Blood Physiology 3 PDF

Lecture 9: Physiology of Blood 3 Prepared by: Dr. Marianne Basta Lecturer of Physiology, faculty of Medicine, Alexandria university  BLOOD PLATELETS (THROMBOCYTES) They are small round or oval discs. They are formed in the bone marrow from cell called megakaryocyte...

Lecture 9: Physiology of Blood 3 Prepared by: Dr. Marianne Basta Lecturer of Physiology, faculty of Medicine, Alexandria university  BLOOD PLATELETS (THROMBOCYTES) They are small round or oval discs. They are formed in the bone marrow from cell called megakaryocytes, which are extremely large cells that fragment into platelets. They have no nuclei and cannot reproduce.  Life span: about 8 days in Count: The normal the blood. They are platelet count ranges removed from the from 250,000-500,000 circulation by the tissue cell/cmm. macrophage system. Fu n c t ion s of platelets The platelet cytoplasm contains 1 - Contractile proteins: actin and myosin, that cause platelets to contract, facilitating clot retraction. 2- Granules: secreted in response to platelet activation, including serotonin and ADP. 3-Clotting factors and platelet-derived growth factor (PDGF), which stimulates wound healing. 4 - Mitochondria and enzymes synthesize ADP and ATP. Haemostasis and Blood Coagulation Haemostasis means prevention of blood loss or stoppage of bleeding. When a vessel is ruptured or cut, a series of reactions occur to stop bleeding from the cut ends.  Haemostasis Hemostasis means prevention of blood loss or stoppage of bleeding. Stages of Haemostasis Vascular spasm Formation of Platelet Plug Formation of blood clot Clot retraction Immunology and blood module 1)Local Vascular spasm: Immediately after a blood vessel is cut, the stimulus of the traumatized vessel causes the wall of the blood vessel to contract to reduce blood flow from the ruptured vessel. The contraction results from; - Nervous reflexes initiated by pain, - Local myogenic contraction of the blood vessel - Factors from the traumatized tissues and blood platelets. The blood platelets are responsible for much of the vasoconstriction by releasing the vasoconstrictor substances, thromboxane A and serotonin. This local vascular spasm can last for many minutes or even hours during which the processes of platelet plugging, and blood coagulation can take place. II- Platelet plug formation Mechanism: Platelet adherence Platelet activation Platelet aggregation 10 Immunology and blood module 11 Immunology and blood module 12 Immunology and blood module 13  When vascular wall is damaged, the endothelium is removed, and the underlying layers of collagen Platelet fibers are exposed. When the platelets come in contact with collagens adhesion fibers, they change their shape within a few seconds after damage. Platelets in contact with the collagen fibers undergo and release immediately series of morphological and biochemical changes. reaction They become sticky so that they stick to the collagen fibers and secrete large amounts of ADP and thromboxane A, serotonin, lysosomal enzyme, platelets factors and other factors.  The ADP and the thromboxane A in turn act on nearby platelets to activate them causing them to adhere to the originally activated platelets and so on until the platelet plug is Platelet formed. This platelet plug is usually successful in aggregation stopping the blood loss completely if the vascular opening is small, but if there is a large hole, a blood clot in addition to the platelet plug is required.  The clot begins to develop few minutes after the trauma to the vascular wall. It is due to formation of network of insoluble fibrin threads with blood cells in its meshes. Blood clot formation Activated substances both from the traumatized vascular wall and from platelets (platelet factors) and blood proteins (coagulation factors) adhering to the traumatized vascular wall initiate the clotting process.  It is the mechanism which blood forms clot. In the blood some substances formed promoting coagulation Blood called procoagulant, other inhibit coagulation called anticoagulant. Coagulation Normally the anticoagulant predominates, and blood does not coagulate, but when the vessels are ruptured or damaged, the activity of procoagulant in damaged areas become greater than the other anticoagulant so clot develop.  Blood clotting take place in three essential steps: 1.Formation of a complex substance called prothrombin activator in response to injury of the blood vessel. 2.The prothrombin activator catalyzes the conversion of prothrombin into thrombin. 3.The thrombin acts as an enzyme to convert fibrinogen into fibrin threads that form the clot itself. Prothrombin activator is formed in by two basic ways, a) The extrinsic pathway that begins with trauma to the vascular wall and surrounding tissues or tissue outside the blood vessels. b) Intrinsic pathway that begins in the blood itself. Extrinsic Intrinsic Role of Vitamin K in blood clotting: Vitamin K is a complex required for synthesis of four of the most important clotting factor by the liver, they are: - Factor II prothrombin. - Factor VII. - Factor IX. - Factor X. Deficiency of vit K leads to deficiency of the previous coagulation factor, which leads to serious bleeding tendency.  They become attached to the fibrin threads in a way Platelets that they bind different threads together. are Platelets entrapped in the clot secrete some of fibrin stabilizing factor (factor XIII), which causes more necessary cross-linking bonds between the fibrin threads. for clot Inside the platelets there is contractile proteins which retraction activated by thrombin and calcium ions, It causes strong contraction of the platelets attached to the to occur: fibrin. When the clot retracts, the edges of the broken blood vessels are pulled together. Course of the clot: Once a blood clot is formed, it can follow two separate courses: 1. It may be invaded by fibroblasts which subsequently form connective tissue. 2. It may be dissolved (lysis). Lysis of blood clot: It is a system in the body responsible for lysis of fibrins, which is formed inside the vessels and allows reopening of vessels. Lysis of the clot occurs by: - The plasma protein called plasminogen (profibrinolysin) which, when activated, it is converted to plasmin (fibrinolysin). - Plasmin is a proteolytic enzyme it digest the fibrin threads and other substances in the clot. - The plasmin can cause complete lysis (dissolving) of the clot. o plasminogen (profibrinolysin) convert to plasmin (fibrinolysin) by Plasminogen activators. Plasminogen activators are factors from injured vascular endothelium and damaged tissues. Fibrin degradation products  Rapid flow of blood through the vessels preventing Normally sticking and disintegration of blood platelets. coagulation Presence of healthy living endothelium of blood vessels. of the blood Presence of clotting factors in inactive form. inside the body does Removal of some activated clotting factor from not occur circulation by the liver. due to: Presence of anti-thrombin III factor in the plasma. Presence of heparin in small amount.  Shedding of the endothelium of blood Intravascular vessels, e.g., in atherosclerosis or thrombosis is injury to a blood vessel by trauma. promoted by: When blood flow becomes slow, e.g. prolonged lying in bed. Increase in blood viscosity and increase in the number of blood platelets, e.g., after operations.  The most important factor preventing clotting in normal vascular system is the smoothness of the endothelium, which prevents contact of clotting Anticoagulants factor. Any roughed endothelial surface of the blood vessels initiate clotting reaction. Anticoagulants are effective in interrupting the coagulation cascade. Types of anticoagulants: In vitro anticoagulants: (Outside the body) In vivo anticoagulants: “Inside the body” In vitro anticoagulants: (Outside the body) Oxalate compounds: cause precipitation of calcium oxalate so decreases the Ca++ levels so much that blood clotting is blocked. Oxalate is toxic to the body and is not added to blood for transfusion. Citrate compounds: combines with Ca++ in the blood to form a calcium citrate compound. Citrate as anticoagulants are not toxic, thus can be added to blood used for transfusion (Blood Bank). Collection of blood in siliconized containers, Heparin: Can be used for preventing blood clotting outside the body as well as inside the body. In vivo anticoagulants: “Inside the body”: They are indicated in the treatment of many cases including thrombo-embolic disease and valvular heart diseases. 1) Heparin: 2) Coumarin compounds: “Oral anticoagulants”: 1) Heparin: It is a naturally occurring anticoagulant and it is used very widely in medical practice. Heparin is a polysaccharide produced by the mast cells, which are extremely abundant in the connective tissues surrounding the capillaries of the lung and the liver. It can be administrated intravenous or subcutaneous.  Mechanism of action: 1. It acts by increasing the activity of anti-thrombin III, anti-thrombin III blocks the effect of thrombin on fibrinogen by removing thrombin. Heparin combines with anti-thrombin III forming complex called anti-thrombin-heparin co-factor which: - Is very highly effective in removing thrombus. - Remove other activated coagulation factors. 2. It stimulates fibrinolysis: When gives I.V. Its anticoagulant action starts immediately. 2) Coumarin compounds: “Oral anticoagulants”: Coumarin derivatives such as dicumarol and warfarin are also effective anticoagulants. Action of Coumarin compounds: They act as an anti- vitamin K i.e. competitive inhibition of vitamin k, which catalyzes the liver formation of coagulation factors ll, VII, IX and X. These drugs are given orally and their anticoagulant action starts after about 2 days as the prothrombin and other factors already present in the plasma must be consumed first Hemorrhagic disorders Excessive bleeding can result from deficiency of any one of the many different blood coagulation factors and blood platelets. Three types of bleeding tendencies will be discussed: Vitamin k deficiency Vitamin k is necessary for promotion of formation of four of the most important clotting factors: factor II, factor VII, IX and X by the liver. In the absences of vitamin k, insufficiency of these coagulation factors can lead to a serious bleeding tendency. Vitamin k deficiency occurs because of poor absorption of fats from the gastrointestinal tract because it is a fat-soluble vitamin. One of the most prevalent vitamin k deficiency is failure of the liver to secrete bile; either due to obstruction of the bile duct (obstructive jaundice) or liver disease (hepatitis C or B). Lack of bile prevents adequate digestion and absorption of fats, therefore, inhibits vitamin k absorption as well. Hemophilia It is a bleeding tendency in which the clotting time is very much prolonged (the normal clotting time is 6-10 minutes) and it occurs almost exclusively in males. It is a hereditary disease. Types of hemophilia: 1-Haemophilia A or classic hemophilia: It is due to deficiency of factor VIII (anti hemophilic globulin) 2-Haemophilia B:It is due to deficiency of factor IX Manifestations of hemophilia; The bleeding tendency in hemophilia can have serious degree of severity. A mild trauma can cause severe and prolonged bleeding for several hours. A bleeding after tooth extraction can last for weeks. The patient may suffer from hemorrhages into joints. Thrombocytopenic purpura Thrombocytopenic purpura is due to an autoimmune reaction. Specific antibodies are destroying the normal own platelets leading to decrease the platelet count below 50,000 cell/cmm. The bleeding time is very much prolonged. Manifestations: The bleeding is usually from many small capillaries. Platelets are especially important for repair of minute breaks of capillaries and other small vessels. As a result, small punctuate hemorrhages occur throughout all the body tissues. The skin of this person has many small purplish blotches THANK YOU