Pathogenesis of hemolytic-uremic syndrome

The variety of factors that cause the development of hemolytic-uremic syndrome with the same clinical manifestations, indicate the common mechanism of their action. It is shown that the main property of the agent that causes hemolytic-uremic syndrome is its ability to damage endothelial cells (EC). Special ultrastructural studies reveal in patients with hemolytic uremic syndrome edema of endothelial cells, their separation from the basal membrane and a decrease in the lumen of the capillaries. Direct destroying effect on endothelial cells is exerted by microbes, bacterial toxins, viruses, antigen-antibody complexes. EC damage against a background of intestinal infection is caused by the action of verotoxin E. Coli and shigatoxin S. Dysenteriae, which are both cytotoxins and neurotoxins. Recently, a special role is assigned to E. Coli 0157: H7, which has various verotoxins. In the destruction of ECs, proteolytic enzymes and free metabolites of oxidation are extracted from polymorphonuclear leukocytes (PMNL). Enhance the pathological process in the EC and mediators of inflammation - interleukin-1 (IL-1) and the facts of tumor necrosis (TNF), which are produced PMNL under the influence of bacteria and endotoxins released from them. PMNAL are activated in case of hemolytic-uremic syndrome with interleukin-8. Another mechanism of EC damage is the activation of the complement system.

There are two starting points that preceded the development of hemolytic-uremic syndrome. In diarrheal forms of hemolytic-uremic syndrome, activation of clotting factors and the development of disseminated intravascular coagulation (DVS) are observed, which determines the characteristic clinical and morphological picture of the disease. In variants of hemolytic-uremic syndrome not associated with intestinal infections, intravascular platelet activation is most often detected over a long period of observation, often without any signs of internal combustion engine. However, it has now been proven that the main starting point for the development of hemolytic-uremic syndrome is damage to endothelial cells. The subsequent predominant involvement of either coagulative or platelet-derived hemostasis is apparently due to the degree and qualitative disorders of the vascular endothelium. The accumulation of vasoactive substances released from activated platelets and damaged EC, the swelling of the endothelial cells themselves and the accumulation of platelet aggregates contribute to a narrowing of the lumen of the capillaries and arterioles of the kidneys. This leads to a decrease in the filtering surface, as a result of which the glomerular filtration rate decreases and acute renal failure develops. The development of hemolytic anemia in hemolytic-uremic syndrome is explained, on the one hand, by mechanical damage to erythrocytes during passage through thrombosed vessels of microcirculation, another cause of hemolytic erythrocytes are pronounced electrolyte disturbances in the blood. In this case, the red blood cells take the form of "shells" or "hoods".

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