1. Blood Part 2

2. Hemostasis Responses that stop bleeding When blood vessels are damaged or ruptured, the hemostatic response must be quick, localized to the region of damage and carefully controlled. Involves –Vascular spasm –Platelet plug formation –Blood coagulation (clotting)

3. Vascular Spasm Smooth muscle in the walls of arteries and arterioles contract immediately when damaged Reduces blood flow for minutes to hours

4. Platelet Plug Formation Platelet Adhesion Platelets contact and stick to parts (collagen fibers) of damaged blood vessels.

5. Platelet Plug Formation Platelet Release Reaction Platelets become activated, extend projections to contact each other and release the contents of their vesicles (clotting factors, ADP, ATP, Ca2+, enzymes that make thromboxane A2, prostaglandins, serotonin)

6. Platelet Plug Formation Platelet Release Reaction ADP and thromboxane A2 activate near by platelets Thromboxane A2 and serotonin act as vasoconstrictors

7. Platelet Plug Formation Platelet Aggregation Gathering platelets Eventually forms the platelet plug Platelet plug prevents blood loss in a small vessel and can stop blood loss completely if the vessel damage is not too large Platelet plug built in one minute Plug inhibited by prostacyclin released from intact endothelial cells

8. Blood Coagulation Clot is a gel consisting of a network of insoluble protein fibers (fibrin) in which the formed elements of blood are trapped. Involves clotting factors –Number I- XIII by order of discovery –Most are plasma proteins made by liver that circulate in the inactive form –Ca2+, inactive enzymes synthesized in liver and molecules associated with platelets or released by damaged tissues

9. Blood Coagulation Blood clotting involves a cascade of reactions that may be divided into three stages –1. Formation of prothrombinase (prothrombin activator) Either by the Extrinsic or Intrinsic Pathway –2. Conversion of prothrombin ( a plasma protein) into thrombin –3. Conversion of soluble fibrinogen into insoluble fibrin by thrombin

10. Extrinsic Pathway Occurs rapidly Tissue protein called Tissue Factor (TF)/thromboplastin leaks into blood from cells outside of blood vessels and starts the formation of prothrombinase TF released from surface of damaged cells, in the presence of calcium ions, after a series of reactions it activates clotting factor X, factor X combines with Factor V to form the active enzyme prothrombinase

11. Intrinsic Pathway Occurs slower Its activators are either in blood or in direct contact with blood Contact with collagen fibers underlying endothelium of blood vessels walls activates clotting factor XII, after a series of reactions Factor X is activated, it combines with Factor V and forms prothrombinase

12. Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca 2+ Damaged platelets Ca 2+ Platelet phospholipids Activated X Activated platelets Activated X PROTHROMBINASE Ca 2+ V V 1 Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca 2+ Damaged platelets Ca 2+ Platelet phospholipids Activated X Activated platelets Activated X PROTHROMBINASE Ca 2+ V Prothrombin (II) Ca 2+ THROMBIN (c) Common pathway V 1 2 + + Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca 2+ Damaged platelets Ca 2+ Platelet phospholipids Activated X Activated platelets Activated X PROTHROMBINASE Ca 2+ V Prothrombin (II) Ca 2+ THROMBIN Ca 2+ Loose fibrin threads STRENGTHENED FIBRIN THREADS Activated XIII Fibrinogen (I) XIII (c) Common pathway V 1 2 3 + +

13. Coagulation

14. Detailed Events of Coagulation

15. Common Pathway The formation of prothrombinase starts the Common Pathway Prothrombinase and Ca2+ catalyze the conversion of prothrombin to thrombin Thrombin, in presence of Ca2+, converts fibrinogen (soluble) to loose fibrin threads (insoluble) Thrombin also activates Factor XIII/fibrin stabilizing factor which strengthens and stabilizes the fibrin threads into a sturdy clot The formed clot plugs the ruptured blood vessel and stops blood loss, usually within 3-6 minutes of damage

16. Clot Retraction The consolidation of the fibrin clot As the platelets pull on the fibrin, fibrin contracts and pulls the edges of the damaged blood vessel closer together In time the fibroblasts form CT in the ruptured area and new endothelial cells repair the vessel lining

17. Vitamin K Need adequate levels for clotting Not actively involved in clotting but required for synthesis of four of the clotting factors

18. Fibrolytic System Dissolves small inappropriate clots Dissolves clots at site of damage once damage is repaired (begins within two days and continues slowly over several days) Fibrinolysis is the dissolution of a clot Inactive enzyme plasminogen is incorporated into the clot Body tissues and blood contain substances that can activate plasminogen and convert it to plasmin Plasmin(fibronolysin) dissolves the clot by digesting fibrin and inactivating fibrinogen, prothrombin, factor V and factor XII

19. Control of Clotting Fibrolytic System Prostacyclin –A prostaglandin produced by WBC and endothelial cells, opposes the action of thromboxane A2 and inhibits platelet adhesion and release Anticoagulants in blood –Substances that delay, suppress or prevent blood clotting Antithrombin which blocks factor XII, X and II Heparin produced by mast cells and basophils, combines with antothrombin and increases its effectiveness Activated protein C which inactivates 2 major clotting factors and enhances activity of plasminogen activators

20. Clotting If blood takes too long to clot can have hemorrhage If blood clots too easily get thrombosis, clotting in undamaged blood vessel

21. Thrombosis Intravascular clotting Clot called a thrombus Thrombus may dissolve spontaneously or may break away A blood clot, bubble of air, fat from a broken bone or piece of debris transported by blood stream called an embolus –In lung Pulmunary Embolus Virchow ’ s Triad –Damage to venous wall –Change in flow –Blood hypercoagulability –I AM CLOTTED

22. Blood Groups and Blood Types The surface of RBCs contain a genetically determined assortment of antigens composed of glycoproteins and glycolipids Antigens called agglutinogens occur in characteristic combinations Blood is categorized into different groups based on the presence or absence of various antigens Within a blood group there may be two or more types At least 24 groups and 100 antigens, ABO and Rh are two major blood groups

23. ABO Blood Group Based on two glycolipid antigens A and B Only antigen A displayed-Type A Only antigen B-Type B Both antigens-Type AB Neither A or B-Type O

24. ABO Blood Group Blood plasma contains antibodies that react with the A or B antigens if the two are mixed Anti-A antibody reacts with antigen A Anti-B antibody reacts with antigen B You do not have antibodies that react with antigens of your own RBCs but you do have antibodies for antigens your RBCs lack

26. Transfusions Transfer of whole blood or blood components into bloodstream Incompatible blood transfusions the antibodies in the recipient ’ s plasma bind to antigens on donors RBC which causes agglutination or clumping of RBCs Type AB-universal recipients Type O-universal donors, can only receive Type O Blood is cross-matched or screened before transfusions

27. Rh Blood Groups Antigen discovered in blood of rhesus monkey Rh antigen on RBC Rh+ Lack antigen, Rh- Normally blood plasma does not contain anti-Rh antibodies –If an Rh- recieves an Rh+ transfusion the immune system will start to make anti Rh antibodies –Hemolytic Disease of Newborn

28. Hemolytic Disease of Newborn Normally do direct contact between maternal and fetal blood but leakage possible at delivery If Rh+ leaks into Rh- mother she will make anti Rh antibodies which will cause maternal and fetal incompatibility in 2 nd pregnancy All Rh- women should receive Anti-Rh gamma globulin(RhoGAM) soon after every delivery, miscarriage or abortion

29. Typing Blood –Single drops of blood are mixed with different antisera –Agglutination with an antisera indicates the presence of that antigen on the RBC