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Questions and Answers
What is the primary role of coagulation factors in the coagulation cascade?
Which pathway of coagulation is activated by tissue factor expression?
What is the role of activated platelets in blood clotting?
Which condition is characterized by abnormal coagulation leading to bleeding disorders?
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What initiates the physiological process of coagulation?
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What is the role of Prostaglandin I2 (PGI2) in platelet activation?
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How do phosphodiesterases affect cAMP levels in platelets?
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What is the effect of thromboxane A2 (TXA2) on platelets?
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What mechanism does ADP use to activate platelets?
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What is the overall result of platelet activation?
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Which pathway is stimulated by factors outside the blood during hemostasis?
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What is the first step in the clot formation process?
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What role do glycoproteins on the platelet surface serve?
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What type of cell do platelets arise from in the bone marrow?
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Which physiological stimuli do platelets have receptors for?
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What occurs when a blood vessel is damaged regarding platelets?
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What substance forms a mesh during the clot formation process?
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How long is the average lifespan of a platelet?
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What is the primary difference between plasma and serum?
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What are the normal ranges of erythrocytes (RBC) in microliters?
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What role do anticoagulants play in the blood?
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Which of the following anticoagulants is produced by leeches?
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What physiological process facilitates the spontaneous arrest of blood loss?
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Which statement accurately describes thrombus formation?
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Which type of blood vessel is responsible for carrying blood away from the heart?
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What function do anticoagulants serve in ectothermic animals like Anopheles and Culex?
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Which glycoproteins are primarily involved in platelet adhesion?
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What happens when vascular injury occurs?
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What is the function of thromboxane A2 (TXA2) in platelet activation?
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Which receptors are activated by ADP in the platelet activation process?
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Which of the following is a major product of COX-1 that impacts platelet activation?
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What role does fibrinogen play in platelet aggregation?
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What activates the protease-activated receptors PAR1 and PAR4?
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How does activated platelets' secretion contribute to platelet activation?
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Study Notes
Plasma vs Serum
- Plasma is the liquid portion of blood with anticoagulants added
- Serum is the liquid portion of blood after clotting
Blood Vessels
- Arteries carry blood away from the heart
- Arterioles are small arteries
- Veins carry blood towards the heart
- Venules are small veins
Blood Cells
- Erythrocytes (RBC) are red blood cells:
- Normal range is 4.2-6.1 million per microliter of blood
- Leukocytes (WBC) are white blood cells:
- Normal range is 5-10 thousand per microliter of blood
- Platelets are cell fragments, involved in blood clotting, also called thrombocytes:
- Normal range is 250-500 thousand per microliter of blood
Hemostasis
- The process of stopping bleeding from injured blood vessels
- Thrombosis is a pathological process where thrombi (blood clots) prevent blood flow
Coagulation
- The process of turning liquid blood into a gel (blood clot)
- Activation of coagulation factors leads to clot formation
- Inappropriate activation of coagulation factors leads to thrombus formation
- Decreased activation (deactivation) of coagulation factors can lead to excessive bleeding
Anticoagulants
- Substances that prevent coagulation
Anticoagulants in Nature
- Anopheles mosquitos produce thrombin-directed anticoagulants in their saliva
- Culex mosquitos produce Factor Xa-directed anticoagulants in their saliva
- Animals that feed on blood have evolved mechanisms to interfere with blood coagulation of their prey
- Leeches (Hirudo medicinalis) produce:
- Hirudin: Inhibits thrombin; A recombinant version of hirudin is Lepirudin
- Antistatin: Inhibits Factor Xa
Why Study Coagulation & Anticoagulants
- Plays a role in thrombosis prevention and treatment
- Treats blood clotting disorders like hemophilia
- Treatments for disseminated intravascular coagulation disorder
Physiology of Coagulation
- Initiated by injury or stasis
- Platelets and coagulation factors are crucial
- Coagulation factors are designated I-XIII
- Activated platelets, fibrin, and red blood cells form a thrombus/clot
Coagulation Factors & Pathways
- Most coagulation factors are plasma glycoproteins
- They are produced by hepatocytes
- They are typically inactive serine proteases in a zymogen form
- The active form is created by proteolytic cleavage of a specific peptide bond
- In the coagulation cascade, an active coagulation factor cleaves and activates its substrate
- The goal of coagulation cascades is to convert soluble fibrinogen to insoluble fibrin
- Extrinsic pathway is activated by tissue factor expression
- Intrinsic pathway is activated by contact of Factor XII with an anionic surface (collagen)
Coagulation Factors & Pathways (2)
- Platelet procoagulant activity is essential for blood clotting
- Platelets provide a phospholipid surface for Ca2+ dependent coagulation complexes
- Thrombin activates platelets to aggregate
- Platelet activation and blood coagulation are inter-dependent events for clot formation
Coagulation Pathways
- Contact Activation Pathway (Intrinsic pathway)
- Stimulated by factors in the blood
- Tissue Factor Pathway (Extrinsic pathway)
- Stimulated by factors outside the blood
- Both pathways contribute to clot formation
Clot Formation
- An example of a video that describes hemostasis and clot formation: https://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.htm
- An example of a video that describes hemostasis and clot formation: https://www.hopkinsmedicine.org/hematology/Coagulation.swf
Steps Involved in Clot Formation
- Vasoconstriction (triggered by endothelin secretion at site of injury from endothelial cells)
- Platelet adhesion
- Platelet activation
- Platelet aggregation (plug formation)
- Fibrin mesh formation
- Incorporation of red blood cells and additional platelets into the clot
Platelets
- Platelets are cell fragments that arise from megakaryocytes in the bone marrow
- They have a lifespan of around 10 days
- They contain cytoplasm but lack nuclei (anucleated)
- They play essential roles in hemostasis and thrombosis
- The platelet surface contains many glycoproteins (GP) which serve as adhesive receptors for adhesive proteins such as:
- Fibrinogen
- Fibronectin
- Von Willebrand Factor (vWF)
Platelets (2)
- Platelets contain receptors for interaction with physiological stimuli, such as:
- ADP
- Thrombin
- Thromboxane A2 (TXA2)
- Collagen
- Epinephrine
- Activated platelets undergo a series of reactions leading to hemostatic plugs and thrombi
Platelet Adhesion, Activation & Aggregation (1)
- Platelets normally do not adhere to shielded/masked subendothelium of a blood vessel
- When a blood vessel is damaged, platelets adhere to the exposed subendothelium
- This initiates their activation processes
- This adhesion is mediated by the platelet membrane glycoproteins:
- GPVI binds to collagen
- GPIb binds to Von Willebrand Factor (vWF)
- Vascular injury causes endothelial denudation (loss) and exposes collagen
Platelet Secretion (Release Reaction)
- Activated platelets release contents from their dense granules
- These contents include potent platelet agonists/activators such as:
- ADP (adenosine diphosphate)
- Serotonin
- Activated platelets also make TXA2
Platelet Adhesion, Activation & Aggregation
- Activation of other platelets results from binding of ADP and TXA2 to their respective receptors:
- P2Y1 and P2Y12 are receptors (GPCRs) for ADP
- Thromboxane A2 (TxA2) is the major product of COX-1 involved in platelet activation through binding to the thromboxane A2 receptor (GPCR)
- Stimulated by agonists, these receptors activate the fibrinogen-binding glycoprotein GPIIb/IIIa to promote platelet aggregation (platelet-to-platelet interaction)
Platelet Adhesion, Activation & Aggregation
- PAR1 and PAR4 are protease-activated receptors (GPCRs) that are activated by thrombin (clotting factor IIa)
- Stimulated by agonists, these receptors activate the fibrinogen-binding glycoprotein GPIIb/IIIa to promote platelet aggregation (platelet-to-platelet interaction)
Platelet Adhesion, Activation & Aggregation (2)
- The symmetrical fibrinogen molecule will act as a molecular bridge linking the activated platelets together
Platelet Adhesion, Activation & Aggregation (3)
- Prostaglandin I2 (PGI2) synthesized by endothelial cells inhibits platelet activation
- PGI2 binds to its receptor (GPCR) and raises cAMP levels
- cAMP is a platelet inhibitor preventing platelets from aggregating and forming a clot
- Phosphodiesterases are enzymes that degrade or breakdown cAMP reversing its inhibitory effects on platelet activation
Thromboxane A2 Formation by COX
- Cycloxygenase (COX) is an enzyme involved in the formation of thromboxane A2
Platelet Activation by Thromboxane A2
- TXA2 activates platelets by increasing intracellular calcium levels
Platelet Activation
- Scanning electron micrographs are shown for resting platelets, and platelets undergoing activation
Platelet Activation by ADP (Adenosine DiPhosphate) and Thrombin
- ADP activates by lowering cAMP levels and increasing intracellular calcium levels
Clot Formation
- The text indicates √ which could be indicating a visual depiction of clot formation that is missing
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Description
Test your knowledge on the components of blood including plasma, serum, blood cells, and the processes of hemostasis and coagulation. This quiz will cover key concepts and normal ranges related to erythrocytes, leukocytes, platelets, and the blood vessels' roles. Challenge yourself and see how well you understand the essentials of blood physiology.
