Term
| What kind of tissue is blood? |
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Definition
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Term
| What are some features of blood? |
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Definition
Oxygenated blood is scarlet
pH of 7.4
Used for distribution, regulation, and protection |
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Term
What is the ratio of intracellular fluid to extracellular?
How much blood is in the body? |
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Definition
~28L intracellular fluid
~14L extracellular fluid
~5L of blood |
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Term
| What are the different layers of the blood? |
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Definition
55% - plasma
1% - buffy coat/white cells
45% RBCs |
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Term
| What are the components of plasma? |
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Definition
90% water
8% protein
other minerals, hormones, etc |
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Term
| What are the components of the protein layer of plasma? |
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Definition
60% Albumin - exert osmotic pressure, important as a carrier and in pH
36% Globulins - gamma globulins are immune (Y monomers). IgM in the circulation - pentamer. Heavy chain + light chain, Fac + Fc to bind antigen and complement |
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Term
| What is the difference between humoral and cellular immunity? |
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Definition
Humoral - involves antibodies such as IgG
Cellular - Only T cells involved |
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Term
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Definition
| Development of blood cells starting with a pleuripotent stem cell --> myeloid or lymphoid cell |
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Term
| What are the functions of red blood cells? |
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Definition
- transport hemoglobin/oxygen
- transport hemoglobin/CO2
- Possess CA to transform CO2 into bicarbonate
- Possess hemoglobin as a buffer |
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Term
| Where are red blood cells produced? |
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Definition
At an early age, in the axial skeleton AND in the tibia/femur, after 25 only in the axial skeleton
The head of bones contains spongy red bone marrow |
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Term
| At what point is an RBC committed? |
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Definition
When a hemocytoblast --> proerythroblast.
Reticulocytes are last stage before mature erythrocytes/RBCs, which have no DNA/nucleus |
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Term
| What is the role of erythropoietin? |
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Definition
| If there is a decrease in oxygen from hypoxia or an increase in oxygen demand --> HIF-1 in the kidney induced release of EPO --> red bone marrow produces RBC |
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Term
| What is the size and shape of an RBC and hemoglobin? What is their life span? |
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Definition
A concave cell with no nucleus that is 2 micrometers wide and 7.5 micrometers long. Life span of ~120 days!
Hemoglobin has 2 alpha and 2 beta polypeptide chains, 4 iron molecules which bind oxygen |
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Term
| What is the origin of bilirubin and how is it excreted? |
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Definition
| Dead/fragile/old RBCs are broken down into bilirubin by the liver --> secreted into small intestines and converted to urobilinogen. IF it is reabsorbed into the kidney, converted to urobilin and colors urine. If not, excreted as oxidized Sterobilin and colors feces. |
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Term
| What are the characteristics and examples of anemia? |
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Definition
- Low hematocrit and RBCs. Hemolytic, aplastic, pernicious (B12) anemia
- From abnormal hemoglobin:
- sickle cell anemia (hemoglobin has a genetic defect in the beta chain b/c of a one amino acid substitution, forms crystals in low oxygen and clog blood vessels)
- thalassemias (body does not make proper amount of hemoglobin) |
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Term
| What are the characteristics and examples of polycythemia? |
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Definition
- excess of RBCs that increases hematocrit and blood viscosity
- Primary - cancer
- Secondary - decreased oxygen due to altitude, hypoxia, etc |
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Term
| What causes Aldomet Hemolytic Anemia? |
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Definition
2 kinds: phagocytosis or hemolytic
Aldomet binds to RBC, IgG binds to abnormal RBC and activation of the complement system, C1 binds --> C3b binds
- in phagocytosis, C3b allows opsonization by PMN/neutrophil
- in Hemolysis, after C3b, rest of complement is activated through C9 and hemolysis occurs. Much rarer |
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Term
| What are the symptoms and causes of sickle cell anemia? |
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Definition
| In the presence of low oxygen, due to deficient beta chains, cells sickle and block vessels, causing anemia and pain, possible stroke, vision problems, swollen hands and feet. |
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Term
| What are the 2 subtypes of leukocytes? |
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Definition
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Term
| What are the types of granular leukocytes? What is their life span? |
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Definition
Basophils - in tissue, also called mast cells. allergic rxns
Neutrophils - greatest %, also called PMN
Eosinophils - cause asthma
All are end cells, do not undergo division. Life span 6-9 days |
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Term
| What are the types of agranular leukocytes? What are their life spans? |
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Definition
- lymphocytes - divide into NK cells (cellular), and T/B cells (Humoral) for immune rxns. Last hours-years
- Monocytes/macrophages - phagocytosis, cellular immunity, present antigens to T cell. Last months |
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Term
| What is the primary cell in the formation of leukocytes? |
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Definition
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Term
| What are the 2 different types of stem cells in leukocytes? |
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Definition
- Myeloid line - forms granular cells AND monocytes
-Lymphoid line - forms only lymphocytes |
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Term
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Definition
| Step before mature granular leukocytes, have a curved nucleus that is not lobed. An infection causes more band cells |
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Term
| What are the signs of short and long term inflammation? |
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Definition
- Acute - Heat, redness, swelling, pain. Caused by neutrophils
- Chronic - Loss of function, caused by macrophages |
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Term
| What is Neupogen and Neulasta? |
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Definition
| Neupogen stimulates the growth and proliferation of neutrophils. Attachment to PEG (Neulasta) gives a longer half life, improved solubility, and decreased immunogenicity |
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Term
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Definition
| Have a 10 day lifespan, bud off from megakaryocytes. Pinched off cytoplasm. Also called thrombocytes |
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Term
| What is the only prostaglandin produced by the platelet? |
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Definition
| Thromboxane (TxA2) - constricts blood vessels and aggregates platelets |
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Term
| What is the function of actin and myosin filament in the platelet? The golgi/ER? |
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Definition
Enhanced secretion of material/granule
Golgi - synthesis/storage of calcium, production of prostaglandins |
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Term
| What granules are associated with platelets? |
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Definition
Dense granules - ADP, serotonin, calcium
Alpha - vWF, fibrinogen, factors 5/13 (stabilize clots) |
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Term
| What is the difference between a clot and a thrombus? |
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Definition
A clot is formed in response to an injury to maintain hemostasis, mass of platelets and fibrin
A thrombus forms intravascularly and impedes blood flow, normally when a fibrous cap on a plaque ruptures. More platelets in arterial clots and more fibrin in venous clots. |
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Term
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Definition
| Maintaining blood in a fluid state as well as prevention of hemorrhage. There are 4 phases which occur simultaneously |
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Term
| What are the 4 stages of hemostasis? |
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Definition
1)Response to injury - vasoconstrictors such as TxA2, 5-HT, endothelin decrease blood flow (raise critical closing pressure)
2) Platelet plug stops capillary bleeding
3) coagulation/clot formation
4) repair and dissolution of the clot. |
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Term
| What are the 4 steps in the formation of a platelet plug? |
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Definition
- Adhesion - when an area is injured, exposing fibrinogen and vWF, platelets adhere.
- Activation - platelet changes shape, adhesion irreversible
- Release reaction
- Aggregation |
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Term
| What 3 receptors on the platelet surface are always expressed, and what do those receptors bind? |
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Definition
- Gp1b9 - binds vWF bound to injured tissue, most common receptor
- Gp1a2a - binds collagen exposed by injury
- gp1c2a - binds fibronectin/laminin (adhesion molecules) of injured tissue |
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Term
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Definition
| When Gp1b9 binds to vWF, Gp2b3a is expressed and can aggregate more platelets by binding more vWF or fibrinogen |
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Term
| What is the RGD recognition site? |
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Definition
| On gp2b3a, recognizes a 3 AA sequence on vWF or fibrinogen (mostly). |
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Term
| Once platelets become activated, what 3 events lead to aggregation? |
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Definition
1) PL exposed --> Phospholipase A2 is activated --> conversion of Arachidonic acid into TxA2 using COX1 and thromboxane synthase (only enzyme in platelet)
2) release of granules by actin/myosin - ADP
3) activation of Gp2b3a |
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Term
| Overall, how does activation proceed to aggregation in platelets? |
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Definition
| vWF (gp1b9), collagen (gp1a2a) or Thrombin (PAR) either increase phospholipase C (PLC) OR decrease adenylyl cyclace (AC). Either one increases calcium --> platelet changes shape, expression of gp2b3a, and release of granules |
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Term
| What is the difference between thromboxane formation and prostacyclin formation? |
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Definition
Thromboxane synthase is found only in platelets, makes thromboxane out of pgH2 --> constriction and aggregation
Prostacyclin synthase is found in the endothelium, converts PgH2 to prostacyclin --> vasodilation/anticoagulation |
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Term
| What is the release reaction? |
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Definition
| After Calcium increase and gp2b3a expression, myosin and actin release substances from granules including ADP. ADP binds to the P2Y12 receptor --> irreversible aggregation and more thromboxane |
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Term
| What mediators express gp2b3a and it's binding to fibrinogen, and what are their receptors? |
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Definition
- ADP - P2Y12 - see a decrease in cAMP and increase in calcium just like other mediators
- vWF - gp1b9 or (less) gp2b3a
- Collagen - gp1a2a
- Thrombin - PAR1
- Thromboxane
- PAF |
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Term
| Which factors are vitamin K dependent? |
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Definition
| Factors 2, 7, 9, 10 as well as protein C/S |
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Term
| Which factors are enzymatic, and must be activated to form a fibrin clot? |
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Definition
| 2 (Prothrombin), 7, 9, 10, 11, 13, and Kallikrein |
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Term
| Where is fibrinogen mainly found? |
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Definition
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Term
| What are the purposes of factors 1 and 2? |
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Definition
| Fibrinogen links platelets together for aggregation. When cleaved by thrombin (factor 2a), Fibrin forms the lattice for a stable clot. |
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Term
| Which factors are cofactors? |
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Definition
- Factor 3 - Tissue factor released from injured tissue. First step in extrinsic pathway
- Factor 5 - Component of the prothrombinase complex. Inactivated by protein C/S. Must be activated by thrombin
- Factor 8 - in the Tenase complex, must be activated by thrombin. Inactivated by protein C/S |
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Term
| At which factor do the internal and external cascades meet? |
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Definition
| Factor X, site of many drugs |
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Term
| What is the 1st factor in the intrinsic pathway? |
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Definition
| Factor 12, the glass factor |
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Term
| What is the function of Factor 13? |
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Definition
| FSF acts on fibrin monomers to polymerize them, stabilizing the clot. Maintains the platelet plug. |
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Term
| How are Factors 2,7,9,and 10 synthesized? |
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Definition
| When Glutamate is carboxylated, the process oxidizes Vit K. KO reductase reduces it back to start. |
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Term
| What are the steps of the extrinsic pathway? When is this pathway used? |
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Definition
The normal pathway activated upon injury for formation of a clot.
- Tissue factor (Factor 3) becomes exposed and combines with circulating factor 7 (K synthesized) --> activated by either thrombin (2a) or 10a. Then TF/7a can convert 10 to 10a in the presence of calcium and then tenase complex |
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Term
| What are the components of the tenase complex? |
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Definition
| Factor 9a (last step of the intrinsic pathway), calcium (factor 4), factor 8a (activated by thrombin, cofactor), and phospholipid |
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Term
| What are the components of the prothrombinase complex? |
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Definition
| 5a (activated by thrombin, cofactor), calcium, phospholipid |
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Term
| How is factor 12 converted to 12a in the initiation of the intrinsic pathway? |
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Definition
Exposed collagen
Formation of Kallikrein, release of BK
Negatively charged surface exposure on the platelet |
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Term
| What is the intrinsic pathway? |
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Definition
Many more steps than the extrinsic, forms a thrombus instead of a clot.
Begins with factor 12, the glass factor.
12a converts 11 --> 11a. 11a converts 9 to 9a with the presence of calcium (factor 4). 9a is a component in the tenase complex --> reduction of 10 to 10a and then prothrombin to thrombin using the prothrombinase complex |
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Term
| What is the purpose of Thrombin/ Factor 2a? |
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Definition
| Thrombin Cleaves fibrinogen into fibrin monomers. Thrombin also reduces factor 13 (FSF) with calcium to 13a, and 13 polymerizes fibrin, stabilizing a clot. |
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Term
| What is fibrinolysis and what processes are involved in it and anticoagulation? |
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Definition
Fibronolysis is clot dissolution.
1) Plasminogen - converted to plasmin by t-PA (high affinity for fibrin)
2) Antithrombin 3 - anticoagulation, important w/ heparin. Inhibits Xa
3) Protein C/S - clot lysis and anticoagulation
4) TFPI - anticoagulation
Antiplasmin inhibits plasmin directly while PAI inhibits t-PA |
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Term
| What is the difference between fibrinolysis and fibrinogenolysis? |
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Definition
- Fibrinogen is circulating. If unbound plasminogen in the plasma is converted to plasmin by t-PA/urokinase/factor 12, it will break up circulating fibrinogen which causes bleeding
- Fibrin is bound to the clot. Plasminogen bound to fibrin is converted to plasmin, and splits up fibrin on the clot --> dissolving the clot. |
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Term
| What is the difference between Glu-plasminogen and Lys-plasminogen? |
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Definition
Lys-plasminogen has a greater affinity for the clot
- If Lys-Plasminogen is bound to a clot, t-PA QUICKLY binds to it, conversion to plasmin, and dissolution of the clot
- Glu-plasminogen circulates, and t-PA can slowly bind to it. Circulating plasmin is inhibited by antiplasmin, and t-PA inhibited by PAI --> control of systemic bleeding |
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Term
| What triad of factors is the optimum for fibrinolysis? |
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Definition
Plasminogen, t-PA, and fibrin
Plasminogen binds to fibrin on a clot, t-PA converts to plasmin, breakdown of fibrin. |
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Term
| What is thrombin? How does thrombin promote clot formation? |
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Definition
Factor 2a, produced by 10a.
Cleaves fibrinogen into fibrin, allowing a clot to form. Activates 13, stabilizing fibrin.
Activates cofactors 5 and 8, factor 11 in the intrinsic cascade.
Release of ADP and vWF - increase presentation of gp2b3a and activation of platelets.
Activates TAFI - inhibits plasminogen from binding to fibrin |
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Term
| How does thrombin inhibit clot formation? |
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Definition
Activation of protein C
Inhibits active cofactors 5a and 8a |
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Term
| What is the role of protein C, and how does it function? |
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Definition
| Thrombomodulin changes the structure of thrombin. Changed thrombin activates Protein C --> Protein C/S complex binds to platelet --> inhibits cofactors 5a and 8a, releases tPA, and inhibits PAI --> fibrinolysis. |
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Term
| What is the difference between TAFI and TFPI? |
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Definition
TAFI - Inhibits plasminogen and therefore fibrinolysis. Clot remains
TFPI - binds Xa --> TFPI/Xa complex blocks TF. Blocks extrinsic pathway --> Anticoagulation |
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