Cardio L18 Thrombosis

Question 1

Thrombosis

Answer 1

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

!!!Distinction from blood clot!!!

Question 2

Blood clot

Answer 2

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

Question 3

When a thrombus forms

Answer 3

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

Question 4

Layers of thrombus

Answer 4

Lines of Zahn

Question 5

Arterial site thrombus type

Answer 5

Tiny, consisting largely of platelets (Very small dimension)

Question 6

Venous site thrombus type

Answer 6

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

Question 7

Capillaries thrombus type

Answer 7

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

Question 8

Virchow’s triad →

Answer 8

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

Question 9

Changes in the vessel wall

Answer 9

Loss of endothelial integrity (most common: atheroma)

Question 10

Changes in local blood flow

Answer 10

Nature of blood flow – laminar vs. turbulent

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

Question 11

Changes in co-agulative qualities of the blood

Answer 11

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

Question 12

→ Thrombus forms at

Answer 12

sites of endothelial injury.

Question 13

Intact endothelium tend to discourage thrombosis by 3

Answer 13

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

Question 14

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

Answer 14

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

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

Question 15

Heparin causes

Answer 15

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

Question 16

Endothelium expresses

Answer 16

Tissue plasminogen activator (TPA)

Question 17

Plasminogen is the

Answer 17

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

Question 18

Endothelial TPA activates

Answer 18

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

Question 19

Damaged endothelial cells generates

Answer 19

Prostacyclin (PGI2)

Question 20

PGI2 function

Answer 20

Dilates vessels

Disaggregates platelets

Question 21

Opposition to PGI2

Answer 21

Prostaglangin generated by platelets

Question 22

Platelets description

Answer 22

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

Question 23

Platelets structure

Answer 23

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

Question 24

Platelets Contain two sorts of cytoplasmic granules

Answer 24

Alpha granules

Dense bodies

Question 25

Alpha granules

Answer 25

Coagulation factors Platelet derived growth factors Fibrinogen

Question 26

Dense bodies

Answer 26

Unique to platelets Adenine nucleotides (ADP) 5 Hydroxytryptamine Calcium

Question 27

Platelet Adhesion

Answer 27

Rapid adherence to collagen exposed by endothelial damage

Question 28

Platelet releases reaction

Answer 28

Degranulation of the platelets

Question 29

Platelet aggregation

Answer 29

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

Question 30

Prostaglandins Generated from

Answer 30

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

Question 31

Endothelial cells generate

Answer 31

Prostacyclin (PGI2)

Question 32

Endothelial cells generating prostacyclin (PGI2) function

Answer 32

Dilates vessels | Disaggregates platelets

Question 33

Thromboxane produced by

Answer 33

Platelets

Question 34

Thromboxane function

Answer 34

Constricts vessels | Aggregates platelets

Question 35

PGI2 Function

Answer 35

Vasodilation | Platelet disaggregation

Question 36

PGI2 Derived from

Answer 36

EPE PGI3 TXA3

Question 37

PGI3 function

Answer 37

Vasodilation | Platelet disaggregation

Question 38

TXA2 function

Answer 38

Vasoconstriction | Platelet aggregation

Question 39

TXA3 function

Answer 39

Almost without action

Question 40

Diet that reduce thromboxane activity

Answer 40

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

Question 41

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

Answer 41

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

Question 42

Normal platelet numbers

Answer 42

200-400x10(9) /L

Question 43

Platelet numbers Can increase to

Answer 43

900-1200 x 10 (9)/L

Question 44

Risk of elevated platelets

Answer 44

Increased risk of thrombosis

Question 45

Coagulation Cascade:

Answer 45

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.

Question 46

Coagulation: steps

Answer 46

amplification | Control

Question 47

Amplification

Answer 47

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

Question 48

Control

Answer 48

Antithrombin 3 | Heparin

Question 49

Anticoagulation

Answer 49

* Enhancing the action of Antithrombin 3 by adding Heparin | * Reducing the concentration of coagulation factors

Question 50

Reducing the concentration of coagulation factors how

Answer 50

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

Question 51

Nature of blood flow

Answer 51

laminar vs. turbulent.

Question 52

Disturbance =

Answer 52

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

Question 53

Laminar Flow

Answer 53

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.

Question 54

Turbulent Flow

Answer 54

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

Question 55

Common Sites for formation of thrombus: arterial

Answer 55

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

Question 56

Common Sites for formation of thrombus: venous

Answer 56

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