Moath Darweesh. Omar Sami. Saleem Khreisha. 1 P a g e

Transcription

1 7 Moath Darweesh Omar Sami Saleem Khreisha 1 P a g e

2 -First of all, I want to give a quick revision to simplify the whole hemostasis mechanism, it will be much easier here with me. Enjoy (you can skip ) hemostasis: To stoop blood bleeding it happens in 4 stages 1) Vasoconstriction.. )سدادة) 2) Formation of temporary platelet plug 3) Formation of blood clot. 4) Dissolve the blood clot by plasmin. 1) Vasoconstriction: by two main mechanisms A) local myogenic spasm : normally, when any blood vessels is injured it's smooth muscle contracts without any stimulus. B) external stimulus found in the plasma : endothelin derived from endothelium), serotonin and Thromboxane A2 ( derived from platelets ), all of these substance are vasoconstrictors. 2) Formation of temporary platelet plug (this mechanism is effective in small injuries) : it takes place in 5 stages: A) Platelet adhesion to the subendothelial surface ( just few platelet ) B) Platelet activation (swelling): to become able to release their content C) Platelet aggregation: more platelets stick to each other & come to the site of injury. D) Platelet fusion. *ADP is important in (B,C,D ) stages *thromboxane A2 is important in C stage. 3) Formation of blood clot: simply, clot is a network of fibrin and blood cells restricted within it. blood clotting is a cascade of reactions involve activation of enzymes by cleavage. By two pathways end in activation of factor 10. factor 10 along with factor 5 activate prothrombin to be become thrombin. 2 P a g e

3 thrombin activates fibrinogen to become active fibrin, which forms the fibrin sealant; thus the clot. Important note: we have two groups of factors (have similar structures and functions) fibrinogen group: factor 5,8 and 13. to memorize ( 5+8=13) prothrombin group : factor 7,9 and 10. we will use these two groups to simplify memorization for many upcoming information. 4) Dissolve blood clot by plasmin : which is the first subject of our lecture today the doctor revised some information from the last lectures, I have written it here alone because it has no relation with our subject. 1) Factor 5 is involved in the intrinsic, extrinsic and common pathway of coagulation. 2) - Factor 8-related Antigen: for Aggregation - Factor 8 (vwf): for Adhesion - Factor 8-c: for Clotting. The main subjects of this sheet 1)FIBRINOLYSIS 2) THROMBOEMBOLIC CONDITIONS 3) CONDITIONS THAT CAUSE EXCESSIVE BLEEDING IN HUMANS FIBRINOLYSIS *The plasma proteins contain a coenzyme called plasminogen (Also found in liver, eosinophil and endothelium), that, when activated, becomes a protein called plasmin. Plasmin digests fibrin fibers and some other protein coagulants such as fibrinogen, Factor V, Factor VIII (fibrinogen group except factor XIII). *there is a balance between coagulation and fibrinolysis, for example, factor XII play role in the intrinsic pathway of coagulation, and play role in the fibrinolysis system by releasing a vasodilator bradykinin. plasminogen activators extrinsic (exogenous ) : 3 P a g e

4 A) Urokinase B) Streptokinase Note : urokinase is discovered in urine, and found in plasma. Streptokinase is produced by streptococcus bacteria. -intrinsic (endogenous): a- Tissue plasminogen activator: produced by endothelial cells. b- Contact phase of coagulation NOTE : Tissue plasminogen activator and streptokinase are lifesaving injection, because they lyse the clot (thrombus) within seconds. *on the other hand, there is a substances that inhibit plasmin Alpha2- antiplasmin. Clot Retraction and Expression of Serum Within a few minutes after a clot is formed, it begins to contract and usually expresses most of the fluid from the clot. The fluid expressed is called serum because all its fibrinogen and most of the other clotting factors have been removed; in this way, serum differs from plasma. Serum cannot clot because it lacks these factors. Two factors which play a vital role in clot retraction: a. Platelets b. Calcium (for actin and myosin contraction ) -plasma doesn't coagulate without Ca++ THROMBOEMBOLIC CONDITIONS * usually clot is dissolved immediately,but Sometimes, unwanted clots are formed in the blood vessels & they don t move forming Thrombus. * This thrombus is either dissolved, or sometimes under the effects of the circulation is pushed & removed from its attachment and circulates in the blood vessels too. this circulating clot is called an Embolus. -Embolus also could be an air bubble. * The embolus can sneak into narrow spaces, & if this embolus reaches 4 P a g e

5 the heart or the brain, this results in a serious condition because the embolus obstructs the blood supply. However, embolism in arteries is more dangerous than veins Two conditions are related to embolism and thrombosis 1) Atherosclerosis: the accumulation of lipids inside the blood vessels, so they become relatively narrow. 2) Arteriosclerosis: losing the flexibility of the arteries, due to aging for example. Cause of Thromboembolic Conditions. 1) Injury to a blood vessel: as may be caused by trauma or infection, the endothelium becomes rough resulting in platelet adhesion then activation and aggregation, in this case both extrinsic and intrinsic pathway are activated, Infections, however, mediate the inflammatory response which could cause injury of endothelium. 2) Blood often clots when it flows very slowly through blood vessels, this usually occur in operation or childbirth, we advise patients to walk in the room to increase the blood flow, otherwise we give them anticoagulants. 3) Also, when blood flow is very slow, the composition of blood changes, high amount of plasma protein like fibrinogen is produced with slow elimination of them from liver (because of slow circulation), this usually occur also in operations, childbirth or any other cause of dehydration. CONDITIONS THAT CAUSE EXCESSIVE BLEEDING IN HUMANS 1. Increased fragility of vessels. 2. Platelet deficiency or dysfunction. 3. Defect of coagulation factors. 4. Excessive fibrinolysis. the most common cause is platelet number deficiency, then coagulation factors defects. 5 P a g e

6 1. Increased fragility of vessels (Vascular disorder) The problem here is either in the blood vessel itself or the connective tissue around it, this disorder is either genetic or acquired, result in minor bleeding, in small blood vessels. Genetic: usually appears mild during childhood and then becomes more numerous (more vessels affected) during adulthood. Acquired (latent): examples: what is Purpura it's a condition that occurs when skin or mucous membrane of such a person displays many small, purplish blotches. That's what Guyton says. "prof Saleem said that purpura is easily bruised blood vessels" I think he means just the senile purpura in this definition: 1. Senile purpura: easily bruised blood vessels because of advancing age. 2. Purpura associated with chronic infection: especially viral infection, due to microbial damage of the vessels. 3. Scurvy: vitamin C deficiency, it causes purpura. 4. Steroid purpura: a result of prolonged steroid therapy 2. Platelet count abnormality Remember: platelets are especially important for repair of minute breaks in capillaries and other small vessels.(responsible for integrity of blood vessels) thrombocytopenia causes easily bruised blood vessels (purpura) characterized by skin and mucous haemorrhage Causes of thrombocytopenia Failure of platelets production due to some toxins, chemicals, or viral infections. depression of bone marrow due to Leukaemia, Aplastic anemia, and megaloblastic anemia. REMEMBER : leukaemia causes thrombocytopenia (affects Platelets) and anemia (affects RBC s). 6 P a g e

7 Increased destruction of platelets because of high concentration of heparin, or a condition called Disseminated Intravascular Coagulation; characterized by excessive clots formation; thus causing a depletion in platelets, which will eventually lead to unhealed bruises Purpura Formation. Sequestration: The spleen normally sequesters little amount of the body s platelets, but this amount can rise when the spleen is enlarged, producing moderate degrees of thrombocytopenia massive blood transfusion: because of the short half-life of WBC s and platelets, we can t donate them frequently, but we can for RBC s. Thrombocytopenic purpura: It is a purpura due to low platelets count, when platelets' count is low, clot retraction is deficient, so there is poor repair of the injured blood vessels. This leads to higher susceptibility to bruising and multiple subcutaneous hemorrhages. 3. Platelets function abnormalities: Thrombocytopathies: characterized by abnormal platelet function and normal platelet count: It's either: Genetic: problem in adhesion ( deficiency of vwf or deficiency in glycoprotein-1 on the platelet ) or defect in production of substances like thromboxane. Acquired: Aspirin therapy; aspirin is an inhibitor of the enzyme cyclooxygenase, which is required for the synthesis of thromboxane A2 and prostaglandins. These mediators play important roles in platelet aggregation and subsequent release reactions. Thrombasthenia purpura; due to defect in platelets function. here, the thrombocyte count is normal. 7 P a g e

8 EXTRA NOTES FOR MORE UNDERSTANDING (YOU CAN SKIP) purpura is called with this name because when bleeding occur, blood firstly is red in color because presence of iron, after minutes the iron is lost from blood, so the color will change to blue or purple so we call it purpura. atherosclerosis distrust the smooth endothelium of vessels,leading to exposure of collagen which causes platelet adhesion and activation of intrinsic pathway, it's mainly caused by eating too much fat, so be carful with eating fat!l because atherosclerosis causes myocardial infarction which kill one person among 3 *DISSEMINATED INTRAVASCULAR COAGULATION: This condition often results from the presence of large amounts of traumatized or dying tissue in the body that releases great quantities of tissue factor into the blood activating clotting mechanism, A peculiar effect of disseminated intravascular coagulation is that the patient on occasion begins to bleed. The reason for this bleeding is that so many of the clotting factors are removed by the widespread clotting that too few procoagulants remain to allow normal hemostasis of the remaining blood. * vitamin C deficiency causes defect in the vessels because vitc is important in the synthesis of collagen which is an important component of any blood vessel steroid purpura: we know that steroid is a catabolism hormone, that decrease protein synthesis. However, With long usage of steroid, collagen synthesis in blood vessel decrease, leading to fragile vessel and bleeding. *leukemia causes thrombocytopenia because the accumulation of neoplastic blasts in the bone marrow suppresses normal hematopoiesis by physical crowding, competition for growth factors, and other poorly understood mechanisms * megaloblastic anemia causes thrombocytopenia Because DNA synthesis is impaired in all proliferating cells in bone marrow. However, the derangement in DNA synthesis causes most precursors to undergo apoptosis in the marrow (an example of ineffective hematopoiesis) and leads to pancytopenia 8 P a g e

9 this was my first sheet, sorry for extra information but I wanted to make the sheet more understood. forgive me for any mistake, and good luck on Saturday 9 P a g e