7 Blood Vessel Order, Function and Specialisation Flashcards
(37 cards)
Q: What are the 3 layers of blood vessels? Describe what each layer contains and role.
A: Tunica adventitia
- External layer containing fibrous tissue, elastin, collagen
- Helps keep the shape of the blood vessel
Tunica media
- Predominantly smooth muscle cells
- able to contract or dilate depending on the type of stimulus
Tunica intima
- Predominantly vascular endothelium has the elastic basal lamina as well
- this is the exchange surface
Q: What is the vascular endothelium? 5 role?
A: single cell layer that acts as the blood-vessel interface
- vascular tone:
- thrombostasis:
- absorption/secretion: active/passive transport via diffusion/channels
- barrier
- growth/repair: mediates cell proliferation
Q: Vascular endothelium role. How does it control vascular tone? allowing? (2) acts as? Explain.
A: secretes and metabolises vasoactive substances – this can cause vasoconstriction or vasodilation (kind of like a local paracrine gland)
= blood vessels locally sense and locally react and change because of endothelium
Q: Vascular endothelium role. Thrombostasis?
A: prevents clot formation or molecules adhering to wall (secretes anti-coagulant substances)
Q: Vascular endothelium role. How does it act as a barrier? (2)
A: prevents atheroma (fatty material which forms deposits in the arteries) development and impedes pathogens
Q: What are the 5 key mediators of vasoconstriction and dilation?
which inhibits platelet _?
A: VASODILATORS
- Nitric Oxide
- PGI2 (prostacyclin) also inhibits platelet aggregation
VASOCONSTRICTORS
- TXA2 (thromboxane)
- ET-1 (endothelin 1)
- Angiotensin II (ANG II)
Q: What causes hypertension in terms of vascular tone? Treated hypertension?
A: HT: vasoconstriction aspect is more active <= trying to close off vessel
tHT: given drugs that allow the balancing out of it (shift in other direction)
- ignore vasoconstricting factors OR
- increase vasodilating ones
Q: What 2 methods allow the assessment of endothelial function? Clinical practice?
A: laser doppler flowmetry
flow-mediated dilation
not used clinically as not accurate enough and difficult to interpret (lots of variability)
Q: What is laser doppler flowmetry? Describe (3).
A: method of assessing endothelial function
- Intact endothelium with regular delivery of ACh -> blood flow increased more and more with each delivery= blood vessels get wider
- No endothelium with delivery of ACh= no response
- Exogenous NO-donor = vasodilator -> creates similar graph to 1 (acts as control test)
Q: What is flow mediated dilation? (5)
A: method of assessing endothelial function
measure blood flow through brachial artery and can stimulate an increase in blood flow
leads to increase in local shear stress= force of blood going across the endothelial cells
stimulator - it can upregulate endothelial NO
get vasodilation/ artery widens
Q: How is arachidonic acid made? What is it is? What happens to it?
A: formed from phospholipid from lipid bilayer via E: phospholipase A2
precursor to many molecules
converted to Prostaglandin H2 (PGH2) by the COX1 and 2 enzymes (COX = cyclooxygenase)
Q: What is PGH2? What can it become? (3) (include actions of molecules produced)
A: molecule made from arachidonic acid (by COX 1 and 2 enzymes-cyclooxygenase)
E: Thromboxane Synthase -> thromboxane A2 (TXA2)
- vasoconstricter
- pro-atherogenic
- pro-platelet
E: prostacyclin synthase -> prostacyclin
- vasodilator
- anti-atherogenic
- anti-platelet
PGD2, PGE2, PGF2
-all are typically involved in pain, fever and inflammation
Q: How and where is nitric oxide produced (NO)? (6) 2 other stimuli?
A: 1. stimulus: ACh binding to G protein associated receptor that has phospholipase C attached
- PLC migrates along membrane until it reaches PIP2 (which is embedded in the membrane)
- PLC converts PIP2 to IP3 and DAG
- IP3 triggers Ca2+ influx from ER
- rise in intracellular calcium concentration upregulates endothelial nitric oxide synthase (eNOS)
- eNOS catalyses the following conversion:
L-arginine + Oxygen -> L-citrulline + NO
eNOS = also stimulated by:
- sheer stress of blood flow
- NO can be delivered (attached to inert molecule) and taken to target tissue-> where it dissociates
made in the endothelial cells
Q: What happens to nitrous oxide once it is made? (7) Effect on blood vessel?
A: made in the endothelial cells
- exits and enters vascular smooth muscle via diffusion
- enzyme guanylase cyclase is upregulated as a result
- GC converts GTP to cGMP= part of smooth muscle cell secondary messenger system
- cGMP upregulates protein kinase G
- PKG activates K+ channels
- membrane hyperpolarises
- cell relaxes-> vessel dilation
Q: How and where is prostacyclin made? (4-making precursor, 1 alternative, 2)
A: endothelial cells
PGI2= prostacyclin
(1. stimulus: ACh binding to G protein associated receptor that has phospholipase C attached
2. PLC migrates along membrane until it reaches PIP2 (which is embedded in the membrane)
3. PLC converts PIP2 to IP3 and DAG
4. DAG-> via E: DAG ligase-> arachindonic acid)
ORRR
comes from phospholipid -> E: phospholiase A2
- arachnadonic acid -> converted to Prostaglandin H2 (PGH2) by the COX1 and 2 enzymes (COX = cyclooxygenase)
- PGH2 -> PGI2 by E: prostacylcin synthase
Q: What happens to prostacyclin once it’s made? Effect on blood vessel? What else does it affect?
A: made in endothelial cells
- PGI2 diffuses out of endothelial cells and binds to AT2 receptor on vascular smooth muscle cells
- upregulation of adenylase cyclase (attached to receptor)
- AC converts ATP-> cAMP
- cAMP inhibits myosin light chain kinase (MLCK)
- reduction of cross bridge cycling
- cell relaxes and blood vessel vasodilates
also secreted into the blood where it has anti-platelet aggregation properties
Q: How and where is thromboxane A2 produced? (4-making precursor, 1 alternative, 2)
A: endothelial cells
TXA2
(1. stimulus: ACh binding to G protein associated receptor that has phospholipase C attached
2. PLC migrates along membrane until it reaches PIP2 (which is embedded in the membrane)
3. PLC converts PIP2 to IP3 and DAG
4. DAG-> via E: DAG ligase-> arachindonic acid)
ORRR
comes from phospholipid -> E: phospholiase A2
- arachnadonic acid -> converted to Prostaglandin H2 (PGH2) by the COX1 and 2 enzymes (COX = cyclooxygenase)
- PGH2 -> TXA2 by thromboxane synthase
Q: How does TXA2 act when it’s made? (6,5) How does it affect blood vessels?
A: thromboxane A2 = made in epithelial cells
(can diffuse through both the apical and basal membrane)
- diffuses through basal membrane
- binds to TP beta receptor on the vascular smooth muscle cell (which is associated with phospholipase C)
- PLC converts PIP2 into IP3 in smooth muscle cell
- IP3 triggers Ca2+ influx into cell from extracellular space and sER
- Ca2+ upregulates myosin light chain kinase MLCK= increased amount of cross bridge cycling
- VSMC contracts and vessel constricts
- diffuses through apical membrane
- binds to TP-alpha on quiescent platelets
- platelets are activated and produce more TP-alpha
- more platelets activated-> positive feedback (continues until stimulus is removed)
- platelets aggregate
Q: How is angiotensin II made? (4) Where?
A: in blood
- from liver: precursor= angiotensinogen made (not metabolically active/ zymogen)
- in presence of renin (made in kidney in response to low blood flow/hypoxia) will become angiotensin I (by cleavage process)
- angiotensin I is exposed to endothelial enzymes- either in pulmonary or renal circulation-> both express ACE
- angiotensin I -> II (cleavage process)
Q: What are the 5 roles of angiotensin II? 2 overarching results? Overall effect?
A: -Stimulates ADH/vasopressin secretion from (post) pituitary gland
- Increases aldosterone production= increases reabsorption in kidneys-> changes osmotic fluid balance
- Increases tubular sodium reabsosorption (local receptors)
ALL THREE OF THESE CAUSE INCREASED WATER RETENTION
- Increased sympathetic activity / sympathoexcitation -> leads to vasoconstriction
- Arteriolar vasoconstriction (binds to receptors on VSMC -> shortening of cells)
BOTH CAUSE AN INCREASE IN VASCULAR RESISTANCE
overall= increased blood pressure
Q: What happens to angiotensin II when it is made? (6) Effect on blood vessel?
A: 1. diffusion from blood across endothelium
- binds to AT1 receptor on vascular smooth muscle cells (associated with PLC)
- PLC migrates along membrane and converts PIP2 into IP3
- IP3 triggers calcium influx
- Ca2+ upregulates myosin light chain kinase MLCK= increased amount of cross bridge cycling
- VSMC contracts and vessel constricts
Q: How in endothelin 1 made? (2) Where?
A: endothelial cells
- endothelial cell nucleus produces Big Endothelin 1 (precursor)
- endothelin converting enzyme (on inner cell membrane) converts zymogen to ET-1 (active form)
Q: How does ET-1 act once it’s produced? (6,4)
A: endothelin 1
- diffuses out of endothelial cell
- binds to ETalpha and ETbeta on vascular smooth muscle cell that are associated with PLC
- PLC migrates along membrane and converts PIP2 into IP3
- IP3 triggers calcium influx
- Ca2+ upregulates myosin light chain kinase MLCK= increased amount of cross bridge cycling
- VSMC contracts and vessel constricts
OR
- binds to ET beta receptor on endothelial cells
- causes upregulation of eNOS (endothelial nitric oxide synthase)
- eNOS catalyses the following conversion:
L-arginine + Oxygen -> L-citrulline + NO => means you get more NO produced - enters vascular smooth muscle via diffusion-> low intra [Ca2+] -> relaxation -> vasodilation
Q: Which effect of endothelin 1 dominates? Generally?
A: depends on which receptors are more expressed- those on endothelial cell (ET beta) or VSMC (ET alpha and beta)
has a contracting effect/ vasoconstricting
