Good afternoon, dear colleagues. The topic of my lecture for today is pathophysiology of inflammation. But, what is inflammation? It is said, "the history of medicine is a history of inflammation studies." That's why probably inflammation is a keystone of the whole pathology building. Inflammation is the typical pathological process developing in vascularised organs and tissues in response to any local injury. It manifests in the form of incremental changes of microcirculation, blood, and stromal elements of the organs. Do you remember our previous lecture about histion, about stromal? Which is first in all defensive reactions. So what is obligatory involved in any inflammation? Microcirculatory bed, blood, and stromal or connective tissue is the central nervous system obligatory for inflammation. We shall see, but please remember that it is possible to model acute inflammation in early chick embryo which not yet formed central nervous system, no brain in early chick embryo, but inflammation is already possible. Also you know, there are some organs in human body which have no innervation like placenta. It is not innervated neither from baby, nor from maternal side. But nevertheless, inflammation of placenta, placentitis is possible and may cause harm. So, connective tissue, blood, microcirculatory bed, they are obligatory for inflammation. No blood vessels, no inflammation in its typical shape and kind. But central nervous system at least is not obligatory to control inflammation, it is self controlled process with predominance of local regulation over central one. Also the aim of this process, the aim is localization, dilution, isolation, elimination of the agent that caused the damage and triggered the inflammation. The aim is also to restore the damaged tissue and to delineate, separate as close as it's possible, the focus of conflict from the rest part of the organism to prevent spreading of a flogogenic agents and inflammatory mediators beyond the borders of the inflammatory focus. Inflammation as typical pathological process displays all key attributes of typical pathological processes learned before this lecture. Inflammation is Evolutionary conditioned, it is Stereotypic, it has similar display in different organs and tissues, it is Universal and Polyaetiologic, may be caused by various reasons. It is also Autochtonic. Autochthony of inflammation is the ability for self-regulation and self-perpetuating. Inflammatory process is at the equifinal. It means, it may start from various triggers or from various links, but finally develops into a universal final result. At least all these characteristics are peculiar to acute inflammation. Chronic inflammation is a little bit different process and we will consume that later. There are five main theories of inflammation based on natural science. And the author of the pioneering first theory was Rudolf Virchow, who suggested so-called nutritive attraction theory based on microscopic studies and the images. The main idea was that, inflammation always starts with tissue damage, alteration. And as a result of alteration, first the cells participating in inflammation, they experience nutritive attraction, they attract some resources, and microscopist can observe some inclusions in their cytoplasm, and finally, these inclusions disappear. Rudolf Virchow believed that cells used that material for renovation, for reparative process. So he delineated initial stage alteration, nutritive attraction and finally, the use of that attracted inclusions as in materials for reparative process. Many things in this old theory were absolutely correct. Inflammation really starts from alteration of tissues, tissue damage. No damage, no inflammation. Something looking like cell inclusions really can be located in the cytoplasm of the cells participating in inflammation. For example, in cytoplasm of white blood cell you can locate certain granules. But modern science knows that these are not inclusions. These are organoids and what you have believed to be material for building is in fact a source of signals driving the inflammation because granules contain inflammatory mediators, local autocoids, which are released into focus of inflammation, activated and driving the process and determining the cell behavior. So, attractive nutrition theory Virchow was inherited by medicine but transformed, transformed with the participation of second contributor, Julius Cohnheim. Julius Cohnheim investigated the vascular dynamic of inflammation by means of biomicroscopy and he managed to understand that there is a regular, universal consequence of vascular events. A short-time Ischemia prolonged, Hyperemia, gradual slow running of blood flow, active hyperemia in course of inflammation in transfiguring it into venous congestion and even to complete stasis. The most brilliant discovery by Cohnheim was margination and emmigration of white blood cells into the foci of inflammation. So Cohnheim constructed vascular theory of inflammation and according to him, many manifestations like rubor, edema, and so on, they result from vascular changes and all vascular changes, repair, process of leukocyte immigration. But what is the purpose of that leukocyte immigration? Why they get out of blood vessel? What do they do in tissues? That question was without an answer in Cohnheim's theory. That question was answered by a Russian evolutionary biologist, associate professor of our university, Ilya Mechnikov. Mechnikov discovered the phenomenon of phagocytosis and which is more important. He interpreted phagocytosis in evolutionary and in a patophysiological sense of that word. He understood why, for which purpose blood cells immigrate. Mechnikov's theory of inflammation was phagocytic theory or phagocytosis theory. He paid much attention to phagocytosis as a central event in the whole dynamic of inflammation and he has shown that phagocytosis is a display of activity of a newly discovered system later called immune system. So Mechnikov's theory interpreted inflammation as a kind of polygamy for the immune phenomena, but what was the precise mechanism of leukocyte motion, vascular dynamic, and other events of inflammation. In 20th century, German scientist, Schade, Heinrich Schade, constructed physical chemical theory of inflammation. He insisted that all biological events in the course of inflammation are based on physical and chemical phenomena, like acidity, changes of osmotic pressure, and changes of surface tension within inflammatory foci. By means of micro electrode technique, he managed to measure the concentrations of ions within inflammatory foreskin, osmotic pressure, local temperature, local acidity, and so on, and he concluded that there are certain gradients, gradient of acidity, gradient or osmotic pressure, regular changes of surface tension, and these physical changes influence the behavior of cell and they substantiate the external medical manifestations of the process. For a long time, it was believed that everything in organism is under a strict central control. And even Virchow interpreted the organism as a state of cells with a tsar in the brain. And inflammation studies were not exclusion. Many theoreticians believed that inflammation is also under strict central control and the first person who explained the cybernetic and biochemical basis for inflammation, automaticity, and autonomy was an American pathologist of Russian origin, Valy Menkin. Valy Menkin separates the inflammatory exudates by means of chromatography in two separate portions and after that, injecting these portions to experimental element. He was able to reproduce the elements of inflammation separately. For example, edema without pain, pain without edema, a rubor without other manifestations, and so on and so forth. That was first important step to the discovery of the mediators of inflammation. The conclusion of Menkin's experiments was that the whole dynamic of inflammation is not centrally controlled but is a result of certain locally produced or locally activated chemical signals and by means of that humoral self-regulation. The cells establish that whole process of inflammation from the very beginning and until the reparative regeneration phase. And by means of that humoral self-regulating chemical signals, damaged cells are able to control the whole process of inflammation dynamics from the very beginning until the very end and final reparative stage. So, finally, pathophysiology came to the idea of inflammation as self-regulating autoctonomous process.
