Haemostasis and Atherosclerosis Flashcards

1
Q

What is an atheroma?

A
  • Abnormal accumulation of material in the inner layer of the wall of an artery
  • Material consists of macrophages, debris, lipids, fibrous material
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2
Q

Describe the process of atherogenesis

A
  • White blood cells attach to damaged endothelial cells which express adhesion molecules - diapedesis occurs (monocyte enters intima)
  • Cholesterol accumulates and oxidises causing an inflammatory response in the tunica intima
  • Monocytes enter the artery turning to macrophages and then foam cells once they digest cholesterol
  • Foam cells degenerate releasing there contents which are engulfed by other macrophages
  • This process produces an area with a lipid core that forms a plaque which endothelial cells cover
  • The plaque grows and accumulates more lipids, dead cells and calcium salts, additionally, SM cells proliferate and produce collagen
  • If endothelial cells are compromised blood clots can form on vessel wall (thrombus), these may break off
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3
Q

What is arteriosclerosis?

A

The process by which blood vessels become thick and stiff - often restricting blood flow

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4
Q

What are foam cells?

A
  • Type of macrophages that localise to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins.
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5
Q

What cells are contained in the tunica media?

A

Smooth muscle cells

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6
Q

What is the tunica adventitia/externa made up of?

A

Connective tissue (mainly collagen)

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7
Q

What is the process called by which monocytes enter the tunica intima?

A

Diapedesis

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8
Q

What causes LDLs to become oxidised in the tunica intima?

A

Dysfunctional endothelial cells release reactive oxygen species (ROS) and metallo-proteases
- Oxidation means the LDLs become trapped in the tunica intima

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9
Q

What triggers endothelial cells to express adhesion molecules for WBCs? (there are 2 main factors)

A
  • Dysfunctional endothelium (due to damage) and subsequently the:
  • Oxidised LDL
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10
Q

What do foam cells release to attract more macrophages?

A

Chemokines

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11
Q

What do foam cells release which cause SMCs to migrate and proliferate?

A

IGF-1

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12
Q

What can cause inflammation within the tunica intima?

A
  • Foam cells can release DNA material which attracts neutrophils
  • Foam cells can release proinflammatory cytokines and ROS
  • T cells bind to adhesion receptors on endothelial cells and enter plaque area, release IF-y after activation by macrophages
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13
Q

What is the blood supply called that supplies larger vessles?

A

Vasa vasorum (when a plaque is formed this blood supply increases)

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14
Q

What substance do endothelial cells release when injured to cause smooth muscle contraction?

A

Endothelin

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15
Q

What is protein C activated by?

A

Thrombin

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16
Q

What does protein C degrade?

A

factors V and VIII

17
Q

What does ATIII (Antithrombin 3) degrade?

A

Factors II, IX, X

18
Q

What does heparin sulphate (glycosaminoglycan) bind to to activate?

A

ATIII (antithrombin 3)

19
Q

What receptor on the platelet binds to VWF?

A

GPIb

20
Q

What does the binding of GPIb to VWF cause the platelet to release?

A
  • ADP
  • TxA2
  • Serotonin
21
Q

What receptors on the platelets bind together to create a platelet plug?

A

GPIIb/GPIIIa

22
Q

What do TxA2 and ADP cause?

A

Platelets to aggregate at the site of the injury

23
Q

What does TXA2 and 5HT do?

A

Cause vasoconstriction

24
Q

What are the 3 factors in vascular spasm?

A
  • Endothelin release, activating SM contraction
  • Myogenic mechanism by SM (due to contact)
  • Inflammatory molecules stimulating nociceptors which initiate constriction of blood vessels
25
Q

What is the function of NO and PGI2?

A

Inhibit platelets

26
Q

What does plasmin degrading fibrin cause the release of?

A
  • fibrinogen

- D-dimers

27
Q

What converts plasminogen to plasmin?

A

TPA (tissue plasminogen activator)

28
Q

What 2 main molecules are involved in clot retraction and repair? (and what are their functions)

A

PDGF (platelet derived growth factor)
- Triggers mitosis of SM lining
- Connective tissue repairs patches
VEGF (vascular endothelial growth factor)
- Causes regeneration of endothelial lining

29
Q

Factor 9 and 8 require what else to produce factor Xa?

A

PF3

30
Q

What are the 2 stages of haemostasis?

A
  • Primary haemostasis (platelet plug)

- Secondary haemostasis (fibrin mesh, coagulation cascade)

31
Q

What clotting factors require vitamin K?

A

II, VII, IX, X

32
Q

What can clotting factor III also be referred to?

A

Tissue factor