HEMA 312 Hematology 2 PDF

HEMA 312 - HEMATOLOGY 2 LECTURE | PRELIMS | BSMLS - 3RD YEAR | RGV & AYC Principle of Coagulation -​ Red: endoth...

HEMA 312 - HEMATOLOGY 2 LECTURE | PRELIMS | BSMLS - 3RD YEAR | RGV & AYC Principle of Coagulation -​ Red: endothelium(blood vessel)(endothelial cells(EC)) ★​Coagulation is a critical component of hemostasis, the process -​ Yellow: Platelets that prevents excessive bleeding when blood vessels are injured. -​ Adhesion = GPIb + von Willebrand Factor(vWF) ​ It involves a complex cascade of events leading to the formation of -​ Platelet to non-platelet a stable blood clot -​ Receptors are responsible for the attachment to EC ​ Hemostasis is the physiological process that stops bleeding at -​ Aggregation = GPIIb/GPIIa + Fibrinogen the site of vascular injury while maintaining blood flow within the -​ Platelet to platelet vascular system. ​ It is a dynamic and tightly regulated mechanism that involves the 3. Coagulation Enzymes Activation interplay of vascular, cellular, and molecular components. What does “a” mean? ​ Factor VII a - Stable factor(FVII) activated by tissue factor ​ Factor IX a - Christmas factor na activated HEMOSTASIS ​ Factor X a - Stuart-Prower factor na activated ​ Involves the interaction of -​ Where extrinsic and intrinsic pathways meet 1.​ Vasoconstriction, ​ Factor II a - Thrombin(FIIa) 2.​ Platelet adhesion and aggregation and -​Inactivated form Prothrombin(FII) 3.​ Coagulation enzymes activation -​Thrombin activates fibrinogen to fibrin -​Also activates FXIII to FXIIIa 1. Vasoconstriction ​ Factor XI a - ​ Vasoconstriction is the narrowing of blood vessels caused by ​ Factor XIII a - Fibrin stabilizing factor contraction of the smooth muscle in the vessel walls. Therefore -​ Stabilizes fibrin clot slowing down the blood flow ​ Plasmin - a protein responsible for the dissolution of fibrin during ​ Reflexive response to a injury fibrinolysis ​ It plays a critical role in the hemostatic process, especially during vascular injury, by minimizing blood loss and facilitating the next HEMOSTASIS steps of hemostasis. ​ A complex process that: ​ Produces a clot to stop the bleeding 1.​ Reducing Blood loss -​ Primary Hemostasis → Platelet Plug to stop the bleeding temporarily ​ Keeps the clot confined through the help of coagulation factors + calcium (ionized) to stabilize the platelet plug -​ Secondary Hemostasis → Fibrin Stable Clot (thrombus) -​Thrombus composed of: -​ Fibrin -​ Platelet -​ flow of blood will slow down = slow down bleeding -​ WBC -​ RBC 2.​ Facilitating Platelet Adhesion ​ Dissolves the clot as the wound heals -​ In the process of fibrinolysis -​ Dissolution of fibrin The Key Cellular Elements of Hemostasis ​ Vascular intima ​ Extravascular tissue factor (TF)(factor III) ​ Platelets ​ Blood Coagulation Factors 3.​ Enhancing the Coagulation Cascade(pathways) ​ Fibrinolytic proteins Vascular Intima in Hemostasis ​ Blood vessels, or the vasculature, carry blood throughout the body. ​ A blood vessel is structured into three layers: an 1.​Vascular intima (Inner layer) -​ Platelet→adhesion→aggregation, secretion→clot -​ Thinest layer -​ Where stable fibrin clot is found -​ Composed of Endothelium -​ Secondary Hemostasis because of the presence of fibrin and collagen fibers -​ Fibrin is the activated form of fibrinogen 2.​Vascular media (Middle layer) -​ Eventually will be removed via fibrinolysis -​ Tunica media -​ Composed of Smooth muscles and elastic fibers 2. Platelet Adhesion and Aggregation 3.​Vascular adventitia (Outer layer) -​ Strongest layer -​ Collagen and elastic fibers Roles of Endothelial Cells ​ Immune response: Leukocyte Recruitment, Cytokine Production, Antigen Presentation -​ Barrier to prevent transmigration of cells ​ Vascular permeability: Barrier Function, Increased permeability in Inflammation, Dysregulation in Disease -​ Characterize the capacity of the vessel to allow the blood to flow ​ Proliferation: Angiogenesis, Vascular remodeling, Role in cancer and cell renewal. -​ Maintains the survival and the self renewal of hematopoietic stem cells.  ​ Hemostasis: Anticoagulant properties, Procoagulant role, Regulation of Fibrinolysis Extravascular Component ​ The extra-vascular (tissues surrounding blood vessels) involved in hemostasis when local vessel is injured, through swelling and inflammation -​ Swelling and inflammation is part of the hemostasis -​ It will inflame because it is the body’s response to injury -​ Will it limit the blood loss? Yes. ​ It plays a part in hemostasis by providing back-pressure on the injured vessel through swelling and trapping of escaped blood. Role of Coagulation in Hemostasis -​ Does inflammation attract platelets? Yes!!!!! ​ Coagulation: Is the process whereby on vessel injury, Plasma protein, Tissue factors and Calcium interact on the surface of the Hemostatic Mechanisms Involving Extra-Vascular Tissues: platelets to form a Fibrin clot. ​ Physical Support -​ Without ionized calcium there will be no activation of -​ Vessels are surrounded by inflamed tissue and will be coagulation factors = bleeding compressed, therefore reduce blood flow. ​ Platelets provide a surface for the coagulation reaction, and ​ Chemical Signals interact with fibrin to form a stable platelet fibrin clot. -​ Will release chemical signals(cytokines and Tissue factor) -​ Platelet membrane has receptors that interact with fibrin to ​ Barrier Function form clot because activated na ang factors -​ Minimizes further bleeding and help in the formation of clot Normal blood flow in intact vessels. Platelets Normal ECM suppresses ​ The platelets and plasma proteins that circulate within the blood hemostasis: vessels. ​ Prostacyclin - secreted by ​ These components are involved in Coagulation (clot or thrombus endothelial cells that inhibits formation) or Fibrinolysis (clot or thrombus dissolution). platelets -​ In the concept of normal coagulation, Hypocoagulation and ​ Heparan sulfate Hypercoagulation ​ Tissue factor pathway inhibitor Role of Blood Vessels in Hemostasis ​ Nitric oxide ​ Blood flows through the vascular system to” and from” all parts of ​ Thrombomodulin the body. ​ ​ ​ ​ ​ ​ ​ ​ The vascular system consists of capillaries, arteries, and veins -​ Wbc are close to endothelial cells -​ Arteries - “a”alis sa heart -​ If nagkasugat may bleeding -​ Veins - “v”avalik sa heart -​ Why is blood not clotting if there is no injury? -​ Because of those ECM Capillaries ​ Responsible for micro circulation that links between arterial and Tugon: The major role of the hemostatic system is to maintain a venous circulation. complete balance of the body’s tendency toward clotting and ​ Smallest blood vessel bleeding. ​ Thinnest walled and most numerous of blood vessels compose of basement membrane that is tightly anchored with collagen that Concept of NORMAL COAGULATION offers support for microvascular units. Arteries and Veins ​ Arteries have the thickest wall of the vascular system -​ Oxygenated blood away from the heart to tissues ​ Veins are larger and have more irregular lumen than arteries -​ Deoxygenated blood back to heart from tissue ​ Blood vessels is coated into 3 layers -​ Tunica Intima (composed of???) -​ In this picture they are balanced there no fibrinolysis that will -​ Tunica media lead to bleeding -​ Tunica adventitia -​ Number of platelets are normal therefore, there are no clot that causes thrombosis Arterioles and Venules ​ Smaller blood vessels ​ Arterioles: Microscopic continuation of arteries giving off meta Concept of HYPOCOAGULATION arterioles joining capillaries ​ Venules: microscopic size of veins connecting to capillaries Role of Blood Vessels in Hemostasis ​ Blood normally carried within vessels whose physical capabilities include Contraction(narrowing) and Dilation(widen), which are controlled by the smooth muscle of the vessel media. -​ Contraction = slow blood flow -​ Dilation = increase blood floooow  -​ Poor clot formation = Platelets are below normal range = -​ Excess fibrinolysis - leading to bleeding ​ There are certain conditions associated with excessive bleeding that are referred to as: Hypocoagulable states. ​ Hemophilia A, B, and C or deficiency in one of the plasma coagulation proteins such as factors VIII. ​ Acquired conditions such as DIC, Liver and Kidney diseases. -​ Most of the coagulation factors are synthesized in the liver -​ DIC is a secondary condition - baka may infection or cancer Concept of HYPERCOAGULATION -​ Uncontrolled production of thrombi - too much platelet - lead to thrombosis -​ Hypercoagulable state ​ Other conditions related to uncontrolled thrombosis are called Hyper-coagulable states. ​ This is related to an appropriate formation of thrombi in the vascular vessels that occlude normal blood flow. ​ If the thrombi enlarged eventually it will block the blood vessels resulting to Myocardial Infarction(MI) or Stroke = happy peanuts and starbucks coffee Kaya daw importante ang fibrinolysis para maging normal ang lahat