circulation

Question 1

define vascular endothelium

Answer 1

single cell layer of cells (tunica intima) that acts as the blood-vessel interface on top of a basement membrane

Question 2

5 key physiological functions of vascular endothelium

Answer 2

vascular tone, thrombostasis, absorption and secretion, barrier, growth (and angiogenesis)

Question 3

key physiological functions of vascular endothelium: vascular tone

Answer 3

secretes and metabolises vasoactive substances

Question 4

key physiological functions of vascular endothelium: thrombostasis

Answer 4

prevents clots forming or molecules adhering to vessel wall

Question 5

key physiological functions of vascular endothelium: absorption and secretion

Answer 5

allows active/passive transport via diffusion/channels (regulates flux of fluids and molecules from blood to tissues)

Question 6

key physiological functions of vascular endothelium: barrier

Answer 6

prevents atheroma development and impedes pathogens

Question 7

key physiological functions of vascular endothelium: growth

Answer 7

mediates cell proliferation

Question 8

what are prostaglandins

Answer 8

group of compounds that affect vascular tone

Question 9

what is the first stage of prostahlandin synthesis

Answer 9

phospholipase A2 catalyses conversion of membrane phospholipids to arachidonic acid

Question 10

what is the second stage of prostaglandin synthesis

Answer 10

COX-1 and COX-2 convert arachidonic acid to PGH2 precursor

Question 11

what three compounds can be synthesised from PGH2

Answer 11

thromboxane A2 (pro-platelet vasoconstrictor); prostacyclin (anti-platelet vasodilator); prostaglandins associated with inflammation, pain and fever

Question 12

2 vasodilator molecules

Answer 12

nitric oxide, prostacyclin

Question 13

key features of vasodilator molecules

Answer 13

use -yl second messenger in vascular smooth muscle cells and xTP/cXMP to cause vascular smooth muscle cell relaxation and platelet inhibition

Question 14

exogenous source of nitric oxide

Answer 14

diffuse from blood to vascular smooth muscle cells

Question 15

endogenous source of nitric oxide

Answer 15

produced in response to Ach/bradykinin binding and shear stress (upregulates eNOS)

Question 16

nitric oxide: production after ACh stimulation

Answer 16

ACh binds to GPCR → PLC migrates along membrane → converts PIP2 to IP3 → IP3 triggers Ca2+ influx from ER → upregulate eNOS → nitric oxide produced

Question 17

nitrix oxide: pathway and effect on vascular smooth muscle cells

Answer 17

diffuses into vascular smooth muscle cell → activates guanylate cyclase → upregulates protein kinase G → activates K+ channels, causing hyperpolarisaton, relaxation of cells and vessel dilation

Question 18

2 sources of prostacyclin

Answer 18

phospholipids (converted to arachidonic acid), PIP2 (phospholipase C converted to IP3 and diacyl glycerol, which is converted by DAG to arachidonic acid)

Question 19

prostacyclin synthesis

Answer 19

COX-1 or COX-2 convert arachidonic acid to PGH2, which is converted to PGI2 (prostacyclin)

Question 20

prostacyclin: pathway and effect on vascular smooth muscle cells

Answer 20

PGI2 diffuses into vascular smooth muscle cell → binds to membrane IP receptors → upregulates adenyl cyclase→ cAMP inhibits MLCK → reduced cross bridge cycling, causing relaxation of cells and vessel dilation

Question 21

3 vasoconstrictor molecules

Answer 21

thromboxane A2, angiotensin II, endothelin I

Question 22

what does thromboxane A2 do

Answer 22

vasoconstrictor that activates platelets

Question 23

2 sources of thromboxane A2

Answer 23

phospholipids (converted to arachidonic acid), PIP2 (phospholipase C converted to IP3 and diacyl glycerol, which is converted by DAG to arachidonic acid)

Question 24

thromboxane A2 synthesis

Answer 24

COX-1 or COX-2 convert arachidonic acid to PGH2, which is converted to TXA2

Question 25

thromboxane A2: pathway and effect on vascular smooth muscle cells

Answer 25

TXA2 binds to TPB receptor on vascular smooth muscle cell → phospholipase C migrates along membrane → converts PIP2 to IP3 and DAG → IP3 causes Ca2+ to diffuse in → upregulates MLCK → VSMC contracts and the vessel constricts

Question 26

thromboxane A2: pathway and effect on platelets

Answer 26

TXA2 binds to TPa receptor on platelets → activates and releases more TXA2 (positive feedback) → increased ability to aggregate and stick to endothelium

Question 27

what is angiotensin II produced by

Answer 27

renin-angiotensin-aldosterone system

Question 28

basic angiotensin II synthesis

Answer 28

angiotensinogen (liver) → angiotensin I (bloodstream by renin) → angiotensin II (lungs by ACE)

Question 29

what else does ACE do

Answer 29

metabolises bradykinin to reduce nitric oxide synthesis

Question 30

5 angiotensin II mechansisms

Answer 30

increase ADH secretion (more vasoconstriction and water retention), increase aldosterone secretion (more Na+ absorbed so more water retention), increase kidney Na+ reabsorption, upregulates sympathetic system excitation to cause vasoconstriction and increase heart rate, arteriolar vasoconstriction

Question 31

angiotensin II: endothelial pathway and effect on vascular smooth muscle cells

Answer 31

binds to AT1 receptor → PLC migrates along membrane → converts PIP2 to IP3 → IP3 triggers Ca2+ influx from ER → Ca2+ upregulates MLCK → vascular smooth muscle cells contract

Question 32

what does endothelin I stimulate

Answer 32

majorl stimulation of vasoconstriction, minor stimulation of vasodilation

Question 33

agonist sources of endothelin I

Answer 33

adrenaline, angiotensin II, ADH

Question 34

antagonist sources of endothelin I

Answer 34

nitric oxide, heparin, prostacyclin

Question 35

endothelin-1: production after ACh stimulation

Answer 35

big endothelin 1 produced in endothelial cell nucleus → converted to ET-1 in presence of endothelin converting enzyme

Question 36

endothelin-1: pathway and effect on vascular smooth muscle cells in presence of agonists

Answer 36

ET-1 binds to ETA and ETB receptors on vascular smooth muscle cells → activates PLC → PIP2 converted to IP3 → Ca2+ influx → cell contracts and vessel constricts

Question 37

endothelin-1: pathway and effect on endothelial cells and subsequently vascular smooth muscle cells in presence of antagonists

Answer 37

ET-1 binds to ETB receptor on endothelial cells → upregulates eNOS → increased nitric oxide production → nitric oxide diffuses into vascular smooth muscle cells → cell relaxes and vessel dilates

Question 38

blood vessel structure from lumen to exterior

Answer 38

lumen → tunica intima (endothelium) → internal elastic tissue → tunica media (smooth muscle) → external elastic tissue → tunica adventitia (fibrous connective tissue)

Question 39

role of lumen

Answer 39

hollow area through which blood flows

Question 40

roles of tunica intima (endothelium)

Answer 40

one cell thick, allows for exchange and homeostasis, production of: adhesion molecules, matrix molecules, anti-thrombotic or procoagulant factors, vasodilating or vasoconstricting factors, growth factors

Question 41

features of resting endothelium

Answer 41

inactivated and anti-inflammatory, anti-thrombotic and anti-proliferative

Question 42

features of activated endothelium

Answer 42

pro-inflammatory, pro-thrombotic and pro-proliferative

Question 43

activating factors of endothelium

Answer 43

viruses, smoking, thrombosis, mechanical stress, hypertension, hyperglycaemia, inflammation (chronic activation leads to pro-inflammatory and pro-thrombotic effects)

Question 44

activated endothelium processes

Answer 44

thrombosis, senescence, increased permeability, increased leukocyte recruitment

Question 45

describe senescence

Answer 45

damaged or aging cells undergo growth arrest to halt proliferation in response to stress or damage

Question 46

advantage of senescence

Answer 46

stops damaged cells replicating

Question 47

disadvantages of senescence

Answer 47

pro-inflammatory, contributes to cardiovascular disease

Question 48

effect of increased permeability

Answer 48

allows plasma protein leakage, and for lipoproteins to pass over and bind to proteoglycans

Question 49

fate of lipoproteins bound to proteoglycans

Answer 49

oxidised before macrophages engulf them to form foam cells

Question 50

how is there increased leukocyte recruitment

Answer 50

bind strongly using integrin, not selectin, and transmigrate to tissues in post-capillary venules

Question 51

increased leukocyte recruitment in large arteries

Answer 51

leukocytes adhere strongly using integrin to endothelium, transmigrate, and become stuck in the subendothelial space

Question 52

formation of endothelial tight junctions

Answer 52

monolayer that stop proliferating when they touch (contact inhibition), forming tight junctions