Atheroma Flashcards
What is atheroma
Formation of focal elevated lesions (plaques) in the intima of large and medium sized arteries for example coronary for ischaemia
Can cause angina due to myocardial ischemia
Arteriosclerosis
Non atheromatous
Is an age related change where smooth muscle in muscular arteries hypertrophies with an apparent reduplication of internal elastic laminae.
Causes intimal fibrosis and decreases vessel diameter
Arteriosclerosis effects
Cardiac, cerebral, colonic and renal ischemia in the elderly. Effects most noticeable when CVS stressed eg haemorrhage, surgery, infection, shock
Fatty streak
Earliest significant lesion, in young children
A yellow linear elevation of the intimal lining made of lipid laden MQ. No clinical significance, may disappear or in at-risk patients cause atheromatous plaques
Fatty streak
Earliest significant lesion, in young children
A yellow linear elevation of the intimal lining made of lipid laden MQ. No clinical significance, may disappear or in at-risk patients cause atheromatous plaques
Early atheromatous phase
Young adults onwards, smooth yellow patches in intima made of lipid laden MQ
Fully developed atheromatous plaque
Central lipid core rich in cellular lipids/debris
with a fibrous tissue cap, covered by arterial endothelium
Collagens from smooth muscle cells in cap can give structural strength
Inflammatory cells reside in fibrous cap from arterial endothelium and can have run of foamy (uptake of oxidised lipoproteins) MQ
Form at bifurcations
Late stage atheromatous plaque
Dystrophic calcification is extensive and the plaque will cover a large area
Complicated atheroma
Haemorrhage into plaque (calcification)
Plaque rupturing
Thrombosis
Aetiology of atheroma
Hypercholesterolemia is biggest risk factor
1/500 Caucasians are heterogeneous for no LDL cell membrane receptors, this causes elevated plasma levels
1 in a million are homozygous and usually due from coronary artery atheroma in infancy or teens
Signs of major hyperlipidemia
Biochemical- LDL, HDL, total cholesterol, triglycerides
Clinical- corneal arcus (lipid in eyes)
Tendon xanthomata (nodules in tendons)
Xanthelasmata (yellow cholesterol on eyes etc)
Risk factors for atheroma
HYPERLIPIDEMIA Smoking Hypertension Diabetes mellitus Male Elderly (obesity, sedentary, low socioeconomic status, low birth weight)
2 steps for start of atheromatous plaque development
- injury to endothelial lining
2. chronic inflammation and healing response
Atheromatous plaque formation process after inflam
LDL accumulate
Monocytes adhere and go into intima to transform into foamy MQ
Platelets adhere and this causes factor release causing smooth muscle recruitment
ECM and t cell recruitment
Lipids accumulate
Causes of endothelial injury
Haemodynamic disturbance
Hypercholesterolemia (increases local production of reactive oxygen species)
How are injured endothelial cells functionally altered
Enhanced expression of cell adhesion molecules (icam1, e-selectin)
High LDL permeability.
Increased thrombogenecity
how are Microthrombi formed
Form at denuded areas of plaque surface and organized by smooth muscle cell invasion and collagen deposition (repeated cycles increase plaque volume)
Progressive lumen narrowing due to high grade plaque stenosis effects
Stenosis of >50-75% of lumen causes a critical reduction of blood flow and reversible tissue ischemia
Very severe stenosis causes ischaemic pain at rest (unstable angina) eg iliac, popliteal
Long-standing tissue ischemia will cause atrophy of the affected organ
Acute atherothrombotic occlusion
Rupture exposes highly thrombogenic collagen, lipid and debris to blood stream so thrombus is formed very fast
Total occlusion causes irreversible ischemia and necrosis
Eg stroke, myocardial infarction, lower limb gangrene
Embolization of distal Arterial bed
Small thrombus fragments occlude small vessels and cause small infarcts in organs eg heart for dangerous arrythmias
Or kidney, skin etc OR carotid for stroke
Ruptured atheromatous abdominal aortic aneurysm
The media under the plaque is gradually weakened by lipid inflammation.
It will gradually dilate
A sudden rupture can cause massive retroperitoneal haemorrhage with high mortality
Mural thrombus emboli to legs
Vulnerable atheromatous plaques
High risk of thrombotic complications
Typically thin fibrous cap, large lipid core and prominent inflammation
This secretes proteolytic enzymes, cytokines and reactive oxygen species
However highly stenotic plaques often have large fibrocalcific components and little inflammation
Prevention and therapy
Stop smoking, control BP, weight loss, regular exercise, diet modification
Cholesterol lowering drugs, aspirin (inhibits platelet aggregation)
Surgery
