L25-28: Vascular Biology I-III and Atherosclerosis Flashcards
Layers of blood vessels. Composition of each layer
- ) Tunica intima
- Endothelium and basal lamina
- Subendothelial layer: loose CT, scattered fibroblasts and in arteries, occasional SM cells (depending on vessel type)
- Internal elastic lamina (membrane) composed of elastin with fenestrations for diffusion - ) Tunica media
- Concentric layers of SM cells, variable amounts of elastin, elastic fibers, fibronectin and fibrillin-1, also reticular fibers and proteoglycans in this layer
- External elastic lamina (membrane) comprised of elastin with fenestrations - ) Tunica adventitia/externa
- CT layer: type I collagen, elastic fibers, fibroblasts
What are vasa vasorum? Difference in arteries and veins?
- Vasa vasorum are vessels of vessels, ie. blood vessels for blood vessels greater than 1 mm diameter
- These supply wall to tunica media, tunica intima gets supply by blood in lumen
- In veins, vasa vasorum penetrates closer to tunica intima than for arteries. Why? Veins typically carry deoxygenated blood and have greater dependence on vasa vasorum’s oxygenated blood
What structure provides innervation of blood vessels? In what layer of arteries are nerve endings found? For veins? Differences?
- Nervi vasorum or vascularis
- Arteries: nerve endings found in adventitia, don’t penetrate media usually
- Veins: nerve endings found in adventitia and media, less density
- SNS mainly, some receive PSNS
Unique histological feature of endothelial cell
- Weibel-Palade bodies/granules containing Von Willebrand (clotting) factor, tissue plasminogen activator, IL-8, P-selectin etc.
What are pericytes?
- Mesenchymal cells that are contractile and can transform into smooth muscle cells and fibroblasts. Seen in tunica media position (not true media) in capillaries and are also associated with pericytic venules
Compare and contrast key differences between: a.) elastic arteries, b.) muscular arteries, c.) arteriole, d.) capillary, e.) venule, f.) small vein, g.) medium vein and h.) large vein
a. ) elastic arteries
- alternating SM and elastic lamellae with fenestrations in tunica media, which is a very thick layer
b. ) muscular arteries
- diminishing elastic component in tunica media, increase in muscle in this layer with this
c. ) arteriole
- 1-2 SM layers in tunica media, adventitia thin, lumen to wall ratio of 1
d. ) capillary
- tunica intima = endothelium and basal lamina (continuous or discontinuous depending on type of capillary)
- tunica media absent in true sense, replaced by pericytes
- tunica adventitia absent
e. ) venule
- 2 types: muscular and pericytic. Both have larger lumen than arteriole
- pericytic: thin walled surrounded by pericytes
- muscular: SM with and in tunica media
f. ) small vein
- smooth muscle in tunica intima continuous with smooth muscle in tunica media
g. ) medium vein
- CT predimonates here, thickest adventitia with few SM cells. No internal or external elastic layer typically
h. ) large vein
- longitudinally arranged SM cells in adventitia
Three types of capillaries. Location? Describe each
- ) Continuous: CNS, muscle, lungs, CT exocrine glands
- tight junctions between endothelial cells
- no pores or fenestrae in endothelial cells
- numerous pinocytotic vesicles in endothelial cells
- well-developed BL - ) Fenestrated: kidney (non-glomerular and glomerulus with absent diaphragms), intestines, endocrine glands – where rapid exchange is necessary
- Fenestrae in walls of endothelial cells
- Pores closed by thin diaphragm usually
- BL continuous - ) Sinusoidal: spleen, liver, red bone marrow and adrenal cortex – where cells can be exchanged
- discontinuous endothelial lining with large openings between
- macrophages associated with these vessels
Distinguish between: vasculogenesis, angiogenesis, arteriogenesis, neovascularization, blood vessel remodeling
- ) Vasculogenesis: de novo vessel formation via EPCs from bone marrow
- ) Angiogenesis: growth from existing ECs
- ) Arteriogenesis: formation of arteries, arterioles and collateral vessel remodeling – predominantly in heart
- ) Neovascularization: overarching term that includes above three
- ) Remodeling: vascular response to alterations in environment
Discuss steps of angiogenesis using pre-existing blood vessels
- Vasodilation via NO, increase vascular permeability via VEGF
- Degradation of basal lamina via MMPs, loss of intercellular junctions via plasminogen activator
- Migration and proliferation of ECs via VEGF and angiopoietin 2 (destabilizes) and FGF-2
- ECs mature into endothelial capillary tube
- Elaboration of BL via TGF-beta and recruitment of periendothelial cells (pericytes, smooth muscle cells) via Ang-1 (stabilizes) with Tie2 receptor on ECs, PDGF recruits SM cells specifically
Clinical benefit of proangiogenesis
- Ischemia (myocardial, peripheral, cerebral), wound healing (diabetic ulcers), fracture repair, reconstructive surgery, transplantation of islets of Langerhans
Clinical benefit of antiangiogenesis
- tumor growth/metastases, ocular neovascularization, hemangiomas, RA, atherosclerotic plaque neovascularization, birth control
Discuss the use of great saphenous vein in CABG
- Great saphenous is a unique atypical vein
- Tunica intima = endothelium with BL, subendothelium, poorly developed IEM
- Tunica media has 2 or 3 muscular layers, which is thicker than other veins
- Has tunica adventitia
Describe changes to vascular wall and lumen as a result of: a.) high flow, b.) low flow, c.) increased pressure (in large artery vs small artery vs arterioles)
a. ) high flow
- increase in outside diameter, increase in lumen diameter, no change in thickness wall
b. ) low flow
- decrease in outside diameter, decrease in lumen diameter, no change in wall thickness
c. ) increased pressure
- large artery: outward hypertrophy = increase in wall thickness, but lumen diameter is unchanged
- small artery: inward hypertrophy = increase in wall thickness, but outside diameter is unchanged, therefore decrease in lumen diameter
- arterioles (three options): 1.) inward hypertrophy (as above), 2.) inward remodeling which is a decrease in wall thickness and diameter or 3.) rarefaction which is vessel loss
Describe histology of endocardium
- Endothelium (simple squamous epithelium) with BL
- Subendothelial layer
- Myoelastic layer: SM with elastic and collagen fibers
- Subendocardium: loose CT, small BVs, nerve fibers and Purkinje cells or fibers in ventricles only
Describe histology of myocardium
- Contain three types of cardiocyte cells: Contractile cells, Myoendocrine cells, Specialized conductive cells
Describe histology of epicardium
- Mesothelium (simple squamous epithelium) with basal lamina and subepicardium
In what layer of the heart are Purkinje cells / fibers found?
- Subendocardium of ventricles only
In what layer of the heart are myoendocrine cells found? What do they secrete? Function?
- In myocardium of heart
- ANP and BNP (in ventricles)
- Diuresis and vasodilation through kidneys
- BNP elevated in CHF
Layers of AV valves. Composition, function of each layer?
- Atrialis: elastic and collagen tissue subadjacent to endothelium of atrial surface. Helps to contract valve
- Spongiosa: middle loose CT. Shock absorber
- Fibrosa: dense irregular collagenous tissue subadjacent to endothelium of ventricular surface. Mechanical integrity
Layers of semilunar valves. Composition?
- Fibrosa: dense irregular collagenous tissue subadjacent to endothelium of aortic or pulmonic surface. Mechanical integrity
- Spongiosa: middle loose CT layer
- Ventricularis: layer of elastic and collagen tissue subadjacent to endothelium of ventricular surface
Difference between spongiosa layer for AV and semilunar valves. Functional relevance?
- Thicker for semilunar valves
- Since this layer is a shock absorber of sorts, needs to be thicker in semilunar valves that reside in an environment of bigger pressure difference
Histological features of SA/AV node
- Cells smaller than atrial muscle cells, contain fewer myofibrils therefore less acidophilic than contractile cells
Histological features of AV bundle/bundle of His
- Composed of Purkinje fibers / cells that travel in subendocardium
- Connected by gap junctions to muscle cells
- Twice diameter of cardiac muscle cells, few myofibrils
- Appear white under some light staining preparations d/t abundance of glycogen.
- 1-2 nuclei per cell
Nonmodifiable vs modifiable risk factors for development of atherosclerosis and IHD
- ) Nonmodifiable: age (5 fold increase of MI between 40-60), sex (males at greater risk in comparison to premenopausal women), family history, genetics
- ) Modifiable: hyperlipidemia, HTN, smoking, DM, elevated CRP
