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127 Cards in this Set
- Front
- Back
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What is the definition of coagulation?
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A cascade process by which soluble fibrinogen is converted to insoluble fibrin in the end.
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What part of the blood hold the ability to coagulate?
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The plasma, not the hematocrit
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How is blood kept in liquid form in circulation?
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Endothelial cells produce products that prevent platelets from sticking to the endothelial cells. They also provide a physical barrier to the collagen in the BM.
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What antiplatelet factors do healthy endothelial cells produce?
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NO, PGI2, and ADP phosphatases
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How do these antiplatelet factors work? (NO/PGI2/ADP Phosphatase)
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They inhibit the binding sites on the platelets.
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What is the cell structure of a platelet?
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It is a membrane bound cell with no nucleus
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How long is the lifespan of a platelet?
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8-10 days
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How big is a platelet?
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2-3 um
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How big is a RBC?
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8-10um
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How can you remember this?
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You can fit about 2-3 platelets in a RBC?
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What is the daily role of platelets?
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to plug up all the micro punctures in our vascular system.
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WHat is thrombocytopenia?
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Low platelet count
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What is the clinical manifestation for an uninjured person with thrombocytopenia?
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micro hemorrhages and pupura all over the body
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What antiplatelet/coagulation proteins are present on every healthy endothelial cell?
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heparin sulfate, thrombomodulin, and t. PA
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What does heparin sulfate that is secreted by the endothelial cells do?
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binds to and activates Antithrombin III
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What does antithrombin III do?
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It cuts down THROMBIN and also the activated factors 9-12 (intrinsic pathway) which will make thrombin.
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Why is this advantagerous to healthy cells near a site on injury?
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It prevents coagulation from happening in non injured sites.
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What is the naughty molecule that is also expressed on healthy endothelial cells.
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Thrombomodulin
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What does thrombbomodulin do?
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It binds thrombin and prevents it from coagulating., which activates protein C.
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What does protein C do?
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It eats up factors 5a and 8a
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Draw thrombomodulin process.
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What is the substance produced by healthy endothelial cells that deal with plasminogen?
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t. PA (tissue plasminogen activator), which is an enzyme that sits on the endothelial cells.
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What does t. PA do?
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It converts plasminogen in the blood to plasmin.
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What does plasmin do?
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It will take fibrin and break it down into fibrin degradation product.
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Draw the function of tPA in a normal cell.
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Name all the normal defense mechanisms to keep blood liquid in the body by HEALTHY endothelial cells.
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1. Antiplatelet stickiness factors like NO, PGI2, and ADP phosphatase
2. Heparin sulfate 3. Thrombomodulin 4. t.PA |
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What is the goal of your body when the endothelial cells are damaged?
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To stop the bleeding
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What is the order of the three steps to stop bleeding?
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1. vasoconstriction
2. platelet plug 3. coagulation |
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how does the vasoconsriction occur?
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1. reflexive neurogenic constriction
2. reflexive myogenic constriction 3. endothelial cells produce endothelin and stop being able to produce anticoagulation stuff. |
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What does endothelin do and when is it released?
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it is released by damaged endothelial cells and constricts blood vessels.
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What anticoagulation things are lost in injured endothelial cells?
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All of the ones mentioned before are no longer present.
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What do damaged endothelial cell secrete?
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They cry because they are sad and secrete von Willebrand factor.
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What does vWF do?
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It attaches onto the exposed collagen and attracts and binds platelets.
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What is on the membrane of platelets that allow them to stick onto vWF?
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Gp1b (glycoprotein 1b)
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What is platelet adhesion?
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The process by which platelets stick to a surface that has no platelets.
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What happens after platelet adhesion?
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The vWF initiates an intracellular cascade which causes the platelet to start secreting TXA2.
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What are the two functions of TXA2?
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A vasoconstrictor and platelet aggregator.
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What does aspirin do to the platelets?
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It irreverssible acetylates the COX in their membrane so they can't produce TXA2.
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What happens to activated platelets?
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They undergo a release reaction that releases granules.
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What are the two types of granules that are released?
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alpha granules and dense/delta granules
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What do the dense/delta granules look like and how can you use this to remember what they secrete?
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They look like big SACS!
Serotonin ADP Calcium |
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What does serotonin do?
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Produces vasocontriction
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What does ADP do?
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It increases ADP concentration at the area of injury and that ACTIVATES platelets that are passing by, making their receptors active.
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What are some drugs that inhibit ADP activation of platelets?
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Ticlopidine and Plavix
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How can you remember Plavix?
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PLAtelets = PLAvix
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Where are the coagulation factors located?
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they are located in the blood
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What does calcium do?
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It binds to the negatively charged coagulation factors and fixes them onto the platelet membrane surface.
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Where does calcium stick onto the coagualtion factors?
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On carboxyglutamic acid residues. It sticks the coagulation factors together in this way by their COO- which have high calcium affinity.
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What does carboxyglutamic acid look like?
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What makes the post translational modification that leads to gamma carboxylation of glutamic acid?
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vitamin K in the liver!
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Which coagulation factors down vitamin K carboxylate?
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2, 7, 9, and 10. And protein Z.
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What do alpha granules of platelets release? (3)
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1. coagulation factors (especially 5 and 8)
2. fibrinogen 3. platelet derived growth factor |
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Draw the alpha and delta granules with their products.
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What are the two main platelet products that attract more platelets to the scene?
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TXA2 and ADP
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What does it mean for platelets to be activated?
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They secrerte granule products
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What is platelet aggregation?
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When platelets start sticking to one another (not vWF or BM.. that is platelet adherence)
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What is the initial platelet plug produced by adherence/degranulation/and aggregation of paltelets called?
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The primary platelet plug.
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Is the primary platelet plug loose or tight?
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loose
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How do you make it tight?
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Attract a bunch of fibrin fibers to cement it down.
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What is the primary platelet plug with fibrin overlying it called?
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The secondary platelet plug
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Is the coagulation of blood in a clean glass tube by the intrinsic or extrinsic pathway?
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The intrinsic pathway
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Why is it called the intrinsic pathway?
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Because scientists knew the tube was very clean so deducted that it must be due to something intrinsic in the blood that isn't added.
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Why is the extrinsic pathway called what it is?
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it forms when you add "tissue juice" to the blood.
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How was the extrinsic pathway discovered?
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Some sadistic scientist took citrated blood (which removed the intrinsic pathway) and added the "tissue juice" from the brain of a mouse he killed and found coagulation.
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What was in the "tissue juice" that turned on coagulation?
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Thromboplastin. (tissue factor)
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What charge is citrate?
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negatively charge (-ate = COO-)
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Why does citrate prevent coagulation?
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it binds calcium
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What is thromboplastin made from and how is it creatied?
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It is just lipids and lipoproteins from macerated tissued.
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How is intrinsic pathway started?
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When Hageman factor/factor 12 comes into contact with collagen from the BM or damaged endothelial cells or activated platelets.
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Draw the intrinsic cascade of coagulation factors.
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What are the cofactor coagulation factors and what do they always need to work? Why?
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Factors 8 and 5, which work by binding other coagulation factors to the cell membrane by their carboxyglutamates so they need phospholipids from the cell membrane and calcium
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What is the order of factors activated in the intrinsic pathway?
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12 (hageman) --> 11 --> 9 (presence of PL, Ca, and 8) --> 10 --> Thrombin --> 13 (TSF) and fibrin
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Which coagulation factors are involved in intrinsic pathway?
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Factors 8-13
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How does the extrinsic pathway work?
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Tissue factor (thromboplastin) activates factor 7, which goes to activate the common pathway 10 and also the intrinsic pathway at factor 9.
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What is the trigger for the intrinsic vs extrinsic pathway?
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Intrinsic- factor 12 comes into contact with collagen
Extrinsic- tissue factor (thromboplastin) comes into contact with factor 7 |
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What gets stuck in the platelet plug besides fibrin and platelets?
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RBC's and WBC's
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What is the whole secondary plug with the platelets, RBC's, WBC's, and fibrin called?
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A Thrombus!
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Why don't you get lower body edema with vasoconstriction?
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Because edema is due to blood being too volumous for even the veins to handle. The arteries add little to capacitance.
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What two cytokines are constantly being balanced in the body for coagulation/anticoagulation signals? (hint: COX)
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Procoaglation- TXA2
Anticoagulation- PGI2 |
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What does COX-1 inhibit?
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production of both thromboxanes and prostaglandins
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What does COX-2 inhibit?
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it inhibits more prostaglandins than thromboxanes
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What are the benefits of selective COX-2 inhibitors?
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You don't get the bad side effects of typicals NSAIDs because COX-2 is only in inflammed tissue.
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What are the downsides to COX-2 inhibitors?
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You have an unbalance of TXA2 vs PGI2, which predisposes you to blood clots.
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What binds factor 9 and 10 together besides calcium?
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Factor 8 links them together.
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What factor is prothrombin/thrombin?
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Factor 2
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What is heparan sulfate?
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A glycosamino glycan attached to collagen responsible for the negative charge on basement membranes.
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What is heparin sulfate?
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A membrane bound protein on epithelial cells that binds antithrombin III, which cleave thrombin, factor 9a, and factor 10a.
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What does PDGF do?
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a growth factor for cells and angiogenesis.
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What does it mean to have a coagulation?
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Just to have fibrinogen converted to fibrin.
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What does it mean to have a thrombus>
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To have the platelet plug and the fibrin within the circulatory system
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What does it mean to have a clot?
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To have the platelet plug and the fibrin that can be either inside or outside the circulatory system.
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What are the fates of a clot/occluded vessel? (4)
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1. Break off and become an embolus
2. Dissolve 3. Undergo organization 4. Recanalization |
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How does the clots dissolve?
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when plasmin created by healthy endothelial cells with t.PA cuts the fibrin down.
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How do clots get organized?
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When fibroblasts are mobilized and lay new collagen over the thrombus
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What do the surrounding endothelial cells do when a thrombus has completely occluded the vessel?
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They proliferate and grow over the thrombus under the influence of platelet derived growth factor, grow in to meet each other, and dissolve the center in order to make a new canal for blood to flow. RECANALIZATION.
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What are all the functions of platelet derived growth factor (PDGF)?
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1. Induce smooth muscle growth
2. Induce fibroblasts to cover thrombus 3. Induce new endothelial growth (angiogenesis) |
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Which COX enzyme created TXA2 in platelets? How can you remember this?
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COX-1. This is what low doses of aspirin inhibits and COX-2 inhibitos tend to decrease PGI2 more and are being pulled because this causes clots.
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So what process does coumadin treatment target?
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The coagulation cascade (by inhibiting synthesis of factors 2,7, 9, and 10)
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So what process does t. PA treatment target?
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It actually busts the clots because it cuts down fibrin to fibrin degradation product
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So what process does aspirin treatment target?
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It inhibits platelet adhesion and aggregation by inhibiting synthesis of TXA2, which signals platelets to express gp1b to attache to von Willebrand factor.
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So is aspirin a clot buster?
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No. It just prevents the progression of clots.
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BEGIN PATHOMA
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Go
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What is the very first action after endothelial damage? How can you remember this?
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vasoconstriction. Remember this because you tend to immediately clutch an injured site to reduce blood flow so it's important!
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What mediates this immediate vasoconstriction?
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nervous system and endothelin from endothelial cells
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Where does vWF come from?
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Mostly the endothelial cells in the weibel palade bodies and also the alpha granules of the platelets.
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What are all the steps in the primary plug formation?
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1. vasoconstriction
2. binding of platelets to vWF 3. platelet degranulation |
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What does ADP do?
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It induces platelets to express Gp2b/3a
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What does Gp2b3a do?
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It allows platelets to aggregate to one another when they are linked together with fibrinogen..
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What does vWF bind to?
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subendothelial collagen which includes tissue collagen and BM collagen
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What does activating of coagulation require? (3)
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1. Calcium
2. Phospholipid (from membrane) 2. Activation factors |
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What does PT measure?
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Measures the extrinsic and common pathways
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What does PTT measure?
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Measures the in trinsic and common pathways
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how do you remember which pathway PTT vs PT measure?
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PTT has more letters and so measures the intrinsic pathway which has more coagulation factors. They both measure the common pathway.
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Draw Pathoma's method of memorizing the cascade.
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What activates factor 12 to start the initial intrinsic cascade?
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Sub Endothelial Collagen (SEC)
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What activates factor 7 to start the initial extrinsic cascade?
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Tissue Thromboplastin (TT)
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how do you remember which pathway has which activator?
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The activator acronym has the same number of letters as the test. (SEC and PTT, TT and PT)
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How do you remember which test measures coumadin and which measures heparin according to pathoma?
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Heparin is often abbreviated Hep, which also has 3 letters. Also PTT converts to 911, which is used more in emergencies.
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What is thrombosis?
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WHen a thrombus forms that is pathological, not physiological.
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What is virchow's triad?
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The three biggest risk factors for thrombosis.
1. hypercoagulable state 2. disturbed blood flow or blood stasis (activates coagulation factors) 3. endothelial damage |
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What is the biggest cause of venous vs arterial thrombosis?
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venous- blood stasis
arterial- atherosclerosis |
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How can you tell if a thrombus was formed while the person was still alive?
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If they have lines of Zahn (alternating layers of fibrin/platelets and RBC's indicating high blood flow dring thrombus formation) and are attached to the vessel wall.
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Why would people form clots after they die?
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the circulatory system is in stasis.
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What are the three biggest risk factors for coagulation as a results of blood flow disturbance/stasis?
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1. Long term immobilization (bedridden or long car ride)
2. Aneurysm 3. Cardiac wall dysfunction (a fib or MI) |
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What happens to GFR in pregnancy?
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increasez
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What happens to GFR in old people?
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it decreases
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Why does iron increase acidosis?
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too much will detroy you mitochondira, which will force you to use more aneorobic respiration and build up ethanol.
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