L25-27 - vascular bio Flashcards
1
Q
tell me about the tunica intima
- placement
- 4 layers
- functions
A
- innermost blood vessel layer, faces lumen
- four layers from inner to outer:
1. endothelium - simple squamous
2. basal lamina
3. subendothelial CT - ECM + cells to synth ECM *sometimes smooth muscles (path)
4. internal elastic lamina - fenestrated for gas/nutrient exchange + elastin (NOT elastic fibers) - elastin
2
Q
tell me about the tunica media
A
- middle blood vessel layer
- smooth muscle + external elastic lamina - fenestrated for vasa vasorum feeds it
- no nervi vasorum
- elastin, elastic fibers (BOTH!), ibronectin, fibrillin-1, reticular fibers, proteoglycans
3
Q
tell me about the tunica adventitia (externa)
A
- CT layer, contains nerves and blood vessels
- type 1 collagen, elastic fibers, fibroblasts
- vasa vasorum - BV go through ext elastic lamina fenestrations to media
- nervi vasorum - nerves to BV, sympathetic, “fluorescent light halo” - gap junctions
4
Q
vasa vasorum and disease
- athero
- syphilis
A
- required vessels >1mm
- contributes to angiogenesis and inflammation in atherosclerosis
- syphilis = inflamed ascending aorta –> endarteritis and periarteritis –> obliterated vasa vasorum –> focal necrosis/scarring media –> degeneration elastic lamellae –> tree bark appearance to intima
5
Q
tell me about vascular endothelial cells
- type of cells
- elongation
- connections
A
- simple squamous
- elongated in direction of blood flow
- connected by cellular junctions
- have myoendothelial junction to communicate with smooth m. through fenestrations in internal elastic lamina for vasodilation
- many pinocytotic vesicles
- some apical microvilli
- contain Weibel-Palade bodies
6
Q
describe innervation of blood vessels
A
- arteries - nerve endings found in adventitia, not media
- veins - nerve ends found in both, less density than arteries
- mainly sympathetic
7
Q
process of vasodilation?
A
shear stress by blood flow => hyperpolarization of endothelial cell => through gap junctions to vascular smooth m. => vasodilation
8
Q
functions of endothelial cells?
A
- promote/inhibit blood coagulation (protein S)
- make prostacyclin = vasodilator
- modulate smooth muscle activity (endothelin-1 is a vasoconstrictor and NO is a vasodilator)
- regulate inflammatory cell traffic
- transport (pinocytotic vesicles)
- regulate angiogenesis
- movement of inflammatory cells from lumen to tissue (selectin = adhesion molecule)
9
Q
tell me about Weibel-Palade bodies
A
- contain Von Willebrad factor (coag VIII)
- tissue plasminogen activator
- interleukin 8
- P-selectin (allows leuks to connect to endothelial cells memb)
10
Q
differences between arteries and veins and capillaries
A
- arteries have lots of smooth muscle vs. veins have lots of CT
- capillaries are just endothelium and BL
- arteries have prominent internal elastic membrane
11
Q
describe an elastic artery
+ examples of them?
A
- characteristic alternating layers of smooth muscle and fenestrated elastic lamellae (NO elastic fibers)
- vasa vasorum down to middle of tunica media
- fibroblasts in adventitia only usually
- aorta, brachiocephalic trunk
12
Q
Marfan’s
A
- elastic fibers instead of just elastin which disrupts the structural integrity
- microfibrils cause disarray, leading to degeneration of elastic components and lakes of mucopolysaccharides (GAG deposits)
13
Q
how does the aorta change with age?
A
- incr. # elastic lamellae in media with age (smooth m. incr. also)
- subendothelial compartment thickens + moderate intimal fibrosis (normal)
- minor elastic lamellae fragmentation (normal)
- some picketing in intima
14
Q
describe a muscular artery
A
- medium artery
- lots of smooth muscle in the tunica media (brown/yellow, dark nuclei)
- less elastic elements
- prominent internal and external elastic membranes (dark)
- elastic fibers in adventitia
15
Q
how does the muscular artery change over time?
A
- fragmentation
- intimal hyperplasia (fibrosis)
- duplication of internal elastic lamina
- aneurysm - circle of Willis
16
Q
arteriole wall-lumen ratio?
A
1
17
Q
describe 3 types of capillaries
A
- continuous - specific transport without leakage
- found in CNS, lungs, muscle, adipose, exocrine
- tight junctions, no pores
- numerous pinocytotic vesicles
- well developed basal lamina - fenestrated
- found in kidneys, intestines, endocrine
- fenestrations in endothelial wall for rapid movement of material between lumen and EC
- diaphragms close pores (no diaphragms in glomerulus)
- continuous BL - sinusoid
- found in red bone marrow, spleen, adrenal cortex, liver
- very rapid exchange
- larger diameter, huge pores (larger than fenestrations)
- absent BL
18
Q
generally describe venous circulation vessels (compared to arterial)
A
larger lumen, thinner walls, no IEL or EEL, less smooth m. and elastic elements
19
Q
describe 2 types of venules
A
- pericytic - smallest venules surrounded by pericytes, in microcirculation
- muscular - larger venules, with smooth muscle in tunica media
20
Q
describe pericytes
A
- mesenchymal cells
- contractile
- can transform into smooth m. and fibroblasts
- contribute to scar tissue in CNS, etc.
21
Q
define vasculogenesis, angiogenesis, arteriogenesis, neovascularization and remodeling
A
vasculogenesis = de novo blood vessel formation
angiogenesis = BV growth from existing endothelial cell-derived channels
arteriogenesis = formation of arteries, arteriole/collateral vessel remodeling
neovascularization = umbrella term for vasculo-, angio- and arterio- genesis
remodeling = vascular changes due to change in the environment
22
Q
name 2 ways BV formation occurs in adults? which do tumors use?
A
- from endothelial precursor cells (EPCs)
- from pre-existing vessels
*tumor angiogenesis uses both of these
23
Q
what is vasculogenesis, what is it used for and describe the steps
A
vasculogenesis = new BV formation from EPCs
used to:
- replace lost endothelial cells
- re-endothelization of vascular implants
- neovascularization of ischemic organs, wounds, and tumors
steps:
- stimuli
- EPCs leave bone marrow
- EPCs enter vasculogenesis site
- BV form
24
Q
what is angiogenesis and describe the steps
A
angiogenesis = new BV from pre-existing BV
- vasodilation (NO) + increased permeability (VEGF)
- degradation of BL (metalloproteases) + loss of cell-to-cell contact/junctions (plasminogen activator)
- those endothelial cells migrate and proliferate (proangiogenic factors -VEGF/angiopoietin 2 and FGF2)
- endothelial cells mature into endothelial capillary tube
- elaborate BL (TGF-B) + recruit periendothelial cells (pericytes by Ang 1 with Tie2 and smooth m. by PDGR)
*also Ang 2 blocks stabilizing activity of Ang 1 so remodeling can occur
25
what are clinical benefits of proangiogenesis?
myocardial/peripheral/cerebral ischemia
wound healing and fx repair (Regranex for diabetic ulcers)
reconstructive sx
transplant of islets of Langerhans
26
what are clinical benefits of antiangiogenesis?
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tumor growth/mets (TEM8)
ocular neovascularization
hemangiomas
RA
atherosclerotic plaque neovascularization
birth control
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27
what is TEM8 and why is it useful?
tumor endothelial marker 8 is preferentially expressed in tumor vessels' epithelium, so drugs can target this to inhibit tumor angiogenesis
28
explain the architecture of the great saphenous vein that makes it useful for CABG
it has atypical venous architure in that it has a thick media (2-3 smooth muscle layers with inner longitundinally arranged and outer circularly arranged) allowing it to withstand high pressure environments
after graft, saph. v. remodels, thickens the media and intima due to high pressure environment
29
explain the process of vascular wall remodeling
change in BP or tensile strength --> vascular stress --> vascular remodeling to normalize wall stress
30
what is the response of a large artery, a small artery, and an arteriole in response to increased pressure?
- which is inward/outward hypertrophy?
1. large artery will increase outer diameter, increase wall thickness, maintain lumen (outward hypertrophy)
2. small artery will increase lumen diameter, increase wall thickness, but maintain outside diameter (inward hypertrophy)
3. arteriole will respond with either inward hypertrophy or inward remodeling (by decreasing both wall thickness and diameter), or rarefaction (vessel disappears)
31
define rarefaction
vascular remodeling leading to loss of arteriole in response to increased pressure
32
describe the innermost heart layer
endocardium = tunica intima
- endothelium = simple squamous + BL
- subendothelial layer
- myoelastic layer = smooth m. and elastic/collagen fibers
- subendocardium = loose CT, small BV, nerves, purkinje fibers
33
describe the middle heart layer
myocardium = tunica media
- 3 types of cardiocytes = contractile, myoendocrine, and specialized conductive
*myoendocrine cells has vesicles that contain atrial natriuretic factor, B-type natriuretic factor (ventricles)
= function in diuresis and vasodilation
34
describe the outermost heart layer
epicardium = tunica adventitia
- mesothelium = simple squamous + BL
- subepicardium
35
which natriuretic factor is elevated in CHF?
B-type
36
where are purkinje fibers found?
only in ventricles
| only in subendocardium of endocardium - innermost heart wall layer
37
describe the cardiac skeleton composition and fxn
dense CT, anchors cardiac muscle and valves
includes annuli fibrosa, trigona fibrosa, and septum mambranaceum
38
describe the makeup of AV valves and each layer's function
3 major layers
1. atrialis = elastic and collagen tissue beneath atrial surface endothelium
- fxn = contraction/spring
2. spongiosa = middle layer loose CT
- fxn = shock absorption
3. fibrosa = core denser irregular CT beneath ventricular surface endothelium
- fxn = mechanical integrity
39
describe the makeup of semilunar valves and each layer's function
3 layers
1. fibrosa = core denser irreg. CT beenath aortic/pulmonic endothelium
- fxn = spring recoil
2. spongiosa = middle
3. ventricularis = elastic/collagen beneath ventricular endothelium
- fxn = structural integrity
40
compare/contrast AV and semilunar valves
AV has atrialis subjacent to atrial surface
semilunar has ventricularis subjacent to ventricular surface
- similar composition of these layers
both valve pairs have similar spongiosa and fibrosa but fibrosa for AV is subjacent to ventricular surface whereas fibrosa for semilunar is subjacent to aortic/pumonic surface
*ALSO fibrosa for semilunar is THICKER than AV due to higher pressure - need more structural integrity
41
myxomatous degeneration of AV valve
- most common cause of mitral valve prolapse
- high dermatan sulfate deposition in spongiosa plus disorganization of collagen and elastin leads to disrupted structural integrity
42
describe the cardiac conduction tissue
- size
- myofibril content
- other inclusions
SA node - smaller than atrial muscle cells, contain fewer myofibrils
- humans lose 90% of SA nodal cells by age 80 => decreased basal HR
AV node is similar to SA node
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AV bundle (of His) - contains purkinje fibers whcih travel in subendocardium, connected to muscle cells by gap junctions
- 2x diameter of cardiac muscle cells (30 vs 15 micrometers), few myofibrils, abdundant glycogen, 1-2 nuclei/cell
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43
what's the importance of cardiac stem cells and early committed cells?
CSCs and ECCs can be activated to reconstitute necrotic myocardium
- both are found in the AV sulcus, from where they migrate to injury site, differentiate into cardiomyocytes/SMCs/endothelial cells
- hCSCs can replace myocyte compartment 11-15x
44
describe each component of the lymphatic vascular system
- capillaries
- vessels
- ducts
lymph capillaries
- thin, blind-ended, lined by single layer of endothelial cells
- BL incomplete/absent
- has anchoring fibrils (microfibrils)
- NO pericytes and SMCs and RBCs - might have leuks
lymph vessels
- similar to veins, but thinner walls + has valves
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lymph ducts (ex: thoracic ad right lymphatic duct)
- similar to veins + smooth muscle + vasa vasorum
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45
what's the clinical relevance of lymphatics?
lymph vessel density (defined by the marker LYVE-1) can be used as a prognostic indicator for spread of malignant tumors
46
clinical teaser:
15yo, sore throat, joint pain, fever, heart murmur, pericardial friction rub
what's going on?
- rheumatic fever - strep pharyngitis infxn
- immune response on mitral valve where attaching to chroda tendineae leads to mitral valve vegetations and Aschoff body formation
47
what are Aschoff body formations and what do they indicate?
- collection of lymphyctes, plasma cells, macrophages
- signature feature of rheumatic fever caused by streptococcal pharyngitis
- mitral valve immune response
