Page 314 - Anatomy and Physiology of Farm Animals, 8th Edition

Blood and Other Body Fluids / 299

cascade is the activation of factor XII. This antithrombin III, prevent coagulation
from continuing inappropriately. Protein C
could occur when a vessel is damaged and
VetBooks.ir the underlying tissue is exposed or when circulates in an inactive form that is acti-
vated by thrombin. Thrombin forms as
blood is drawn into an untreated glass
tube. part of both the intrinsic and extrinsic
Coagulation can also be initiated when a pathways and is also responsible for one of
protein from interstitial fluid (tissue factor the final steps in both, the production of
or tissue thromboplastin) forms an active fibrin from fibrinogen (Fig. 15‐4). Thus, as
complex with an inactive plasma protein, formation of thrombin by the coagulation
factor VII (Fig. 15‐4). Tissue thromboplas- pathways promotes clot formation, throm-
tin is a component of cell membranes of bin also restrains the process so that it does
various cell types and apparently may be not become uncontrolled. Antithrombin
released from injured cells. The factor III is also inactive by itself, but when bound
VII–tissue factor complex activates factors to heparin (present on normal endothelial
X and IX. Factor X is a component of the cell membranes), the heparin–antithrom-
intrinsic cascade, so from this point on, the bin III combination inactivates thrombin.
pathway to fibrin formation and linkage is Here again, the presence of intact, healthy
the same as in the intrinsic cascade. The endothelial cells acts to prevent or halt
cascade that is initiated by tissue thrombo- coagulation. Inhibition or inactivation of
plastin is the extrinsic cascade, or extrin­ thrombin is a very efficient means of
sic pathway. The final product of both the inhibiting coagulation in that thrombin
extrinsic and intrinsic cascades is a fibrin has a positive feedback effect on coagula-
clot, and some clotting factors are com- tion by activating several clotting factors
mon to both. The only differences are some that precede it in the cascade.
of the factors found in the early steps of the In many cases, the damage to small
cascades (Fig. 15‐4). vessels can be repaired so that normal
Calcium ions are required as cofactors blood flow can again occur. These repair
at various steps in both cascades (Fig. 15‐4), mechanisms include removal of the clot
and several anticoagulants used to prevent and proliferation of endothelial cells to
blood clotting outside the body do so by re‐establish normal vascular lining. A key
binding calcium ions and making them element in clot removal is the activation
unusable for the clotting factors. These of the fibrinolytic system. This system is
include sodium citrate, potassium citrate, similar to the clotting cascade in that an
ammonium citrate, and ethylene diamine- inactive plasma protein or proenzyme,
tetraacetic acid (EDTA). EDTA is usually plasminogen, is activated to plasmin,
in the form of a sodium or potassium salt. which converts fibrin to soluble fragments.
Clot formation at the site of injury There appear to be several different
reduces blood loss and occludes the open- pathways by which plasminogen can be
ing in the damaged vessel. This tends to activated to plasmin, but these are not as
remove stimuli necessary for continuation well understood as the activation of clotting
of coagulation by covering the exposed factors. However, the presence of fibrin may
collagen and preventing the entry of tissue stimulate several of these pathways. It seems
fluid into the vessel. The undamaged that as fibrin is generated, it also begins
endothelial cells adjacent to the damaged to initiate its own ultimate destruction.
area also secrete prostacyclin, an inhibitor Plasminogen is also activated by tissue
of platelet adhesion and aggregation. If plasminogen activator, an enzyme secreted
coagulation continued unchecked beyond by normal, intact endothelial cells.
the site of injury, blood vessels throughout The majority of the plasma factors for
the body would be occluded inappropri- both the coagulation and fibrinolytic cas-
ately, and blood flow would be halted. Two cades are synthesized in the liver, and this
additional plasma proteins, protein C and synthesis is vitamin K dependent. Vitamin K