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Hemodynamic Derangements
Introduction To Atherosclerosis
Thrombosis And Embolization
Hemodynamic Derangements
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Hemostasis
A) Primary Hemostasis = weak platelet plug
1. Vascular Damage

2. Transient vasoconstriction of damaged vessels

(mediated by re exive neuronal stimulation + endothelin release
Endothelins:
*21-amino acid vasoconstricting peptides produced primarily in the endothelium
*have a key role in vascular homeostasis.
*are among the strongest vasoconstrictors known
*endothelins are implicated in vascular diseases ex: heart, general circulation and brain
3. Platelet Adhesion:
a. vWF binds exposed subendothelial collagen
-vWF @ Weibel-Palade Bodies @ Endothelial Cells
-vWF @ a-Granules of platelets
b. Platelets bind vWF using GPIb Receptor
4. Platelet degranulation: adhesion induces shape change in platelets and degranulation of platelet mediators
a. ADP is released from dense platelet granules: promotes exp[osure of GP2b/3a receptors on platelets
b. TXA2 is synthesized by platelet COX1
(TXA2 promotes PLATELET AGGREGATION)
5. Platelet Aggregation
a. Platelets cross link using GP2b/3a receptors and Fibrinogen from the plasma
6. This platelet plug is weak, the coagulaiton cascade stabilizes it

B) Secondary Hemostasis =stabilized platelet plug, mediated by the Coagulation Cascade

1. Coagulation cascade generates Thrombin

2. Thrombin converts brinogen to brin, stabilizing the platelet plug

#platelet- brin thrombus
3. Coagulation Cascade Activators
Coagulation Cascade requires
1. Exposure to activating substances
a. Extrinsic Pathway: exposure to Tissue Thromboplastin activates factor 7a
b. Intrinsic Pathway: subendothelial collagen activates factor 12a
2. Phospholipids @ platelet surface
3. Calcium derived from platelet dense granules

VASOCONSTRICTION BY VSM
-SLOW BLOOD FLOW
-SLOWS BLOOD LOSS
-MOVES PLATELETS CLOSER TO ENDOTHELIAL SURFACE

3) Hypercoagulative state
Cancer
Pregnancy: hormones (estrogen)
Estrogen therapy: postmenopausal
Estrogen therapy: The PILL --> clotting
Trauma or Surgery of lower extremity
Inflamitory bowel disease
Nephrotic syndrome: urinating antithrombin 3
Sepsis
Inhereted THROMBOPHILLIA

FLOW GRADIENT
1) Reflexive vasoconstriction: sympathetic
2) platelet mediated vasconstriction
Vasoactive substances dense granules
NPE, 5HT ...

VIRCHOWS Triad
(more than one is what causes problems)

2) Vascular wall injury

Trauma or surgery
Venepuncture
Chemical irritation
Heart valve replacment
Athlersclerosis
Indwelling catheters

1) Circulatory Stasis
Varicose Veins
Venous obstruction
(Tumor, Pregnancy-fetus--X IVC)
A-Fib: clots around valve
LV-dysfunction