Lecture in normal Physiology for the second year students

The coagulation of blood, or its transformation from a fluid into a jelly-like clot, is a biologically important defense reaction of the organism against loss of blood. A blood clot, or thrombus, forms inside blood vessel at the site of injury, and acts as a plug, sealing the vessel and stopping further bleeding. Human blood escaping from the blood vessels begins to coagulate in 3 or 4 minutes and solidifies completely into a gelatinous mass within 5-6 minutes.

Arrest of bleeding or stoppage of bleeding is called hemostasis. When a blood vessel is injured, number of physiological mechanisms are activated that promote hemostasis, or the cessation of bleeding (hemo = blood; stasis = standing). Breakage of the endothelial lining of a vessel exposes collagen proteins from the subendothelial connective tissue to the blood. This initiates three separate, but overlapping, hemostatic mechanisms: (1) vasoconstriction, (2) the formation of a platelet plug, and (3) the production of a web of fibrin proteins that penetrates and surrounds the platelet plug.

Platelet plug formation Platelets Platelet factors Blood coagulation Coagulation factors

Adhesion (adherence) Aggregation (loose plug) Stable aggregation (unyielding plug) Plug retraction Vasoconstriction

Damage to the endothelium exposes subendothelial tissue to the blood. Platelets are able to stick to exposed collagen proteins that have become coated with a protein (von Willebrand factor) secreted by endothelial cells. When platelets stick to collagen, they degranulate as the secretory granules release their products. Serotonin, thromboxane A2 stimulate vasoconstriction, which helps to decrease blood flow to the injured vessel. Phospholipids that are exposed on the platelet membrane participate in the activation of clotting factors. The release of ADP and thromboxane A2 from platelets that are stuck to exposed collagen makes other platelets sticky, so that they adhere to those stuck to the collagen. The second layer of platelets, in turn, undergoes a platelet release reaction, and the ADP and thromboxane A2 that are secreted cause additional platelets to aggregate at the site of injury. This produces a platelet plug in the damaged vessel, which is strengthened by the activation of plasma clotting factors.

There are two reaction pathways to coagulation. One of them, the extrinsic mechanism, is initiated by clotting factors released by the damaged blood vessel and perivascular tissues. The word extrinsic refers to the fact that these factors come from sources other than the blood itself. Blood may also clot, however, without these tissue factors for example, when platelets adhere to a fatty plaque of atherosclerosis or to a test tube. The reaction pathway in this case is called the intrinsic mechanism because it uses only clotting factors found in the blood itself. In most cases of bleeding, both the extrinsic and intrinsic mechanisms work simultaneously to contribute to hemostasis.

LYSIS OF BLOOD CLOT The lysis of blood clot inside the blood vessel is called fibrinolysis. This occurs by a substance known as plasmin or fibrinolysin. Plasmin is formed from the plasminogen, which is incorporated with other proteins in the blood clot. During injury, the blood leaks into the tissues and clots. Sometimes, the blood clots inside minute blood vessels and causes occlusion of blood flow. Few days after the formation of blood clot, some sub­ stances are released from the damaged tissues and damaged endothelium. These substances are lysosomal enzymes and tissue plasminogen activator (TPA). These substances along with thrombin convert the plasminogen into plasmin.

Smooth endothelial surface Glycocalyx layer causing charge Normal velocity of blood flow Anticoagulants (antithromboplastins, antithrombins, heparin, peptone) Continuous fibrinolysis

Intravenous administration of blood to help replenish excess blood loss is known as blood transfusion. It is very effective therapeutic tool when judiciously applied. It is sometimes necessary to inject a large quantity of blood, taken from a healthy person (donor), directly into the vein of the patient (recipient). If the bloods are not compatible hemolysis of the donors RBCs will take place, leading to disastrous effects to the recipient. For this reason before providing blood transfusion compatibility between the donors and recipients blood must be carefully tested.

Another group of antigens found on the red blood cells of most people is the Rh factor. There are different antigens in this group, but antigen D is the most active and indicated as RhD. If this Rh antigen is present on a persons red blood cells, the person is Rh positive; if it is absent, the person is Rh negative. The Rh factor is of particular significancein blood transfusion and when Rh-negative mothers give birth to Rh-positive babies. Since the fetal and maternal blood are normally kept separate across the placenta the Rh-negative mother is not usually exposed to the Rh antigen of the fetus during the pregnancy. At the time of birth, however, a variable degree of exposure may occur, and the mothers immune system may become sensitized and produce antibodies against the Rh antigen.