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Cardio Week 1 > Lecture 4: Histology and Biology of the Vascular System > Flashcards

Lecture 4: Histology and Biology of the Vascular System Flashcards

1
Q

What is the gradient of blood flow?

A

Blood flow in the vasculature flows along a pressure gradient that gradually DECREASES
Cross section of aorta = 3 cm^2 …. SMALL
Cross section of capillary bed = 3000 cm^2 … LARGE

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2
Q

Where is blood flow fastest? Slowest?

A

Aorta

Gets slower as the individual vessels become progressively smaller but cross section gets collectively bigger

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3
Q

What is responsible for macrocirculation?

A

Arteries

Veins

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4
Q

What is responsible for microcirculation?

A

Arterioles
Capillaries
Venules

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5
Q

What is a tunica?

A

Coat or layer (intima, media, adventitia)

Applies to arteries/veins but not capillaries, which only have intima

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6
Q

Are lymphatics a circuit?

A

No, they are one way

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7
Q

In general, what is present in the tunica intima?

A
  1. ENDOTHELIAL CELLS
  2. basal lamina
  3. subendothelial loose connective tissue
  4. Internal elastic lamina (arteries and veins ONLY)
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8
Q

In general, what is present in the tunica media?

A
  1. Smooth muscle cells
  2. Elastic fibers (elastic art > musc art > veins)
  3. collagen
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9
Q

In general what is present in the tunica adventitia?

A
  1. External elastic lamina (arteries only)
  2. Smooth muscle cells (esp. larger veins)
  3. Loos connective tissue
  4. vasa vasorum
  5. nerves (nervi vascularis)
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10
Q

What is the source of basal lamina?

A

Whatever cell that it is attached to (ie endothelial cells)

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11
Q

What is the source of the internal elastic lamina?

A

Smooth muscle cells

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12
Q

What are the similarities between arteries and veins? Differences?

A

Similarities
i. have similar intima
ii. predominantely differentiated by features of media
iii. lesser differences in their adventitia
Differences
Arteries tend to have THICKER walls, relative to their luminal diameter than do corresponding veins

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13
Q

What is the only vessel that has external elastic lamina?

A

Arteries

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14
Q

What are elastic arteries? What is it composed of?

A

Helps propel blood during cardiac diastole to dampen difference between systolic and diastolic arterial pressure
Example: aorta and primary branches
Elastic fibers allow aorta to expand during systole, storing energy, which can then propel arterial blood downstream during ventricular diastole
“snap” back of fibers to relaxed means closure of A-V valves

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15
Q

What is the vasa vasorum?

A

A network of small blood vessels that supply the walls of large blood vessels
Vessels of vessels

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16
Q

What is the function of MUSCULAR arteries?

A

Control regional blood flow as needed
Regulated by varying luminal diameter and resistance to flow by contraction/relaxation
Controlled by autonomic nervous system and endothelium

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17
Q

What are the key characteristics of small arteries/arterioles?

A

Major determinant of arterial RESISTANCE to blood flow and therefore arterial blood pressure
Controls flow to microvascular bed
If you want to control local blood flow and BP, you turn to the arterioles ninja

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18
Q

How are the small arteries/arterioles regulated?

A
  1. autonomic nervous system
  2. angiotensin II
  3. endothelial factors
    i. NO
    ii. endothelin
    iii. Prostacyclin
  4. chemical environment including O2, CO2, pH, etc.
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19
Q

At what point do the vessels stop having 3 layers?

A

Capillaries

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20
Q

What are the characteristics of the capillaries?

A

Responsible for fluid, gas, electrolyte and small molecule exchange between blood and tissues
Comprised of very thin endothelial cells with a basal lamina
Pericytes may surround capillaries
Lacks media and adventitia!

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21
Q

What are pericytes?

A

Contractile cells that wrap around endothelial cells of capillaries
Aka Rouget or mural cells

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22
Q

What are the mechanisms of exchange between capillary lumen and extravascular space?

A
  1. Passive diffusion across the membranes and cytoplasm
  2. Active transport across membranes via pinocytic vesicles (w/ or w/o receptors)
  3. Passage between adjacent endothelial cells
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23
Q

What is the function of venules?

A

Controls permeability and leukocyte emigration

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24
Q

What are the key characteristics of venules?

A

Capacitance vessels readily distend and can store variable volume of blood
Site of egress of inflammatory cells from blood to tissues

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25
What are the function of venous valves?
Endothelial covered semi-lunar flaps of INTIMA that protrude into venous lumen in direction of forward flow
26
What are the key characteristics of veins?
Tend to have thinner walls, esp media, and larger lumen compared to arteries Have less muscle and elastic fibers in media More easily stretched so can be capacitance (or Storage) vessels for blood volume have SEMILUNAR valves that prevent backflow
27
What are the three kinds of capillaries?
1. Continuous capillaries 2. Fenestrated capillaries 3. Discontinuous capillaries
28
What are continuous capillaries?
Lined by complete layer of endothelial cells with tight junctions and COMPLETE basal lamina Transport takes place across the endothelial cells by diffusion or via pinocytotic vesciles Most COMMON type of capillary
29
What are fenestrated capillaries?
Endothelial cells with pores w/ or w/o a diaphragm Basal lamina is CONTINUOUS Pore diaphragm fenestrated capillaries in gall bladder, intestine, endocrine and renal tubules NO DIAPHRAGMS in fenestra are seen in RENAL GLOMERULI
30
What are discontinuous capillaries?
``` Incomplete endothelial lining + basal lamina Holes in cytoplasm and basal lamina E.g. sinusoids in spleen Most permeable capillary structures Guarded by Kupfer cells in the liver ```
31
Where do you see discontinuous capillaries?
Liver | Spleen
32
What are sinusoids?
Larger diameter capillaries with sinuous (sinusoidal) profiles Associated with DISCONTINUOUS ENDOTHELIUM e.g. liver sinusoids
33
What are the exceptions to the usual microcirculation?
1. Portal ARTERIAL circulation e. g. renal circulation (2 sets of capillaries) 2. Portal VENOUS circulation e. g. hepatic portal and hypophyseal portal 3. Hypothalamic/anterior pituitary
34
What is the purpose of different aspects of macro/microcirculation?
Elastic arteries = CONDUCTANCE (propels blood during ventricular diastole) Muscular arteries = regional distribution of blood flow Small arteries/arterioles = RESISTANCE (BP and local blood flow) Capillaries = exchange Venules = immune cell migration Veins = CAPACITANCE (accommodate increased intravascular volume
35
What are the four key features of vascular endothelial biology and function? (Starred)
1. Anti-thrombotic/prothrombotic properties 2. Exchange of fluids, gases and solutes, etc. 3. Modulation of inflammatory cell migration 4. Modulation of vascular smooth muscle contractility
36
How do endothelial cells act to induce thrombosis?
1. reduced prostacyclin and thrombomodulin 2. increased von Willebrand factor (factor VIII) exposure Endothelials cells become prothrombotic with stasis (lack of movement of legs, etc.)
37
What is factor VIII?
Von willebrand factor
38
Where are vWF synthesized? Stored?
Endothelial cells | Stored in cytoplasm by Weibel-Palade bodies (W-P bodies)
39
What is Prostacyclin?
A prostaglandin produced in the walls of blood vessels that acts as a VASODILATOR and INHIBITS platelet aggregation
40
What is thrombomodulin?
Integral membrane protein that is a cofactor of thrombin | REDUCES coagulation by turning thrombin into an anticoagulant enzyme
41
What modulates inflammatory cell migration?
Expresses E-selectins and ICAMs (immunoglobulin cell adhesion molecules) that latch onto to circulating leukocytes
42
What modulates vascular smooth muscle contractility?
``` Endothelial cells produce molecules that can either vasodilate or vasoconstrict Vasodilators i. NO ii. Prostacyclin iii. endothelin (if it acts INDIRECTLY) Vasoconstrictors i. endothelin (if it acts DIRECTLY) ```
43
What are key features of vascular smooth muscle?
Always in a constant state of tension Requires very little motion Classified as a tonic smooth muscle Depends on constant sympathetic stimulation Can proliferate and MIGRATE into the intima in response to stimuli
44
What are the differences between smooth and skeletal muscle?
Smooth muscle has NO sarcomeres, no T tubules and no Troponin Multiple triggers of contraction Functions can be modulated Can proliferate and migrate Actin-myosin linkage for smooth muscle can maintain tension with little expenditure of energy, LATCH STATE Thin filaments are attached to DENSE BODIES in either the cytoplasm of plasma membranes -attachment to dense bodies mediated by desmin and vimentin
45
What are dense bodies of smooth muscle?
``` Composed of alpha actin Bodies that anchor THIN filaments of smooth muscle either in cytoplasm or plasma membranes Attachment set by intermediate filaments i. desmin ii. vimentin ```
46
What is the structure of myosin in smooth muscle?
Has 2 heads, each with actin binding site Each side of myosin filament can bind to actin filament with OPPOSITE POLARITY Higher proportion of Actin to myosin than in skeletal muscle
47
What is the latch state?
The state in smooth muscle in which there is tension maintained for a prolonged period with little energy expenditure Does not require further stimulation
48
What is the significance of the lack of organized sarcomeres in smooth muscles?
Possibility of interaction of myosin with multiple actin of differing polarity and location allows vascular smooth muscle to undergo i. greater degrees of contraction ii. maintain maximal contractile force at multiple different lengths Smooth muscle = side polarity while skeletal muscle = end polarity
49
What are the control mechanisms for contraction of vascular smooth muscle?
``` 1. Increased intracellular calcium Derived from extracellular space or ER Increased calmodulin AP can open ENaC in plasma membrane to allow for influx of extracellular calcium 2. Can be triggered by chemical mediators such as i. norepinephrine ii. angiotensin II iii. endothelin iv. vasopressin v. thromboxane A2 Binding of chemical mediators activates phospholipase C and produces IP3 which then opens calcium channels 3. Can also be triggered by STRETCH ```
50
What is the MoA of smooth muscle contraction?
Phosphorylation of myosin by MLC KINASE | MLC kinase activated by increased Ca (which is activated by AP)
51
What is the MoA of smooth muscle relaxation?
Dephosphorylation of myosin by MLC PHOSPHATASE How does smooth muscle relax? 1. reduction of intracellular calcium via ATP dependent Ca pumps 2. stimulation of GPCR to increase adenyl cyclase and cAMP which increase Ca efflux 3. At any given level of intracellular calcium, NO causes increased cGMP, which then increase phophotases
52
What is cGMP broken down by?
Phosphodiesterase | So more phosphodiesterase, less vasodilation
53
What is the structure of the myosin molecule?
1. Regulatory light chain 2. Essential light chain 3. Head
54
What does calmodulin do?
Activates myosin light chain kinase In context of smooth muscle Ca-Calmodulin complex activates the light chain
55
What are the non-contractile functions of vascular smooth muscle?
1. collagen secretion (type IV, I and III) 2. elastin secretion (internal elastic fiber for instance) 3. ECM components like proteoglycans and glycoproteins 4. can contribute to the formation of the atherosclerotic plaque
56
What are the characteristics of lymphatics?
Delicate vascular structures that drain excess EXTRAcellular fluid out of tissues into systemic veins One way flow (presence of valves) so it is not a circuit No internal pump so depends on external compression
57
Where are lymphatics not found?
In the CNS, cartilage, bone, bone marrow, thymus, placenta, cornea, teeth and fingernails
58
What is the function of the lymphatics?
Drain extracellular fluid from most tissues and transport FATS Also a CONDUIT for APCs and travel of LYMPHOCYTES to target tissue
59
What does chylous mean?
Description of the OPAQUE color seen in the usually clear lymph after a high fat meal
60
What is the course of lymphatics?
Extravascular space  lymphatics  lymph nodes  thoracic duct and right lymphatic duct  left and right brachiocephalic veins
61
What is contained in lymphatics?
Chylomicrons Proteins APCs
62
What are lymphangions?
Segments of the lymphatics that are divided by valves
63
What diseases may present in elastic/muscular arteries?
1. Atherosclerosis 2. aneurysms 3. thromboemboli (systemic arterial, aortitis, arteritis)
64
What disease may present in small arteries and arterioles?
Arteritis (polyarteritis nodosa) Arteriolosclerosis Microvasculitis (Wegener granulomatosis)
65
What disease may present in capillaries?
Capillaritis (Goodpasture syndrome) Microvasculitis Role in acute inflammation
66
What disease may present in venules?
Microvasculitis
67
What disease may present in veins?
Varicose veins Venous thrombosis Thromboemboli
68
What disease may present in lymphatics?
Lymphedema

Cardio Week 1 (11 decks)

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