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Hemostasis
Jul 30, 2024
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Hemostasis Lecture Notes
Introduction to Hemostasis
Definition
: Hemostasis = Hemo (blood) + Stasis (stop) => Localized blood stoppage.
Context
: Occurs when blood vessels are damaged, with the goal of stopping blood loss.
Steps
: Hemostasis involves five key steps.
Vascular spasm
Platelet plug formation
Coagulation
Clot retraction and repair
Fibrinolysis
Natural Inhibitors of Blood Clotting
Endothelial Cells
: Secrete Nitric Oxide (NO) and PGI2 (Prostacyclin) to inhibit platelets.
Heparin Sulfate
: Binds and activates antithrombin 3, degrading clotting factors 2, 9, and 10.
Thrombomodulin
: Binds thrombin leading to activation of Protein C which degrades factors 5 and 8.
Vascular Spasm
Definition
: Contraction of blood vessels to reduce blood loss.
Mechanisms
:
Endothelin
: Secreted by injured endothelial cells, causes smooth muscle contraction.
Myogenic Mechanism
: Direct injury to smooth muscle prompts contraction.
Nociceptor Activation
: Inflammatory chemicals cause pain reflex leading to vasoconstriction.
Platelet Plug Formation
Von Wildebrand Factor (vWF)
: Protein that binds platelets to sites of injury.
Platelet Activation
:
Inhibited NO and PGI2 -> Platelet binds to vWF using glycoprotein 1B.
Activated platelets release ADP, Thromboxane A2, and Serotonin.
Aggregations
: Platelets bind together using glycoprotein 2B/3A and fibrinogen.
Vasoconstriction
: Enhanced by thromboxane A2 and serotonin binding to smooth muscles.
Coagulation (Beast Mode)
Intrinsic Pathway
:
Factor 12 -> Factor 11 -> Factor 9 (with Factor 8) -> Common Pathway (Factor 10).
Extrinsic Pathway
:
Tissue factor (Factor 3) + Factor 7 -> Either Factor 9 activation or direct pathway to Factor 10.
Common Pathway
:
Factor 10 (with Factor 5) -> Prothrombin activator converts Prothrombin to Thrombin.
Thrombin converts Fibrinogen to Fibrin -> Fibrin mesh created and stabilizes clot (Factor 13 cross-links).
Clot Retraction and Repair
Platelet Contraction
: Actin and myosin in platelets pull edges of blood vessel together.
Secretions
:
PDGF (Platelet-derived growth factor)
: Smooth muscle proliferation, collagen repair.
VEGF (Vascular endothelial growth factor)
: Regenerates endothelial lining.
Fibrinolysis
Tissue Plasminogen Activator (TPA)
: Converts Plasminogen to Plasmin.
Plasmin
: Degrades fibrin mesh and releases D-dimer (diagnostic marker).
Clinical Applications
: TPA in strokes to dissolve blood clots.
Recap with Drug Info
Natural Anticoagulants
: Nitric oxide, prostacyclin, heparin sulfate, thrombomodulin, antithrombin 3.
Drugs
:
Heparin
: Enhances activity of antithrombin 3.
Clopidogrel
: Inhibits ADP for platelet aggregation.
Aspirin
: COX-2 inhibitor, prevents Thromboxane A2 formation.
Abciximab
: Blocks glycoprotein 2B/3A.
Dabigatran
: Direct thrombin inhibitor.
Warfarin
: Vitamin K oxide reductase inhibitor, prevents activation of clotting factors.
Tricks to Remember Coagulation Cascade
Intrinsic Pathway
: X marks the spot -> 12 -> 11 -> 9 -> 8 -> 10
Extrinsic Pathway
: 3 + 7 = 10
Common Pathway Formation
: 5x2x1 = 10
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