Pathology Of Atherosclerosis

Question 1

What is atherosclerosis?

Answer 1

Disease characterised by the formation of atherosclerotic plaques in the intima and media of high pressure large (aorta) and medium-sized arteries, such as the coronary arteries
The extent of atherosclerosis does not increase significantly until 50’s

Question 2

What are the first signs of atherosclerosis?

Answer 2

Fatty streaks: Yellow linear elevation of the intimal lining and is composed of masses of lipid-laden macrophages

Question 3

Distribution of atherosclerosis

Answer 3

Never in low pressure systems such as pulmonary arteries
Common in high pressure systems such as aorta & systematic arteries

Question 4

Constituents of plaque

Answer 4

Lipids
Smooth muscle
Macrophages (+ FOAM CELLS = macrophages that phagocytose LDLs)
Platelets
Fibroblasts

Question 5

Risk factors of atherosclerosis

Answer 5

Smoking
Hypertension
Diabetes
Obesity
Hyperlipidemia
Increase in age
Male
Highly confluent with social deprivation

Question 6

Endothelial damage theory

Answer 6

Endothelial cells are delicate high energy cells - susceptible damage despite Teflon coating
Smoking has free radicals, nicotine and CO which are all damaging to endothelial cells
Hypertension - sheering forces on endothelial cells - blood pressing on endothelial lining
Diabetes - superoxide anions glycosylation products
Hyperlipidemia - direct damage to endothelial cells

Question 7

What function alterations do injured endothelial cells undergo at sites of plaque formation

Answer 7

• Enhanced expression of cell adhesion molecules for monocytes
• High permeability for macromolecules such as LDL
• Increased thrombogenecity

Question 8

Clinical manifestations of atherosclerosis
- The processes which lead to clinical disease include

Answer 8

1. Progressive lumen narrowing due to plaque stenosis:
   Stenosis > 50-70% of the vessel lumen = critical reduction of blood flow in the distal arterial bed
   Reversible tissue ischaemia, esp during activity e.g. angina
   When the stenosis is severe = unstable angina
   Large intraplaque haemorrhage may increase the rate of stenosis is a short time span
2. Acute atherothrombotic occlusion:
   Plaque ruptures exposes HIGHLY THROMBOGENIC plaque components (collagen and lipid debris) to the blood stream
   Coagulation cascade activated = thrombotic occlusion of the vessel lumen
   Total occlusion = irreversible ischeamia, causing infarction of the tissue supplied by the obstructed artery
3. Embolisation of the distal arterial bed:
   Complication = detachment of small thrombus fragments (emboli)
   These will then embolism to the arterial bed DISTAL to the ruptured plaque
4. Ruptured abdominal atherosclerotic aneurysm:
   Rupture of weakened dilated atheromatous abdominal aneurysm cause retroperitoneal haemorrhage and death

Question 9

Formation of a atherosclerotic plaque

Answer 9

1. Fatty streak
2. Lipid accumulation = increase in LDLs, macrophages recruited to phagocytose them = FOAM CELLS
3. Platelet aggregation = plaque protrudes into artery lumen, disrupts laminar flow therefore platelets accumulate here = thinning of media occurs
4. Fibrin mesh + RBC trapping = platelet plug forms fibrin marsh over itself (stable 2’ clot) + RBCs trapped within this
5. Fibrous cap - fibroblasts form smooth muscle cap over the 2’ platelet plug = STABLE ANGINA
   - in UNSTABLE ANGINA - fibrous cap damaged and continuous platelet plug formation over this = lumen narrowed