Circulation 6: Local Regulatory Mechanisms

Question 1

What two main factors determine total peripheral resistance? Describe them.

Answer 1

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

Question 2

What is blood flow primarily controlled by? Describe.

Answer 2

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

Question 3

What is the role of vascular smooth muscle?

Answer 3

responsible for control of total peripheral resistance, arterial and venous tone, and distribution of blood flow throughout the body

Question 4

Is venous resistance relatively low or high? What are the implications of this?

Answer 4

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.

Question 5

Will mechanical activity have a larger effect on venous or arterial activity?

Answer 5

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…

Question 6

How do mechanisms that regulate or determine EC coupling in vascular smooth muscle affect pre-capillary resistance?

Answer 6

…

Question 7

What is auto-regulation?

Answer 7

The intrinsic property of an organ or tissue to maintain constant blood flow despite changes in arterial perfusion pressure.

Question 8

Show how an increase in arterial pressure affects blood flow over time when the vascular bed is auto-regulated. Graph.

Answer 8

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.

Question 9

Does auto-regulation regulate pressure or flow?

Answer 9

does NOT regulate pressure regulates FLOW in face of changes from pressure.

Question 10

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?

Answer 10

baroreceptors.. tend to increase CO and bring more blood to cerebral circulation in face of gravity. and auto-regulation

Question 11

In what situation does auto-regulation occur? How is it overcome?

Answer 11

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.

Question 12

What if auto-regulation was gone? What would occur to vascular smooth muscle? What would happen when you stood up?

Answer 12

vascular smooth muscle dilated all time and when stand up feet turns red bc so much blood flow into feet bc of gravity.

Question 13

What happens to bp when there is a spike in arterial bp (resting conditions)?

Answer 13

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

Question 14

What might increase resistance in the auto-regulation mechanism?

Answer 14

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.

Question 15

Does arteriole pressure affect capillary hydrostatic pressure? Explain.

Answer 15

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.)

Question 16

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?

Answer 16

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.

Question 17

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?

Answer 17

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

Question 18

Describe the metabolic hypothesis of auto-regulation.

How is resistance and flow affected?

Answer 18

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. )

Question 19

Where do you have strong auto-regulation, weak auto-regulation, and little autoregulation?

Answer 19

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.)

Question 20

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?

Answer 20

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.

Question 21

What happens to diameter of an arteriole when pressure gradient (flow) through arteriole is increased with/without endothelium? Graph.

Answer 21

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.

Question 22

Why would an arteriole lined with endothelium vasodilate when flow increased but would not vasodilate without endothelium present? What causes this response?

Answer 22

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)

Question 23

How do you increase blood flow to skeletal muscle during exercise?

Answer 23

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

Question 24

Describe endothelial mediated regulation in the lungs.

Answer 24

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.

Question 25

How is blood flow in a given tissue regulated to increase? What is the effect?

Answer 25

Blood flow in a given tissue is regulated by the metabolic activity of the tissue. In other words, metabolites are released from the tissue and act locally to dilate resistance vessels to increase blood flow to the tissue.

this is mech. where when spec. tissue becomes metabolically active it vasodilates. its LOCAL. how blood is regulated from one tissue to another…by local control

Question 26

What will happen if there is a reduction of O delivery to a tissue?

Answer 26

a reduction in oxygen delivery to a tissue stimulates the formation of metabolites that are vasodilators.

Question 27

What is the response if the heart becomes ischemic?

Answer 27

when you become ischemic, when heart becomes globally ischemic it releases metabolites and then vasodilates to bring more blood flow to tissue to try to overcome ischemia

Question 28

What is active (functional) hyperemia? Graph. (increased metabolism on x axis, vs organ blood flow)

Answer 28

Slide 12.
Increased blood flow caused by enhanced tissue activity. K+, inorganic phosphate, and interstitial osmolarity are among the factors responsible for this type of control.

increased metabolism, blood flow up dramatically… this metabolic activity same mech. that talked about in auto-regulation. when you exercise you increase metabolic activity dramatically and get dramatic vasodilation. and they’re no longer being auto-regulated. this OVERCOMES. same mech. but larger effect overcomes auto-regulation. now increase in blood flow

Question 29

How does active hypermia apply in the heart/lungs?

Skeletal muscle?

Answer 29

active hyperemia—usually talk about in relation to 2 organs: skeletal muscle and cardiac muscle. these tissues enhance metabolic activity. when increase HR increase contractility or increase afterload, you increase metabolic O consumption which produces metabolites, which causes coronaries to vasodilate, which brings more blood flow to meet work load

when exercise skeletal muscles you release metabolites dep. on extent of exercise and that det. vasodilation of that organ and amount of blood flow coming to that tissue.

Question 30

What is reactive (passive) hyperemia? Graph.

Answer 30

Slide 12 and 13.

2) Reactive (passive) Hyperemia - Transient increase of blood flow that follows a brief arterial occlusion. Thus, metabolic debt increases blood flow.

passive- idea is here completely stop blood flow then when you release the occlusion, blood flow doesn’t just come back to where it was… it overshoots… longer time held, larger the reaction

The longer the occlusion the greater the response. .

Question 31

When might you see reactive hyperemia clinically? What might result?

Answer 31

happens clinically when angioplasty on someone put in catheter and open it up to open clot and restore flow, momentarily when balloon expanded you’re cutting off blood flow through the coronary artery then when bring flow back by deflating balloon you get re-perfusion and increase in blood flow through that artery. re-perfusion injury…can generate arrhythmia as result of rapid regeneration of O back in system. as result of overshoot… when occlusion, metabolites accumulate so when flow restored you have vasodilation that causes increase in blood flow.

Question 32

Describe mechanical (tissue pressure) and possible causes.

Answer 32

An increase in tissue pressure can mechanically compress small vessels and alter blood flow.
Possible causes:
a) muscle contraction (heart, skeletal muscle)
b) alveolar pressure (lungs)
c) tumors (venous obstruction)

usually initially venous side then arterial side if goes on too long.

Question 33

Give an example of mechanical/tissue pressure in skeletal muscle.

Answer 33

skeletal muscle- when you do isometric contraction, it cuts off blood flow to muscle, thats why you cant hold for more than couple minutes bc becomes ischemic and painful

Question 34

How does mechanical or tissue pressure affect the heart? When is this dangerous?

Answer 34

coronaries located on outside of heart, to get from epicardium to endocardial muscles get smaller and smaller to endocardium. when heart in systole creates lots of mechanical force and compresses small vessels. normally thats ok. but what about if aortic stenosis=tremendous after load on the heart? instead of heart generating 120 mmHg, 220… to try to overcome that afterload, that will cut off blood flow to endocardial surface first. area of heart most at risk for ischemia and infarction is the endothelial surface of the heart and this is the reason why. bc vessels that dive from epicardium to endocardium are rel. small by time they get to endocardium and are more easily compressed under abnormal conditions. so muscle contraction is important.

Question 35

What area of heart is most at risk for ischemia? Why?

Answer 35

to try to overcome that afterload, that will cut off blood flow to endocardial surface first. area of heart most at risk for ischemia and infarction is the endothelial surface of the heart and this is the reason why. bc vessels that dive from epicardium to endocardium are rel. small by time they get to endocardium and are more easily compressed under abnormal conditions. so muscle contraction is important.

Question 36

How does mechanical pressure affect the lungs? tumors?

Answer 36

alveolar pressure- when you expand lungs, squeezes blood vessels in pul. system and alters blood flow through lungs. resistor. positive pressure ventilator can change blood flow in lungs dramatically as result of mechanical compression.

tumors- in brain or anywhere in body, first vessel compressed are venous bc lowest pressure. can impede venous return. this v important.

Question 37

What is shock? What are the 5 major classes?

Answer 37

A serious condition that occurs when the cardiovascular system is unable to supply enough blood flow to the body, causing inadequate tissue perfusion.

The 5 major classes of shock include:

Cardiogenic Shock (associated with heart problems)
Hypovolemic Shock (caused by inadequate fluid volume)
Anaphylactic Shock (caused by allergic reaction)
Septic Shock (associated with infections)
Neurogenic Shock (caused by damage to the nervous system)

Question 38

Describe cardiogenic shock. When does it occur? What results?

What other causes can compromise CO?

Answer 38

This occurs when heart muscle damaged, most commonly by a severe myocardial infarction, and therefore is not able to pump enough blood to meet the needs of the body.

Other causes which can compromise cardiac output are:

• dysrhythmias such as ventricular tachycardias and bradycardia caused by complete heart block.
• cardiac tamponade where blood/fluid builds up in the pericardial space preventing the ventricles from fully expanding and filling with blood normally.

Question 39

What is hypovolumic shock?

What are some other causes of loss of blood volume?

Answer 39

A condition where the heart is unable to supply enough blood to the body because of inadequate blood volume due to blood loss. Clinical symptoms may not present until 10-20% of total whole-blood volume is lost. Also known as Hemorrhagic Shock.

Other causes of loss of blood volume:
Dehydration, vomiting, diarrhea or burns

hypovolumic- have to lose a lot of blood to get this bc baroreceptors maintain bp pretty well in face of loss of volume. but at some point cant compensate for VERY large loss
burns- capillary permeability increase and lose fluid from CV system can’t maintain bp.

Question 40

Describe anaphylactic shock. What are some possible causes?

Answer 40

A sudden, severe, potentially fatal, systemic allergic reaction that can involve various areas of the body. Minute amounts of allergens may cause a mild to life-threatening reaction. Death results from obstruction to breathing or extreme low blood pressure.

Possible causes:
Food, Medication, Insect stings, Latex

Question 41

What is septic shock?

Answer 41

An inflammatory (immune) response that results from a severe infection and sepsis. The inflammatory response results in massive vasodilation, increased capillary permeability, decreased systemic vascular resistance and hypotension, resulting in tissue hypoxia..

Question 42

What is neurogenic shock?

Answer 42

A sudden disruption of signals that maintain autonomic nervous system control over vasoconstriction leading to hypotension; occurs after an acute spinal cord injury that blocks sympathetic activity.