Pathogenesis of toxic injuries

Damage to biomembranes and mitochondria

Cytoplasmic membranes, as well as the membranes of the endoplasmic reticulum and Golgi apparatus, serve as an organizing matrix for enzyme systems. The exposure of these structures to xenobiotics inevitably disrupts cell vitality.

Membrane damage can develop through three pathways:

• Direct non-specific action: heavy metals, benzene, toluene, chloroform, soaps, and denaturing agents physically disrupt the membrane structure. This leads to its deformation and cell death (e.g., erythrocyte hemolysis).
• Selective action: targeted attack on membrane-bound enzymes, transport systems, and receptors. This is how ion channel blockers, glycosides, and neurotransmitter antagonists work.
• Mediated damage: the poison triggers lipid peroxidation (LPO) or excessively activates phospholipases.

A separate role is played by mitochondrial poisons. They can disrupt links in cellular bioenergy, block protein synthesis on the rough endoplasmic reticulum, alter xenobiotic metabolism on the smooth reticulum, or rupture lysosomal membranes, which triggers cell autolysis (self-digestion). During these pathochemical reactions, secondary biologically active substances are formed, exacerbating the course of the disease.

Toxic liver dystrophy

The liver is the main target organ for hepatotropic poisons causing acute massive necrosis (toxic hepatitis).

The classification of such toxins distinguishes:

1. Plant poisons: mushroom toxins (amanitin, phalloidin — the active substances of the death cap Amanita phalloides).
2. Industrial and household poisons: arsenic, phosphorus, carbon tetrachloride.
3. Heavy metals.
4. Medicinal products: agents with a direct damaging effect (methotrexate) and drugs with hepatotoxic properties (isoniazid, cytostatics, methyldopa, high-dose paracetamol).

Hepatocyte death upon exposure to xenobiotics is realized through three main mechanisms:

• Direct toxic action. The poison immediately destroys the cell. A classic example is the amanitotoxins of the death cap, which specifically block RNA polymerase II and completely halt protein synthesis.
• Bioactivation (metabolite toxicity). An initially weakly toxic substance (e.g., salicylates, tetracycline, or paracetamol) is converted during metabolism into an aggressive compound that destroys membranes.
• Immune (hapten) mechanisms. The drug (e.g., halothane) acts as a hapten. It binds to hepatocyte proteins, turning them into immunogens. The body stops recognizing these proteins as its own and launches an autoimmune attack against them.

Prognosis and age-related features

An important difference between toxic hepatitis and viral lesions lies in the prognosis. If the patient successfully survives the acute stage of chemical poisoning with massive necrosis, the disease, as a rule, does not progress to a chronic form.

The course of toxic processes in pediatrics requires special attention. In children (especially early age), intoxications are significantly more severe than in adults. This is due to three anatomical and physiological factors:

• High permeability of histohematic barriers: poisons penetrate tissues faster and in larger quantities, especially into central nervous system structures.
• Metabolic lability: metabolic processes are extremely unstable and easily tip over into pathology.
• Reduced tolerance: the child's body as a whole is less resilient to the effects of any chemical xenobiotics.

Class and exam questions

What else to study on this topic

• The pathogenetic role of biologically active substances (BAS) formed during the breakdown of cell membranes.
• Mechanisms of induction and inhibition of xenobiotic metabolism in the smooth endoplasmic reticulum.
• Cell autolysis due to toxic damage to lysosomal membranes.
• Detailed classification of medicinal products with hepatotoxic properties.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.