L2: Physiological basis of haemostatic mechanisms Flashcards
What is the definition of hemostasis?
Prevention of blood loss after injury.
What are the steps of hemostasis?
- Vascular spasm: occurs immediately after the blood vessel has been cut
- Formation of a platelet plug (temporary hemostatic plug).
- Formation of a blood clot (definitive hemostatic plug).
- Fibrosis of the blood clot to close the hole in the vessel permanently.
What does vascular constriction result from?
- Nervous reflexes are initiated by the pain from the traumatized vessel.
- Local myogenic contraction due to direct damage.
- Local vasoconstrictor factors as serotonin and thromboxane A2 (from platelets).
What causes more constriction to the vascular walls?
Transverse cut & traumatized vessels βnervous reflexβ
What is the function of vascular spasms in blood clotting?
The vascular spasm reduces the flow of blood from the vessel rupture.
What is the functional structure of the platelet membrane?
βΊ It is extensively invaginated membrane with a complex canalicular system that allow contact with the ECF.
βΊ Contain a coat of glycoprotein
β’ Repulses adherence to normal endothelium
β’ Allow adherence to the injured vessel wall.
βΊ Contains large amounts of phospholipids
β’ Play several roles in the process of blood clotting.
What is the Functional structure of the platelets cytoplasm?
Contains many active structures as:
- Contractile proteins for platelet contraction as actin, myosin, and thrombosthenin
- Residual of both endoplasmic reticulum and Golgi apparatus for synthesis of enzymes and storage of Ca2+.
- Mitochondria
β’ Can form ATP & ADP. - Enzyme system
β’ Can synthesize prostaglandins - Clotting factors as fibrin-stabilizing & von Willebrand factors
- A growth factor that helps repair damaged vessel walls.
What are the steps of the formation of the platelet plug?
Platelet adhesion
Platelet activation
Platelet aggregation
What is the adhesion of platelets potentiated by?
Such adhesion is potentiated by the von Willebrand factor (a glycoprotein presents in the plasma and subendothelial tissue) and the platelets membrane glycoprotein
When do platelets adhesion take place?
When a blood vessel is injured, the platelets adhere to the exposed subendothelial collagen.
What initiates platelet activation?
Initiated by platelet adhesion.
What happens in platelet activation?
- The activated platelets swell, develop pseudopodia, become sticky, and discharge their granules mainly ADP.
- Also, its enzyme system is activated to form thromboxane A2. βVCβ
What happens in platelet aggregation?
- The released ADP and thromboxane βA2 activate the nearby platelets, Making them stickier and adhere to the originally activated platelets and release ADP and thromboxane β A2 which, in turn, activates more and more platelets.
- Thus, a vicious circle of platelets activation and aggregation is elicited leading to the formation of a loose platelet plug. βPurpura is due to non-formation or non-function of plateletsβ
What is the effect of salicylates (aspirin) on blood clotting?
Salicylates (aspirin) can inhibit the thromboxane βA2 formation and so inhibits platelets activation and aggregation.
What is the importance of platelet plugs?
Platelet plugs are extremely important for closing the minute ruptures occurring in the wall of vessels many thousand times daily
What is the duration of blood clot formation?
The active process occurs within 3-6 minutes.
What does blood clot formation need?
- The clotting process is initiated by active substances from the traumatized vascular wall, platelets, and coagulation factors.
- The clotting process to occur, certain factors named clotting factors (plasma protein of beta globulin type) must be activated.
What are the clotting factors?
- Plasma proteins of beta globulin type, are proteolytic enzymes present in an inactive form
Give examples of the clotting factors.
Factor I: Fibrinogen
Factor II: Prothrombin
Factor III: Tissue thromboplastin
Factor IV: Calcium ions (Ca++)
Factor V: Proaccelerin or labile factor
- ββ- Prekallikrein
- ββ- HMW kininogen
- ββ- Platelets F3
Factor VII: Proconvertin or stable factor
Factor VIII: Antihaemophilic factor
Factor IX: Christmas factor
Factor X: Stuart prewar factor
Factor XI: Plasma thromboplastin antecedent
Factor XII: Hegeman factor
Factor XIII: Fibrin stabilizing factor
What are the steps of clot formation?
ο Formation of prothrombin activator
ο Conversion of prothrombin into thrombin
ο Conversion of fibrinogen into fibrin
What initiates the extrinsic pathway?
It is initiated by contact of blood with traumatized vascular walls or extra-vascular tissues.
Mentions steps of the extrinsic pathway.
It is a rapid process and occurs according to the following steps:
- Traumatized tissues release a complex of several factors called tissue thromboplastin (composed of phospholipids and lipoprotein that functions as a proteolytic enzyme).
- The lipoprotein of tissue thromboplastin activates factor VII and then complexes with it.
β’ This complex in the presence of Ca2+ and tissue
phospholipids act on factor X to form activated factor X - Formation of the prothrombin activator.
β’ The activated factor X complexes immediately with the
tissue phospholipids, Ca2+and with activated factor V to form the complex called prothrombin activator.
What initiates the intrinsic pathway?
It begins with trauma to the blood itself or exposure of the blood to collagen from a traumatized vessel wall or contact of the blood with water β wettable surface e.g., glass.
What are the steps of the intrinsic pathway?
It continues through the following series of cascading reactions:
1) Trauma to the blood or exposure of the blood to vascular wall collagen βslow blood flow, roughy intimaβ
2) leads to 2 effects; first, activation of factor XII; second, the release of platelet phospholipids (platelet factor 3 or PF3).
3) The activated factor XII activates factor XI.
β’ This reaction requires high molecular weight kininogen
(HMW) and is accelerated by prekallikrein
4) The activated XI acts on factor IX to activate it.
5) The activated factor IX together with factor VIIIa and platelet phospholipids (PF3) activate factor X.
6) The activated factor X combines with activated factor V, Ca2+, and platelets phospholipids to form the prothrombin activator
