Endogenous intoxication syndrome severity. Endogenous intoxication of the body. Causes of endogenous poisoning

The concept of endogenous intoxication.

Main types of endotoxicosis in surgical patients

General clinical and laboratory signs of endotoxicosis

Criteria for the severity of endogenous intoxication in a surgical clinic.

Principles of treatment of endotoxicosis

Elimination of tissue hypoxia

Artificial removal of toxic products from the body

Basic methods of extracorporeal detoxification.

The concept of endogenous intoxication.

Endogenous intoxication syndrome (EIS) is understood as a complex of symptoms caused by the accumulation of endotoxins in tissues and biological fluids.

Endotoxicosis – accumulation of toxic metabolites in high concentrations in tissues and biological fluids (blood, lymph, cerebrospinal fluid).

Endotoxemia is the accumulation of toxic metabolites in the blood.

Main types of endotoxicosis in surgical patients

Traumatic endotoxicosis– occurs when the body is released from compression and the products of autolysis of crushed tissue are absorbed into the victim’s blood.

Ischemic endotoxicosis– disruption of the delivery of oxygen and oxidation substrates to tissues, and removal of tissue metabolic products.

Infectious-inflammatory endotoxicosis– formation of a local infectious-inflammatory focus as the main source of endogenous intoxication.

Metabolic endotoxemia– against the background of high activity of the source of formation of toxic substances, one’s own natural detoxification mechanisms turn out to be imperfect.

Dishormonal endotoxicosis– increased release of hormones by pathologically altered internal secretion organs.

General clinical and laboratory signs of endotoxicosis

Clinical assessment of endotoxemia:

CNS– excitement or depression of consciousness. Detection of CNS pathology does not require any special methods.

With severe degrees of endotoxemia, patients experience deep mental stupor (stupor or coma).

With less severe intoxication, patients experience stupor, delirium, and twilight stupefaction.

Hemodynamic disorders

Tachycardia in the absence of blood loss, severe impairment external respiration- one of the signs of endogenous intoxication.

With tachycardia 120 bpm. and more tachycardia is accompanied by a decrease in blood pressure. Heart sounds are muffled, the ECG shows diffuse muscle changes. Then microcirculation disorders develop: pallor and marbling of the skin.

Disturbances in the external respiration system

In the absence of chest trauma or massive pneumonia, acute respiratory failure develops as a consequence of developing tissue hypoxia. The lungs are one of the first target organs to be damaged.

Microcirculation disorders

Increasing the content of biologically active substances in the blood that affect vascular tone and permeability (histamine).

An increase in the content of substances that damage and disrupt the synthesis of pulmonary surfactant (endotoxins, molecules of average weight, products of lipid peroxidation).

Acute respiratory failure manifests itself in shortness of breath and decreased saturation.

Acute hepatic-renal failure – more often a consequence of microcirculation disorders.

Fluid and electrolyte disturbances

Manifestations of dehydration (dryness and decreased skin turgor, disappearance of the relief of the saphenous veins, sunken eyeballs, thirst, dry tongue).

Loss of water (peritonitis, acute intestinal obstruction, infectious and inflammatory processes of other localization, accompanied by exudation and hyperthermia)

Other types of endotoxemia in surgical patients (stimulation of natural detoxification mechanisms: endogenous hemodilution and interstitial edema in the area of ​​the inflammatory process)

Thermoregulation disorders

Hyperthermia, in critical condition hypothermia

Decreased gastrointestinal motility

Laboratory assessment of endotoxemia:

Leukocytosis, shift leukocyte formula to the left, toxic granularity of neutrophils

In severe cases of endotoxemia, leukocytosis increases in the peripheral blood with a tendency to very high numbers - 25-30∙10 9 . The leukocyte formula changes due to an increase in the number of neutrophils (band and myelocytes). This change in the leukocyte formula is called a shift to the left. Neutrophilia indicates the activity of the inflammatory process, eosinophilia indicates relative insufficiency of adrenal function, lymphopenia indicates a state of immune depression.

Acceleration of ESR

Decrease in total blood protein content

Hyperfermentemia (increased levels of ALT and AST in the blood)

Increased bilirubin content in the blood

Hyperazotemia (increased levels of urea and creatinine in the blood)

Decreased levels of cellular and humoral immunity.

Markers of endotoxemia:

Medium molecules (SM, c.u.), norm up to 0.2 c.u.

Medium molecules include lysosomal enzymes, proteolysis products and oligopeptides. The main source of their formation is considered to be increased catabolism and non-enzymatic proteolysis, including blood proteins. They inhibit erythropoiesis, inhibit gluconeogenesis and DNA synthesis, have a cytotoxic effect, and cause microcirculation disorders.

Leukocyte intoxication index (LII, cu), norm 1.0-1.4

LII according to Kalf-Kalif:

LII=(4 mon+3 yun + 2 pal + segm)×(plasm + 1) / (mon + lymph) × (eos + 1)

Plasma cells in small numbers can appear in any infectious-inflammatory process, in malignant neoplasms.

Proteolytic activity of blood serum (PA, min.), norm up to 4

Circulating immune complexes (CIC, units), norm up to 40

Lipid peroxidation (LPO), increase.

CONCEPT AND CLASSIFICATION OF ENDOTOXICOSIS,
ENDOGENOUS INTOXICATION
AND ENDOGENOUS TOXIC SUBSTANCES

Endotoxicosis is a typical pathological process, which is the structural and functional response of the body to toxic aggression of both endogenous and exogenous nature. From a narrower practical point of view, it can be characterized as a clinical manifestation of endogenous intoxication, which is not restrained by the mechanisms of adaptation and compensation of toxic information.

Distinguish

• acute endotoxicosis [show] .

  In acute endotoxicosis, endogenous intoxication steadily progresses despite the development and tension of compensatory mechanisms (the content and range of ETS progressively increase), which leads to disruption of homeostasis regulation, the formation of multiple organ failure syndrome, disintegration of body functions and often death.

• subacute endotoxicosis [show] .

  Subacute (protracted) endotoxicosis can be considered a variant of acute endotoxicosis, which is characteristic of a slowly (over several days or even weeks) progressive pathological condition. Compensatory reactions long time inhibit its progression. In the future, in the absence effective treatment, there is a breakdown of compensatory mechanisms and the rapid development of poorly correctable metabolic disorders, usually leading to death.

• chronic endotoxicosis [show] .

  Chronic endotoxemia is a pathological process in which the maintenance of homeostasis and, consequently, the viability of the body is achieved due to the development of compensatory mechanisms. Fatal disturbances of homeostasis do not occur, but excessive activity of detoxification systems for a long time leads to their gradual depletion and a decrease in the body’s resistance and reactivity to damaging environmental factors. Chronic endotoxicosis can exist for many years. Its manifestations are diverse and have specificity due to the disease that caused it.

Endogenous intoxication (EnI) there is a polyetiological and polypathogenetic syndrome, characterized by the accumulation of endogenous toxic substances (ETS) in tissues and biological fluids - an excess of products of normal or perverted metabolism or cellular response. It is a complex multicomponent phenomenon, including:

• a source of toxemia that ensures the formation of ETS;
• biological barriers that prevent the breakthrough of endogenous toxins beyond the source;
• mechanisms of transfer of these toxic products to target cells, to organs of biotransformation and/or excretion;
• mechanisms of immobilization and deposition, biotransformation (neutralization) and excretion of toxic products;
• effector responses to intoxication in the form of so-called secondary toxic aggression, as a result of which EnI largely loses its specificity.

Although endogenous intoxication is polyetiological, the following main primary mechanisms of its development can be distinguished:

• production or metabolic, caused by excess production of endogenous toxic substances (general peritonitis, acute pancreatitis, acute pneumonia);
• resorptive, when resorption of toxic substances occurs from a limited focus of infection, decaying tissue (intestinal obstruction, soft tissue phlegmon, abscesses, etc.);
• reperfusion, in which the systemic bloodstream receives substances that have accumulated in long-term ischemic tissues, as well as those released from the cells of these tissues when they are damaged by active oxygen and excess free radicals against the background of failure of antioxidant protection (shock, reperfusion syndrome, operations using a heart-lung machine and etc.);
• retention, in which the accumulation of ETS occurs as a result of a violation of their excretion by natural detoxification organs (acute renal (AR) and liver (AL) failure);
• infectious, as a result of the entry of microorganisms, products of their metabolism and decay from the focus of invasive infection or by translocation from a perversely contaminated gastrointestinal tract.

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.

The question of what could be such toxic substances and determine the severity of the patient’s condition is complex and controversial, since many substances, depending on their concentration, can have both beneficial and unfavorable functional effects, and most of them have not been identified at all. You can try to classify them depending on the etiology [show] and excretion mechanism [show] .

Division of ETS by formation mechanism

• products of normal metabolism in high concentrations (lactate, pyruvate, uric acid, urea, creatinine, bilirubin glucuronide, etc.);
• substances that are excessively formed during perverted metabolism (ketones, aldehydes, alcohols, carboxylic acids, ammonia, etc.);
• decay products of cells and tissues from foci of tissue destruction and/or from the gastrointestinal tract in case of disruption of the barrier functions of membranes (lipases, lysosomal enzymes, cationic proteins, myoglobin, indole, skatole, phenol, etc.);
• components and effectors of the body's regulatory systems in pathological concentrations;
• activated enzymes (lysosomal, proteolytic, activation products of the kallikrein-kinin cascade, blood coagulation and fibrinolysis systems);
• inflammatory mediators, biogenic amines, cytokines, prostaglandins, leukotries, acute phase proteins and other biologically active substances;
• active compounds formed during lipid peroxidation;
• microbial toxins (exo- and endotoxins) and other pathogenicity factors of microorganisms (pathogenic, opportunistic, non-pathogenic);
• immunoforeign products of cellular decay, antigens and immune complexes-aggressors.

Division of ETS according to the mechanism of excretion

• gaseous substances - 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;
• hydrophobic low- and medium-molecular substances - bind to blood plasma proteins, acquire the properties of haptens and are absorbed by cells of the immune system;
• high molecular weight compounds are eliminated by the monocyte-macrophage system (up to 80% of the body's macrophages are located in the liver).

Acute endotoxicosis occurs as a cascade process. Its development and progression is associated with a discrepancy between the formation (intake, etc.) of toxic substances, including those formed as a result of subsequent toxic autoaggression, and the ability of the organs included in the functional detoxification system (lungs, liver, kidneys, gastrointestinal tract, skin, immunological surveillance system), transform, neutralize and eliminate them. Disturbances in the relationships between antagonistic substances in humoral regulatory systems (enzymes-antienzymes, oxidants-antioxidants, cytokines-anticytokines, etc.) may be of significant importance.

Based on the relationship between endogenous intoxication and the possibilities functional system detoxification (FSD), 4 stages of development of endotoxemia can be distinguished (Table 16.1 [show] ).

In the compensation stage, FSD completely compensates for the toxemic load. In the tension stage, the rate of production of toxic substances coincides with the maximum capabilities of the FSD. In the subcompensation stage, the production of toxic substances definitely exceeds the capabilities of the FSD. And finally, in the stage of decompensation, failure of the FSD organs develops and life-threatening metabolic and functional disorders appear.

The concentration of any ETS in a specific clinical situation reflects the resulting rates of formation of this substance, the rates of its accumulation and distribution in tissue and cell-membrane depots, and the rate of its biotransformation or elimination through the main and additional pathways (Fig. 16.1).

To determine treatment tactics and select the optimal intensive therapy program for endotoxicosis, it is necessary to establish not only the fact of toxemia and intoxication, which in acute and subacute cases is usually obvious, but also to ensure a diagnosis of the severity of secondary toxic autoaggression. An attempt to rely in solving these problems only on markers of intoxication, like studying the content of xenobiotics, or on studying the final and intermediate products of metabolism in body fluids - in blood plasma, lymph, cerebrospinal fluid - is not informative enough. Such a study undoubtedly provides information about the primary affect of intoxication, provides guidance in its sources and mechanisms, but in practice this is always not enough to determine the direction and entire treatment program. A more complete picture is formed when considering endotoxicosis from the perspective of the balance of endogenous intoxication and the capabilities of FSD.

All these approaches can be implemented in the practical activities of the laboratory service, which ensures the daily activities of intensive care units and units, offices, departments and extracorporeal hemocorrection centers.

We believe that laboratory criteria of several levels should be distinguished:

• markers of acute poisoning or endogenous intoxication, if they are clearly defined in a given clinical situation;
• laboratory criteria characterizing secondary toxic autoaggression, focused on assessing the response of the patient’s body to primary and secondary intoxication, and also allowing to determine the dynamics of the toxicity of components of the internal environment and the stage of endotoxicosis;
• indicators characterizing the work of the FSD, organs and life support systems of the body.

At the same time, it is important to evaluate the impact of the most active detoxification effect, which can often be an additional stress factor, sometimes quite aggressive. Sufficiently frequent and rapid acquisition of these parameters is the main condition for prompt medical control during intensive care. The algorithm for assessing such indicators is presented in Table. 16.2 [show] .

DIAGNOSIS OF INITIAL TOXINEMIA

Complete information can only sometimes be provided quantification endogenous toxic substance - a specific marker of this form of endogenous intoxication, but this is not always an absolute criterion for initial toxinemia.

Determining the level of blood lactate against the background of a critical condition of the patient’s body and hyperglycemia allows us to assess the severity of lactic acidosis, but only its comparison with other indicators of carbohydrate metabolism allows us to attribute this phenomenon to posthypoxic acidosis or to lactic acidosis as a manifestation of critical decompensation diabetes mellitus. Another option that confirms the presence of the diabetogenic nature of endogenous intoxication is the determination of ketone bodies, especially if it is correlated with data from a study of the acid-base state of the blood and the level of osmolarity.

When assessing the depth of EI in obstructive jaundice, one can focus on the level of blood bilirubin, which correlates with the severity of mental disorders and the severity of hepatocellular failure. However, in many cases, information only about the level and dynamics of hyperbilirubinemia is clearly not enough to diagnose endotoxemia against the background of liver failure.

A sustained increase in plasma potassium levels (hyperkalemia above 6 mmol/l) allows us to think about the danger of its further retention in the body with the development of a critical condition and vital necessity active detoxification. This should especially attract attention if urination is significantly reduced and signs of hyperkalemia are detected on the ECG.

High level of nitrogenous wastes in the blood (residual nitrogen, urea, uric acid) allows us to associate the development of initial toxinemia with kidney damage and retention of these toxic substances, although a production mechanism for the development of azotemia is also possible. Typically, in the background of many EI variants, there is a combination of these two mechanisms. It is necessary to expand the study to assess the predominant nature of this disorder: along with urea, examine residual blood nitrogen, and also determine the splitting index, that is, the proportion of polypeptides in the total pool of residual nitrogen. Normally, the cleavage index is 0.16-0.24; with production azotemia it increases to more than 0.32. A purely retentional nature of azotemia is also possible, which is associated with electrolyte disorders in the form of chloroprivate azotemia. It is usually observed in hypochloremic hypokalemic alkalosis, which additionally requires determination of the concentration of chloride and bicarbonate ions in the blood plasma and extracellular fluid.

Determination of the activity of pancreatic enzymes in blood serum, especially proteinases and lipases and their inhibitors, can characterize the level of enzyme-producing EnI in destructive pancreatitis. The location of blood sampling for testing is of certain importance. If we imagine the importance of the lungs as a detoxification organ, the greatest information about the markers of this type of EI can be provided by mixed venous blood (from the central vein or right atrium), which gives an idea of ​​​​the level of these markers before such toxic information is “processed” by the lungs.

Much more accurately, the depth of the pathological process in the pancreas is reflected by the study of pancreatic enzymes in the lymph of the thoracic lymphatic duct (if it is drained for the purpose of detoxification).

This approach reveals the meaning lymphatic system in the transport of ETS from the interstitium of damaged organs into the blood. Certain information can be provided by studying the protein spectrum of lymph and its colloid osmotic pressure (COP). In patients with severe intoxication, analysis of the first samples reveals a tendency towards an increase in total protein (above 40 g/l) with an increase in the concentration of coarse proteins (IgM, sialoproteins, haptoglobins and other macroglobulins), which indicates the presence of not only dysproteinemia, but also destructive degenerative process causing intoxication.

A criterion for the severity of EI in rhabdomyolysis as a result of soft tissue crushing, in long-term crush syndrome of large muscle masses or its non-traumatic analogue - positional compression syndrome, reperfusion syndrome after operations on the great vessels of the extremities may be the level of blood myoglobin. The possibility of obtaining information using this marker in traumatological and surgical practice allows, with a certain assumption, to use it for ischemic lesions of the myocardium. Although the share of this EnI factor in the general pool of ETS in such a pathological phenomenon as acute heart attack myocardium, significantly less than with conventional rhabdomyolysis.

At the initial stage of septicemia, the determination of microbial lipopolysaccharides using the LAL test, in which the main reagent is the amebocyte lysate of the land crab Limulus Poliphemus, makes it possible to fairly objectively judge the level of the microbial factor of endogenous intoxication. But the same test can indicate a significant level of endotoxemia in the absence of a clearly defined focus of purulent infection, for example, in the so-called “septic syndrome”, which is detected against the background of refractory circulatory shock.

Undoubtedly, it is of interest to study the content of regulatory factors (hormones, biologically active substances and mediators of tissue metabolism and inflammatory mediators) as ETS. Indeed, identifying pathological levels of thyroid hormone or a regulatory peptide, for example, vasointestinal peptide, or prostaglandins, makes it possible to judge the severity of EnI and suggest ways of its further development. Important information To determine treatment tactics, a study of the primary messengers of the immune response IL-1 and TNF can also provide information. But these techniques are available only to large domestic hospitals and diagnostic centers.

Among the tests reflecting the immunopathological effects of the primary affect of endotoxemia, the most often used are studies of tissue antigens, the level of circulating immune complexes (CIC) and blood complement. In any case, an increase in the concentration of CEC with a simultaneous decrease in the level of the C 3 component of complement may indicate excessive formation of immune complexes. They can become both a factor of primary pathogenic impact and a factor of secondary autoaggression and contribute to tissue and organ manifestations of endotoxicosis.

The multicomponent factors of aggression that underlie even initial stages endotoxicosis, the possibility of direct and indirect potentiation of pathogenic factors against the background of primary toxinemia, the individuality of the adaptive reactions of the body of a particular patient create difficulties for direct monitoring of the severity of EI using the “factor - level of intoxication” or “factor - stage of endotoxemia” algorithm. The functional background against which endotoxinosis develops is also important, for example, the severity of dehydration, hypoproteinemia and anemia, and the state of the functional detoxification system.

LITERATURE [show] .

1. 1. Artsishevskaya R. A., Samoilova K. A. Functional and structural changes surface of human red blood cells after irradiation with UV rays different lengths waves. 2. Sorption of Alcian blue by external near-membrane components // Tsitology. - 1983. - T. 25, No. 12. - P. 1387-1392.
2. Belyakov N.A., Miroshnichenko A.G., Malakhova M.Ya., Izotova O.G. Verification of endotoxicosis in patients with generalized peritonitis // Efferent Therapy. - 1995. - T. 1, No. 2. - P. 14 -19.
3. Bobrinskaya I.G., Zavyalov R.P., Tishkov E.A. Arteriovenous difference between osmotic and hemostatic parameters as a criterion early diagnosis pulmonary complications with severe combined trauma // Anesthesiology and Reanimatology. - 1997. - No. 4. - P. 56-60.
4. Vladyka A. S., Levitsky E. R., Poddubnaya L. P., Gabrielyan N. I. Medium molecules and the problem of endogenous intoxication in critical conditions of various etiologies // Anesthesiology and Reanimatology. - 1987. - No. 2. - P. 37-42.
5. Gabrielyan N.I., Dmitriev A.A., Kulakov G.P. Diagnostic value of determining medium molecules in blood plasma in nephrological diseases // Clinical. medicine.- 1981.- No. 10.- P. 38-42.
6. Galaktionov S.G., Tseytin V.M., Leonova V.I. et al. Peptides of the group of “medium molecules” // Bioorganic chemistry. - 1984. - T. 10, No. 1. - P. 5-17.
7. Gelfand E. B., Gologorsky V. A., Gelfand B. R. Clinical characteristics abdominal sepsis in surgical patients // Infection and antimicrobial therapy. - 2000. - T. 2, No. 1. - P. 6-11.
8. Goncharova V. A., Zhangelova M. B., Voinov V. A. et al. Study of biologically active substances in the blood in post-perfusion pulmonary syndrome // Anesthesiology and Reanimatology. - 1988. - No. 1. - P. 17-20.
9. Gryzunov Yu. A., Dobretsov G. E. Serum albumin in clinical medicine. - M.: Irius, 1994. - -226 p.
10. Ershov A. L. Diagnosis of the stages of endogenous intoxication during postoperative complications in abdominal surgery //Endogenous intoxications. - St. Petersburg: SPbMAPO, 1994.- P. 70-71.
11. Eryukhin I.A., Shashkov B.V. Endotoxicosis in a surgical clinic. - St. Petersburg: Logos, 1995. - 304 p.
12. Malakhova M. Ya. Method of recording endogenous intoxication. - St. Petersburg: SPbMAPO, 1995. - 35 p.
13. Marusanov V.G., Mikhailovich V.A., Domanskaya I.A., Gulo S.L. Characteristics of the stage of endogenous intoxication // Efferent Therapy. - 1995. - T. I, No. 2. - P. 26-30.
14. Medical laboratory technologies and diagnostics: Handbook. Medical laboratory technologies. T. 2 / Ed. prof. A. P. Karpishchenko. - St. Petersburg: Intermedica, 1999. - 656 p.
15. Masyutin V. A., Shirokov D. M., Pivovarova L. P., Nokhrin S. P. Assessment of laboratory data in critical conditions (interpretation, prediction, drug correction) / Ed. prof. S. I. Peregudova. - St. Petersburg: V. p., 1999. - 76 p.
16. Nikolaychik V.V. Molecular mechanisms of development of endogenous intoxication and improvement of detoxification pathways: Abstract of thesis. dis....doctor of medical sciences. - M., 1984.- 43 p.
17. Obolensky S.V., Malakhova M.Ya., Ershov A.L. Metabolic status of the body, methods of recording and interpreting results // Extreme states and post-resuscitation pathology. - Novosibirsk, 1989. - P. 79-86.
18. Obolensky S.V., Malakhova M.Ya., Ershov A.L. Diagnosis of the stages of endogenous intoxication and differentiated use of efferent therapy methods // News of Surgery. - 1991. - T. 146, No. 3. - P. 95-100.
19. Rybachkov V.V., Malafeeva E.V. The nature and mechanisms of action of endogenous intoxication // Clinic and treatment of endointoxication in acute surgical diseases. - Yaroslavl, 1986. - P. 5-43.
20. Togaibaev A. A., Kurguzkin A. V. Hemosorption in emergency conditions. - Alma-Aga: Science of the Kazakh SSR, 1988. - P. 136.
21. Tulikova Z.A. Medium molecular uremic toxins: (literature review) // Questions of honey. chemistry.- 1983.- T. 29. issue 3. pp. 108-111.
22. Umansky M. A., Pinchuk L. B., Pinchuk V. G. Endogenous intoxication syndrome. - Kyiv: Nauk, Dumka, 1979. - 204 p.
23. Fedorovich V. Yu., Ostrovskaya E.L. Spectrophotometric express diagnosis of postoperative infectious complications in cardiac surgery patients // VI All-Russian Congress of Anesthesiologists and Reanimatologists. - Tez. report - M.: B.I., 1998.- P. 245.
24. Filin V.I., Kostyuchenko A.P., Tsibin Yu.N. // Modern ideas about acute endogenous intoxication // Forced diuresis in a surgical clinic. - L.: B.I., 1976.- P. 3-21.
25. Khapevich M.D. Pathogenetic and clinical significance of medium-weight molecules and lipid peroxidation in the development of endogenous intoxication syndrome in general peritonitis: Abstract of thesis. dis. ...cand. honey. Sciences - L., 1987. - 14 p.
26. Chalepko V. V., Kutushev F. X. Endogenous intoxication in surgery // Bulletin of surgery. - 1990. - T. 144, No. 4. - P. 3-8.
27. Shifrin A. G., Shifrin G. A. Scientific Basics integrative medicine. - Zaporozhye: Wild Field. 1999.- 298 p.
28. Endogenous intoxication in acute surgical diseases / Ed. prof. Yu.N. Belokurova and V.V. Rybachkova. - 2nd ed. with changed. and additional - Yaroslavl, 2000. - 184 p.
29. Endogenous intoxications / Proc. International symposium - St. Petersburg, 1994.- 280 p.
30. Engervall P., Granstrom M., Andersson B. et al. Monitoring of endotoxin, interleukin-6 and c-reactive protein serum in neutropenic patients with fever // Eur. J. Haematol.- 1995.- Vol. 54, N4. - P. 226-234.
31. Knaus W. A., Draper E. A., Wagner D. P. et al. The APACHE-III prognostic system // Chest.- 1991.- Vol.100, N6. P. 1619-1636.
32. Reinke P., Docke D. W., Syrbe U. et al. Einsatz von Blut-reinigungsverfahren bei Sepsis auf der Basis neuer Erkentnisse zur Immunopathogenese der Sepsis // Kontinuierliche Blutreinigungsverfahren in der Intensivmedizin.- Lengerich; Berlin: Pabst, 1994.- S.23-37.
33. Steinmetz H.T., Herbertz A., Bertram M., Diehl V. Increase in interleukin-6 serum level preceding fever in granulocytopenia and correlation with death from sepsis // J. Infect. Dis.- 1995.- Vol.171, N1. - P.225-228.
34. Topfer G., Thomae R., Zawta B. Proteine ​​- Fragen und Antworten fur die medizinische Diagnostik.- Manncheim: Boehringer Mannheim GmbH.- 1996.- 111 S.

Source: Medical laboratory diagnostics, programs and algorithms. Ed. prof. Karpishchenko A.I., St. Petersburg, Intermedica, 2001

Acute intoxication is a severe pathological condition of the body, which is caused by an infectious process, poisoning with chemicals or toxins. It is important to know the stages of intoxication of the body, what this definition means, what exogenous toxins are the causes of this condition, what clinical signs And unspecified symptoms it is expressed, as well as methods of treatment.

General definition of acute poisoning

The term “intoxication of the body” is a collective and very broad definition that is used for many pathological conditions and diseases. Intoxication means poisoning of the body some microorganisms or substances. There are exogenous and endogenous, as well as chronic and acute intoxication.

During acute poisoning, the body simultaneously receives a large amount of poisons or toxins. This condition is expressed by the rapid deterioration of a person's condition. If a patient comes into contact with a substance for a long time, for example, at the workplace, then he begins to experience chronic poisoning.

Exogenous intoxication of the body

During this type of intoxication, a toxic substance enters the body from the external environment. This poisoning can be both chronic and acute. The main reasons for the appearance of exogenous intoxication are as follows:

Causes of endogenous poisoning

During this intoxication, toxic substances begin to be produced directly by the body. Endotoxins can be products of metabolic and inflammatory reactions, hormones and enzymes. Under certain circumstances, for example, with increased physical activity or acute inflammation, acute renal failure, dehydration, substances that are produced by the body itself become poisonous and dangerous.

In addition, endotoxins are produced malignant neoplasms during the growth and progression of cancer tumors. Patients who suffer from cancer are constantly low-grade fever body, and the level of inflammatory indicator in the blood test is off the charts.

Signs and clinical symptoms

Symptoms and signs of intoxication will depend on the cause of the poisoning and the method of penetration of the toxin into the body. Let us describe the main features of the clinical symptoms of intoxication, taking into account the etiology of development.

Food poisoning

On average, the first symptoms appear within the first 8 hours after eating a contaminated or spoiled product. During poisoning poisonous mushrooms clinical picture appears after 15−20 minutes, and in case of infection with botulism or intoxication with canned food - after 20−24 hours.

Main features food poisoning:

• Vomiting and nausea are protective reactions of the body. By vomiting, the stomach removes bacteria and toxins. In the masses of vomit you can see mucus, bile and food debris.
• General weakness, dizziness and headache- the main symptoms of intoxication of the body.
• An increase in body temperature during food poisoning does not always appear. The manifestation of this symptom indicates a severe course of the disease and a pronounced intoxication syndrome.
• Diarrhea. Its frequency and volume will depend on the degree of intestinal intoxication and the cause of poisoning. So, with salmonellosis, the stool is foamy and green, and with dysentery, it is watery.
• With the development of botulism, the patient’s signs of central nervous system damage increase over time: vision, coordination, swallowing, speech deteriorate, paresis, paralysis and convulsions may appear.
• Tachycardia is a sign of severe intoxication, dehydration, and an accelerated pulse is noted.

Drinking large amounts of alcohol

Alcohol intoxication appears 2-3 hours after drinking alcohol. During poisoning methyl alcohol Symptoms may only appear after 24 hours.

Initially, the disease occurs on the principle of food poisoning. The patient vomits, develops diarrhea, and has abdominal pain. But later they can develop seizures, hallucinations, the person may fall into a coma.

Alcohol poisoning is often complicated by damage to the kidneys and liver. During severe poisoning syndrome, breathing and heart function are impaired.

Please note that when intoxicated with methyl alcohol, visual impairment may occur. At first, a person notices a decrease in the clarity and sharpness of what he sees. Without treatment, complete blindness begins, and after death.

Damage from alkalis and acids

A characteristic feature of this intoxication is a burn of the mucous membrane of the esophagus and stomach, caused by substances that the patient drank. Alkalies and acids can cause damage to the integrity of the walls of blood vessels and eat away the mucous membrane. Poisoning with alkalis and acids is often accompanied by bleeding in the gastrointestinal tract.

Clinical symptoms of intoxication with acids and alkalis:

• Tachycardia.
• Burning and pain in the stomach and along the esophagus.
• Hypotension (low blood pressure).
• Dyspnea.
• Impaired consciousness.
• Vomiting bloody or black contents is a sign of bleeding.

When alkalis and acids enter the body, the pancreas, liver, and kidneys are affected.

Drug overdose

Any medicinal product if taken incorrectly, it can cause overdose and intoxication. Signs of poisoning medical supplies will depend on the active substance. Most often, in the next half hour after taking a toxic dose of medicine, the first symptoms of poisoning appear. They can be similar to a toxic food infection (manifest by abdominal pain, diarrhea, vomiting) or be expressed by symptoms of damage to various systems and organs.

Please note that the instructions for any medication describes the symptoms that may appear during an overdose.

Infections of a bacterial or viral nature

Any infection that enters the body begins to lead to intoxication syndrome. For example, in case of blood intoxication, sepsis, bacteria cause an inflammatory systemic reaction; bacterial infection is observed in many systems and organs.

Intoxication syndrome during infections is expressed by an increase in body temperature to subfebrile or febrile levels, headache, chills, dizziness and general severe weakness. Muscle pain, joint aches, diarrhea and vomiting may occur.

Household or natural gas

The rate at which symptoms increase during gas intoxication will depend on its concentration in the air. The higher the concentration, the faster the damage to the body develops.

During the inhalation of fumes, protein and hemoglobin, which delivers oxygen to all cells, begin to turn into methemoglobin - a substance that is not able to bind oxygen. Which leads to hypoxia - a lack of oxygen, which primarily affects the kidneys, heart and brain.

Signs of gas intoxication include:

Basic diagnostic methods

Intoxication is considered a very general concept, and for a doctor to determine the correct etiological treatment its cause must be determined. The diagnosis is made by a specialist after examining the patient, examining him and taking a detailed history. It is important to tell your doctor the following information:

• Time of appearance of the first signs of the disease.
• Having had contact with an infectious person in recent weeks (the incubation period for certain infections can be quite long).
• Recent illnesses.
• Availability chronic diseases(for example, hypertension, diabetes, irritable bowel syndrome, coronary disease hearts, etc.).
• What could trigger the disease (you need to tell your doctor what foods you ate in Lately and took medications).

Do not forget that if you are allergic to any food components or medications, you must definitely tell your doctor about it.

To establish an accurate diagnosis, determine the pathogen and assess the person’s condition, additional instrumental and laboratory examination of the patient may be required. If a person’s condition is serious, then diagnosis is carried out simultaneously with first aid.

List of diagnostic methods that can be necessary to establish a diagnosis during intoxication:

Intoxication is a collective concept that reflects infection or damage to the body by microorganisms or toxins. Toxic substances can come from outside or be produced directly by the body. Treatment is prescribed by a specialist after diagnosis is made. Why is a detailed examination of the patient carried out, which allows us to establish the cause of the development of intoxication.

Currently, one of the most difficult problems in intensive care is endogenous intoxication syndrome(SEI), which accompanies a significant number of pathological conditions (shock, peritonitis, pancreatitis, etc.), which, as they develop, can lead to death.

Progression of endotoxemia is caused by the accumulation in the blood of substances of different origin, chemical structure and biological effects called endotoxins. Endotoxins contribute to the development of acute renal and hepatic failure, cardiovascular failure, acute respiratory distress syndrome, ultimately leading to the appearance of an extremely serious condition - multi-organ dysfunction syndrome.

Endogenous intoxication - clinical syndrome, which occurs in pathological conditions of various etiologies, caused by the accumulation in the tissues and biological fluids of the body of products of impaired metabolism, metabolites, destructive cellular and tissue structures, destroyed protein molecules, pi accompanied by functional and morphological lesions organs and systems of the body.

There are three main links that determine the severity of the patient’s condition and severity clinical symptoms: toxemia, impaired microcirculation, inhibition of the functions of the body’s own detoxifying and protective systems.

The main link pathogenesis of endogenous intoxication syndrome is toxemia. Unfortunately, clear differentiation of toxic substances of endogenous origin is practically impossible. However, in each specific case, “primary” and “secondary” endotoxins can be distinguished. So, for burns, long-term crush syndrome, obliterative vascular diseases“primary” are the products of protein degradation, “secondary” are the products of natural metabolism, the accumulation of which in the body is a consequence of inhibition of the functions of natural detoxification and excretion.

Endotoxemia, disrupting the tone of peripheral vessels, blood rheology, kinetic and mechanical properties of blood cells, leads to tissue hypoxia, which is one of the important links in the pathogenesis of SEI, the course of which is aggravated by a decrease in the function of natural detoxification and excretion organs. Toxins block the binding sites of albumin molecules, which leads to a decrease in the effectiveness of the drug treatment, since this protein is a transport agent for many pharmacological drugs.

Clinic of endogenous intoxication syndrome.

A comparison of experimental and clinical studies made it possible to identify the following stages development of endogenous intoxication syndrome.
Stage I of endogenous intoxication syndrome. Reactive toxicity occurs in response to the formation of a primary destructive focus or traumatic injury. Laboratory signs of this stage are an increase in the blood levels of average mass molecules (MSM), lipid peroxidation products (LA and MDA), and an increase in LII.

Stage II of endogenous intoxication syndrome- the stage of severe toxemia develops after a breakthrough of the gastrohematic barrier, when endotoxins formed in the primary focus of intoxication enter the circulating blood, followed by distribution and accumulation in the body. Depending on the state of the body, its resistance and the initial level of detoxifying and immune systems There are compensated and decompensated stages of severe toxemia.

Stage III of endogenous intoxication syndrome- multi-organ dysfunction (MOD) is observed with further progression of the pathological process as a consequence of severe damage to various organs and systems by endotoxins with the development of their functional decompensation!. Clinically, this stage is manifested by impaired consciousness, hypoxia, severe heart failure, oliguria, and paralytic intestinal obstruction. A high concentration of creatinine, urea, and bilirubin is determined in the blood.

From a general point of view, the concept of “endogenous intoxication” (endotoxicosis) means pathological condition(syndrome) that develops when various diseases due to the accumulation in the body of various toxicants of endogenous origin with insufficient function of the natural biological detoxification system.

Thus, the development of endogenous intoxication (toxicokinetics) and its clinical manifestations(toxicodynamics) obey the general laws of toxic action discussed above.

results scientific research conducted over the past 10-15 years, have made it possible to formulate the concept of the biochemical substrate of endogenous intoxication, which most often is a number of substances of medium molecular weight. Clinically, the syndrome was first described by L. Babb (1971) in patients with chronic renal failure with severe neurotoxic syndrome. It consists of products of final metabolism, intermediate and altered metabolism, and the level of their content in the blood correlates with the severity of the patient’s condition, the severity of clinical and laboratory manifestations of intoxication, as well as mortality.

In the general pool of substances with an average molecular weight First of all, oligopeptides with a molecular weight of up to 10 kDa should be isolated, among which regulatory and non-regulatory peptides are distinguished.

Regulatory peptides are hormones that play an important role in the process of life, ensuring homeosgas and the pathogenesis of various diseases, for example, neurotensins, neurokinins, endorphins, vasoactive intestinal peptide, somatostatin and others, providing analysis of the influence of the external environment on the body.

Non-regulatory peptides - biologically active substances, toxins received from outside (bacterial, burn, intestinal, etc.) or formed inside the body as a result of autolysis, ischemia or hypoxia of organs, intense proteolysis of products of various metabolic processes, and the most extensive group of constantly identified peptides consists of fragments of collagen, fibrinogen and other blood plasma proteins , excreted in urine in a wide variety of diseases and syndromes, burns, renal and liver failure, injuries with tissue compression, infections (especially with sepsis), pancreatitis, oncological and autoimmune diseases and etc.

In addition, there is also a large group of non-protein medium and low molecular weight substances - metabolites, catabolic and anabolic, the biological activity of which is very diverse from participation in homeostasis to altering action in toxic concentrations. These include, for example, urea, creatinine, cholesterol, bilirubin, etc.

Individual components of the medium molecule pool:

• have a neurotoxic effect,
• cause secondary immunosuppression,
• give an inhibitory effect on erythropoiesis, protein and nucleotide biosynthesis, tissue respiration, increase membrane permeability, enhance lipid peroxidation,
• have a cytotoxic effect,
• disrupt the sodium-potassium balance, microcirculation of blood, lymph, etc.

It is obvious that the main pathological process of endotoxicosis unfolds at the cellular and molecular level and is associated with changes in the properties of cell membranes, which leads to disruption of intracellular homeostasis.

According to the above data, the main reason for the development of endotoxicosis syndrome in critical conditions is the accumulation of a pool of medium molecular compounds with various biological activities as a result of pathological protein degradation due to increased proteolysis and other destructive influences aimed at urgently supplying the body with a certain set of amino acids necessary in extreme conditions. conditions to ensure hormone and enzyme formation, protein regeneration, hematopoiesis and other physiological functions. During the formation of these medium-molecular compounds, a kind of “vicious circle” is formed, in which an increase in the concentration in the blood and consumption of these substances entails their further production of a pathological nature. Therefore, the main goal of therapeutic detoxification measures is hemocorrection aimed at reducing the concentration in the blood of the most biologically active medium-molecular compounds or their neutralization.

In clinical toxicology, the concept of endotoxemia has long been associated mainly with toxic damage to the liver and kidneys as important components of the body’s natural detoxification system. At the same time, clinical and laboratory signs of endotoxicosis were detected in the somatogenic stage of poisoning with hepato- and nephrotoxic substances 3-4 days after the onset of the disease during the formation of hepatic-renal failure. However, endotoxicosis also develops in the toxicogenic stage of acute poisoning with substances of neuro- and psychotropic effects soon after a chemical injury without noticeable impairment of liver and kidney function.

Already upon admission to the hospital, 80% of severe and moderate patients (comatose state) show an increase in the level of “medium molecules” in the blood by 23-83% of the norm. At the same time, a significant increase in the aggregation activity of erythrocytes, platelets and ESR is noted (by 40,8,80 and 65%, respectively). At the same time, critical concentrations of the above toxicants in the blood are determined, which indicates a high intensity of chemical injury to the body, and the most informative markers of blood toxicity are the level of “medium molecules” in it and the degree of increase in the leukocyte intoxication index and the neutrophil shift index.

Treatment of endogenous intoxication

For many centuries, the main direction in the treatment of poisoning was the use of antidotes, which began at the beginning of the new era (Avicenna, ca. 1000 AD), which in most cases did not give the expected clinical results with further expert assessment of them practical application Back in the 60s of the XX century, as the accumulation clinical experience the work of the first specialized toxicology departments, the use of antidotes - analeptics for poisoning with sleeping pills and drugs due to their low effectiveness and the risk of complications. Later, towards the end of the century, it became clear that in general the implementation clinical effect pharmacotherapy for acute poisoning Toxigenic blockade of many drug receptors and the development of hypoxia are prevented, which leads to the absence or distortion of the expected results. The second historical direction in the treatment of toxicosis was the use of methods of stimulating the natural detoxification of the body in the form of so-called galenic drugs (Galen, ca. 200 AD), which were found in any pharmacy from ancient times as emetics, laxatives and diuretics plant origin, called "Alexifarmica".

Subsequently, with the development of general clinical toxicology and resuscitation, which makes it possible to effectively support the basic functions of the body, including detoxification, it became possible to significantly stimulate the latter, which, at the suggestion of Academician Yu. M. Lopukhin (1989), was called “efferent therapy” and soon became the main direction in the treatment of poisoning.

The third direction, the purpose of which was to reduce the concentration of toxicants directly in the blood, includes bloodletting, which was apparently used already in Ancient Egypt, and the later developed operation of partial replacement of the patient’s blood with the blood of a donor O. S. Glozman (1963). This idea found a further solution in the form of modeling various devices for extracorporeal blood purification, the first of which were the “artificial kidney” (60s) and the hemosorption device (70s).

1. Taking into account the above traditionally established directions in the treatment of acute toxicosis, E. A. Luzhnikov (1977) proposed clinical classification modern methods detoxification, currently widely used in medical science and practice. According to this classification, the first separate group (A) includes methods for stimulating the natural processes of detoxification, elimination, biotransformation, transport and binding of toxicants.
2. The second separate group (B) presents all methods of artificial physicochemical detoxification, so named in connection with the artificially created extracorporeal (often hardware) additional channel for the elimination of toxicants, designed to relieve natural system detoxification and even temporarily replace it.
3. The third separate group (C) contains all pharmacological preparations for specific (antidote) treatment of poisonings, which, for the reason stated above, occupy a modest place in the arsenal of detoxification agents and are used mainly at the prehospital stage.

In addition to the methods of active detoxification, which have the nature of etiological treatment and therefore are most effective in the earliest phase of the toxicogenic stage of poisoning (toxicokinetic correction), in the complicated form of the disease, as its severity increases, the role of symptomatic therapy, usually having intensive care content, which allows maintaining a certain minimum of vital functions important organs to ensure the possibility of detoxification measures (toxicodynamic correction). Most often, the main types of complications are the well-known pathological syndromes of toxic shock, acute respiratory failure, toxic-hypoxic encephalopathy, cardiomyopathy and endotoxicosis.

In case of endogenous intoxication, the main attention is paid to the treatment of the underlying disease that caused the development of this syndrome (poisoning, burns, hepato- and nephropathy, pancreatitis, etc.), however, methods of efferent detoxification therapy always occupy a significant place in the complex therapeutic measures, especially hemosorption, dialysis and HF, plasmapheresis.

In clinical toxicology, early use of efferent therapy contributes to a noticeable reduction in the severity of endogenous intoxication and the prevention of multiple organ damage.

In acute poisoning, the syndrome of endogenous intoxication clearly manifests itself only in the somatogenic phase of the disease due to chemical burns of the digestive tract, the development of renal-liver failure and toxic-hypoxic encephalopathy.

In the toxicogenic phase, the phenomena of endogenous intoxication spontaneously stop during efferent detoxification therapy aimed at removing from the body the main exotoxicants that caused acute poisoning.

It is important to know!

It should be noted that immune detoxification is a relatively late evolutionary acquisition, characteristic only of vertebrates. Its ability to “adapt” to fight a foreign agent that has entered the body makes immune defense a universal weapon against almost all possible compounds with a large molecular weight.