What do I mean by damage control? I mean that our blood responds to injury (and infection) in a manner to stop the damage and prevent any worsening or further infection. So, if you get cut, you bleed-- but that cannot go on and on, right? Your blood must clot. The process by which blood clots at the right time, but doesn't clot when it doesn't need to is called hemostasis. Another example is when you get an infection, your blood has to somehow get rerouted to send white blood cells to the scene, or the infection (bacteria, etc.) might spread even worse. So let's look into these two main ideas: inflammation and hemostasis.
With injury or infection, an inflammatory reaction occurs. We end up with an inflammation, which produces a region that appears swollen.
What is going on here? If we already have an injury, why does it swell more? Isn't that counterproductive? What's the point?
In order to get rid of an infection and/or the cellular debris from an injury, you know what you need? You need macrophages, neutrophils, and you even need lymphocytes (to fight the infection with an immune response). Even eosinophils can destroy some bacteria on occasion. These are all white blood cells. So, if you need white blood cells in the area of injury, how do you get them?
When tissue damage occurs, the damaged cells are like chemical beacons. You see, they release their cell contents, which are chemicals, and these chemicals are stimulants for other cells. There are cells in the connective tissue, mast cells, (remember those from Unit 3) that release histamine when they recognize the chemicals of damaged cells. This gets the inflammatory reaction going.
Histamine causes the nearby blood vessels dilate to bring more blood around to the damaged area. But not much histamine is released by the mast cells. As more blood starts to come through the area, that means that more white blood cells will reach the damaged tissue. The basophils that enter the area also begin to release histamine, and this brings the inflammatory response into full gear. Now the blood really gets flowing into the damaged area, and many, many white blood cells enter the damaged tissue to begin taking care of business. Macrophages, neutrophils, eosinophils, and lymphocytes can all get to work. Even plasma gets to work-- you will learn about clotting below... clotting tends to happen around the area of inflammation (but not in it), preventing further spread of any infectious agents.
You should now be able to figure out why an inflammation is a swelling that is also red. Have you figured it out? All that blood has entered the area, so it has swollen with blood... the blood is red, so it causes the area to look red.
Now, let's go on to hemostasis!
When you are cut, your blood vessels are cut, and you bleed. Yuck. But it happens. You also know that you don't bleed to death, but instead, the blood stops flowing when you get a clot. Actually, a lot more than just a clot occurs. Here are the steps to stopping blood loss after injury:
The list above describes (in general terms) the major topics within hemostasis. Here's a little bit more on these, and then we need to discuss the chemical steps of blood coagulation in more detail.
Blood Vessel Spasm
This doesn't really need much more explanation... basically, if you cut through a muscle, what's left of it contracts. And smooth muscles are in the wall of the blood vessel (you'll see more about this soon). So, the smooth muscles contract right away. This is immediate, occurring at the moment of the injury.
It won't last forever, this vasospasm, but it lasts long enough for the next thing, the platelet plug to get underway. And, since platelets secrete serotonin, and serotonin forces muscle to contract, when the platelet plug forms, the vasoconstriction caused by the vasospasm continues for a much longer period.
You learned about normal, healthy platelets running through blood on the platelet page. What I didn't tell you is that the entire platelet changes when there's an injury. You see, normally, the platelets are travelling in the blood, and they just zoom along. But, when there's been an injury, the platelets spill out of the blood vessels with the rest of the blood. This spill puts the platelets in contact with an environment that they do not normally see-- the environment outside of the blood vessel. Now things change.
When platelets spill out of blood vessels, they come in contact with all sorts of connective tissues. Connective tissue is not a smooth, slick tissue, like the inner lining of a blood vessel normally is. Instead, connective tissue has all sorts of fibers in it. The platelets come zooming out of the blood vessel and run head on into collagenous fibers. Suddenly, they change! They go from being smooth little cellular pieces, to being sticky, pointy, rough chunks of cells. The change in appearance is schematized in the drawing to the right.
Meanwhile, a change in their appearance is not their only change. As they change the way they look, they change to start actively secreting serotonin. They also get very sticky, and start clumping up together. As more and more stick together, they form a huge, sticky clump which is the platelet plug.
Clotting is what makes the blood loss stop for a long period of time. Clotting occurs through some sets of chemical reactions. But the final action that leads to a clot is based in a chemical change of fibrinogen, one of the blood plasma proteins you learned about.
Fibrinogen is one of the plasma proteins, and it is dissolved in the plasma. That means that it doesn't stand out from the plasma, it acts like a part of the plasma solution. Like when sugar is dissolved in water, you don't necessarily see it in the water, but it is a part of the solution (as you can tell if you taste it). But, when blood needs to clot, a chemical reaction of the fibrinogen occurs. Fibrinogen gets changed in this chemical reaction into fibrin. Fibrin, unlike fibrinogen, is not soluble in the plasma. That means that fibrin stands out in the plasma like string would stand out in water... So, when fibrinogen is converted to fibrin, the fibrin comes out of solution and is a material we can build with.
Fibrin is a thread-like protein. When enough of it forms, it ends up sticking together in a mesh-like lattice. This mesh is tight enough to prevent other materials from flowing through it-- especially when platelets get caught up in it and plug up any holes. The fibrin threads plus the platelets stuck in it forms into a clot.
This diagram is one I made using RasMol. You can see that fibrinogen is all balled up, and then it flips open into a strand when it becomes fibrin. Both molecules are pretty big (4 polypeptides each). The colors just represent their secondary protein structure (pink for alpha helices and yellow for beta pleated sheets). You don't need to know this detail, but I thought it might be helpful to see the molecules toward understanding how a simple enzymatic step could change a globular soluble protein into a fibrous insoluble protein.
How does blood coagulation get started?
Your book talks about extrinsic and intrinsic clotting mechanisms. Both mechanisms occur simultaneously to get coagulation started. It is just that different factors cause the different mechanisms. So, after an injury, the damaged tissue itself signals for coagulation to start and the blood cells themselves that are reacting to damaged tissues simultaneously begin their own process for coagulation. In a little bit more detail:
The term "extrinsic" above refers to anything outside of the blood itself, and the term "intrinsic" above refers to within the blood.
I do not want you to try to memorize all of the chemical steps in coagulation. I do, however, want you to understand that either clotting mechanism (extrinsic or intrinsic) leads to the activation of prothrombin. Once prothrombin is activated, it is then called thrombin. Thrombin is the enzyme that changes fibrinogen into fibrin. After that, there is just one more factor, "factor XIII," that helps to stabilize the fibrin meshwork into a clot. If you look at figure 14.19 in your book, then, you only need to understand the steps after the two mechanisms merge together to activate prothrombin. Got it? Good!
Clot Retraction and Repair
© 2011 STCC Foundation Press