The thesis is devoted to the determination of tissue, cellular and ultrastructural changes in the haemomicrocirculation and parenchymatous-stromal elements of the pancreas and liver in experimental acute pancreatitis, taking into account the degree and localization of morphological lesions.
Based on the quantitative histological, electron microscopic and biochemical analysis of changes in the modeling of acute pancreatitis in rats, it has been proved that the dynamics of the level of blood amylase, pathomorphological changes in microcirculation, parenchyma and pancreatic stroma are similar in both of the studied models of acute pancreatitis. Pathological changes of microvessels after administration of L-arginine are combined with diffuse damage to the parenchyma of the pancreas in apoptotic and necrotic mechanisms. The particularity of the model using sodium taurocholate is the prevalence of hemorrhagic manifestations along with inflammatory and necrotic changes that have a significant gradient from head to tail of the pancreas. It is shown that in the model of acute pancreatitis using sodium taurocholate there is a faster rate of amylase recovery, a microvessel and a common tissue structure of the pancreas in comparison with L-arginine.
It is shown that the fastest reaction in the modeling of acute pancreatitis reveals the microcirculatory channel of the pancreas, but the most vulnerable component is the exocrine part of the gland. In particular, 4 hours after administration of L-arginine in the maximal dose, the proportion of necrotized acinar epitheliocytes is 5,1 %, after 24 hours – 42,.1 %, remaining at a high level of up to 72 hours of experiment in those surviving animals. Similar changes occur in the model with the use of the maximum dose of sodium taurocholate in the pancreas head, but in the tail of the pancreas, there is a reduction in necrotic manifestations with a decrease in the proportion of necrotic cells in 72 hours of the study.
In this work, reactions from the hepatic microcirculation in acute pancreatitis are investigated and their sequence is presented, which includes: 1) activation of liver circulation, primarily portal component, against the background of an enzyme toxicemia from the pancreas; 2) the development of inflammatory, dystrophic, destructive and necrotic changes in the liver parenchyma, along with microcirculatory disorders in the context of necrotic toxemia; 3) rehabilitation-adaptation or decompensation processes in the microcirculation system and liver parenchyma, depending on the degree of pancreatic toxemia.
For the first time the data of electronic microscopy is given that the morphological substrate of the haemomicrocirculation of the pancreas in the development of acute pancreatitis is a complex of ultrastructural changes of the microvessels, namely: 1) deformation and destruction of the arteriolar wall; 2) hypoxic damage of the fenestral endothelium of haemocapillars of pancreatic islets and vessels of the insulin-acinar portal system; 3) sweating red blood cells and thrombosis of somatic hemocapillars in pancreatic acinus with endothelial fragmentation; 4) dilation and desolation of the drainage link of the microcirculatory bed.
It has been proved that irreversible ultrastructural changes of the exocrine and endocrine cells of the pancreas with a violation of their secretory cycle are partially offset by the preservation of functionally active cells due to the restructuring of the microcirculatory channel due to formation of primitive somatic type hemocapillars. The high mortality of animals during the three days from the beginning of the experiment with the application of maximum doses of L-arginine and sodium taurocholate is due to blockage of transcapillary metabolism, deep destruction of mitochondria and ultrastructures of protein synthesis of acinocytes, progressive thrombosis of microvessels, and increased intercellular manifestations of pancreatogenic toxemia.
For the first time, with the help of ultrastructural analysis, data are presented on the chronological sequence of pathological changes of the microcirculatory channel of the liver in acute pancreatitis, depending on the dose of L-arginine or sodium taurocholate. In particular, within 72 hours of the experiment, at the minimum and average doses of these factors, in the context of reduction of acute pancreatitis, there is a gradual renovation of the structure of the microvessels and normalization of the microcirculation of the liver. In the maximum doses, L-arginine (5 g/kg) or sodium taurocholate (5% solution) cause degradation of the liver microvessels with the progression of hemorrhages, slit red blood cells and platelet aggregation, which causes blockage of the microcirculation and the development of necrotic changes in the hepatic parenchyma.
