Pathogenesis of hemolytic uremic syndrome

The diversity of factors causing the development of hemolytic-uremic syndrome with similar clinical manifestations indicate a common mechanism of their action. It has been shown that the main property of the agent causing hemolytic-uremic syndrome is its ability to damage endothelial cells (EC). Special ultrastructural studies reveal edema of endothelial cells, their detachment from the basement membrane and a decrease in the lumen of capillaries in patients with hemolytic-uremic syndrome. Microbes, bacterial toxins, viruses, and antigen-antibody complexes have a direct destructive effect on endothelial cells. Damage to EC against the background of intestinal infection is caused by the action of E. Coli verotoxin and S. Dysenteriae shiga toxin, which are both cytotoxins and neurotoxins. Recently, a special role has been given to E. Coli 0157: H7, which has various verotoxins. Proteolytic enzymes and free oxidation metabolites secreted from polymorphonuclear leukocytes (PMN) participate in the destruction of EC. The pathological process in EC is also enhanced by inflammatory mediators - interleukin-1 (IL-1) and tumor necrosis factors (TNF), which are produced by PMN under the influence of bacteria and endotoxins secreted from them. PMN are activated by interleukin-8 in hemolytic uremic syndrome. Another mechanism of EC damage is the activation of the complement system.

There are two triggering moments preceding the development of hemolytic-uremic syndrome. In diarrheal forms of hemolytic-uremic syndrome, activation of blood coagulation factors and development of disseminated intravascular coagulation (DIC) are observed, which determines the characteristic clinical and morphological picture of the disease. In hemolytic-uremic syndrome variants not associated with intestinal infections, intravascular activation of platelets is most often detected over a long period of observation, often without any signs of DIC. However, it has now been proven that the main triggering moment for the development of hemolytic-uremic syndrome is damage to endothelial cells. Subsequent preferential involvement of either the coagulation or platelet link of 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, swelling of the endothelial cells themselves and accumulation of platelet aggregates contribute to the narrowing of the lumen of the capillaries and arterioles of the kidneys. This leads to a decrease in the filtering surface, resulting in a decrease in the glomerular filtration rate and the development of acute renal failure. The development of hemolytic anemia in hemolytic uremic syndrome is explained, on the one hand, by mechanical damage to erythrocytes when passing through thrombosed microcirculation vessels, and another cause of erythrocyte hemolysis is pronounced electrolyte disturbances in the blood. In this case, erythrocytes acquire the appearance of "shells" or "hoods".

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