Vascular Disease 1- Leah (6)- Arteriosclerosis* Flashcards
List the three layers of an arterial wall.
What are they comprised of?
1) intima, made up of endothelium (blood/ tissue barrier)
2) Media, made up of Muscle “M”
3) Adventitia, made up of CT, nerves, vasa vasorum
* adventitia is outermost*
Describe the function of the vasa vasorum:
Supplies blood to the outer 1/2 –> 2/3 of a vessel
List the four types of arteries:
- elastic
- muscular
- small arteries (less than 2mm diameter)
- arterioles
Describe elastic artery properties.
Which arteries are classified as elastic?
- Large arteries that actively expand and contract (recoil) at systole and diastole
- Elastic, hence rich in elastic tissue
- Aorta and its large braches are elastic
Describe muscular arteries.
Which arteries are classified as muscular?
- rich in smooth muscle
1. smaller aortic branches (carotids)
2. coronary
3. renal vessels
Function of arterioles:
- maintain TPR
- transition blood from pulsatile –> steady state as enters capillary bed
- reduce pressure and velocity of blood
Describe makeup of capillaries: wall, diameter, xs surface area?
-made up of intima/ endothelial cells only
(lacks adventitia and media)
-diameter of a single RBC
(smallest individual vessel types)
-largest overall cross sectional area of all vessel tpyes
Preferred site of inflammation in vasculature?
post capillary venules
Describe structure of veins: lumen? wall thickness? special features?
- large lumens
- thin walls
- have valves to direct flow (loss of valves = venous insufficiency/ varicose veins)
Describe structure of wall (1) and function of lymphatic vessels (3):
- Thin walled, endothelium lined
- Fxn: drain interstitial fluid
- disseminate disease*
- play a role in edema*
Normal function of endothelial cells in vessels (5):
- prevent thrombosis (maintain blood/ tissue interface)
- metabolize hormones
- regulate immune/ inflammatory processes
- modulate resistance
- affect growth of other cells (mostly SMCs)
Most “biochemically” active vascular cells
Normal function of SMCs in vessels (3):
- **VASCULAR REPAIR:
- synthesize ECM/ CT***
- migration/ proliferation
- contraction/ dilation
**Most “physically” active vascular cells.
How might tight endothelial junctions be loosened in the vasculature (2)?
What is the result?
- HTN or HISTAMINE most commonly loosen tight junctions.
- Result: EDEMA–> loss of leukocytes, proteins, and/or electrolytes
Basic definition of activation and dysfunction of endothelial cells:
Gaining some inducible property
(activation - good property; dysfunction- bad property)
*Not easy to distinguish the two processes, not testable
Describe abilities that an endothelial cell may gain during activation (4)
- production of adhesive molecule
- cytokines
- coagulants/ anticoagulants
- vasoactivators etc.
Describe abilities that an endothelial cell may gain during dysfunction:
adhesive/ thrombogenic properties
List three disease processes that involve endothelial cell dysfunction:
1) Hypertension
2) Thrombus
3) Atherosclerosis
Describe three events that may lead to vascular smooth muscle injury:
- mechanical (angioplasty)
- immunologic (i.e. transplant arteriosclerosis)
- multifactoral (atherosclerosis)
“neointimal formation” may be used to describe?
“new intima” –> intimal thickening; a response to injury
Result of intimal thickening:
some stenosis and occlusion, but less so than atherosclerosis
What are three steps of intimal thickening after injury is induced?
1) recruitment of SM–> intima either from adjacent tissue or circulating precursors
2) SMC mitosis and proliferation
3) SMC elaborate intimal ECM; create new CT
Compare and contrast SMCs in normal vasculature vs during intimal thickening
- During intimal thickening, SMCs are in a PROLIFERATIVE state, located in the intima
- In a normal vessel, SMCs are in a CONTRACTILE state, located in the media
Define arteriOsclerosis.
What are three types?
“Hardening of the arteries”- blanket term that includes:
1- atherosclerosis
2- arteriOLOsclerosis
3- Monckeberg medial sclerosis
Arteriolosclerosis effects what vessels?
What are the causes of arteriolosclerosis?
- small arteries and aterioles (usually renal)
- caused by HTN and DM
What are two types of arteriOLOsclerosis?
What are their causes?
-HYALINE
(mild chronic HTN, DM)
-HYPERPLASTIC thickening/ onion skinning
(malignant hypertension)
Monckeberg medial stenosis:
What is it and in what population is it observed?
- benign ring calcifications found in muscular arteries
- media layer
- elderly population
- may be palpable or visible on Xray (pipestem appearance)
- Does NOT lead to occlusion of vessels
Common benign finding on mammogram
Cause of 50% deaths in the western world?
atherosclerosis
Atherosclerosis effects what types of arteries?
Arteriolosclerosis?
Who gets atherosclerosis?
- Atherosclerosis = elastic and muscular
- ArteriOLOsclerosis = aterioles and small arteries
Old men + post menopausal women, esp w. genetic risk
Function of LDL and HDL
LDL (bad): transports cholesterol to tissue
HDL (good): transports cholesterol out of tissue and into the liver for biliary excretion
Dietary way to reduce LDL
Omega-3-FAs, statins
Surpising way to
1)lower
2)increase
HDL:
- EtOH may INCREASE GOOD FAT/HDL!! (Yay beer!)
- Statins may decrease HDL
By how much does smoking increase the risk of Ischemic HD? HTN? DM?
smoking 1 ppd- doubles IHD risk
HTN- increasesd IHD risk by 60%
DM- doubles risk of MI (induces hypercholesterolemia)
How is inflammation related to atherosclerosis?
-Along with cholesterol, it leads to plaque formation
(^MMP–>Destabilize plaque–> rupture–> ^ disease)
-CRP* (acute phase reactant) levels are indicative of MI, stroke, and PVD risk
How is hyperhomocystinuria related to atherosclerosis (3)?
-assc with CAD, PVD, stroke like inflammation
How is metabolic syndrome (prediabetes/ biscuit poisoning) related to atherosclerosis (3)?
Induces:
- HTN
- dislipidemia
- proinflammatory state
Major hypothesis for the pathogenesis of atherosclerosis:
“response to injury hypothesis”
Chronic inflammatory and healing response of arterial wall to endothelial injury
Three general steps of plaque formation:
HTN, hypercholesteremia, or hyperglycemia–>
- ENDO INJURY–>
- VASCULAR PERMEABILITY + LEUKOCYTE ADHESION–>
- FAT ACCUMULATION + THROMBOSIS
6 detailed steps of plaque formation
1) VASCULAR PERM–> lipoproteins enter vessel intima
2) MONOCYTES enter intima and subendothelium
3) MONOCYTES convert to MQs –> FOAM CELLS
4) PLATELETS stick to endothelium + recruit SMC
5) SMCs proliferate + produce ECM
6) LIPIDS (cholesterol/ esters) continue to accumulate in ECM and within cells
Where are plaques most commonly observed?
ostia of branching vessels due to turbulence
What are fatty streaks?
- earliest atherosclerotic plaques
- seen as early as age 1yoa and always by 10yoa
- composed of only foam cells in the intima of vessels
three
layers of a mature plaque:
- intima (thickened)
- fibrous cap
- necrotic center/ lipid core
- *media uneffected by disease process**
What does a plaque contain (cells, fat, ECM)?
- Cells: SMCs, MQs, T cells = chronic inflammation
- Fat: cholesterol and cholesterol esters
- ECM: fibrin, proteoglycans, CT
What is the fibrous cap of a plaque made up of (3)?
SMCs, collagen, inflammatory cells
Top five sites for atherosclerotic plaque
#1: abdominal aorta 2-coronaries 3-popliteal 4-internal carotids 5-circle of willis
Four plaque “change” types:
- acute (which consists of three subtypes)
- massive calcification/patchy (loss of elasticity)
- aneurysm (plaque weakens wall)
- atheroembolism (possible infarct)
What are the three acute changes assc with plaque formation?
- RUPTURE/ fissure
(releases plaque contents –> thrombosis) - EROSION/ ulceration
(exposes plaque BM –> thrombosis) - HEMORRHAGE into plaque (expands volume)
What makes plaque hemorrhage possible?
neovascularization at plaque shoulders
Describe CRITICAL stenosis and 4 consequences:
- small artery occlusion–> O2 demand»>O2 supply–> INTERMITTENT PROCESSES:
- angina (AT LEAST 70% occlusion)
- claudication
- chronic ischemic disease
- bowel ischemia
What is the most common cause of MI
thrombosis caused by plaque rupture or erosion
How does vasoconstriction contribute to ischemic injury?
- may be a response to ruptured plaques
- can cause a partial occlusion–>complete occlusion
Describe vulnerable plaques that are likely to undergo acute changes:
What makes them so vulnerable?
Do they typically cause critical stenosis?
Why are they clinically important?
- THIN fibrous cap + THICK necrotic center*–> ^MMPs + Inflammation–> ^ Likelihood rupture
- Usually DO NOT cause critical stenosis–> ASYMPTOMATIC until rupture–> unexpected EMERGENCY
common cause unexpected/sudden cardiac death is rupture of previously non-critical plaque
4 Important modifiable risk factors for atherosclerosis:
- Hyperlipidemia
- HTN
- Cigarette smoking
- DM
Two types of cells that can become “foamy”:
SMC, MQs
