vascular endothelium 1 Flashcards
what are the anatomical and physiological aspects of the heart
muscular pump
generate flow
what are the anatomical and physiological aspects of the arteries
thick muscular walls
stabalise pulsatile flow
what are the anatomical and physiological aspects of the capillaries
very thin walls
fascilitate gas and solute exchange
what are the anatomical and physiological aspects of the veins
one way valves
maintain unidirectional flow
which way does the anatomy physiology relationship go
both directions
anatomy always determines function
in angiogenesis the function determines the anatomy
what is the vascular endothelium
single layer of cells that acts as a blood-vessel interphase
5 functions of the endothelium
vascular tone thrombostasis and haemostasis absorbtion and secretion barrier growth
describe vascular tone
secrete and metabolise vasoconstrictive substances - cause constriction and vasodilation
describe thrombostasis and haemostasis
mechanism to stop flow of blood - but ensure that clots don’t form unnecessarily
describe absorption and secretion
active or passive transport
diffusion or channels
nutrients, co2 and o2
describe action as a barrier
selective control of what enters and leaves
prevents atheromas and impedes pathogens
describe the growing action
mediate cell proliferation
if bv blocked so an area is not being perfused by blood
another bv grow in order to perfuse the other vessel with blood
what does regulation of hypertension depend on
downstream delivery and local forces
want ot be normotensive and adequately pressured
describe the normal relationship between vasodilation and vasoconstriction forces
they normally work in tandem
one way might pull slightly more than the other if needed
describe the hypertensive relationship between vasodilation and vasoconstriction forces
vasoconstriction more powerful than it should be
drugs can be used to balance both sides
describe laser doppler flowmetry
it measures the ACh response via endothelium to change the size of bv
the blue line is perfusion and is measured in arbituary units
in intact endothelium when ACh is supplied, after the 7th dose the perfusion plateaus
when no endothelium there is no response
when there is an exogenous NO donor (sodium nitropusside) a response is generated
describe flow mediated dilation
stimulate forearm ischemia - cuff at 300mmHg
want to increase sixe on bv - so that cells can get o2
dilate vessels and reduce resistance
the purple line on the ultrasound shows the blood vessel diameter
what is the colour of the hand caused by
Hb
describe the formation of prostacyclin and thromboxane
from phospholipids
phospholipase A2 makes Arachidonic acid
COX 1 and 2 make PGH2
[thromboxane synthase make thromboxane]
[prostacyclin synthase make prostacyclin]
also make PGD2, PGE2, PGF2 (prostaglandins for pain, fever and inflammation)
action of arachidonic acid
precursor for lots of things
lipoxygenase
leukotrienes
PGH2
PGD2, PGE2, PGF2 action
pain
fever
inflammation
prostacyclin action
vasodilator
anti-atherogenic
anti-platelet
these are useful characteristics
thromboxane A2 action
vasoconstrictor
proatherogenic
proplatelet
in time of haemostatic crisis - form plug for bleed
aspirin affect on COX 1 and 2
reduces the effect
what is PGH2
prostaglandin precurser `
explain how NO acts as a vasodilator
ACh binds to the GPCR on the endothelium membrane
this interacts with the membrane bound enzyme Phospholipase C
PLC converts PIP2 to IP3
IP3 triggers Ca influx from the ER
Ca upregulates eNOS - cytoplasmic enzyme
eNOS convert L-arg and O2 to NO and L cit
NO diffuse into vascular SM cell
activates GC (Guanylyl cyclase) which converts GTC to cGMP (cGMP can be broken down by to GMP by phosphodiesterase to reduce NO)
this upregulates PKG
activate K channels
membrane hyperpolarises
cell relaxes
vessel dilates
how does shear stress affect vasodilation in brachial artery
when there is low pressure in forearm - blood flows to forearm increase flow rate greater pressure dilate also influences how much NO is produced
effect of the endothelium:SM ratio on the effect of NO
when large there is a large effect
effect of exogenous NO in the blood on SM
it diffuses across the endothelium and causes vasodilation
effect of prostacyclin
produced via COX 1 diffuses into SM binds to IP receptor upregulation of andenylyl cyclase convert ATP to cAMP inhibits MLCK (myosin light chain kinase) reduced cross bridge cycling cell relaxes vessel dilates [stops clots too]
effect of Thromboxin A2 on SM
thromboxane diffuses through apical and basement membrane binds to TPbeta on VSMC PLC migrate along the membrane PIP2 - IP3 Ca release form SER and extracellular space upregulate MLCK VSMC contracts vasoconstriction
effect of TXA2 on platelets
bind to TPalpha on platelets platelet becomes active makes more TXA2 positive feedback enhances the response platelets aggregate integration with the clotting cascade
where is TXA2 more active SM, or plateleyt
platelet
production of angiotensin 2
angiotensinogen - precursor
cleaved by renin - make angiotensin 1
ACE act on ang 1 to make ang 2
where is ACE expressed
endothelial cells, lungs and kidneys
effects of ANG2
interact with the ADH secretion, aldosterone secretion, tubular sodium reabsorption - increase water retention arteriolar vasoconstriction (direct effect on bv - sm response), sympathoexcitation ( excite CNS - increase HR, pressure and constriction) - increased vascular resistance
both effects increase BP
describe the mechanism of action for ANG2
ang 2 diffuse across the endothelium bind to AT1 receptor on SM PLC PIP2 - IP3 Ca influx upregulate MLCK contraction
alternative action of ACE
metabolise Bradykinin which casues vasodilation
what is the balance between ANG 2 and bradykinin
if ACE high
net vasoconstriction by ANG2
little bradykinin effect
endothelin - 1 mechanism of action on SM cell
endothelial cell nucleus produces Big endothelin 1
endothelin converting enzyme converts zymogen to ET- 1 on membrane
ET-1 bind to ET alpha and beta receptors on VSMC
PLC
PIP2-IP3
Ca influx
cell contracts
vessel constricts
endothelin - 1 mechanism of action on endothelial cell
ET-1 bind to ETb receptor upregulate eNOS increased NO production diffuse into VSMC cell relaxes vessel dilates
what is the main effect of ET-1
vasoconstriction
what can change the affect of endothelin
molecule that intercommunicate and can interact and be sensed by the nucleus or membrane
Antagonists: PGI2, NO, ANP, heparin, HGF, EGF
Agonists: adrenaline, ADH, Ang II, IL-1
what is the effect of ACE inhibitors and ANG blockers
block processes downstream
early phase treatment for hypotension
describe the ratio between extracellular and intracellular Ca
extracellular 2mmol L-1
intracellular 100nmol L-1
up to 20000x difference
effect of aspirin on COX 1
COX 1 is expressed all of the time
aspirin acetylation inactivates the enzyme
effect of aspirin on COX 2
COOX 2 is upregulated at times of physiological insult
aspirin acetylation switches its function - to generating protective lipids
general effect of aspirin on COX enzymes
causes irreversible inhibition
other non-specific NSAIDs cause reversible inhibition
COX- 2 specific inhibitors cause reversible inhibition of COX 2 only
effect of aspirin on prostacyclin
no effect - nucleus makes more enzyme
effect of aspirin on thromboxane
proportion of thromboxane decreases
greater effect in platelets - they cant make more COX enzymes (other way in prostacyclin)
describe drug drug interactions
when keep adding drugs it makes biochemistry and lifestyle very complicated
the body can use the same chemicals for different processes
interaction between systems in the body
drugs not tissue specific
receptor expression and distribution varies between tissues
2 people taking same medication can have very different outcomes
what is the BNF
catalogue of all dugs in the UK
biggest part of it is side effects
the number of people needed to show it is a side effect varies
what system do the vasoconstrictors rely on
PLC
regulates Ca metabolism
what do calcium blockers do
prevent Ca entering VSMCs
mechanism of drug to treat hypertension
block flow of Ca into cells
impede cross bridge cycling which is ca dependant
this is endothelium dependant
the effect is on the vasculature, not the heart so it is a good drug
issue with inhibiting cholinesterase enzymes
too complicated
ACh many other effects
issue with inhibiting the phosphodiesterase enzyme - reduces breakdown on NO
undesired side effects
resold as Viagra
issue with a medication that involves a NO functional group
too short acting to be useful - have to take it every 15minutes
it is used to treat angina though
