Cardio L18 Thrombosis Flashcards Preview

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Flashcards in Cardio L18 Thrombosis Deck (56):
1

Thrombosis

Formation of a solid mass from the constituents of the blood within the living circulation.

!!!Distinction from blood clot!!!

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Blood clot

When blood solidifies outside the living circulation the solid and fluid components separate and form blood clots.

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When a thrombus forms

The cellular and serum phases are mixed and form a series of alternating layers of cell poor and cell rich zones.

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Layers of thrombus

Lines of Zahn

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Arterial site thrombus type

Tiny, consisting largely of platelets (Very small dimension)

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Venous site thrombus type

Small and pale; platelet and fibrin rich (Fast local blood flow)

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Capillaries thrombus type

Large and red; Red cell rich (Slow local blood flow)

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Virchow’s triad →

The conditions, which predispose to thrombosis, were first addressed by Virchow in the mid 19th Century.
Changes in the vessel wall
Changes in local blood flow
Changes in co-agulative qualities of the blood

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Changes in the vessel wall

Loss of endothelial integrity (most common: atheroma)

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Changes in local blood flow

Nature of blood flow – laminar vs. turbulent
Disturbance of blood flow allows large numbers of platelets to come into contact with endothelium.

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Changes in co-agulative qualities of the blood

Alteration in coagulability of the blood
Increased platelet numbers:
1. Major injury
2. Surgery
3. Post partum
Increased fibrinogen concentration

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→ Thrombus forms at

sites of endothelial injury.

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Intact endothelium tend to discourage thrombosis by 3

1. Expressing sulphated mucopolysacchardies (heparin and heparin like molecules)
2. Expressing tissue plasminogen activator (TPA)
3. Synthesizing prostacyclin (PGI2)

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The endothelial cell surface is covered by and are potent activators ok

covered by sulphated mucopolysaccharides, which carry a large negative charge.

These molecules are potent activators of circulating antithrombotic enzymes such as anti-thrombin 3.

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Heparin causes

A conformational change in the anti-thrombin molecule which enhances its activity a hundredfold.

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Endothelium expresses

Tissue plasminogen activator (TPA)

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Plasminogen is the

Circulating, inactive, precursor of the enzyme Plasmin which destroys thrombus.

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Endothelial TPA activates

Plasminogen with the result that there is active destruction of thrombus at the endothelial surface.

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Damaged endothelial cells generates

Prostacyclin (PGI2)

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PGI2 function

Dilates vessels
Disaggregates platelets

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Opposition to PGI2

Prostaglangin generated by platelets

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Platelets description

Circulating anuclear fragments of the cytoplasm derived from megakaryocytes (multinucleate bone marrow cells, each of which will generate between 2000 & 4000 platelets).

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Platelets structure

3 microns diameter
Conc – 200-400 x 10 to the 9/L
Approx 10 day life span

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Platelets Contain two sorts of cytoplasmic granules

Alpha granules
Dense bodies

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Alpha granules

Coagulation factors
Platelet derived growth factors
Fibrinogen

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Dense bodies

Unique to platelets
Adenine nucleotides (ADP)
5 Hydroxytryptamine
Calcium

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Platelet Adhesion

Rapid adherence to collagen exposed by endothelial damage

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Platelet releases reaction

Degranulation of the platelets

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Platelet aggregation

1. Platelets rapidly clump together to cover the area of endothelial cell loos
2. Mediated by ADP and Ca2+

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Prostaglandins Generated from

Cell wall phospholipids, which are released when cells are injured.

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Endothelial cells generate

Prostacyclin (PGI2)

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Endothelial cells generating prostacyclin (PGI2) function

Dilates vessels
Disaggregates platelets

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Thromboxane produced by

Platelets

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Thromboxane function

Constricts vessels
Aggregates platelets

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PGI2 Function

Vasodilation
Platelet disaggregation

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PGI2 Derived from

EPE
PGI3
TXA3

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PGI3 function

Vasodilation
Platelet disaggregation

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TXA2 function

Vasoconstriction
Platelet aggregation

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TXA3 function

Almost without action

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Diet that reduce thromboxane activity

Diets rich in EPE, such as oily fish, evening primrose oil result in reduced thromboxane (TXA3) activity and thus have an anti-thrombotic effect.

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Virchow’s Triad 2: Co-agulative qualities of the blood:

1. Changes in blood constituents
a. Alteration in coagulability of the blood
b. Increased platelet numbers
i. Major injury
ii. Surgery
iii. Post partum
c. Increased fibrinogen concentration

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Normal platelet numbers

200-400x10(9) /L

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Platelet numbers Can increase to

900-1200 x 10 (9)/L

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Risk of elevated platelets

Increased risk of thrombosis

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Coagulation Cascade:

Consists of a series of circulating plasma proteins which, with the appropriate stimulus, are activated sequentially with the goal of precipitating Fibrin which forms a fibrous mesh, or scaffold, fo the formation of thrombus.

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Coagulation: steps

amplification
Control

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Amplification

The sequential activation of the clotting factors leads to enormous amplification of the initial signal.

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Control

Antithrombin 3
Heparin

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Anticoagulation

• Enhancing the action of Antithrombin 3 by adding Heparin

• Reducing the concentration of coagulation factors

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Reducing the concentration of coagulation factors how

Achieved by reducing their production in the liver (using dicoumarols such as Warfarin) or by removing the clotting factors from the circulation.

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Nature of blood flow

laminar vs. turbulent.

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Disturbance =

allows large numbers of platelets to come into contact with endothelium.

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Laminar Flow

Minimal mixing between layers
Cellular component of the blood moves in the fast flowing, lower pressure zone, in the centre of the vessel with the result that platelets have little contact with endothelium.

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Turbulent Flow

With disturbance of aminar flow and the introduction of turbulence large numbers of platelets are brought into contact with the endothelial surface.

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Common Sites for formation of thrombus: arterial

1. Atheromatous plaque
a. Coronary arteries
b. Aorta
2. Endocardium
a. ‘mural thrombus’
b. following myocardial
c. infarction

56

Common Sites for formation of thrombus: venous

Venous side of the circulation
1. Deep veins of the leg
2. Pelvic veins

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