Atherosclerosis

Question 1

What is an 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 atherosclerosis?

Answer 2

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

Question 3

What is arteriosclerosis?

Answer 3

The thickening of the walls of arteries and arterioles usually as a result of hypertension/diabetes mellitus (unlike atherosclerosis, due to atheroma).

Question 4

What are the macroscopic features of atherosclerosis?

Answer 4

Fatty streak- lipid deposits in intima, yellow, slightly raised, relationship to atherosclerosis debatable,
Simple plaque - raised yellow/white irregular outline, widely distributed, enlarge and coalesce,
Complicated plaque - thrombosis, haemorrhage into plaque, calcification, aneurysm formation (when something else happens to an atherosclerotic plaque).

Question 5

List some common sites of atherosclerosis.

Answer 5

The aorta (especially the abdominal), coronary arteries, carotid arteries, cerebral and leg arteries.

Question 6

Describe the normal arterial structure.

Answer 6

Endothelium, subendothelial connective tissue, internal elastic lamina, muscular media (location determines amount), external elastic laminar and connective tissue adventitia.

Question 7

What early changes might be seen in atherosclerosis’ microscopic features?

Answer 7

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

Question 8

What microscopic features of atherosclerosis might be described as later changes?

Answer 8

Fibrosis (fibroblasts proliferate), necrosis, cholesterol clefts (needle shaped crystals), +/- inflammatory cells, disruption of the internal elastic lamina, damage extending to the media, ingrowth of blood vessels and plaque fissuring (blood allowed in -> expansion and exposure of substances -> thrombus).

Question 9

List some clinical effects of atherosclerosis.

Answer 9

IHD -> sudden death, MI, angina pectoris, arrhythmias, cardiac failure. Cerebral ischaemia -> transient ischaemic attack (mini stroke), cerebral infarction, multi infarct dementia. Mesenteric ischaemia -> ischaemic colitis, malabsorption, intestinal infarction. Peripheral vascular disease -> intermittent claudication (pain in calves when walking a certain, decreasing distance), Leriche syndrome (buttock), ischaemic rest pain and gangrene.

Question 10

Which factors trigger the pathogenesis of atherosclerosis? Give 3 - A, G, L.

Answer 10

Age - slowly progressing throughout life, risk factors operate over years.
Gender - women are relatively protected pre-menopause, with a presumed hormonal basis.
Lipidaemia - high plasma cholesterol is associated - LDL is the most significant and HDL is protective.

Question 11

Lipid metabolism - lipid in the blood is carry on lipoproteins which carry ___________ and triacylglycerols with a _______________ lipid core and a _______________ outer layer of phospholipid and ____________ A-E.

Answer 11

Cholesterol
Hydrophobic
Hydrophilic
Apolipoproteins

Question 12

What are the functions of: chylomicrons, VLDL, LDL, HDL?

Answer 12

Chylomicrons transport lipid from the intestines to the liver. VLDL carry cholesterol and TG from the liver, TG are removed, leaving LDL, which are rich in cholesterol and carry it to non-liver cells. HDL carry cholesterol from the periphery back to the liver.

Question 13

Genetic variation of which apolipoprotein is associated in changes in LDL levels and how does this relate to atherosclerosis?

Answer 13

Apolipoprotein E - polymorphism of the genes involved. There are at least 6 ApoE phenotypes, so it can be used as a risk marker for atherosclerosis

Question 14

Familial hyperlipidaemia is a set of genetically determined abnormalities of lipoproteins, which leads to early development of atherosclerosis. What are the associated physical signs?

Answer 14

Corneal arcus (white ring around iris), tendon xanthomas and xanthelasma (smaller).

Question 15

Which factors trigger the pathogenesis of atherosclerosis? Give 3 - S, H, DM.

Answer 15

Cigarette smoking - powerful risk factor for IHD, risk falls if quit, mode of action uncertain.
Hypertension - strong pink with IHD, mechanism uncertain.
Diabetes Mellitus - doubles IHD risk, loss of premenopausal effect in women, also associated with a high risk of cerebrovascular disease and peripheral vascular.

Question 16

Which factors trigger the pathogenesis of atherosclerosis? Give 2 - A and I.

Answer 16

Alcohol consumption - over 5 units/day increase IHD risk, often associated with other risk factors, but still independent, smaller amounts may be protective.
Infection - Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus.

Question 17

Other (softer) risk factors for atherosclerosis include: lack of ___________, obesity, ______ water, oral ____________, stress and _____________ type. Genetic _______________- familial link is well known - may be variation in apolipoprotein metabolism or ________. Compounded by other factors.

Answer 17

Exercise
Soft
Contraceptives
Personality
Predisposition
Receptors

Question 18

What are the 4 main ideas about atherosclerosis pathogenesis?

Answer 18

Thrombigenic theory (encrustation), Insudation theory, Reaction to injury hypothesis and the Monoclonal hypothesis.

Question 19

What is meant by the Thrombogenic theory?

Answer 19

Plaques are formed by repeated thrombi, which lipid is derived from and there is an overlying fibrous cap. Supposedly resulting in atherosclerosis.

Question 20

How does the Insudation theory explain atherosclerosis?

Answer 20

Endothelial injury leads to inflammation, meaning meaning increased permeability of lipid from the plasma.

Question 21

How does the Reaction to injury hypothesis explain atherosclerosis?

Answer 21

Plaques are a response to endothelial injury, hypocholesterolaemia leads to endothelial damage; the injury increases permeability and allows platelet adhesion, monocytes penetrate the endothelium, smooth muscle cells proliferate and migrate. (Endothelial injury may be subtle/virtually undetectable - oxidised LDL may do damage)

Question 22

What does the monoclonal hypothesis describe in terms of atherosclerosis formation?

Answer 22

Smooth muscle proliferation had a crucial role, with each plaque being monoclonal, representing abnormal growth - each a benign tumour.

Question 23

What are the main processes involved in atherosclerosis?

Answer 23

Thrombosis, lipid accumulation, production of an intracellular matrix, interactions between cell types.

Question 24

What types of cells are involved in the process of atherosclerosis?

Answer 24

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

Question 25

What role do endothelial cells and platelets have in atherosclerosis?

Answer 25

Endothelial cells have a key role in haemostasis, with an altered permeability to Lipoproteins, they produce collagen, stimulate the proliferation and migration of smooth muscle.
Platelets also have a key role of haemostasis and produce PDGF (platelet derived growth factor).

Question 26

What role do smooth muscle cells and macrophages have in atherosclerosis?

Answer 26

Smooth muscle cells take up LDL and other lipid to form foam cells. They synthesis collagen and proteoglycans.
Macrophages oxidise LDL and take up lipids to become foam cells. They secrete proteases to modify the matrix and stimulate proliferation and migration of smooth muscle cells.

Question 27

What role do lymphocytes and neutrophils have in atherosclerosis?

Answer 27

Lymphocytes produce TNF, which may affect lipoprotein metabolism and stimulate the proliferation and migration of smooth muscle cells.
Neutrophils secrete proteases leading to continued local damage and inflammation.

Question 28

Explain a unifying hypothesis for atherosclerosis formation.

Answer 28

Endothelial injury (due to: raised LDL, ‘toxins’, hypertension, haemodynamic stress) causes (platelet adhesion, PDGF release, SMC proliferation and migration, insudation of lipid, LDL oxidation, uptake of lipid by SMCs and macrophages, migration of monocytes to the intima), stimulated SMCs producing matrix material, foam cells producing cytokines (-> further SMC stimulation and recruitment of other inflammatory cells).

Question 29

What is done by way of atherosclerosis prevention?

Answer 29

No smoking, reduced fat intake, treat hypertension, no excessive alcohol, regular exercise/weight control, but some who are genetically predisposed will still develop atherosclerosis.

Question 30

What may an atherosclerosis intervention try to do?

Answer 30

Stop smoking, modify diet, treat hypertension/diabetes and perhaps give
lipid lowering drugs.