pathophysiology of atheroma Flashcards
what is atheroma/ atherosclerosis?
formation of focal elevated lesions (plaques) in intima of large and medium-sized arteries
what does atheroma lead to when the lumen of arteries is narrowed?
ischaemia
what does myocardial ischaemia from atheroma lead to?
angina
what is arteriosclerosis?
age-related change im muscular arteries that causes smooth muscle hypertrophy, apparent redulpication of internal elastic laminae, intimal fibrosis that causes a decrease in vessel diameter
what sorts of ischaemia can be caused by arteriosclerosis?
cardiac, cerebral, colonic and renal
when does arteriosclerosis become clinically apparent?
when cvs is further stressed by haemorrhage, major surgery, infection, shock
what is the earliest lesion present in atheroma?
a fatty streak, yellow linear elevation of lipid-laden macrophages
in what age of patients are fatty streaks (earliest significant lesion of atheroma)?
young children
what is the stage of atheroma prior to fully developed atheromatous plaque?
early atheromatous plaque
what are the characteristics of an early atheromatous plaque?
smooth yellow patches in intima, lipid-laden macrophages
describe the composition of a fully developed artheromatous plaque
central lipid core with fibrous tissue cap, covered by arterial endothelium
what does collagen in the fibrous cap of an atheromatous cap do?
provides structural strength to the structure
what is the core of an atheromatous plaque made from?
it is risch in cellular lipids/debris from macrophages
what is often found around the rim of the atheromatous plaque?
foamy macrophages
what often forms in late development of artheromatous plaques?
dystrophic calcification
where are atheromatous plaques most likely to form?
at arterial branching points/bifurcations
what are some features of complicated atheroma?
haemorrhage into plaque which can then calcify, plaque rupture/fissuring ,thrombosis
what is the most important risk factor form atheroma?
hypercholesterolaemia
what is the congenital abnormality that can cause primary lipidaemia?
lack of cell membrane receptors for LDL, carriers affected, homozygous individuals affected more severely
what is the familial form of hyperlipidaemia called?
primary hyperlipidaemia
what is the acquired form of hyperlipidaemia called?
secondary
what are some signs of hyperlipidaemia?
-biochemical evidence- increased LDL, HDL, total cholesterol, triglycerides
-premature corneal arcus
-tendon xanthomata
-xanthelasmata
-risk of MI/atheroma
premature MI/atheroma
-family history of MI or atheroma
what is corneal arcus?
an opaque ring forms around the margin of the cornea
what is tendon xanthomata?
deposits of fat in the tendons, usually of the knuckles and achilles
what is xanthelasmata?
cholesterol deposits under the skin, usually around eyelids
what are the main risk factors for aheroma?
- cholesterol levels
- smoking
- hypertension
- diabetes mellitus
- male
- elderly
what are less strong risk factors for atheroma?
obesity sedentary lifestyle low socioeconomic background low birthweight ?microorganisms
what are the two main steps in the development of atheromatous plaques?`
- injury to endothelial lining
2. chronic inflammation and healing response of vascular wall to agent causing injury
describe in detail the formation of atheromatous plaques?
- endotheial injury and dysfunction
- accumulation of LDL in vessels wall
- monocyte adhesion to endothelium, these then migrate into intima and transform into foamy macrophages
- platelets adhere
- smooth muscle recruitment caused by release of factors from platelets and macrophages
- smooth muscle cell prolfieraton, ECM production and T-cell recruitment
- lipid accumulation (extracellular and in foamy macrophages)
what are some common causes of endothelial disturbance that can cause atheroma?
- haemodynamic disturbances
- hypercholesterolaemia
how does hypercholesterolaemia cause endothelial damage?
increases local production of reactive oxygen species
how does hypercholesterolaemia cause atheromatous plaques?
- lipoproteins aggregate in intima, modified by freeradicals produced by inflammatory cells
- modified LDL is taken up by macrophages forming foamy macrophages
- these are toxic to endothelial cells plus release growth factors (cytokines)
how are injured endothelial cells functionally altered to bring about atheroma?
- enhanced expression of cell adhesion molecules such and ICAM-1 and E-selectin
- high permeability for LDL
- increased thrombogenicity
describe the formation of an advanced atheromatous plaque
- lipid-laden macrophages die through apoptosis forming a lipid core
- in response to the core there is an inflammatory process in which there is proliferation of intimal smooth muscle, synthesis of collagen, elastin and mucopolysaccharides
- this forms a fibrous cap round the lipid core
how do established plaques grow in volume?
1 small areas of endothelial loss
- microthombi form at denuded areas of plaque surface
- there is organised repair with smooth muscle invasion and collagen deposition
what is the main symptom of ileal, femoral or popilteal artery stenosis?
intermittent claudication
what causes stable angina?
stenosed atheromatous coronary artery, small obstruction
what causes unstable angina (ischaemic pain at rest)?
very severe stenosed atheromatous coronary artery
what does long standing tissue ischaemia cause?
atrophy of the affected organ
what are the major complications of atheroma?
- rupture of plaque
- total occlusion of artery
what occurs when a plaque ruptures?
exposes highly thombogenic plaque contents to blood stream, this can cause occlusion thrombotic occlusion very quickley
what are the outcomes of total occlusion of an artery from atheromatous plaque?
irreversible ischaemia causing necrosis (infarction)
what causes a myocadial infarction?
total occlusion of the coronary artery
what causes a stroke?
total occlusion of the carotid or cerebral artery
what causes lower limb gangrene?
total occlusion of ileal, femoral or popliteal artery
what can be a cause of small infarcts in organs distal to a atheromatous plaque?
small thrombus fragments can emolise and block smaller arteries when the large original plaque ruptures
what can small emboli from atheromatous plaques cause if the block a coronary artery branch?
small foci of necrosis which can cause life-threatening arrhythmias
what can debris from a carotid artery atheromatous plaque cause?
stroke, TIA, cerebral infarct
what can happens when an atheromatous plaque slowly extends in to the media of the aorta and weakens it?
an aneurysm
or sudden rupture causing retroperitoneal haemorrhage
what are the features of atheromatous plaques that give them a high risk of having thrombotic complications?
thin fibrous cap
large lipid core
prominent inflammation
what are the approaches to prevent atheromatous plaques from forming?
smoking cessation blood pressure control weight loss regular exercise dietary modifications
what are the some general drugs used to prevent atheromatous plaques?
cholesterol lowering drugs
aspirin
