Circulation 6: Local Regulatory Mechanisms Flashcards
What two main factors determine total peripheral resistance? Describe them.
arteriolar radius and blood viscosity
arteriolar radius is controlled by local (intrinsic) and extrinsic control
intrinsic (myogenic response, metabolites, endothelium-mediated regulation like EDRG, NO, endothelin)
extrinsic- hormonal, sympathetic, baroreceptor reflex
What is blood flow primarily controlled by? Describe.
Blood flow primarily controlled by resistance vessels
- arterioles
- precapillary sphincters
- metarterioles (regulate some blood flow from arterial to venous side)
- venous resistance
Venous R is low, venous is affected by compression
What is the role of vascular smooth muscle?
responsible for control of total peripheral resistance, arterial and venous tone, and distribution of blood flow throughout the body
Is venous resistance relatively low or high? What are the implications of this?
venous resistance relatively low. not that imp. in regulating blood flow to organs (but are sensitive to mechanical compression)
regulation is primary pre-cap. resistors.
Will mechanical activity have a larger effect on venous or arterial activity?
venous resistance affected more by compression than arterial resistance bc pressure low
- mechanical activity has dramatic effect on venous resistance. compression of veins. veins compressed before arteries. so if something compresses CV system effects veins before arteries bc veins have low pressure -subdural hematoma…
How do mechanisms that regulate or determine EC coupling in vascular smooth muscle affect pre-capillary resistance?
…
What is auto-regulation?
The intrinsic property of an organ or tissue to maintain constant blood flow despite changes in arterial perfusion pressure.
Show how an increase in arterial pressure affects blood flow over time when the vascular bed is auto-regulated. Graph.
Slide 5.
In the bottom panel, there is an initial abrupt increase in blood flow followed by a gradual decline toward the original baseline. The gradual decrease in blood flow results from an increase in resistance due to autoregulation by the vascular bed.
Does auto-regulation regulate pressure or flow?
does NOT regulate pressure regulates FLOW in face of changes from pressure.
Every time you stand there is more pressure in feet and less in the head. How does the brain maintain flow of blood to brain?
baroreceptors.. tend to increase CO and bring more blood to cerebral circulation in face of gravity. and auto-regulation
In what situation does auto-regulation occur? How is it overcome?
maintains flow under RESTING conditions. it can be overcome by lots of regulatory mech. skel. muscle auto-regulated under resting conditions but mech. that can overcome that and increase flow, when exercise for ex. (don’t have constant blood flow to muscles any longer, now have much larger flow) not as though auto-regulation always there..its under resting changes to mitigate changes in gravitational forces.
is a range of auto-regulation cant increase or decrease pressure forever. flow in diagram, changes in auto-regulation so it is a range of arterial pressures… above 180 you will be out of range and flow will go up, starting from low value, resistance goes up and maintains flow constant. below this point, 50 mmHg then you will drop blood flow through capillary bed. if you go too high you will increase flow through a capillary bed. there is a range. absolute level of blood flow vary through diff tissues so this range is different in diff tissues.
What if auto-regulation was gone? What would occur to vascular smooth muscle? What would happen when you stood up?
vascular smooth muscle dilated all time and when stand up feet turns red bc so much blood flow into feet bc of gravity.
What happens to bp when there is a spike in arterial bp (resting conditions)?
bp? goes up when u increase arterial pressure but it doesn’t stay up even though arterial pressure up, it comes back down to rest. formula -flow increased bc pressure increased. directly proportional. then what happened? reduced flow and increased in resistance. brought flow back down
What might increase resistance in the auto-regulation mechanism?
anytime you stretch vascular smooth muscle (in arterioles and pre capillary sphincters), increase pressure, constricts in response to stretch and that increases resistance and keeps flow downstream from arterioles constant.
Does arteriole pressure affect capillary hydrostatic pressure? Explain.
bc if you do get increase in arterial pressure auto-reg. prevents increase in flow going into capillary, keeps it constant. auto-regulation, pre-cap. resistance, constant flow in tissues auto-regulated. capillaries. if you reduce pressure, vascular smooth muscle recoil and when it does that it relaxes and dilates again and maintains flow constant.
(anytime you stretch vascular smooth muscle (in arterioles and pre capillary sphincters), increase pressure, constricts in response to stretch and that increases resistance and keeps flow downstream from arterioles constant.)
Draw a figure showing the steady state relationship between pressure and flow in a vascular bed that exhibits the property of auto-regulation. (2 figures that both have arterial pressure on x-axis)
What happens to arterial resistance as arterial pressure increases? What happens to flow? What happens at very high or very low pressures?
Slide 6.
Note that as arterial pressure increases, arterial resistance increases and flow remains relatively constant over a defined range.
The autoregulatory range and the absolute level of blood flow vary for each tissue. Autoregulation fails at very low or very high pressures.
Describe the myogenic hypothesis of autoregulation.
- How does vascular smooth muscle respond to stretch increase and decrease?
- How does an increase in pressure affect vascular smooth muscle? How will this affect resistance and flow?
Vascular smooth muscle contracts in response to stretch and relaxes in response to a reduction in stretch.
An increase in pressure causes an initial stretch of the vessel wall which in turn causes the vascular smooth muscle to contract (vasoconstrict), resulting in an increase in resistance and decrease in flow.
A decrease in pressure causes a reduction in stretch of the vessel wall which in turn causes the vascular smooth muscle to relax (vasodilation) resulting in a decrease in resistance and increase in flow.
myogenic- relaxes in response to reduction in stress … inherent property of actin and myosin in vascular smooth muscle. if stretch it, it relaxes, if relax it, it stretches
Describe the metabolic hypothesis of auto-regulation.
How is resistance and flow affected?
Metabolic activity produces substances (adenosine, H+, and CO2) that relax vascular smooth muscle.
The concentration of these inhibitory metabolites in the microvascular bed depends on the level of blood flow. When pressure is increased there is a brief increase in blood flow which removes the inhibitory metabolites and thereby allows the resistance vessels to constrict. As they constrict, resistance increases and flow decreases.
Conversely, when pressure is decreased less blood flow allows an accumulation of inhibitory metabolites causing vessels to dilate. Dilation decreases resistance and increases flow.
(metabolically active tissues… always prod. metabolites. basal amount of activity and those metabolites cause vasodilation of nearby vascular smooth muscle. (See Slide 8.) here have pre capillary resistance, arterioles in metabolically active - metabolites always causing some amount of vasodilation in this tissue. so what happens when you increase pressure? initially when increase pressure upstream, increase flow, increase in flow initially washes out metabolites. if wash them out less vasodilation and then get constriction..thats auto-regulation. removal or breakdown causes vasoconstriction. if you lower pressure then you lower flow initially which allows metabolites to accumulate and get more vasodilation.
thats what auto-regulation is. )
Where do you have strong auto-regulation, weak auto-regulation, and little autoregulation?
strong auto-regulation: heart, brain, kidney, skeletal muscle
weak auto-regulatoin: splanchnic
little autoregulation- skin, lungs (none in lungs bc when you increase CO you want 100 percent of blood going into lung, don’t want lung constricting when increase in pressure. so that doesn’t auto-regulate at all. skin doesn’t bc it depends on temperature)
(auto-regulation is under RESTING conditions/basal conditions for heart.
skeletal muscles auto-regulated when sitting, lying down, standing up, when exercise they no longer are auto-regulated though.)
Look at the graph on slide 10. What do these results indicate about auto-regulation vs. endothelium-mediated regulation?
What happens to diameter of an arteriole when transmural pressure is increased but flow held constant? How is this result affected by endothelium?
These recordings show that when transmural pressure within an arteriole is increased (but flow is held constant), the diameter of the arteriole decreases (constricts).
This constriction is NOT dependent on the endothelium because it is the same with endothelium intact or removed. This is an example of autoregulation.
Endothelium has nothing to do with autoregulation
when pressure goes up if its auto-regulated it will contract and diameter will get smaller. not flow in diagram but implication if diameter smaller then flow reduced.
What happens to diameter of an arteriole when pressure gradient (flow) through arteriole is increased with/without endothelium? Graph.
Slide 11.
These recordings show that when the pressure gradient (flow) through an arteriole is increased (but transmural pressure is held constant), the diameter of the arteriole is increased (dilates) when the endothelium is intact but NOT when the endothelium is removed.
Why would an arteriole lined with endothelium vasodilate when flow increased but would not vasodilate without endothelium present? What causes this response?
Slide 11.
This vasodilation is due to the release of endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) in response to shear stress caused by the increase in flow through the vessel. In other words, an increase in blood flow directly releases endothelial-mediated vasodilators to further increase blood flow, e.g.
Local blood flow, increases metabolic production of NO, causes vasodilation exercise.
(in this …pressure gradient, pressure through vessel. showing if you do that you get vasodilation and if you take endothelium out you don’t get vasodilation anymore so means that something is regulating the diameter of the vessel that is based on movement of fluid through the vessel. not auto-regulation its endothelial derived relaxing factor. when blood flows through vessel creates shear stress and movement of fluid through vessel causes endothelial cells to release EDRF which will vasodilate the vessel. main component of EDRF is NO. (release of EDRF in response to blood flow)
How do you increase blood flow to skeletal muscle during exercise?
when you exercise, you increase blood flow through skeletal muscle through metabolic vasodilation. when blood flow increases, releases additional factors through endothelial cells (NO) which causes additional vasodilation
Describe endothelial mediated regulation in the lungs.
in lungs when blood forced into lungs, when CO goes up, that increase in flow does not auto-regulate, it vasodilates, part of mech is NO. shear stress of blood flowing across endothelial wall stimulates release of EDRF or NO from endothelial cells which relaxes nearby vascular smooth muscle, causing it to vasodilate. dep. of FLOW, flow can cause vasodilation.
dep. on inherent properties of vessel. other due to release of NO due to shear stress against wall.
