Mechanism of Vascular Disease: Atheroma

Question 1

Causes of myocardial infarction?

Answer 1

Muscle cell death (left ventricle - rarely in right as muscle is thinner)
Loss of blood supply
Occlusion of anterior descending branch of left coronary
Coronary artery thrombosis

Question 2

What does infarction mean?

Answer 2

Necrosis due to loss of blood supply

Question 3

Blood test for myocardial infarction?

Answer 3

Elevated troponin and cardiac enzymes - released when cells undergo death by necrosis (contents released can leak into blood)

Question 4

What is an atheroma?

Answer 4

Disease process of elastic ARTERY walls, in response to injury mechanism; complications are common and serious and there is a degree of preventability to the disease

Accumulation of degenerative material in the tunica intima (inner walls) - narrows lumen

Referred to as FIBRO-FATTY PLAQUE

Question 5

Formation of an atheroma?

Answer 5

Deposition of fat and fibrosis (scar tissue) - myofibroblasts produce collagen and fibrinite (scar tissue that has no elasticity, instead of smooth muscle)

Deposition of needle-shaped cholesterol crystal, scar tissue and lipid and platelet accumulation

Question 6

Structure of a coronary artery?

Answer 6

Endothelium
Tunica intima
Internal elastic lamina
Tunica media 
External elastic lamina
Tunica adventitia

Question 7

Risk factors for atheroma?

Answer 7

Family history - unchangeable 
Male
Smoking
Hypertension
Diabetes
Plasma lipids
Obesity
Age
Geography

Question 8

Reducing atheroma risk?

Answer 8

Family history cannot be changed
Cannot change gender but pre-menopausal females have reduced risk
Non-smoker
BP control
Diabetes control/prevention
Diet
Exercise
Moderate alcohol
Low lipids
Geography often cannot be changed

Question 9

Pathogenesis of atheroma?

Answer 9

Fatty streak
Fibrofatty plaque
Proliferative atheroma
Complicated atheroma

Different blood vessels can display different stages

Question 10

Aetiology of atheroma?

Answer 10

Endothelial injury:
Response to injury (inflammatory)
Macrophages, platelets - exit circulation between injured cells leading to:
Lipid accumulation
Smooth muscle proliferation - instead of being contractile, scar tissue is laid down

Question 11

Causes of endothelial injury?

Answer 11

Lipids
Pressure
Toxins
Sheer stress

Question 12

Describe endothelial injury

Answer 12

Neutrophils activate their integrins, which bind to endothelial ICAMS

Leukocyte attachment via expression of selectins, then VCAMs and ICAMs (for firmer adhesion) on endothelium

Due to certain chemicals, expression is increased

Transepithelial migration may be guided by further adhesive interactions, involving molecules such as PECAM1, which endothelial cells express at intercellular junctions

Accumulation of macrophages, containing uptaken lipid

wbcs release substances that activate other cells, like IL-1 and MCP-1 (MCP-1 is for chemotaxis so other cells accumulate)

All forms a fatty streak -early stage of atheroma

Question 13

Leucocyte surface adhesion is increased by?

Answer 13

Complement component C5a
Leukotriene B4
Tumour Necrosis Factor (TNF)

Question 14

What chemicals increase expression of ICAM-1 and ELAM-1 (Endothelial Leucocyte Adhesion Molecule)?

Answer 14

IL-1
Endotoxins
Tumour Necrosis Factor

Question 15

Where do atheroma tend to form?

Answer 15

Tend to develop earliest and most severely around vascular bifurcation sites

Question 16

Histology of fatty streak?

Answer 16

Will see intimal lipid

When removing parafin wax, lipids removed so macrophages containing lipids can be seen

Question 17

Plaque formation?

Answer 17

Platelets accumulate and release PDGF (Platelet Derived Growth Factor) - drives proliferation and migration of smooth muscle towards higher conc. of it, so media is broken down

More cells accumulate - adventitia prevents spread outwards so lumen is narrowed instead

Myofibroblasts produce collagen and fibrinite (scar tissue that has no elasticity)

Fibrofatty plaque formation, due to cholesterol crystals, scar tissue and lipid and platelet accumulation

Question 18

What is complicated atheroma?

Answer 18

Triggers coagulation cascade leading to a thrombus

Plaque rupture and intramural haemorrhage also leads to thrombus

Question 19

Complications of atheroma?

Answer 19

Thrombosis
Aneurysm
Dissection
Embolism
Ischaemia

Question 20

Describe aneurysm

Answer 20

Marked dilatation of atheromatous vessel and are common in aorta
Thus, lose elasticity, so no recoil, and so tearing and rupture/thrombus formation

Question 21

Describe dissection

Answer 21

Blood tears layers of vessel walls apart and pours into wall

Life-threatening

Question 22

What is atherosclerosis?

Answer 22

Similar process affecting arterioles

May cause functional target organ damage, like retinopathy (blindness), renal failure, vascular dementia, foot ischaemia and poor healing

Infarction is rare

Question 23

Risk factors for atherosclerosis?

Answer 23

Hypertension
Diabetes
Vasculitis