Download CASE 14

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CASE 14
A 21-year-old woman presents to her primary care physician because she
wants to begin an exercise program for weight loss. She is concerned because
when she exercised in the past, she noticed that her heart seemed to beat rapidly. She has no known medical history and has no family members with medical problems. She denies chest pain. After a thorough physical examination,
everything appears to be normal and the physician reassures the patient that
her increased heart rate is probably a normal response to exercise.
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In what two ways is blood flow to skeletal muscle controlled?
What are some differences between cerebral circulation and
skeletal circulation?
What are some forms of extrinsic control of blood flow?
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CASE FILES: PHYSIOLOGY
ANSWERS TO CASE 14: REGIONAL BLOOD FLOW
Summary: A 21-year-old woman who is beginning an exercise program has a
normal examination and normal physiologic increased heart rate with exercise.
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Control of blood flow in skeletal muscle: Sympathetic innervation and
local metabolic control.
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Differences between cerebral circulation and skeletal circulation:
Cerebral blood flow demonstrates autoregulation and is controlled
almost entirely by local metabolic factors. Skeletal muscle relies on
input from both sympathetic innervation and local metabolic factors.
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Forms of extrinsic control of blood flow: Sympathetic innervation and
vasoactive hormones (bradykinin, serotonin, prostaglandins, angiotensin
II, antidiuretic hormone [ADH], etc.).
CLINICAL CORRELATION
A more complete understanding of the cardiovascular changes that take place
under varying physiologic conditions and under the influence of medications
requires knowledge about the factors that regulate blood flow to specific vascular beds. Exercise is a common physiologic condition during which there are
many changes. Increases in blood flow to contracting skeletal muscle are
caused by both extrinsic and intrinsic factors. With increased muscle metabolism, there is an increase in vasodilator metabolites such as lactic acid, potassium, and adenosine. The increase in vasodilator metabolites represents
intrinsic control over skeletal circulation. Extrinsic factors include sympathetic system activation, which results in increased heart rate and elevated
venous pressure, thus increasing cardiac output. If the exercise is intense, sympathetic stimulation results in increased arteriolar resistance in the gastrointestinal tract, kidneys, and other organs, resulting in shunting of blood toward
the exercising muscles. Adequate blood flow to a tissue allows for exchange of
substrates and metabolites between cells of the tissue and the blood as blood
flows through capillaries.
APPROACH TO REGIONAL BLOOD FLOW
Objectives
1.
2.
3.
4.
Describe the mechanisms of intrinsic control of regional blood flow.
Describe the mechanisms of extrinsic control of regional blood flow.
Compare and contrast the control of blood flow to the heart, brain,
skeletal muscle, and skin.
Describe the transfer of substrates, metabolites, and volume between
capillaries and interstitial fluid.
CLINICAL CASES
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Definitions
Autoregulation: The process of maintaining blood flow constant in the
face of varying mean arterial pressures.
Active hyperemia: The increase in blood flow in response to an increase
in metabolic activity.
Reactive hyperemia: The temporary increase in blood flow seen following
a period of ischemia.
Edema safety factor: Compensatory mechanisms (mostly increases in
lymph flow) that can accommodate increases in capillary filtration and
mitigate edema formation.
DISCUSSION
Blood flow to any organ of the body over any period of time normally is correlated closely with that organ’s metabolic activity. If activity increases,
blood flow increases to that organ, but not to others unless their levels of activity change as well. This local control of blood flow is accomplished by intrinsic and extrinsic factors that act to alter the resistance of small arteries and
arterioles in the vascular beds of the organ.
Local changes in resistance can result in local changes in blood flow, as
described by the following equation:
Local flow = mean arterial pressure/local resistance
As discussed in Cases 12 and 13, mean arterial pressure (MAP) is maintained at a fairly constant level and is determined by the interplay of cardiac
output (CO) and total peripheral resistance (TPR). Because a change in resistance in any vascular bed will affect TPR, the only way MAP can remain constant is for CO to change or for there to be equal and opposite changes in
resistance in other vascular beds to keep TPR constant. Normally, unless the
local changes in resistance are great, CO will change so that the metabolic
demands of all the organs of the body are met.
Many organs, especially the brain, exhibit autoregulation of their blood
flow. As long as their metabolic activities do not change, they are able to maintain a constant blood flow over a wide range of mean arterial pressures.
Thus, in circumstances in which MAP does deviate from normal levels, local
arteriolar resistance will change so that blood flow still matches metabolic
demand.
All organs, especially skeletal and cardiac muscles, exhibit active and reactive hyperemia. Active hyperemia is the increase in blood flow that occurs as
the metabolic activity of an organ increases. The mechanism for the
increased blood flow is a decrease in local resistance in the face of a stable
MAP. The result is a matching of blood flow to metabolic demand. Reactive
hyperemia is the increase in blood flow that occurs after restoration of blood
flow to an organ that has been deprived temporarily of blood. The mechanism
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CASE FILES: PHYSIOLOGY
also is a decrease in local resistance, but one that develops during the period
of ischemia.
The changes in local arteriolar resistance that occur during autoregulation, active hyperemia, and reactive hyperemia are due mostly, if not solely, to
local intrinsic mechanisms. During autoregulation, a change in MAP initially
causes a change in blood flow. If MAP is increased, flow initially increases
and local concentrations of metabolites (CO2, K+, H+, adenosine) decrease as
a result of washout; local concentrations of substrates (O2) increase because
supply is greater than demand. Opposite changes in metabolite and substrate
concentrations occur if MAP is decreased to decrease flow initially. Because
metabolites relax and substrates support the contraction of arteriolar smooth
muscle, changes in their local concentrations alter local resistance to blood
flow to bring flow back to its previous state.
During active hyperemia, increased organ metabolic activity tends to
increase metabolite concentrations and decrease substrate concentrations and
thus bring about relaxation of arteriolar smooth muscle, decreased local resistance, and increased local blood flow. During reactive hyperemia, local
metabolites accumulate and local substrates decrease during the period of
ischemia, causing arteriolar dilation and a decrease in local resistance. Then,
when the obstruction causing the ischemia is removed, blood flow is increased
as a result of the arteriolar dilation. Most often, reactive hyperemia is thought
of in relation to those times when flow is obstructed by resting on an arm or
leg in such a way that flow is obstructed temporarily. However, reactive hyperemia also occurs along with active hyperemia during muscle contraction. For
example, during contraction of ventricular muscle, vessels embedded in the
myocardium are compressed to block flow. Metabolites continue to build further, relaxing resistance vessels, so that when flow can begin again during ventricular relaxation, it is increased.
In addition to the intrinsic control described above, regional blood flow
may be regulated by extrinsic factors, mainly the sympathetic nervous system. The degree of sympathetic innervation of small arteries and arterioles
varies from organ to organ. In some organs (eg, skin, intestine, kidney) it is
quite dense, and sympathetic tone exists even under normal resting conditions.
The norepinephrine released by these nerves contracts the smooth muscle of
these vessels to varying degrees, thus regulating local resistance to blood flow.
Under most conditions, this extrinsic mechanism works in concert with intrinsic mechanisms to provide blood flow that is adequate to meet the metabolic
demands of the organs or, in the case of the kidney, to fulfill its role in maintaining homeostasis. However, under conditions in which the baroreceptor
reflex or other reflexes are elicited, sympathetic tone will increase to override
intrinsic mechanisms temporarily. This will result in an increase in both local
and total peripheral resistance to restore MAP. The result of this is a decrease
in blood flow to organs with a high degree of extrinsic regulation (eg, skin,
intestine, kidney) and a maintenance or increase in blood flow to organs with
a lower degree of extrinsic control (eg, brain and heart).
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CLINICAL CASES
Capillary Physiology
Exchange of substrates and metabolites between the blood and tissues of the
body takes place at the level of the capillary. Exchange is possible because
every cell of the body is within a few microns of one of the billions of capillaries in the body and because the capillary wall is thin, being composed of a
single layer of endothelial cells. In addition, endothelial cells abut one another
in such a way that there are clefts between them, resulting in a high permeability. Thus, small molecules such as oxygen, carbon dioxide, ions, glucose,
amino acids, urea, and lactate, as well as water, can move readily between the
capillary lumen and the interstitial fluid. The majority of exchange between
the capillary and the interstitium takes place by means of diffusion. However,
the relatively high permeability results in bulk flow of volume either out of
(filtration) or into (absorption) the capillary, depending on the balance of
forces across the capillary wall.
There is a hydrostatic pressure in the capillary (Pc) that is owing to the
forces responsible for blood flow. This pressure favors filtration. There also is
a hydrostatic pressure exerted by the interstitial fluid (PIF). This pressure, if
above atmospheric pressure, will favor absorption into the capillary. The
other forces across the wall are osmotic forces that are due mainly to the presence of proteins in the blood and the interstitium. Proteins in the blood,
mainly albumin, cannot cross the capillary wall readily and thus exert an
osmotic force (often called an oncotic force, πc). This force favors absorption.
Proteins in the interstitial fluid exert a force (πIF) that favors filtration. The
interaction of all these forces can be expressed in what is called the Starling
equation for the capillary:
Jv = Kf [(Pc - PIF) - (πc - pIF)]
where Jv represents the net flux of volume and Kf is the filtration coefficient
(a measure of the permeability of the capillary wall that will vary from one
capillary bed to another). If the algebraic sum of the forces favoring filtration
exceeds the sum of those favoring absorption, fluid will leave the capillary at
a rate determined by Kf and the net force.
Capillary hydrostatic force (Pc) changes along the length of the capillary, being higher at the arteriolar end than at the venule end. This can result
in net filtration at the arteriolar end and absorption at the venule end. Pc also
can change from moment to moment because of contraction and relaxation of
arteriolar and precapillary sphincter smooth muscle. The presence of this muscle also means that pressure in the large arteries can increase and decrease with
little change in Pc. In contrast, changes in venous pressure always result in
changes in Pc. Elevations in venous pressure often lead to a marked increase
in filtration and the development of edema.
Although capillary oncotic pressure (πc) does not change acutely, decreases
in plasma albumin do occur with many liver and kidney diseases. With
hypoalbuminemia, the main force responsible for absorption, pc will
decrease, and this too can result in edema.
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CASE FILES: PHYSIOLOGY
Interstitial fluid hydrostatic force (PIF) is interesting in that it normally is
subatmospheric and thus favors filtration rather than the expected absorption.
PIF is subatmospheric as a result of the action of lymphatic vessels. These
blind-ended vessels are responsible for the return of the net filtered fluid and
protein to the circulation via the thoracic duct. Because of their pumping
action, small increases in capillary filtration can be accommodated without
interstitial volume increasing to the point of edema. Thus, lymphatics are
responsible for an edema safety factor. However, if lymphatic function is
impaired, edema will form even if capillary forces are normal.
COMPREHENSION QUESTIONS
[14.1]
A 22-year-old subject who is sitting quietly begins to squeeze a rubber
ball repetitively in her right hand, using moderate strength. During this
time her mean arterial pressure does not increase. Using her cardiovascular state prior to the exercise as a baseline, which of the following would best describe her cardiovascular state during the exercise?
A.
B.
C.
D.
E.
[14.2]
A 25-year-old otherwise healthy patient is involved in a motor vehicle accident, and suffers appreciable blood loss. The cardiac output is
falling because of a loss of blood. As a compensatory mechanism, the
total peripheral resistance increases to attempt to maintain MAP.
Which of the following vasculature corresponding to the listed organ
is contributing the least to the elevated TPR?
A.
B.
C.
D.
E.
[14.3]
Increased blood flow through her right brachial artery
No change in cardiac output
Increased total peripheral resistance
Decreased blood flow through her left brachial artery
Decreased heart rate
Brain
Small intestine
Kidney
Skeletal muscle
Skin
If blood flow to an arm is obstructed for more than 30 seconds or so
during the process of a blood pressure measurement, the release of the
blood pressure cuff will be followed by a temporarily higher than
resting level of blood flow through the arm. Which of the following
best describes the temporarily higher blood flow?
A.
B.
C.
D.
Accompanied by an increase in total peripheral resistance
Called active hyperemia
Caused by a temporary increase in mean arterial pressure
Caused by local vasodilation resulting from the buildup of local
metabolites
E. Caused by the shifting of blood flow from other organs
CLINICAL CASES
[14.4]
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A patient has a renal condition that results in the loss of albumin in
the urine that exceeds the body’s albumin production. The resulting
hypoalbuminemia will lead to edema of the hands, face, and feet.
Which of the following is likely to be noted?
A.
B.
C.
D.
E.
Decrease in interstitial fluid hydrostatic pressure (PIF)
Increase in capillary hydrostatic pressure (Pc)
Increase in lymph flow
Increase in plasma oncotic pressure (πc)
Increase in the filtration coefficient (Kf) of capillaries in the skin
Answers
[14.1]
A. The increased metabolic activity of the muscles in the subject’s
right arm will induce relaxation of small arteries and arterioles, thus
reducing local resistance as well as total peripheral resistance. This,
along with no change in mean arterial pressure, will result in an
increase in blood flow through her right brachial artery. The increased
blood flow to the right arm will be accomplished by an increase in
heart rate and cardiac output, not by a decrease in flow to other
organs.
[14.2]
A. In cases in which cardiac output is inadequate, compensatory
mechanisms come into play so that blood flow to vital organs such as
the heart and brain is preserved as much as possible. One of these
mechanisms is activation of sympathetic nerves to constrict small
arteries and arterioles in organs whose vessels are heavily innervated.
Vessels in the brain and heart undergo the least vasoconstriction.
[14.3]
D. During the occlusion, metabolites build up in the arm tissues.
These metabolites cause relaxation of arteriolar smooth muscle and
decreased local vascular resistance. When the dilated local vessels are
exposed again to blood under normal mean arterial pressure, flow is
greater than it was before occlusion. This reactive hyperemia is temporary because the increased flow will return metabolites to their normal resting value. Neither mean arterial pressure nor blood flow to
other organs need be altered during this time.
[14.4]
C. Hypoalbuminemia results in a decreased πc, the major force favoring absorption. This results in an increase in capillary filtration, an
increase in lymph flow, and an increase in PIF to levels above atmospheric. Once the edema safety factor is exceeded, edema results.
Unless endothelial cells were damaged, there would be no change in
Kf. Also, hypoalbuminemia has no direct effect on Pc (it most likely
would decrease as a result of arteriolar constriction to maintain mean
arterial pressure).
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CASE FILES: PHYSIOLOGY
PHYSIOLOGY PEARLS
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Local resistance to blood flow in all tissues changes such that blood
flow is adequate to meet the metabolic demands of the tissues.
In certain tissues—skin, gastrointestinal, renal—but not in others—
heart, brain—local regulation can be temporarily overridden by
extrinsic factors in attempts to maintain mean arterial pressure.
Changes in blood flow through any vascular bed normally are met
by changes in cardiac output.
The exchange of substrates and metabolites between blood and tissue occurs at the level of the capillaries, mostly by means of
diffusion.
Fluid filtration out of and absorption into capillaries depend on the
balance between hydrostatic and osmotic forces across the capillary wall. Disruptions in this balance can lead to edema.
REFERENCES
Levy M, Pappano A. Cardiovascular system. In: Levy MN, Koeppen BM, Stanton
BA, eds. Berne & Levy, Principles of Physiology. 4th ed. Philadelphia, PA:
Mosby; 2006:298-319.
Granger DN. Regulation of regional blood flow and capillary exchange. In: Johnson
LR, ed. Essential Medical Physiology. 3rd ed. San Diego, CA: Elsevier
Academic Press; 2003:245-258, 235-244.