Atheroma

Question 1

What is atheroma

Answer 1

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

Question 2

Arteriosclerosis

Answer 2

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

Question 3

Arteriosclerosis effects

Answer 3

Cardiac, cerebral, colonic and renal ischemia in the elderly. Effects most noticeable when CVS stressed eg haemorrhage, surgery, infection, shock

Question 4

Fatty streak

Answer 4

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

Question 5

Fatty streak

Answer 5

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

Question 6

Early atheromatous phase

Answer 6

Young adults onwards, smooth yellow patches in intima made of lipid laden MQ

Question 7

Fully developed atheromatous plaque

Answer 7

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

Question 8

Late stage atheromatous plaque

Answer 8

Dystrophic calcification is extensive and the plaque will cover a large area

Question 9

Complicated atheroma

Answer 9

Haemorrhage into plaque (calcification)
Plaque rupturing
Thrombosis

Question 10

Aetiology of atheroma

Answer 10

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

Question 11

Signs of major hyperlipidemia

Answer 11

Biochemical- LDL, HDL, total cholesterol, triglycerides

Clinical- corneal arcus (lipid in eyes)
Tendon xanthomata (nodules in tendons)
Xanthelasmata (yellow cholesterol on eyes etc)

Question 12

Risk factors for atheroma

Answer 12

HYPERLIPIDEMIA
Smoking
Hypertension
Diabetes mellitus
Male
Elderly
(obesity, sedentary, low socioeconomic status, low birth weight)

Question 13

2 steps for start of atheromatous plaque development

Answer 13

1. injury to endothelial lining

2. chronic inflammation and healing response

Question 14

Atheromatous plaque formation process after inflam

Answer 14

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

Question 15

Causes of endothelial injury

Answer 15

Haemodynamic disturbance

Hypercholesterolemia (increases local production of reactive oxygen species)

Question 16

How are injured endothelial cells functionally altered

Answer 16

Enhanced expression of cell adhesion molecules (icam1, e-selectin)

High LDL permeability.
Increased thrombogenecity

Question 17

how are Microthrombi formed

Answer 17

Form at denuded areas of plaque surface and organized by smooth muscle cell invasion and collagen deposition (repeated cycles increase plaque volume)

Question 18

Progressive lumen narrowing due to high grade plaque stenosis effects

Answer 18

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

Question 19

Acute atherothrombotic occlusion

Answer 19

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

Question 20

Embolization of distal Arterial bed

Answer 20

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

Question 21

Ruptured atheromatous abdominal aortic aneurysm

Answer 21

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

Question 22

Vulnerable atheromatous plaques

Answer 22

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

Question 23

Prevention and therapy

Answer 23

Stop smoking, control BP, weight loss, regular exercise, diet modification

Cholesterol lowering drugs, aspirin (inhibits platelet aggregation)

Surgery