Transcription
Finally, we have arrived at platelet damage and dysfunction during cardiopulmonary bypass. You see that we were able to discuss aritroytes and lucasytes right away. But for platelets, we needed to go through several other topics first so that you could better understand this relatively short part of the lecture.
So, one thing that happens during cardiopulmonary bypass is mechanical damage to platelets and what could be described as receptor shedding or receptor damage. We already discussed sheer stress when talking about aritroytes, which occurs during cardiopulmonary bypass. The same applies here; when platelets are deformed, some of them are damaged. For ariththraittytes, we call this hemolysis. But for platelets, we say they undergo micro fragmentation, meaning that these already small platelets break into even smaller fragments. This micro fragmentation is further promoted by hypothermia and fluctuations in pH because these factors make the platelet membrane more fragile and more sensitive to sheer stress. Additionally, due to artificial surfaces, some platelets have the external part of their receptors effectively cut off, so to say. This means that the receptors lose their function, and this process is sadly irreversible. These include glyoprotein 1B receptors, as well as glyoprotein 2B 3A receptors, which we already discussed. You might recall that GP2B3A receptors are present only on activated platelets. But in cardiopulmonary bypass, some platelets do indeed become activated. So, I will also remind you that what happens if both of these receptors are lost and what consequences there are.
The glyoprotein 1B receptor is the one through which platelets bind to fonvillibbrand factor on exposed collagen. This means that later heostatic processes will be impaired because platelets will not be able to adhere to collagen via fonvran factor. The second reason why heasis is disrupted is due to the damage of the GP2B3A receptor. This receptor is responsible for linking platelets together via fibbrronogen. Therefore, fibbrronogen bridges between platelets will not form.
Of course, not all platelets will lose their receptors. In fact, on the contrary, some platelets will become activated and will express these receptors. Platelet activation occurs because on the surfaces of cardiopulmonary bypass systems, within a few seconds after initiation, substances such as plasma proteins, you see here, meaning albamin, fibbrinogen, imunoglobulins, and fragments of villibbran factor. All these substances deposit. When a platelet comes into contact with this protein coating, it interprets it as a site of injury and becomes activated. In this way, platelets respond chemically as if they were interacting with damaged tissue. Additionally, compliment component C5A is a strong activator of platelets. Earlier, we discussed how this compliment factor activates luccoytes, such as neutrfils, but it also affects platelets. Furthermore, cytoines such as tumor necrosis factor alpha, interlucin 6, and interlucan 8 also activate platelets and their metabolic activity.
Activated platelets will release the substances that activated platelets normally release, and that is: adinazine, defosphate, serotonin, tromoxane A2, and calcium. So, all these substances we have already talked about. Additionally, these same substances can enter the plasma because platelets are being damaged, as these substances are stored in the platelet granules. Among other substances not mentioned earlier, fonvillibbran factor is also released here. Platelets that are not microfed but simply activated essentially release their ammunition prematurely, and later, as a result, when they are actually needed to activate and function properly in hemostasis, they are no longer able to do so effectively.
Additionally, it should be noted that microtrumbi can form in the microirculation. So, micro clots in capillaries. These are usually formed by neutrfil extracellular traps. As we recall, that neutrfils become activated through interaction with platelets and fibbrin. All of this together can lead to the formation of these microclots in the lungs, kidneys, and other capillary networks.
It should be also added that endothelial damage occurs, and this has already been mentioned earlier, but in reality, endothelial damage can arise from many different causes. One factor you can already understand is turbulent flow. This is a type of flow that is not smooth, where layers of blood mix, and in particular, it's the mechanical force from cardiopulmonary bypass that creates this type of flow, making the endothelium more vulnerable. Additionally, complements C3A and C5A further activate the endothelium and increase its permeability. Neutrfil adhesion to the endthelium, we discussed already, also contribute to the damage. And furthermore, citine storm and systemic inflammatory response syndrome, if they are present, increase endothelial permeability even more. And lastly, there are also many other contributing factors, including various biochemical reactions occurring during cardiopulmonary bypass, which can activate additional substances and further make the endothelium more permeable and fragile.
To summarize simply, mechanical stress damages platelets and their receptors. Some platelets are destroyed, and the contents of fragmented and activated platelet granules enter the plasma. And as a result, after surgery, platelets have impaired adhesion and aggregation. Even if the platelet count appears normal, mechanical stress damages the platelets, removes their receptors, and depletes their granules. Therefore, heasis after the procedure is not very effective because the key mechanisms of adhesion and aggregation are compromised.
The most clinical consequences are diffused bleeding and petiki. Petiki are small red spots, about 1 to 2 mm in size, which can appear on any part of the body. They are caused by intrammal capillary bleeding, meaning that small skin capillaries have ruptured. This occurs because the endothelium becomes weakened, making capillaries more fragile and more prone to rupture. Normally, primary hemoasis would repair these capillaries. But in this situation, heasis is weak and prolonged. As a result, bleeding persists for a longer time. Importantly, the platelet count may still be normal, although it can also be reduced, but the platelets do not function properly. The good news is, though, that this condition is usually reversible, and platelet function recovers over time.
Finally, how to reduce platelet damage. There's nothing fundamentally new here. The main mechanisms are essentially the same as those discussed for aritroytes and lucasytes. This includes the use of more biompatible surfaces, correction of the temperature and pH, and administration of heperin. Earlier, when discussing lucasite activation, it was already mentioned that heperin helps preserve the endothelial health. Now, after understanding anti-coagulation mechanisms, it becomes clear how important heperin is in preventing activated platelets from forming clots and causing serious post-operative complications. Stable blood flow is also important. Hypothermia control is essentially part of temperature correction. In certain cases, after cardiopulmonary bypass, additional treatment may be required. If necessary, then fibbrronogen and platelet transfusions are given. Usually, treatment starts with fibbrronogen because if fibrogen levels are low, platelets cannot form a stable clot. After fibbrronogen replacement, platelet transfusion becomes more effective. Fibbrronogen is typically administered either shortly before discontinuing cardiopulmonary bypass, if urgently needed, or more commonly after the procedure. And with this, we have essentially completed the discussion of blood elements and their behavior. Next, we will move on to circulation and the overall function of blood.