intro homostasis

• Hemostasis: The balance between bleeding, coagulation, and fibrinolysis.
• Definition of Hemostasis: The arrest of bleeding by repair of vessel wall and maintaining a balance between coagulation and fibrinolysis.
• Hemostatic Events: Tissue injury, vasoconstriction, platelet activation (adhesion and aggregation), coagulation (thrombin generation and fibrin polymerization), fibrinolysis (blood clot dissolution), and restoration of vascular patency.
• Platelet Production, Structure, & Function: Platelets are anucleated blood cells that arise from megakaryocytes in the bone marrow and play a role in primary hemostasis.
• Secondary hemostasis involves enzymatic activation of the coagulation proteins to produce fibrin from fibrinogen.
• The intrinsic pathway of hemostasis is triggered by contact with collagen or glass.
• Erythropoietin (EPO) is produced in the kidney.
• Primary hemostasis refers to the response to vascular injury that produces a platelet plug at the site of damage.
• The extrinsic pathway of hemostasis is initiated by the release of tissue thromboplastin and calcium from damaged tissue.
• Thrombopoietin (TPO) is produced in the liver.
• The common pathway of hemostasis leads to clot formation including the platelet plug and fibrin production.
• Megakaryocytopoiesis: The process of platelet production involving stages such as megakaryoblast, promegakaryocyte, granular megakaryocyte, and mature megakaryocyte.
• IL-3, IL-6, and IL-11 are cytokines that stimulate megakaryocyte differentiation and maturation
• MK I: Size - 14-18um, N:C Ratio - 3:1, Cytoplasm - Basophilic, a-granules and δ-granules present, DMS present
• MK III: Size - 30-50um, N:C Ratio - 1:4, Cytoplasm - Eosinophilic and Granular, a-granules and δ-granules present, DMS present
• The categories of haemostasis include primary hemostasis (involving the vascular system and platelets) and secondary hemostasis (involving the coagulation system)
• Thrombopoietin (TPO) is a hormone produced in the liver that stimulates megakaryocytopoiesis
• MK II: Size - 15-40um, N:C Ratio - 1:2, Cytoplasm - Basophilic and Granular, a-granules and δ-granules present, DMS present
• The major systems involved in haemostasis are the vascular system, platelets, coagulation system, and fibrinolytic system
• Platelets and the haemostatic mechanism involve interactions between blood vessels, platelets, coagulation proteins, fibrinolysis, and serine protease inhibitors
• Inhibitors of fibrinolysis: Plasminogen Activator Inhibitors (PAl), a2-antiplasmin, a2-macroglobulin.
• Key components: Plasminogen (inactive form), Plasminogen activators, Plasmin, Fibrin, Fibrin Degradation Products (FDP), Inhibitors of plasminogen activators and plasmin.
• Bleeding disorders: Disorders of Hemostasis, Vascular disorders, Platelet disorders, Coagulation disorders, Mixed/Consumption (DIC).
• Fibrinolytic system: A system in the body that gradually dissolves temporary fibrin clots as the blood vessel heals.
• Activators of fibrinolysis: Intrinsic activators (Factor Xlla, Xla, kallikrein), Extrinsic activators (Tissue type plasminogen activator (t-PA), Urokinase type plasminogen activator (u-PA)), Exogenous activators (Streptokinase).
• Tests of Hemostasis: Screening tests (Bleeding Time, Platelet & BV function, Prothrombin Time (extrinsic), aPTT (intrinsic), Thrombin Time (common path - DIC)), Specific tests (Factor assays - hemophilia, Tests of thrombosis - TT, FDP, DDA, Platelet function studies: Adhesion, Aggregation, Release tests), Bone Marrow study.
• Thrombopoietin (TPO) and cytokines influence the differentiation of CFU-GEMM to the megakaryocyte lineage.
• MK I cytoplasm possesses a-granules and a demarcation system (DMS).
• Megakaryocyte progenitors undergo fragmentation to produce platelets.
• Megakaryocyte-specific and platelet-specific immunologic markers include Platelet factor 4 (PF4), von Willebrand factor (vWF), Platelet glycoproteins ib (GPIb, CD42b), and Platelet glycoproteins|kb/Illa (GPIlb/Illa, CD41).
• Terminal megakaryocyte differentiation includes MK I (megakaryoblast), MK II (promegakaryocyte), MK III (megakaryocyte), and MK IV (post-mature).
• MK III is the stage from which platelet shedding, thrombopoiesis, proceeds.
• MK I cannot be distinguished from the myeloblast and pronormoblast but can be identified using immunologic probes for membrane structures.
• MK I possesses most of the ultrastructure associated with MK I and III stages and with platelets.
• MK III is the largest cell in the bone marrow, with an intensely lobulated nucleus and eosinophilic, granular, and platelet-like cytoplasm.
• Each megakaryocyte can produce 500-5000 platelets.
• There are three stages of megakaryocyte lineage-committed progenitors: BFU-Meg, CFU-Meg, and LD-CFU-Meg.
• MK II is easily recognized as megakaryocytic and has an indented or lobulated nucleus.
• Blood is the most important tissue in the body as it transports oxygen, protein, blood cells, and drugs.
• Blood metabolizes through ion exchanges.