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Chapter 1. Morphology of metabolic disorders - dystrophy

The sum of mechanisms determining body metabolism is termed trophism. These mechanisms are implemented at the cellular and extracellular levels. Cellular mechanisms are maintained by structural cell organization and its genetically determined autoregulation. Extracellular trophism mechanisms include transport (blood, lymph) and integrative (nervous, endocrine, and humoral) systems. Dystrophy (Greek dys - deviation from the norm and trophe - nutrition) is a pathological process based on the disruption of tissue and/or cellular metabolism leading to structural changes.

Dystrophy is a type of organ and tissue damage that can be either reversible or irreversible. It manifests as a violation of normal content or physico-chemical properties of various compounds, emergence of usual substances in unusual locations, or the formation of substances not normally found in cells, extracellular substances, vascular walls, and organ stroma.

The causes of dystrophy include any effects leading to the violation of cellular and extracellular trophic mechanisms: hypoxia, toxic effects, genetic impairment, various enzyme defects (fermentopathies), viruses, nutritional imbalance, diseases of the nervous or endocrine systems, blood or urine composition disorders in case of internal organ diseases, etc.

Depending on the type of metabolic disturbances, dystrophy can be of protein, fatty, carbohydrate, mineral, aqueous, or mixed type.

Based on the predominant localization of metabolic disorders and deposits of certain substances, dystrophy can be parenchymal, stromal-vascular, or mixed.

Depending on the involvement of genetic factors, dystrophy can be inherited or acquired. Inherited dystrophy is caused by genetic defects of an enzyme. Thus, metabolic products are accumulated rather than utilized, and in these cases, accumulatory di­seases (thesaurismoses) develop. Acquired dystrophies are associated with developed enzymopathies, often combined with a disruption of transport or metabolism of substances that provide tissues or cells with energy.

Depending on the prevalence of the process, general and local dystrophies are manifested.

Four morphogenetic development mechanisms of dystrophy are distinguished: infiltration, decomposition, transformation, and altered synthesis.

Infiltration is excessive penetration of substances or metabolic products into cells, vascular walls, inter-cellular substances, and/or the impairment of their inclusion in metabolism, with further intracellular or extracellular accumulation. For instance, protein infiltration of the proximal tubular epithelium of the kidneys with increased protein levels in the primary urine in cases of glomerulopathies. It is also possible for exogenous substances to accumulate, which the cell can neither destroy with enzymes, nor transport to another place (for example, coal particles).

Decomposition (phanerosis) is a breakdown of cell ultrastructures and intercellular substance leading to metabolic disorders and accumulation of disturbed metabolic products in the cell. For example, the breakdown of matrix polysaccharide-protein complexes underlies fibrinoid changes in connective tissue during rheumatic d­iseases.

Transformation is a transition of one substance into another. For example, transformation of carbohydrates into fats in the case of diabetes mellitus.

Perverted synthesis is the formation in the cell or in tissues of substances that are not normally encountered in them. Such a mechanism underlies the synthesis of abnormal amyloid protein and its deposition in the intercellular substance.

The mechanisms of dystrophy development can be combined.

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