Operations on the superior mesenteric artery. Surgery for damage to the superior mesenteric artery. Tactics. Symptoms of intestinal thrombosis
The accumulation in the body of an excessive amount of exo- and endotoxins leads to the inevitable occurrence of a condition known as endogenous intoxication of the body. As a rule, this condition is accompanied by a background course of various inflammatory processes in the tissues.
Endogenous toxins, which have a decomposing effect and provoke a rather dangerous syndrome of endogenous intoxication, spread equally quickly to all organs of the abdominal cavity. Consistently, the affected organ, liver, kidneys, myocardium, and nervous system fall under the influence of a foreign substance. In case of untimely detection, endogenous poisoning with toxins can provoke irreversible toxic-dystrophic processes of tissue decomposition.
The phenomenon itself is a multi-stage process, built around the source of toxemia. A number of systems simultaneously take part in the process, including biological barriers designed to prevent the breakthrough of toxins from the source, mechanisms for transferring toxins to uninfected cells, as well as neutralizers, whose task is to neutralize knowingly harmful substances that have broken through the barrier. In other words, in a whole body with a healthy immune system, the development of endogenous intoxication syndrome is practically excluded, therefore, people with poor health who have undergone surgery, severe poisoning, inflammation, etc. are at risk for the disorder.
Clinical picture 
The clinical picture practically does not depend on the cause of endogenous toxic pathology. As a rule, the following signs are present in the primary symptoms:
- general weakness, weakness, apathy;
- headaches and muscle pains of aching and pressing nature;
- nausea, urge to vomit, vomiting;
- tachycardia;
- drying of mucous membranes.
The development of phases occurs rapidly and, if untreated, intoxication leads to serious problems, including falling into a state of encephalopathy, coma, catalepsy, and problems with hemodynamics.
stages
There are three main stages of the course of the syndrome of endogenous intoxication. The reactive-toxic process that occurs against the background of the initial focus of inflammation or traumatic injury, including the surgical incision, is considered primary. At this stage, the detection of intoxication is possible only through a clinical blood test, which will show an increase in lipid peroxidation products and MSM levels, as well as an increase in the leukocyte index of intoxication (denoted as LII).
The second stage, called the stage of severe toxemia, manifests itself after the toxins pass the hematological barrier of the circulatory system. The blood is saturated with toxins, which are evenly distributed through the bloodstream to all organs and systems. Depending on the state of the body at the time of the breakthrough of toxins, the phase can proceed in a compensated and decompensated by nature.
Prolonged progression of intoxication with endotoxins leads to the onset of the third phase of the pathology - multiorgan dysfunction. The stage occurs against the background of severe damage to many body systems by toxic compounds, which causes functional decompensation at all levels. In the clinical picture, unlike the previous stages, multiorgan dysfunction manifests itself clearly as oliguria, hypoxia, intestinal obstruction, impaired consciousness, etc. A clinical blood test, among other things, shows a high concentration of urea, bilirubin, aminotransferases.
Causes
Endogenous intoxications in surgery are much more common than in other medical branches of knowledge. The reason for this is the main diseases-sources of self-poisoning, namely:
This is not a complete list of the primary sources of the syndrome, but the most common cases occur precisely in the aforementioned pathologies.
Often, endogenous intoxication occurs in the postoperative period during abdominal operations. In this case, its occurrence is caused by problems with breathing, blood loss, the ingestion of tissue autolysis products and drugs administered for anesthesia, more precisely, their residual effect on tissue cells.
Under the sources of the disease, one can mean both directly the diseases that cause the birth of toxic compounds alien to the cell, and the compounds of a toxic nature themselves. Moreover, even useful elements, such as products of normal metabolism, such as urea, creatinine, pyruvate, lactate, etc., can be retrained into poisons within a single system of the human body. In addition, the destructive effect is characteristic of products derived from impaired metabolism, namely: aldehydes, ketones , ammonia and carboxylic acids. Further, according to the degree of risk of manifestation of toxic properties, tissue decay products at the cellular level follow, released in the presence of tissue destruction or problems in the barrier functions of membranes. The list includes lipases, cationic proteins, skatole, indole, phenol, etc.
As mentioned earlier, endogenous intoxication in surgery is a relatively common occurrence, and, therefore, mediators of inflammation, as well as other biologically active substances generated by the secretion of the body, become its source. The same list includes microbial toxins of all types, active compounds that are born in the process of lipid cross-oxidation, antigens and aggressor immune complexes.
Therapy for endogenous intoxication syndrome
In general, the treatment of endogenous intoxication, as well as the fight against poisoning of an exogenous nature, is based on the removal and neutralization of the primary source of toxic substances that interfere with the normal functioning of the body. If in exogenous poisoning the primary is the leaching of the remnants of a poisonous substance from the body, then endogenous poisoning necessarily begins with the treatment of a disease that causes secretory poisons to enter the blood and tissues.
Any first aid provided without the use of detoxification drugs and substances does not make sense. The only possible help for a person poisoned by an internal source of poisons will be his transportation to the nearest medical facility, where qualified assistance will already be provided to him.
The source, which lies in the inflammatory processes of the tissues of the internal organs, is usually neutralized by the surgical method. Inflammation and sepsis are subjected to washing, aspiration of the contents, infusion therapy, and in some cases, foci of inflammation are removed.
After neutralization of the source, obligatory blood purification is carried out. For these purposes, the optimal procedure is hemodilution, which involves the drip administration of drugs that have diuretic properties and improve the perfusion of tissues and organs with blood. In particularly severe cases of intoxication, intensive therapy can be applied. In intensive care, the patient undergoes hemodialysis with mandatory blood transfusion.
Non-pharmacological adaptive treatment
As with other diseases affecting the integrity of internal organs and the normal functioning of body systems, endogenous type intoxication, in addition to the main treatment, needs proper background health maintenance. At severe stages of the disease, most of the useful elements enter the patient's body through drip administration, but with the timely detection of toxic changes, it is important to take care of the following way to normalize metabolism.
Experts recommend that all patients adhere to a fasting diet without fail. The toxic effect is strongest and primarily affects the digestive system; during the period of treatment and rehabilitation, it needs mandatory saturated and light nutrition. It is advisable to diversify the diet with steamed dishes, include meat and fish dishes in the daily menu, and increase the amount of protein consumed. Fresh vegetables and fruits, juices and fruit purees are required. With normal health and the absence of concomitant contraindications, bath procedures, saunas, and steam rooms can help detoxify the body.
Consequences of endogenous intoxication
With timely diagnosis of intoxication with self-generated poisons, a complete cure occurs. But since it is not always possible to quickly determine the source of toxins generated by the body, more than 32% of cases of detection of endogenous intoxication in the early stages are accidents.
ENDOGENOUS INTOXICATION SYNDROME IN THE PATHOGENESIS OF VIRAL HEPATITIS
Kuznetsov P. L., Borzunov V. M.
GBOU VPO UGMA of the Ministry of Health of Russia
Kuznetsov Pavel Leonidovich
The article presents a review of the literature on the mechanisms of development of the syndrome of endogenous intoxication. Various definitions of endogenous intoxication syndrome, phases of pathogenesis, basic mechanisms of its development are given. The characteristics of endotoxic substances, their effect on the body as a whole and on the detoxification organs in particular are given. The main role of the liver in the detoxification of the body and the violation of its functions in case of hepatitis viruses are shown. Methods for diagnosing the syndrome of endogenous intoxication 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 hepatitis virus. 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 the deciphering of the pathogenetic aspects of the 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 a link in the general syndrome of intoxication, accompanies many diseases and is often the main cause of death. Along with the specific features inherent in one or another nosological form, diseases that occur with endotoxemia syndrome have many common biochemical and pathophysiological mechanisms.
The definition of the syndrome of endogenous intoxication (SEI) given by V. K. Gostishchev: “The syndrome of endogenous intoxication is a clinical complex of symptoms of pathological conditions of organs and systems of the body, due to the accumulation in tissues and biological fluids of endotoxins - 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 normal or perverted (pathological) products.
metabolism or cellular response. Endotoxicosis is a complex multifactorial autocatalytic process that acquires a universal character over time, depending on the mechanisms that triggered it. Unbalanced acting biologically active substances, which acquire the properties of ETS, become damaging agents. Components of the syndrome: toxinemia, the concentration of circulating ETS, both from the primary focus and secondary to tissue damage.
PATHOGENESIS OF THE SYNDROME OF ENDOGENOUS INTOXICATION
The causes of the development of the syndrome can be conditionally divided into two groups. First of all, these are destructive processes, as a result of which an excessive amount of intermediate and final metabolic products accumulate 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 the binding, inactivation and elimination of both natural metabolites and toxic products. Primary damage to these systems or disruption of their adaptation and compensation in any pathological process also leads to the emergence of SEI.
Among the main ways of SEI formation in the body are the following:
1. Retention - as a result of a violation of the elimination from the human body of the end products of the metabolism of low molecular weight compounds (molecular 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 in obstructive jaundice, products of nitrogen metabolism in renal failure). The main route of their elimination is renal filtration and excretion.
2. Resorptive - as a result of massive formation with subsequent resorption in the body of tissue decay products (toxins with an MM of more than 500 daltons and a molecular size of more than 200 nm); entry into the internal environment of the body of decay products of tissues or contents of the intestine, bladder, wound cavity, etc.
3. Exchange (production) - as a result of violation of intracellular homeostasis and accumulation in excess of secondary metabolites (molecular size - more than 10 nm, MM - less than 500 daltons); develops as a result of a violation of tissue metabolic processes with a change in the composition of the tissue
fluid, 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 MM up to 500 daltons.
According to modern concepts, five phases of the development of endogenous intoxication are distinguished, consisting in the redistribution of substances of low and medium molecular weight (LH and SMM) between biological media. In the first (latent) phase, an increase in VL and SMM in erythrocytes is observed without a significant increase in their concentration in plasma. There is an elimination of incoming toxins from the focus of intoxication. 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 plasma, and in erythrocytes, due to impaired membrane permeability, their concentration decreases. This is the phase of irreversible decompensation of systems and organs of detoxification. In the fifth terminal phase, catabolism products enter intracellularly, the concentration of VH and SMM in erythrocytes and in plasma decreases.
It is possible to draw parallels with the classification of SEI phases proposed by M. Ya. Malakhova (1991), according to which 5 consecutive phases are distinguished in the pathogenesis of SEI: 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 systems and organs of detoxification or terminal.
ENDOTOXIC SUBSTANCES
In the development of acute endotoxicosis, several mechanisms of ETS formation and their accumulation in the internal environment of the body can simultaneously or sequentially participate. 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), is one of the most common molecular mechanisms of tissue damage in pathological conditions. MSM (medium mass molecules - from 500 to 5000 a.m.u.) are substances, mainly of a peptide nature, formed in tissues as a result of proteolytic breakdown of proteins and causing a state of intoxication in the body. The toxic effect of MSM is due to the total effect of all their constituent compounds due to the development of potentiation and synergism effects. Activation of proteolysis is prevented by antiproteases - substances of a protein nature that form complexes with proteases, in which the latter lose their activity, these include inhibitors of serine proteases alpha-1-AT, alpha-1-antichymotrypsin and alpha-2-MG.
Lipid peroxidation (LPO) is one of the ways in which oxygen is utilized in the cell. The main substrate in LPO 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 endotoxicosis, a large role is given to microbial toxins, which are the waste products of microbial cells. Intoxication usually occurs as a result of the action of toxic substances circulating in the blood; the circulation of endogenous poisons in the blood is often referred to as toxemia, and the circulation of toxins as toxemia. About 80 microbial toxins have been described and isolated in relatively pure form. By origin, microbial toxins are divided into three classes:
1) exotoxins - products secreted by microorganisms to the outside in the course of life;
2) endotoxins - substances firmly associated with the stroma of microbial cells and released only after the death of the microbial population; 3) mesotoxins - toxic substances that are loosely bound to the stroma of a microbial cell and, under certain conditions, are released into the environment while maintaining cell viability. By functional activity, membrane toxins are distinguished that are capable of lysing cell membranes (leukocidins, hemolysins, phospholipase A2), cytotoxins, functional blockers (neuro- and enterotoxins), exfoliatins - erythrogenins (found in staphylococci and streptococci, have a pyrogenic effect, cause desquamation surface layers of the skin epithelium), modulators of cell responses to endogenous mediators.
Modern classifications divide toxins according to the mechanism of action, according to size
particles, according to the 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) toxins of microorganisms.
According to particle size, there are: 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) macromolecular (up to tens of thousands of daltons) - proteins and lipoproteins; 4) ultra-high molecular weight (million daltons) - protein compounds, such as CEC, soluble complexes of fibrin-momnomers, cryoglobulins, cryofibrinogen, which play an important role in the pathogenesis of immunocomplex vasculitis and DIC.
According to the impact on the body, causing: 1) violation of organs and systems at the level of the macroorganism (water); 2) violation of the functioning and metabolism of the cell (potassium, sodium, bilirubin, ammonia, digoxin); 3) cell death (nephro-, hepato-, neuro- and ototoxic substances); 4) violation of microcirculation and homeostasis (bacterial endotoxins, fibrin degradation products, fibrin-monomeric complexes, cryofibrinogen); 5) violation of vascular permeability (CEC, serotonin).
Endogenous toxins are capable of exerting a destructive effect on cellular structures and on their metabolism. This influence also extends to cells remote from the site of the primary release of the toxin. 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 interrelated 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. Violation of the relationship between the monooxygenase and immune systems determines the discrepancy between the rate of formation and elimination of both pathological and physiological metabolic products in the fluid sectors and tissues. Consequently, EI develops either as a result of an imbalance in the components of the detoxification system, or with the failure of one of the links, or at the same time all of its components.
Elimination of endogenous toxins occurs as follows: gaseous substances are excreted through the lungs; hydrophilic low- and medium-molecular substances - are removed by the kidneys, through the skin, gastrointestinal tract in the form of solutions; hydrophobic low- and medium-molecular substances - are 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, gastrointestinal tract; either bind to blood plasma proteins, acquire the properties of haptens and are absorbed by the cells of the immune system; macromolecular compounds - are transported through the 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 the protective mechanisms, the body is able to withstand the onslaught of toxic effects. 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 violations of the structure and function of the immune system, leads to a decrease in the body's resistance. By the severity of SEI, one can judge the severity of the underlying disease and predict its course.
THE ROLE OF THE LIVER IN THE PATHOGENESIS OF ENDOGENOUS INTOXICATION SYNDROME
In clinical practice, SEI is considered as a clinical symptom complex that occurs in acute or chronic insufficiency.
functions of the body's natural detoxification system. Given 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, contributing to the triggering of the mechanisms of endotoxin aggression. In addition, toxins that enter the bloodstream from any focus of inflammation can have a damaging effect on liver tissue (I. I. Sirotko et al., 1998). In particular, in patients with severe and moderate 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 transaminases in the blood. Changes in the liver can contribute to the protracted course of pneumonia and require correction already in the early period of the disease.
The 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 non - specific inflammatory diseases of the lungs and a violation of the 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 injuries, gynecological diseases, etc. . Most of these conditions are characterized by: hyperbilirubinemia, hyperglobulinemia, violation of the synthesis of proteins, amino acids due to a violation of the synthetic, detoxifying function of the liver; with the accumulation of products of nitrogenous metabolism (creatinine, uric acid), which occurs during the blockade of kidney function; with peritonitis, burn disease, putrefactive processes, polyamines predominate (biogenic amines - cadaverine, putrescine), which are products of protein biodegradation.
Data on the long duration of metabolic disorders in patients with acute viral hepatitis B were obtained. 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, established in patients with viral hepatitis B with previous types of pathology: degenerative diseases, signs of a decrease in the body's reactivity, toxic effects, disorders of the excretory function of the digestive system.
In the study by A. R. Umerova, patients with chronic hepatitis (CH) and liver cirrhosis (LC) showed a significant increase in the CIC value compared to the norm. The MSM index in patients with CG and cirrhosis was also significantly increased compared to the norm, which indicates a high incidence of SEI in chronic liver pathology. The role of plasma fibronectin is shown - a glycoprotein, the leading function of which in the body is opsonic, that is, the removal of various microparticles from the bloodstream, including microbial lipopolysaccharides, immune complexes, etc. A significant decrease in its amount in the blood plasma in CG in 41% of cases, and with the CPU - in 64%. Regulatory proteins (RPs) are a cumulative product of the catabolite breakdown of cell receptors of very different specificity and are universal endogenous toxins. The correlation between RB and CIC levels was direct: with an increase in RB content, the amount of CIC increased, especially in patients with class C cirrhosis. The relationship between RB and serum albumin levels, on the contrary, was inverse: with an increase in RB titers, the albumin concentration decreased. A similar negative correlation was also observed to the maximum extent in patients with class C cirrhosis. Thus, the determination of plasma fibronectin, RB in blood serum can be used in clinical practice as a sensitive marker of endogenous intoxication syndrome in chronic hepatitis and cirrhosis.
Currently, a direct relationship has been established between the level of endotoxemia and hemodynamic disorders in cirrhosis. It was revealed that bacteremia most often occurs in patients with bleeding from esophageal varices (EVV). Developing as a result of the movement of bacteria through the intestinal mucosa, endotoxemia directly or indirectly through the cytokine cascade stimulates inducible nitric oxide synthase in the vascular endothelium, increasing its production. Endotoxemia, which plays an important role in the genesis of hyperdynamic circulatory status, worsens liver function and disrupts hemostasis in patients with cirrhosis, may be a critical risk factor for bleeding from EVV. A direct correlation between the level of endotoxemia and the risk of bleeding from RVV in patients with cirrhosis has been proven.
LABORATORY CRITERIA FOR ASSESSING THE SYNDROME OF ENDOGENOUS INTOXICATION
The situation with the 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 fairly simple and acceptable methods for quantifying the severity of endotoxicosis in the conditions of most medical institutions is very relevant today.
Evaluation of the severity of the syndrome of endogenous intoxication SEI is based on clinical and laboratory data. The latter include the following groups of studies:
1. Hematological: NST-test (reflects the activation of peroxidase systems of neutrophils); lysosomal-cationic test (determination of cationic proteins of granulocytes); degenerative changes in leukocytes (toxigenic granularity, inclusions of Knyazkov - Dele, Amato grains, hypersegmentation of nuclei, etc.); inhibition of migration and spontaneous lysis of leukocytes; hemolytic resistance of erythrocytes; the ability to transport substances of low and medium molecular weight.
2. Biochemical and biophysical: SMM substances in biological fluids and oligopeptic fractions; components of lipid peroxidation and antioxidant system (AOS); chemiluminescence of biological fluids and homogenates; electron paramagnetic resonance; determination of hydrocarbon in exhaled air; components of inflammatory mediators (biogenic amines, kallikrein-kinin-new system, prostaglandins).
3. Microbiological and immunological: bacterial toxins (limulus test - determination of bacterial lipopolysaccharides, immunological methods for detecting 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-helpers of the first (IL-2 , IFN-y) and the second type (IL-4) by enzyme immunoassay in blood serum, in culture of mononuclear cells, in body secrets; dynamics of the microflora of the oral cavity, pharynx and skin; determination of complement components; integral assessment of the severity of immunosuppression.
4. Calculation criteria: leukocyte index of intoxication (LII); nuclear index of intoxication (NII); hematological index of intoxication (GII); clinical and laboratory indices (Marchuk, Shugaev, Gabrielyan, Malakhova, Grinev, etc.).
5. Biological testing (evaluation of the critical condition on 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 non-specific.
1. Specific allow you to identify the effect of toxic agents that cause intoxication syndrome: the release of a toxic agent; bioassay method; reaction of the valvular apparatus of the lymphatic vessel of the mesentery of the intestine; paramecium test; tetrachymen test; bull semen test; limulis test; biomicroscopy of the conjunctiva of the eye; mobility of the nuclei of the buccal epithelium in an electric field.
2. Conditionally specific allow to detect intoxication on blood cells - erythrocytes and leukocytes: inhibition of migration of leukocytes; fragmentation of the nucleus of leukocytes; vesicle formation reaction; reaction of spontaneous lysis of leukocytes; NST-test; cationic lysosomal test; leukocyte index of intoxication; toxicogenic granularity of neutrophils; osmotic resistance test of erythrocytes; test for the ability of red blood cells to absorb methylene blue; erythrocyte toxic granularity test; assessment of VN and SMM and erythrocyte oligopeptides according to M. Ya. Malakhova.
3. Non-specific reflect either the inflammatory response of the body or changes in metabolism: a 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; oligopeptides according to Lowry; registration of infraslow potential fluctuations in the millivolt second and decasecond ranges; the level of urea 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 (Kpl) and erythrocytes (Ker) and superoxide dismutase. The hydrophilic component of toxicity is judged by the accumulation of MSM in the blood. Their toxic effect is associated with a separating 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 promote hemolysis of erythrocytes, inhibit the utilization of glucose in them, reduce 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 able to reversibly bind 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 sites. By binding ligands, it ensures their transportation to detoxification systems (liver, kidneys). The presence of albumin in the blood within the 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, in connection with which the transport capacity is sharply reduced. The most advanced methods for assessing the blocking and binding of albumin binding sites by metabolites and toxic ligands are those using fluorescent probes.
In order to objectify the assessment of SEI, it is proposed to use the so-called integral index of intoxication, calculated using multivariate statistics methods based on the determination of a complex of biochemical, hemorheological, biophysical and optical-polarization indicators, united in the concept of "endotoxicogram" .
CONCLUSION
In conclusion, we emphasize the features of the syndrome of endogenous intoxication in viral hepatitis:
1. Hepatitis viruses cause cytolysis of hepatocytes due to direct or immune-mediated damaging effect, which is the fundamental mechanism of pathogenesis that forms the syndrome of endogenous intoxication.
2. The pathological process leads to disruption of many functions of the liver, especially protein-synthesizing, which is accompanied by a decrease in both albumin synthesis and its nonspecific detoxification and transport function.
3. Activation of lipid peroxidation leads to the accumulation of free radicals, which enhances endotoxicosis.
4. Immune imbalance, manifested in viral hepatitis as a quantitative and qualitative dysfunction of immunocompetent cells and humoral factors of immunity,
leads to the activation of the vital activity of the 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. An additional damaging effect on cell membranes, organs and systems of the body is exerted by the resulting endogenous toxic substances, including the main organ of the detoxification system - the liver.
6. Laboratory manifestations of the syndrome of endogenous intoxication are recorded against the background and after 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 magnitude and depth of changes in the liver as the main organ and regulator of the detoxification system.
LITERATURE
1. Pavelkina, VF Dynamics of indicators of endogenous intoxication in patients with recurrent tonsillitis / VF Pavelkina, SV Shchipakina, SG Pak, AA Erovichenkov // Vrach. - 2008. - No. 11. - S. 64-66.
2. Belyakov, N. A. Criteria and diagnosis of endogenous intoxication / N. A. Belyakov, M. Ya. Malakhova // Endogenous intoxication. - St. Petersburg, 1994. - S. 60-62.
3. Laboratory diagnosis of endogenous intoxication syndrome: methodical. recommendations / ed. prof. I. P. Koryukina //
V. M. Aksenova, V. F. Kuznetsov, Yu. N. Maslov, V. V. Shchekotov, A. P. Shchekotova. - Perm, 2005. - 22 p.
4. The use of efferent methods of therapy in critical conditions: guidelines / V. I. Cherniy, P. I. Novikova, V. S. Kostenko, E. K. Shramenko, L. V. Logvinenko. - Donetsk: Publishing house of DonGMU im. A. M. Gorky, 2007. - 24 p.
5. Laboratory methods for diagnosing emergency conditions / G. I. Nazarenko, A. A. Kishkun. - M.: Medicine, 2002. - 568 p.
6. Endointoxication of the human body: methodological and methodological aspects: textbook / N. A. Dobrotina, T. V. Kopytova. - Nizhny Novgorod: Publishing House of the Nizhny Novgorod State. un-ta im. N. I. Lobachevsky, 2004. - P. 72.
7. Sadovnikova IV Clinical and pathogenetic aspects of the treatment of chronic viral hepatitis in children / IV Sadovnikova // Mat. visiting plenum of the board of Ho^ "New horizons in gastroenterology". - Novosibirsk, 2004. - S. 203.
8. Malakhova, M. Ya. Endogenous intoxication as a reflection of the compensatory restructuring of metabolic processes in the body / M. Ya. Malakhova // Efferent ter. - 2000. - V. 6, No. 4. - S. 3-14.
9. Koryakina, E. B. Features of the pathogenetic mechanisms of endogenous intoxication in patients with rheumatoid arthritis / E. V. Koryakina,
S. V. Belova // Scientific and Practical. rheumatol. - 2001. - No. 1. - S. 23-33.
10. Veremeenko, K. N. Proteolysis in normal and pathological conditions. - Kyiv: Health, 1988. - 220 p.
11. Koeppel, M. C. Proteolytic enzymes and their inhibitors / M. C. Koeppel, J. Sayag // Allerg. Immunol. Paris. - 1993. - Vol. 25, no. 7. - P. 286-288.
12. Van Steenbergen, W. Alpha 1-antitrypsin deficiency: an overview / W. Van Steenbergen // Acta. Clin. Belg. - 1993. - Vol. 48, no. 3. - P. 171-189.
13. Skulachev, V.P. Oxygen in a living cell: good and evil / V.P. Skulachev // Sorosovsky obrazovat. magazine - 1996. - No. 3. - S. 4-10.
14. Vladimirov, Yu. A. Free radicals and antioxidants / Yu. A. Vladimirov // Vestn. PAMH. - 1998. - No. 7. - S. 43-51.
15. Halliwell, B. Lipid peroxidation: its mechanism, measurement, and significance / B. Halliwell, S. Chirico // Amer. J.Clin. Nutr. - 1993. - Vol. 57, no. 5. - P. 715-725.
16. Pak, S. G. Experience and prospects of studying the syndrome of intoxication in infectious pathology / S. G. Pak, O. F. Belaya, V. A. Malov et al. // Zhurn. infectol. - 2009. - T. I, No. 1. - S. 9-17.
17. Bojic, I. ^e significance of endotoxins in clinical medicine / I. Bojic // Vojnosanit. Pregl. - 1993. - Vol. 50, No. 6. - P. 596-602.
18. Shano, V.P. Endogenous intoxication syndrome / V.P. Shano, E.A. Kucher // Acute and urgent conditions in the practice of a doctor. - 2011. - No. 1 (25). - S. 35-41.
19. Karyakina, E. V. Molecules of average mass as an integral indicator of metabolic disorders (literature review) / E. V. Karyakina, S. V. Belova // Klin. laboratory diagnostics. - 2004. - No. 3. - S. 3-8.
20. Prokhorov, D. V. Molecules of average weight - a marker of endogenous intoxication in patients with microbial eczema / D. V. Prokhorov, O. A. Pritulo // Dermatovenerol., kosmetol., sexopathol. - 2001. - No. 1 (4). - S. 95-97.
21. Khimkina, L. N. Significance of endogenous intoxication in chronic dermatoses. Correction methods / L. N. Khimkina, N. A. Dobrotina, T. V. Kopytova // Vestn. dermatol. and venerol. - 2001. - No. 5. - S. 40-43.
22. Marshall, J. Multiple Organ Dysfunction Score: descriptor of a clinical complex outcome / J. Marshall, D. Cook, N. Christou // Crit. Care Med. - 1995. - Vol. 23, no. 10. - P. 1638-1651.
23. Sibai, B.M. Immunological Aspects of Preeclampsia / B. M. Sibai // Clin. obstet. and Gynecol. - 1991. - Vol. 34, no. 1. - P. 27-34.
24. Vetrov, VV Endogenous intoxication syndrome in obstetric and gynecological practice / VV Vetrov // Efferentnaya ter. - 2001. - No. 1. - S. 4-9.
25. Eryukhin, I. A. Endotoxicosis as a problem of clinical surgery / I. A. Eryukhin, O. S. Naeomkin, V. L. Shamkov // Surgery. - 2001. - No. 3. - S. 23-26.
26. Syndrome of endogenous intoxication / N.V. Leontieva, M.V. Belotserkovsky. - St. Petersburg: Publishing house of St. Petersburg State Medical University, 1998. - 48 p.
27. Biochemistry of endotoxicosis. Mechanisms of development and assessment of severity in inflammatory diseases of the lungs / E. A. Borodin, E. V., Egorshina V. P. Samsonov. - Blagoveshchensk: AGMA, 2003. - 129 p.
28. Huang, C.J. Degree of protein deficiency affects the extent of the depression of the antioxidative enzyme activities and the enhancement of tissue lipid peroxidation in rats / C. J. Huang, M. L. Fwu // J. Nutr. - 1993. - No. 123. - P. 803-810.
29. Shin, S. J. Enhanced oxidative damage induced by total body irradiation in mice fed a low protein diet / S. J. Shin, K. Yamada, A. Sugisawa et al. // Int. J. Radiation Biol. - 2002. - Vol. 78, no. 5. - P. 425-432.
30. Dorokhin, K. M. Pathophysiological aspects of endogenous intoxication syndrome / K. M. Dorokhin, V. V. Spas // Anesthesiol. and resuscitator. - 1994. - No. 1. - S. 56-60.
31. Dean, R. Disintegration processes in the cell. - M.: Mir, 1981. - 120 p.
32. Khokhlova, N. I. Criteria for assessing endogenous intoxication in patients with acute viral hepatitis B / N. I. Khokhlova, N. P. Tolokonskaya, N. M. Lapitskaya et al. // Klin. laboratory diagnostics. - 2007. - No. 8. - S. 35-38.
33. Umerova, A. R. Endogenous intoxication syndrome in chronic hepatitis and liver cirrhosis. Pathogenesis, diagnosis, treatment: Ph.D. thesis____ Dr. med. Sciences / A. R. Umerova. - Astrakhan, 2010. - 36 p.
34. Garbuzenko, DV Pathophysiological mechanisms and new directions in the treatment of portal hypertension in liver cirrhosis / DV Garbuzenko // Klin. prospects gastroenterol., gepatol. - 2010. - No. 6. - S. 11-20.
35. Garbuzenko, DV The role of intestinal microflora in the development of complications of portal hypertension in liver cirrhosis / DV Garbuzenko // Klin. honey. - 2007. - No. 8. - S. 15-19.
36. Vallance, P. Hypothesis: induction of nitric oxide synthase in the vasculature underlies the hyperdynamic circulation of cirrhosis / P. Vallance, S. Moncada // Lancet. - 1991. - Vol. 337. - P. 776-778.
37. Mikurov, A. A. Comparative analysis of the level of endotoxinemia in patients with liver cirrhosis with portal hypertension / A. A. Mikurov, D. V. Garbuzenko // Fundam. research - 2011. - No. 6. - S. 126-128.
38. Dashtayants, G. A. Clinical hematology. - Kyiv, 1978. - 230 p.
39. Malakhova, M. Ya. Method of registration of endogenous intoxication: methodical. recommendations. - St. Petersburg, 1995. - 33 p.
40. Parfenova, G. A. Medium molecules - a marker of endogenous intoxication / G. A. Parfenova, I. F. Chernyadyva, V. K. Sitina // Vrach. case. - 1987. - No. 4. - S. 72-77.
41. Gabrielyan, N.I. Medium molecules and the level of endogenous intoxication in resuscitation patients / N. I. Gabrielyan, A. A. Dmitriev, O. A. Savostyanova // Anesthesiol. and resuscitator. - 1985. - No. 1. - S. 36-38.
42. Chalenko, V. V. Possible reasons for the increase in the concentration of medium-weight molecules in pathology / V. V. Chalenko // Pat. physiol. - 1991. - No. 4. - S. 13-14.
43. Fedorovsky, N. M. Indirect electrochemical detoxification: a manual for postgraduate training of doctors. - M.: Medicine, 2004. - 144 p.
44. Kuznetsov, N. N. Syndrome of endogenous intoxication in critical conditions in young children. New diagnostic and prognostic possibilities / N. N. Kuznetsov, E. V. Devaykin, V. M. Egorov // Anest. and resuscitator. - 1996. - No. 6. - S. 21-24.
Syndrome of endogenous intoxication(endotoxemia) is the accumulation of endotoxins in the blood and tissues of the body.
Endotoxins are substances that have a toxic effect on the body. They, in turn, can be the products of the vital activity of the organism itself, or they can enter it from the outside.
Endogenous intoxication syndrome is one of the most acute problems in intensive care, as it accompanies a large number of pathological conditions, including shock, pancreatitis, peritonitis, etc. A pronounced endogenous intoxication syndrome can lead to death.
Causes of endogenous intoxication syndrome
The causes of endogenous intoxication syndrome can be very diverse. However, this process always develops when endotoxins enter the bloodstream from the sites of their formation. Through the blood, endotoxins are distributed to organs and organ systems, as well as to all tissues of the body. When the amount of aggressive components and endotoxins exceeds the natural capacity of the body in their biotransformation, endogenous intoxication syndrome occurs.
There are the following causes of endogenous intoxication syndrome:
Diseases that occur with a purulent-inflammatory reaction in the body. These include cholecystitis, acute pneumonia, peritonitis, pancreatitis, etc.
Severe and complex injuries: crash syndrome.
Some chronic diseases in the acute stage, for example, diabetes mellitus, thyrotoxic goiter.
Body poisoning.
The primary mechanisms for the occurrence of endogenous intoxication syndrome are as follows:
resorption mechanism. When this occurs, the resorption of toxic substances (necrotic masses, inflammatory exudate) from a limited focus of infection throughout the body. This process can be started with intestinal obstruction, with, with phlegmon of soft tissues, etc.
Exchange mechanism for the development of endogenous intoxication syndrome. It is caused by excessive production of toxic substances. This mechanism of development is typical for pneumonia, acute pancreatitis, diffuse peritonitis.
retention mechanism. According to this type, the syndrome of endogenous intoxication develops if the process of removing toxins from the body directly suffers, that is, the work of the detoxification organs is disrupted.
reperfusion mechanism. The penetration of endotoxins into the blood occurs from tissues that have been in a state of ischemia for a long time, while the antioxidant barrier of the body has lost its consistency. This can occur in shock conditions, during surgical intervention using AIC, etc.
The mechanism of secondary toxic aggression, in which tissues respond with a toxic reaction to the effects of endotoxins.
An infectious mechanism in which pathogenic microorganisms from the foci of invasive infection act as endotoxins.
Endotoxins are those substances that lead to the formation of endotoxemia and endogenous intoxication syndrome.
The following endotoxins are distinguished, depending on the mechanism of their formation:
Enzymes that, after activation by one or another pathological process, begin to damage tissues. These can be proteolytic and lysosomal enzymes, as well as activation products of the kallikrein-kinin system.
The products of the natural vital activity of the body can act as endotoxins, provided they are accumulated in high concentrations. This includes urea, etc.
All biologically active substances that are present in the human body. These can be inflammatory mediators, cytokines, prostaglandins, etc.
Aggressors that arise from the breakdown of foreign antigens and immune complexes.
Toxins released by microbes or other pathological agents.
Medium molecular substances (viruses, allergens, etc.).
Products that arise during lipid peroxidation.
Products that appear as a result of cell breakdown when their membranes are damaged by destructive processes. These can be proteins, myoglobin, lipases, phenol, etc.
High concentrations of components of regulatory systems.
Endotoxins can have a direct and indirect effect on the body, they can affect microcirculation, the processes of synthesis and metabolism in tissues.
One of the leading symptoms of endotoxemia is depression of consciousness. Its complete loss or partial reduction is possible. In parallel, the patient has severe headaches, muscle weakness appears, and myalgia is characteristic.
As the intoxication of the body progresses, nausea and vomiting join. As the patient's body loses fluid, the mucous membranes become dry.
Tachycardia or bradycardia develops. Body temperature can rise and, conversely, fall.
Since endogenous intoxication often occurs against the background of a state of shock, the symptoms of endotoxic shock come to the fore. Certain bacterial endotoxins will definitely be present in the blood in severe human conditions, even in the absence of bacteremia. This does not depend on what provoked the syndrome of endogenous intoxication: trauma, burns, tissue ischemia, etc. Only the severity of the person's condition is important.
Degrees of endogenous intoxication
Doctors distinguish three degrees of severity of endogenous intoxication syndrome, each of which has its own criteria:
|
The reaction of the body occurs in response to the formation of a focus of destruction, or to an injury:  The pulse does not exceed 110 beats per minute. The consciousness of a person is not very clouded, he is in a slight euphoria. The skin is not changed, their color is normal. Intestinal peristalsis is impaired and is defined as sluggish. The respiratory rate does not exceed 22 breaths per minute. The volume of urine excreted per day exceeds 1000 ml. |
|
The second degree of endogenous intoxication is characterized by the ingress of endotoxins into the blood, which enter it from the source of intoxication. With the blood flow, they spread throughout the body and accumulate in all tissues:  The pulse quickens and can reach 130 beats per minute. The patient's consciousness is inhibited, or, on the contrary, psychomotor agitation is observed. This parameter depends on the cause of endotoxic shock syndrome. The respiratory rate increases, the number of breaths per minute is from 23 to 30. The patient's skin is pale. The daily volume of urine decreases and ranges from 800 to 1000 ml. There is no intestinal peristalsis. |
|
This degree of endotoxication is characterized by a violation of the work of all organs. The pathological process progresses up to the development of functional multiorgan dysfunction:  The patient's pulse exceeds 130 beats per minute. The patient's consciousness is disturbed, starting from a clouded consciousness and ending with a coma. This condition is called intoxication delirium. Breathing increases significantly and exceeds 30 breaths per minute. The skin may have a cyanotic or earthy hue. Hyperemia of the dermis is not excluded. The daily volume of urine does not exceed 800 ml. The intestines do not function, there is no peristalsis. |
Diagnosis of endogenous intoxication syndrome is built on the basis of an assessment of the severity of a person's condition according to characteristic symptoms (skin tone, respiratory and heart rate, etc.). In addition, blood tests are required.
The results obtained are processed, and they will show a change in such indicators as:
A significant increase in the number of leukocytes in venous blood.
Exceeding the leukocyte and nuclear index of intoxication. Although sometimes these indicators can be underestimated, which indicates the failure of the hematopoietic system and detoxification of the body.
Increase in the index of intoxication. If it exceeds 45, then this clearly indicates an imminent death.
It is necessary to estimate the concentration of total protein in blood plasma.
An increase in bilirubin levels.
Increase in creatinine and urea levels.
Increasing the concentration of lactic acid.
An increase in the coefficient of cells of non-specific protection relative to cells of specific protection. A coefficient greater than 2.0 indicates a serious condition of the patient.
The most sensitive sign of endotoxication is an increase in the level of the medium mass molecule.
Treatment of endogenous intoxication syndrome involves the removal of toxic components from the body and from the blood with an initial decrease in their concentration. Active detoxification is prescribed when 2 or 3 degrees of severity of the pathological syndrome are established.
Biological intoxication is always based on the following mechanisms:
Biological transformation of endotoxic components in the liver. To start this mechanism, hemooxygenation, chemical oxidation of blood (indirect), its photomodification are performed. It is possible to carry out perfusion through cell suspensions or xenoorgans.
Binding and dilution of endotoxic components. For this purpose, it is possible to perform sorption measures aimed at removing endotoxic components from the blood, from plasma, from lymph, from cerebrospinal fluid.
Removal of endotoxic components. To implement this mechanism, the liver, kidneys, gastrointestinal tract, skin and lungs are involved. The patient undergoes intestinal dialysis, hemodialysis, enterosorption, plasmapheresis, hemo- and ultrafiltration, blood replacement, diuresis is forced.
During the period of acute intoxication, the total daily volume of water administered through a dropper should be at the level of 4-5 liters. Moreover, 2.5-3 liters should be crystalloid solutions, and the rest - colloidal and protein blood products: plasma, albumin, protein.
Forced diuresis is considered a simple and commonly used treatment for endotoxicity, which is based on the application of the body's natural process of removing toxins from the body.
The prognosis for the syndrome of endogenous intoxication directly depends on the severity of the patient's condition and on the root cause that led to the development of pathology.
About the doctor: From 2010 to 2016 practicing physician of the therapeutic hospital of the central medical unit No. 21, the city of Elektrostal. Since 2016, she has been working at the diagnostic center No. 3.
Intoxication refers to the poisoning of the body, in which its vital functions are disturbed due to the penetration of toxins and their effects.
When alcohol is abused, the functioning of the brain worsens. In particular, inhibitory processes are suspended, provoking secondary excitation.
With alcohol intoxication, the movement of neurons worsens, which is why reflexes work much worse.
Summing up, we can say that alcohol in large quantities can lead to irreversible processes. Therefore, they cannot be abused.
As you can see, intoxication can be both endogenous and exogenous. But both of these species are extremely dangerous to human health. Therefore, in case of a sharp deterioration in the condition (sharp pains, signs of a cold and high temperature), do not self-medicate - seek medical help immediately.
Tell your friends! Share this article with your friends on your favorite social network using the social buttons. Thank you!
Telegram
Along with this article read:
Does activated charcoal help with heartburn, features of taking ...