Unit Six: Blood Cells, Immunity, and Blood

Coagulation

Chapter 36: Hemostasis and Blood Coagulation

Guyton and Hall, Textbook of Medical Physiology, 12th edition

Events in Hemostasis

• Vascular Constriction

a. Local myogenic spasm-most effectiveb. Local autacoid factorsc. Nervous reflexes-from pain receptors

• Formation of a Platelet Plug

a. Small cut in a vessel; have a pluginstead of the complete clottingmechanism

Events in Hemostasis

• Platelets

a. Fragmented megakaryocytesb. 150,000-300,000c. Do not have nuclei and cannot reproduced. Contain actin and myosin (thrombosthenin)e. Produce ATPf. Release prostaglandinsg. Release endothelial cell growth factorh. Surface glycoproteins for adherence to damaged

vesselsi. Half-live of 8-12 days

Events in Hemostasis

• Mechanism of the Platelet Plug

a. Platelets swell; irregular shape with pseudopodsb. Become sticky and adhere to collagenc. Thromboxane A2 and ADP enhance adherenced. Damaged wall activates increasing numbers of

plateletse. Important in closing small tears or ruptures in very

small vessels

Blood Coagulation

• Basic Theory

a. Depends on the activation of 50 or more possibleblood procoagulants

b. Formation of prothrombin activatorc. Conversion of prothrombin to thrombind. Conversion of fibrinogen to fibrin

Fig. 36.2

Blood Coagulation

• Conversion of Prothrombin to Thrombin

a. Prothrombin activator is formed as a result ofdamage to a blood vessel

b. In the presence of Ca++ causes the conversionof prothrombin to thrombin

c. Thrombin causes the polymerization of fibrinogen molecules into fibrin fibers

d. Prothrombin attaches to receptors on plateletse. Prothrombin is a plasma protein formed

continually by the liverf. Vitamin K is required for the production of

prothrombin

Blood Coagulation

• Conversion of Fibrinogen into Fibrin

a. Fibrinogen is produced by the liverb. In the early stages of polymerization, the molecules

are held together by hydrogen bondsc. Fibrin-stabilizing factor is released by platelets;

acts as an enzyme to form covalent bonding andmultiple cross-linkages

Blood Coagulation

• Blood Clot

a. Meshwork of fibrin fibers running in all directionsand entrapping blood cells, platelets, and plasma

b. Within a few minutes the clot contracts and expresses fluid (serum)

c. Platelets contribute directly by activation thrombosthenin and myosin (contractile proteins)

• Positive Feedback of Clot Formation

Blood Coagulation

• Initiation of Coagulation

a. Trauma to the vascular wall and adjacent tissues

b. Trauma to the blood

c. Contact of the blood with damaged endothelialcells or collagen and other tissue elements

d. All lead to the formation of prothrombin activator

Blood Coagulation

• Extrinsic Pathway

a. Release of tissue factor

b. Activation of Factor X-role of Factor VII and tissuefactor

c. Effect of Xa to form prothrombin activator-role ofFactor V in the presence of calcium to split prothrombin to thrombin

Fig. 36.3 Extrinsic pathway for initiating blood clotting

Blood Coagulation

• Intrinsic Pathway

a. Blood trauma causes activation Factor XII andrelease of platelet phospholipids

b. Activation of Factor XI

c. Activation of Factor IX by activated XI

d. Activation of Factor X-role of Factor VIII

e. Action of activated Factor X to form prothrombinactivator-role of Factor V

Fig. 36.4 Intrinsic pathway for initiating blood clotting

Blood Coagulation

• Role of Calcium in Extrinsic and Intrinsic Pathways

a. Except for the first two steps in the intrinsicpathway, calcium ions are required for promotionor acceleration of all blood clotting reactions

b. Normally, calcium levels do not fall low enough toaffect blood clotting mechanisms

Blood Coagulation

• Interaction Between Extrinsic and Intrinsic Pathways

a. Clotting occurs by both pathways simultaneously

b. Extrinsic pathway is more explosive and faster (as little as 15 seconds)

c. Intrinsic is slower requiring 1-6 minutes

Blood Coagulation

• Intravascular Anticoagulants- prevention of bloodclotting in the normal vascular system

a. Endothelial surface factors-smoothness, glycocalyx,thrombomodulin (binds thrombin), protein C (inhibitsFactors V and VIII

b. Antithrombin action of fibrin and antithrombin III

c. Heparin-released by basophils and mast cells

d. Plasmin-digests fibrin fibers and other clotting factors(from plasminogen-serum protein trapped in clot)

Excessive Bleeding

• Decreased Prothrombin, Factors VII, IX, and X CausedBy Vitamin K Deficiency

• Hemophilia

• Thrombocytopenia