2023 LEC 3 HEMOSATSIS AND COAGULATION.pdf

PHYSIOLOGY Hemostasis and Coagulation of Blood What is the difference between homoeostasis and hemostasis  ? Hemostasis: is the arrest or stoppage of bleeding. Homeostasis: is the process by which variablees are regulated so that internal conditions remain stabl...

PHYSIOLOGY Hemostasis and Coagulation of Blood What is the difference between homoeostasis and hemostasis  ? Hemostasis: is the arrest or stoppage of bleeding. Homeostasis: is the process by which variablees are regulated so that internal conditions remain stable and relatively constant. STAGES OF HEMOSTASIS When a blood vessel is injured, the injury initiates a series of reactions resulting in hemostasis. It occurs in three stages: 1. Vasoconstriction Immediately after injury, the blood vessel constricts and decreases the loss of blood from damaged portion. 2. Formation of Platelet Plug The platelets get adhered to the collagen of ruptured blood vessel and secrete ADP and hromboxane A2. 3. Coagulation of Blood During this process, the fibrinogen is converted into fibrin. The fibrin threads get attached to the loose platelet plug, which blocks the ruptured part of blood vessels and prevents further blood loss completely.  \ Figure 8.1 States of hemostasis. PAF = platelet activating factor. BLOOD COAGULATION Coagulation or clotting is defined as the process in which blood loses its fluidity and becomes a jelly like mass few minutes after it is shed out or collected in a container. FACTORS INVOLVED IN BLOOD CLOTTING Coagulation of blood occurs through a series of reactions due to the activation of a group of substances. The substances necessary for clotting are called clotting factors. Thirteen clotting factors are identified: 1. Factor I Fibrinogen 2. Factor II Prothrombin 3. Factor III Thromboplastin (Tissue factor) 4. Factor IV Calcium 5. Factor V Labile factor (Proaccelerin or Accelerator globulin) 6. Factor VI Presence has not been proved 7. Factor VII Stable factor 8. Factor VIII Antihemophilic factor (Antihemophilic globulin) 9. Factor IX Christmas factor 10. Factor X Stuart-Prower factor 11. Factor XI Plasma thromboplastin antecedent 12. Factor XII Hegman factor (Contact factor) 13. Factor XIII Fibrin stabilizing factor (Fibrinase). The clotting factors were named either after the scientists who discovered them or as per the activity except factor IX. Factor IX or Christmas factor was named after the patient in whom it was discovered. SEQUENCE OF CLOTTING MECHANISM ENZYME CASCADE THEORY Most of the clotting factors are proteins in the form of enzymes. Normally, all the factors are present in the form of inactive proenzyme. These proenzymes must be activated into enzymes to enforce clot formation. It is carried out by series of proenzyme-enzyme conversion reactions. The first one of the series is converted into an active enzyme that activates the second one, which activates the third one; this continues till the final active enzyme thrombin is formed. Enzyme cascade theory explains how various reactions involved in the conversion of proenzymes to active enzymes take place in the form of a cascade. Cascade refers to a process that occurs through a series of steps, each step initiating the next, until the final step is reached. Stages of Blood Clotting In general, blood clotting occurs in three stages: 1. Formation of prothrombin activator 2. Conversion of prothrombin into thrombin 3. Conversion of fibrinogen into fibrin. BLOOD CLOT Blood clot is defined as the mesh of fibrin entangling RBCs, WBCs and platelets. CLOT RETRACTION After the formation, the blood clot starts contracting. And after about 30 to 45 minutes, the straw colored serum oozes out of the clot. The process involving the contraction of blood clot and oozing of serum is called clot retraction. The contractile proteins namely, actin, myosin and thrombosthenin in the cytoplasm of platelets are responsible for clot retraction. FIBRINOLYSIS The lysis of blood clot inside the blood vessel is called fibrinolysis. It helps to remove the clot from the lumen of the blood vessel. This process requires a substance called plasmin or fibrinolysin. Plasmin is formed from inactivated glycoprotein called plasminogen. Plasminogen is synthesized in liver and it is incorporated with other proteins in the blood clot. Plasminogen is converted into lasmin by tissue plasminogen activator (t-PA), lysosomal enzymes and thrombin. Plasmin causes lysis of clot by dissolving and digesting the fibrin threads. Significance of Lysis of Clot In vital organs, particularly the heart, the blood clot obstructs the minute blood vessel leading to myocardial infarction. The lysis of blood clot allows reopening of affected blood vessels and prevents the development of infarction. The fibrinolytic enzymes like streptokinase are used for the lysis of blood clot during the treatment in early stages of myocardial infarction. ANTICLOTTING MECHANISM IN THE BODY Under physiological conditions, intravascular clotting does not occur. It is because of the presence of some physicochemical factors in the body. 1. Physical Factors Continuous circulation of blood and Smooth endothelial lining of the blood vessels. 2. Chemical Factors heparin and thrombomodulin ANTICOAGULANTS The substances, which prevent or postpone coagulation of blood, are called anticoagulants. Anticoagulants are of three types: 1. Anticoagulants used to prevent blood clotting inside the body, i.e. in vivo 2. Anticoagulants used to prevent clotting of blood that is collected from the body, i.e. in vitro 3. Anticoagulants used to prevent blood clotting both in vivo and in vitro.  1. HEPARIN Heparin is a naturally produced anticoagulant in the body. Heparin is a conjugated polysaccharide. The commercial heparin is prepared from the liver and other organs of animals. APPLIED PHYSIOLOGY A. BLEEDING DISORDERS Bleeding disorders are the diseases characterized by prolonged bleeding time or clotting time. The bleeding disorders are of three types: 1. Hemophilia Hemophilia is a group of sex linked inherited blood disorders characterized by prolonged clotting time. In this disorder, males are affected and the females are the carriers. Cause for hemophilia Lack of prothrombin activator is the cause for hemophilia. The formation of prothrombin activator is affected due to the deficiency of factor VIII, IX or XI. 2. Purpura It is a disorder characterized by prolonged bleeding time. However, the clotting time is normal. The characteristic feature of this disease is spontaneous bleeding under the skin from ruptured capillaries. It causes small tiny hemorrhagic spots under the skin which are called purpuric spots (purple colored patch like appearance). That is why this disease is called purpura. Types and causes of purpura The purpura is classified into different types depending upon the causes.  1. Thrombocytopenic purpura Thrombocytopenic purpura is due to the deficiency of platelets (thrombocytopenia). In bone marrow disease, platelet production is affected leading to deficiency of platelets. 2. von Willebrand Disease is a deficiency of von Willebrand factor which is a protein secreted by endothelium of damaged blood vessels and platelets. This protein is responsible for adherence of platelets to endothelium of blood vessels during hemostasis after an injury. B.THROMBOSIS Thrombosis or intravascular blood clotting refers to coagulation of blood inside the blood vessels. Normally, blood does not clot in the blood vessel because of some factors which are already explained. But some abnormal conditions can cause thrombosis. Complications of Thrombosis 1. Thrombus During thrombosis, lumen of blood vessels is occluded. The solid mass of platelets, red cells and/or clot, which obstructs the blood vessel, is called thrombus. The thrombus formed due to agglutination of RBC is called agglutinative thrombus. 2. Embolism and embolus Embolism is the process in which the thrombus or part of it is detached and carried in bloodstream and occludes the small blood vessels resulting in arrests of blood flow to any organ or region of the body. Embolus is the thrombus or part of it, which arrests the blood flow. The obstruction of blood flow by embolism is common in lungs (pulmonary embolism), brain (cerebral embolism) or heart (coronary embolism).