HEMOSTASIS/COAGULATION CASCADE - Intrinsic/Extrinsic/Common Pathways, Amplification, and Propagation
Vložit
- čas přidán 7. 06. 2019
- / neuralacademy
Hemostasis is the process which causes bleeding to stop. Primary hemostasis involves the formation of a platelet plug. Secondary hemostasis involves the assembly of activated coagulation factors involved in the coagulation cascade, which converts soluble fibrinogen into insoluble fibrin strands that stabilize the aggregated platelets and define the strength of the clot. The coagulation cascade involves clotting factors, which are designated by Roman numerals (1-13).
The coagulation cascade has three pathways - intrinsic, extrinsic, and common. The intrinsic pathway comes into play when blood comes into contact with exposed collagen from damaged endothelial walls. Collagen is the main structural protein in the extracellular space in connective tissues. The extrinsic pathway begins when vascular tissue trauma causes blood to escape from the vascular system. It is initiated by factors external to the blood.
The intrinsic & extrinsic pathways each work towards the production of a tenase, an activating complex, which activates Factor 10. Factor 10 is part of prothrombinase, which cleaves prothrombin to form thrombin. Thrombin is an enzyme that causes the formation of a fibrin clot.
Blood vessel walls are lined by endothelial cells with antithrombic properties. However, the subendothelial layer, contains collagen, von Willebrand Factor (or VWF), and proteins involved in platelet adhesion, making it highly thrombogenic.
Platelets do not adhere to intact vascular endothelium, but stick to an injured site, recruiting and activating fellow platelets, aggregating, and aiding the coagulation cascade.
Von Willebrand Factor, or VWF - When there is an injury, it binds to both collagen and to platelets, anchoring platelets to the subendothelium.
Platelet activation begins and 4 things happen:
1. Platelets undergo a morphological change
2. The platelet’s outer phospholipid membrane becomes negatively charged - which is important for the coagulation cascade to proceed. This happens thanks to scramblase, which moves negatively-charged phospholipids from the inner to the outer membrane surface
3. Platelets secrete granules
4. Platelets cause a conformational change in their GPIIB/IIIa receptor, increasing its affinity for fibrinogen. This results in aggregation
Rapid formation of a platelet plug temporarily seals off vascular injury, but this plug is not very strong. So the coagulation cascade is needed - to reinforce the blood clot with insoluble fibrin strands. The extrinsic pathway is kicked off by Tissue Factor and is the primary initiator of thrombin production.
For the tenase to form, the next critical step is activation of Factor 7. Proconvertin is activated by polyphosphates secreted by activated platelets. Tissue Factor then acts as a receptor for Factor 7a. With calcium as the activating ion, the tenase can cleave Factor 10 to convert it into the active Factor 10a.
Now, let’s look at the Intrinsic Pathway. The intrinsic tenase includes the enzyme Factor 9, or Christmas Factor, its cofactor Factor 8, or Anti-Hemophilic Factor, the substrate Factor 10, and calcium ions. It takes a few steps to produce Factor 9.
First, Factor 12, or Hageman Factor, is activated. Factor 12a cleaves Factor 11, or Plasma Thromboplastin, to produce Factor 11a. Factor 9, becomes an active enzyme when it is cleaved by either Factor 11a or Factor 7a.
Factor 8 circulates bound to VWF, which acts as its carrier protein. Injury activates Factor 8 and makes it separate from VWF so it can interact with Factor 9. Factor 8a is a cofactor and Factor 9a is an enzyme.
Factor 9a can convert Factor 10 to its active form with the help of its cofactor, Factor 8, in the presence of calcium ions and negatively-charged membrane phospholipids.
The common pathway, which has three goals:
1. Produce the prothrombinase complex, which converts the inactive zymogen prothrombin to the active serine protease thrombin
2. Produce a stable fibrin clot
3. Amplify the coagulation cascade
The prothrombinase complex is assembled on the negatively-charged membrane of platelets in the presence of calcium ions. Factor Xa cleaves prothrombin to form thrombin.
Thrombin cleaves fibrinogen, producing insoluble fibrin monomers that spontaneously polymerize. This polymerized fibrin is held together through noncovalent and electrostatic forces. Thrombin also activates Factor 13, a transamidating enzyme that stabilizes the fibrin by cross-linking strands.
Initially, the extrinsic pathway producing a small amount of thrombin. However, numerous positive feedback loops amplify its production. Amplification involves thrombin cleaving and activating Factor 5, Factor 8, and Factor 11, while Factor 10a activates Factor 2.
Propagation: Accumulated tenase and prothrombinase complexes on platelet surfaces results in a large burst of thrombin production. One molecule of Factor 10a leads to the formation of 1000 molecules of thrombin!
Lol, as a paramedic student that ambulance drawing and calling platelets first responders at 3:20 made me chuckle. Great video btw, very helpful!
You have made a good effort to understand. 🎉
I love you. I have been into med school for three years and not one doctor taught me concepts this way
Wonderfully explained! Please make a video on anticoagulation also
You made my day (well its night time) plz keep on uploading such informative stuff . Well explained with pictorial representation thanks a lot
thank you so much for this video! The coagulation cascade image is brilliant - did you make it yourself?
Thank you so much!! ^_^ And yes, I did make it!
Thank you for uploading this helpful content
I love you so much ,carry on what ever difficult you❤
Awesome video! Thanks a ton
Very impressive! thank you much
بارك الله بيك اعتبرك super استاذ
does the intrinsic and extrinsic pathways occur at the SAME time for them to meet and unite into one common pathway?
Vow just amazing....
Why does factor-x111 ( 13 ) always stabilize? Was that because they are afraid to lose blood? Friday the 13th, though with pretty chicks movie. Counters the fear. He he
Why all healthcare lectures explain it differently. Everybody tells coagulation cascade story differently. Some lectures don’t take the thing that is discussed in other videos. It is confusing. Nobody tells how intrinsic pathway and extrinsic pathway starts. What causes the intrinsic pathway and extrinsic pathway to occur. I know whenever our blood vessels are injured and there is bleeding so in order to stop bleeding our platelets will try to stop bleeding. But is intrinsic pathway initiated by internal injury somehow there is injury in our body, so can it initiate intrinsic pathway? And extrinsic pathway means there is injury from outside such as you cut yourself by knife or by any accident so extrinsic pathway can happen?????
So enzymes are the versatile thing in the body with quick reaction process depends on use, though the double function body substance or signallers are more versatile such as prostaglandins, acetylcholine, autoregulatory etc. Extrinsic and Intrinsic merged to form tenase effect factor x, there's something in number 10, 10 commandments, 10th percentage from the 100% income as tithes in born again Christians, Jews, INC etc. 10 fingers in both hands, tennis with small ball back and forth the net, then soluble and insoluble, hard and flow, software and hardware. Hmmm.
The fibrin stabilizing strands appears similar to atoms structural arrangements like squared structural arrangements same as scaffoldings in construction though atoms have more square structures connections which can be enlarged or shrinked if manipulated by modern science and technology like the movie " honey how I shrink the kids",or creating Giants. Hmmm
U r damm good
Extrinsic and intrinsic are for in vitro right?....in vivo,there’s no factor 12 necessary ( acc to robbins)and the processes arent separated isn’t it?...so no matter the cause,is the invivo process always same?
배운 건 다 알아듣겠는데 처음 배운 건 한국말 동영상 다시 보고 와야 이해될 듯..