Transcription
It's the tenth video in my series on bleeding and coagulation disorders. In the previous video, we had an introduction about hemostasis. Today, we'll talk about primary hemostasis—how the platelets can form a plug. This is Medicosis Perfection; elsewhere, medicine makes perfect sense. And let's get started. [Music]
And these are my previous videos. Come on, they are awesome; that's why you subscribe and save this playlist. Hemostasis is prevention of blood loss and has many steps: basic instruction, temporary platelet plug (primary hemostasis), coagulation (also known as secondary hemostasis), fibrinolysis to destroy the clot and restore the function, and then regeneration of the injured, traumatized, hurt tissue.
Primary hemostasis is a balance on the dynamic, harmonious antagonism between the smooth endothelium (which wants the blood to flow) and the thrombocytes (which favor clotting and coagulation). Again, vasoconstriction is the first step, and we have talked about this in the previous video. Today, we'll talk about the temporary platelet plug, also known as primary hemostasis. The hero here is the thrombocytes—your foolish ones; that's why you injure yourself. Into vasoconstriction, then temporary platelet plug (primary hemostasis), depending on the type of the trauma. If it's very small, the platelet plug is sufficient—more than enough. Thank you so much. If it's a larger trauma, we need the secondary hemostasis to kick in—the coagulation cascade to convert fibrinogen into fibrin to form a meshwork to trap the red blood cell and form a nice, rounded, tough, tough plug that can stop bleeding. After this, the clot contracts, producing serum (which is the plasma minus the clot), then fibrinolysis to restore the blood flow and start regeneration.
We talked about vasoconstriction in the previous video, but in brief, here's the small, normal blood vessel traumatized. The surrounding tissue exerts back pressure because the endothelium is falling, causing back pressure here, decreasing the blood flow going forward. The muscles around and in the surrounding tissue will start to contract; this will force the blood vessel to constrict. These muscles help the tissue contract and decrease the bleeding, especially in the uterus—piece of construction, which is the local myogenic spasm, and it's not dependent on nerves or hormones. Then the local autocoid factor suggests, unboxing a to the nervous reflexes secondary to pain. So vasoconstriction, local myogenic spasm, autocoid factors, nervous reflexes. The margin expansion is independent of nervous or hormone stimulation; it's stretch-induced depolarization, calcium release, and calcium is the hero of contraction. Also, calcium is the hero of coagulation—very nice. Pro-constriction substances: serotonin and thromboxane A2 (thanks to the platelet), epinephrine (thanks to the adrenal gland because it's a sympathetic response—fight-or-flight; you injure yourself). If the sympathetic is not going to work now, when is it ever going to work? Five-dollar peptide—beef, which is produced by the fibrinogen. General rules: the greater the trauma, the stronger the vasoconstriction; the spasm can last for hours.
The quiz time of last lecture was: which trauma is worse—cutting your vessel transversely or longitudinally? And the answer is: longitudinally is way worse. Why? Let's say that you cut the vessel like this, so you cut it in this plane, okay? Yeah, you cut it into two halves, but the muscles are concentric; they can still contract and constrict the vessel. On the other hand, if you cut it longitudinally, you cut through all of the layers of muscles; even if they try to contract, they will never constrict the blood vessel. So these can constrict; these cannot constrict. That's why the longitudinal trauma is worse than the transverse one. So when life hits you hard, here is a more efficient way to cut your wrist and put an end to your life. I'm just kidding; don't ever do this, and please, for heaven's sake, don't tell this to patients. This piece of information should stay between you and me. If you couldn't imagine this because you can't imagine three-dimensional stuff, it means that you have a lesion in your temporal lobe; you should get your brain scanned.
We have talked about the platelets' structure before, but in brief, it's biconvex; they are pieces of the megakaryocyte. They have the plasma membrane and the cytoplasm; they got the membrane from the megakaryocyte and the cytoplasm from the megakaryocyte. The plasma membrane is a lipid bilayer, but it's covered by a glycoprotein coat containing the receptors, such as GP1b and GPIIb/IIIa. GP1b will help in the platelet adhesion; GPIIb/IIIa will help in platelet aggregation. Calcium can occur system because they will contract and release, just similar to ejaculation. I'm sorry. Cytoplasm, actin, myosin to contract and release; from Boston, from thrombus, thenin, which means to make them stronger. Residual of Golgi and rough endoplasmic reticulum because they need to synthesize the cyclooxygenase to make the thromboxane A2. My, my talk on you for ATP and ADP. ADP is a hero, and it will help in platelet aggregation. Fibrin-stabilizing factor to stabilize the fibrin after the clot formation. Platelet-derived growth factor will help and repair—like a nice cat; it cleans after itself. And will have the granules; the granules are two types: alpha or dense. The alpha—they are all for their proteins: factor 13, platelet-activating factor, platelet-derived growth factor, von Willebrand, fibrinogen, platelet factor 4, and platelet factor 3 (which is a procoagulant). Dense granules—they are non-protein; they include ADP, calcium, and serotonin. The arachidonic acid comes from the membrane phospholipid liberated by the phospholipase A2 enzyme. The arachidonic acid has two choices: to be converted into prostaglandins by the cyclooxygenase enzyme or the leukotrienes by the lipo-oxidase enzyme. The prostaglandins are either thromboxane A2 in the platelets or prostaglandin I2, also known as prostacyclin, in the endothelium.
For talking about the platelets, we have thromboxane A2. Thromboxane causes thrombosis by vasoconstriction and promoting platelet aggregation. On the other hand, prostacyclin will keep the blood cycling. Just before I lose you, we are talking about the temporary platelet plug. Now let's get started. The platelet is like the policeman who works in a very safe neighborhood in the suburbs; everything is safe and secure, and he is so bored out of his mind; he's desperate for some action. He keeps checking the security gate; it's safe and secure; everything is fine. He cannot see the area underneath because this is opaque, but one day he saw the gates open, and the layer underneath—also a nether subendothelial collagen—was exposed. He became activated; he went crazy, and baby, it's on, and the rest is history. He's gonna call his friends, and it's gonna be a huge issue. Instead of the policeman, imagine the platelet; instead of the gate, imagine the normal smooth endothelium; the layer beneath the gate is the subendothelial collagen. When it's exposed, it means the endothelium is injured; it means we are in trouble, and we need to make a clot, baby.
Another example is an engineer who inspects the building after an earthquake, looking for leaks—such as gas leaks or water leaks, cracked walls, and leaning walls. If the walls are intact on the inside, then the outside is most likely intact, but if the walls are cracked from the inside, it could mean that the earthquake damaged the building from the inside; because when you damage the building from the inside, it has to damage the walls and make them crack, revealing the subendothelial collagen, also known as the area beneath the wall paint. This is how the platelets inspect the endothelium day in and day out. Instead of an engineer, imagine a platelet; instead of a wall, imagine endothelium; instead of the paint or whatever is the break behind the wall, imagine a subendothelial collagen.
So primary hemostasis: we start with the normal, intact endothelium; the endothelium is here; the platelets are rolling, and they are just fine; everything is happy; the gate is safe and secure, and the subendothelial collagen is not exposed because the endothelium is intact; there is no trauma. But then there is a trauma; the endothelium is damaged; the subendothelial collagen is exposed; the platelets get crazy; they start to swell and form pseudopods. The pseudopods will help them attach to this subendothelial collagen. After they swell and they form a pseudopod, they adhere to the subendothelial collagen, specifically to the von Willebrand factor coming from the endothelium and the platelets. The platelet has a receptor, which is part of its glycoprotein coat, called the GP1b (part of the glycoprotein; GPS stands for glycoprotein). 1b hashtag sec exposed. Some authors will say platelet adhesion occurs first before the swelling and the pseudopod formation; other authors will say no; they will activate first, and they will adhere. I couldn't care less; they happen probably at the same time. After adhering to the subendothelial collagen, thanks to the von Willebrand factor on one side and the GP1b on the other side, they activate more swelling, and then they will contract thanks to the calcium canaliculus system, and then they will release their granules, such as the ADP—the whistleblower—to other platelets to aggregate and come, and baby, it's on. Hashtag one platelet is not enough.
Other than being a whistleblower, the ADP has another function: it's to express this GPIIb/IIIa receptor on the surface of the platelet. We call this—it's an amazing sentence—an ADP-dependent expression of GPIIb/IIIa receptor. If you want to be more sophisticated, it's not an expression; it's a conformational change because this receptor is already expressed, but it's not active; ADP will activate it. Half, if you wanna be super sophisticated, pay attention. ATP will stimulate two receptors: P2Y1 and P2Y12 or P2Y1/2. After stimulating both of these receptors, will convert the GPIIb/IIIa in the inactive form into the active GPIIb/IIIa. This is called a conformational change; it will help aggregate other platelets because when the other platelet has come, they will attach to the other platelet by the same receptor, GPIIb/IIIa, because every platelet deserves a receptor, and baby, it's on. The ADP is a whistleblower; that's why I drew a whistle and wrote ADP in it. The thromboxane A2 is a more potent whistleblower; that's why it's a whistle plus Y plus because it will promote platelet aggregation, but this is not new; ADP also promotes platelet aggregation. But wait; it's also a vasoconstrictor par excellence; it's also a bronchoconstrictor, so it has several functions; that's why it's a whistle plus. Platelets will contract and release thromboxane A2 and ADP thanks to the calcium canaliculus system because calcium contraction, calcium coagulation. After releasing two major whistleblowers, they will aggregate other platelets—come on, come play; they will come; each platelet deserves a receptor; ADP will stimulate the receptor of the platelet and the other platelet; they have GPIIb, and then a fibrin molecule will be in between, and this is how they will attach together. This is called platelet aggregation. The next step is to convert this fibrinogen here into a very strong fibrin meshwork between the two platelets, making them adhere together even stronger. This fibrin meshwork will start to trap the red blood cells in the meshwork, forming a bigger plug to stop bleeding. This is just astonishing.
Platelets dead aggregate thanks to those two major whistleblowers: ADP and thromboxane A2. Then procoagulant activity: the platelets possess platelet factor 3, as I've told you like four minutes ago. This platelet factor 3 will help start a cascade to convert the fibrinogen into fibrin fibers, trapping the red blood cells, forming a strong meshwork—a stronger plug. And now this fibrinogen will be fibrin, and these platelets will adhere together even stronger. After this procoagulant activity, platelet fusion will occur, and why not? If the fibrinogen is being converted into strong fibrin, of course they fuse. Hashtag fibrin fusion. At the same time, platelets do their thing; coagulation cascade is going on until we end up with strong fibrin fibrils. Then the coagulation cascade is done; fibrin meshwork is being made, trapping the red blood cell—strong, permanent thrombus because the platelet plug alone, without the coagulation factor, was a weak and temporary plug, but the coagulation fibrin meshwork is strong and permanent. By permanent, I mean it's—yeah, it's gonna be destroyed by fibrinolysis at the end, but if you compare it to that weak platelet plug, it's relatively permanent.
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