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31 Cards in this Set
- Front
- Back
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Blood Vessel Functions:
Structure – -All blood vessels have single layer of ... cells -Blood should only contact ... -... is a complex extracellular matrix – *substances that will react with platelets *substances that react with circulating chemical factors -Damage to endothelium exposes the ... *Initiates blood clotting *May be external (traumatic) or due to internal disease such as atheroscleoris, turbulence, etc. |
endothelial
endothelium Subendothelium subendothelium |
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Vasoconstriction:
Physical injury to blood vessels causes - -locally mediated contraction of vascular smooth muscle by direct mechanical stimulation of vascular smooth muscle and of perivascular nerves -serotonin, thromboxane A2, other factors released by ... also constrict smooth muscle -... blood (blood leaked into tissue) compresses the vessels Healing promoted by ... |
platelets
extravasated platelet derived growth factor (PDGF) |
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Subendothelium:
Key substances contained in the subendothelium – -... -..., multimeric form High affinity for ... contained in plasma membrane of platelets |
collagen
von Willebrand’s factor (vWF) glycoproteins |
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Platelet Structure:
Non-nucleated with flattened, highly invaginated surface Extensive microfilament system with Ca++-sensitive actin/myosin system Granules of 3 types – 1. ... -Ca++, ADP, ATP serotonin 2. ... -heparin antagonist, PDGF, β-thromboglobulin, fibrinogen, vWF, other clotting factors 3. ... -hydolytic enzymes |
electron dense
α-granules lysosomal |
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Platelet functions in clotting:
1. ... -- reaction of platelet membrane to subendothelium begins process of “platelet activation” 2.... – binding of additional platelets to previously bound ones 3.... – release of substances from dense granules and α-granules that promote clotting |
Adhesion
Aggregation Secretion |
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Adhesion:
Reaction of the platelet membrane to exposed subendothelial matrix Platelet membrane glycoproteins (GP) -Collagen binds GPIa (integrin α2β1); assumes spherical shape, extends ... Platelet activation begins vWF binds ... - tightens bond, exposes other binding sites GPIIb/IIIa (integrin αIIbβ3) to ... and vWF -promote binding of platelets to each other |
psuedopods
GPIb fibrinogen |
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Platelet Aggregation:
Aggregation is adherence of ... to injured vessels and to each other. Adhered platelets release ... and ..., which promote platelet aggregation ... from platelets and injured RBCs is essential -It increases exposure of GPIIb/IIIa binding sites ... (circulating and platelet) binds to receptor formed from GPIIb/IIIa – aggregation |
platelets
ADP and thromboxane A2 ADP Fibrinogen |
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Platelet aggregation (cont.):
Collagen at injury site and first thrombin formed activate platelets ... (tissue factor) released by platelets provides binding site Thrombin acts on the bound fibrinogen to produce fibrin monomers Fibrin monomers polymerize to form the ‘...’ Thrombin acts directly on platelets to activate them via a specific platelet membrane receptor |
Thromboplastin
soft clot |
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Secretions by platelets:
After adhesion platelets begin to release contents of ... and ... ... is especially important – essential Ca++ required for many reactions Clotting factors Serotonin and thromboxane A2 to ... blood vessels Platelet derived growth factor to ... damage |
dense granules and α-granules
ADP constrict heal |
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Coagulation Cascade:
Key step is the final one: conversion of fibrinogen to ... (soluble) and its conversion to ...(insoluble) Two pathways: Intrinsic and Extrinsic Intersect at the common pathway: the dollars ... – factors of common pathway |
fibrin monomer
fibrin polymer I, II, V and X |
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look at slide 14
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ok
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know slide 15
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ok
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what factor does not require activation?
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III (tissue factor)
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Intrinsic pathway starts with activation of Factor ... by contact with negatively charged surface (collagen)
Extrinsic pathway starts with ... (released by platelets) and Factor ... Pathways intersect at Activation of Factor ... Many steps require ... as a cofactor Factor ... is not a serine protease: it cross-links fibrin by transamidation. Role of Vitamin K The proteolytic activation of Factors VII, IX, X and II (...) requires prior carboxylation of glutamate within the liver before release into the circulation. |
XI
thromboplastin VII X Ca++ XIII prothrombin |
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Sources of vitamin K:
Natural -Vitamin K1 (phylloquinone) from ... -Vitamin K2 (menaquinone) from ... Synthetic -Vitamin K3 (menadione), provitamin, potentially dangerous Note carboxylation also required for Protein C, Protein S and Protein Z |
green leaves
intestinal bacteria |
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Inhibitory regulation:
Protein C and Protein S form an activated complex. APC attaches its Protein S part to platelet PLs APC destroys Factors ... and ... by proteolysis Protein Z-related protease inhibitor degrades factor ...; it is relatively inactive without the presence of protein Z, which produces a 1000-fold ... of activity. |
VIIIa
Va Xa increase |
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Serpins:
-Serine protease inhibitors -Over 1,000 known -Serpins bind covalently, ... -Destroy activated coagulation factor by attacking a peptide bond and attaching Example: -Antithrombin III binds irreversibly to thrombin; heparin from mast cells and loose CT of vessels potentiates binding |
irreversibly
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look at slide 20
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ok
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Principles of feedback: homeostasis and response:
...: maintenance of homeostasis by function of control systems ...: failure of control systems to maintain system function within tolerable limits |
Health
Disease |
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look at slide 22
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ok
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Feedback systems:
... area of clot Prevent ... clotting 1. Terminate coagulation 2. Fibrinolysis Serpins (e.g. ATIII), IIa, Xa & IXa APC (VIIIa & Va) Heparin + ATIII Protein Z-related protease inhibitor degrades factor ...; |
Limit
unrestrained Xa |
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Fibrinolysis:
... is the dominant mechanism to degrade fibrin clots Precursor is ...: more responsive to activators after it binds to fibrin Activated by: -...: tissue plasminogen activator secreted by endothelial cells -Single chain urokinase from many cell types -Streptokinase (bacteria) |
Plasmin
plasminogen tPA |
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look at slide 25
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ok
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Fibrinolytic system:
Activated by fibrin deposition ... is a potent proteolytic enzyme Produced from plasminogen when activators are present: tPA - tissue plasminogen activator and urokinase, both released by endothelial cells, also epithelial cells Therapeutically - ..., a bacterial palsminogen activator and recombinant tPA (alteplase) are administered to dissolve clots |
Plasmin
streptokinase |
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Disorders of Hemostasis:
Bleeding Disorders Thrombotic (hypercoagulation and thromboembolic) Bleeding disorders 1. Blood ... abnormalities 2. Platelet defects, either genetic or acquired 3. Defects of the clotting ... 4.Exaggerated ... |
vessel
cascade fibrinolysis |
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Vascular – weakened walls; genetic or acquired
Platelet disorders -... are uncommon. -von Willebrand’s disease lack of vWF reduces adhesion, aggregation and activation Acquired are common -Many drugs: aspirin and NSAIDs (cyclooxygenase inhibitors) inhibit aggregation and clotting cascade -Uremia and metabolic diseases ... is common (drugs, disease of bone marrow; consumptive due to shock or sepsis; infectious diseases |
Genetic
Thrombocytopenia |
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Disorders of the cascade:
... is the most common genetic disorder of the clotting cascade. Hemophilia A is defect of Factor .... 80% of cases Hemophilia B is defect of Factor .... X-linked, female carriers, sometimes some clotting defects. Males, usually more severe disorder. Internal hemorrhages with or without apparent trauma. |
Hemophilia
VIIIa IXa |
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Vitamin K deficiency usually due to ... disorder.
-Loss of vitamin K that normally is produced by intestinal flora. Anticoagulant therapy or poisons -... – analogue, competitive antagonist -prevents activation of Factors II, VII, IX and X Heparin activates ATIII which irreversibly inactivates Factors VIIIa, IXa, Xa and XIa Excessive ... – extremely rare genetic deficiency of α2-antiplasmin. Treatment with streptokinase, altaplase, etc. |
GI
warfarin Fibrinolysis |
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Summary:
-Exposure of ... is a key initiator -... depends on vascular, platelets and circulating clotting factors -Platelets function as physical matrix and in chemical reactions -Coagulation cascade results in deposition of ... and cross-linking to form the hard clot -Clotting is regulated by factors that inhibit the cascade or cause ... -Hypercoagulation or thrombotic disorders cause ... clotting. |
subendothelium
Hemostasis fibrin fibrinolysis excessive |
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Deficiency of von Willebrand factor would most directly impair which function?
a. platelet adhesion b. fibrinolysis c. fibrin deposition as monomers d. cross-linking of fibrin e. activation of factor VIIa |
a. platelet adhesion
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A patient produces abnormal Protein C that cannot be activated. What disorder is most likely to occur?
a. Excessive fibrinolysis b. Hemophilia A c. Hemophilia B d. Hypercoagulation e. Thrombocytopenia |
d. Hypercoagulation
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