Endogenous intoxication, or endotoxicosis

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

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

The results of scientific research conducted over the last 10-15 years have allowed us to formulate a concept of the biochemical substrate of endogenous intoxication, which is most often 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 pronounced neurotoxic syndrome. It includes products of final metabolism, intermediate and altered metabolism, and their level in the blood correlates with the severity of the patient's condition, the degree of clinical and laboratory manifestations of intoxication, and mortality.

In the general pool of substances with medium molecular weight, oligopeptides with a molecular weight of up to 10 kD should be primarily distinguished, among which regulatory and non-regulatory peptides are distinguished.

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

Non-regulatory peptides are biologically active substances, toxins that have entered from outside (bacterial, burn, intestinal, etc.) or formed inside the body as a result of autolysis, ischemia or hypoxia of organs, intensive proteolysis of the products of various metabolic processes, and the most extensive group of constantly identified peptides are fragments of collagen, fibrinogen and other blood plasma proteins excreted in the urine in a variety of diseases and syndromes: burns, renal and hepatic failure, injuries with tissue compression, infections (especially 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, the biological activity of which is very diverse from participation in the work of 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 immunodepression,
• have 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 a 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 effects aimed at urgently supplying the body with a certain set of amino acids necessary in extreme conditions to ensure hormone and enzyme formation, protein regeneration, hematopoiesis and other physiological functions. When these medium-molecular compounds are formed, 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 measures is considered to be hemocorrection, aimed at reducing the concentration in the blood of the most biologically active medium-molecular compounds or neutralizing them.

In clinical toxicology, the concept of endotoxicosis has long been associated mainly with toxic damage to the liver and kidneys as important components of the body's natural detoxification system. 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 liver and kidney failure. However, endotoxicosis also develops in the toxicogenic stage of acute poisoning with substances with neuro- and psychotropic effects soon after chemical trauma without noticeable impairment of liver and kidney function.

Already upon admission to hospital, 80% of severe and moderately severe 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 trauma 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.

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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, circa 1000 AD), which in most cases did not give the expected clinical results during further expert assessment of their practical application. Back in the 60s of the 20th century, as the clinical experience of the first specialized toxicology departments accumulated, the use of antidotes - analeptics in poisoning with sleeping pills and narcotics was discontinued due to their low efficiency and the risk of complications. Later, by the end of the century, it became clear that the implementation of the clinical effect of pharmacotherapy in acute poisoning is generally hindered by the toxicogenic blockade of many drug receptors and the development of hypoxia, 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 to stimulate the body's natural detoxification in the form of so-called galenic preparations (Galen, ca. 200 AD), which have been available in any pharmacy since ancient times as emetic, laxative and diuretic agents of plant origin, called "Alexipharmica".

Later, as general clinical toxicology and resuscitation developed, allowing for the effective support of the body's basic vital functions, 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, apparently used already in Ancient Egypt, and the operation of partial replacement of the patient's blood with donor blood developed later by 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" (1960s) and the device for hemosorption (1970s).

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

In addition to active detoxification methods, which have the nature of etiologic treatment and therefore are most effective in the earliest phase of the toxicogenic stage of poisoning (toxicokinetic correction), in complicated forms of the disease, as its severity increases, the role of symptomatic therapy increases, usually having a resuscitation content, which allows maintaining a certain minimum of functions of vital organs to ensure the possibility of detoxification measures (toxicodynamic correction). Most often, the main types of complications are known pathological syndromes: toxic shock, ARF, 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 of treatment 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 endogenous intoxication syndrome is clearly manifested only in the somatogenic phase of the disease due to chemical burns of the digestive tract, the development of renal and hepatic failure and toxic-hypoxic encephalopathy.

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