Endogenous intoxication, or endotoxicosis

From the general point of view, the term "endogenous intoxication" (endotoxicosis) means a pathological condition (syndrome) that develops in various diseases due to accumulation in the body of various endogenous toxicants when the function of the natural biological detoxification system is inadequate.

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

The results of scientific research conducted during the last 10-15 years have made it possible to form an understanding of the biochemical substratum of endogenous intoxication, which is most often a number of medium-molecular weight substances. Clinically, the syndrome was first described by L Babb (1971) in patients with CRF with severe neurotoxic syndrome. Its composition includes the products of final metabolism, intermediate and altered metabolism, the level of their content in the blood correlated with the severity of the patients' condition, the severity of clinical and laboratory manifestations of intoxication, as well as lethality.

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

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

Non-regulatory peptides are biologically active substances, external toxins (bacterial, burn, intestinal, etc.) or formed within the body as a result of autolysis, ischemia or hypoxia of organs, intensive proteolysis of products of various metabolic processes, the most extensive group of constantly identified peptides are fragments of collagen, fibrinogen and other plasma proteins, excreted in the urine with a variety of diseases and syndromes burns, renal and hepatic insufficiency, trauma ah with the compression of tissues, infections (especially with sepsis), pancreatitis, oncological and autoimmune diseases, etc.

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

The individual components of the pool of medium molecules:

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

It is obvious that the main pathological process of endotoxicosis develops 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 states is the accumulation of a pool of medium-molecular compounds possessing different biological activity as a result of pathological protein degradation due to increased proteolysis and other destructive influences aimed at emergency supply of the organism with a certain set of amino acids required in extreme states for providing hormone and enzyme formation, protein regeneration, hematopoiesis and other physiological functions nktsy. When these medium-molecular compounds form, a kind of "vicious circle" is formed, in which an increase in the concentration in the blood and the consumption of these substances entails their further production of a pathological nature. Therefore, the main goal of therapeutic detoxification activities is considered 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 endotoxicosis has been associated for a long time, mainly with toxic damage to the liver and kidneys as important components of the natural detoxification system of the body. At the same time, clinical and laboratory signs of endotoxicosis were detected in the somatogenic stage of hepatocellular and nephrotoxic substance poisoning 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 by substances of neuro- and psychotropic action shortly after a chemical trauma without noticeable violations of the function of the liver and kidneys.

Even at admission to the hospital, 80% of severe and moderate patients (coma) show an increase in the blood level of "medium molecules" by 23-83% of the norm. At the same time, a significant increase in aggregation activity of erythrocytes, platelets and ESR (respectively, by 40.8.80 and 65%) was noted. At the same time, critical concentrations of the above toxicants in the blood are determined, which indicates a high intensity of the chemical trauma of the organism, and the most informative markers of blood toxicity are the level of "medium molecules" in it and the degree of increase in the leukocyte index of intoxication and the neutrophil shift index.

[1], [2], [3], [4], [5]

Treatment of endogenous intoxication

For many centuries, the main direction in the treatment of poisonings was the use of antidotes, started at the beginning of a new era (Avicenna, ca 1000 AD), which in most cases did not give the expected clinical results with further expert assessment of their practical application. 60s of the XX century, as the clinical experience of the first specialized toxicology departments was accumulated, the use of antidotes - analeptics for poisoning with hypnotics and narcotics was stopped due to their low effect Nost and the risk of complications. Later, by the end of the century, it became clear that in general the realization of the clinical effect of pharmacotherapy in acute poisoning is hindered by the toxicogenic blockade of many medicinal receptors and the development of hypoxia, which leads to the absence or perversion of the expected results. The second historical direction in the treatment of toxicoses was the use of methods to stimulate the natural detoxification of the body in the form of so-called galenic preparations (Galen, ca. 200 AD), which were from ancient times in any pharmacy as emetic, laxatives and diuretic agents of vegetable origin, Alexifarmika ".

In the future, as the development of general clinical toxicology and resuscitation, which allows to effectively support the basic functions of the vital functions of the organism, including detoxification, there was the possibility of considerable stimulation of 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, aimed at reducing the concentration of toxicants directly in the blood, is bloodletting, which is apparently used already in Ancient Egypt, and the later developed operation of partial replacement of the blood of a patient with donor blood O. S. Glozman (1963). This idea found a further solution in the form of modeling various devices for extracorporeal cleansing of blood, the first of which were the "artificial kidney" (60s) and apparatus for hemosorption (70s).

1. Given the traditionally established trends in the treatment of acute toxicosis, EA Luzhnikov (1977) proposed a clinical classification of modern methods of detoxification, which is widely used at present in medical science and practice. According to this classification, the methods for stimulating the natural processes of detoxification, biotransformation, transport and binding of toxicants are singled out as the first separate group (A).
2. The second separate group (B) presents all the methods of artificial physicochemical detoxification, named in this way in connection with the artificially created extracorporeal (often hardware) supplementary toxicant removal channel, designed to relieve the natural system of detoxification and even temporarily replace it.
3. In the third separate group (C), all pharmacological preparations for specific (antidote) therapy of poisoning are collected, which for the above reason occupy a modest place in the arsenal of detoxification products and are used mainly at the prehospital stage.

In addition to the methods of active detoxification, which have the character of etiological treatment and therefore are most effective in the earliest phase of the toxicogenic stage of poisoning (toxicokinetic correction), with the complicated form of the disease, as the severity of its severity increases, the role of symptomatic therapy, usually having resuscitative content, a certain minimum of functions of vital organs to ensure the possibility of carrying out detoxification activities (toxicodynamic correction). The most common types of complications are known pathological syndromes toxic shock, ODN, toxic-hypoxic encephalopathy, cardiomyopathy and endotoxicosis.

When 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 nephropathies, pancreatitis, etc.), but the methods of efferent detoxification therapy always occupy a significant place in the complex of therapeutic measures, especially hemosorption, dialysis and GF , plasmapheresis.

In clinical toxicology, the early use of efferent therapy contributes to a marked decrease in the severity of endogenous intoxication and prevention of polyorganous lesions.

In acute poisoning, the syndrome of endogenous intoxication is clearly manifested only in the somatogenic phase of the disease due to chemical burns in the digestive tract, the development of renal and hepatic insufficiency, and toxic-hypoxic encephalopathy.

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