26 - Vascular biology II Flashcards

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1
Q

What are the important features of a continuous capillary?

A

Continuous capillary

  • Endothelial cells join together, and at the point of uncion, there will be an intracellular junction - there are two types of junctions that may exist here:
    • Completely tight zonula occludens
    • Interrupted incomplete fascia occludens
  • When endothelial cells join, one of the cells will have a marginal fold, which extends from the endothelial cell and covers the connection
  • Large volume of pinocytotic vesicles within the cytoplasm of endothelial cells
  • Intact basal lamina external to the endothelium - this is essentially the capillary wall, which will be thin to allow for rapid exchange
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2
Q

Where will you find continuous capillaries?

A

Locations

  • Areas where you would want specific transport of materials with no leakage
  • Examples: lungs, CNS, muscle, adipose tissue
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3
Q

Why is there a large volume of pinocytotic vesicles in the cytoplasm of endothelial cells that comprise a continuous capillary?

A

Pinocytotic vesicles

  • Pinocytosis is a mode of endocytosis in which small particles are brought into the cell, forming an invagination, and then suspended within small vesicles that have been formed by the plasma membrane of the cell it entered

Why is this needed in continuous capillaries?

  • Tight junctions limit the movement of material across endothelial cells
  • Pinocytic vesicles are able to make up for this restriction by ferrying materials across endothelial cells
  • Vesicles can fuse, forming c_ontinuous temporal channels_ across an entire endothelial cell
  • This allows for the movement of materials from the lumen to the extracellular environment
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4
Q

Describe a fenestrated capillary without diaphragms

A

Features

  • Numerous permanent fenestrations in the endothelial cell wall
  • This allows for rapid movement of material between the lumen and the extracellular environment

Where would you find fenestrated capillaries without diaphragms?

  • Glomerular capillaries of the kidneys where blood is filtered in renal corpuscle
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5
Q

Describe a fenestrated capillary with diaphragms

A

Note that most fenestrated capillaries have diaphragms

  • Some pinocytotic vesicles will still be present, but the fenestration alone will allow for rapid exchange
  • On an image of a fenestrated capillary with a diaphragm, you will see small lines that block the gaps of the fenestrations

Where would you find fenestration capillaries with diaphragms?

  • Glomerular capillaries in the kidney
  • Elsewhere in the kidney
  • Intestines (allows for rapid movement of absorbed nutrients into the blood stream)
  • Endocrine organs (allows for rapid pickup of released hormones by the blood
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6
Q

Describe a sinusoidal capillary

A

Sinusoidsal capillary features

  • Larger in diameter compared to continuous and fenestrated capillaries
  • Huge pores, larger than fenestrations
  • Basal lamina is absent, or discontinuous if it is actually present
  • This allows for more rapid exchange of materials

Where would you find sinusoidal capillaries?

  • Bone marrow (allows for movement of cells into the blood stream that were developing in the bone marrow)
  • Liver
  • Spleen
  • Adrenal cortex
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7
Q

What are venules? What are the two types?

A

Venules

  • The smallest structure in the venous circulation
  • Two types
    • Pericytic venules: these venules are bound in microcirculation and have pericytes around them
    • Muscular venules: these are larger than pericytic venules and have smooth muscle in the tunica media
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8
Q

Describe the movement of lymphocytes from the blood into the extracellular environment

A

Lymphocyte movement

  1. Lymphocyte recognizes adhesion molecules on wall of endothelium
  2. Lymphocyte attaches to endothelium at region of marginal fold
  3. Lymphocyte disrupts junctional complex
  4. Lymphocyte moves between endothelial cell junction
  5. Lymphocyte crosses endothelial cell wall and enters extracellular environment
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9
Q

How much exchange occurs across the wall of a pericytic venule? A lot or a little?

A
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10
Q

Describe a dilated pericytic venule in the area of inflammation

A

Pericytic venules in inflammation

  • Many nuclei will be visible at the margins of pericytic vesicles
  • This indicates that neutrophils are undergoing margination
    • This is the movement of margins so that they attach to endothelial cells
    • This allows them to emigrate across the pericytic venule wall and enter the extracellular environment
    • Upon doing so, they can clean up debris from the inflammatory state
  • Note that many RBCs will also be visible
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11
Q

What constitutes a “small vein”?

A

Small vein

  • A little larger and more muscular than a venule
  • The following layers will be visible
    • Endothelium (white)
    • Muscle within the tunica media (thin, dark blue)
      • In the low pressure venous system, the tunica media will be thin and not much smooth muscle will be present
      • In the higher pressure venous system, more tunica media and smooth muscle will be present
    • Tunica adventitia collagen fibers (light blue)
      • This will be the thickest layer
  • You will see valve leaflets - these are extensions of the endothelium
    • You need to know which direction the blood is flowing based on the orientation of the leaflets
    • Remember, the leaflets look like arms that are down by your sides, but out at a 30 degree angle - your head would be the direction of blood flow
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12
Q

What constitutes a “medium vein”?

A

Medium vein

  • Walls will be a little thicker
  • Smooth muslce, elastic elements and connective tissue will be present, with the connective tissue predominating
  • Layers
    • Tunica intima
    • Endothelium resting on the basal lamina
    • The tunica media will only have about 2 layers of smooth muscle (still pretty thin-walled layer)
    • Tunica aventitia is the thickest layer
      • Some smooth muscle components will be shown here
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13
Q

Would you see internal elastic lamina or external elastic lamina in a medium vein?

A

No!

  • These are seen in arterial circulation, NOT venous circulation
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14
Q

Describe the characteristics of a “large vein”

A

Large veins

  • Examples: protal vein, inferior vena cava
  • Unique tunica adventitia
    • Contains longitudinally arranged smooth muscle bundles
  • Tunica media will contain 2 smooth muscle layers that are circularly arranged
  • Tunica intima will be similar in size to other veins
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15
Q

What is the purpose of having longitudinally arranged smooth muscle bundles in the tunica adventitia of large veins?

A

Longitudinally arranged smooth muscles

  • Contract and force blood back to the heart against gravity
  • Circularly arranged muscles (such as in the tunica media) do not do this as effectively
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16
Q
A
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17
Q

Define vasculogenesis

A

De novo vesell formation

  • Making vessels “from scratch”
  • NOT from existing vessels
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18
Q

Define angiogenesis

A

Growth from existing EC-derived channels (extracellular?)

19
Q

Define arteriogenesis

A

Formation of arteries, arterioles and collateral vessel remodeling

20
Q

Define neurovascularization

A

This is an overarching term that includes

  • Vasculogenesis
  • Angiogenesis
  • Arteriogenesis
21
Q

Define remodeling

A

A vascular response to alterations in the environment

  • Occurs in existing vasculature as a response to alterations such as
    • Changes in blood flow
    • Changes in pressure in vasculature
22
Q

When would vsculogenesis occur in adults?

A

Recall that vasculogenesis is new vessel formation “from scratch”

  • Vasculogenesis occurs to…
    • Replace lost endothelial cells
    • Re-endothelialize vascular implants
    • Neovascularize ischemic organs, wounds and tumors
23
Q

Why is vasculogenesis is used by tumors?

A

Vasculogenesis is used by tumors to maintain their O2 requirement and metabolic needs

24
Q

What are EPCs and why are they important for vasculogenesis?

A

Vasculogenesis will occur from EPCs

  • EPCs = endothelial precursor cells
    • Bone marrow is one source of EPCs (#1 source)
    • Non-bone marrow niches exist and are mobilized in response to alterations in the environment
25
Q

Describe the process of angiogenesis of pre-existing vessels

A

Angiogenic steps

  1. Vasodilation from nitric oxide (NO) and increased permeability from VEGF will occur to pre-existing vessels
  2. Degradation of the basal lamina and disruption of intercellular junctions
    • BL degradation is mediated by matrix metalloproteases (MMPs)
    • Disruption of junctions is mediated by plasminogen activators
    • This includes separation of basal lamina and epithelial cells as well as disrupting junctions between endothelial cells
  3. ANG-2 destabilizes vessels
  4. Migration and proliferation of endothelial cells
    • This is mediated by VEGF and FGF
  5. Formation of an endothelial capillary tube
  6. Stabilization of the capillary tube
    • Elaboration of the basal lamina by TGF-beta
    • Recruitment of periendothelial cells (pericytes or smooth muscle cells)
      • This is mediated by ANG-1, TIE-2 and PDGF
26
Q

What is the difference between ANG-2 and ANG-1?

A

REMEMBER

  • ANG-2: destabilizes an existing vessel for angiogenesis
  • ANG-1: stabilizes a newly formed capillary tube following angiogenesis
27
Q

Outline the steps of proliferation and migration of endothelial cells

A
  1. Vasodilation and increased permeability of vasculature
  2. Basal lamina disruption
  3. Disruption of endothelial cell junctional complexes
  4. Further destabilization by ANG-2
  5. Proliferation and migration of endothelial cells
  6. Formation of endothelial capillary tubes
  7. Stabilization of capillary tube
28
Q

Describe the step of vasodilation and increased permeability of the vasculature during proliferatino and migration of endothelial cells

A

Vasodilation and increased permeability of vasculature

  • Pre-existing vasculature: endothelial cells attach to basal lamina and form junctional complexes with other endothelial cells (zippers)
  • NO and VEGF signals result in vasodilation and increased permeability, respectively
29
Q

Describe the step of basal lamina disruption in the proliferation and migration of endothelial cells

A

Basal lamina disruption

  • Matrix metalloproteases (MMPs) degrade basal lamina, separating it from endothelial cells
30
Q

Describe the step of disruption of endothelial cell jucntional complexes in the process of proliferation and migration of endothelial cells

A

Disruption of endothelial cell junctional complexes

  • Plasminogen activator disrupts intercellular endothelial cell junctions
31
Q

Describe the acutal step of proliferation and migration of endothelial cells within this process

A

Proliferation and migration of endothelial cells

  • In the presence of VEGF and FGF-2, endothelial cells from the pre-existing vasculature proliferate and migrate
32
Q

Describe the step of formation of endothelial capillary tubes in the process of proliferation and migration of endothelial cells

A

Formation of endothelial capillary tubes

  • Endothelial cells form capillary tubes, delicate precursor vessels
33
Q

Describe the step of stabilization of the capillary tube in the process of proliferation and migration of endothelial cells

A

Stabilization of capillary tube

  • Basal lamina elaboration and formation mediated by TGF-β
  • Endothelial cells connect to basal lamina
  • ANG-1 binds TIE-2 receptor on endothelial cells and recruits periendothelial cells (pericytes or smooth muscle cells)
34
Q

What is proangiogenesis? What are some examples?

A

Proangiogenesis

  • Definition: the clinical benefits of promoting angiogenesis
  • Examples
    • Myocardial ischemia
    • Peripheral ischemia
    • Cerebral ischemia
    • Wound healing
    • Fracture repair
    • Reconstructive surgery
    • Transplantation of islets of Langerhans
35
Q

What is antiangiogenesis? What are some examples?

A

Antiangiogenesis

  • Definition: the clinical benefits of inhibiting angiogenesis
  • Examples
    • Tumor growth and metastases (TEM8)
    • Ocular neovascularization
    • Hemangiomas
    • Rheumatoid arthritis
    • Atherosclerotic plaque neovascularization
    • Birth control
36
Q

What is Regranex? What does it treat?

A

Regranex (beclapermin)

  • A pro-angiogenic factor that increases wound healing by promoting the formation of new blood vessels
  • Commonly used in the treatment of diabetic ulcers
37
Q

What is TEM8?

A

TEM8

  • Tumor endothelial marker 8
  • Tumor vessels express TEM8
  • TEM8 aids in targeting drug molecules to tumor vessels in order to inhibit tumor angiogenesis, but not affect normal vessels
  • This means that normal vessels do NOT express TEM8 marker
38
Q

Where is the great saphenous vein? Why is it suitable for a graft in coronary bypass surgery?

A

Great saphenous vein

  • Longest vein in the body - runs along the length of the leg
  • The great saphenous vein is a suitable graft for coronary bypass surgery because its construction is unique and allows the vein to be taken from a low pressure (venous) environment and grafted to a high pressure (arterial) environment
39
Q

What are the specific features of the great saphenous vein that make it unique?

A

Great saphenous vein

  • The tunica intima contains the following…
    • Endothelium and a basal lamina
    • A subendothelium
    • A poorly developed IEM
  • It has a uniquely thick tunica media as compared to other veins
    • 2 to 3 smooth muscle layers
    • The inner muscle is longitudinally arranged
    • The outer layer is circularly arranged
    • Sometiems a third layer also exists
  • Also contains a tunica adventitia
40
Q

Describe the great saphenous vein before harvesting

A

Great saphenous vein

  • More muscular than the typical vein
  • Some intimal hyperplasia will be present
    • The tunica intima will be somewhat fibrous
    • This is because the procedure is usually done on an aging patient, not a young, healthy patient
41
Q

Describe the process of preparing the great sphenous vein for grafting

A

Must be careful – too much pressure applied to vein will damage tunica intima and endothelial cells, ultimately accelerating rate at which bypass graph will become restenotic

  • Restenotic: the recurrence of stenosis, a narrowing of a blood vessel, leading to restricted blood flow
42
Q

Describe the process of bypass grafting

A
43
Q

Grafted vessel is in a new, high pressure environment and will remodel over time due to the pressure change

  • Tunica media will thicken (media hypertrophy)
  • This will accelerate degree of hyperplasia and intimal thickening
A
44
Q

What is the lifespan of a great saphenous graft?

A

Approximately 10 years

  • Patients may need another bypass graft but may or may not be a candidate for a second bypass surgery