Blood 3: Platelets, Hemostasis, and Immunity PDF

Blood 3 “Platelets, Hemostasis, and Immunity” Presented by: Dr. Yasmine Gamal Sabry Lecturer in the physiology department, Ain Shams university Faculty of Physiotherapy 1  Intended Learning Outcomes By the end of this lecture, the student shoul...

Blood 3 “Platelets, Hemostasis, and Immunity” Presented by: Dr. Yasmine Gamal Sabry Lecturer in the physiology department, Ain Shams university Faculty of Physiotherapy 1  Intended Learning Outcomes By the end of this lecture, the student should be able to: 1. Understand the importance of platelets and their role in hemostasis 2. Describe mechanisms for hemostasis 3. Describe the anticlotting mechanisms 4. Mention general functions of white blood cells Faculty of physiotherapy 2  Platelets ▪ The platelets are small granulated non-nucleated bodies, 2 – 4 m in diameter. ▪ The normal platelet count is 300.000 / L (mm3) [Range is 200.000 – 500.000]. Life span: platelets remain functional for an average of 10 days. Origin of Platelets: The bone marrow contains giant cells, the megakaryocytes, which form platelets by pinching of bits of cytoplasm, and extrude them into the circulation. Faculty of physiotherapy 3 ❖ Platelets are responsible for HEMOSTASIS by stimulating:- 1- Vasoconstriction of the injured blood vessel → to minimize the amount of blood loss. 2- Formation of temporary platelet plug. This occurs in two steps: A. platelet adhesion. B. platelet aggregation. 3- Blood clotting → due to activation of clotting factors to form fibrin threads. 4- Release of growth factors → that help healing of the blood vessel. Faculty of Physiotherapy 4  Hemostasis Platelets have a major role in natural Hemostasis (the spontaneous prevention of blood loss). It is effective in stopping bleeding from small vessels. STEPS 2- Platelet plug 3- Fibrin clot 4- Healing of 1-Vasoconstriction formation formation blood vessel Faculty of Physiotherapy 5  1-Vasoconstriction Contraction of the injured vessel slows the flow of blood causing decreased blood loss. It is due to: i. Nervous reflexes: induced by pain impulses ii. Local myogenic spasm iii.Chemicals released by endothelial cells and platelets e.g. thromboxane A2 & serotonin. Faculty of Physiotherapy 6  2- Platelet plug formation This occurs through: platelet adhesion, platelet activation and platelet aggregation as follows: 1. Damage (injury) of blood vessel causes exposure of the underlying collagen. 2. The platelets adhere to the collagen (platelet adhesion) 3. Binding of platelets to the collagen causes platelet activation. 4. The activated platelets change their characteristics and become sticky, and start to aggregate (platelet aggregation) 5. The plug is very effective in preventing blood loss in a small vessel. Because, it physically seals the break in the vessel. Faculty of Physiotherapy 7  3- Fibrin clot formation It is the transformation of blood into a solid gel termed a clot or thrombus. ▪ It occurs around the original platelet plug. ▪ In response to rupture of the vessels, a complex cascade of chemical reactions occurs in the blood involving many blood coagulation factors (clotting factors). Faculty of Physiotherapy 8  3- Fibrin clot formation The clotting factors are enzymes which activate each other. ▪ The net result is formation of a complex of activated substances called prothrombin activators that catalyze the conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin. Faculty of Physiotherapy 9 Faculty of Physiotherapy 10 ❖ Functions of thrombin: 1.Causes conversion of fibrinogen to fibrin. 2.Acts in a positive feedback to facilitate its own formation through the activation of factors VIII & V. 3.Enhances platelet aggregation, which is essential to clotting process. 4.Activates factor XIII to stabilize the resulting fibrin meshwork. 5. Activates plasminogen to plasmin (anticlotting). Faculty of Physiotherapy 11 It is a fat soluble vitamin, requires bile for its absorption from the small intestine. Sources of vitamin K in the human body: ❖Intestinal bacteria flora continually synthesize vitamin K. ❖Diet. Importance of Vitamin K: It is necessary for the liver formation of prothrombin, factor VII, IX and X. In the absence of vitamin K subsequent deficiency of these factors from blood leads to bleeding tendency. Faculty of Physiotherapy 12  Natural Anti-Clotting Mechanisms These are limiting mechanisms that tend to prevent clotting inside blood vessels and to breakdown any clots that do form. Mechanisms: 1. Rapid flow of blood facilitates the removal of activated clotting factors by the circulating blood and their inactivation by the liver. 2. Intact smooth endothelium prevents contact activation of the intrinsic clotting system & platelets. 3. Layer of glycocalyx on endothelium: It repels clotting factors & platelets Faculty of Physiotherapy 13  Natural Anti-Clotting Mechanisms 4. Anticoagulant proteins: protein C and protein S. ▪ Inactivates factors VIII, V. ▪ Increases the formation of plasmin 5. Thrombomodulin - Is a protein present in the endothelium and binds thrombin to prevent clot formation. Thrombomodulin-thrombin complex activates protein C. 6. Anti-thrombin III (heparin cofactor I): - It causes inactivation of factors IX, X, XI, XII. Its action is facilitated by heparin. Faculty of Physiotherapy 14  The Fibrinolytic System A fibrin clot is a transitory device until permanent repair of the vessel occurs. The fibrinolytic system is the mechanism for: ▪ Clot removal. ▪ Restriction of clotting to a limited area, thereby preventing excessive intravascular coagulation. Faculty of Physiotherapy 15 The fibrinolytic system Causes activation of Faculty of Physiotherapy 16  The Fibrinolytic System Mechanism: ▪ Plasminogen is produced by the liver. ▪ Plasminogen is converted to plasmin (fibrinolysin) by : ▪ Thrombin. ▪ Tissue plasminogen activator (t-PA), which is released very slowly from damaged tissues and vascular endothelium. ▪ Urokinase plasminogen activator (u-PA). ▪ Plasmin is a proteolytic enzyme that digests: Fibrin fibers changing it into fibrin degradation product (FDP) or fibrin split product (FSP). Faculty of Physiotherapy 17 Faculty of Physiotherapy 18  Abnormalities in Hemostasis Bleeding diseases Intravascular thrombosis Increased tendency to bleeding Abnormal formation of after trauma or spontaneously. clot inside the blood vessel is called Defect in Defect in thrombus platelet number clotting factors Defect in blood (50.000/µL) or like Liver like in vessels like Vit function disease, vit K Atherosclerosis C deficiency (purpura, deficiency Aspirin) hemophilia 19  White Blood Cells They are the mobile units of the body's defense system. They defend against foreign invasion in 2 different ways: 1-Humoral response by secreting molecules that can eliminate the foreigner. 2-Cellular response by engulfing or killing the foreigner immune cells Their defensive role includes destruction of cancer cells that arise within the body. Some of them also function as cleaners that remove the body's debris resulting from injured cells. 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