The next part of our talk is devoted to ischaemia. Ischemia, the term goes from the Greek ischaimos, to detain, to stop. Ischaemia is reduction of blood supply to an organ or tissue due to reduced blood inflow. This is very important typical pathological process. The most common cause of hypoxia in human life and in human death, unfortunately. In ischaemic tissue, hypoxia occurs. And also, hypercapnia or excess of carbon dioxide, which may lead to local tissue acidosis at the place of ischaemia. Exterior symptoms of ischaemia include local hypothermia and change of color. Superficial tissues get pale, pallor or sometimes, expression of the natural own tissue of some color of some tissue. As you can see in this photograph is a main external manifestation of the ischaemia. Also, in ischaemia, we have reasonable reduction in the number of blood vessels and the loss of their natural convoluted shape and disappearance of pulsation, which is the case for that photo with diabetic foot. Diabetic foot, by the way, is one of the most dangerous results of ischaemia. Also, sometimes in some organs, ischaemia can cause the reduction of the organ volume. And always, ischaemia drastically diminishes the organ's functionality, functional potential. Ischaemia play very important role in pathophysiology as a protective, defensive mechanism, limiting bleedings during the vascular injury, redistributing blood in the body. In emergency, it is used for heat exchange regulation. But, nevertheless, first of all, for medical doctor, ischaemia is interesting as a matter of pathology. It is highly pathogenic. Even the initial manifestations of ischaemia are unpleasant and they cause characteristic complaints of a patient like subjective discomfort, feeling of pain, feeling of tingling, numbness in ischaemic part of the body, something like pins and needles under one's skin. And if ischaemia is prolonged or deep, the cells may enter into hypoxic necrobiosis. First, they will enter into reversible necrobiosis. But if the process is prolonged, they may enter into irreversible necrobiosis and get ischaemic necrosis, which you can see in this picture. The etiology of ischaemia is divided into three possible reasons, hematogenous, drawn by emboli, which cause obstructive ischaemia. Second type is endogenous or vascular, ischaemia related to the status of vascular wall, even without thrombi like in vascular spasm, for example, in Raynaud phenomenon in scleroderma morphea. And the third group of reasons, exogeneous reasons for ischaemia or tissue compression, compression of blood vessels by some exogenous force like in strangulation. The main cause of coronary vascular ischaemia and ischaemic heart disease is atherosclerosis of the coronary arteries. And this reason involves both hematogeneous and vascular reasons because atherosclerotic coronary vessel is less inclined to dilatation and more prone to constriction, as well as effect of thrombi we cannot neglect. So, in this scheme, you can see pathogenesis of ischaemia. While ischaemia reduces blood flow, the outflow is still equal to the inflow. That's why there is no edema in pure ischaemia. Arteriole, and to a lesser extent, also venules, become narrower. The number of functioning capillaries is always reduced in ischaemic organ. And the blood pressure drops. It drops greatly in arteriole, and it drops significantly less in venule. So pulse difference in ischaemia is reduced that's why the velocity, the speed of blood, both linear and volumetric, in ischaemia is also greatly reduced. Ischemia can lead to post-ischaemic stasis, complete stop of blood in blood vessels. Tissue fluid production in ischaemia is diminished. Lymph drainage is adequate. Swelling is not observed. Division on the central blood flow and peripheral plasmatic layers of blood flow is absent in ischaemic blood vessels. And the general character of bloodstream is closer to turbulent. You can also observe pendulum-like and jerky pulse flow of blood in ischaemia as it was shown in previous movies. Now The next thing to discuss is consequences of ischaemia and a few examples from clinics. There are different modes of cell death. Hypoxic necrobiosis, free radical necrobiosis, apoptosis and so on and so forth, later we'll dedicate to this matter special lecture. But now, please notice that ischaemia is very important reason of ischaemic hypoxia. The main pathogenetic of ischaemic hypoxia are depicted in this figure. Please notice that hypoxia caused by ischaemia leads first to reversible and later after some critical point to irreversible changes within the cells and tissues finalized by ischaemic necrosis. And another very important thing, every ischemic hypoxia tissue produces inflammatory mediators, because it is just enough to cause irreversible hypoxic injury to the cell, in order to force these cells to produce inflammatory outer course. Dying cell is spreading a kind of SOS signals around it and ischaemic hypoxia is one of the ways to start inflammation around necrobiotic and necrotic tissues. Local tissue necrosis caused by acute disorder of blood circulation is called infarction. Infarction can occur in various organs. It is a zone of necrosis having a conical or pyramidal shape in organs with dichotomic branching of blood vessels like lung, spleen, kidney, or it may be irregular in its shape like in heart, brain. A variety of infarctions is observed in pathology and it is divided into the white infarctions and red ones. White infarctions are always ischaemic in origin, but red infarctions can be either ischaemic or haemorrhagic. And the white ischaemic infarcts occur in the organs with an absolute or relative lack of collaterals, or in solid organs. So you can observe white ischemic infarction of kidney, brain, spleen, myocardial, spinal cord. And in these circumstances there is no secondary filling of blood vessels in necrotic area from neighboring collateral branches with blood. That's why we have wide ischaemic infarction in collateral circulation failure. Another thing is when those red hemorrhagic infarction it occurs in gonads, in brain, in retina, and ischaemic red infarction is observed in those organs which possess with double circulation like liver. And as a rule they have relatively sufficient collaterals like lungs, small intestine and so on, under such conditions after initial ischaemia. Ischaemic vessels get secondary blood filling from collaterals or from doubled circulation like in a portal system. Of course myocardial infarction probably is most well known cause of disease and the cause of death among all infarctions, it is focal portion of ischaemic hypoxic necrosis of a heart muscle, supplied by certain coronary vessel which enter into ischaemia. Myocardial Infarction disturbs partial properties of the whole heart as an organ, because the zone of infarction and neighboring zone of ischemia they have different abnormal electric properties. So contractility, excitability, conductivity and automatism of the whole heart is disturbed in myocardial infarction and it has a reflection on electrocardiogram and it may result in severe acute complications of myocardial infarction like arrhythmia, heart block, acute heart failure, cardiac shock, cardiogenic shock and so on and so forth. Even those who survived an acute stage of myocardial infarction later may suffer from chronic complications like scars, focal cardiosclerosis, and sometimes most often in transmural myocardial infarctions, so-called heart aneurism maybe formed in chronic perspective. Now about the general consequences of chronic organ ischaemia. In organ ischaemia, the rate of cell death is always greater than the rate of cell renewal because organs has not enough resources in ischaemic stage for cell renewal. That's why step by step the number of white blood cells diminishes and chronically ischaemic organ enters into organ atrophy like in these photos, where you can see atrophic bone fragments after the fracture in poor vascularisation. Or, for example, there can be atrophy of cerebrum. Literally, atrophy of cerebrum, because of severe atherosclerosis of cerebral arteries and chronic partial ischaemia of brain. Sometimes vice versa, well dysfunction of organ is a reason for poor blood supply and relative ischaemia. Like for example, jaws may get ischaemic atrophy because of lack of function after teeth loss or for example bone in stump of a hip may get atrophy because of poor function, lack of functional hyperemia and relative ischaemia. Chronic repeated ischaemia in heart and in brain may result not only information of focal sclerosis at the place of infarction, sometimes there is no infarction and there was not infarction in anamnesis, but the number of functional cardiomyocytes year by year diminishes because in chronic partial ischaemia they may get a protopic death without necrosis and without infarction, but still they perish and instead of functional liable cells, person has so-called diffuse cardiosclerosis. Very important, well for health care, is ischaemic lower limb disease. It may occur due to different reasons, one of them is atherosclerosis and thrombosis of aortic bifurcation, and or branching of pelvic arteries, or femoral arteries, it is called Leriche syndrome. Also, the ischaemia of lower limbs is typical for advanced poorly treated sugar diabetes and it is called diabetic foot syndrome. We have also so-called Buerger's disease or occlusive endarteritis mostly of lower limb arteries. This severe disease with immune pathological component occurs preferentially among hearty smokers. Outcome of all these lower limb ischaemia cases is dry gangrene and the critical ischaemia manifest clinically in such patients as an intermittent claudication, insufficiency of muscular strength in lower limbs on prolonged if what and the feet get cold and acquire various skin infections. That's probably the sad and versatile list of the clinical consequences of ischaemia.
