Atherosclerosis

Question 1

Define arteriosclerosis

Answer 1

-Characterised by proliferative or hyaline thickening of the walls of small arteries& arterioles

Question 2

Define atherosclerosis

Answer 2

• A progressive disease affecting the intima of elastic& muscular arteries characterised by focal atheromas ( fibrofatty plaques)
• Overwhelmingly accounts for more death& serious morbidity in the western world than any other disorder

Question 3

Define Monckeberg’s medical sclerosis

Answer 3

charactersied by the calcification of the media of muscular arteries

Question 4

What are the major predisposing factors for atherosclerosis?

Answer 4

• Diet& hyperlipidaemias (hypercholestolaemia and hypertriglyceridemia)
• Hypertension: (both systolic and diastolic hypertension)
• Cigarette smoking ( esp. responsible for increasing heart disease in women)
• Diabetes Mellitus ( 2x risk of MI, 8x-150x risk of gangrene of the extremities

Question 5

What are the minor predisposing factors for atherosclerosis?

Answer 5

• Obesity
• Physical inactivity
• Male gender
• Increasing age
• Family history
• Stress (“type A” personality- competitive,stressful lifestyle) -controversial
• Oral contraceptives- controversial
• High carbohydrate intake-controversial

Question 6

Outline the 4 stages in the development of an atheromatous plaque according to the american heart association

Answer 6

• Type I: Lipid is present in the macrophages in the intima
• Type II: Lipid is present in both macrophages& SMCs
• Type III: fibrous plaque; lesions in the aorta in which lots of the fibrous tissue has accumulated
• Type IV: Complex plaque ( fibrous cap overlying a lipid core) ; Elastic van Gieson stain stains elastic tissue a black colour

Question 7

How does the fat get into the intima?

Answer 7

• Some of it is thought to get between the gaps between adjacent endothelial cells
• There’s also a receptor mediated process ( receptor mediated transcytosis) that takes lipid from the intimal surface across the endothelial cell cytoplasm and then deposits it on the internal side of the endothelial cell cytoplasm

Question 8

What is the role of endothelial injury in atherosclerosis?

Answer 8

• Endothelial damage is a major risk factor in atherogenesis but early lesions in humans develop at sites of intact endothelium
• Thought to start the process due to increased permeability, blood monocyte adhesion and EC replication
• Risk factors e.g hypertension & smoking increase endothelial permeability
• Increased expression of the vascular cell adhesion molecules ICAM-1 & VCAM-1 (possibly via an injury-induced activation of specific transcription factors that regulate inducible EC genes) increases monocyte adhesion

Question 9

What is the role of macrophages& other inflammatory and immunological mechanisms in atherosclerosis?

Answer 9

• Monocytes migrate into the intima and then accumulate LDL to produce foam cells
• Monocytes/ macrophages express the LDL receptor and a specific receptor ( scavenger receptor) for oxidised LDL ( oxidised by EC, platelet or WBC enzymes)
• T cells are found in plaques but their role is uncertain

Question 10

What is the role of hyperlipidaemia in atherosclerosis?

Answer 10

Hyperlipoproteinaemia is the abnormality common to most syndromes of premature atherosclerosis

• Can be primary (genetic defect) or secondary to some other disorder (nephrotic syndrome. diabetes, alcoholism, hypothyroidism)
• Increases in the plasma level of LDL may increase the level of lipid penetration in the arterial wall.
• Hyperlipoproteinaemia may also directly alter EC function

Question 11

How can Oil red O stain be useful in seeing in depicting an atheromatous plaque?

Answer 11

-Can be used to see neutral triglycerides and lipids so allows us to see how much lipid is in the plaque

Question 12

How can H&E stain be useful in depicting an atheromatous plaque?

Answer 12

-Can be used to see cholesterol crystals

Question 13

What is the role of thrombosis in atherosclerosis?

Answer 13

• Complication of late-stage atherosclerosis
• may contribute to plaque formation& luminal enroachment
• Fibrin often detectable in plaques

Question 14

What effects may atherosclerosis have on other major arteries

Answer 14

1. ) INTERMITTENT CLAUDICATION in the legs: slow, insidious narrowing of the vascular lumina, resulting in ischaemia of the tissues perfused by the involved vessels
2. ) MI: sudden occlusion of the lumen by super-imposed thrombosis or haemorrhage into an atheroma, producing ischaemia, and if severe and prolonged, infarction
3. ) Providing a site for THROMBOSIS and then EMBOLISM e.g cholesterol emboli in kidney
4. ) ANEURYSM/ RUPTURE: due to weakening the wall of a vessel e.g ruptured abdominal aortic aneurysm