The development of intensive care and resuscitation, expanding the limits of resuscitation, revealed a number of unresolved problems. One of them should be considered the problem of endogenous intoxication (EI).
The modern concept of EI is associated, first of all, with the concept of multiple organ failure or multiple organ failure, or the 80-year-old syndrome, or MOF syndrome. This implies the simultaneous or sequential onset of failure of the heart, lungs, liver, kidneys, brain, which leads to high mortality - from 60 to 80% or more. Moreover, mortality is directly dependent on the number of organs involved in this syndrome.
It should be noted that among the components of multiple organ dysfunction syndrome (MODS), priority is traditionally given to circulatory and respiratory disorders, which develop in 60% and 65% of cases, respectively. However, it is considered a reliably established fact that the failure of the liver, kidneys, and digestive tract, which accompany MODS in 60%, 56% and 53% of cases, respectively, play a significant role in the outcome of multiorgan damage syndrome. Thus, failure of metabolic homeostasis due to hepatic-renal failure is as common as cardiopulmonary failure. However, the clinical picture of metabolic disorders does not manifest itself as clearly as respiratory and circulatory disorders, especially in the early stages of its development. Therefore, the diagnosis of impaired metabolism, as a rule, lags behind the events of developing processes. This leads to a statement of facts in cases of far-reaching or already irreversible changes that determine the outcome of diseases.
EI can be defined as a syndrome of inconsistency between the formation and elimination of both products of “normal” metabolism and substances of impaired metabolism, which is nonspecific in terms of most clinical, biochemical and immunological manifestations.
The essence of EI is based on the concept of representing it as a reflection of the consequences of disturbances in macrocirculation and microhemolymphocirculation, gas exchange and oxygen budget, immunity and anti-infective “defense” with failure to manage the integration of these processes. In this case, metabolic disorders occur in accordance with the nature of the damaging factor and the response of the macro- and microcirculation system to it in accordance with the disruption of transport and extraction of oxygen by tissues, activation of the sympathetic-adrenal system. This leads to a hypermetabolism syndrome typical of a critical condition - the need of tissues for various substrates to provide compensatory and adaptive mechanisms for energy conservation, prevent protein breakdown, reduce the utilization of fatty acids, increase gluconeogenesis and glucose tolerance, and intensify endothelial permeability.
Depending on the predominance of the mechanism of EI formation, the following forms are conventionally distinguished: retention, exchange, resorption, sepsis, mixed.
The retention mechanism provides mainly a violation of the natural mechanism of removal, as a rule, of the end products of metabolism of low molecular weight compounds (molecule size less than 10 nm, molecular weight [MM] less than 500 daltons). The main route of their elimination is renal filtration and excretion.
The metabolic mechanism is characterized by the accumulation of intermediate metabolic products(molecule size - more than 10 nm, mm - less than 500 daltons), the elimination of which is carried out by the liver and through the alimentary canal.
intoxication endogenous marker
Resorption EI is accompanied by the accumulation of toxins with a molecular weight of more than 500 daltons and a molecular size of more than 200 nm due to the absorption of tissue and cell destruction products.
The infectious component of EI is caused by microbial toxins, including molecules up to 200 nm with MW up to 500 daltons.
Thus, the list of autointoxication substances can be dozens of names, and the level of their “toxic” concentration can be increased hundreds of thousands of times.
Conventionally, 5 classes of endotoxins can be distinguished: 1) substances of normal metabolism in non-physiological concentrations (urea, lactate, glucose, creatinine, bilirubin, etc.); 2) products of impaired metabolism (aldehydes, ketones, acids); 3) immunologically foreign substances (glyco- and lipoproteins, phospholipids); 4) enzymes; 5) inflammatory mediators, including cytokines, biogenic amines, antibodies, circulating immune complexes, adhesion molecules, protein degradation products and others.
In this regard, determining the essence of EI requires taking into account the state of natural detoxification, which includes three interconnected systems: monooxygenase, immune, and excretory.
The activities of the monooxygenase system of microsomal oxidation and immunity are coupled and functionally coordinated to ensure the recognition of toxins with their subsequent sorption and excretion by the liver, kidneys, skin, lungs, spleen, and digestive tract. At the same time, the differences between the monooxygenase and immune systems are determined by the recognition of target toxins: the microsomal system metabolizes free xenobiotics and low molecular weight substances, and the prerogative immune system(macrophage-lymphocyte complex) is the recognition and neutralization of compounds conjugated with a macromolecular carrier. The essence of these processes is explained by: the theory of non-infectious immunity, including ideas about immunological tolerance (P. Medawar et al., Nobel Prize in Immunology, 1953), immunological surveillance of the genetic constancy of the integrity of the body (F. Bwenet, Nobel Prize in Immunology, 1960); theory of natural immunity to low molecular weight compounds (I.E. Kovalev, 1970), discovery of a cytokine-mediated signaling system in the immune response, hematopoiesis, inflammation. These theories define the role of immune mechanisms in ensuring “chemical” homeostasis, and the immune system is considered an integral part of the detoxification system, recognizing and neutralizing macromolecules of compounds conjugated with a macromolecular carrier.
At the same time, it becomes clear that a violation of the relationship between the monooxygenase and immune systems determines the discrepancy in the rate of formation and elimination of both pathological and physiological metabolic products in fluid sectors and tissues.
Similarities in the reaction to toxins can be traced in the nature of the immune and microsomal systems. In both the first and second systems, the induction of specific proteins occurs, ensuring the binding and metabolism of the indicator molecule. Memory for xenobiotics metabolized by the monooxygenase system is similar to immune memory: repeated administrations of a low-molecular-weight xenobiotic are more powerful than the first time, activating enzymes of the monooxygenase system, just as the height of the immune response increases with reintroduction antigen.
Various xenobiotics, when interacting with oxidases, compete for binding sites, and antigens compete in inducing antibody synthesis.
In addition, numerous low-molecular compounds are capable of inducing an immune response, and immunocytes can produce immunoglobulins. Liver cells that metabolize xenobiotics synthesize albumin, the main protein of plasma detoxification, reminiscent of immunoglobulins, but with lower specificity.
These facts are evidence that microsomal oxidation and immunity - equivalent components of the detoxification system - provide the corresponding link in metabolic homeostasis.
In this case, a violation of the relationship in the system between the monooxygenase and immune links is manifested by a discrepancy between the rate of accumulation of both pathological and physiological metabolites through their biotransformation and excretion. This leads to the accumulation in tissues and fluid sectors of pathological products of cellular decay, endotoxins, pyrogens, biologically active substances of various types, neurotransmitters, free radicals and other products.
The result of this is two processes affecting the cells of the monooxygenase system and immunity: uncoupling of redox phosphorylation, which leads either to cell death or to a decrease in its functional activity, as well as, possibly, direct toxic damage to cell structures. The consequence of this is, on the one hand, a violation of the biochemical composition of cells, tissues, including blood cells; on the other hand, a violation of antibody production, lymphocytotoxicity, and a violation of the synthesis of response mediators.
Consequently, EI develops either as a result of an imbalance in the components of the detoxification system, or due to the failure of one of the links, or simultaneously all its components. This determines the essence of EI, its general and distinctive features depending on the main cause, i.e. etiology of the disease, as well as the degree of its severity according to the number of organs and components of detoxification involved in the pathological process (Fig. 1).
Along with this, the place of the microbial factor in the structure of endogenous intoxication in a critical condition of any origin should be especially noted. The microbial factor constitutes one of the so-called paradoxes of critical illness:
The role of the microbial factor is transformed, first of all, due to the release of endotoxins and/or exotoxins, the molecules of which can imitate the structures of enzymes, hormones, neurotransmitters, disrupting physiological metabolic processes.
Thus, exotoxin is the secretion of a living microorganism; it is a thermolabile protein that is highly immunogenic and disrupts intracellular metabolic processes through enzyme-irreversible transformation of A5DF; lytic enzymes damage the cytoplasmic membrane and block synaptic transmission of motor neurons due to inhibition of neurotransmitters (Fig. 2, 3).
Endotoxin is a complex complex of the shell of a microorganism with an active substance - liposaccharide LPS, lipid A. This toxin is thermolabile, it lacks immunogenicity, the main points of its application are endothelial cells and the immune response. As a result of its effect on monocytes/macrophages, endotoxin ensures the release of biologically active substances: interleukins, leukotrienes, prostaglandins, TNF-, oxygen metabolites, platelet activating factor, serotonin, von Willebrand factor, nitric oxide, Hageman factor, lysosomal enzymes (Fig. 2, 3) .
The liposaccharide substance is an integral part of the membrane toxin of gram-negative microorganisms. Gram-positive microbes are the source of a number of toxins, including toxin-1, pyrogenic endotoxin, L-toxin, O-streptolysin, L-hemolysin, lymphotoxin, shock toxin, teichyonic acids (Fig. 4).
When assessing the role of endotoxins of microbial origin in the development of EI syndrome, one should take into account the fact that under physiological conditions, gram-negative microbes inhabit the surface of the skin and mucous membrane, being a source of endotoxin, which in a “physiological” concentration of 0.001 mg/kg stimulates polymorphonuclear leukocytes, macrophages, and other cells immune natural defense, coagulation system, myelopoiesis. However, with an increase in endotoxin concentration due to the failure of antiendotoxin immunity, EI is formed.
Thus, EI, as a component of a critical condition of any origin, develops as a result of the failure of the main components of the detoxification systems: monooxygenase, excretory and immune - to utilize and eliminate both the products of normal and impaired metabolism, and microbial toxins.
Conventionally, indicators reflecting the state of the detoxification system can be divided into:
. Endogenous intoxication is a syndrome based on the massive intake of various toxins into the internal environment of the body.
Normally, a number of organs and systems are responsible for the removal and inactivation of endogenous toxins: the immune system, liver and intestines, kidneys, lungs. In case of pathology of any of the listed organs, other normally functioning organs take over part of its lost functions. This partially compensates for the toxemia, but makes them work harder.
With failure of one organ or system, the mortality rate is 23-40%, with failure of two organs – 5360%, three or more organs – 73-89%. The universal pathogenetic factor for such progression of the disease is endotoxicosis.
Intoxication is a clinical manifestation of a pathological condition resulting from the action of substances of endogenous or exogenous origin on the body. From a biochemical point of view, endogenous intoxication is the body's metabolic response to any aggressive factor. Toxic substances or toxins are compounds of various natures and chemical structures that, when they enter the body, can cause disease or death. Toxemia is the presence of toxins in the blood. This is a physiological condition associated with the transport of toxic substances in the blood to the organs of detoxification and excretion (elimination). Toxicosis is a pathological syndrome caused by the action of toxins, accompanied by pronounced morphological and functional changes at the level of organs and body systems
The biochemical substrate of endogenous intoxication is a medium-molecular pool of substances, which includes products of final metabolism in high concentrations, products of intermediate metabolism and products of altered metabolism.
The substances that make up the medium molecular weight pool are usually divided into substances mainly of non-protein origin and oligopeptides with a molecular weight of 10 -15 kD (kilo Dalton). Medium molecular substances of non-protein origin are represented by substances of various natures: 1. urea, creatine, uric acid, amino sugars, lactic and other organic acids, amino acids, fatty acids, bilirubin, cholesterol, phospholipids and their derivatives, products of intermediate metabolism, free radical oxidation, and other products. 2. High concentrations of intermediate metabolites (ammonia, aldehydes, ketones); 3. Substances of abnormal metabolism (alcohols, carboxylic acids) and toxic components of the body’s cavity media (phenol, skatole, indole, putrescine, cadaverine).
The oliropeptide component of the medium molecular pool of substances: Regulatory peptides are hormones that play an important role in the process of life, in ensuring homeostasis and the pathogenesis of various diseases. Among them, neurotensins, neurokinins, vasoactive intestinal peptide, somatostatin, somatomedin, substance P, endorphins, enkephalins and other biologically active substances were identified. Non-regulatory peptides are biologically active substances formed from toxins received from outside (bacterial, burn, intestinal) and products formed inside the body (due to autolysis, ischemia, organ hypoxia, inorganic proteolysis processes), peptides with unregulated content and unpredictable properties.
“Endogenous intoxication syndrome” is a pathological condition based on damage to organs and body systems caused by the accumulation of endogenous toxins in tissues and biological fluids.
Endotoxicosis should be understood as an extreme degree of endogenous intoxication syndrome, causing a critical condition of the body. A critical state of the body is characterized by the fact that the body cannot independently compensate for the resulting homeostasis disorders.
ETIOLOGY AND PATHOGENESIS. The triggering factor can be represented by a focus of traumatic, ischemic or inflammatory tissue destruction. Endogenous intoxication syndrome occurs with peritonitis, cholecystitis, pancreatitis, jaundice, phlegmon, severe tissue crushing (crash syndrome), diabetes mellitus, thyrotoxic goiter, etc., various poisonings. All of these diseases are characterized by a combination of toxemia, tissue hypoxia, and inhibition of the function of the body’s own detoxifying and protective systems.
Tissue hypoxia leads to intensification of lipid peroxidation and anaerobic transformation of glycolysis with the formation of lactates and acidosis. The intensification of lipid peroxidation occurs as a result of the transition from conventional oxidation to oxygenase oxidation, which results in the formation of toxic substances: superoxide anion and hydrogen peroxide. These processes lead to damage to all types of biological membranes.
Medium-weight molecules have an inhibitory effect on a number of metabolic processes: mitochondrial respiration, DNA synthesis in alveolar macrophages and lymphocytes, inhibit the processes of intracellular glucose utilization, inhibit hemoglobin synthesis, reduce the activity of a number of cellular enzymes, have a vasoconstrictor effect, and cause hyperosmolar syndrome. Even a slight increase in MSM content can have serious consequences for the body and determine the severity clinical condition. This is due to the fact that MSM freely penetrates the blood-brain barrier, disrupting the regulation of autonomic functions of the brain and producing a psycho- and neurotropic effect. High concentrations of MSM are depressive contractility myocardium and excretory function of primarily uncompromised kidneys.
In 1941, Kal-Kalif proposed a leukocyte index of intoxication: Norm 1+ 0.6. LII = (4 monocytes + 3 young + 2 stab + segmented) (pl. cells + 1) (monocytes + lymphocytes) (eosinophils + 1) Number neutrophil shift is the main criterion characterizing the severity of the inflammatory process and the degree of intoxication. The degree of shift is determined by the formula: M+Yu+P C, where M-myelocytes, Y – young, P – stab, C-segmented neutrophils. Normally, this value is 0.05 – 0.08.
A severe inflammatory process, accompanied by severe intoxication, occurs with a shift from 1 to 2. A process of moderate severity with a shift of 0.3 - 0.5. With a mild degree, less than 0.25. With an extreme degree of severity, pathological granularity of neutrophils, vacuolization of the cytoplasm and their nuclei, violation of the integrity of cell membranes. Pathological granularity is determined long before the appearance of a band shift and is a good test for determining the presence of nonspecific inflammation (Kassirsky I.A. 1970).
In 1980-1981, Reis B.A. and co-authors established that a number of plasma substances, the molecular weight of which lies in the range of 1000 - 5000 Daltons, have the greatest activity in the purulent-septic process. It was found that substances of average molecular weight play a certain role in the pathogenesis of the development of renal and liver failure. In 1983, Gabrielian proposed a laboratory test to determine the content of medium molecules in plasma. The method is not complicated and gives a very realistic approximate picture of the content of toxic substances in the plasma. It is currently most commonly used to evaluate endotoxemia. Norm 0.24 + 0.02 cu. e.
To date, it has been shown that determining the concentration of molecules of average mass in plasma makes it possible to assess the level of endogenous intoxication, studying the sorption capacity of erythrocytes, determining the effective concentration of albumin and albumin indices allows us to assess the level of the system of temporary binding and transport of toxins, calculating leukocyte intoxication indices allows us to assess the body's response to endogenous intoxication syndrome.
The state of cell membranes may reflect the degree of intoxication, as an indicator of the influence of membrane-damaging factors on the cell. High degree correlation of changes in the properties of erythrocyte membranes and cell membranes of internal organs allows the use of biological erythrocyte membranes to study general membrane characteristics.
The triggering factor in the development of endotoxemia can be represented by a focus of traumatic, ischemic or inflammatory tissue destruction. It has been established that initial stages development of endotoxemia, the main mechanism of its formation is production-resorption against the background of instability of the main systems of detoxification and biotransformation of toxins. During this period, there is an active accumulation and production of toxins with their subsequent resorption into the active bloodstream from the site of destruction. This period corresponds to the stage of toxemia. At this stage of development of endotoxemia, there is no clinical and laboratory involvement of other organs and systems in the process. The patient’s body at this stage copes with toxemia, which does not go beyond the hemic spectrum.
The next stage of development of endotoxemia is the stage of tension of detoxifying systems, in which endotoxemia leads to the development of organopathies. This stage of endotoxemia is characterized by the inability of the pulmonary protective barrier to cope with increased venous toxemia. Here the processes of disruption of the elimination and biotransformation of toxins already predominate.
The next stage is the most formidable - the stage of multiple organ failure. Here, circulatory hypoxic processes predominate, which lead to the creation of a block of peripheral microcirculation. The body seems to be trying, by centralizing hemodynamics and removing toxins into the interstitium, to protect life as much as possible. important organs from toxic hematogenous load.
The optimal point for extracorporeal detoxification, which will be discussed further, is the tension stage functional system detoxification, when endotoxemia as a process has already gone beyond the hemic spectrum, but has not yet reached the stage of multiple organ failure.
TREATMENT - Surgical debridement of the source of infection. - Correction of microcirculatory disorders of blood circulation, lymph circulation. Preventive and rational antibacterial therapy. - Reducing endotoxicosis - as a prevention of multiple organ and systemic failure. - Immunocorrection. Energy supply.
biological transformation of toxic substances in the liver. In the body, this function is performed by the monoamine oxidase system of the liver, the cytochrome P-450 system. . In efferent therapy, this mechanism is modeled by the following operations: indirect electrochemical oxidation of blood, oxygenation of blood, perfusion of blood through xenoorgans and cell suspensions, photomodification of blood (laser and ultraviolet irradiation of blood).
Dilution and binding of toxic substances: In the body, this is realized by autohemodilution, a function of the immune system. In efferent therapy, this mechanism is modeled by: - hemosorption, - plasma sorption, - lymphosorption.
Elimination (removal) of toxic substances. In the body, this is realized by the functioning of the liver, kidneys, lungs, gastrointestinal tract, and skin. In efferent therapy, this mechanism is modeled by: peritoneal dialysis, plasmapheresis, enterosorption, hemodialysis, hemofiltration.
Indications for extracorporeal detoxification methods: high blood toxicity at the height of the disease; lack of effect from routine detoxification therapy in combination with extensive tissue destruction; severe intoxication due to intolerance to antibiotics; rapid increase in the clinical picture of endotoxicosis in the postoperative period. -
Effects of extracorporeal hemocorrection A prerequisite for extracorporeal detoxification is radical sanitation of the focus of purulent destruction. “Bartyrin's syndrome” involves the entry of toxins from tissue depots into the central bloodstream. To prevent this syndrome, immediately before perfusion, it is recommended to create “imposed toxinemia” as a result of improving the rheological properties of blood, to carry out lymphostimulation, and to use pre-perfusion photomodification of blood.
Extracorporeal hemocorrection has a complex effect on the body. The diverse effects that arise can be divided into three groups: specific, nonspecific, additional. The main specific effects of extracorporeal hemocorrection are detoxification, immunocorrection, rheocorrection. Nonspecific effects of extracorporeal hemocorrection are determined by contact with the surfaces of lines and mass transfer devices. This may include temperature reactions, hemodynamic reactions caused by the redistribution of fluid and blood cells. Additional effects are associated with the use of both mandatory and special drugs during surgery. medications. They are associated with the use of special transfusion and drug programs carried out in parallel with extracorporeal hemocorrection.
According to the criterion of removing toxins from the body, efferent extracorporeal methods are divided into: non-selective, semi-selective and selective. The most specific methods for removing strictly defined substances are immunosorption, biospecific sorption of blood or its components. The less selectively the elimination of blood components occurs, the greater the adverse effects of these procedures. These include violation electrolyte balance during hemodialysis and plasmapheresis, disturbances in the hormonal profile of the blood (removal of catecholamines and glucocorticoids) - collaptoid reactions during plasmapheresis and hypoglycemic reactions are associated with this.
Characteristics of individual methods of efferent therapy. Hemodialysis is a method of intravital liberation of blood from low and medium molecular weight substances through selective diffusion using the “Artificial Kidney” apparatus. It is based on the mechanism of molecular diffusion and ultrafiltration. There is a diffusion exchange and filtration transfer of low molecular weight substances and water through a semi-permeable membrane from extracorporeally circulating blood into the dialysate solution. Azotemia, electrolyte imbalance, and acid-base imbalance are corrected.
Main indications for the use of hemodialysis: terminal stage chronic renal failure; acute renal failure of any origin; acute poisoning with alcohols, technical liquids; hyperkalemia, azotemia due to renal failure.
Enterosorption is a method based on detoxification through the absorption of toxins in the intestines on ether sorbent (lignin derivatives - polyphepam, enterosgel). The action of enterosorption is carried out in 2 directions: - reverse passage of toxins from the blood into the intestines with its further binding on sorbents; -cleaning chyme from its toxic products; Hemosorption is a method of extracorporeal hemocorrection based on the removal of toxic substances from the patient’s blood by extracorporeal perfusion through a sorbent. Indications for this operation have recently decreased significantly, mainly because preference is given to less traumatic operations: plasmapheresis and enterosorption. The only absolute indication for hemosorption remains acute poisoning. The volume of perfusion in acute endotoxicosis is 1.5 - 2.5 bcc, in acute exotoxicosis - 10 -12 bcc.
Plasmapheresis and plasmafiltration are a method of extracorporeal hemocorrection based on replacing the patient's blood plasma with components, blood products or blood substitutes. Plasmafiltration is a variant of plasmapheresis in which membrane technology is used to separate plasma. Depending on the volume of plasma removed, the method is divided into: plasmapheresis, which removes up to 70% of the plasma; plasma exchange, - this removes 70-150% of the CP; massive plasma exchange - this removes more than 150% of the CP. During plasmapheresis with the removal of up to 50% of the VCP, plasma loss can only be replenished with crystalloid solutions in a volume 50-100% greater than exfusion. With more voluminous plasmapheresis, the plasma loss compensation program includes colloidal plasma substitutes and crystalloid solutions in a volume of 70% of the removed plasma. .
The main indications for plasmapheresis: severe decompensated stages of endotoxicosis of various origins; severe generalized forms of infectious diseases; chronic autoimmune diseases ( bronchial asthma, systemic diseases connective tissue, hematological diseases); chronic endotoxicosis in diseases of the liver, kidneys, lungs; total hemolysis during myolysis in case of poisoning with hemolytic poisons, long-term compression syndrome).
Xenoperfusion is a method of extracorporeal hemocorrection based on modification of blood or plasma upon contact with living xenogeneic tissues. The donor animal, as a rule, is a pig. Most often in our country, xenoperfusion is carried out in the form of plasma perfusion through a suspension of isolated hepatocytes. This procedure is carried out in an “artificial liver” apparatus. According to domestic researchers, the absolute indications for this operation are fulminant liver failure, hepatic coma, and decompensated endotoxicosis during liver transplantation.
After infusion of sodium hypochlorite, restoration of sensitivity to antibiotics of previously resistant microbial flora is observed. Nathium hypochlorite also has an immunomodulatory effect, improves microcirculation and rheological properties of blood.
Photomodification of blood is a method of hemocorrection based on the effect on blood outside the body or in the vascular bed of photons - quanta of optical radiation in the ultraviolet, visible and infrared ranges available in the solar spectrum. The therapeutic effect of blood photomodification is due to immunocorrection, improvement of the rheological properties of blood, improvement of microcirculation, stimulation of erythropoiesis, increase in the oxygen capacity of the blood, stimulation of regenerative and metabolic processes. New possibilities for photomodification of blood is a photophoresis method used in oncology and hematology. The essence of this method is to administer to the patient a photosensitizer (8 methoxypsoralen), which, after long-wave ultraviolet irradiation, is activated and binds to DNA, causing damage to rapidly dividing cells. Damage to pathological cells increases their immunogenicity and causes a powerful immune response towards them.
Efferent therapy is a continuously developing branch of medicine and we are still learning a lot of interesting things about its achievements.
ENDOGENOUS INTOXICATION SYNDROME IN THE PATHOGENESIS OF VIRAL HEPATITIS
Kuznetsov P. L., Borzunov V. M.
GBOU VPO UGMA Ministry of Health of Russia
Kuznetsov Pavel Leonidovich
The article provides a review of the literature on the mechanisms of development of endogenous intoxication syndrome. Various definitions of endogenous intoxication syndrome, phases of pathogenesis, and the main mechanisms of its development are given. The characteristics of endotoxic substances are given, their effect on the body as a whole and on the detoxification organs in particular. The main role of the liver in detoxifying the body and the disruption of its functions when affected by hepatitis viruses are shown. Methods for diagnosing endogenous intoxication syndrome are described.
Key words: viral hepatitis; endogenous intoxication; pathogenesis. SUMMARY
This paper presents a review of the literature on the mechanisms of development of the syndrome of endogenous intoxication. Given the different definitions of the syndrome of endogenous intoxication, the phase of pathogenesis, the basic mechanisms of its development. The characteristic of endotoxic substances, their effects on the body as a whole and on the organs of detoxification, in particular. It is shown that the main role of the liver to detoxify the body and its functions in violation of the incidence of viral hepatitis. The methods of diagnosis of the syndrome of endogenous intoxication. Keywords: viral hepatitis; endogenous intoxication and pathogenesis.
INTRODUCTION
In modern conditions, the priority direction of scientific research is to decipher the pathogenetic aspects of intoxication syndrome as a universal syndrome complex, the severity of which acts as a criterion for the severity of the disease and determines its outcome. Endogenous intoxication of the body is part of the general intoxication syndrome, accompanies many diseases and is often the main cause of death. Along with the specific features inherent in one or another nosological form, diseases occurring with endotoxemia syndrome have many common biochemical and pathophysiological mechanisms.
The definition of endogenous intoxication syndrome (EIS) given by V.K. Gostishchev: “Endogenous intoxication syndrome is a clinical complex of symptoms of pathological conditions of organs and systems of the body, caused by the accumulation of endotoxins in tissues and biological fluids - products of natural metabolism in abnormally high concentrations, inflammatory mediators, exo- and endotoxins, products of cellular and protein degradation, etc.” Thus, this syndrome is considered as polyetiological and polypathogenetic, characterized by the accumulation of endogenous toxic substances (ETS) in tissues and biological fluids - an excess of products of normal or perverted (pathological)
metabolism or cellular response. Endotoxicosis is a complex multifactorial autocatalytic process that acquires a universal character over time, depending on the mechanisms that trigger it. Unbalanced biologically active substances that acquire the properties of ETS become damaging agents. Components of the syndrome: toxinemia, the concentration of circulating ETS, both coming from the primary focus and arising secondarily as a result of tissue damage.
PATHOGENESIS OF ENDOGENOUS INTOXICATION SYNDROME
The causes of the syndrome can be divided into two groups. First of all, these are destructive processes, as a result of which an excess amount of intermediate and final metabolic products accumulates in the human body, which cause a toxic effect on the most important life support systems. The second group is a violation of the functional state of the physiological systems of the body responsible for binding, inactivation and elimination of both natural metabolites and toxic products. Primary damage to these systems or failure of their adaptation and compensation in any pathological process also leads to the occurrence of SEI.
Among the main ways of formation of SEI in the body are the following:
1. Retention - as a consequence of a violation of the elimination from the human body of the end products of metabolism of low molecular weight compounds (molecule size - less than 10 nm, molecular weight (MM) - less than 500 daltons); the result of a delay in the final or intermediate products of normal metabolism (carbon dioxide during hypoventilation, bile components during obstructive jaundice, products of nitrogen metabolism during renal failure). The main route of their elimination is renal filtration and excretion.
2. Resorptive - as a consequence of massive formation with subsequent resorption in the body of tissue decay products (toxins with a molecular weight of more than 500 daltons and a molecular size of more than 200 nm); entry into the internal environment of the body of tissue breakdown products or contents of the intestines, bladder, wound cavity, etc.
3. Metabolic (productive) - as a result of disruption of intracellular homeostasis and accumulation of excess secondary metabolites (molecule size - more than 10 nm, MW - less than 500 daltons); develops as a result of disruption of tissue metabolic processes with changes in the composition of tissue
fluids, lymph and blood. Elimination is carried out by the liver and through the alimentary canal.
4. Infectious - as a result of the action in the body of toxic agents of an infectious nature, including molecules up to 200 nm with MW up to 500 daltons.
According to modern concepts, there are five phases in the development of endogenous intoxication, which consist in the redistribution of substances of low and medium molecular weight (LM and MW) between biological environments. In the first (latent) phase, an increase in VL and SMM in erythrocytes is observed without a significant increase in their concentration in plasma. Elimination of incoming toxins from the source of intoxication occurs. In the second phase, the concentration of VN and SMM in erythrocytes increases significantly with a moderate increase in their concentration in plasma. This is the phase of accumulation of toxic products, in which their formation exceeds elimination. In the third phase (complete saturation) there is a maximum concentration of VN and SMM in erythrocytes; In parallel, there is an increase in toxic substances in the plasma. The fourth phase is characterized by an increase in the amount of VN and SMM in the plasma, and in erythrocytes, due to a violation of membrane permeability, their concentration decreases. This is a phase of irreversible decompensation of detoxification systems and organs. In the fifth terminal phase, catabolic products enter intracellularly, and the concentrations of VN and SMM in erythrocytes and plasma decrease.
It is possible to draw parallels with the classification of EI phases proposed by M. Ya. Malakhova (1991), according to which in the pathogenesis of EI there are 5 successively replacing each other phases: I - compensatory-adaptive phase; II - phase of incomplete compensation; III - phase of reversible decompensation of detoxification systems; IV - phase of failure of homeostasis systems and irreversible decompensation of detoxification systems and organs; V - phase of complete disintegration of detoxification systems and organs or terminal.
ENDOTOXIC SUBSTANCES
Several mechanisms of ETS formation and their accumulation in the internal environment of the body may simultaneously or sequentially participate in the development of acute endotoxicosis. There are three main biochemical mechanisms for the development of endotoxicosis:
1. activation of tissue proteolysis;
2. activation of free radical oxidation processes;
3. action of bacterial toxins.
Activation of proteolysis, the hydrolytic breakdown of proteins carried out by tissue proteases (cathepsins), represents one of the most common molecular mechanisms of tissue damage under pathological conditions. MSM (medium weight molecules - from 500 to 5000 amu) - substances, predominantly of a peptide nature, formed in tissues as a result of the proteolytic breakdown of proteins and causing the condition intoxication in the body. The toxic effect of MSM is due to the total influence of all its constituent compounds due to the development of potentiation and synergism effects. Activation of proteolysis is prevented by antiproteases - protein substances that form complexes with proteases, in which the latter lose their activity, these include serine protease inhibitors alpha-1-AT, alpha-1-antichymotrypsin and alpha-2-MG.
Lipid peroxidation (LPO) is one of the ways to utilize oxygen in the cell. The main substrate in lipid peroxidation reactions are unsaturated fatty acid residues of biological membrane lipids. LPO products - organic peroxides and hydroperoxides, are unstable and highly reactive compounds with pronounced toxic properties.
In the development of endotoxemia, a large role is played by microorganism toxins, which are waste products of microbial cells. Intoxication usually occurs as a result of the action of toxic substances circulating in the blood; circulation of endogenous poisons in the blood is more often referred to as toxemia, and circulation of toxins as toxemia. About 80 microbial toxins have been described and isolated in relatively pure form. Based on their origin, microbial toxins are divided into three classes:
1) exotoxins - products released by microorganisms during their life activity;
2) endotoxins - substances firmly bound to the stroma of microbial cells and released only after the death of the microbial population; 3) mesotoxins - toxic substances loosely associated with the stroma microbial cell and under certain conditions stand out in environment while maintaining cell viability. Based on their functional activity, they distinguish membrane toxins that can lyse cell membranes (leukocidins, hemolysins, phospholipase A2), cytotoxins, functional blockers (neuro- and enterotoxins), exfoliatins - erytrogenins (found in staphylococci and streptococci, have a pyrogenic effect, cause desquamation superficial layers of the skin epithelium), modulators of cell responses to endogenous mediators.
Modern classifications toxins are divided according to the mechanism of action, according to size
particles, according to their effect on the body. There are groups of endotoxins: 1) substances of normal metabolism in non-physiological concentrations (urea, lactate, pyruvate, glucose, creatinine, bilirubin, etc.); 2) products of impaired metabolism (aldehydes, ketones, alcohols, carboxylic acids); 3) immunologically foreign substances (glyco- and lipoproteins, phospholipids); 4) enzymes and inflammatory mediators, including cytokines, biogenic amines, prostaglandins, leukotrienes, antibodies, circulating immune complexes, adhesion molecules; 5) products of protein degradation and amino acid conversion (phenol, cresol, indole, skatole, putrescine, cadaverine); 6) microorganism toxins.
Based on particle size, they are divided into: 1) low molecular weight (particle size less than 500 daltons) - water, sodium potassium ions, creatinine, urea; 2) medium (particle size 500-5000 daltons) - the majority of biologically active substances, which play a major role in intoxication in most diseases (hormones, serotonin, vitamin B12, fibrin degradation products); 3) large-molecular (up to tens of thousands of daltons) - proteins and lipoproteins; 4) ultra-high molecular weight (million daltons) - protein compounds, such as CEC, soluble fibrin-monomer complexes, cryoglobulins, cryofibrinogen, which play a large role in the pathogenesis of immune complex vasculitis and DIC syndrome.
According to the effect on the body, causing: 1) disruption of organs and systems at the level of the macroorganism (water); 2) disruption of cell functioning and metabolism (potassium, sodium, bilirubin, ammonia, digoxin); 3) cell death (nephro-, hepato-, neuro- and ototoxic substances); 4) disturbance of microcirculation and homeostasis (bacterial endotoxins, fibrin degradation products, fibrin-monomer complexes, cryofibrinogen); 5) impaired vascular permeability (CIC, serotonin).
Endogenous toxins can have a destructive effect on cellular structures and metabolism in them. This influence also extends to cells distant from the site of primary toxin release. The massive intake of toxic products from the primary lesions and their humoral redistribution with the flow of lymph and blood in the organs and tissues of the body predetermine the generalization of endotoxicosis.
BODY DETOXIFICATION SYSTEMS
The state of natural detoxification combines three interconnected systems: monooxygenase, immune, excretory. The activities of the monooxygenase system of microsomal oxidation and immunity are coupled and functionally coordinated to ensure the recognition of toxins with their subsequent sorption and excretion by the liver, kidneys, skin, lungs,
spleen, digestive tract. At the same time, the differences between the monooxygenase and immune systems are determined by the recognition of target toxins: the microsomal system metabolizes free xenobiotics and low molecular weight substances, and the prerogative of the immune system (macrophage-lymphocyte complex) is the recognition and neutralization of compounds conjugated with a macromolecular carrier. A disruption in the relationship between the monooxygenase and immune systems determines the discrepancy in the rate of formation and elimination of both pathological and physiological metabolic products in fluid sectors and tissues. Consequently, EI develops either as a result of an imbalance in the components of the detoxification system, or due to the failure of one of the links, or simultaneously all its components.
Elimination of endogenous toxins occurs as follows: gaseous substances are released through the lungs; hydrophilic low- and medium-molecular substances - are removed by the kidneys, through the skin, and the gastrointestinal tract in the form of solutions; hydrophobic low- and medium-molecular substances - transported by proteins and/or blood cells to the liver and lungs, where they are biotransformed with the participation of the monooxygenase system or undergo changes in binding reactions with subsequent removal through the kidneys, skin, and gastrointestinal tract; or bind to blood plasma proteins, acquire the properties of haptens and are absorbed by cells of the immune system; high-molecular compounds - transported through lymphatic vessels, eliminated by the monocyte-macrophage system (up to 80% of the body's macrophages are located in the liver).
With a sufficient level of functioning of protective mechanisms, the body is able to withstand the onslaught of toxic influences. Under these conditions, there is no clinical manifestation of SEI, although the possibility of the existence of latent or transient endotoxicosis is not denied. In the case of functional failure of protective antitoxin and regulatory systems in the body, the content of endogenous toxins increases, which, against the background of deep disturbances in the structure and function of the immune system, leads to a decrease in the body’s resistance. Based on the severity of SEI, one can judge the severity of the underlying disease and predict its course.
ROLE OF THE LIVER IN THE PATHOGENESIS OF ENDOGENOUS INTOXICATION SYNDROME
In clinical practice, SEI is considered as a clinical symptom complex that occurs during acute or chronic insufficiency
functions of the body's natural detoxification system. Considering that the leading function of the liver is detoxification, it is natural to assume that the development of organ pathology leads to the accumulation of ETS in the body, helping to trigger the mechanisms of endotoxin aggression. In addition, toxins entering the blood from any source of inflammation can have a damaging effect on liver tissue (I. I. Sirotko et al., 1998). In particular, in patients with severe and moderately severe pneumonia, signs of a reactive process in the liver are revealed, manifested by hypoalbuminemia and an increase in gamma globulins, an increase in the activity of alkaline phosphatase and trans-aminases in the blood. Changes in the liver can contribute to the protracted course of pneumonia and require correction in the early period of the disease.
A consequence of liver failure is the development of hypoproteinemia, which can also contribute to the development of inflammation in the lungs due to the activation of lipid peroxidation. This conclusion is based on the results of an experimental study by C. J. Huang and M. L. Fwu (1993), who studied the content of lipid peroxidation products and the activity of antioxidant enzymes in the lungs of rats with protein deficiency. There is a two-way relationship between nonspecific inflammatory lung diseases and impaired detoxifying function of the liver.
Severe endogenous intoxication, as a rule, accompanies chronic diseases of the liver, kidneys, pancreas, burn toxicosis, peritonitis, acute intestinal obstruction, sepsis, extensive trauma, gynecological diseases, etc. . Most of these conditions are characterized by: hyperbilirubinemia, hyperglobulinemia, impaired synthesis of proteins and amino acids due to impaired synthetic, detoxification function of the liver; with the accumulation of nitrogen metabolism products (creatinine, uric acid), which occurs when kidney function is blocked; in case of peritonitis, burn disease, putrefactive processes, polyamines (biogenic amines - cadaverine, putrescine), which are products of protein biodegradation, predominate.
Long duration data obtained metabolic disorders in patients with acute viral hepatitis B. Thus, changes in albumin test parameters (decrease in effective albumin concentration (ECA) and albumin binding reserve (ARB)) and malondialdehyde (increase in MDA) were recorded during the height of the disease and coincided with clinical manifestations , did not return to normal, even in patients in the period of convalescence
in the absence of clinical symptoms. A greater severity of EI was shown, its slow and sometimes negative dynamics were established in patients with viral hepatitis B with previous types of pathology: degenerative diseases, signs of decreased body reactivity, toxic effects, disorders of the excretory function of the digestive system.
In a study by A. R. Umerova, a significant increase in the CEC value was observed in patients with chronic hepatitis (CH) and liver cirrhosis (LC) compared to the norm. The MSM indicator in patients with chronic hepatitis and cirrhosis was also significantly increased compared to the norm, which indicates high frequency occurrence of SEI in chronic liver pathology. The role of plasma fibronectin is shown, a glycoprotein whose leading function in the body is opsonic, that is, the removal of various microparticles from the bloodstream, including microbial lipopolysaccharides, immune complexes, etc. There is a significant decrease in its amount in the blood plasma during chronic hepatitis in 41% of cases, and with CPU - 64%. Regulatory proteins (RP) are a cumulative product of the catabolite breakdown of cellular receptors of various specificities and are universal endogenous toxins. The correlation between the levels of RB and CEC was direct: with an increase in the content of RB, the number of CEC increased, especially in patients with class C cirrhosis. The relationship between the levels of RB and serum albumin, on the contrary, was inverse: with an increase in RB titers, the concentration of albumin decreased. A similar negative correlation was also observed to the maximum extent in patients with class C cirrhosis. Thus, the determination of plasma fibronectin and RB in blood serum can be used in clinical practice as a sensitive marker of the syndrome of endogenous intoxication in chronic hepatitis and cirrhosis.
Currently, a direct relationship has been established between the level of endotoxemia and hemodynamic disorders in cirrhosis. It has been revealed that bacteremia is most common in patients with bleeding from esophageal varices (EVV). Endotoxemia, which develops as a result of the movement of bacteria through the intestinal mucosa, directly or indirectly through the cytokine cascade stimulates inducible nitric oxide synthase of the vascular endothelium, increasing its production. Endotoxemia plays an important role in the genesis of hyperdynamic circulatory status, worsening liver function and impairing hemostasis in patients with cirrhosis, and may be a critical risk factor for bleeding from varicose veins. A direct correlation has been proven between the level of endotoxemia and the risk of bleeding from varicose veins in patients with cirrhosis.
LABORATORY CRITERIA FOR ASSESSING ENDOGENOUS INTOXICATION SYNDROME
The situation with laboratory assessment of the severity of endogenous intoxication is twofold. On the one hand, the arsenal of methods used is quite wide. On the other hand, the data obtained using different methods are difficult to compare. Many of the proposed methods only indirectly reflect the level of intoxication. Most biological methods cannot be performed in clinical diagnostic laboratories. Therefore, the problem of developing methods for quantitatively assessing the severity of endotoxicosis that are quite simple and acceptable in the conditions of most medical institutions is very relevant today.
Assessment of the severity of the endogenous intoxication syndrome EI is based on clinical and laboratory data. The latter include the following groups of studies:
1. Hematological: NBT test (reflects the activation of neutrophil peroxidase systems); lysosomal-cationic test (determination of cationic proteins of granulocytes); degenerative changes in leukocytes (toxigenic granularity, Knyazkova-Dele inclusions, Amato grains, hypersegmentation of nuclei, etc.); inhibition of migration and spontaneous lysis of leukocytes; hemolytic resistance of erythrocytes; ability to transport substances of low and medium molecular weight.
2. Biochemical and biophysical: SMM substances in biological fluids and oligopeptic fractions; components of LPO and antioxidant system (AOS); chemiluminescence of biological fluids and homogenates; electron paramagnetic resonance; determination of hydrocarbons in exhaled air; components of inflammatory mediators (biogenic amines, kallikrein-kinin system, prostaglandins).
3. Microbiological and immunological: bacterial toxins (limulus test - determination of bacterial lipopolysaccharides, immunological methods for identifying bacterial antigens); determination of the concentration of the soluble fraction of CD14 macrophage receptors; determination of pro-inflammatory (IL-1^, TNF-a, IL-6, interferons, etc.) and anti-inflammatory cytokines (IL-4, IL-10, etc.), cytokines secreted by T-helper cells (IL-2 , IFN-γ) and the second type (IL-4) by enzyme immunoassay in blood serum, in culture of mononuclear cells, in body secretions; dynamics of microflora of the oral cavity, pharynx and skin; determination of complement components; integral assessment of the severity of immunosuppression.
4. Calculation criteria: leukocyte intoxication index (LII); nuclear intoxication index (NII); hematological intoxication index (HII); clinical and laboratory indices (Marchuk, Shugaeva, Gabrielyan, Malakhova, Grinev, etc.).
5. Biological testing (critical condition assessment according to the SOFA scale).
At the same time, according to M. Ya. Malakhova (1995), all methods of laboratory diagnosis of intoxication can be divided into specific, conditionally specific and nonspecific.
1. Specific ones make it possible to identify the effect of toxic agents that cause intoxication syndrome: release of a toxic agent; biotesting method; reaction of the valve apparatus of the lymphatic vessel of the mesentery of the intestine; paramecium test; tetrahymene test; bull semen test; limulis test; biomicroscopy of the conjunctiva of the eye; mobility of buccal epithelial nuclei in an electric field.
2. Conditionally specific ones make it possible to detect intoxication on blood cells - erythrocytes and leukocytes: inhibition of leukocyte migration; fragmentation of the leukocyte nucleus; vesicle formation reaction; reaction of spontaneous lysis of leukocytes; NST test; cation-lysosomal test; leukocyte index of intoxication; toxicogenic granularity of neutrophils; erythrocyte osmotic resistance test; test for the ability of red blood cells to absorb methylene blue; toxic erythrocyte granularity test; assessment of VL and SMM and oligopeptides of erythrocytes according to M. Ya. Malakhova.
3. Nonspecific reflect either the inflammatory reaction of the body or changes in metabolism: laboratory indicator (Marchuk et al.); intoxication index: Grineva et al., M. Ya. Malakhova et al.; MSM according to N. I. Gabrielyan; oligopeptides according to M. Glinsky; Lowry oligopeptides; registration of ultra-slow potential oscillations in the millivolt second and decasecond ranges; urea level in biological fluids; plasma fibronectin and ceruloplasmin levels.
To assess the hydrophilic component of toxicity, the level of malondialdehyde in the blood serum is determined, which is one of the resulting indicators of the state of prooxidant-antioxidant balance in the body. The state of antioxidant protection is assessed by the activity of plasma catalase (Cpl) and erythrocyte catalase (Cer) and superoxide dismutase. The hydrophilic component of toxicity is judged by the accumulation of MSM in the blood. Their toxic effect associated with a dissociating effect on the processes of oxidative phosphorylation, with changes in the permeability of cell membranes and membrane transport, with a membrane-destructive effect,
which predetermines the activation of LPO processes. In addition, MSM promotes hemolysis of red blood cells, inhibits the utilization of glucose in them, reduces globin synthesis and DNA synthesis in erythroblasts.
The hydrophobic component of endogenous intoxication is assessed by determining the binding capacity of serum albumin. It has been established that albumin is capable of reversibly binding fatty acids, metal ions, many metabolites, and exotoxic (mainly hydrophobic and amphiphilic) substances. Non-esterified fatty acids and bilirubin interact most strongly with albumin binding centers. By binding ligands, it ensures their transport to detoxification systems (liver, kidneys). The presence of albumin in the blood is within physiological norm(45-55% of the total protein) does not always reflect the usefulness of its transport function. Its binding centers can be blocked by toxic ligands, and therefore the transport capacity is sharply reduced. The most advanced techniques for assessing the blocking and binding of albumin binding sites by metabolites and toxic ligands are techniques using fluorescent probes.
In order to objectify the assessment of ESI, it is proposed to use the so-called integral index of intoxication, calculated using multivariate statistical methods based on the definition of a complex of biochemical, hemorheological, biophysical and optical-polarization indicators, combined into the concept of “endotoxigram”.
CONCLUSION
In conclusion, we emphasize the features of the endogenous intoxication syndrome in viral hepatitis:
1. Hepatitis viruses cause cytolysis of hepatocytes due to direct or immune-mediated damaging effects, which is the fundamental mechanism of pathogenesis that forms the syndrome of endogenous intoxication.
2. The pathological process leads to disruption of many liver functions, especially protein-synthesizing, which is accompanied by a decrease in both albumin synthesis and its nonspecific detoxification and transport functions.
3. Activation of lipid peroxidation leads to the accumulation of free radicals, which enhances endotoxicosis.
4. Immune imbalance, manifested in viral hepatitis by both quantitative and qualitative dysfunction of immunocompetent cells and humoral immunity factors,
leads to activation of the vital activity of endogenous flora and an increase in the products of its metabolism, which leads to an increase in the load on the body’s detoxification systems.
5. Additional damaging effects on cell membranes, organs and body systems are exerted by the resulting endogenous toxic substances, including the main organ of the detoxification system - the liver.
6. Laboratory manifestations of endogenous intoxication syndrome are recorded against the background and at the end of an acute pathological process, in the chronic course of viral hepatitis without clinical manifestations and in the formation of liver cirrhosis, which confirms the scale and depth of changes in the liver as the main organ and regulator of the detoxification system.
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> Intoxication of the body
This information cannot be used for self-medication!
Consultation with a specialist is required!
What is intoxication?
Intoxication of the body is a pathological condition caused by negative impact various toxic substances that can enter the body from the outside or form within it as a result of the development of certain diseases. Depending on how the poison entered the body, exogenous and endogenous intoxication are distinguished.
Exogenous poisoning
Exogenous intoxication is also called general poisoning. This condition occurs and develops when poisons and toxic substances enter the human body: arsenic, selenium, beryllium, heavy metals, fluorine, chlorine, iodine. The poisonous substance can be toxins from poisonous plants, microorganisms or animals. The poison can enter the body through the skin, mucous membranes, through the digestive tract and respiratory tract. Sometimes the cause of general poisoning is not the toxic substance itself, but the products of its transformation. The most common is exogenous intoxication, caused by an overdose of alcohol or drugs.
Endogenous intoxication
Endogenous intoxication is designated by the terms “endotoxicosis”, “autointoxication”. This condition develops as a result of a violation of the removal of metabolic products from the body in certain diseases. Endogenous intoxication is always observed in malignant neoplasms, infectious diseases, in case of impaired functioning of the kidneys and intestines. Self-poisoning can develop if the body produces excess quantity and biologically active substances accumulate (thyroid hormones, adrenaline, etc.). Endogenous intoxication is accompanied by burns and serious injuries of various origins. Endotoxicosis occurs in rheumatoid arthritis, acute pancreatitis, sepsis and other pathologies.
Clinical manifestations
Clinical manifestations of intoxication are quite wide. It all depends on the nature and concentration of the toxic substance, as well as the degree of poisoning. Acute intoxication is manifested by the following symptoms: high fever, severe pain in joints and muscles, vomiting, diarrhea. If the toxins are very poisonous, loss of consciousness and even coma may occur.
The state of subacute intoxication is indicated by low-grade fever (up to 38 degrees), headache and muscle pain, disturbances in the functioning of the gastrointestinal tract, drowsiness and constant feeling fatigue.
Chronic intoxication develops as a result of incomplete treatment acute poisoning or in case of impaired excretion of metabolic products from the body and is characterized by the following symptoms: irritability, depression, insomnia, general weakness, chronic headaches, weight changes, serious gastrointestinal problems (flatulence, diarrhea, constipation).
Intoxication in most cases negatively affects the state of the immune system and skin. An unpleasant body odor appears, various skin diseases(dermatitis, furunculosis, acne), allergic reactions appear, the body's resistance to viruses and bacteria is significantly reduced, and sometimes autoimmune pathologies develop.
Treatment of intoxication
When treating intoxication, the main efforts are aimed at neutralizing toxic substances through the use of antidotes ( Vaseline oil, activated carbon, sodium hypochlorite, potassium permanganate) or antitoxic serums. The next step is to accelerate the removal of toxins from the body (rinsing the cavities, drinking plenty of fluids, use of laxatives and diuretics, oxygen therapy, transfusion of blood substitutes). Anyway correct treatment can only be prescribed by an experienced doctor, so at the first symptoms of poisoning you must seek help without delay. Self-medication is dangerous for health, and sometimes even for human life.
