Flashcards in MoD 7 Atheroma Deck (32):
What is atheroma?
The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is atherosclerosis?
The thickening and hardening of arterial walls as a consequence of atheroma
What is arteriosclerosis?
Thickening of walls of arteries and arterioles, usually as a result of hypertension or diabetes mellitus
What causes the fatty streak?
Lipid deposits in intima, yellow, slightly raised
relationship to atheroma debatable
What are the features of a simple plaque?
enlarge and coalesce(join together)
What are the features of complicated plaques?
Haemorrhage into plaque
What are some common sites of atheroma?
Aorta- especially abdominal
What are the early microscopic changes in atheroma formation?
Proliferation of smooth muscle cells
Accumulation of foam cells
What are the later microscopic changes in atheroma formation?
+/- inflammatory cells
disruption of internal elastic lamina
damage extending into media
ingrowth of blood vessels
Why does the smooth muscle proliferate?
Endothelial damage leads to platelet aggregation and release of PDGF which stimulates smooth muscle proliferation
How do foam cells form?
Proliferation and migration of smooth muscle cells taking lipid with it.
Macrophages arriving and phagocytosing the fat
What are the consequences of coronary artery atherosclerosis?
Ischaemic Heart Disease-
What are the consequences of atherosclerosis that give cerebral ischaemia?
cerebral infarction (stroke)
multi-infarct dememntia (lots of little strokes impairing cognitive function)
What consequences can mesenteric ischaemia have?
Anneurism from high pressure, hardening and weakening
What can peripheral vascular disease cause?
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)
What are the risk factors for atheroma?
Gender (women protected before menopause)
Hyperlipidaemia (corneal arcus, xanthalasma)
Infection (chlamydia, helicobacter pylori)
Lack of exercise
What is the unifying hypothesis of atherogenesis?
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
How can atheroma be prevented?
lipid lowering drugs
What can increase susceptibility to CHD?
genetic disorders like Familial hypercholesterolaemia
geographical location- less common in Mediterranean die to diet
Ethnicity- common in asians
What are risk factors for CHD?
infection e.g H. pylori
What do chylomicrons do?
transport lipid from intestine to liver
What do VLDLs do?
carry cholesterol and TG from liver
TG removed leaving LDL
What do LDLs do?
they are rich in cholesterol and carry cholesterol from liver to non liver cells
What do HDLs do?
They carry cholesterol from peripheries back to liver
How does apolipoprotein E link to atheroma?
Genetic variation in this protein are associated with changes in LDL levels and polymorphisms (dif phenotypes) can be used as risk markers for atheroma
What are some associated physical signs of hyperlipidaemia?
xanthelasma (eyelid ones)
How do we know hypertension isnt a sole cause of atheroma?
BP is high in arms and very uncommon for atheroma to be in arms
What cells are involved in atheroma formation?
smooth muscle cells
What do smooth muscle cells do?
Take up LDL and lipid to become foam cells
Synthesis collagen and proteoglycans
What do macrophages do?
Take up lipids to become foam cells
Secrete proteases which modify matrix
Stimulate proliferation and migration of smooth muscle cells
What do lymphocytes do in atheroma?
stimulate proliferation and migration of smooth muscle cells