Hemostasis

A) Primary Hemostasis = weak platelet plug1. Vascular Damage

2. Transient vasoconstriction of damaged vessels(mediated by re exive neuronal stimulation + endothelin releaseEndothelins:

*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 mediatorsa. ADP is released from dense platelet granules: promotes exp[osure of GP2b/3a receptors on plateletsb. TXA2 is synthesized by platelet COX1

(TXA2 promotes PLATELET AGGREGATION)

5. Platelet Aggregationa. 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 Cascade1. Coagulation cascade generates Thrombin

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

3. Coagulation Cascade ActivatorsCoagulation Cascade requires

1. Exposure to activating substancesa. Extrinsic Pathway: exposure to Tissue Thromboplastin activates factor 7ab. Intrinsic Pathway: subendothelial collagen activates factor 12a

2. Phospholipids @ platelet surface3. Calcium derived from platelet dense granules

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

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

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

Hemodynamic Derangements

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DD wk2Hemodynamic DerangementsIntroduction To AtherosclerosisThrombosis And Embolization

FLOW GRADIENT

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

1) Re!exive vasoconstriction: sympathetic2) platelet mediated vasconstriction

Vasoactive substances dense granulesNPE, 5HT ...