Session 6 - Atheroma formation Flashcards Preview

Semester 2 - Mechanisms of Disease > Session 6 - Atheroma formation > Flashcards

Flashcards in Session 6 - Atheroma formation Deck (70):
1

Define atheroma

The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

2

Define atherosclerosis

The thickening and hardening of arterial walls as a consequence of atheroma

3

Define arteriosclerosis

The thickening of the walls of arteries and arterioles usually as a result of hypertesnion or diabetes mellitus

4

What are the three types of atheroma?

Fatty streak
Simple plaque
Complicated plaque

5

What is a fatty streak atheroma?
What does it look like?

Lipid deposits in intima
Yellow, slightly raised

6

What does a simple plaque atheroma look like?

Raised yellow/white
Irregular outline
Widely distributed
Enlarge and coalesce

7

What is another name for a complicated plaque?

Thrombosis

8

How is complicated plaque caused?

Haemorrhage into plaque with subsequent calcification

9

What can a complicated plaque cause?

Aneurysm formation

10

Name five common sites of atheroma formation

Aorta
Coronary arteries
Carotid arteries
Cerebral arteries
Leg arteries

11

What is this image?

************ Fatty streak atheroma

12

What is this an image of?

************Simple plaque

13

What is this an image of?

************ Complicated plaque

14

Give structure of normal artery

Endothelium
Sub endothelial ct
Internal elastic lamina
Muscular media
External elastic lamina
Adventitia

ESIMEA
Even sexy idiots make ellen angry

15

What are the early microscopic changes in atheroma?

Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid

16

What are later micrscopic changes involved in atheroma?

Fibrosis
Necrosis
Cholesterol clefts
Change in number of inflammatory cells

17

What are the clinical effects of atheroma formation?

Ischaemic heart disease
Cerebral ischaemia
Mesenteric ischaemia
Peripheral vascular disease

18

What five conditions are associated with ischaemic heart disease?

Sudden death
MI
Angina pectoris
Arrhythmias
Cardiac failure

19

What are three effects of cerebral ischaemia?

Transient ischaemic attack
Cerebral infarction ( stroke)
Multi-infarct dementia

20

What are three effects of mesenteric ischaemia?

Ischaemic colitis
Malabsorption
Intestinal infarction

21

What are the four effects of peripheral vascular disease?

Intermittent claudication
Leriche syndrome
Iscaemic rest pain
Gangrene

22

Give eight risk factors for atheroma formation

Age
Gender
Hyperlipidaemia
Cigarette smoking
Hypertension
Diabetes mellitus
Alcohol
Infection

23

How does age affect the risk of having an atheroma form?

Slow increase in risk as you age
Risks factors accumulate over the course of your life

24

How does gender effect your risk of atheroma formation?

Women protected before menopause due to hormones

25

How does hyperlipidaemia cause atheroma?

High plasma cholesterol associated with atheroma

26

What are the most significant factors in hyperlipidaemia?

LDL levels are dangerous
High HDL are protective

27

How are lipids carried in the blood?

Lipoproteins

28

What do lipoproteins carry (be specific)

Cholesterol, triglycerides, phospholipids and apolipoprotein, to be precise

29

What is the structure of a lipoprotein

Hydrophobic lipid core, hydrophillic outer layer of phospholipid and apolipoprotein

30

Name four different types of lipid

Chylomicrons
LDL
VLDL
HDL

31

What is the role of chylomicrons?

Transport lipid from intestine to liver

32

What is the role of LDL's?

Carry cholesterol to non-liver cells

33

What is the role of VLDL's?

Carry cholesterol and TG from liverr

34

What is the role of HDL?

Carry cholesterol from adipose tissue to the liver

35

What apolipoprotein are atheromas linked to?

Apo E
Polymorphisms of genes involved lead to at least 6 Apo E phenotypes

36

What can polymorphisms of genes causing increased Apo E be used for?

Risk markers for atherome

37

What is familial hyperlipidaemia?

Genetically determined abnormalities of lipoproteins which leads to early development of atheroma

38

What are the associated physical signs of familial lipidaemia?

- Corneal arcus
- Tendon xanthomas
- Xanthelasma

39

What is cigarette smoking a powerful risk factor for, other than atheroma? (Vascular disease)

Ischaemic Heart Disease

40

Give three possible modes of action of cigarette smoking causing atheromas

Coagulation system
Reduced prostacyclin (PGI2, eicosanoids)
Increased platelet aggregation

41

What is hypertension linked to? How does it cause damage?

Strong link to IHD? Endothelial damage caused by raised blood pressure

42

What affect does DM have on IHD risk?

Doubles the chance

43

What effect does DM have on premenopausal women?

Lose their protected status

44

What three atheroma related diseases are associated with DM?

IHD, cebrovascular and peripheral vascular disease,.

45

What two other risk factors is DM related to?

Hyperlipidaemia and hypertension

46

How many units of alcohol per day must be consumed for their to be increased risk IHD

>5

47

Why is alcohol so potent a risk factor?

Often associated with other lifestyle related risk factors

48

What is interesting about alcohol consumption?

Smaller amounts are protective of atheroma

49

Give five more risk factors of atheroma formation

Lack of exercise
Obesity
Soft water
Oral contraceptive
Stress and personality

50

What two variations in phenotype can account for increased genetic predisposition

Variations in apolipoprotein metabolism
Variations in apolipoprotein receptors

51

What are the four theories concerning atheroma pathogenesis?

Thrombogenic theory
Insudation theory
Monoclonal hypothesis
Reaction to injury hypothesis

52

What is the insudation theory of atheroma formation?

Endothelial injury
Inflammation
Increased permeability to lipid from plasma

53

What is the reaction to injury hypothesis?

Plaques form in response to endothelial injury as a result of hypercholesterolaemia
Injury increases permeability and allows platelet adhesion
monocytes penetrate endothelium
Smooth muscle cells proliferate and migrate

54

How does hypercholesterolaemia damage endothelium?

Oxidised LDL can cause subtle and undetectable injury

55

What is the monoclonal hypothesis?

Belief that artheroma may have viral aeitology, stemming from the observation that each plaque is monoclonal, and may thus represent abnormal growth control .

56

What is given a crucial role in the monoclonal hypothesis?

Smooth muscle prolifeation

57

What are the four processes involved in atheroma formation?

Thrombosis
Lipid accumulation
Production of intercellular matrix
Interactions between cell types

58

What are the six cells involved in atheroma?

Endothelial cells
Platelets
Smooth muscle cells
Macrophages
Lymphocytes
Neutrophils

59

What the four roles of endothelial cells in atheroma formation?

Key role in haemostasis
Altered permeability to lipoprotein
Secretion of collagen
Stimulation of proliferation and migration of smooth muscle cells

60

What are the two rolls of platelets in atheroma formation?

Key role in haemostasis
Stimulate proliferation and migration of smooth muscle cells (PDGF - platelet derived growth factor)

61

What are the two roles of smooth muscle cells

Take up LDL and other lipid to become foam cells
Synthesis collagen and proteoglycans

62

What are the four roles of atheroma formation of macrophages?

Oxidise LDL
take up lipids to become foam cells
Secrete proteases which modify matrix
Stimulation proliferation and migration of smooth muscle cells

63

How are lymphocytes involved in atheroma formation?

Tumour necrosis factor (TNF) may affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells

64

What is the role of neutrophils in atheroma formation?

Secrete proteases leading to continues local damage and inflammation

65

What are the two steps of the unifying hypothesis?

Endothelial injury
Results of endothelial injury

66

What causes endothelial injury under the unifying hypothesis?

Raised LDL
Toxins
Hypertension
Haemodynamic stress

67

What does endothelial injury result in under the unifying hypothesis?

- Platelet adhesion, PDGF release, smooth muscle cells (SMC) proliferation and migration
- Insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages
- Migration of monocytes into intima
- Stimulated SMC produce matrix material
- Foam cells secrete cytokines

68

What does the secretion of cytokines by foam cells cause in atheroma formation?

Further SMC stimulation
Recruitment of other inflammatory cells

69

What are the five ways of reducing risk of atheroma formation?

No smoking
Reduce fat intake
Treat hypertension
Not too much alcohol
Regular exercise/weight control

70

What are five interventions to halt atheroma formation?

Stop smoking
Modify diet
Treat hypertension
Treat diabetes
Lipid lowering drugs