Good afternoon, dear colleagues. The topic of this lecture is typical pathological processes involving the system of microcirculation. Microcirculation is most important part of general hemodynamics. The definition of microcirculation: microcirculation is blood flow in micro vessels with diameter less than 100 micrometers. But, of course, the quantitative border is not the most essential. Most essential is that microcirculation is tightly related to fluid exchange between the blood and tissues, the microcirculatory dynamics includes microcirculation in blood vessels, flow of lymph and extravasal tissue fluid. We need to emphasize that microvasculature represents a kind of frame or if you want tissue "plumbing and sanitation system". But the tubes of this plumbing and sanitation system are embedded, built into the walls of a house. And microcirculation is closely associated with mesenchymal stroma or connective tissue, skeleton of all organs and tissues. At the stromal and vascular metrics, the parenchymal cells of an organ settle and maintain their differentiated specialized functions. Without stroma and microcirculatory bed, their life is not possible. Also, the whole construction is known as a structural functional element of an organ or tissue. And in various organs and tissues, the names for these units are different. In connective tissue, we call them histions; in kidney, it is called nephron; in liver, it is called hepaton but the principle structure is similar. Stromal skeleton, microcirculatory blood vessels embedded into that stromal walls and differentiated parenchymal cells living on it. Stroma plays a prior part in tissue defense. All typical pathological processes like inflammation, thrombosis, embolism, allergic reaction, they mechanistically take place within that stromal carcasses or on that histions, on that microcirculatory bed. It is like in bank, when robbers attacked the bank, it is not cashier who will defend the bank. It is not director or some other official. For that purpose, you have special custodians, and they are obliged to be the first in protection against aggression. The same thing in organs in tissues. If for example some organ is involved in inflammation, it is not the whole organ which responds at once. Primarily, stromal cells will be involved, and primarily, stromal elements, including microcirculatory vessels and their content, will establish these kinds of defense like inflammation and so on. So we will speak about the arena or stage where other pathological processes are performed. Microcirculatory bed consists of different types of blood vessels. Every type has its own specific function. These are distributive vessels, exchange vessels, accumulating vessels and shunt vessels. Blood-distributing vessels are terminal arteriole, also known as precapillaries or metarteriolae. They are provided with the precapillary sphincters. The diameter of these vessels is small, about 9-12 micrometers and they are involved in the creation of general peripheral resistance. Their spasm will stop the blood flow in the capillaries. Precapillary sphincters are not complicated multicellular structures as many students believe. In fact, every precapillary sphincter is just a single, one, smooth muscle cell surrounding the mouth of a capillary. We need to emphasize that in skeletal muscles, precapillary sphincters are missing and their role is performed by short metarteriolae. Now, few words about exchange vessels, capillaries and the partially also exchange takes place in post-capillary portions of venulae. This portion of microcirculatory bed is serving to organize at transcapillary exchange and immigration of blood elements into tissues. The total surface area of the whole capillaries of our body is huge, approximately 1500 hectares, and only one glass of blood every second is presented there. So you can imagine that the system can smash one glass, 250 milliliters of blood, on that territory, on the surface, which is greater than a dozen of football fields. That's why the conditions for exchange between blood and tissue are very great because the wall is very thin and the surface of diffusion is huge. Capillaries have no smooth muscle cells. They have no active contractility, and in the majority of organs, they are not innerated at all. So there is no possibility to organize some active contraction of capillaries. Everything which is related to active contraction ends at the level of precapillary sphincters. Each organ involved in blood flow in resting stage, approximately 25 percent of its capillaries and others are turned off the circulation. So capillary may either be turned on function or turned off function. And these, alternatively, depends on the state of supply vessel, arteriole, and it depends also on flickering of precapillary sphincters. The next portion of this bed belongs to accumulating vessels. These are venular collectors and muscular venulae. They have function of blood depot. More than 70 percent of blood volume at any moment resides in venous compartment of circulation bed. And although venules have much poorer muscular layer and their innervation is meager, compared to that of arteriole, but they nevertheless are able to make some contribution into post-capillary function and into change of general peripheral resistant. And, finally, there are also shunt vessels, arterio-venular anastomoses. They present not everywhere. In particular they exist in the skin, in lungs, in kidneys, and this is the shortest pathway between arterial side and venular side of circulation equipped with special sphincters. Sphincter can be either closed or opened, and the blood may go either flow capillary bed, or if the sphincters of the anastomoses will open, the blood will enter the wean directly bypassing the capillaries. These two modes of function are very essential. First one, when anastomoses are closed is nutritional mode, nutritional because the blood supply for tissue is maximal. And another one is non-nutritional. It means that blood supply goes almost entirely into shunts and bypass their living tissue. Again let me remind you With this picture, that the pre-capillary sphincters can be either closed or open. They have no intermediate positions. The question how it regulates if it has not intermediate position. The regulation is achieved by means of blinking. It can blink with some frequency. And this frequency of blinking, frequency of opening and closure may be either increased under the influence of certain local regulators, metabolites, or neural signals, or it may be decreased and thus, the change of the blood flow in capillary bed is established. Now, look at this picture please. You can see microlymph circulation, and it's time to say a few words about role and place of lymphatic vessels. These resorptive vessels. Lymphatic capillaries are valveless, and lymphatic postcapillaries are supplied with lymphatic valves. You can see one of lymphatic valves in this picture here. What is the main purpose of lymphatic drainage? Most people believe that it is most essential to return some fluid into blood, but the fluid can also return at the postcapillary side of venous hemodynamic vessels. Another purpose is most essential for lymphatics to return protein into blood circulation. Everyday, lymphatic capillaries establish the return into circulation protein, protein exudated from blood and protein formed in tissues. If this function will be stopped, it will be very difficult to support the normal protein concentration in blood plasma. Next thing to discuss is the task of microcirculation as a system. The main task of course is local perfusion at the level of minimal metabolic sufficiency, plus it has several additional tasks to save resources of blood flow for surge, for mobilization. And in addition, in specific organs, microcirculator vessels are used for specific tasks like local transport of bioregulators in portal systems between two capillary beds, this existing pituitary, in the liver, in gonads, in kidney, and in all that areas local portal system with two capillary beds, takes the hormones or other bioregulators in one place and transports them for a short distance to second capillary bed. Also, microcirculation is involved in thermal regulation like vessels of skin and mucus membranes. It is involved in erection like in nipples and corpora cavernosa. You can see here the distribution of blood between microcirculatory bed of various organs: brain, gut and liver, skeletal muscles, skin, kidney, myocardial, bones. And can will see that the level of blood flow in a resting state is quite different in different organs. Their record highest level of perfusion is observed in kidney, 360 milliliter per minute per 100 gram of kidney tissue, and in adrenal glands, 300 milliliter. And the next place is occupied by thyroid gland, 160 milliliters per minute. And liver occupies the fourth place with 95. And medical students commonly believe that heart and brain are most essential, and they are traditionally perceived as priority organs, but they are significantly inferior to these leading organs with most generous perfusion because the rate of perfusion in brain is 70 milliliters per minute per 100 grams of brain tissue. And in heart, it is about 50. And very, very sparingly supplied with blood, resting muscle, four milliliters, and bones, three milliliters. And that's minimally enough. In function and in inflammation, this level of perfusion may dramatically change, greatly increase, because of local vasomotor signals. You can see here portal system of pituitary and hypothalamus. And you can see here vascular bed of the skin, which is used for thermoregulation purposes. These are additional tasks of the microcirculatory bed. And now, it is time to have a look on the overall map of typical microcirculatory unit. Here is it with arteriole, metarteriole, preferencial channel, capillary bed, and venous portion. Commonly in many organs, we have one supplying arteriole and two venule, in every microcirculatory unit, but there are exclusions. For example, in penis. For better establishment of erection, the construction of microcirculatory units is opposite to arterioles, a supply in-flow, and only one venula in every unit is responsible for out-flow, to make it easy to create local venous congestion.