Pathology Of Atheroscleorsis And Lipid Disorders

Question 1

Three layers of larger vessels

Answer 1

Tunica Intima (inner layer)

Tunica Media

tunica Externa (outter most layer)

Question 2

What is the basis for the majority of vascular disorders?

Answer 2

Injury to vessel walls (ESPECIALLY the endothelial cells in the vessels)
- stimuli can be biochemical, immunologic or hemodynamic

Question 3

What pathological issues can endothelial cell injuries contribute to?

Answer 3

HTN, thrombosis

Vascular lesions

Atherosclerosis

*Note the endothelial cells and the underlying muscles are integrated and are critical for vascular Ute to respond to injury

Question 4

How are is healing are injured vessels repaired?

Answer 4

Smooth muscle cells migrate into the tunica intima layers
- they then proliferate and synthesize extracellular matrix and from a “neo-intima” layer which are covered by endothelial cells

note that while this process repairs damaged vessels, it can also eventually lead to luminal occlusion overtime, especially in the presence of repeated damage

Question 5

Atherosclerosis

Answer 5

Intima lesions that are called “atheromas” and impinge on vascular lumen and decrease the elasticity of the vessel
- overtime this increases chances of sudden complete occlusion, stenosis and/or vessel rupture

also produce atherosclerotic plaques (raised lesions of lipids and fibrous caps which are prone to rupture and produce a thrombus*

Question 6

What two factors can be exaggerated as the thickening of the atherosclerotic plaques/lesions increases?

Answer 6

Ischemia to the tunica media of the vessels/ muscles

Bystander Inflammation

both of these combined increase chances of aneurysms to occur

Question 7

Non modifiable and modifibile causes of atherosclerosis

Answer 7

Non modifiable:

• genetic abnormalities
• family history
• increasing age
• being male
• post menopausal women (not associated w/ decreasing estrogen levels)

Modifiable

• hyperlipidemia (bad diet)
• HTN
• smoking (2x increase)
• diabetes (2x increase)
• chronic inflammation (obesity or not being cured of a lingering disease)
• LVH
• having more than one risk factor increases your chances in a multiplicative effect (i.e having 2 increases chances by 4x; having 3 increases chances 7-8x; etc.*

Question 8

What is the most important independent (non modifiable) risk factor for atherosclerosis?

Answer 8

Family history/genetics

Question 9

What is the age range where atherosclerosis risk starts to increase noticeably?

Answer 9

40-60+

Question 10

What is the main cholesterol component associated with increase risk of atherosclerosis?

Answer 10

Low density lipoproteins (LDL cholesterol)
- increased levels causes immobile plaques to form at a higher rate

• High density lipoprotein cholesterol (HDL) mobilizes cholesterol in general and prevents plaque build up. Also moves already built up plaque to the liver to be destroyed*

Question 11

How much of an increase risk does HTN give someone for developing atherosclerosis?

Answer 11

Roughly 60%

Question 12

Familial hypercholesterolemia

Answer 12

Genetic receptor disease that is caused by a loss of function mutation in the gene that encodes for the LDL receptors
- LDL receptors bind to free floating LDL, trap it and bring it to the liver via intracellular transport to be catabolized

• this mutation prevents LDL receptors fro efficiently binding to LDL and promotes accumulation on tunica intima layers of vessels*
• induce premature atherosclerosis and greatly increase the risk of MI

Question 13

Secondary risk factors for atherosclosis

Answer 13

Hyper homocysteinemia

Metabolic syndromes

High lipoprotein levels

High levels of procoagulant

Question 14

Step by step process of how atherosclerosis can develop from endothelial damage

Answer 14

1) EC injury: endothelial dysfunction causes increased leukocyte adhesion, permeability and thrombosis risk
2) lipoproteins accumulate in vessel wall (especially if LDL levels are high)
3) platelet adhesion to the damage site occurs
4) monocytes adhere to the damaged endothelial and migrate into the intima. They then differentiate into macrophages -> foam cells (macrophages with LDL and cholesterol)
5) foam cells release inflammation cytokines

6) cytokines recruit Smooth muscle cells to proliferate and produce ECM
- this step leads to the conversation of the earliest lesion of atherosclerosis (which is a fatty streak -> mature atheroma)

Question 15

Fatty streaks definition

Answer 15

Begin as a small yellow fat macula that is formed by SMC’s repairing the vessels

• composed of lipid-filled foamy macrophages
• is not significant to flow disturbance and is not raised at this point

Question 16

Atherosclerotic plaque definition

Answer 16

Develop from maturation of a fatty streak

• lipid accumulation that eventually hardens (calcifies) and causes tunica intima thickening and further lipid accumulation
• these are raised lesions at this point
• may or may not have thrombus involved in them (gives a red-brown color in the yellow fat tissue)
• only affect a portion of the arterial wall and appear patchy in histology slides . Also a appear eccentric*

Question 17

Order of severity of the most serious sites for atherosclerosis (from most serious to least serous)

Answer 17

Circle of Willis

Internal carotid arteries

Popliteal arteries

Coronary arteries

Abdominal aorta

Question 18

3 principal components of atherosclerotic plaques

Answer 18

1) cells that include SMCs, foam cells and T cells
2) ECM produces by SMCs (include collagen, elastic fibers and proteoglycans
3) intracellular and extraceullar fat

Question 19

What are the most common vessels for atherosclerosis

Answer 19

Large elastic arteries are #1
(include aorta, carotid and iliac arteries

Large-medium sized muscular arteries are #2 but are not far behind
(Include coronary renal and popliteal arteries)

Question 20

Clinicopathologic symptoms and consequences of atherosclerosis s

Answer 20

Nothing directly but leads to the following symptoms
- ischemic heart/brain/kidney/lower extremity tissues

Leads to the following consequences

• MI
• strokes
• gangrene

Question 21

Critical stenosis definition and consequences

Answer 21

Expanding atheromas eventually grow to a point where they impinge blood flow

• most common with acute plaque changes
• usually occlusion is > 70%

often marked by stable angina of the chest

Consequences:

• bowel ischemia
• SCD
• Chronic IHD
• ischemic encephalopathy
• ischemic leg pain (intermittent claudication)

Question 22

What does acute plaque change almost always triggers?

Answer 22

Thrombosis (rupture of the atheroma in the vessel walls)

- often leads to nearby tissue infraction

Question 23

Vulnerable plaques

Answer 23

Atheromas that contain an unusually large about of foam cells and abundant extracellular lipids, and inflammatory cells
- have unusually low amounts of fibrous caps and SMCs

Most likely atheromas to form thrombosis