Atherosclerosis Flashcards

1
Q

define atherosclerosis

A

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

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2
Q

Common sites

A
  • Aorta- especially abdominal (AAA- Abdominal aortic aneursym)
  • Coronary arteries
  • Carotid arteries
  • Cerebral arteries
  • Leg arteries
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3
Q

normal arterial structure

A
  • Endothelium
  • Subendothelial connective tissue
  • Internal elastic lamina
  • Muscular media
  • External elastic lamina
  • Adventitia
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4
Q

macroscopic features of atherosclerosis

A
  • Fatty streak
  • Simple plaque
  • Complicated plaque
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5
Q

fatty streak

A

early age of atheroma

  • Lipid deposits in intima
  • Yellow
  • Relationship to atherosclerosis somewhat debatable
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6
Q

Simple plaque

A
  • Raised yellow/white
  • Irregular outline
  • Widely distributed
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7
Q

Complicated plaque

A
  • Thrombosis
  • Haemorrhage into plaque
  • Calcification- degenerate lipid material
  • Aneurysm formation
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8
Q

microscopic features: early changes

A

1) Proliferation of smooth muscle cells
2) Accumulation of foam cells
3) Extracellular lipid

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9
Q

microscopic features: later changes

A

4) Fibrosis
5) Necrosis
6) Cholesterol cleft- where cholesterol used to be
7) +/- inflammatory cells
8) Disruption of internal elastic lamina
9) Damage extends into media
10) Ingrowth of blood vessels
11) Plaque fissuring

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10
Q

clinical effects of atherosclerosis

A

ischaemic heart disease

cerebral ischameia

mesenteric ischaemia

abdominal aortic aneurysm (AAA)

peripheral vascular disease

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11
Q

ischaemic heart disease

A
  • Sudden death
  • MI
  • Angina pectoris
  • Arrhythmias- irregular heart beats
    • Tachycardia
    • Bradycardia
    • Atrial fibrillation
    • Ventricular fibrillation
  • Cardiac failures
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12
Q

Cerebral ischaemia

A
  • Transient ischaemic attack
  • Cerebral infarction (stroke)
  • Multi-infarct dementia
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13
Q

Mesenteric ischaemia

A

in which injury to the small intestine occurs due to not enough blood supply

  • Ischaemic colitis
  • Malabsorption
  • Intestinal infarction
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14
Q

Abdominal aortic aneurysm (AAA)

A

is a localized enlargement of the abdominal aorta such that the diameter is greater than 3 cm or more than 50% larger than normal. They usually cause no symptoms, except during rupture.

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15
Q

peripheral vascular disease

A
  • Intermittent claudication
  • Leriche syndrome
  • Ischaemic rest pain
  • Gangrene
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16
Q

intermittent claudication

A

painful to walk

  • pain onset for a given distance gets shorter overtime
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17
Q

Leriche syndrome

A
  • pain the buttock on exercise (erectile dysfunction)
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18
Q

Ischaemic rest pain

A
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19
Q

risk factors of atherosclerosis pathogenesis

A

age

gender

hyperlipidaemia

cigarette smoking

hypertension

DM

alcohol consumption

infection

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20
Q

Age

A
  • Slowly progressive throughout adult life
  • Risk factors operate over years
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21
Q

Gender

A
  • Women protected relatively before menopause
  • Presumed hormonal basis
22
Q

Hyperlipidaemia

A
  • High plasma cholesterol associated with atherosclerosis
  • LDL most significant
  • HDL protective
23
Q

lipid in the blood is carried on

A

lipoproteins

24
Q

lipoproteins carry

A

cholesterol and TAG

25
Q

lipoprotein structure

A

Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesterol esters and triglycerides. This hydrophobic core is surrounded by a hydrophobic membrane consisting of phospholipids, free cholesterol, and apolipoproteins (A-E)

26
Q

chylomicrons

A

transport lipids from the intestine to the liver

27
Q

VLDL

A

carry cholesterol and TAG from the liver

  • TAG get sremoved leaving LDL
28
Q

LDL

A

rich in choelsterol

carry cholesterol to non-liver cells (formation of foam cells)

29
Q

HDL

A

carries cholesterol back to the liver

30
Q

Apolopoprotein E and atherosclerosis

A
  • Genetic variation in ApoE are associated with changes in LDL levels
  • Polymorphisms of genes involved lead to at least 6 Apo E phenotypes
  • Polymorphisms can be used as risk markers for atherosclerosis
31
Q

Familial hyperlipidaemia

A
  • Genetically determined abnormalities of lipoprotein
  • Lead to early development of atherosclerosis
32
Q

physical signs of hyperlipidaemia

A

corneal arcus

tendon xanthomas

xanthelasma

33
Q

corneal arcus

A

deposition of lipid in the peripheral cornea and is generally considered a concomitant of normal ageing process and expected in the elderly patient.

34
Q

tendon xanthomas

A

Appears as slowly enlarging subcutaneous nodules related to a tendon or ligament; Most commonly found on the hands, feet and knees

35
Q

Xanthelasma

A

yellowish deposit of cholesterol underneath the skin. It usually occurs on or around the eyelids

36
Q

genetic predisposition to familial hyperlipidaemia

A
  • Possibly due to
    • Variation in apolipoprotein metabolism
    • Variation in apolipoprotein receptors
37
Q

Other risk factors for hyperlipidaemia

A
  • Lack of exercise
  • Obesity
  • Soft water
  • Oral contraceptives
  • Stress
  • Personality type
38
Q

Cigarette smoking

A
  • Powerful risk factor for IHD
  • Risk falls after giving up
  • Mode of action uncertain
39
Q

Hypertension

*

A
  • Strong link between IHD and high systolic blood pressure
  • Mechanism uncertain
  • Endothelial damage caused by raised pressure?
40
Q

DM

A
  • Double risk of IHD
  • Protective effect tin premenopausal women lost
  • DM also associated with high risk of cerebrovascular and peripheral vascular disease
  • Related to hyperlipidaemia and hypertension
41
Q

Alcohol consumption

A
  • More than 5 units a day associated with increased IHD
  • Alcohol consumption associated with other risk factors
  • Smaller amount of alcohol may be protective
42
Q

Infection

A
  • Chlamydia pneumonia
  • Helicobacter pylori
  • Cytomegalovirus
43
Q

pathogenesis theories

A
  • thrombogenic theory
  • insudation theory
  • monoclonal hypothesis
  • reaction to injury hypothesis
44
Q

thrombogenic thoery

A

due to repeated thrombosis

45
Q

insudation theory

A

lipid leaked out of vessel into vessel wall due to endothelial injury such as inflammation hat made the vessel more permeable.

46
Q

Monoclonal hypothesis

A
  • Smooth muscle proliferation
  • Each plaque monoclonal
  • Might represent abnormal growth control
  • Is each plaque a benign tumour?
  • Viral aetiology?
47
Q

Reaction to injury hypothesis

A
  • Endothelial injury
  • Hypercholesterolaemia leads to endothelial damage (LDL)
  • Injury increases permeability and allows platelet adhesion
  • Monocytes penetrate endothelium
  • Smooth muscle cells proliferate and migrate
48
Q

which cells become foam cells

A

smooth muscle cells and macrophages

49
Q

summary of atherosclerosis

A
  • Thrombosis
  • Lipid accumulation
  • Production of intercellular matrix
  • Interaction between cell types
    • Endothelial cells
      • Key role in haemostasis
      • Altered permeability to lipoproteins
      • Production of collagen
      • Stimulation of proliferation and migration of smooth muscle cells
    • Platelets
      • Key role in haemostasis
      • Stimulate proliferation and migration of smooth muscle cells (PDGF)
    • Smooth muscle cells
      • Take up LDL and other lipid to become foam cells
      • Synthesise collagen and proteoglycans
  • Macrophages
    • Oxidise LDL
    • Take up lipids to become foam cells
    • Secrete proteases which modify matrix
    • Stimulate proliferation and migration of smooth muscle cell
  • Lymphocytes
    • TNF may affect lipoprotein metabolism
    • Stimulation proliferation and migration of smooth muscle cells
  • Neutrophils (often no inflammation)
    • Secrete proteases leading to continued local damage and inflammation
50
Q

atheroscelrosis prevention

A
51
Q
  • No smoking
  • Reduce fat intake
  • Treat hypertension
  • Not too much alcohol
  • Regular exercise/ weight control
  • but some people will still develop atherosclerosis
A
52
Q

atheroscleorsis intervention

A
  • stop smoking
  • modify diet
  • treat hypertension
  • treat diabetes
  • lipid lowering drugs