , and positive, leading to the development of edema and hydropsy. The total water content in the body (total body water) depends on age, body weight and gender (tab. 12-12). As you can seen from the table, the total water content of the body decreases with age, and this process continues permanently to extreme old age. At the same time the amount of water in the cells decreases, while the volume of extracellular fluid increases slightly. Table 12-12. Body water content,% to body weight

Age Total bodyExtracellular Intracellular period water fluid fluid

Embryo 2m 95 - - Fetus 5m 87 - -

Children Newborn months year years Grown-ups Men

+ Women

+ The total body water in an adult man body aged 25–30 years is on average about 60% of his body weight (about 42 liters with a body weight of 70 kg), in an adult woman - 50%. Normal variations of average values should not be more than 15%. Intracellular water sector of the body (intracellular water of the body). A significant part of water (30-35% of body weight) is concentrated inside the cells - the intracellular water sector of the body. It is the water of the cell mass of the body. A 25-year-old man with a weight 70 kg has about 25 liters of water inside the cells, a woman of the same age weighing 60 kg has about 17 liters (with a total body water volume = 32 liters). Intracellular fluid is presented in the form of three states: 1) protoplasmic water associated with hydrophilic structures; 2) water of attraction on the surface of colloidal structures; 3) capillarity water - in the gaps of protoplasm - the most mobile, relatively free water of cells. In various pathological conditions, the volume of the intracellular water sector can vary in the direction of its increase (for example, during water intoxication), and in the direction of decrease (water depletion). These changes occur more often due to the variation of the volume of mobile water in cells. As usually, the change in the volume of the intracellular sector of the organism develops more slowly and later in comparison to the change of the volume of the extracellular water sector (especially the volume of blood plasma). Extracellular water sector of the body (extracellular body water). Its volume is 20-24% of human body weight (about 17 liters for men weighing 70 kg). This sector includes plasma water, interstitial and transcellular fluids. Blood plasma water is part of the extracellular water sector (intravascular water sub-sector of the body). One of the most important functions of blood plasma is the formation of the environment for the normal functioning of blood corpuscles. The volume of blood plasma is 3.5-5% of body weight. The content of proteins in the blood plasma for an adult is 70-80 g / l (it creates a colloid osmotic pressure of 3.25-3.64 kPa, or 25-28 mm Hg), which significantly exceeds their content in the interstitial liquids (10-30 g / l). Pure water in blood plasma constitutes 93% of its volume. Interstitial fluid is an extracellular and extravascular fluid. It washes the cells directly, is close in ionic and molar composition to the blood plasma (with the exception of protein content) and, together with lymph, makes up 15-18% of body weight. This fluid is in constant exchange with blood plasma, so about 20 liters of fluid with substances dissolved in it pass from the vessels into the tissues in a day, and the same amount returns from the tissues to the general circulation, with 3 liters through the lymphatic vessels. Transcellular fluid is a special group of body fluids. It does not balance with the blood plasma, but is formed as a result of the cell activity, which is why it occupies a special position in the body. This group of fluids includes digestive juices, the contents of the renal tubules, synovial, articular and cerebrospinal fluids, chamber moisture of the eyes, etc. The proportion of an adult person accounts for 1-1.5% of his body weight. Changes in the volume of water sectors of the body. The volume of all these body fluids that make up the extracellular water sector, as well as the fluids of the intracellular water sector, can significantly decrease and increase. These changes can occur as a result of: 1) the primary change in the electrolyte composition of the body fluids (decrease or increase of electrolytes); 2) primary dehydration; 3) pathological water retention in the body. Wherein, mobile body fluids - intravascular and interstitial - change their volumes first of all. The body fluids have a fairly constant electrolyte composition (Table 12-13), are electrically neutral and are in a state of osmotic equilibrium. However, the electrolyte composition of extracellular fluids is significantly different from the electrolyte composition of intracellular fluids. Cellular fluids contain significantly more ions of potassium, magnesium, phosphates, extracellular fluids - ions of sodium, chlorine, calcium, bicarbonates. The content of proteins in the cells is much higher than their content in the interstitial fluid.

Table 12-13. Molar and ionic composition of human body fluids * *The concentration of non-dissociating compounds (glucose, urea, etc.) is not taken into account; it is approximately 7-9 mmol / l. The constancy of the electrolyte composition of the body fluids maintains the constancy of the volumes of these fluids and their definite distribution among the body’s water sectors. And, on the contrary, the constancy of the volumes of body fluids maintains the constancy of their electrolyte composition. Neurohumoral regulation of water and electrolyte metabolism Human drinking behavior is caused by changes in the state of the thirst center in the hypothalamus, which consists of neurons sensitive to angiotensin-II, and in less degree to angiotensin-III (these substances activate the center of thirst), to atriopeptin - the atrial natriuretic factor (it reduces the activity of the center of thirst). In addition, thirst can be caused both by an increase in the osmotic concentration of extracellular fluid and irritation of the osmoreceptors of the hypothalamus (this is a so-called hyperosmotic thirst), and by a decrease in circulating blood volume (BCC) and the effect of angiotensin-II on the thirst center (hypovolemic thirst).

Humoral regulation is carried out by antidiuretic and anti-natriuretic systems, the main executive organ of which are the kidneys. Osmoreceptors serve as sensors of the antidiuretic system, the main reflexogenic zone of which is laid in the anterior hypothalamus. In addition, there are less sensitive osmoreceptors of the liver (signals from the liver through afferent nerve pathways reach the hypothalamus). With an increase in osmotic blood pressure, osmoreceptors are irritated, which leads to an increase in the release of antidiuretic hormone (ADH) by the hypothalamus. ADH increases the reabsorption of water in the distal tubules of the nephron, and diuresis decreases. Sensors of the antinatriuretic system are atrial volume receptors (volume receptors), an adequate irritant for which is the change in the volume of body fluids (mainly BCC). With a decrease in BCC, irritation of the volumoreceptors is accompanied by an increase in the secretion of aldosterone by the adrenal glands, which increases the reabsorption of sodium in the renal tubules and contributes to its delay in the body. The activation of aldosterone secretion is also carried out through the renin-angiotensin-aldosterone system - the RAAS. Renin-stimulating factors (reduction of the cardiac output, hypovolemia, hypotonic states, renal ischemia, negative sodium balance) ensure renin production by the juxtaglomerular apparatus of the kidneys. Under the influence of renin, angiotensin-I is formed from angiotensinogen. Angiotensinogen is produced by the liver and is in the a2-globulin fraction of plasma. Under the influence of angiotensin-converting enzyme (ACE) from angiotensin-I, angiotensin-II is formed predominantly in the vessels of the lungs. Angiotensin-II is a key effector in the renin system. It is a powerful vasoconstrictor. In addition, the effect of angiotensin-II on the hypothalamus contributes to the activation of the sympathetic nervous system, which leads to hypertension. Angiotensin-II stimulates the center of thirst; in the hypothalamus increases vasopressin production; in the adrenal glands increases the production of aldosterone; in high concentrations, it stimulates glucocorticosteroidogenesis. Angiotensin-II has a mitogenic effect on vascular myocytes. Angiotensin-II inhibits reninization (this phenomenon is called the “short feedback loop” of the RAAS). Atriopeptin and vasopressin also reduce renin production. The lifetime of angiotensin-II in the bloodstream is short - up to 2 minutes. With successive proteolysis, it gives a number of derivatives, among them - angiotensin-III, which has a weak, biological activity similar to angiotensin-II. Angiotensin-II and angiotensin-III stimulate the synthesis of mineralcorticoid - aldosterone. In the renal tubules, aldosterone promotes the reabsorption of sodium. Under the influence of angiotensins, sodium retention also occurs in the sweat and salivary glands, small and large intestines. As a result, the sodium content increases in the blood - hypernatremia is observed. This is accompanied by irritation of the osmoreceptors of the hypothalamus and an increase in the secretion of antidiuretic hormone by the hypothalamus. ADH increases the reabsorption of water in the distal renal tubules. Thus, as a result of the activation of the RAAS, there is a delay of water and sodium in the body , which can lead to the appearance of edema and hydropsy. Atriopeptins (atrial natriuretic factor - ANF) are synthesized in the secretory cells of the atria, CNS, and lungs. Atriopeptin secretion increases with hypervolemia, saline load, atrial stretching. Atriopeptins provide an increase of natriuresis and diuresis in the kidneys. Atriopeptins inhibit the function of RAAS, reduce the secretion of renin, aldosterone, ADH, have a vasodilator effect, inhibit the center of thirst. Thus, they protect the body from overloading with salt and water. In various pathological conditions (cardiovascular and renal failure, fasting, etc.), neuroendocrine regulation, aimed at maintaining water-electrolyte homeostasis in a healthy body, is damaged and can become an important pathogenetic link leading to serious disorders of water and electrolyte metabolism. 12.8.2. Losses and the demand of water of the human body in normal condition and pathology A person per day must consume such amount of fluid, which is able to compensate daily losses through the kidneys and extrarenal pathways. The optimal daily diuresis for a healthy adult is 1200-1700 ml (in pathological conditions, it can increase to 20-30 liters and decrease to 50-100 ml per day). The excretion of water also occurs during evaporation from the surface of the alveoli and of the skin - imperceptible sweating (from the Latin. Perspiratio insensibilis). In normal temperature conditions and air humidity, an adult in this way loses from 800 to 1000 ml of water per day. Under certain conditions, these losses may increase to 10-14 liters. Finally, a small part of the fluid (100-250 ml / day) is lost through the gastrointestinal tract. However, daily fluid loss through the gastrointestinal tract in pathology can reach 5 liters. This occurs in severe disorders of the digestive system. Thus, daily fluid losses in healthy adults while performing moderate physical work and staying in the middle geographic zone can vary from 1,000 (1,500) to 3,000 ml. Under the same conditions, the normal balanced daily water requirement of an adult varies in the same volumes - from 1000 (1500) to 3000 ml and depends on body weight, age, gender, etc. (tab. 12-14).

Table 12-14. Daily losses and the need of water for healthy adults and children, ml * Endogenous (metabolic) water, formed in the process of metabolism and utilization of proteins, fats and carbohydrates, is 8-10% of the daily water needs of the body (120-250 ml). This volume may increase in 2-3 times because of some pathological processes (severe injury, infection, fever, etc.) Under various circumstances and situations in which a person may find himself, and especially in pathological conditions, daily water losses and consumption may differ significantly from the average normal ones. This leads to an imbalance of water metabolism and is accompanied by the development of a negative or positive water balance. 12.8.3. Types of dehydration and the causes of their development Dehydration (hypohydria, eksikoz) develops in cases when water losses exceed its consumption. At the same time, an absolute deficit of total body water occurs, accompanied by the development of negative water balance. This shortage may be associated with a decrease in the volume of intracellular water of the body or with a decrease in the volume of extracellular water, which in practice occurs most often, as well as due to a simultaneous decrease in the volume of intracellular and extracellular water of the body. Types of dehydration: 1. Dehydration caused by primary absolute water shortage (water exhaustion, “desiccation”). This type of dehydration develops either due to restriction of water intake, or due to excessive elimination of hypotonic or no electrolyte containing fluid from the body with insufficient loss compensation. 2. Dehydration caused by a primary deficiency of mineral salts in the body. This type of dehydration develops when the body loses and does not sufficiently restore the reserves of mineral salts. All forms of this dehydration are characterized by a negative balance of extracellular electrolytes (primarily sodium and chlorine ions) and cannot be eliminated only by intake of pure water. With the development of dehydration, it is practically important to consider two points: the rate of fluid loss (if dehydration is caused by excess water loss) and the way of fluid loss. These factors largely determine the nature of the developing dehydration and the principles of its therapy: with rapid (within a few hours) fluid loss (for example, acute small intestinal obstruction), the volume of the extracellular water sector of the body and the electrolyte content of its composition ( primarily sodium ions) decrease. The compensation the lost fluid in these cases should be fast. Isotonic saline solutions should be the basis of the transfused media — in this case, an isotonic solution of sodium chloride with the addition of a small amount of proteins (albumin).

Slowly (within a few days), developing dehydration (for example, with a sharp decrease or complete cessation of water intake) is accompanied by a decrease in diuresis and the loss of significant amounts of intracellular fluid and potassium ions. Recovery of such losses should be slow: for several days, fluids are injected, the main electrolyte component of which is potassium chloride (under the control of diuresis level, which should be close to normal). Thus, depending on the rate of fluid loss, acute and chronic dehydration is released. Depending on the predominant loss of water or electrolytes, hyperosmolar and hypo-osmolar dehydration is released. When a fluid is lost with an equivalent amount of electrolytes, isosmolar dehydration develops. For proper therapeutic correction of various types of dehydration, in addition to understanding the causes of dehydration, changes in the osmotic concentration of fluids and the volume of water spaces, due to which dehydration occurs predominantly, it is also necessary to know about changes in the pH of the body fluid. From this point of view, there are dehydrations with a change in pH to the acidic side (for example, with chronic losses of intestinal contents, pancreatic juice or bile), to the alkaline side (for example, repeated vomiting during pyloric stenosis is accompanied by significant losses of HCl and potassium ions and a compensatory increase in blood HCO3-, which leads to the development of alkalosis), as well as dehydration without changing the pH of body fluids (for example, dehydration, which develops with a decrease in water intake from the outside). Dehydration due to absolute primary water shortages (water exhaustion, “desiccation”). The development of dehydration due to the absolute shortage of water can lead to: 1) nutritional restriction of water intake; 2) excess water loss through the lungs, kidneys, skin (with sweat and through extensive burned and injured body surfaces). In all these cases, hyperosmolar or isoosmolar dehydration occurs. Water restriction. In healthy people, restriction or complete cessation of water intake into the body occurs under extraordinary circumstances: lost in the desert, covered with earthquakes and shipwrecks, etc. However, water shortage is much more often observed in various pathological conditions: 1) difficulty in swallowing (narrowing of the esophagus after poisoning with caustic alkali, with tumors, esophageal atresia, etc.); 2) seriously ill and weakened people (coma, severe forms of exhaustion, etc.); 3) premature and seriously ill children; 4) in some forms of brain diseases accompanied by a lack of thirst (idiocy, microcephaly), as well as the result of hemorrhage, ischemia, tumor growth, with concussion of the brain. With the complete cessation of the supply of nutrients and water (absolute starvation), a healthy person has a daily water deficit of 700 ml (Table 12-15). Table 12-15. The water balance of a healthy adult, ml, in a state of absolute starvation (according to Gembl)

Loss of body fluids, l Formation of body fluids, l Minimum amount of urine 500 Metabolic water 200 Minimum loss through the skin and lungs 900 Water released from depot 500 Total 1400 total 700

When fasting without water, the body begins to use primarily the mobile fluid of the extracellular water sector (plasma water, interstitial fluid), later mobile water reserves of the intracellular sector are used. In an adult weighing 70 kg has reserves of mobile water up to 14 liters (with an average daily need of 2 liters), in a child weighing 7 kg - up to 1.4 liters (with an average daily need of 0.7 liters). The life expectancy of an adult with the complete cessation of water and nutrients (under normal temperature conditions of the environment) is 6-8 days. The theoretically calculated life expectancy of a child weighing 7 kg in the same conditions is 2 times less. The children's body suffers from dehydration much more compared to adults. Under the same conditions, infants per unit of body surface per 1 kg of mass lose 2-3 times more fluid through the skin and lungs. Saving of water by the kidneys in infants is poorly expressed (the concentration ability of the kidneys is low, while the ability to dilute urine is formed faster), and the functional reserves of water (the ratio between the reserve of mobile water and its daily need) in a child is 3.5 times less than in an adult. The intensity of metabolic processes in children is much higher. Consequently, the need of water (see table. 12-15), as well as the sensitivity to its lack in children, is significantly higher compared with the adult body. Excessive water loss because of hyperventilation and excessive sweating. In adults, the daily loss of water through the lungs and skin can increase to 10-14 liters (under normal conditions, this amount does not exceed 1 liter). In childhood, a particularly large amount of fluid can be lost through the lungs in the so-called hyperventilation syndrome, which often complicates infectious diseases. In this case, frequent deep breathing occurs, which lasts for a considerable period of time, which leads to the loss of a large amount of pure (almost without electrolytes) water, gas alkalosis. With fever through the skin (due to sweat with low salt content) and the respiratory tract, significant amounts of hypotonic fluid may be lost. In case of artificial ventilation of the lungs, which is carried out without sufficient moistening of the respiratory mixture, loss of hypotonic fluid also occurs. As a result of this form of dehydration (when water losses exceed electrolyte losses), the concentration of electrolytes of extracellular body fluids increases and their osmolarity increases — hyperosmolar dehydration develops. The concentration of sodium in the blood plasma, for example, can reach 160 mmol / l (norm is 135-145 mmol / l) and more. The hematocrit index increases, the protein content of blood plasma increases relatively (Fig. 12- 43, 2). As a result of an increase in the osmolarity of the plasma, there is a shortage of water in the cells, intracellular dehydration, which is manifested by agitation and anxiety. A painful feeling of thirst, dry skin, tongue and mucous membranes appears, the body temperature rises, the functions of the cardiovascular system are seriously disturbed due to thickening of the blood, central nervous system, and kidneys. In severe cases, there is a life-threatening coma. Excessive water loss through the kidneys. Dehydration because of polyuria can occur, for example, with diabetes insipidus (insufficient production or release of ADH). Excessive water loss through the kidneys occurs when the congenital form of polyuria (congenital reduction of the sensitivity of the distal tubules and collecting tubules of the kidneys to ADH) occurs, some forms of chronic nephritis and pyelonephritis, etc. With diabetes insipidus, the daily amount of urine with a low relative density in adults can reach 20 liters or more.

Fig. 12-43. Changes in the content of sodium (Na, mmol / l), plasma protein (Б, g / l) and hematocrit index (Hct,%) with various types of dehydration: 1 - normal; 2 - hypertensive dehydration (water depletion); 3 - isotonic dehydration (acute loss of extracellular fluid with an equivalent amount of salts); 4 - hypotonic dehydration (chronic dehydration with loss of electrolytes) As a result, hyperosmolar dehydration develops. If the loss of fluid is compensated, the water exchange remains in balance, dehydration and disorders of the osmotic concentration of body fluids do not occur. If the loss of fluid is not compensated, then within a few hours severe dehydration with collapse and fever develops. There is a progressive disorder of the cardiovascular system due to thickening of the blood. Fluid loss from extensive burned and injured body surfaces. In this way, significant losses of water with a low salt content are possible, i.e. loss of hypotonic fluid. In this case, water from the cells and blood plasma passes into the interstitial sector, increasing its volume (see Fig. 12-43, 4). At the same time, the content of electrolytes there may not change (see. Fig. 12-43, 3) - isosmolar dehydration develops. If the loss of water from the body occurs relatively slowly, but reaches a considerable size, then the content of electrolytes in the interstitial fluid may increase - hyperosmolar dehydration develops.

Dehydration because of electrolyte deficiency. The development of dehydration from a lack of electrolytes can result from: 1) predominantly loss of electrolytes through the gastrointestinal tract, kidneys and skin; 2) insufficient intake of electrolytes in the body. The electrolytes of the body have the ability to bind and retain water. Especially active in this regard are ions of sodium, potassium and chlorine. Therefore, the loss and insufficient replenishment of electrolytes is accompanied by the development of dehydration. This type of dehydration continues to develop with the free intake of clean water and cannot be eliminated by the introduction of water alone without restoring the normal electrolyte composition of the body fluids. With electrolyte losses, hypo-osmolar or iso-osmolar dehydration may occur. Loss of electrolytes and water through the kidneys. A large amount of salts and water can be lost in some forms of nephritis, in Addison's disease (aldosterone deficiency), in case of polyuria with a high osmotic density of urine (“osmotic” diuresis in diabetes mellitus), etc. (see fig. 12- 43, 4; fig. 12-44). Losses of electrolytes in these cases exceed the loss of water, and hypo- osmolar dehydration develops. Loss of electrolytes and water through the skin. Electrolyte content in sweat is relatively low. The average concentration of sodium is 42 mmol / l, chlorine - 15 mmol / l. However, with heavy perspiration (heavy physical exertion, work in hot workshops, long marches), their loss can reach significant values. The daily amount of sweat in an adult, depending on the temperature factors of the external environment and muscular load, varies from 800 ml to 10 l, while sodium may lose more than 420 mmol / l, and chlorine - more than 150 mmol / l. Therefore, with abundant perspiration without adequate intake of salt and water, there is as severe and rapid dehydration as with severe gastroenteritis and uncontrollable vomiting. Hypo- osmolar dehydration develops. There is an extracellular hypoosmia and the transfer of water into the cells, followed by cellular edema. If you try to replace the lost water with a salt-free liquid, the intracellular edema is aggravated.

Loss of electrolytes and water through the gastrointestinal tract. With chronic loss of fluid containing a large amount of electrolytes, hypo-osmolar dehydration occurs. Body weight

normal Slow Fast extensive burn massive dehidration dehidration injury blood loss

Changes in the volume of intracellular and extracellular body fluids, as well as changes in water from one space to another in various pathological conditions in an adult: A is the volume of intracellular fluid; B is the volume of interstitial fluid; C is the volume of blood. Пл - blood plasma, Эр - red blood cells More often than others, losses can occur through the gastrointestinal tract: repeated vomiting and diarrhea in gastroenteritis, long-term healing of gastric fistula, pancreatic duct. With acute rapid losses of the gastrointestinal juices (with pyloric stenosis, acute bacterial dysentery, cholera, ulcerative colitis, high small bowel obstruction), changes in the osmolarity and composition of the extracellular fluid practically do not occur. When this occurs, salt deficiency, complicated by the loss of an equivalent amount of fluid. Acute iso-osmolar dehydration develops (see Fig. 12- 43, 3). Iso-osmolar dehydration can also develop with extensive mechanical trauma, massive body surface burns, etc. With this type of dehydration (iso-osmolar dehydration), water is lost by the body mainly due to extracellular fluid (up to 90% of the volume of fluid lost), which extremely adversely affects hemodynamics due to the rapidly advancing blood thickening. Figure 12-44 shows changes in the volume of intracellular and extracellular body fluids, as well as movement (shifts) of water from one water space to another with acute loss of extracellular fluid (see. Fig. 12-44.3, 5). With the rapid dehydration of the body, mainly interstitial fluid and plasma water are lost. In this case, there is a shift of water in the intracellular sector in the interstitial. With extensive burns and injuries, water from the cells and blood plasma moves to the interstitial sector, increasing its volume. After severe blood loss, water quickly (from 750 to 1000 ml per day) moves from the interstitial water sector to the vessels, restoring the circulating blood volume. With indomitable vomiting and diarrhea (gastroenteritis, pregnancy toxicosis, etc.), an adult's body can lose daily up to 15% of the total sodium, up to 28% of the total chlorine and up to 22% of the whole extracellular fluid.

Dysfunctions of organs and body systems during iso-osmolar dehydration manifest occur more quickly and are more severe than with hyperosmolar dehydration — the body mass progressively decreases, the arterial and central venous pressure decreases, the heart’s minute volume decreases, the central nervous system is disturbed, and the renal excretory function is disturbed. Apathy and adynamia quickly increase, the consciousness is upset and a coma arises. During slow dehydration, the volume of water decreases proportionally due to all aquatic spaces of the body. Its manifestations are less rapid and dangerous than while iso-osmolar dehydration. 12.8.4. The effect of dehydration on the body Failures of the cardiovascular system. Significant dehydration leads to thickening of the blood - anhydremia. This condition is accompanied by a disorder of a number of hemodynamic parameters. The volume of circulating blood and plasma decreases during dehydration. Thus, in experimental dehydration of animals (dogs), water loss of 10% of body weight causes a decrease in circulating blood volume on 24% while reducing the amount of plasma on 36%. Redistribution of blood occurs. The vital organs (heart, brain, liver) due to a significant reduction in the blood supply of kidneys and skeletal muscles are supplied with blood relatively better than others. In severe dehydration, systolic blood pressure drops to 70-60 mm Hg. and below. Venous pressure also decreases. Minute heart volume in severe cases of dehydration is reduced to 1/3 and even to 1/4 of normal size. The time of blood circulation is lengthened as the value of the minute volume of the heart decreases. In infants with severe dehydration, it can be lengthened by 4-5 times compared with the norm. Disruption of the central nervous system. The basis of central nervous system disorders during dehydration (convulsions, hallucinations, coma, etc.) is a disruption of the blood supply to the nervous tissue and intoxication with its metabolic products. This leads to the following phenomena: a) insufficient supply of nutrients (glucose) to the nervous tissue; b) insufficient supply of nervous tissue with oxygen; c) disruption of enzymatic processes in nerve cells. The value of the partial pressure of oxygen in the venous blood of the human brain reaches critical numbers, leading to a coma (below 19 mm Hg). The disruption of the central nervous system is facilitated by a decrease of blood pressure in the large circulation, an osmotic imbalance of body fluids, acidosis , which develop during dehydration. Renal impairment. The main reason for the reduction of renal excretory ability is insufficient blood supply of the renal parenchyma. This can quickly lead to hyperazotemia with subsequent uremia.

In severe cases of dehydration, anatomical changes in the kidneys can also be observed (necrotic calcification of the tubules with the disappearance of the phosphatase activity of their epithelium; renal vein thrombosis, obstruction of the renal artery, symmetric cortical necrosis, etc.). The occurrence of hyperazotemia depends on both a decrease in filtration and an increase in the reabsorption of urea in the tubules. The disproportionate reabsorption of urea seems to be associated with damage of the tubular epithelium. The load on the kidneys as an excretory organ during dehydration is increased. Renal failure is a decisive factor in the mechanism of non-gas acidosis (accumulation of acidic products of protein metabolism, ketone bodies, lactic, pyruvic acids, etc.). Disorder of the gastrointestinal tract. Due to the inhibition of enzymatic processes, as well as due to the inhibition of gastric and intestinal motility, dehydration leads to distension of the stomach, paresis of the intestinal muscles, a decrease in absorption and other disorders causing digestive disorders. The leading factor here is a severe anhydremic circulatory disorder of the gastrointestinal tract. 12.8.5. Water retention Water retention in the body (hyperhydration, hyperhydria, watering) is observed when water is excessively injected (water poisoning, water intoxication) or when the release of fluid from the body is limited. At the same time, visible and hidden edema and dropsy can develop. Water poisoning (intoxication). In human and animal body water poisoning occurs in that case when the flow of water into the body exceeds the ability of the kidneys to eliminate it. From excessive water load, the volume of circulating blood increases (oligocytemic hypervolemia), the content of proteins and electrolytes of the blood, hemoglobin decreases, hemolysis of erythrocytes and hematuria occur. This condition is accompanied by the development of hypo- osmolar hyperhydration, the transfer of water into cells with the subsequent appearance of signs of intracellular edema.

Under experimental conditions in dogs organism with repeated (up to 10-12 times) 50 ml of water injected into the stomach per 1 kg of weight with an interval of 0.5 hours, acute water intoxication occurs. This causes nausea, vomiting, muscle twitching, convulsions, a coma, and often fatal outcome. Diuresis initially increases, then begins to lag relatively to the amount of incoming water, and with the development of hemolysis and hematuria, a true decrease in urinary output occurs. Especially sharply these phenomena are aggravated with the simultaneous introduction of antidiuretic hormone or aldosterone. In humans body water poisoning can occur with some renal diseases (hydronephrosis, the second stage of acute renal failure, etc.), in conditions accompanied by an acute decrease or cessation of urine (patients in the postoperative period, in a state of shock with intravenous drip of large quantities liquids). The occurrence of water poisoning in patients with diabetes insipidus, who continued to take large amounts of fluids during treatment with antidiuretic hormonal drugs, in children who drank large amounts of fluids, etc., has been described. Types of hyperhydration. An increase of the total water content in the body can be observed while maintaining its normal osmotic concentration (300-330 mosmol / l). In this case, iso- osmolar hyperhydration occurs. Such condition is observed, for example, when the hydrostatic pressure in the capillaries increases and the filtration of the fluid from the vessels into the interstitial space increases (for example, in case of right heart failure). An accumulation of isotonic fluid in tissues occurs when a sharp decrease in oncotic pressure in the blood (loss of protein through the kidneys, cirrhosis of the liver, protein starvation, etc.), with an increase in capillary wall permeability (diffuse capillary glomerulonephritis), with difficulty lymphatic drainage (lymph vessels, for example, round filarial worms, lymph node metastases and lymph vessels - see the mechanism for the development of edema). Isoosmolar hyperhydration can develop after the introduction of excessive amounts of isotonic solutions (incorrect correction of water and electrolyte disorders).

In the case of a decrease in the osmotic concentration of body fluids below 300 mosmol / l (with an increased mass of total body water), it can be hypo-osmolar overhydration. This condition occurs with water poisoning (the flow of water into the body exceeds the ability of the kidneys to eliminate it), as well as with the overproduction of antidiuretic hormone (Parkhon syndrome). Hypoosmolar hyperhydration is accompanied by the movement of water into cells with the subsequent appearance of signs of intracellular edema. Hyperosmolar hyperhydration (with an increase in the osmotic concentration of body fluids above 330 mosmol / l against the background of an increased mass of total body water) may occur, for example, with forced unlimited consumption of seawater, the osmolarity of which far exceeds the osmolarity of the blood plasma. A similar condition occurs also with the excessive introduction of various hypertonic solutions for therapeutic purposes (incorrect correction of water and electrolyte disturbances). At the same time, life-threatening disorders of organs and systems, caused by dehydration of cells, develop. Signs of cellular dehydration appear especially quickly if hypertonic solutions are introduced into the body when kidney function is impaired with respect to excretion of salts or against the background of excessive aldosterone production (primary, secondary aldosteronism). 12.8.6. Edema and dropsy Edema is a pathological accumulation of fluid in the tissues and interstitial spaces due to disruption of the exchange of water between the blood and tissues. Edema is a typical pathological process that occurs in many diseases. A non-inflammatory swollen fluid is called a transudate. In terms of its physicochemical properties, transudate is significantly different from inflammatory effusion - exudate (see Chapter 10). Edemas differ: • by prevalence: local and general (generalized); • by the speed of development: fulminant (develop within a few seconds, for example, after an insect bite, snakes), acute (develop within an hour, for example, in acute heart failure, pulmonary edema), chronic (for several days, weeks, for example, when fasting); • pathogenesis: hydrostatic (stagnant), oncotic, membranogenic, lymphatic (lymphogenous), osmotic; • by etiology: cardiac, renal (nephrotic and nephritic), hepatic, toxic, neurogenic, allergic, inflammatory, cachectic, hungry. Pathological accumulation of fluid in the serous cavities of the body is called dropsy (ascites - in the abdominal cavity, hydrothorax - in the pleural cavity, hydropericardium - in the pericardium, between the leaves of the serous membrane of the testicle - hydrocele, in the ventricles of the brain and in the subarachnoid space - hydrocephalus, etc.). The mechanisms of edema. The exchange of fluid between vessels and tissues occurs through the capillary wall. This wall is a rather complex biological structure, through which water, electrolytes, some organic compounds (urea) are relatively easily transported, but much more difficult - proteins. As a result, the concentration of proteins in the blood plasma (60-80 g / l) and tissue fluid (10-30 g / l) are different.

According to the classical theory of E. Starling (1896), the disturbance of water exchange between capillaries and tissues is determined by the following factors: 1) the hydrostatic pressure of blood in the capillaries and the pressure of interstitial fluid; 2) the colloid osmotic pressure of blood plasma and tissue fluid; 3) capillary wall permeability. The blood moves in the capillaries with a certain speed and under a certain pressure (Fig. 12-45), as a result of which hydrostatic forces are created, seeking to bring water from the capillaries into the interstitial space. The effect of hydrostatic forces will be the greater, the higher the blood pressure and the smaller the pressure of the tissue fluid. The hydrostatic pressure of blood in the arterial end of the capillary of human skin is 30-32 mm Hg, and in the venous end - 8-10 mm Hg. It is established that the pressure of the tissue fluid is a negative value. It is 6-7 mm Hg. below the value of atmospheric pressure and, therefore, having a suction effect of action, promotes the transfer of water from the vessels into the interstitial space. Thus, an effective hydrostatic pressure (EHD) is created at the arterial end of the capillaries — the difference between the hydrostatic pressure of the blood and the hydrostatic pressure of the extracellular fluid, equal to ~ 36 mm Hg. (30 - (-6)). At the venous end of the capillary, the EHD value corresponds to 14 mmHg. (8 - (-6)). The proteins hold the water in the vessels, its concentration in the blood plasma (60-80 g / l) creates a colloid osmotic pressure of 25-28 mm Hg. A certain amount of protein is contained in interstitial fluids.

Fig. 12-45. Fluid exchange between different parts of the capillary and tissue (according to E. Starling): pa - normal hydrostatic pressure drop between the arterial (30 mm Hg) and venous (8 mm Hg) end of the capillary; bc is the normal value of blood oncotic pressure (28 mm Hg). To the left of point A (section Ab), liquid flows from the capillary into the surrounding tissues, to the right of point A (section Ac) there is a current of liquid from the tissue into the capillary (A1 is the equilibrium point). With increasing hydrostatic pressure (p'a ') or decreasing oncotic pressure (b'c'), point A shifts to positions A1 and A2. In these cases, the transfer of fluid from the tissue to the capillary becomes difficult and edema occurs. The colloid osmotic pressure of interstitial fluid for most tissues is ~ 5 mm Hg. Plasma proteins retain water in the vessels, tissue fluid proteins - in the tissues. Effective oncotic suction force (EEWS) is the difference between the value of colloid-osmotic pressure of the blood and interstitial fluid. It is ~ 23 mm Hg. st. (28-5). If this force exceeds the effective hydrostatic pressure, then the fluid will move from the interstitial space into the vessels. If the EEWS is less than the EHD, the process of ultrafiltration of liquid from the vessel into the tissue is provided. Whith aligning the values of EECS and EHD, an equilibrium point A occurs (see fig. 12-45). At the arterial end of the capillaries (EHD = 36 mm Hg, and EHR = 23 mm Hg), the filtration power prevails over the effective oncotic suction force on 13 mm Hg. (36-23). At the point of equilibrium A, these forces are aligned and amount to 23 mm Hg. At the venous end of the capillary, the EEWS exceeds the effective hydrostatic pressure by 9 mm Hg. (14 - 23 = -9), which determines the transition of fluid from the extracellular space into the vessel. According to E. Starling, an equilibrium takes place: the amount of fluid leaving the vessel in the arterial part of the capillary must be equal to the amount of liquid returning to the vessel in the venous end of the capillary. As the calculations show, such an equilibrium does not occur: the filtration force at the arterial end of the capillary is 13 mm Hg, and the suction force at the venous end of the capillary is 9 mm Hg. This should lead to the fact that in each unit of time, more fluid is released into the surrounding tissues through the arterial part of the capillary than it returns. So it happens - about 20 liters of fluid pass from the blood stream to the extracellular space per day, and only 17 liters return back through the vascular wall. Three liters is transported into the bloodstream through the lymphatic system. This is a fairly significant mechanism for the return of fluid into the bloodstream, with damage to which so-called lymphatic edema can occur. The exchange of fluid between the capillary and the tissue is shown in fig.12-45. The following pathogenetic factors play a role in the development of edema. 1. Hydrostatic (hydrodynamic) factor. With increasing of hydrostatic pressure in the vessels (Fig. 12-45, p, a), the filtration force increases, as well as the surface of the vessel (A1b, not Аb, as normal), through which the liquid is filtered from the vessel into the tissue. The surface, through which the reverse flow of the fluid occurs (A1c, not Ac, as is normal), decreases. With a significant increase in hydrostatic pressure in the vessels, such condition may arise when a fluid flows through the entire surface of the vessel in only one direction — from the vessel to the tissue. The accumulation and retention of fluid in the tissues occurs. An increase in hydrostatic pressure in vessels is observed with an increase in venous pressure (due to stagnation of blood in heart failure) and with an increase in BCC (due to an increase in the production of ADH in chronic heart failure). When the leading pathogenetic factor in the development of edema is an increase in the hydrostatic pressure of the blood, so-called stagnant edema develops. This mechanism plays a significant role in the occurrence of cardiac edema (blood stasis in heart failure), with the development of ascites with liver cirrhosis (blood stasis in portal hypertension). According to this mechanism, edema develops during thrombophlebitis, leg edema of pregnant women, since local venous pressure increases due to obstruction or compression of the veins. 2. Oncotic factor. With a decrease in the oncotic pressure of blood (Fig. 12-45, b, c), edema occurs, the development mechanism of which is associated with a drop in the value of the effective oncotic suction force. Plasma proteins, with a high hydrophilicity, retain water in the vessels and, in addition, due to their significantly higher concentration in the blood compared to the interstitial fluid, they tend to transfer water from the interstitial space to the blood. In addition, the surface of the vascular area increases (b1A2, not bA, as is normal), through which the process of filtration of the fluid occurs while simultaneously reducing of the resorption surface of the vessels (A2C1, and not Ac, as normal).

Thus, a significant decrease in the oncotic pressure of the blood (at least 1/3) is accompanied by the release of fluid from the vessels into the tissue in quantities that do not have time to be transported back into the general circulation, even despite a compensatory increase in lymph circulation. Fluid retention in the tissues occurs and the formation of edema. For the first time, experimental evidence of the significance of the oncotic factor in the development of edema was obtained by E. Starling (1896). It turned out that the isolated paw of the dog, through the vessels of which the isotonic saline solution was perfused, became edematous and added to the mass. The mass of the paw and puffiness decreased sharply when replacing an isotonic solution of sodium chloride with a protein-containing solution of blood serum. Oncotic factor plays an important role in the origin of many types of edema: renal (large losses of protein in urine - proteinuria), hepatic (reduced synthesis of albumin proteins in the liver during its diseases - hypoproteinemia, decrease in albumin-globulin ratio), hungry, kahekticheskih. According to the mechanism of development of edema, in the occurrence of which the leading is the reduction of oncotic blood pressure, are called oncotic. 3. Permeability of the vascular wall. An increase in the permeability of the vascular wall contributes to the development of edema. Such edema on the mechanism of development is called membranogenic. However, an increase in vascular permeability may lead to an increase in the processes of filtration in the arterial end of the capillary, and in resorption in the venous end. In this case, the equilibrium between filtration and water resorption may not be disturbed. Therefore, it is of great importance to increase the permeability of the vascular wall for plasma proteins, as a result of which the effective oncotic suction force drops, primarily due to an increase in the oncotic pressure of the tissue fluid. A clear increase in the permeability of the capillary wall for plasma proteins is observed, for example, in acute inflammation - inflammatory edema. The protein content in the tissue fluid at the same time increases sharply in the first 15-20 minutes after the action of the pathogenic factor, stabilizes within the next 20 minutes, and from 35-40 minutes a second wave begins to increase in the concentration of proteins in the tissue, apparently related with impaired lymphatic drainage and impaired transport of proteins from the source of inflammation (see Chapter 10). Disruption of the permeability of the vascular walls during inflammation is associated with the accumulation of damage mediators, as well as with the disorder of the nervous regulation of vascular tone.

The permeability of the vascular wall may increase with the action of some exogenous chemicals (chlorine, phosgene, diphosgene, lewisite, etc.), bacterial toxins (diphtheria, anthrax, etc.), as well as poisons of various insects and reptiles (mosquitoes, bees, hornets, wasps , snakes, etc.). Under the influence of these agents, in addition to increasing the permeability of the vascular wall, there is a violation of tissue metabolism and the formation of products that increase the swelling of colloids and increase the osmotic concentration of tissue fluid. The resulting edema is called toxic. Membranogenic edemas also include neurogenic (due to impaired nervous regulation of vascular tone, for example, in neurodystrophic processes) and allergic edema.(due to the effects of allergy mediators in allergic diseases). For example, the role of mediators (histamine, complement, etc.) is great in the development of various forms of angioedema (a German general practitioner who described acute local angioedema in 1882). There are allergic (see Chapter 8) and non-allergic (hereditary, associated with a deficiency of protease inhibitors, and in particular an inhibitor of the C1-esterase of the complement system) angioedema. More often, these edemas develop on the face and in the pharynx, but can also affect the internal organs (esophagus, stomach, intestines, uterus and other organs and tissues). Increased permeability of the vascular wall is also observed in thrombocytopenia, acidosis. 4. Lymph circulation (lymphatic factor). The obstruction of fluid and protein transport through the lymphatic system from the interstitial space into the general circulation creates favorable conditions for the retention of water in the tissues and the development of edema. So, for example, when the pressure in the system of the superior vena cava (right heart failure, narrowing of the mouth of the hollow veins) increases, a powerful pressor reflex to the lymphatic vessels of the body occurs, resulting in difficulty in the flow of lymph from the tissues. This failure of lymphatic circulation is called mechanical lymphatic insufficiency and it is one of the most important mechanisms for the development of edema in heart failure, as well as in liver cirrhosis. Mechanical lymphatic insufficiency also develops when the lymphatic vessels are blocked by filarias, when the lymphatic vessels are crushed by a tumor, exudate, scar, enlarged neighboring organ, etc.

With a significant decrease in the protein content in the blood (below 40 g / l), for example, with nephrotic syndrome, the linear and volumetric rates of the lymphatic drainage increase several times. However, despite this, due to the extremely intensive filtration of fluid from the vessels into the tissue (see the role of the colloid-osmotic factor), the lymphatic system is not able to return such significant volumes of tissue fluid to the general circulation. In connection with the overload of the transport capacity of the lymphatic system, the so-called dynamic lymphatic insufficiency occurs. This pathogenetic factor plays an important role in the formation of edema in nephrotic syndrome.

Fig. 12-46. Elephantiasis of the lower limbs (O.G. Mason, 1878) There is also a resorption lymphatic insufficiency that occurs when the concentration of proteins in the tissue increases, for example, during inflammation. Protein molecules retain water in the tissue, the intensity of lymphatic drainage decreases, and edema develops. In some cases, the role of the lymphatic factor in the mechanism of development of edema is so immediate and large that they release so-called lymphatic edema. An example is elephanthood (elephantiasis) (fig. 12-46). The disease occurs mainly in tropical countries and occurs as a result of mechanical blockage of lymphatic vessels with round parasitic worms - filarias. The mechanical lymphatic insufficiency that develops in this process is the leading pathogenetic mechanism for the formation of the strongest swelling of the limbs (the mass of one lower limb can reach 50 kg or more), the genitals and other parts of the body (like anasarca). The disease quickly leads to disability. 5. Active retention of electrolytes and water (osmotic factor). An important link in the development of many types of edema (cardiac, renal, hepatic, etc.) is the inclusion of mechanisms that actively inhibit electrolytes and water in the body. The regulation of the constancy of the electrolyte composition of body fluids and their volume is normally carried out by antidiuretic and anti-natriuretic systems. The irritation of the osmororeceptors of the hypothalamus (with an increase in the osmotic pressure of the blood) and the volumoreceptors of the atria (with a decrease in the volume of circulating blood) is accompanied by an increase in the secretion of ADH by the hypothalamus, as well as aldosterone by the adrenal glands (see section 12.8.1, and also Figs 12-47, 12-48) . The main regulator of aldosterone production is the RAAS.

Fig. 12-47. Automatic regulation of sodium and water homeostasis.

Fig. 12-48. Neurohumoral link in the mechanism of water and salt retention in heart failure. With heart failure, cirrhosis of the liver, insufficient kidney function, accompanied by activation of the RAAS, a significant increase in blood aldosterone levels is found (secondary aldosteronism). The secretion of ADH in these conditions also increases. It has been established that persistent hyperaldosteronism in heart failure and liver cirrhosis is the result of not only increased secretion of the glomerular zone of the adrenal cortex, but also decreased inactivation of aldosterone by the liver. At the same time, there is an increase in the volume of extracellular body fluids, which, it seemed, would have to reduce the secretion of aldosterone and ADH and thereby reduce the retention of water and salts in the body. However, this does not happen. Under these pathological conditions, an excess of aldosterone and ADH no longer plays a protective role, and the mechanisms aimed at maintaining homeostasis in a healthy person are “mistaken” under these conditions, as a result of which water and salt retention is aggravated. In this regard, edematous states can be considered, according to G. Selye, as “adaptation diseases”. In the clinic, the most common are heart, kidney (nephrotic and nephritic), neurogenic edema, as well as ascites with liver cirrhosis. Heart swelling. Such edema occurs with the development of heart failure (see Chapter 15). They are most pronounced in the stage of cardiac decompensation, however, they can be detected long before this stage, especially during exercise. In the formation of cardiac edema, many pathogenetic factors are involved, the significance and sequence of which changes when the damage to the activity of the cardiovascular system increases. There is no doubt that venous blood stasis and increase in hydrostatic pressure (see the role of hydrostatic factor) play a leading role in the development of cardiac edema. Therefore, such swellings are called stagnant. Impaired blood supply to the kidneys due to stagnation is accompanied by activation of the RAAS. An increase in the blood of biologically active peptides (angiotensin-II and angiotensin- III) is accompanied by increased synthesis of aldosterone and antidiuretic hormone (increasing the concentration of these hormones in the blood also contributes to their inactivation in the liver), followed by water and sodium retention in the body and tissues. There is an active delay of electrolytes and water (osmotic pathogenetic factor of edema). Impaired blood supply to the liver due to stagnation is accompanied by a decrease in protein synthesis in the liver, oncotic pressure of the blood decreases, which is also one of the pathogenetic factors of edema. Increased pressure in the hollow veins (in case of insufficiency of the right parts of the heart) causes a reflex spasm of the lymphatic vessels, leading to mechanical lymphatic insufficiency, which is also an important link in the formation of cardiac edema. The growing disorder of the general blood circulation causes tissue hypoxia with subsequent disorder of their trophism, the development of acidosis and an increase in the permeability of the vascular wall (see Fig. 12-48). Renal swelling. In kidney diseases, there is a failure of water and electrolyte metabolism, accompanied by water retention in the body and the occurrence of edema (see Chapter 19). Typical localization of renal edema are the eyelids, the face, as the progression develops swelling of the whole body (anasarca), fluid accumulation in the serous cavities (ascites, hydrothorax, hydropericardium, etc.). Renal nephrotic edema (with nephrotic syndrome). With the development of nephrotic syndrome, the leading place in the formation of edema belongs to a sharp decrease in the protein content of blood plasma - hypoproteinemia. This is due to the large loss of plasma proteins in the urine (mainly albumin, but other proteins are also lost: ceruloplasmin, transferrin, haptoglobin, γ- globulin, etc.). Proteinuria is associated with increased renal glomerular permeability for proteins and impaired protein reabsorption in the renal tubules. The concentration of proteins in the blood can drop to 30-20 g / l and below, and the daily loss of proteins in the urine reaches 30-50 g (normally does not exceed 50 mg / day). From this it becomes clear the significance of the oncotic pathogenetic factor in the development of nephrotic edema. Therefore, this edema on the pathogenesis is called oncotic.

The increased transudation of fluid from the capillaries into the tissues and the development of dynamic lymphatic insufficiency due to this can contribute to the appearance of hypovolemia (decrease in volume). circulating blood) followed by mobilization of the reninangiotensin-aldosterone mechanism of sodium and water retention in the body (Fig. 12-49). In case of nephrotic syndrome, there is an increase in the effective hydrostatic pressure due to compression of venules by the edematous tissue, including hydrostatic pathogenetic factor of edema.

Fig. 12-49. Pathogenetic factors involved in the development of edema in nephrotic syndrome An increase in the permeability of the vascular wall due to intoxication and acidosis, which develop in renal failure, may have a certain significance in the mechanism of edema in nephrotic syndrome. Renal nephritic edema (with glomerulonephritis). In the pathogenesis of edema in chronic glomerulonephritis, the reduction of glomerular filtration is of great importance, which in itself can lead to water and salt retention in the body. In addition, in the blood of patients with glomerulonephritis, an increased concentration of aldosterone and ADH is often observed. This is due to a violation of intrarenal hemodynamics, followed by the inclusion of the RAAS, active retention of electrolytes and water (i.e., the osmotic pathogenetic factor of edema works). When glomerulonephritis is often marked increase in the permeability of the vast part of the capillary system of the body - developing "generalized capillary." There is information about the increased activity of plasma kallikrein in patients with glomerulonephritis, which also leads to an increase in vascular permeability. In glomerulonephritis, the development of edema is also ensured by the inclusion of a hydrostatic pathogenetic factor of edema with extensive water retention in the tissues due to an increase in BCC and the development of arterial hypertension.

Ascites and edema in liver cirrhosis. With cirrhosis of the liver, along with the local accumulation of fluid in the abdominal cavity (ascites), there is an accumulation of it in the tissues and interstitial spaces of the body (hepatic edema). The primary point in the onset of ascites with liver cirrhosis is the difficulty of intrahepatic circulation with a subsequent increase in hydrostatic pressure in the portal vein system (portal hypertension) and the release of fluid into the abdominal cavity. Therefore, ascites pathogenesis is called stagnant. The fluid gradually accumulating inside the abdominal cavity increases the intra-abdominal pressure to such an extent that it counteracts the flow of fluid from the vessels into the cavity and hampers the further development of ascites. An important role in the mechanism of development of edema and ascites in liver cirrhosis is given to the active retention of sodium and water in the body. It is noted that the concentration of sodium in urine, saliva and sweat with ascites is low, and the concentration of potassium is high. All this indicates an increase in secretion in the body of aldosterone, as well as antidiuretic hormone. This happens due to the activation of the RAAS due to insufficient blood supply to the kidneys during portal hypertension. In addition, there is insufficient inactivation of aldosterone and ADH in the liver. When the ability of the liver to synthesize albumin is impaired, the oncotic pressure of the blood decreases due to developing hypoalbuminemia, and the oncotic is also attached to the above factors involved in the mechanism of the development of edema and dropsy. With an increase in hydrostatic pressure in the portal vein, the lymph flow increases sharply. With the development of ascites, the transudation of fluid exceeds the transport capacity of the lymphatic pathways, and dynamic lymphatic insufficiency develops.

In liver diseases (cirrhosis, hepatitis), there is an increase in the content of inflammatory mediators, hypoxia and acidosis in the tissues of the abdominal cavity, this contributes to an increase in vascular permeability (membrane-induced edema). Neurogenic edema. In some types of edema, the role of the nervous system acts most clearly and directly, since the nervous system provides trophism of the vascular wall and metabolic processes in the tissues. Such swelling is called neurogenic. In their origin, an important role is played by the increased permeability of the vascular walls and metabolic disorders in the tissues with the development of metabolic acidosis. For example, edema of the extremities develops in syringomyelia (formation of cavities in the gray matter of the spinal cord) and in the dryness of the spinal cord (damage to the posterior horns and pillars of the spinal cord). Neuralgia of the trigeminal nerve is often accompanied by the development of facial edema. Neurogenic include edema of the skin in hysteria, contusion edema, etc. The value of edema for the body. As mentioned above, many common mechanisms are involved in the formation of various types of edema (cardiac, renal, hepatic, cachectic, toxic, inflammatory, allergic, neurogenic, etc.): an increase in hydrostatic pressure in blood vessels, an increase in vascular wall permeability for plasma proteins, an increase in oncotic pressure of tissue fluid, reduction of oncotic blood pressure, insufficiency of lymph circulation and return of fluid from the tissues to the blood, the inclusion of mechanisms that actively inhibit sodium and do in the body. There are several phases in the formation of edema. In the first phase, there is an increase in mass associated with water fixed to the basic substance of the connective tissue of water. When the mass of bound water levels the interstitial pressure to atmospheric (normally this value is 6–7 mm Hg below atmospheric pressure), a second phase of watering develops, characterized by accumulation of free interstitial fluid — visible edema. During the formation of edema, a number of compensatory mechanisms are activated, aimed at preventing, and, if possible, eliminating edema, the lymphatic drainage increases sharply, finely dispersed proteins from the interstitial fluid are actively washed out, which reduces its colloid osmotic pressure. Visible edema does not develop until the negative pressure of interstitial fluid is equalized with or exceeds the atmospheric pressure. If the reserve capacity of the body increases, and visible edema has not yet been observed, they are talking about a pre-condition. The uniformity of the mechanisms of formation of edema in animals and in humans can be attributed to the typical pathological processes. Like any typical pathological process, the effect of edema on the body is damaging, but it also has a protective and adaptive value for the body. The development of edema leads to mechanical compression of tissues and impaired blood circulation in them. Excess interstitial fluid impedes the metabolism between the blood and cells. Owing to the violation of the trophism, edematous tissues are more easily infected, sometimes the development of connective tissue in them is noted. If the edematous fluid is hyperosmolar (for example, in patients with cardiac edema that interfere with the salt regime), dehydration of cells occurs with a painful thirst, fever, anxiety, etc. If the edema fluid is hypo-osmolar, cell edema develops with clinical signs of water poisoning. Disruption of electrolyte balance in edema can lead to disruption of the acid-base state of body fluids. The risk of edema is largely determined by its localization. The accumulation of fluid in the brain cavities, the cardiac bag, in the pleural cavity disrupts the functions of these important organs and is often life threatening. From protective-adaptive reactions, the following should be pointed out: the transfer of fluid from vessels to tissues promotes the release of blood from (sometimes toxic) substances dissolved in it and the preservation of the iso-osmolarity of liquid organisms lowland; Edematous fluid helps to reduce the concentration of various chemical and toxic substances in the blood, reducing their pathogenic effect. When inflammatory, allergic, toxic and some other types of edema due to difficulty in the outflow of blood and lymph from the source of damage (edematous fluid squeezes the blood and lymph vessels), there is a decrease in absorption and spread throughout the body of various toxic substances. 12.8.7. Principles of treatment of water and electrolyte disorders The most important links in the treatment of water and electrolyte disorders are: 1) the restoration and maintenance of the normal volume of circulating blood and other aquatic spaces of the body; 2) the elimination of the most dangerous imbalances of electrolytes and changes in the acid-base state; 3) restoration and maintenance of diuresis at a level that ensures the balance of water and electrolytes in the body; 4) ensuring the normal distribution of fluid volumes and electrolytes by sector. Meaningful implementation of these measures is impossible without establishing the reasons for the development of water and electrolyte disorders, the correct interpretation of clinical symptoms and laboratory data. An important place in the correction of water and electrolyte disorders belongs to infusion therapy (a treatment method aimed at restoring and maintaining the normal volume and electrolyte composition of body fluids), drug therapy of those pathological conditions that led to a failure of water and electrolyte metabolism, and appropriate diet therapy.

12.9. PATHOPHYSIOLOGY OF MINERAL EXCHANGE 12.9.1. Macroelement metabolism disorders Proteins, lipids, carbohydrates, nucleic acids of the human body and animals consist mainly of carbon, oxygen, hydrogen and nitrogen. A number of other chemical elements are also necessary for the organism to exist, which can be conditionally divided into macroelements (Ca, P, K, Na, S, Cl, Mg) and trace elements (Fe, Cu, Zn, Mn, Se, Mo, Cr, I, Co, F), according to daily needs and content in the body. Sodium metabolism disorders The share of sodium - the main cation of extracellular fluid, which determines its osmolarity, accounts for more than 90% of all cations of blood plasma. The third part of sodium is bound in the bone tissue, the other ions are freely exchanged. The normal serum sodium concentration in adults is 130-145 mmol / l, in erythrocytes - 13-22 mmol / l. Na + / K + -ATPase, which is part of cell membranes and actively removes sodium ions from the cytoplasm into the extracellular environment, supports the sodium gradient. It forms an electrochemical potential on the cell membrane, providing the functions of excitability and conduction of the nervous and muscular tissues. Sodium plays a leading role in maintaining the osmotic pressure of the extracellular fluid and its volume, participates in the regulation of the acid-base state, in the transport of carbon dioxide, in the active transfer of glucose and amino acids into the cell, in maintaining the spatial configuration of biomolecules. The kidneys play a leading role in maintaining sodium homeostasis, which is contained in a normal diet in amounts several times bigger than the body’s need. The main factors regulating renal excretion of sodium are angiotensin-II and aldosterone, which reduce the excretion of ion during periods of limited intake from food, as well as atrial natriuretic factor (secreted by the atria when they are stretched, caused by an increase in blood pressure, sometimes associated with an increase in plasma volume) stimulating the excretion of sodium. Stimulation of the thirst center, as well as the release of vasopressin (antidiuretic hormone - ADH) from the secretory granules in response to an increase in the osmotic pressure of the intercellular fluid, allow the normal concentration of sodium to be restored by increasing the volume of water in the body. Hyponatremia - serum sodium concentration below 130 mmol / l. There are relative and absolute hyponatremia. Absolute hyponatremia occurs with a general deficiency of sodium in the body. Sodium deficiency in the body, due to its insufficient supply, can be caused by inadequate parenteral nutrition, and also occurs when patients with cardiovascular insufficiency are forced to follow a salt-free diet for a long time. Excessive loss of the macroelement through the kidneys is observed in the polyuric phase of acute renal failure, treatment with diuretics, inadequate mineralocorticoid production (Addison's disease, etc.) and some other diseases. Sodium can be lost through the skin with excessive perspiration, burns, generalized dermatitis and through the gastrointestinal tract with prolonged vomiting, diarrhea and bleeding. Relative hyponatremia develops with a normal or even increased total supply of sodium in the body due to its dilution in an increased volume of extracellular fluid, which, for example, takes place with water retention in the body under the action of ADH, with nephrotic syndrome. By the speed of development distinguish acute and chronic hyponatremia. Acute hyponatremia develops quickly, within a period of not more than 48 hours (with the administration of large amounts of sodium-free solutions to patients, for example, up to 15 liters of 5% glucose solution per day or more; with psychogenic polydipsia). Chronic hyponatremia is more common than acute. This condition can be observed in patients with edema (heart failure, liver cirrhosis, nephrotic syndrome, etc.) Hyponatremia can be combined with increased, normal and reduced osmolarity of extracellular fluid. On this basis, hypertonic, isotonic and hypotonic hyponatremia are distinguished. Hypertensive (translocation) hyponatremia occurs when water moves from the cells into the extracellular space. It can be caused by a rapid increase in the content of glucose in the blood plasma or another osmotically active substance, it is observed most often in diabetes mellitus or in the case of intravenous administration of significant amounts of glucose or mannitol in a short time. The concentration of sodium contained in the blood plasma is reduced due to dilution. This condition is characterized by dehydration of cells. Isotonic hyponatremia occurs due to dilution of blood while isotonic liquids, that do not contain sodium, are delayed in the extracellular space (for example, while intravenous infusion of isotonic glucose). Hypotonic (hypo-osmolar) hyponatremia is characterized by an excess of water in relation to sodium concentration in the body, divided into hypervolemic, normovolemic and hypovolemic. Hypervolemic hypotonic hyponatremia develops with inadequate production of ADH (an increase in hormone production in the hypothalamus is observed with nausea, vomiting, emotional disorders, cerebral hemorrhages, inflammation of the brain; ectopic secretion of the hormone is possible in the tumor tissue - bronchi, thymus, mediastinum, prostate gland, etc.), in case of congestive heart failure (in case of severe hypersecretion of ADH in response to a decrease in cardiac output), the oliguric phase of acute renal insufficiency accuracy, primary psychogenic polydipsia. Manifested by headache, apathy, confusion, edema, an increase in body weight, blood pressure, muscle spasms, cramps. Normovolemic hypotonic hyponatremia may develop with marked hypothyrosis, withdrawal of large doses of glucocorticoids, marked reduction in the body's potassium content, administration of thiazide diuretics, etc. Hypovolemic hypotonic hyponatremia can develop with loss of sodium-containing fluid from burns, pathology of the gastrointestinal tract, through the kidneys: overdose of diuretics, primary hypocorticism, nephropathy with salt loss (including polycystic, chronic pyelonephritis, etc.), and after removal of fluid from the body cavity: effusion in the pleura, the rapid development of ascites (in all these cases, sodium loss is usually somewhat dominant over water loss). The same condition can develop with the loss of isotonic fluid through the gastrointestinal tract, kidneys, or skin under conditions of partial replacement of only water, but not sodium. The most common causes of hyponatremia of adults are treatment with thiazides, inadequate production of ADH in the postoperative period, polydipsia of mental patients; newborns and children - loss of gastrointestinal juices while vomiting, diarrhea, multiple enemas with tap water. Debilitated patients often have an increase of the permeability of cell membranes for sodium during normal or reduced activity of the sodium pump (“sick cell syndrome”). In this severe metabolic disorder, sodium ions move along the concentration gradient inside the cells, and potassium ions enter the extracellular space. The inadequate ionic composition of the cell contents leads to even deeper metabolic disturbances, which form a "vicious circle." In addition, in some patients, inadequate vasopressin secretion caused by the effect of stress may occur. The clinical manifestations of hyponatremia mainly concern disorders of the central nervous system - headache, nausea, vomiting, muscle spasm, drowsiness, disorientation, anxiety and inhibition of reflexes. Neurological symptoms of hyponatremia occur when serum sodium level decreases to 125-120 mmol / l. While hypovolemic hyponatremia clinical manifestations are mainly associated with a decrease in the volume of extracellular fluid: weakness, apathy, irritability, dizziness, hypotension, tachycardia, fainting on going from a horizontal to a vertical position, dry mucous membranes. With a rapidly developing hypo-osmolar hyponatremia, convulsions, coma, respiratory arrest, cerebral hernia, and death can occur. The basis of these severe disorders is the increased flow of water into the brain cells, since the osmotic pressure in the cells will be higher than in the extracellular fluid. Brain edema develops, intracranial pressure increases. With the slow development of hyponatremia in the body, adaptive reactions are activated — osmotically active substances begin to leave the brain tissue, which is accompanied by the release of water from the cells. This mechanism prevents the development of cerebral edema. Hypernatraemia always causes the redistribution of water between the intracellular and extracellular media in favor of the latter and cellular dehydration. Hypernatraemia corresponds to a shortage of water in relation to the body's sodium reserves. An increase in serum sodium concentration by 3-4 mmol / l corresponds to a deficit of 1 l of water in the body.The causes of hypernatraemia can be dehydration (profuse sweating with low sodium content in the excreted fluid, observed during heavy physical exertion and high ambient temperature); diabetes insipidus (excess water loss without sodium); failure of the mechanism of thirst; ingestion of seawater, unavailability of drinking water and excess sodium in the case of parenteral administration of hypertonic saline or sodium bicarbonate, as well as in failure of macronutrient elimination (renal failure; mineralocorticoid excess with congestive heart failure, nephrotic syndrome, renal artery stenosis, decompensated liver cirrhosis, Cushing and Conn syndromes). Symptoms of hypernatraemia are associated with the dehydration of primarily nerve cells — they shrink. Subarachnoid vessels and hemorrhages are possible, causing permanent brain damage and death. With the slow development of hypernatremia, the adaptive response of brain cells is activated — electrolytes are captured from the extracellular fluid, followed by water, which normalizes brain volume. Clinical manifestations of hypernatremia - thirst, shortness of breath, edema, venous congestion, hypertension, overweight, sweating, fatigue, anxiety, agitation, increased muscle tone, coma. The daily requirement for an adult human in sodium chloride is about 10 g. Potassium metabolism disorders Potassium is the main intracellular cation. The concentration of this mineral in cells is ten times higher than its content in extracellular fluid (in the serum of potassium contains 3.7-5.2 mmol / l, in erythrocytes - 77-96 mmol / l). In the cells of the body, potassium is in a free and bound form with proteins, glucose, phosphates and other compounds; extracellular fluid contains only 2% of its total amount, mainly in the form of ions, the concentration of which is maintained in a narrow range. The level of potassium in the blood plasma is not an indicator of its total content in the body. The main biological role of potassium is the creation of transmembrane potential, which provides, among other things, the excitability and conductivity of nerve and muscle cells. The main mechanism of its maintenance is the work of Na + / K + -ATPase. The distribution of potassium between the extracellular fluid and the intracellular medium depends on pH (acidosis contributes to the development of hyperkalemia, alkalosis - hypokalemia), some hormones (insulin, adrenaline, aldosterone), as well as the concentration of cations (for example, magnesium affects the activity of the Na + / K + pump). The total amount of potassium in the body and its content in the blood plasma are regulated by the change in the amount of excreted mineral by the kidneys, which at the same time are not able to retain potassium as effectively as sodium, and therefore the excretion of potassium is observed even while a significant lack of it in the body. Potassium is involved in maintaining the acid-base state, osmotic pressure, the transport of carbon dioxide by blood, promotes the absorption of glucose and calcium in the intestine, affects many aspects of intracellular metabolism (for example, activates glycolysis enzymes enolase and pyruvate kinase, participating in the synthesis of ATP). Hypokalemia can develop as a result of reduced intake (irrational parenteral administration, rarely deficiency in food) and / or increased excretion of potassium from the body through the kidneys (polyuric phase of acute renal failure, excess of mineralocorticoids: primary and secondary aldosteronism, Cushing syndrome, etc.), intestinal tract (diarrhea, vomiting, stenosis of the pyloric stomach, etc.), as a result of increased sweating. Hypokalemia may be caused by the movement of potassium into cells (alkalosis, excess of insulin, rapid cell proliferation after burns, injuries or fasting, treatment with β-adrenergic agonists, or increased β-adrenergic activity during stress, myocardial ischemia, etc.). With hypokalemia, there are disorders of the heart, neuromuscular, and renal functions: hypotension, muscle weakness, leg muscle spasms, reduced reflexes, constipation, vomiting, impaired concentration of the kidneys, leading to polyuria; ECG shows tachycardia, arrhythmias, ST segment depression, depression or inversion of the T wave, increased PR and QT intervals, pronounced U wave. Severe hypokalemia (less than 2 mmol / l) causes cardiac arrest in systole or paralysis of the respiratory muscles and death. Hyperkalemia develops when potassium is in excess in the body (intravenous administration of potassium preparations, canned blood transfusion); reduced potassium excretion(taking potassium-retaining diuretics or angiotensin-converting enzyme inhibitors, acute and chronic renal failure, mineralocorticoid insufficiency, for example, in Addison's disease); the output of potassium from the cells (acidosis, lack of insulin, catabolic states during fever, trauma, sepsis, etc.). Neurological symptoms of hyperkalemia include irritability, anxiety, paresthesias, weakness, flaccid paralysis. On the ECG of patients, an increase in the amplitude and sharpening of the T wave, then flattening of the P wave until its disappearance, expansion of the QRS complex, lengthening of the PQ interval, bradyarrhythmia are noted first of all. Severe hyperkalemia (13 mmol / L) causes cardiac arrest in diastole. The daily requirement of an adult in potassium is 2-5 g. Disorders of calcium and phosphorus metabolism An adult human body contains about 1000 g of calcium and 600 g of phosphorus, 99% of calcium and 85% of phosphorus deposited in the skeleton in the form of hydroxyapatite crystals. Calcium and phosphate are contained in blood serum in the form associated with proteins and other compounds, as well as in the form of ions. Ionized forms of calcium and phosphate are physiologically active. The content of total calcium in blood serum is normally 2.3-2.7 mmol / l, ionized - 1.1-1.4 mmol / l, inorganic phosphorus - 0.7-1.4 mmol / l. Calcium and phosphorus homeostasis is influenced by parathyroid hormone, calcitonin and calcitriol, the main organs of which are bones, kidneys and intestines. Parathyroid hormone stimulates the release of calcium and phosphate from bone tissue and the renal synthesis of calcitriol, as well as enhances calcium reabsorption and suppresses phosphate reabsorption in the kidneys. Calcitriol activates bone resorption and enhances the renal reabsorption of calcium and phosphate and the absorption of calcium and phosphate in the intestine. Calcitonin inhibits osteoclastic resorption, thereby reducing the release of calcium and phosphate, and also promotes the entry of phosphate into bone cells and periosteal fluid.

The functions of phosphorus in the body are not limited only to the formation of the mineral component of the bone. It is a part of nucleic acids, phosphoproteins and phospholipids, participates in the metabolism of proteins, lipids and carbohydrates, the formation of macroergic compounds (ATP, creatine phosphate, etc.), maintaining acid-base balance, is necessary for the activation of a number of enzymes and normal functioning of nerves and muscles. Calcium ions are involved in muscle contraction, release of neurotransmitters, control of excitability, intracellular metabolism, blood coagulation, maintenance of membrane integrity, transmembrane transport, release of substances synthesized in the cell (including hormones), entry of substances into the cell by phage and pinocytosis, bone mineralization; are cofactors of many enzymes and non-enzymatic proteins. Calcium acts on a variety of metabolic processes, performing the function of an intracellular messenger (including in combination with calmodulin it mediates the transmission of regulatory signals). The concentration of free calcium ions in the cytosol, maintained in the range of 0.1-10 μmol / l, depends on the activity of Ca2 + -ATPase, calcium channels and the concentration of calcium in the extracellular fluid. A number of hormones (a1-adrenergic catecholamines, vasopressin, etc.) change the permeability of calcium membranes, thereby regulating its entry into the cell, affecting the Na + / Ca2 + exchanger. It is also possible to mobilize calcium from the mitochondria and the endoplasmic reticulum, and its accumulation in these organelles. Under physiological conditions, there is a constant renewal of bone tissue - its resorption proceeds in parallel with the formation of the osteoid and its mineralization. In case of various hormonal regulation disorders (an excess or deficiency of calcitriol, parathyroid hormone, calcitonin, glucocorticoids, estrogens and androgens, thyroid hormones, insulin, glucagon, somatotropin), as well as disturbances in calcium and phosphate metabolism, dynamic equilibrium is stabilized.

Diseases with impaired calcium and phosphorus metabolism include: rickets and osteomalacia, osteoporosis, hyperparathyroidism (generalized fibrous osteodystrophy, Recklinghausen's disease), hypoparathyroidism (parathyroplasty tetany), renal osteodystophy, paraneoplastic hypercalcemia. In addition, hereditary forms of calcium and phosphorus metabolism disorders (familial hypophosphatemic rickets) are distinguished. An increase in the concentration of intracellular calcium, recorded in pathology, may cause impairment of function and even cell death in various organs and tissues of the body. The displacement of calcium from the complex with calmodulin by divalent metal ions (Cu, Zn, Co, Mn) causes the inhibition of cellular processes regulated by Ca2 + calmodulin and plays an important role in the pathogenesis of intoxication with these metals. Hypocalcemia is usually caused by an increase in calcium loss or dysregulation of its exchange between the intercellular fluid and bone tissue, as well as difficulty in absorption of the mineral in the intestine by large amounts of fat, oxalate or phytic acid. The main mechanism for the development of hypocalcemia with a lack of vitamin D in food and / or disruption of its metabolism in patients with chronic hepatic and renal failure, with nephrotic syndrome, malabsorption, treatment with anticonvulsant drugs (phenobarbital), hereditary deficiency of 1-a- hydroxylase is a decrease in the number of calcitriol and a violation Ca2 + absorption in the intestine. The decrease in the concentration of ionized calcium in the serum may also be caused by congenital or acquired hypoparathyroidism; pseudohypoparathyroidism type I (due to a genetic defect, the process of adenylate cyclase activation is impaired, therefore, the binding of parathyroid hormone to the receptor does not lead to the formation of cAMP) and type II (disrupted cell response to cAMP); magnesium deficiency (reduced secretion and parathyroid hormone effect); hyperphosphatemia or the introduction of large amounts of citrate (calcium binding anions); alkalosis (increased binding of calcium to albumin); tumor process (cell elements of the tumor with osteoblastic activity may delay calcium), chronic alcoholism, acute pancreatitis, etc. Clinical manifestations of hypocalcemia are largely associated with increased excitability of neurons and myocytes and convulsive syndrome. Patients have paresthesia, convulsions, muscle spasms, tetany, laryngospasm, Trusso (I) positive symptoms (tonic hand cramps, giving her the shape of an obstetrician's hand, in response to compression in the shoulder area) and Chvostek signs (one-sided contraction of facial muscles during percussion in passage of the facial nerve). Convulsions occur mainly in the flexor muscles. When tetany of flexor muscles of the lower extremities occur, the foot is bent inward, fingers bend to the sole ("horse foot"). The convulsions of the facial muscles are accompanied by a trismus and the formation of a "fish mouth". Pylorospasm may develop with vomiting, nausea, spasms of the muscles of the intestine, bladder. A spasm of the coronary vessels of the heart is accompanied by sharp pains in the region of the heart. A decrease in cardiac contractility leads to the development of congestive heart failure, hypotension, an increase in the QT interval. In severe hypocalcemia, tetanus of the respiratory muscles is fatal. Attacks of tetany can be provoked by various stimuli: pain, mechanical, thermal, hyperventilation. With prolonged hypocalcemia, hypocalcemic cataract, brittle nails, brittleness and dental caries can develop. Changes in the psyche: decreased intelligence, memory impairment, neurosis. An increase of calcium concentration in the blood is observed in primary or secondary hyperparathyroidism, which develops against the background of long-existing hypocalcemia (polyuric phase of acute renal failure - the period of diuresis recovery or gastrointestinal lesion), granulomatous diseases (increased formation of calcitriol by mononuclear phagocytes), granulomatous diseases (increased formation of calcitriol mononuclear phagocytes), granulomatous diseases treatment of thiazide diuretics (reduction of urinary calcium excretion), acromegaly, Cushing's syndrome, thyrotoxicosis, idiopathic hypercalcemia in infancy and others. The causes of hypercalcemia while tumor growth may be the secretion of the peptide by tumor cells similar to parathyroid hormone, excessive production of prostaglandin E, tumor necrosis factor-α or IL-1 activating osteoclasts and bone resorption in the presence of metastasis. An increase in serum calcium concentration is detected while acidosis. Hypercalcemia is manifested by weakness, fatigue, hypotonia of the muscles of the lower and upper extremities, pain in the feet, thirst, loosening and loss of teeth, weight loss. The main symptoms of renal hypercalcemia are polydipsia, polyuria, hypoisostenuria, alkaline urine reaction. The bilateral nephrocalcinosis develops, sometimes a hydronephrosis that at a long current can lead to uremia. Patients are worried about dyspeptic disorders (anorexia, nausea, vomiting, constipation), frequent bouts of renal colic, increased blood pressure. When the visceropathic form of hypercalcemia occur peptic ulcers of the duodenum, stomach, intestines often develop, which are prone to recurrence and the development of bleeding. There may be sleep disturbance, memory loss, depression, confusion. In severe cases, there is a change in personality, stupor, coma. On the ECG of patients, shortening of the ST segment, QT interval, and ventricular arrhythmias are recorded. The deposition of calcium phosphate in the organs (kidneys, cornea, blood vessels, gallbladder, etc.) is observed if hypercalcemia is accompanied by normal or elevated serum phosphate levels. The restoration of calcium in the serum in the event of its increase or decrease is carried out by hormonal regulation of the processes of calcium absorption in the intestine, its reabsorption in the kidneys and bone resorption (Fig. 12- 50, 12-51). Hypophosphatemia may be the result of inadequate total parenteral nutrition or reduced absorption of phosphate from the gastrointestinal tract or its increased losses through the gastrointestinal tract or kidneys in vomiting, diarrhea, malabsorption, deficiency of vitamin D, hyperparathyroidism, use of thiazide diuretics, hypomagnesemia, familial hypophosphatemic rickets, alcoholism and others. The concentration of phosphate in the blood serum may also decrease with increased use of its cells (during wound healing and after fasting), as well as in a result of the transfer of phosphate into cells while alkalosis. Disorders of the central nervous system in hypophosphatemia (memory impairment, confusion, discoordination of movements, lethargy) happen due to decrease in the formation of macroergic phosphate-containing compounds. Developing hypoxemia and hypoxia are associated with a decrease in the content of 2,3-diphosphoglycerate in erythrocytes. Along with this chronic giphosphosphatemia leads to the development of signs of rickets and osteomalacia, manifested by bone pain and fractures. Patients have muscle weakness, in severe cases - acute rhabdomyolysis (the disintegration of the striated muscle tissue), as well as a decrease in myocardial contractility with a decrease in cardiac output and blood pressure. A decrease in the level of ATP and other phosphate-containing compounds in leukocytes and blood platelets leads to the development of infections and the occurrence of bleeding. Hyperphosphatemia most often develops with acute and chronic renal failure, as well as with increased consumption of phosphate (when feeding infants with undiluted cow's milk) or vitamin D, hypoparathyroidism and pseudohypoparathyroidism, when moving phosphate from cells into the extracellular fluid while breathing acidosis, diabetic acidosis , phosphate release under catabolic conditions (tumor lysis, rhabdomyolysis). Severe hyperphosphatemia, leading to the suppression of hydroxylation of 25-hydroxycholecalciferol in the kidneys and impaired calcitriol formation, as well as the formation of metastatic hydroxyapatite deposits, causes hypocalcemia due to these two mechanisms. Most of the clinical manifestations of hyperphosphatemia are associated with the development of hypocalcemia and the deposition of calcium phosphate in the tissues (cornea, blood vessels, kidneys, lungs, etc.). Calcification of the heart muscle causes conduction disturbances and arrhythmias, and joints, arthralgia and restriction of their mobility. In severe cases, hypocalcemic tetany develops. The daily requirement of an adult for calcium is 0.8-1 g, in phosphorus - 1-1.5 g. Magnesium metabolism disorders Of the 25 g of magnesium contained in the body of an adult, 50-60% is concentrated in the bones, 1% in the extracellular fluid, and the rest in the cells of the tissue (among the cations, the concentration in the cells magnesium is inferior only to potassium). 25-35% of serum magnesium is associated with proteins (mainly albumin), a small part is present in complex compounds. Physiologically significant is ionized (free) magnesium. Hypoalbuminemia causes a decrease in the total magnesium content in serum, while the amount of ionized magnesium remains normal. Magnesium is a cofactor or activator of more than 300 enzymes involved in the metabolism of proteins and nucleic acids (peptide hydrolase, arginase, aminoacyl-tRNA synthetase, DNA and RNA polymerase, polynucleotide phosphorylase, DNase, RNase, etc.), carbohydrates (most glycosylase enzymes ); takes part in the transmembrane transport of ions (supports the level of potassium ions in the cell, taking part in the work of the Na + / K + pump). By activating the enzymes of the Krebs cycle and participating in the conjugation of oxidation and phosphorylation (ATP-synthase reaction), Mg2 + affects the cell's energy potential. Interacting with calcium, magnesium affects the permeability of cell membranes and their electrical properties, being a regulator of the mechanism of conduction of neurons and myocardial fibers. Hypomagnesemia (observed in approximately 10% of hospital patients) can be caused by increased magnesium losses from the gastrointestinal tract (vomiting, diarrhea, gastric drainage); absorption disorder - malabsorption syndrome (tumors and resections of the gastrointestinal tract, enteritis, pancreatitis); taking medications that increase renal excretion (loop diuretics, gentamicin, cisplatin, cyclosporine, etc.); impaired renal tubule function; chronic excess mineralocorticoids; chronic alcoholism (reduced food intake, impaired absorption, increased excretion); protein-calorie starvation (hypoalbuminemia is accompanied by a decrease in serum magnesium content associated with proteins). A significant decrease in the content of magnesium in the body, which violates the cAMP- dependent processes of parathyroid hormone secretion and the post receptor transmission of the hormonal signal in target tissue cells, leads to the development of hypocalcemia. Hypomagnesemia is accompanied by hypophosphatemia. The development of potassium deficiency in hypomagnesemia is associated with its increased excretion by the kidneys and, at the same time, dysregulation of the activity of the Na + / K + pump (Mg2 + is a cofactor of Na + / K + -ATPase). Clinical manifestations of hypomagnesemia (with a decrease in the ion concentration below 0.5 mmol / l) are often caused by the following disadvantages of potassium and calcium: nausea, vomiting, anorexia, insomnia, mood changes, mental disorders, delusions, hallucinations, ataxia, tremor, chorea-like movements, seizures , muscle weakness, tetany, positive symptoms of Chvostek and Trusso, paresthesia. The ECG recorded an increase in the duration of the intervals of PR and QT, ST segment depression, flattening of the T wave; possible tachyarrhythmia, atrial fibrillation. The causes of hypermagnesemia (acquiring clinical significance with a concentration of magnesium ions of at least 2.0 mmol / l) may be the use of magnesium-containing drugs (antacids, magnesium sulfate, etc.) and a decrease in magnesium excretion, which occurs in patients with renal insufficiency and adrenal insufficiency ( Addison's disease), increased intake of magnesium in the blood with increased cellular catabolism. Excess magnesium in the body is manifested by nausea, vomiting, sweating, drowsiness, muscle weakness, hypotension due to peripheral vasodilation, a decrease in deep tendon reflexes, and soft tissue calcification. Magnesium in a concentration of not less than 5.0 mmol / l in the serum, affects the conductivity of the heart muscle, causes bradycardia, atrioventricular block. Severe hypermagnesemia (ion concentration in excess of 7.5 mmol / l), which develops only in case of renal failure, causes respiratory paralysis and cardiac arrest.

The content of magnesium in blood serum is normally 0.7-1.1 mmol / l. The daily requirement of an adult human organism in magnesium is 0.3-0.5 g, of which 30-40% are absorbed. 12.9.2. Microelement metabolism disorders Essential (irreplaceable) microelements at the present stage of development of science are Fe, Cu, Zn, Mn, Se, Mo, Cr, I, Co, F, for which the manifestations of true deficiency syndromes in humans are proven. As well as these microelements, As, B, Br, Li, Ni, Si, V. А.P. are indispensable for some animals. Avtsyn (1983) developed the concept and classification of pathological processes caused by deficiency, excess or imbalance of microelements in the body, and proposed for them the unifying name of "microelementoses". Iron metabolism disorders The body of an adult male contains 3-5 g of iron, women - 3-4 g, of which 65-70% of iron is part of erythrocytes and erythrocaryocytes; iron bound to ferritin and hemosiderin makes up 20% of its total amount; 15% is part of myoglobin; about 1% - in the composition of heme enzymes and proteins containing non-heme iron; the share of transport iron associated with transferrin accounts for 0.1-0.2%. Iron is part of the prosthetic groups of redox enzymes (oxidoreductases), provides electron transport by cytochromes and iron seroproteins, transport and deposition of O2 and CO2 by hemoglobin and myoglobin. Iron is involved not only in the processes of oxidative phosphorylation and free oxidation, but also in maintaining the secondary and tertiary structure of DNA and RNA, the transformation of amino acids by the radical (phenylalanine into tyrosine, etc.), activation of β-oxidation of acyl- CoA, and an increase in the activity of peptide hydrolases. In extracellular fluids, iron is found in the form of transferrin and lactoferrin. Intracellular iron compounds can be divided into hemoproteins, the structural element of which is hem (hemoglobin, myoglobin, cytochromes, catalase, peroxidase, etc.); non-heme iron-containing enzymes (acyl-CoA-dehydrogenase, prolyl oxidase, xanthine oxidase, etc.); ferritin and hemosiderin of internal organs; iron loosely bound to proteins and other organic substances. Iron deficiency (hyposiderosis) is one of the most common human microelementosis. Hyposiderosis can develop with insufficient intake of iron from food, as well as as a result of impaired acid-forming functions of the stomach (atrophic gastritis, total and subtotal gastroectomy), impaired intestinal absorption (extensive resection of the small intestine, chronic enteritis, competitive absorption of zinc and copper, lack of ascorbic acid, promoting the transfer of iron in the bivalent form). Acceptance of nonsteroidal antirheumatic drugs and some antibiotics may also cause the development of iron deficiency states. A common cause of iron deficiency is chronic bleeding from the urogenital system and the gastrointestinal tract (including with gastric ulcer, malignant tumors, polymenorrhea, etc.). The need for iron increases during pregnancy, lactation, growth of the body. The first consequence of the excess consumption of iron over its entry into the body is the depletion of its depot in the liver, spleen and other organs and tissues. Further development of hyposiderosis leads to a variety of tissue and organ damage, many of which occur even before the onset of iron deficiency anemia. Non-specific signs of iron deficiency are expressed in mild fatigue, dizziness, headaches, increased excitability or, on the contrary, depression. Children have bad attention, memory worsens, mental development is slowed down. In some patients, there is a lack of appetite or taste perversion (geophagy, pagophagy, amylophagy). Chronic iron deficiency causes damage to the skin and its derivatives (dry and cracked skin, brittle nails, hair loss), mucous membranes of the mouth, pharynx, esophagus, stomach, upper respiratory tract (angular stomatitis, glossitis, esophagitis, laryngo and pharyngotracheitis, gastritis) . When anemization occur, symptoms associated with insufficient oxygen supply to the tissues develop: muscle weakness (also caused by a violation of myoglobin metabolism), shortness of breath, palpitations, and fainting. Iron deficiency causes immunosuppression. Iron-deficient hypochromic microcytic anemia is the most severe consequence of hyposiderosis, leading to the development of hypoxia, damage to all organs and tissues, permanent disability, or even death. First of all, tissues that are sensitive to oxygen starvation - nervous and epithelial - suffer from hypoxia. The reasons for the development of hypoenergetic states in the tissues, along with the lack of oxygen, are disturbances in the mitochondrial electron transfer chain associated with iron deficiency, which is part of cytochromes and iron-gray proteins. It is assumed that disorders of the nervous system with iron deficiency are also associated with changes in the activity of dopaminergic receptors and the metabolism of γ-aminobutyric acid. Hypersiderosis can occur with excessive iron content in food, increased absorption of iron in the intestine, inadequate parenteral administration of iron preparations in the treatment of refractory anemias or multiple blood transfusions (transfusion siderosis), with chronic enhanced hemolysis with thalassemia. Professional siderosis (iron deposits in the lungs) is often observed in miners and metallurgists. Hypersiderosis can be local (for example, siderosis of the eyeball) and generalized. Excess iron accumulates mainly as hemosiderin in the cells of the reticuloendothelial system of the liver and spleen, which over time can lead to liver fibrosis. Myocardial damage in hypersider disease contributes to the development of heart failure. The toxic effect of excessive concentrations of iron is largely due to its participation in free radical processes (Fenton reactions). Prolonged overload of the body with iron leads to the accumulation of ferritin and hemosiderin in the cells, contributing to the disruption of the integrity of the lysosomal membranes and the release of proteolytic enzymes that damage cellular structures. Acute iron poisoning can cause necrotic gastroenteritis, liver necrosis, renal failure, or even death.In humans, two hereditary diseases affecting the metabolism of iron are known - atransferrinemia, the mechanism of which has not been fully studied, and primary hemochromatosis, the main cause of which is excessive absorption of iron in the intestine. Iron deposits in the cells of the liver, spleen, pancreas, heart, adrenal glands, developing in hereditary hemochromatosis, lead to disruption of the structure and functions of these organs (liver cirrhosis, diabetes, hepatosplenomegaly, heart failure, etc.). In animals, the following genetic defects of iron metabolism are known: "sex-linked anemia " in mice (sla); microcytic anemia in mice (mk) and Belgrade anemia in rats (b) are autosomal recessive mutations leading to the development of severe hypochromic anemia. Both excess and iron deficiency have an embryotoxic effect, manifested in impaired development of the nervous and immune systems. With normal nutrition, about 15 mg of iron per day is supplied to the human body, 1-1.5 mg is absorbed from the intestines, and for some types of anemia, up to 2-3 mg per day. Iron is excreted from the body through the bile, through the kidneys and sweat glands, as well as with menstrual blood. With the breakdown of hemoglobin, 90% of the iron in the body is reutilized, and 10% must be replenished by food. Normally, the concentration of serum iron in men is 14-25 µmol / l, in women - 11-22 µmol / l. Copper metabolism disorders Copper is one of the main essential trace elements that make up the most important enzymes that mediate vital processes in the body, such as tissue respiration and erythropoiesis. Copper, taking part in the metabolism and energy (including oxidative phosphorylation and free oxidation), affects the reproduction, growth and development of the organism. Copper is needed to mobilize iron from reserves, it also contributes to its inclusion in the structure of heme cytochrome oxidase and hemoglobin, being respectively an important factor in erythro and granulocytopoiesis. As part of the dopamine-p-hydroxylase active center, copper is involved in the synthesis of neurotransmitters (the conversion of dopamine to norepinephrine). Copper is also necessary for the normal course of keratinization and pigmentation of the skin and hair, the formation of myelin, the synthesis of various derivatives of connective tissue, etc.

Copper ions activate ascorbate oxidase, inhibit xanthine oxidase, are involved in maintaining the secondary and tertiary structure of DNA and RNA. Copper is part of cytochrome oxidase (component of the chain of electron transfer in mitochondria), tyrosinase (catalyzing the oxidation of tyrosine, the transformation of a number of phenols into quinones, from which melanins are formed as a result of further oxidation). The copper carrier is ceruloplasmin (ferroxidase), which has oxidative activity. Copper along with zinc is part of the subunit of cytosolic superoxide dismutase, interrupting free radical processes (protecting cell structures from the damaging effects of superoxide anion radicals). Copper-containing amine oxidases are involved in the catabolism of many amines, such as histamine, tyramine, putrescine, spermine and others, in the oxidation of adrenaline. The causes of hypocuprea in humans can be a nutritional deficiency of copper with irrational artificial feeding of newborns, inadequate parenteral nutrition; competitive absorption of excess zinc in the intestine. The model of food deficiency of copper, obtained in rats and pigs, is characterized by impaired ovulation and abortion. Copper deficiency leads to the development of microcytic anemia and leukopenia. Hypocouparea in humans causes depigmentation of the skin and its derivatives, in rodents - achromothrichia, which is associated with a violation of tyrosinase synthesis. The lack of copper, which is part of lysyl oxidase, an enzyme necessary for the formation of covalent crosslinks between collagen and elastin polypeptide chains, can cause defects in the formation of connective tissue, including the cardiovascular system (vasopathy, aortic dissecting aneurysm) and skeleton (osteopathy with changes in the bones). Impaired catecholamine synthesis and demyelinization in hypocuprecreosity associated with cytochrome oxidase deficiency and dopamine β-hydroxylase, are due to nervous system damage (spinal demyelinating neuropathy in sheep in poor copper regions of Australia, dyscoordination of movements in humans).

A lack of copper in the mother’s body causes severe disturbances in the development of the nervous system, connective tissue defects, reduced immunity in the fetus, and its death is possible. Hereditary forms of hypocuprosis include Menkes syndrome (“curly hair disease” with severe damage to the central nervous system), in which the functions of a number of copper-containing enzymes are violated - tyrosinase (hair depigmentation), sulfidoxidase (impaired keratinization), lysiloxidase (connective tissue damage: aneurysm, emphysema, osteopathy), dopamine-p- hydroxylase and cytochrome oxidase (neurodegenerative effects). Much of the copper in the cells is bound to metallothionein, a protein that contains many cysteine residues and plays an important role in neutralizing potentially toxic heavy metal ions. Excessive accumulation of copper in the liver cells, occurring in some hereditary diseases, as well as under the influence of toxic substances, may be associated with dysregulation of the synthesis of metallothionein and, in turn, lead to the induction of the biosynthesis of this protein: a “vicious circle” is created. An excess of copper leads to damage to the cytoskeleton and membranes, including lysosomal ones, which also contributes to the further accumulation of copper in the cells due to the violation of the excretory function of lysosomes. Increased accumulation of copper in the liver, basal ganglia of the brain, cornea of the eyes and other tissues with a hereditary disorder of its metabolism, known as Wilson's Conovalov's disease, or hepatocerebral dystrophy (decrease in copper excretion with bile, decrease in ceruloplasmin concentration in plasma and copper inclusion, hyperaminoaciduria) , it causes the development of cirrhosis, arthritis, cataracts, motor neurological disorders, hemolytic anemia. The mechanism of violation of the synthesis of ceruloplasmin in hepatocerebral dystrophy is not fully understood. Along with the genetically determined defect of lysosomes of hepatocytes, determining the violation of the most important mechanism for regulating the balance of copper in the body - its excretion with bile, the formation of copper complexes with amino acids that are not absorbed in the renal tubules is possible. Degeneration of the liver parenchyma, proliferation of connective tissue due to damage to the enzyme systems of hepatocytes accumulating copper ions. The accumulation of copper in the tissues is associated with its release from damaged hepatocytes. The development of intravascular hemolysis is due to copper inhibition of the erythrocyte enzyme systems.

Genetic defects of copper metabolism in animals are similar to those in humans and can be considered as their models. Also known are professional (in workers of copper mines and chemical enterprises, welders of non-ferrous metals) and hemodialysis hypocuprosis. In severe hemolysis (hemoglobin in the urine), acute renal failure with anuria and uremia, hemolytic jaundice, and anemia may develop. In the presence of highly dispersed copper dust in the upper respiratory tract, acute casting fever occurs (chills, dry cough, headache, weakness, shortness of breath, fever). Allergic skin reactions are possible. Excess copper may have an embryo toxic effect. The daily diet of adults should contain from 2 to 5 mg of copper, of which about 30% is absorbed. The normal content of copper in the serum of women is 13-24 µmol / l, for men - 11- 22 µmol / l. Zinc metabolism disorders Zinc-containing and zinc-activated enzymes (more than 200 are known) are involved in the synthesis and breakdown of carbohydrates, lipids, proteins and nucleic acids, cell division, tissue respiration, playing an important role in the processes of reproduction and growth of the body, in the photochemical act of vision, osteogenesis, keratinization , the immune response, etc. These enzymes belong to all six known classes (carboxypeptidases A and B, alkaline phosphatase, dipeptidase, carbonic anhydrase, malate, glutamate, alcohol dehydrogenase, etc.), the largest number belongs to the class hydrolases. The trace element can either directly perform a catalytic function, being part of the active center of the enzyme, or stabilize its tertiary or quaternary structure, and also be a regulator of the activity of the enzyme. The biosynthesis of proteins and nucleic acids is carried out with the versatile participation of zinc. The trace element is necessary for the functioning of all nucleotidyl-transferases, DNA and RNA polymerases, thymidine kinases, reverse transcriptases, to stabilize the helical structure of DNA and RNA. Taking part in the formation of a polysome and being part of aminoacyl-tRNA synthetases and polypeptide chain elongation factors in mammals (for example, eEF-1), zinc plays an important role in the translation process.

Zinc is involved in the formation of the active form of insulin. Being a part of cytosolic superoxide dismutase, the trace element inhibits free radical oxidation in cells. The glucocorticoid receptor - hormones that affect all types of metabolism and play an important role in adapting to stress, is a zinc-containing protein. Zinc is involved in the conformational changes that occur with retinol in the retina. The absorption of zinc in the small intestine is inhibited by copper, phosphate, calcium, phytate (contained in large quantities in yeast-free bread made from unrefined flour, which explains the widespread hypozincosis among the villagers of Iran); difficult with enteritis, intestinal tumors and cirrhosis of the liver. Zinc deficiency can occur in catabolic conditions, in particular in severe injuries and chronic hemolytic anemia. Iatrogenic deficiency is possible with parenteral nutrition, treatment with cytostatic and some other drugs. Hypozincosis can manifest as severe anemia, hepatosplenomegaly, physical retardation, dwarfism, hypogonadism, infertility, hypokeratic dermatitis, disruption of normal hairiness, alteration or loss of perception of taste and smell, suppression of immune reactions (reduction of lymphocyte differentiation, differentiation, loss of the proliferation and differentiation of lymphocytes, contor), derangement of the lymphocytes, dehydration, loss of perception of the taste and smell, reduction of the proliferation and differentiation of lymphocytes; Lack of zinc in the mother's body can cause weakness of labor, preterm labor, as well as hydrocephalus, micro- and anophthalmia, spinal curvature, heart defects in newborns. The hereditary disease associated with zinc deficiency is a hereditary enteropathic acrodermatitis caused by impaired zinc binding protein synthesis, which is necessary for normal intestinal absorption of zinc. It appears from the moment breastfeeding stops maternal milk containing zinc binding protein, is characterized by immunodeficiency, dermatitis, neurological disorders, delayed wound healing, symptoms of kwashiorkor, progressive loss of vision and other manifestations of zinc deficiency. Adema disease in cattle, similar to enteropathic acrodermatitis; mutation "lethal milk" in mice (lm), leading to the death of their offspring; testicular feminization syndrome in rats (Tfm), characterized by insensitivity to androgens and cryptorchidism; SM mutation (supermouse) are recessive autosomal mutations affecting zinc metabolism.Zinc vapor poisoning observed in electric welders working indoors, is manifested by headache, cough, hypersalivation, fever and leukocytosis. An excess of zinc has an embryotoxic effect. Excess zinc inhibits copper absorption in the gastrointestinal tract. The use of pharmacological doses of zinc for the treatment of Wilson-Konovalov disease is based on this. The body's daily need for zinc is 10-15 mg, of which 30% is absorbed. Normally, serum zinc content in adults is 11–18 µmol / L. Manganese Exchange Disorders Manganese is an activator or is part of a number of enzymes, among which are known hydrolases, oxidoreductases, transferases, lyases, ligases (pyruvate carboxylase, arginase, peptide hydrolase, amino acid decarboxylase, phosphotransferase, isocitrate dehydrogenase, and malate dehydrogenase). The trace element is necessary for gluconeogenesis and regulation of blood glucose, synthesis of glycoproteins and hemoglobin, it also stimulates the synthesis of cholesterol and fatty acids, participates in the formation of the helical structure of nucleic acids, provides peptidyltransferase reaction in the assembly of polypeptide chains. With manganese deficiency (hypomanganos), there is a decrease in the activity of glycosyltransferases, which play an important role in the synthesis of glycosaminoglycans, including in the bone matrix, and impaired sulfate incorporation into cartilage, causing anomalies of skeletal development with slowing ossification and growth retardation in humans and animals. The lack of trace elements violates the formation of the skeleton in the prenatal and postnatal period of life.

Hypomanganosis leads to the development of hypocholesterolemia associated with impaired activation of dimethylallyltransferase, and anemia caused by impaired hemoglobin synthesis. With the violation of the synthesis of cholesterol - the precursor of sex hormones associated with the effect of trace element deficiency on reproductive function in humans and animals. The effect of manganese deficiency on carbohydrate metabolism is manifested by the deterioration of glucose uptake associated with the death of β-cells of the islets of Langerhans under the action of a superoxide radical (a decrease in the activity of Mn2 + -superoxide dismutase). In humans, the genetic defects of manganese metabolism are unknown. Mice with an autosomal recessive mutation "pallid" (homozygotes) bring offspring with congenital disorders of coordination of movements, which is explained by the anomalous development of otoliths with a shortage of manganese. Excessive intake of manganese in the body leads to the formation in the bones of rickets-like changes ("manganese rickets"), complicates the absorption of iron and copper in the gastrointestinal tract, causing anemia. Professional manganosis in miners who regularly inhale manganese dust manifests itself in parkinson-like syndrome, manifested in a disorder of physical activity (letter disorder, “cocky gait”), mental disorders (euphoria, complacent); patients also develop asthenovegetative syndrome with depression of gonad function and pneumoconiosis. Elevated levels of manganese in pregnant women can lead to fetal death. An adult’s daily requirement for manganese is 2–7 mg. Normally, whole blood contains 30-50 μg / l manganese. Chromium exchange disorders Chromium provides the body's tolerance to glucose, enhancing the effect of insulin in all metabolic processes regulated by this hormone. The mechanism of this effect is probably related to the effect of Cr on insulin reception. The trace element is involved in the formation of the helical structure of nucleic acids; with a magnesium deficiency, it can activate phosphoglucomutase, which reversibly converts glucose-1-phosphate to glucose-6-phosphate.

Chromium deficiency, which develops in humans with prolonged irrational parenteral nutrition, is manifested by impaired carbohydrate metabolism (hyperglycemia, glycosuria) and lipids (an increase in the concentration of triacylglycerols and cholesterol, a decrease in high-density lipoprotein serum levels, an increase in atherosclerotic plaques). With professional hyperchromosis, ulceration of the nasal mucosa, dermatitis, and hepatosis may develop. In high concentrations, chromium compounds may have mutagenic and carcinogenic effects. Cr content in whole blood is 1.4-3.1 nmol / l. A decrease in the content of chromium in the blood is observed in gastrogenic iron deficiency and aplastic anemia, an increase in leukemia. Normal for an adult is considered the daily intake of chromium from food in the amount of 5-200 mg. Disorders of the exchange of selenium Selenium alone or with iron and molybdenum is present in a number of enzymes, such as some oxidoreductases, including glutathione peroxidase, transferase, etc. Glutathione peroxidase is part of the antioxidant cell system that protects the membranes from the toxic effects of hydrogen peroxide and lipid hydroperoxides. The synergist of the antioxidant action of glutathione peroxidase is vitamin E, which may also be involved in the metabolism of selenium, protecting it from oxidation. A microcell, selectively inhibiting gene transcription and taking part in redox processes, affects the metabolism of proteins, lipids and carbohydrates. Selenium has a modifying effect on the xenobiotic biotransformation enzymes. The relatively high concentration of selenium in the retina suggests its participation in photochemical reactions of light perception. Selenium-containing proteins are found in the spleen, testes and other organs. Lack of selenium in the body in people living in the selenium-deficient belt of China, in Transbaikalia and some other regions, is the cause of endemic cardiomyopathy — Keshan's disease (multifocal necrotic myocardial dystrophy) and a risk factor for coronary heart disease and myocardial infarction. Selenium deficiency can also develop with irrational parenteral nutrition or protein-calorie deficiency. Selenodeficiency leads to inhibition of immune responses, reducing antiviral and antitumor resistance of the organism. In severe cases, it may develop dilated cardiomegaly and congestive heart failure. In animals, selenium deficiency is characterized by growth and developmental delay, azo- spermia, alimentary muscular dystrophy (white muscle disease of farm animals), hepatosis, exudative diathesis, necrosis, and pancreatic fibrosis. Genetic defects in selenium metabolism include hereditary selenium-deficient fermentopathies (for example, glutathione peroxidase deficiency of erythrocytes and platelets), hereditary cystic fibrosis of the pancreas (cystic fibrosis), hereditary myotonic dystrophy. The endemic selenosis that is common in some regions (Utah, USA; New Zealand and others) and develops when the recommended daily dose of selenium is 5-6 times higher, is manifested by dermatitis, damage to the tooth enamel, anemia and nervous disorders, liver degeneration, and an enlarged spleen. , damage of nails and hair. Selenosis in cattle in endemic areas leads to the development of alkalosis, focal necrosis and cirrhosis of the liver, as well as intrauterine malformations. The daily requirement of an adult human organism in selenium is 0.2 mg on average. The normal content of selenium in serum is 53-105 mg / l. Molybdenum exchange disorders The lack of molybdenum in the body, which occurs most often during parenteral nutrition, is characterized by a decrease in the activity of molybdenum-containing enzymes: xanthine oxidase, which catalyzes the oxidation of hypoxanthine and xanthine to uric acid; sulfite oxidase converting sulfite to sulfate; aldehyde oxidase, oxidizing aldehydes to organic acids. The genetic defect of xanthine oxidase in humans causes the development of xanthinuria with a simultaneous decrease in the content of uric acid in serum and urine. The hereditary sulfitoxidase defect is characterized by severe impairments in the development of the nervous system, mental retardation, and lens ectopia. In the urine, the content of sulfites, sulfo-L-cysteine is increased in the practical absence of sulfates. It can be assumed that the identified changes occur both due to the accumulation of toxic amounts of sulfites in organs and tissues, and due to the lack of sulfates necessary for the synthesis of complex proteins, sulfogalactosilceramides and other molecules. Children suffering from this disorder die in the first years of life. The accumulation of excess amounts of molybdenum in humans and animals leads to diarrhea, impaired calcium-phosphorus metabolism and copper metabolism, deformation of bones, impaired function of the musculoskeletal system, infertility. Increased activity of xanthine oxidase leads to accelerated disintegration of purine nucleotides in the body, causing an increase in the concentration of uric acid in the blood serum and its accumulation in the form of salts in the joints and tendons - molybdenum gout develops (Kowalski disease). Chronic occupational molybdenosis is characterized by polyarthralgia, arthrosis (accumulation of uric acid salts in the joints), hypotension, anemia, leukopenia.

The daily requirement of an adult in molybdenum is 0.5 mg. The content of molybdenum in the blood plasma is normal - 13.5-15.2 μg / l, with anemia of various origins it may decrease. Iodine metabolism disorders Iodine-containing thyroid hormones thyroxin and triiodothyronine regulate the activity of the central and peripheral nervous system, the growth and differentiation of tissues, the metabolism of proteins, carbohydrates and lipids, water-electrolyte and energy metabolism, affect the functions of the cardiovascular system and the digestive tract, hematopoiesis, etc. . Endemic goiter, which develops with a lack of iodine in the body, is characterized by a compensatory enlargement of the thyroid gland. Chronic iodine deficiency, which causes a decrease in the synthesis of thyroid hormones, in children leads to cretinism (mental retardation, dwarfism, underdevelopment of the skeletal system); fatigue, arthralgia, bradycardia). The ingestion of substances blocking the utilization of iodine by the thyroid gland, damage to the liver and gastrointestinal tract, or impaired intrathyroid iodine metabolism can cause the development of sporadic goiter in people living in iodine-safe areas. Several genetic defects of iodine metabolism are known, which are the cause of "familial goiter": impaired synthesis of thyroxin from monoiodotyrosine and diiodotyrosine; blood circulation of an atypical protein that firmly binds iodine; inability of the gland to concentrate iodine. Violation of deiodination of monoiodotyrosine and diiodotyrosine is caused by a defect in the synthesis of specific deiodinase, leading to increased iodine loss from the body. In Pendred syndrome, a violation of thyroid hormone synthesis is associated with a defect in thyroperoxidase (one of the symptoms is hearing loss).

If you are sensitive to iodine, allergic reactions can occur (angioedema, urticaria). Contact with iodine can cause dermatitis. Inhalation of iodine vapor affects the upper respiratory tract. When concentrated iodine solutions are ingested, severe burns of the digestive tract develop, mucous membranes acquire a characteristic yellow color. The minimum daily need for iodine in adults is 100–150 mcg per day, in pregnant and lactating women - 230–260 mcg per day. Normally, serum contains 45-90 mmol / l iodine. Cobalt exchange disorders Cobalt in vitamin B12 and cobamide coenzymes (methyl- and deoxyadenosylcobalamin), respectively, affects blood formation, the metabolism of proteins, lipids and carbohydrates and nucleic acids, reproductive function and growth of the body. Cobalt ions increase the activity of peptidhydrolases, arginase, aldolase, phosphoglucomutase and other enzymes, and are involved in the stabilization of the secondary and tertiary structure of DNA and RNA. Inadequate intake of cobalt in the composition of vitamin B12 is accompanied by clinical manifestations (pernicious anemia, atrophy of the mucous membrane of the gastrointestinal tract, funicular myelosis, etc.) due to cobamide coenzyme deficiency (see section 12.3.2). Cattle in areas with low cobalt content in the soil suffers from an endemic disease, known as “shrub disease”, characterized by exhaustion, anemia, liver steatosis, osteodystrophy. Staying under production conditions in contact with powdered cobalt compounds causes damage to the respiratory organs (chronic bronchitis, pneumonia and pneumosclerosis), blood formation, cardiovascular and nervous systems, as well as the development of allergic dermatitis.

The excess of cobalt in the body over its excretion, including the oxidative decarboxylation of pyruvate (cobalt in high concentrations can interact with lipoic acid), leads to myocardiodystrophy, damage to the nervous system, polycythemia. Disruption of iodine metabolism with an excess of cobalt in the body leads to hyperplasia of the thyroid gland. The combination of the above symptoms was called “the disease of beer lovers” in those years when cobalt chloride was added to the beer to stabilize the foam. The normal cobalt content in whole blood is 34-48 nmol / l. Fluorine exchange disorders Almost all of the fluoride in the body is concentrated in the bones and teeth, the surface layer of tooth enamel is most saturated with fluoride. The trace element is part of fluorapatite, necessary for imparting strength and acid resistance to bone tissue. Fluorine deficiency (hypoftorosis) in experimental animals causes growth retardation associated with impaired bone mineralization, reduced fertility and longevity. With a lack of fluorine in the bone tissue there is a decrease in the activity of alkaline and acid phosphatases. Fluorine deficiency in people living in endemic areas with a low fluoride content in drinking water leads to tooth decay by caries (enamel and dentin carious teeth are defored), and in old age also the development of fluoride-dependent osteoporosis, which causes frequent fractures, especially in women. Acute fluoride poisoning (for example, insecticides that form part of it) is manifested by vomiting and diarrhea, agitation, neurological disorders, tetany. In severe poisoning, paralysis of the respiratory muscles can cause death of the body. Endemic fluorosis is manifested by damage to the teeth associated with excessive accumulation of fluoride (spotting or mottling of tooth enamel), liver, kidney, central nervous system and endocrine system. Muscle weakness, brittle bones, tendon calcification are noted. In occupational fluorosis, fluorine rhinitis with nasal bleeding, ulcerative necrotic pharyngolaryngitis, atrophic gastritis, fluorine hepatosis and hyperparathyroidism, hypogonadism, myocardiodystrophy are observed. Violations of carbohydrate, lipid and protein exchanges with an excess of fluorine are associated, inter alia, with the formation of its complex compounds with calcium, magnesium and other ions - activators of numerous enzymes.

Normal is the intake of fluoride in the body in the amount of 1.5-4 mg per day. The fluoride content in blood plasma is normally 0.5-10.5 µmol / l.