MoD 7 Atheroma

Question 0

What is atherosclerosis?

Answer 0

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

Question 1

What is atheroma?

Answer 1

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

Question 2

What is arteriosclerosis?

Answer 2

Thickening of walls of arteries and arterioles, usually as a result of hypertension or diabetes mellitus

Question 3

What causes the fatty streak?

Answer 3

Lipid deposits in intima, yellow, slightly raised

relationship to atheroma debatable

Question 4

What are the features of a simple plaque?

Answer 4

raised, yellowe/white
irregular outline
widely distributed
enlarge and coalesce(join together)

Question 5

What are the features of complicated plaques?

Answer 5

Thrombosis
Haemorrhage into plaque
Calcification
Aneurysm formation

Question 6

What are some common sites of atheroma?

Answer 6

Aorta- especially abdominal
Coronary arteries
Carotid arteries
Cerebral arteries
Leg arteries

Question 7

What are the early microscopic changes in atheroma formation?

Answer 7

Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid

Question 8

What are the later microscopic changes in atheroma formation?

Answer 8

Fibrosis
Necrosis
Cholesterol clefts
\+/- inflammatory cells
disruption of internal elastic lamina
damage extending into media
ingrowth of blood vessels
plaque fissuring

Question 9

Why does the smooth muscle proliferate?

Answer 9

Endothelial damage leads to platelet aggregation and release of PDGF which stimulates smooth muscle proliferation

Question 10

How do foam cells form?

Answer 10

Proliferation and migration of smooth muscle cells taking lipid with it.
Macrophages arriving and phagocytosing the fat

Question 11

What are the consequences of coronary artery atherosclerosis?

Answer 11

Ischaemic Heart Disease-
Sudden death
MI
Angina pectoris
Arrythmias
Cardiac failure

Question 12

What are the consequences of atherosclerosis that give cerebral ischaemia?

Answer 12

TIA
cerebral infarction (stroke)
multi-infarct dememntia (lots of little strokes impairing cognitive function)

Question 13

What consequences can mesenteric ischaemia have?

Answer 13

Ischaemic colitis
Malabsorption
Intestinal infarction
Anneurism from high pressure, hardening and weakening

Question 14

What can peripheral vascular disease cause?

Answer 14

Intermittent claudication (pain when walking from poor blood supply to leg)
Leriche syndrome (bifurcation of aorta as splits into iliac arteries)
Ischaemic rest pain (claudication of iliacartery giving gluteal pain)
Gangrene

Question 15

What are the risk factors for atheroma?

Answer 15

Age
Gender (women protected before menopause)
Hyperlipidaemia (corneal arcus, xanthalasma)
Smoking
Hypertension
Diabetes mellitus
Alcohol
Infection (chlamydia, helicobacter pylori)
Lack of exercise
Obesity
Oral contraceptives
Stress

Question 16

What is the unifying hypothesis of atherogenesis?

Answer 16

Endothelial injury due to: raised LDL, toxins, hypertension, haemodynamic stress
Endothelial injury causes: platelet adhesion, PDGF release, SMC proliferation and migration
Insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages, migration, migration of monocytes into intima
Stimulated SMC make matrix material
Foam cells secrete cytokines causing further SMC stimulation and recruitment of inflam cells

Question 17

How can atheroma be prevented?

Answer 17

stop smoking
modify diet
treat hypertension
treat diabetes
lipid lowering drugs

Question 18

What can increase susceptibility to CHD?

Answer 18

genetic disorders like Familial hypercholesterolaemia
geographical location- less common in Mediterranean die to diet
Ethnicity- common in asians

Question 19

What are risk factors for CHD?

Answer 19

smoking
gender
hypertension
diabetes
alcohol
infection e.g H. pylori

Question 20

What do chylomicrons do?

Answer 20

transport lipid from intestine to liver

Question 21

What do VLDLs do?

Answer 21

carry cholesterol and TG from liver

TG removed leaving LDL

Question 22

What do LDLs do?

Answer 22

they are rich in cholesterol and carry cholesterol from liver to non liver cells

Question 23

What do HDLs do?

Answer 23

They carry cholesterol from peripheries back to liver

Question 24

How does apolipoprotein E link to atheroma?

Answer 24

Genetic variation in this protein are associated with changes in LDL levels and polymorphisms (dif phenotypes) can be used as risk markers for atheroma

Question 25

What are some associated physical signs of hyperlipidaemia?

Answer 25

corneal arcus
tendon xanthomas
xanthelasma (eyelid ones)

Question 26

How do we know hypertension isnt a sole cause of atheroma?

Answer 26

BP is high in arms and very uncommon for atheroma to be in arms

Question 27

What cells are involved in atheroma formation?

Answer 27

endothelial cells
platelets
smooth muscle cells
macrophages
lymphocytes
neutrophils

Question 28

What do smooth muscle cells do?

Answer 28

Take up LDL and lipid to become foam cells

Synthesis collagen and proteoglycans

Question 29

What do macrophages do?

Answer 29

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

Question 30

What do lymphocytes do in atheroma?

Answer 30

stimulate proliferation and migration of smooth muscle cells

Question 31

What do neutrophils do in atheroma?

Answer 31

secrete proteases leading to continued local damage and inflammation