Lecture 3 Blood PDF

Platelets thrombocytes  platelets Number: 150.000—350.000 / mm3 Shape : non nucleated rounded discs 2—4 micrometer Formation : in bone marrow from megakaryocytes. Structure: see fig Life span: 10 days  Structure of platelets Platelets consist of platelet wall and cytoplas...

Platelets thrombocytes  platelets Number: 150.000—350.000 / mm3 Shape : non nucleated rounded discs 2—4 micrometer Formation : in bone marrow from megakaryocytes. Structure: see fig Life span: 10 days  Structure of platelets Platelets consist of platelet wall and cytoplasm 1.Platelet wall a) mucopolysaccaride Coat (platelet adhesion) b) Plasma membrane (inward invagination) PF-3 c) sub membranous layer of contractile proteins d) ring of microtubules (maintain platelet shape)  Structure of platelets 2. Platelet cytoplasm dens granules a) 2 types of granules ADP, Ca, serotonin alpha granules clotting factors b) Lysosomes c) other organelles such as glycogen and mitochon  Function of platelets Generally platelets are important in hemostasis 1. Platelets help vasoconstriction of injured blood vessels (serotonin + thromboxane A2) 2. Formation of platelet plug to close injured vess… in.4 steps…adhesion, release, aggregation, fusion **Platelet adhesion Vwf (von will brand) **Platelet release ++enzymes..thromboxanA2 …ADP **Platelet aggregation THMBXA2 and ADP activate next platelet…..become sticky and adhere to each other….Cycle of activation and aggregation …formation of platelet plug **platelet fusion irreversible fusion of aggregated platelet occur due to release enzymes and contraction of contractile protein (thrombasthenin)ll 3. Help blood clot formation (fibrin clot) Platelet membrane act as a surface for activation of clotting factors, platelets release some clotting factors, essential for clot reaction 4. Stimulate growth of vascular wall to repair vascular injury by release of platelet growth factor in the granules Hemostasis by dr aisha alkilani  hemostasis Definition: it stoppage of bleeding from blood vessel Mechanisms of hemostasis when the blood vessel is injured 3 mechanisms occur: vasoconstriction platelet plug blood clot  Firstly Local vasoconstriction occur at the area of injured blood vessel, to slow the blood flow may stop the bleeding. caused by **local nervous reflex **myogenic contraction from pain impulses of smooth muscle of injured blood vessel In addition to ** substances released from platelets : ADP,SEROTONIN, THMBXA2 Secondly Formation of platelet plug (white clot) discussed previous lecture [ stop bleeding from small B.Vessel Thirdly Formation of blood clot (blood coagulation) Needed to close large injuries by formation of meshwork of fibrin threads …by formation of clot factors …..see the next table  I Fibrinogen VIII Anti hemophilic factor A II Prothrombin IX Anti hemophilic factor B III Thromboplastin X Staurt power factor IV Calcium XI Anti hemophilic factor C V proaccelrin XII Contact factor VII proconvertin XIII Fibrin stabilizing factor The clot formed by clotting factors by two pathways: Intrinsic pathway all factors needed are present in the blood and activated by trauma, rough surface Extrinsic pathways needs factors not present in the blood i.e. tissue thromboplastin,,, , this pathway activated by tissue trauma  Intrinsic pathway Extrinsic pathways Factors needed Blood Some in the tissue Site of occurrence Outside and inside Only inside duration 4—8 M 20 Seconds Slow rapid Clot formed Large and firm Small and week Main function Formation of Formation of definitive clot thrombin Extrinsic and intrinsic pathway are complementary Extrinsic pathway leads to rapid formation of thrombin …….++the intrinsic pathway by activation factor V, VIII XIII …………..ACTUAL CLOT Role of calcium in clot formation It should be ionized It is required in all steps of IN and EX pathways except the first 2 steps of IN pathway Classification of clotting factors Fibrinogen group Fibrinogen, factor V, factor VIII, factor XIII Activated by thrombin, stable except F V and F VIII ,not present in serum Prothrombin group Prothrombin FVII, F IX, and X, formed in the liver need VIT K, stable.present in serum except prothrombin Contact group Factor XI, XII, stimulated by contact with wettable surface , stable ,present in serum  clotting factors groups Fibrinogen Prothrombin Contact group group group Composed Fibrinogen, V, Prothrombin, VII, factors XII and of VIII, XIII IX, X XI Activated by / thrombin vit K Contact by formed in Formed in liver rough surface / blood trauma Stability during Stable except stable stable preservation in VIII and V stored plasma Presence in Not present Present except present in serum= (plasma prothrombin serum after blood clot formation) Clot retraction it is due to contractile protein in the platelet, only few minutes after clot formed fibrin thread retract ………sequizing of clear yellowish fluid from the clot …serum Serum = plasma –clotting factor I, V, VIII, XIII and prothrombin Serum = defibrinated plasma Significant of clot retraction //// ***makes the clot more dens and strong , ***pull the edges of the injured blood vessel to facilitate healing Coagulation lll////llll anticoagulatio  anticoagulation Anticoagulants: substances prevent blood coagulation In vitro In vivo 1. Substances that 1. coumarins remove Ca +2: Oxalate Citrates EDTA 2. Heparin 2. Heparin  heparin coumarins Site of action In vivo and in vetro In vivo administration IV IM Orally Onset of action Rapid Delayed 1—3 days Duration of action Short 6 hrs Long days Mechanism of ++ antithrombin III Competitive action in – thrombin and inhibition of vit K factors IX, X, XI in the liver….-VII, IX, X antidote Protamine Large dose of vit K sulphate Causes of fluidity inside blood vessels Natural anticlotting mechanisms It is mechanisms which prevent blood clotting in the normal blood vessels and limit blood coagulation to the site of injury….how???? by two mechanisms 1). Mechanisms related to the endothelium 2). Mechanism related to the blood  Mechanisms related to the endothelium 1. Smoothness of endothelium 2. Presence of negativity charged protein layer lining the endothelium 3. Prostacyclin (prostaglandin I2) (inhibit platalet release and aggregation) 4. Thrombomodulin...(thrombomodulin thrombin complex). +++protein C (an anticoagulant)  Mechanisms related to the blood 1.Blood flow ,,,,continous B flow prevent contact activation of platelet,,,,reticuloendothelial cells remove clotting factor 2. Heparin released by mast cells and basophils 3.Antithrombin III Secreted in the liver. ,,- - thrombin ,f IX, X XI ,,,, heparin stimulate its activity 4. Protein C (THROMBOMODULIN THROMBIN COMPLEX )++Fibrinolysis 5. Protein S formed in the liver ++effect of Protein C 6.Alpha 2 macroglobulin ---inhibit some CF and THROMBIN 7. Fibrinolysis  Fibrinolytic system Definition : lysis of already formed blood clot by plasmin Mechanism: Plasminogen [pro fibrinolysin] = inactive form of plasmin Plasmin [fibrinolysin] active form and it is essential for fibrinolysis process Get activated by 1. tissue plasminogen activators 2. XII a 3. thrombin Plasmin breaks fibrin and fibrinogen to FDPs Plasmin breaks some clotting F e.g. Prothrombin, V, VII,  Mechanism of fibrinolysis: * Tisssue plasminogen activators * Active F XII * THROMBIN plasminogen plasmin Fibrinogen fibrinogen fibrin degradation products FDPs thrombin (--)  Tests of hemostasis 1.Platelet count,,,,, Thrombocytopenic purpura 2. Bleeding time (test for platelet function) 1—5 minutes prolonged in (purpura and vWB disease) 3. Clotting time (5—10 M) non specific test for intrinsic pathway  Tests of hemostasis 4.Prothrombin time (PT) (10—14) seconds ,test for extrinsic pathways,,,,, prolonged in vit K deficiency, coumarin therapy 5. Activated partial thromboplastin time (APTT) (30—40 S) time needed to form clot after activation of contact factors Intrinsic pathway….prolonged in hemophilia heparin therapy 6. specific assay of different coagulation factors  Disorders of hemostasis ***Hypercoagulable disorders (intravascular clotting or thrombosis) * definition: Spontaneous formation of blood clot inside blood vessel Causes: 1. venous venous stasis 2.arterial atherosclerosis 3. Blood componants polycythemia, thrombocytosis, herrditary defeciency of antithrombin III, protein C, protein S Complications 1. Thrombosis of blood vessel …..reduction of blood supply 2. Emboli formation……affect organs brain ****hypocoagulable state (hemorrhagic disease) 1. Purpura it is spontaneous bleeding from small vessel small punctate hemorrhage under the skin causes : thrompocytopenia, thrombasthenia.BT prolonged PT APTT normal 2. Hemophilia heriditary disease characterized by bleeding tendency transmitted as X linked recessive disease from female to male , males affected and females never suffer act as a carries for disease Types of hemophilia hemophilia A….(F VIII) 85% Hemophilia B…..(F IX) 10%) Hemophilia C….(F XI) 5%) in hemophilia BT and PT normal CT and APTT prolonged  PURPURA HEMOPHILI Vit. K Def Von will A brand disease BT prolonged normal normal prolonged CT Normal prolonged prolonged prolonged Prothrombi normal normal prolonged normal n Time (PT) APTT normal prolonged Nearly prolonged normal Deficient platelets VIII or IX or II,VII, IX, X VWPF factor XI 3. Vit K deficiency caused by sterility of intestine, fauilur of absorption, compititive inhibition of vit K by coumarin 4. Vonwillbrand’s disease : bleeding tendency caused by defeciency of VWB factor thanks