L41 – Atherosclerosis and disrupted circulation Flashcards Preview

MBBS I CPRS > L41 – Atherosclerosis and disrupted circulation > Flashcards

Flashcards in L41 – Atherosclerosis and disrupted circulation Deck (43):
1

Define atherosclerosis

A process of progressive thickening and hardening of the walls of medium-sized and large arteries as a result of fat deposits on their inner lining.

2

What is the precursor lesion to atheroma?

Lipid/ fatty streak

3

What are fatty streaks?

Lipid deposits in intima, flat / slightly elevated streaks

4

What are some irreversible risk factors of atherosclerosis?

Age, Sex, Genetics

-Increase risk with age
-Male more likely to die from IHD than female up to 75 years old
-Genetic hyperlipidemia, hypertension

5

What are some reversible risk factors of atherosclerosis?

-Smoking
-Hyperlipidemia
-Hypertension
-Diabetes
-Hyperomocysteinaemia (caused by renal/ liver disease or diet deficiencies)

6

How does smoking increase risk of atheroma?

 Damages endothelium > causes leukocytes to stick (adhere) to vessel wall
 Decreases ability of vessels to relax / dilate

7

How does hyperlipidemia increase risk of atheroma?

oxy-LDL is critical to start atheroma formation in tunica intima

Low HDL levels mean accumulation of lipid

8

How does hypertension increase risk of atheroma?

Mechanical injury to endothelium by applying shear stress

9

How does Diabetes increase risk of atheroma?

-raised LDL levels,lower HDL levels due to abnormal lipoprotein metabolism
-Renal failure > accumulate homocysteine
- Advanced Glycation Endproduct (ACE)

10

How does hyperhomocysteinaemia increase risk of atheroma?

homocysteine auto-oxidises > reacts with reactive oxygen species to damage endothelial cells > stimulate formation of thrombi (stimulate FA-synthesis and fibrous cap formation too)

11

What starts formation of atheroma?

Fluid shear stress damages endothelium > LDL in blood can enter

12

What happens to LDL entering intima at the start of atheroma formation?

oxidized by reactive oxygen
species within vessel wall > form oxidized low density lipoprotein (oxLDL)

13

What do oxidized low density lipoprotein (oxLDL) stimulate production of ?

stimulate production of
cytokines / growth factors (ICAM-1, VCAM-1, P-, E- selectins) within intima > monocytes adhere to
arterial endothelium

14

What happens after monocyte adherence in formation of atheroma?

Adhered monocytes penetrate into artery > grow into macrophages> along with smooth muscles cells phagocytose oxLDL through scavenger receptors (e.g. CD36, SR-A)

15

What happens after macrophage uptake oxLDL ?

phenotypic modulation > apoptosis / necrosis > release extracellular debirs/ lipids to form atheroma and produce cholesterol-rich foam cells

16

What do cholesterol-rich foam cells initiate?

fatty streak

17

What stimulates SMC to form fibrous cap?

Homocysteine stimulates SMC to proliferate > produce matrix > forms fibrous cap

18

High levels of homocysteine can upregulate what?

Fatty acid synthesis
Smooth muscle migration

19

How does increased glucose in diabetes patients exacerbate atherosclerosis?

Increased glucose adhere to amino acids in collagen > form Amadori Products (AGE) > recognized by macrophages, platelets > release cytokines + cause damage to ECM > accelerate tissue stiffening and accelerate sclerosis

20

How can infection worsen atheroma?

Infection > systemic inflammation > cytokines stimulate coagulation and vasoconstriction

21

What growth factor is responsible for change in SM arrangement in atheroma?

platelet-derived growth factor (PDGF)

 Stimulate smooth muscle proliferation
 Attract migration of SMC from media to intima

22

What growth factor is produced by damaged endothelial cell and worsens atheroma?

endothelial cell growth factor (ECGF)

interleukin-1

23

What happens to the endothelium of fibrous cap in its coagulation properties?

Normal = anti-coagulation

Fibrous cap = Pro-coagulation

24

What is the difference between atherosclerosis and thromosis?

Atherosclerosis = deposition of fatty material on the inner walls of their arteries

thrombosis = local coagulation or blood clot in a part of the circulatory system.

25

What is the definition of thrombus?

pathological process whereby blood clot forms in uninjured vasculature / after relatively minor injury

26

What are the normal function of homeostasis to prevent excessive bleeding?

1. Vasoconstriction
2. Temporary blockage by platelet plug
3. Blood coagulation / formation of fibrin clot

27

What is Virchow's Triad criterium of thrombosis?

Abnormal blood flow, endothelial injury, hypercoagulability

28

How can thrombosis cause downstream necrosis?

Obstruct lumen > inadequate flow of oxygenated blood > downstream ischaemia/ necrosis

29

What causes propagation of thrombus?

Thrombus lodge at vein pocket > fibrin and platelets laminate > thrombus propagation

30

What are the 5 fates of thrombus?

- Propagate
- Become recanalised
- Become incorporated into vessel wall
- Dislodge > thromboembolism
- Resolved completely

31

Definition of embolism?

detached intravascular solid / liquid / gaseous mass carried by blood to site distant from its point of origin, causing occlusion of blood flow and ischaemia

32

What are the 5 types of embolism?

Air emboli
Fat emboli
Marrow emboli
Pulmonary thromboemboli
Amniotic fluid emboli

33

Which emboli is most common?

Pulmonary thromboemboli

34

Pulmonary thromboemboli derived from where? Predisposing factors?

Emboli derived from
deep vein thrombosis of lower limbs

Predisposing factors: prolonged immobility, dehydration

35

What causes Fat emoli? Effects?

associated with injuries to adipose tissues (e.g. liposuction), fracture of long bones, stressful states


Lead to extensive occlusion of vessels > hemorrhagic infarcts

36

What causes Marrow emoli?

following fractures of long bones (like fat emboli)

commonly found after fractures of ribs during cardiopulmonary
resuscitation (CPR)

37

What causes Air emboli?

“high-pressure” activities / work, e.g. Scuba diving

Gases are dissolved in blood at high pressures: sudden decompression > gases can
form bubbles within the vascular system > obstruction

38

What causes amniotic fluid emboli?

Induced labour may force contents of fetal amniotic sac into maternal circulation > anaphylactic shock > death

39

What are other much less common emboli?

 Foreign bodies / objects e.g. glass, metal fragments
 Tumor emboli
 Bacteria > septic emboli

40

Effects of obstructed circulation (thrombosis and/or embolism) depends on ?

Location, degree of vascular occlusion

Availability of collateral blood supply

Susceptibility to interruption of blood supply

41

Name some biomarkers for atherosclerosis?

White blood cell count (WBCC)

Fibrinogen

C-reactive protein (CRP)

42

Both thrombosis and embolus cause ishaemia. What follows ishaemia?

Infarction > red (haemorrhagic) or white (pale) depending on collateral supply

Infarction > inflammtion or shock

43

What 4 factors are needed to cause thrombosis?

Atheroma
Fibrinogen
Platelet
Virchow's triad

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