Intensive Care of Acute Poisoning - A. V. Hovenko 2010

General characteristics of acute poisoning
Features of the pathogenesis of acute poisoning and factors determining the development of intoxication

The following factors are distinguished in the Pathogenesis of poisoning.

1. Concentration factor – the concentration of toxic molecules in the biological fluids of the body (mcg/ml). This is the primary factor, as it correlates with the onset of initial clinical symptoms when a toxic concentration is reached in the Blood, as well as with the subsequent progression of poisoning, potentially leading to a fatal outcome in cases of lethal concentrations.

2. Time factor – determines the duration for which a toxic dose remains in the body, alongside its rates of uptake and elimination. In general, it reflects the relationship between the duration of exposure and the resulting toxic effect. Determining the dynamics of the concentration and time factors makes it possible to differentiate between the toxicogenic and somatogenic phases of poisoning, as well as the periods of poison absorption and elimination within the toxicogenic phase.

3. Spatial factor – determines the pathways of entry, elimination, and spatial Distribution of a toxicant, which is primarily associated with the Blood supply to Organs and Tissues. The largest amount of poison per unit of time typically reaches the Lungs, Kidneys, Liver, Heart, and Brain—a process known as dynamic distribution. In addition, static distribution occurs, which is linked to the degree of adsorption and sensitivity of toxicity receptors. The Nature of the interaction between the toxin and the body also depends on numerous additional variables related to both the toxicant itself and the Organism, such as the reactivity of enzyme systems. These, in turn, depend on the specific "toxicological scenario," such as various routes of administration or interactions with Other toxins.

4. Age factor – reflects the degree of susceptibility and systemic response to a toxin across different stages of a human's life. This factor is particularly critical in pediatric and geriatric populations, where resistance to toxic effects is reduced tenfold or more.

5. Treatment efficacy factor – determines the body's response to detoxification therapy, which can significantly raise the concentration thresholds for The Development of major intoxication symptoms and considerably shorten the duration of the toxicogenic phase.

A special place in the pathogenesis of poisoning is held by METABOLISM/2.html">THE CONCEPT OF toxicity receptors, which serve as the specific sites where a toxin interacts with the organism. Toxicological studies by J. Langley (1878) and A. Clark (1937) demonstrated that a bond can form between natural substances and receptors, analogous to the interaction between a substrate and a specific enzyme. For example, the Serine hydroxyl group, which is a structural component of the enzyme acetylcholinesterase, acts as a receptor for organophosphates (such as malathion, trichlorfon, etc.), forming a stable compound with them. As a result, a specific anticholinesterase effect develops, which is characteristic of most organophosphates.

In addition to Enzymes, toxicity receptors include Amino Acids (such as Histidine and Cysteine), Nucleic Acids, purine and pyrimidine NUCLEOTIDES, Vitamins, and the most active Functional groups of Organic compounds—such as sulfhydryl, hydroxyl, carboxyl, amino, and phosphorus-containing groups—which play a vital role in cellular metabolism.

It is believed (A. Albert, 1951) that any chemical substance, in order to elicit a biological effect, must possess at least two characteristics: receptor affinity and intrinsic physicochemical activity. Affinity refers to the degree of binding between a substance and its receptor, measured as the inverse of the dissociation rate constant of the drug-receptor complex. The degree of toxicity of a chemical is determined by the minimum number of its molecules capable of binding to and disabling vital target Cells.

There is a distinct group of substances characterized by specific membrane-toxic action, known as membranotoxins (A. A. Pokrovsky, 1962). These include exogenous and endogenous chemical compounds with phospholipase activity, which lead to the disorganization and destruction of the basic liquid-crystalline Membrane Structure, ultimately resulting in Cell death (such as venoms from snakes, insects, and microorganisms; saponins, synthetic detergents, etc.).

A notable feature in the pathogenesis of many poisonings is the toxification of certain chemical compounds during their biotransformation within the body. In these cases, the metabolites of the toxin become more toxic than the parent substance itself. This process is termed "Lethal synthesis." Examples include the metabolism of methyl alcohol, Ethylene glycol, and certain organophosphates (such as malathion).

The clinical course of Acute Poisoning comprises the following stages.

I. Toxicogenic stage, during which the toxin is present in the body at a dose capable of inducing specific effects (Exotoxic Shock, coma, gastrointestinal bleeding, asphyxia, etc.). These effects are associated with the disruption of specific membranes, Proteins, and other toxicity receptors. Concurrently, adaptive reactions are triggered to counteract Homeostasis disturbances, with the toxic substance acting as the trigger. These include the pituitary-adrenal response ("stress"), the lysosomal response, cardiovascular responses (centralization of Blood Circulation), Blood Coagulation responses, and others related to the somatogenic effect of the chemical injury. Initially, all these reactions function as protective mechanisms.

The toxicogenic stage comprises two periods:

1. The period of poison absorption (until peak blood concentration is reached).

2. The period of poison elimination (until complete clearance from the body).

II. Somatogenic stage begins after the elimination (partial or complete) or breakdown of the toxin, presenting as residual injury to various organs and systems until full recovery is achieved or the organism succumbs (acute respiratory distress syndrome, acute hepatorenal failure, Sepsis, etc.).

Thus, the overall toxic effect resulting from poisoning is the net result of specific toxic interactions combined with the compensatory and adaptive Responses of the human body. At the same time, non-specific responses to poisoning—such as the "centralization of blood circulation," hypocoagulation, or hyperfibrinolysis—when pronounced, become the cause of severe homeostatic imbalances and necessitate urgent medical intervention.