6. Atheroma

Question 1

What are atheromas?

Answer 1

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

Question 2

What is atherosclerosis?

Answer 2

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

Question 3

What is arteriosclerosis?

Answer 3

The thickening and hardening of arteries and arterioles usually as a result of hypertension of diabetes mellitus.

Question 4

What are the macroscopic features of atheromas?

Answer 4

Fatty streak, simple plaque or complicated plaque.

Question 5

What is the fatty streak in atheromas?

Answer 5

Lipid deposits in the intima. Yellow and slightly raised.

Question 6

What is the appearance of atheroma simple plaques?

Answer 6

Raised yellow/white, irregular outline, widely distributed, enlarge and coalesce.

Question 7

What is the appearance of atheroma complicated plaques?

Answer 7

Thrombosis, haemorrhage into plaque, calcification, aneurysm formation.

Question 8

What are the common sites of atheroma?

Answer 8

Aorta, coronary arteries, carotid arteries, cerebral arteries, and leg arteries.

Question 9

What is the normal structure of arteries?

Answer 9

Endothelium, sub-endothelium, internal elastic lamina, muscular media, external elastic lamina, adventitia.

Question 10

What are the early changes seen microscopically with atheromas?

Answer 10

Proliferation fo smooth muscle cells, accumulation of foam cells, extracellular lipid.

Question 11

What are the later changes seen microscopically with atheromas?

Answer 11

Fibrosis, necrosis, cholesterol clefts (needle shaped crystals of cholesterol), and more or less inflammatory cells.
Also disruption of internal elastic lamina, damage can extend into media, ingrowth of blood vessels and plaque fissuring.

Question 12

What are the possible clinical effects of atheromas?

Answer 12

Ischaemic heart disease, cerebral ischaemia, mesenteric ischaemia, peripheral vascular disease.

Question 13

What are the risks of ischaemic heart disease?

Answer 13

Sudden death, myocardial infarction, angina pectoris, arrhythmias, and cardiac failure.

Question 14

What are the risks of cerebral ischaemia?

Answer 14

Transient ischaemic attacks, cerebral infarction/stroke, multi-infarct dementia.

Question 15

What are the risks of mesenteric ischaemia?

Answer 15

Ischaemic colitis, malabsorption, intestinal infarction.

Question 16

What are the risks of peripheral vascular disease?

Answer 16

Intermittent claudication, Leriche syndrome, ischaemic rest pain, gangrene (if untreated).

Question 17

What are the risk factors of developing atheromas?

Answer 17

Age, gender, hyperlipidaemia, cigarette smoking, hypertension, diabetes mellitus, alcohol, infection.

Question 18

How does age affect atheroma development?

Answer 18

Risk increases throughout adult life.

Question 19

How does gender affect atheroma development?

Answer 19

Women are protected before menopause so lower risk, thought to be hormonally linked.

Question 20

How does hyperlipidaemia affect atheroma formation?

Answer 20

High plasma cholesterol is associated with atheroma, LDL more importantly as HDL is protective.

Question 21

What are the roles of the following lipids?

a. Chylomicrons
b. LDL
c. VLDL
d. HDL

Answer 21

a. transport lipid from intestine to liver.
b. rich in cholesterol, carry cholesterol to non-liver cells.
c. carry cholesterol and TG from liver, TG removed leaving LDL.
d. carry cholesterol from periphery back to liver.

Question 22

What is familial hyperlipidaemia?

Answer 22

Genetically determined abnormalities of lipoproteins that lead to early development of atheroma.

Question 23

What are the physical signs associated with familial hyperlipidaemia?

Answer 23

Corneal arcus, tendon xanthomas, xanthelasma.

Question 24

How does cigarette smoking affect atheroma formation?

Answer 24

Powerful risk factor, risks fall after giving up smoking. Could be due to cigarette affect on coagulation system, reduced PIP2, or increased platelet aggregation.

Question 25

What is the possible link between hypertension and atheroma formation?

Answer 25

Could be because of more endothelial damage with raised pressure.

Question 26

How does diabetes mellitus affect atheroma formation?

Answer 26

It doubles the risk of ischaemic heart disease and loses the protective effect in premenopausal women. Could be linked to hyperlipidaemia and hypertension.

Question 27

How does alcohol consumption affect atheroma formation?

Answer 27

>5 units a day are associated with increased risk of ischaemic heart disease. Small amounts of alcohol could be protective though.

Question 28

What infections could raise risk of atheroma?

Answer 28

Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus.

Question 29

Why could genetic predisposition raise risk of atheroma formation?

Answer 29

Because of variations in apolipoprotein metabolism and apolipoprotein receptors.

Question 30

What is Rokitansky's thrombogenic theory?

Answer 30

Plaques formed by repeated thrombi and lipid is derived from thrombi. There is an overlying fibrous cap.

Question 31

What is Virchow's insudation theory?

Answer 31

Endothelial injury causes inflammation and increased permeability to lipid from plasma.

Question 32

What is Ross and Glomset's reaction to injury hypothesis?

Answer 32

Plaques form in response to endothelial injury. Hypercholesterolaemia leads to endothelial damage in experimental animals. Injury increases permeability and allows platelet adhesion, monocytes penetrate endothelium and smooth muscle cells proliferate and migrate.

Question 33

What is Benditt and Benditt's monoclonal hypothesis?

Answer 33

Crucial role for smooth muscle proliferation, each plaque is monoclonal, could represent abnormal growth control. So each plaque could be a benign tumour or have a viral artiology.

Question 34

What are the four main process involved in atheromas?

Answer 34

Thrombosis, lipid accumulation, production of intercellular matrix and interactions between cell types.

Question 35

What are the cells involved in atheroma?

Answer 35

Endothelial cells, platelets, smooth muscle cells, macrophages, lymphocytes, and neutrophils.

Question 36

What is the role of endothelial cells in atheroma?

Answer 36

In haemostasis: altered permeability to lipoproteins, production of colalgen and stimulation of proliferation and migration of smooth muscle cells.

Question 37

What is the role of platelets in atheroma?

Answer 37

In haemostasis: stimulate proliferation and migration of smooth muscle cells (PDGF).

Question 38

What is the role of smooth muscle cells in atheroma?

Answer 38

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

Question 39

What is the role of macrophages in atheroma?

Answer 39

Oxidise LDL, take up lipids to becomes foams cells, secrete proteases which modify matrix, and stimulate proliferation and migration of smooth muscle cells.

Question 40

What is the role of lymphocytes in atheroma?

Answer 40

TNF may affect lipoprotein metabolism, stimulate proliferation and migration of smooth muscle cells.

Question 41

What is the role of neutrophils in atheroma?

Answer 41

Secrete proteases leading to continues local damage and inflammation.

Question 42

What is the unifying hypothesis of atheroma?

Answer 42

Endothelial injury due to: raised LDL, toxins, hypertension, and 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 of monocytes into intima. Stimulated SMC produce matrix material. Foam cells secrete cytokines causing further SMC stimulation and recruitment of other inflammatory cells.

Question 43

How can atheromas be prevented?

Answer 43

No smoking, reduce fat intake, treat hypertension, not too much alcohol, regular exercise and weight control.