Pathology Of Atheroscleorsis And Lipid Disorders Flashcards
Three layers of larger vessels
Tunica Intima (inner layer)
Tunica Media
tunica Externa (outter most layer)
What is the basis for the majority of vascular disorders?
Injury to vessel walls (ESPECIALLY the endothelial cells in the vessels)
- stimuli can be biochemical, immunologic or hemodynamic
What pathological issues can endothelial cell injuries contribute to?
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
How are is healing are injured vessels repaired?
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
Atherosclerosis
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*
What two factors can be exaggerated as the thickening of the atherosclerotic plaques/lesions increases?
Ischemia to the tunica media of the vessels/ muscles
Bystander Inflammation
both of these combined increase chances of aneurysms to occur
Non modifiable and modifibile causes of atherosclerosis
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.*
What is the most important independent (non modifiable) risk factor for atherosclerosis?
Family history/genetics
What is the age range where atherosclerosis risk starts to increase noticeably?
40-60+
What is the main cholesterol component associated with increase risk of atherosclerosis?
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*
How much of an increase risk does HTN give someone for developing atherosclerosis?
Roughly 60%
Familial hypercholesterolemia
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
Secondary risk factors for atherosclosis
Hyper homocysteinemia
Metabolic syndromes
High lipoprotein levels
High levels of procoagulant
Step by step process of how atherosclerosis can develop from endothelial damage
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)
Fatty streaks definition
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
Atherosclerotic plaque definition
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*
Order of severity of the most serious sites for atherosclerosis (from most serious to least serous)
Circle of Willis
Internal carotid arteries
Popliteal arteries
Coronary arteries
Abdominal aorta
3 principal components of atherosclerotic plaques
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
What are the most common vessels for atherosclerosis
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)
Clinicopathologic symptoms and consequences of atherosclerosis s
Nothing directly but leads to the following symptoms
- ischemic heart/brain/kidney/lower extremity tissues
Leads to the following consequences
- MI
- strokes
- gangrene
Critical stenosis definition and consequences
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)
What does acute plaque change almost always triggers?
Thrombosis (rupture of the atheroma in the vessel walls)
- often leads to nearby tissue infraction
Vulnerable plaques
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
