Download Control of Cardiac Output 2 - Dr. Ford

Control of Cardiac Output 2
George D. Ford, Ph.D.
OBJECTIVES:
1. Discuss the consequences of having a closed circulatory system.
2. Discuss how the right heart and left heart are coupled physiologically.
3. Know the three major factors governing venous return to the heart. Be able to
show these graphically as well as how variations in each factor affect this
graphical representation. Specifically:
a. Describe the role that the ratio of arterial to venous compliance and total
peripheral resistance plays in the graphical description of the venous
return.
b. Discuss the notions of mean systems pressure and stressed and unstressed
volume and the effect variations in these parameters have on the graphical
representation above.
4. Graphically display the relationship between venous return and cardiac output.
5. Translate the concepts discussed into clinically observable parameters.
6. Discuss at least three other factors which could influence venous return but are
not easily assimilated into the graphical analysis used for the other concepts
above.
I.
REVIEW OF THE HIGHLIGHTS FROM LAST LECTURE IN THIS
SEQUENCE:
A.
B.
In the steady-state, flow must be equal everywhere in the closed
cardiovascular system.
The Vascular Function Curve is the relationship between venous return
and right atrial pressure. It depends on 3 things:
1.
2.
3.
II.
The mean systems pressure (Pms) which determines the zero
intercept, i.e. pressure in the system with no flow. The mean
systems pressure is primarily a function of the effective circulating
blood volume.
The venous to arterial compliance ratio (Cv/Ca) and total
peripheral resistance (TPR) which determine the slope of the
vascular function curve.
Intrathoracic pressure which determines the “knee” of the
vascular function curve.
CARDIAC OUTPUT IN THE STEADY STATE IS DETERMINED BY
THE PROPERTIES OF THE HEART, VASCULAR SYSTEM, AND
BLOOD VOLUME. THESE DETERMINE THE SHAPES OF CARDIAC
FUNCTION AND VASCULAR FUNCTION CURVES. CARDIAC
OUTPUT WILL BE IN A STEADY STATE WHEN THE VASCULAR
FLOW RATE AND CARDIAC OUTPUT ARE EQUAL AT THE SAME
RIGHT ATRIAL PRESSURE.
Since flow must be equal everywhere in the system, the system can only exist at
flows compatible with both functions, i.e. the intersection of the two curves as
shown in Fig. 1 below.
Figure 1. Superposition of normal cardiac and vascular function curves. Pretty much like Fig. 22-8 on p. 401
of Berne, et al, “Physiology”, 5th Edition or Fig. 4-26 on p. 151 of L. Costanzo, “Physiology”, 3rd edition.
It is important to note here that the heart is an organ composed primarily of
striated muscle, that the vascular system is composed primarily of smooth muscle
and elastic elements, and that the vascular system is filled with blood. The cardiac
and vascular function curves are generated by the properties of these two
muscular systems and blood. It follows from this that to change the shape or
position of the cardiac and vascular function curves requires either that the
contractility of cardiac muscle change, the contraction of vascular muscle change,
or that blood volume changes.
III.
CHANGES IN CARDIAC OUTPUT IN CARDIOVASCULAR SYSTEMS
ARE ACHIEVED BY MODIFYING THE VASCULAR FUNCTION
CURVE, THE CARDIAC FUNCTION CURVE, OR BOTH.
A.
Positive changes in the cardiac function curve under resting
circumstances produce little change .
Figure 2 shows that increases in the inotropic (↑ contractility) state of the
heart will have little effect on cardiac output. Under normal conditions the
cardiovascular system equilibrium point is near the heel of the vascular
function curve and the improved ability of the heart to increase cardiac
output can not lead to an increased cardiac output. (That the equilibrium
point for the cardiovascular system is close to a right atrial pressure of 0
mm Hg indicates that normal heart has successfully transferred almost as
much blood to the arterial reservoir as possible and therefore created as
great a pressure gradient for flow as possible. Any additional transfer of
blood to the arteries would collapse the veins.)
B.
Negative changes in cardiac function lead to elevated right atrial
pressures.
On the other hand, decreases in cardiac contractility (negative inotropic
state) can have fairly profound effects as seen in curve C of Fig. 2. Note
the elevated right atrial pressure (RAP) at the new steady state. The
negative inotropic state makes the heart less able to transfer blood from
the veins to the arteries and hence the higher right atrial pressure and the
lower vascular flow rate. Elevated RAPs are strong clinical indicators of
heart failure.
Figure 2. The effect of inotropic state on cardiac output and Pra. Curve b control. Curve a, a cardiac function
curve shifted by a positive inotropic intervention, Curve c, a cardiac function curve shifted by a negative
inotropic intervention. See Fig. 22-12 on p. 404 of Berne, et al, “Physiology”, 4th Edition or Fig. 4-28 on p. 153
of L. Costanzo, “Physiology”, 3rd edition.
C.
Changes in blood volume cause changes on cardiac output.
Fig. 3 shows the effect of an increase or decrease in blood volume on
cardiac output/venous return and right atrial pressure. Note that changes in
blood volume affect only Pms. Otherwise the cardiac function curve is
virtually unaffected and the slope of the vascular function curves are also
relatively unaffected.
Figure 3. Effect of blood volume changes on cardiac output/venous return and right atrial pressure. Curve b is
the control condition, curve a is produced by-an increase in blood volume, curve c is produced by a decrease in
blood volume. The transfusion part is shown in Fig. 22-11 on p. 403 of Berne, et al, “Physiology”, 5th Edition or
Fig. 4-29 on p. 154 in L. Costanzo, “Physiology”, 3nd edition.
D.
Changes in stressed volume also effect change in cardiac output and
right atrial pressure.
Increases in stressed volume produce changes in the vascular function
curve identical to that of a blood volume increase. Curve A of Fig. 3 could
be produced by an increase in stressed volume (or a decrease in unstressed
volume). Curve C of Fig. 3 could be produced by a decrease in stressed
volume (or an increase in unstressed volume).
E.
The effect of the sympathetic nervous system on cardiac output and
right atrial pressure.
As a quick review, fibers from the sympathetic nervous system innervate,
among other structures, veins, arterioles, and myofibers of the cardiac
ventricles. The neurotransmitter released from these fibers is
norepinephrine. In vascular smooth muscles this transmitter binds to
alpha1 receptors and causes the muscle fibers to contract. The effect on
veins is to decrease the unstressed volume and thereby to increase Pms.
The effect on arterioles is to decrease the caliber of the arterioles, to
increase total peripheral resistance (TPR), and thereby to rotate the
vascular function curve counterclockwise. The myofibers in the
ventricular walls of the heart increase their contractility (positive inotropic
response) in response to an increase in the release of neurotransmitter
from the sympathetic nervous system. The norepinephrine binds to beta
receptors to produce this increase in cardiac contractility. The
consequence of these three effects of sympathetic stimulation on the
cardiovascular system is shown in Fig. 4.
Figure 4. The effect of sympathetic stimulation on cardiac output/venous return and right atrial pressure. Figs.
22-9 on p. 402 and 29-13 on p. 468 of Berne, et al, “Physiology”, 4th Edition, have some of this same
information.
There are two points which need to be made about this figure and the
response of the cardiovascular system to increases in sympathetic nervous
system activity. 1) The effect of the decrease in unstressed volume
(contraction of the veins) is sufficiently great so that the vascular function
curve produced in response to sympathetic nervous system activation
always lies to the right and above the control curve. The counterclockwise
rotation of the vascular function curve due to contraction of arterioles does
not bring the curve produced by sympathetic stimulation below the control
curve. 2) It is difficult to predict precisely how right atrial pressure will
change. If there is a change in it will be small.
IV.
DURING THE TRANSIENT STATE VENOUS RETURN MAY DIFFER
FROM CARDIAC OUTPUT
When the equilibrium condition (steady-state) changes from one value to another
the cardiovascular system goes through a transient-state in which cardiac output
differs from venous return. An example of such a transient-state is the response of
the cardiovascular system to a sudden addition of fluid into the cardiovascular
system. The response is plotted in Fig. 5.
Figure 5. The transient effects of intra arterial infusion on venous return and cardiac output.
After rapid infusion of fluid into an artery a new venous return curve is created
because of the increase in Pms from 7 mm Hg to 10 mm Hg produced by the
infusion of fluid. Note that at the time of infusion the equilibrium condition was a
right atrial pressure of 0 mm Hg and a cardiac output of 5 liters/min. After
infusion the venous return at 0 mm Hg is, however, 7.5 liters per minute. This is
greater than cardiac output. With venous return greater than cardiac output,
venous volume and hence venous pressure will increase. The increase in venous
pressure will increase right atrial pressure. In this example the increase is first to 1
mm Hg and then to 2 mm Hg. At a right atrial pressure of 2 mm Hg the cardiac
output and venous return become equal at 7.0 liters/min, the new equilibrium
(steady-state) condition.
V.
OTHER FACTORS INFLUENCE VENOUS RETURN
A.
THE SKELETAL MUSCLE “PUMP”
Standing upright has a potential price to pay with regard to venous return.
Consider the force of gravity acting on a column of fluid represented by
the blood in our feet leading to our heart. This is a column of say 130 cm
of H2O or the equivalent of 10 cm of Hg. This could be a damper on
venous return, a condition referred to as orthostatic hypotension. This
doesn’t usually happen for two reasons. First there is a corresponding
effect on the arterial side which tends to push with nearly equal force.
Think of what happens in an U-tube. Increasing the pressure has an equal
effect on both sides. More physiologically though, the veins have valves
which prevents any significant back flow. In addition, as the veins course
through the skeletal muscle systems of our legs and thighs, they are
exposed to the rhythmic contractions of our postural muscles. In effect this
acts like a peristaltic pump, rather like squeezing a tube of tooth paste.
This action, combined with the unidirectionality conferred by the valves
acts as an effective pump for venous return from the lower extremities.
This is generally enough to offset the influence of gravity. How does this
get reconciled with the Guyton approach? I’m sure Dr. Guyton would
argue this effect is equivalent to an increase in stressed volume.
B.
THE RESPIRATORY “PUMP”
During inspiration the pressure within the thorax and around the heart
decreases. This decrease increases ventricular transmural pressure and
increases the flow of blood into the ventricles. This is most important for
the right ventricle. Thus inspiration increases venous return to the right
heart and increases right heart output.
During expiration the pressure within the thorax increases and reduces
venous return. However venous return during apnea (cessation of
breathing) is lower than during normal rates of respiration indicating the
normal breathing facilitates venous return more than impeding it.
There are some times when the respiratory effect is more prominent. For
example, the Valsalva maneuver is used clinically to test the competence
of the baroreceptor reflex. (This reflex will be discussed in a later lecture.)
During the Valsalva maneuver intrathoracic pressure is increased to very
high pressures by contracting the thoracic muscle when the glottis is
closed. This very high intrathoracic pressure can bring venous return to the
right heart to zero. Coughing, defecation, heavy lifting, and the playing of
brass instruments are modifications of this maneuver and can produce high
intrathoracic pressures which impede venous return.
Another possible ramification is in the application of artificial respiration.
Positive pressure inspiration with normal pressure expiration, as done in
some types of positive pressure ventilation, impedes venous return
markedly. If positive pressure inspiration is followed by negative pressure
expiration venous return is increased.
VI.
RECOMMENDED READING
Berne, R. M., Levy, M. N., Koeppen, B.M. & Stanton, B.A. "Physiology", 5th
Edition, Mosby Year Book, Boston, 2004. Chapter 22, pp 395 -412.
Guyton, Jones, and Coleman, "Circulatory Physiology: Cardiac Output and its
Regulation", 1973, W.B. Saunders, Philadelphia, Chapter 14, pp 237-248.
Costanzo, Linda S., “Physiology”, 3rd Edition, 2006, Saunders, Philadelphia,
Chapter 4, pp. 151-156.
VII.
SAMPLE QUESTIONS
Instructions: Identify all correct answers.
1. If the mean circulatory pressure in an isolated non-flowing vascular
system is 10 mm Hg, the unstressed volume is 3.5 liters and the
capacitance of the stressed volume is 100 ml/mm Hg, the total volume of
fluid in the vascular system is?
A.
3.0 liters
B.
3.5 liters
C.
4.0 liters
D.
4.5 liters
E. 5.0 liters
2. A reduction in the amount of norepinephrine released by the sympathetic
nervous system would produce which change or changes in a vascular
function curve?
A.
decrease mean system pressure
B.
decrease unstressed volume
C.
decrease total peripheral resistance
D.
rotate the slope of the vascular function curve counterclockwise
E. rotate the slope of the vascular function curve clockwise
3. Which of the following changes would increase right atrial pressure in a
cardiovascular system?
A.
increase in cardiac contractility
B.
increase in blood volume
C.
increase in total peripheral resistance
D.
decrease in unstressed vascular volume
E. decrease contraction of veins
4. Which of the following changes would decrease cardiac output in a
cardiovascular system?
A.
increase in total peripheral resistance
B.
decrease in cardiac contractility
C.
decrease in mean system pressure
D.
increase in unstressed vascular volume
E. increase contraction of veins
ANSWERS
1. D (Calculation: volume = unstressed + stressed = 3.5 L + 10mmHg x
100ml/mmHg = 3.5 + 1 L = 4.5 L)
2. A, C, E (yes A, ↓NE means ↓ venoconstriction and hence ↓stressed
volume and ↓Pms; not B, ↓stressed volume means ↑unstressed; yes C,
↓NE means ↓ vasoconstriction; not D, see explanation for E; yes E, ↓
vasoconstriction means ↓ TPR which causes ↑slope)
3. B, D (not A, shift of CFC to left causes ↓ RAP; yes B, ↑BV means ↑Pms
means VFC shifts upward; not C, ↑TPR means VFC shifts downward; yes
D, ↓ UV means ↑stressed volume which means ↑Pms as in D; not E,
venodilation means ↑unstressed and ↓stressed volume hence ↓Pms)
4. A, B, C, D (really same question as one above asking which parameters
would shift either the VFC or CFC in the right direction to move the
intersection of the two curves upward; yes D because ↑unstressed and
↓stressed volume hence ↓Pms; not E because venoconstriction leads to
↑Pms)