Transcription
Accordingly, another topic we need to discuss is processes that inhibit hemostasis. Because as I mentioned earlier in our body, the mechanisms of hemostasis are balanced on a knife's edge with anti-hemmoatic mechanisms. On the one hand, we need to ensure that blood clots when there is an injury, but at the same time, we do not want coagulation mechanisms to occur when they are not needed. And even when heostasis occurs, anti-coagulation mechanisms play an important role.
First, they prevent formation of an exclusively large clot because a clot that is too large would block blood flow, which would be harmful. And second, anti-coagulation mechanisms help prevent the formation of emblei. Embley are thrombi or fragments of a thrombus that have detached from the vessel wall. These detached clots now called emblei are even more dangerous than a clot that simply blocks blood flow because they can travel to the heart or brain and the outcome can be fatal. Therefore, it is very important that hemostasis occurs only at the site of injury and does not lead to excessive clot formation or fragmentation.
For this reason, the body has several anti-coagulation mechanisms. And we will now look not at all of them but at the most important ones. First, one mechanism we already discussed earlier, prostaglandins and nitric oxide. We concluded that these two substances are released by healthy intact endothelial cells and they inhibit platelets preventing their activation. In addition, they also cause vasoddilation widening of blood vessels. These two substances which is the opposite of the vaso constriction that occurs at the site of injury.
Another substance released by healthy endothelial cells around the wound is a factor that actually has several names. The most common probably is tissue pathway factor inhibitor. Sometimes called also tissue tromboplastin inhibitor. In some sources, it is also referred to as an intrinsic pathway inhibitor. Damaged endothelial cells do not release it, but healthy ones secrete it continuously. The role of this substance is to inhibit factor 7. In other words, it prevents factor 7 from activating factor 10, thereby inhibiting the pathway. This is why it sometimes is referred to as intrinsic pathway inhibitor.
Another anti-coagulation mechanism is trombomodulin. This time this is not a substance released by the endothelium but rather a receptor. As we have previously established from plays a major role in secondary hemostasis activating many processes. Therefore it is logical that there are also mechanisms to limit this activity. Trombomodulin is a receptor located on the surface of intact so undamaged endothelium. Frombin can bind to it and when it does thrombin changes its properties. Hence the name modulin meaning to modify or transform. So when trombin binds to trombomodulin these changes happen and trombin binds to additional plasma proteins called protein C and protein S which are produced of course in the liver like other plasma proteins. This binding has an important effect. Excess thromben that is not needed at the injury site becomes occupied by binding thrombomodulin reducing its availability for further coagulation processes. In this way the intact endothelium with its trombomodulin receptors ensures that heatic processes remain localized at the site of the injury. At the same time it helps remove excess thrombin that is not needed.
When thrombin has bound protein C and protein S, further anticulant effects take place. So the binding forms a kind of complex and this complex then inactivates two factors. First it inactivates factor 5. As a result, factor 5 can no longer bind with factor 10 to form the complex and thus the common pathway is inhibited. And secondly, this complex inactivates factor 8 which can no longer bind with factor 9 in the intrinsic pathway. As a result, that pathway is also inhibited. However, at the site of the wound, these processes will still continue. So, it's very tightly regulated.
And finally, the last substance I will present here is anti-throbin free. Sometimes also simply called antitroen. This is also a plasma protein produced of course by the liver. What does this plasma protein do? First it can bind to trombin thereby removing part of the excess tromben same as trombomodulin. It can also bind to factor 10. Factor 10 is also crucial for converting protrin into tromben in the common pathway. So this is where the common pathway begins. Therefore, inhibiting factor 10 significantly reduces the likelihood that hemostasis will occur at all. In addition, although its effect is weaker than that on trombin and factor 10, antitroen 3 also inhibits factors 7, 9, 11, and 12. The good news is that I will not ask you about inhibition of these factors in the final test. Although that does not mean that I could not ask them in a class in the final test. However, questions may involve the binding to thromben and factor 10.
Another very important point we should look at here concerns the medication heperin. The mechanism of heperin is that it binds to antitroen free and increases its activity by a thousandfold. This means that when heperin is used, the balance between coagulation and anti-coagulation shifts very very strongly towards anti-coagulation. In practice, coagulation can barely occur at all because the activity of anti-throen becomes overwhelmingly strong.
Now and this is everything about anticoulation mechanisms.