Download The blood cell wall has three layers: intima, media and adventitia

Normal hemostasis
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Hemostatis is a balance of the physiological processes which on one hand
prevent excessive bleeding after vessel injury, and which on the other hand
maintain a viable circulation by keeping the blood in an uncoagulated state.
These processes are part of a complex system with many feedback loops and
parallel circuits. The purpose of this course is to discuss the (known) physiology of
the human coagulation system, by systematically presenting the individual
components.
Thrombosis
Bleeding
Coagulation
Fibrinolysis
Bleeding
Thrombosis
Hemostasis can be divided into 4 components:
Vessel function - constriction of injured vessels
Platelet function - formation of platelet plugs
Coagulation - formation of fibrin plugs
Fibrinolysis - dissolution of blood clots
To fulfill that:
• Blood must be fluid
• Must coagulate (clot) at appropriate time
– Rapid
– Localized
– Reversible
 The normal haemeostasis depends on a delicate balance and complex
interaction between at least five components:
1. Platelet.
2. Blood vessels.
3. Plasma coagulation proteins.
4+5. Inhibitors and the fibrinolytic system.
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Vascular haemostasis.
 Humans have evolved a complicated hemostatic system that is
designed to maintain blood in a fluid state under physiologic conditions,
but that is primed to react to vascular injury in an explosive manner to
stem blood loss by sealing the defect in the vessel wall.
 The blood cell wall has three layers: intima, media and adventitia.
 The intima consists of the endothelium and subendothelial connective
tissue and is separated from the media by the elastic lamina interna.
 Endothelium cells form a continuous monolayer lining all blood
vessels.
 The function and the structure of these cells are vary
according their location in the vascular tree, but they are all
share three important characteristics:
1. They are "non thrombogenic" that is do not react with plasma or the
cellular elements of the blood.
2. They play an active role in supplying nutrients to the subendothelial
structures.
3. And act as a barrier to macromolecules and particles matter circulating
in the blood stream.
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The intact vessel wall has an important role in preventing haemostasis.
Endothelial cells produce:
 Prostacyclin, which causes vasodilatation and inhibits platelets
aggregation.
 Protein C (PC) activator (Thrombomodulin), which inhibits
coagulation.
 And tissue plasminogen activator (TPA) which activates fibrinolysis.
Endothelial cell function:
 The luminal surface of the endothelial cell is covered by Glycocalyx
coat.
 It contains heparin sulphate and other substances which are capable of
activating antithrombin III, an important inhibitor of coagulation
enzymes.
 Beneath the glycocalyx, there is a trilaminar membrane containing
ADPase, an enzyme which degrades ADP which is a potent platelets
agonist.
 The endothelial cells can also generate angiotensin II, a local
vasoconstrictor.
 Thrombin generated at the site of the injury is rapidly bound to a
specific cofactor of the endothelial cell, Thrombomodulin. When
bound this protein, thrombin can activate the protein C system to
degrade and inhibit factor Va and VIIIa.
 Thrombin can also stimulate the endothelial cells to produce
plasminogen activator.
 Finally, the endothelial cells produces von Willebrand factor (vWF),
essential for platelets adhesion to the subendothelium. vWF is secreted
partly into the circulation and partially towards the subendothelial
matrix.
The subendothelium:
 The subendothelium is consists of connective tissues composed of
collagen, elastic tissues, proteoglycans, fibronectin and vWF.
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 After endothelial damage has taken place, components of
subendothelium are exposed and platelets adhere to various elements
collagen of basement membrane and micofibrils.
 The adhesion of platelets is regulated by specific properties of the
platelet membranes and biochemical characteristics of the
subendothelial structures.
 Other factors, such as plasma concentration of vWF and the
characteristics of the blood flow also effect adhesion.
Vasoconstriction:
 Vessels with muscular coat contract following injury, thus assisting
haemostatic plug formation by reducing the blood flow.
 Vasoconstriction occurs, however, even in the microcirculation in
vessels without smooth muscle cells.
 Endothelial cells can themselves produce vasoconstrictors such as
angiotensin II; in addition, activated platelets produce prostaglandins
(TXA2) with vasoconstricting properties.
 Vasoconstriction occurs after vessel injury. This is mediated by
serotonin and tromboxan A2 released from platelets, and is the
beginning of primary hemostatis which leads to the formation of a
reversible platelet plug within minutes of the injury.
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Investigation of the Disorders of Vascular Haemostasis:
 The disorder in this part may be due to increase permeability, reduction
of vessels strength and failure to contract in injury.
 An accurate history and careful clinical examination are almost always
the keystone of diagnosis.
 Tests of defective vascular function are difficult to perform and
interpret.
 Tests of capillary resistance are of limited value.
 In some cases skin biopsy with specific staining or even biochemical
analysis of the micro-sample may be helpful.
 The bleeding time test is normal and the other tests of haemostasis are
also normal.
Capillary fragility (resistance) test:
This test is used to determine the presence of vascular disorder, a circle 2.5
cm in diameter, the upper edge of which is 4 cm below the crease of the
elbow, is drawn on the inner aspect of the forearm, pressure midway between
the systolic and diastolic blood pressure is applied using sphygmomanometer
above the elbow for 15 minutes, and a count of petechiae within the circle is
made: 10, normal; 10–20, marginal; more than 20, abnormal.
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