Transcription
Let's resume our discussion on bleeding and coagulation. In the previous video, we have talked about the pro-clotting and the anti-clotting mechanisms. Today, let's talk about prostacyclin versus the great thromboxane A2. Let's get started. [Music]
Prostacyclin is also an as prostaglandin I2. Thromboxane A2 is also known as TXA - okay. Prostacyclin is secreted by the great smooth endothelium. Thromboxane A2 is secreted by the glorious thrombocytes, from work from their membrane, specifically the membrane phospholipid, the lipid bilayer. Same thing here. Prostacyclin is made from the cell membrane of the smooth endothelium. That's why we have the arachidonic acid coming from the phospholipid membrane through the great enzyme phospholipase A2. Who makes the prostacyclin? The great enzyme prostacyclin synthase. Synthesis of prostacyclin, it can't be either easier than that. Who makes thromboxane? Thromboxane synthase. Wow.
Functions: Prostacyclin: vasodilation and decreased platelet aggregation. Thromboxane A2: vasoconstriction and increased platelet aggregation. In short, prostacyclin is anticoagulation. Thromboxane A2 is very much pro-coagulation. If you are a mnemonic maniac, you can make this: decreased and decreased, and here we have increased and increased. So, decreased what? Decrease the vessel tone and decrease the platelet aggregation. Then here you have increased the vessel tone and increase platelet aggregation.
To make it easier, what's the effect of aspirin on prostacyclin? We have two theories. Some people say no effect or level effect. Others will say it inhibits prostacyclin formation, followed by stimulation or followed by release of inhibition. Here, aspirin irreversibly inhibits formation of thromboxane A2 by inhibiting the enzyme cyclooxygenase. That's why, my friends, aspirin is anti-platelet. Aspirin makes you bleed.
For those who are very sophisticated among you, how does thromboxane A2 actually cause vasoconstriction? Okay, lesson: it's a G-protein coupled receptor, specifically Gi. I for inhibition. Okay, there are two things happening at the same time: GDP being converted into GTP and this great receptor approves this message, and then there's another pathway: ATP to cyclic AMP by the great enzyme adenylate cyclase. And the Gi is so angry at and will inhibit this cyclic AMP formation. What's the function of cyclic AMP in the first place? It decreases calcium and causes relaxation. Oh yeah, no kidding. If you decrease calcium, you will cause relaxation, because calcium is the heart of contraction. So, when you have less cyclic AMP, you have more calcium. Calcium contraction, calcium coagulation. That's how thromboxane A2 causes vasoconstriction and increased or enhanced platelet aggregation.
Okay, the sympathetic stimulation, the alpha-1 stimulation. How does the alpha-1 constrict your blood vessel? Oh, do my blood vessels constrict when I'm in the fight-flight mechanism? Yes. I'll give you an example. Let's say you are running for your life from your enemies, and suddenly while running for your life you hit a sharp object and injured your teeny little finger. At the time of running, you do not bleed. Take it to the bank. And then after running for ten minutes, thank God my life is saved, I'm rescued, I'm safe now, and then you really realize, oh my small little finger is bleeding. How come I didn't notice? You didn't notice because it didn't bleed under the sympathetic response. It vasoconstricted the vessel to the point of occlusion, because who cares about the superficial blood vessels in your skin? We would like to protect the viscera and the internal organs first, to protect your life, you idiot. So how does the sympathetic system cause vasoconstriction? How does it cause it? By the alpha-1 stimulation, which is Gq coupled. Gq coupled receptor will stimulate IP3. IP3 increased calcium. Calcium contraction, calcium coagulation. Coagulation is really good and really superb under sympathetic stimulation.
Quick review of the arachidonic acid pathway by the cyclooxygenase: you have prostaglandins. Depending on the tissue, if you are in the platelet, you can have thromboxane A2, which will cause thrombosis by vasoconstriction and increased platelet aggregation. Or if you are in the endothelium, let's form prostacyclin to keep the blood cycling by vasodilation and preventing platelet aggregation. And now for the first time you know how thromboxane A2 causes vasoconstriction, and this is by decreasing cyclic GMP and leaving the calcium free. Calcium contraction, calcium coagulation. That's it for today, and I'll see you in the next video. Don't forget to subscribe and go to Patreon if you'd like to get all of my notes. Thank you for watching. Until next time, be safe, stay happy, and study hard. This is medical is perfection elsewhere. Medicine makes perfect sense.