hemostasis : blood clotting
Post on 12-Apr-2017
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Hemostasis
Dr Alok TripathiDepartment of Biotechnology
Hemostsis & Thrombosis: Definition
•Hemostasis is result from well regulated process that maintain blood in a fluid clot free state in a normal vessel while inducing a rapid formation of localized hemostatic plug at the site of vascular injury.•haemostasis—the rapid arrest of blood loss upon vascular damage, in order to maintain a relatively constant blood volume.•The process by which blood is maintained in a fluid state and confined to the circulatory system
Hemostasis
•The formation of blood clot (Thrombus) in uninjured vessel. Or•Thrombotic occlusion of a vessel after a relatively minor injury.
Thrombosis
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Main processes of hemostasis
1. Platelets adhesion and aggregation, formation of the platelet plug
2. Vasoconstriction
3. Blood clotting
4. Final repair by connective tissue
NB! The phases are not separated but rather manyfold interconnected
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Hemostasis
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2
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Classics of blood clotting
Alexander Schmidt and Paul Morawitz discovered the enzymatic cascade nature of blood clotting
1st phase – activation (of thrombokinase which converts prothrombin to thrombin)
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Adhesion of platelets, white thrombus
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2
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Thrombocytes
Production from megakaryocytes, 1.5-3.0 x 1011 in 1L
blood
Reservoirs of bioactive
substances
Serotonin (5-HT) and thromboxan
A2 potent vasoconstrictors
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Factors influencing platelets adhesion
Collageen and plasma von Willebrand factor (vWf) iniate adhesion.
Adhesion is blocked by negative surface charge of platelets, certain biochemical regulators (e.g. NO, prostacyclin etc), and endothelial barrier between collagen and blood.
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Platelets in “normal” state
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The activated platelets
Thrombin and collagen are the two most important platelet activators. ADP is considered a weak agonist; it causes aggregation but not granule release. (GP, glycoprotein; R1–R5, various receptors; AC, adenylyl cyclase; PLA2, phospholipase A2; PL, phospholipids; PLCβ,phospholipase Cβ; PIP2, phosphatidylinositol 4,5-bisphosphate; cAMP, cyclic AMP; PKC, protein kinase C; TxA2, thromboxane A2; IP3, inositol 1,4,5-trisphosphate; DAG, 1,2-diacylglycerol. The G proteins that are involved are not shown.
Diagrammatic representation of platelet activation.The external environment, the plasma membrane, and the inside of a platelet are depicted from top to bottom
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Intergrine: A cell surface receptors
•Cell-cell adhesion•Cell to matrix adhesion•Signal Transduction•Spreading •Apoptosis•Migration •Proliferation
Role of integrine
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Blood clots. “red thrombus”
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•inflammation, •epithelialization, •angiogenesis•and matrix deposition.
Fig. 1. Wound healing is a complex process encompassing a number of overlapping phases, including
•the formation of a blood clot re-establishes hemostasis and provides a provisional matrix for cell migration. •CK play significant role in the evolution of granulation tissue through• recruitment of inflammatory leukocytes•and stimulation of fibroblasts and epithelial cells.
During inflammation,
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Conversion of prothrombin to thrombin
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Fibrinogen
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Conversion of fibrin from fibrinogen
2nA+2nB
n(A)2 (B) 2 2 n222(2222)n
Fibrin Monomer Fibrin Clot
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Fibrinogen structure
The disulfide rings are region containing 3 di-sulfide bonds cyclic linking homologous segment of , and chains. N-linked polysaccharides are represented by filled hexagons. The Arg-Gly bonds that are cleaved by thrombin in fibrin activation are indicated
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Fibrin network
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Initiation of coagulation
The extrinsic pathway is critical in initiating of blood clotting.
The intrinsic pathway plays an important role in maintenance of coagulation.
There is no bleeding disorders in case of lack XII
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Regulation of coagulationSerine protease
inhibitors (antithrombin III)
The protein C system activated
by thrombin
The regulatory influences of
intact endothelial and blood cells
The fibrinolytic
system
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Serine protease inhibitors
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Protein C system
Proteiin C destroys factors V and VIII
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Fibrinolysis
Endothelium
Modulate several aspect of anti-cougulating properties
It may activated by infectious agents, hemodynamic factors plasma mediators &
CK
Anti-platelet ,Anti-couagulent & fibrinolytic
Exerts pro-couagulent functions
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Endothelium and coagulation
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Blood cells and coagulation
Platelets contain procoagulant anticoagulant substances
Polymorphonuclear leukocytes and monocytes produce tissue factor, factor V and present phospholipids, which all support blood coagulation
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Disturbances of blood coagulation
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Hypocoagulation
Thrombocytopenia
Deficiency of
coagulation factors
Deficiency of vitamiin
K
Vitamiin K is important to add gamma-
carboxyglutamate (gla) to
factors II, VII, IX ja X.
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Blood coagulation and blood cells
Platelets contain both substances which activate or inhibit blood clotting
Neutrophilic granulocytes and monocytes produce the tissue factor, the factor V, and phospholipids which all support blood clotting processes.
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Endothelium and blood clotting
In case of intact endothelium there is no clotting
Endothelial cells produce plasminogen activators.
A good overview and illustrations: http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
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