integrated control of the cardiovascular system
DESCRIPTION
Integrated control of the cardiovascular system. Integrated control of the cardiovascular system acts to adjust cardiac output to support metabolism in the face of Wide variations in metabolic demands (rest vs. exercise) Diseases that may compromise cardiac or vascular function - PowerPoint PPT PresentationTRANSCRIPT
Integrated control of the cardiovascular system
Integrated control of the cardiovascular system acts to adjust cardiac output to support metabolism in the face of
Wide variations in metabolic demands (rest vs. exercise)
Diseases that may compromise cardiac or vascular function
To understand how cardiac output is maintained first consider the function of individual components (heart, capacitance veins, arterioles, blood volume, baroreflexes)
Then consider how these factors interact during (for example) exercise or heart failure.
Outline
1. Control of the circulation is dependent on the fact that the circulation is a closed loop: cardiac output = venous return.
2. Changes in cardiac output affect the distribution of blood between the arterial and venous systems.
3. The relation between CVP and CO is shown by the vascular function curve.
a. The vascular function curve may be defined by two points:
venous pressure when CO = zero and when CO = 5 L/min.
b. The vascular function curves are affected by changes in blood volume, venous capacitance, or TPR
4. The relation between CVP and stroke volume is shown by the cardiac function curve.
5. The intersection of vascular and cardiac function curves is the equilibrium point for the circulation under a given set of conditions.
6. The equilibrium point is changed by changes in physiological conditions or disease (for example, exercise or heart failure).
1. Control of the circulation is dependent on the fact that thecirculation is a closed loop: cardiac output = venous return.
A closed loop model can be used to show how the venous and arterial systems interact with cardiac output.
In the model, for simplicity, the heart and lungs are grouped together as a pump-oxygenator similar to a heart-lung machine.
Arterial system
Heart & lungs
Venous system
Peripheral resistance
Normal volumes & pressures
DP is (102 – 2) = 100 mm Hg
Total peripheral resistance(primarily due to arterioles)
Veins contain ~ 67% of blood volume (venules, veins, vena cava)
Arteries contain ~ 11% of blood volume (aorta, arteries, arterioles)
Cardiac output = 5 L/min
Venous systemPressure = 2 mm Hg
Arterial systemPressure = 102 mm Hg
2. Changes in cardiac output affect the distribution of blood between the arterial and venous systems.
As an extreme example consider the effect of cardiac arrest (CO = zero):Initially the arteriovenous DP is (102 – 2) = 100 mm Hg.Blood flows from arteries to veins until at equilibrium DP = zero.At equilibrium the pressure throughout the circulation = 7 mm Hg.This equilibrium pressure is called the mean circulatory filling pressure, MCFP. The value of MCFP is set by blood volume & the capacitance of the vascular system (primarily the venous capacitance).In other words, how much blood is present and how big the “container” (vascular system) is.
When the heart stops, blood flows down the pressure gradient from the arterial to the venous system
Arterial volume Venous volume
CO = zero
flow
Graphical representation of determination of the MCFP
Pre
ssur
e, m
m H
g
Seconds
125
100
75
50
25
0 5
Mean circulatory filling pressure (~ 7 mm Hg)
Arterial pressureVenous pressure
Mean circulatory filling pressure is the pressure measured when arterial and venous pressure are equal.
Cardiac arrest at t = 0
Resuscitation reverses the effect of cardiac arrest on vascular pressures & volumes
Increasing cardiac output causes blood to shift to the arterial system
Arterial volume & pressure increase
Venous volume & pressure decrease
Heart begins to beat, CO = 5 L/min
flow
Effect of restoring CO to normal
Heart begins to beat, CO = 5 L/min
CO transfers blood from venous to arterial circulation
venous volume
arterial pressure ( 7 → 102 mm Hg) venous pressure (7 → 2 mm Hg)
arterial volume
An isolated increase in CO without any other changes in the circulation decreases central venous pressure by transferring blood from the venous to the arterial circulation.
Measuring CVP at different levels of CO further defines the vascular function curve
As cardiac output increases blood shifts to the arterial system & CVP decreases
Car
diac
out
put,
L/m
inC
entra
l ven
ous
pres
sure
m
m H
g
0
2
4
6
1 2 3 4 5
Minutes1 2 3 4 5
0
2
4
6
Venous pressure & capacitance
Venous pressure is determined by the volume of blood in the venous circulation and the capacitance of the venous system.
Venous capacitance is determined byThe structure of the veins and surrounding tissueSympathetic nerve activity.Sympathetic stimulationconstricts veinsdecreases venous capacitancedecreases venous compliance (constriction makes vessels stiffer)
3. The relation between CVP and CO is shown by the vascular function curve.
This graph of CVP as a function of CO is a vascular function curve
Cardiac output, L/min
Cen
tral v
enou
s pr
essu
re, m
m H
g
CO = zero, MCFP = 7 mm Hg
CO = 5 L/min, CVP = 2 mm Hg
-1
0
1
2
3
4
5
6
7
1 2 3 4 5
3a. The vascular function curve may be defined by two points:venous pressure when CO = zero and when CO = 5 L/min.
Theoretically cardiac output is limited by CVP = zero
As CO increases, CVP decreases.Hypothetically, at CVP = zero,distending pressure = 0large veins collapse & CO = 0.
Physiologically, CO may increase above 7 L/min due to changes in blood volume or vascular function.
CO = zero, MCFP = 7 mm Hg
Cardiac output, L/min
Cen
tral v
enou
s pr
essu
re, m
m H
g
-1
0
1
2
3
4
5
6
7
CO = 5 L/min, CVP = 2 mm Hg
1 2 3 4 5 6
CO = 7 L/min, CVP = zero
7
Patency of veins depends on transmural pressure
Positive transmural pressure keeps veins open.In the thorax the tissue pressure external to the large veins is negative (negative intrathoracic pressure is a result of normal respiratory function).This negative intrathoracic pressure helps keep the large veins open even if CVP is close to zero.
Venous pressure = +2 Tissue pressure zeroTransmural pressure = +2Vein is patent
Venous pressure = 2 mm Hg
If venous pressure & tissue pressure both = zero, then transmural pressure = zero & veins collapse
3b. The vascular function curve is affect by changes in blood volume.
An increase in blood volume will increase CVP & MCFP; a decrease in blood volume will have the opposite effect.
MCFP
Cardiac output, L/min
1 2 3 4 5 6 7 8-1
0
1
2
3
4
5
6
7
8
Blood volume
Blood volume
Cen
tral v
enou
s pr
essu
re, m
m H
g
An increase in blood volume will allow the heart to increase CO
3b. Effect of a change in venous capacitance on vascular function
Sympathetic stimulation decreases capacitance (constricts veins).
When venous capacitance is decreased CVP is higher at any level of CO.
venomotor tone (decreased capacitance)
venomotor tone(increased capacitance)
MCFP
Cardiac output, L/min
Cen
tral v
enou
s pr
essu
re, m
m H
g
0
1
2
3
4
5
6
7
8
1 2 3 4 5 6 7 8
When venous capacitance is increased CVP is lower at any level of CO.
1) Steady state cardiac output = flow across arterioles = flow through veins
2) If TPR (arteriolar constriction) with no change in CO, then flow across resistance (QR)
decreases below CO, that is:
3) The heart pumps blood into the arterial system (decreasing venous volume) so arterial pressure increases until QR equals CO
4) The steady state is restored but venous volume and therefore CVP are decreased
An increase in TPR without a change in CO decreases CVP
VR QQCO
RQCO
COQR
VR QQCO
Arterial system
Heart & lungsVenous system
TPR (arterioles)QR
QV CO
3c. Changes in TPR & the vascular function curve
The arterioles contain only a small fraction of the total blood volume so changes in TPR have only a small effect on MCFP
-1
0
1
2
3
4
5
6
7
8
1 2 3 4 5 6 7 8
Cardiac output, L/min
MCFP = 7 mm Hg(not affected by changes in TPR)
Cen
tral v
enou
s pr
essu
re, m
m H
g
TPR (vasoconstriction)
TPR (vasodilation)
TPR (vasoconstriction) decreases venous volume, lowering CVP.Vasodilation has the opposite effect.
Summary of factors affecting the vascular function curve
Since the circulation is a closed loop, venous return & cardiac output are equal except for transient responses to perturbations
Mean circulatory filling pressure (MCFP) is set by the blood volume and vascular (mostly venous) capacitance.CVP is increased by an increase in
Blood VolumeVenomotor Tone (decrease in capacitance due to sympathetic stimulation)A decrease in arteriolar resistance
4. The relation between CVP and CO is shown by the cardiac function curve (Frank-Starling mechanism)
Preload: the degree to which the myocardium is stretched just before contraction.Preload for the right ventricle is estimated as CVP, or right atrial pressure.Preload for the left ventricle is estimated as left atrial pressure by measuring PCWP (Pulmonary capillary wedge pressure)
Afterload: the pressure against which blood is ejected from the heart.Afterload for the right ventricle is pulmonary artery pressure during ejection.
Afterload for the left ventricle is aortic pressure during ejection.
The Frank-Starling Mechanism: stretch (preload) affinity of troponin C for Ca++ force of contraction.An equivalent statement is: EDVV stroke volume
Initial myocardial fiber lengthor EDVV or atrial pressure
Forc
e of
con
tract
ion
or S
troke
Vol
ume
Cardiac function curve
The cardiac function curve is an expression of the Frank Starling mechanism
An increase in cardiac output without any other changes in the circulation, shifts blood from the venous to the arterial vasculature, decreasing venous volume and therefore CVP.
CO
1 2 3 4 5 6
0
2
4
6
CV
P
Vascular function curve
CVP
CO
Frank-Starling Mechanism
An increase in central venous pressure increases right atrial filling pressure, stroke volume and CO.
Relationship between CVP and CO
Conditions that challenge the cardiovascular system in the intact organism act via the baroreflex to
increase cardiac output &constrict capacitance vessels in the venous systemConsequently, CVP may remain constant or increase.
To allow comparison of the vascular and cardiac function curves, the vascular function curve is rotated to put cardiac output on the y axis.
CO
0
2
4
6
1 2 3 4 5 6
CV
P
Vascular function curve
CO
0 2 4 6
1
2
3
4
5
6
CVP
CVP
5. The intersection of vascular and cardiac function curves is the equilibrium point for the circulation under a given set of conditions
Central venous pressure, mm Hg
Car
diac
out
put,
L/m
in
2
4
6
-1 1 2 3 4 5 6 70
The intersection is called the equilibrium point.Normally this point is at CO = 5 L/min and CVP = 2 mm Hg.
The location of the equilibrium is determined by:sympathetic tonecardiac contractilityblood volume
Car
diac
out
put,
L/m
in
2
4
6
-1 2 4 60
AD
C B
The next five slides show examples of how changes in cardiac or vascular function affect the equilibrium point.
D: CVP CO; equilibrium is restored.Changes occur within a few beats.
A: CVP increases
C: CO CVP (blood transferred from venous to arterial system)
B: on the cardiac function curve, CVP CO
Central venous pressure, mm Hg
Equilibrium is restored if CVP increases with no change in CO or sympathetic tone.
An increase in cardiac contractility shifts the cardiac function curve upwards and moves the equilibrium point.
In this hypothetical example assume that sympathetic stimulation only affects the heart, not the blood vessels, so there is no change in the vascular function curve.
A: sympathetic stimulation increases the contractility ( - - - - )B: increased CO lowers CVP to the new equilibrium point ()At the new equilibrium, CO is greater than before stimulation and CVP is less.
Central venous pressure, mm Hg
Car
diac
out
put,
L/m
in
2
4
6
-1 2 4 60
A
B
contractility
Effect on CO of transfusing blood into a normal subject
CVP is determined by blood volume and venous capacitance. CVP venous pressure & transmural pressureVeins remain open at CO > 7 L/min
End-diastolic ventricular volume
Stro
ke V
olum
e
Cardiac function curve
blood volume
CVP
atrial pressure
End diastolic volume
Stroke volume
CO
Frank Starling Mechanism
An increase in blood volume shifts the equilibrium point upwards
A: Initial equilibrium pointB: Blood volume CVPC: CVP CO ()New equilibrium point at higher CO
blood volume
CVP
atrial pressure
End diastolic volume
Stroke volume
CO
-1 2 4 60 8 10
Central venous pressure, mm Hg
Car
diac
out
put,
L/m
in
2
4
6
8
10
BA
C Blood volume
A decrease in venous capacitance increases CO
CVP is determined by blood volume and venous capacitance.Capacitance is capacity, i.e. the capacity of the venous system. capacitance → venous transmural pressureVeins remain open at CO > 7 L/min
capacitance
CVP
atrial pressure
End diastolic volume
Stroke volume
CO
Venous capacitance is determined byThe structure of the veins and surrounding tissueSympathetic nerve activity.Sympathetic stimulation constricts veins (increases venomotor tone) and decreases venous capacitance.
The effect of a decrease in venous capacitance is similar to the effect of an increase in blood volume.The equilibrium point is shifted upward along the cardiac function curve to a higher cardiac output.
Summary: effect of isolated interactions between vascular function & cardiac output
Cardiac output is increased by an isolated increase inCentral venous pressureCardiac contractilityVenomotor toneBlood volumetotal peripheral conductance.
Central venous pressure is increased by an isolatedDecrease in cardiac outputIncrease in venomotor toneIncrease in blood volumeDecrease in total peripheral resistance
It would appear that:
CO CVP CO
If this were correct how can CO be increased in response to metabolic demands?
These are isolated effects; in the intact organism CO increases with increased metabolic demand and CVP remains constant or increases.
Integrated response of CO & CVP to increased metabolic demand
In response to exercise, changes in the cardiovascular system act to maintain or increase CVP and increase cardiac output.
Muscular activity
Venous volume
Arterial pressure
Cardiac output
Muscle blood flow
CVP
Central nervous system
Sympathetic activity
Venomotor tone
Mobilize venous reservoirs
HR, contractility, ejection fraction
TPR
Venous capacitance
Interaction of right and left ventricles
Normal values:Right atrial pressure ~ 2 - 7 mm Hg (recumbent)Left atrial pressure ~ 5 – 10 mm HgHigher left atrial pressure provides the necessary preload to pump the CO against the systemic arterial pressure (afterload).
The right ventricle:Drives blood through the pulmonary circulation at the same rate that blood is delivered from the systemic veins &Provides sufficient pulmonary venous & left atrial pressure to allow an equal rate of pumping from the left ventricle.
Lft ventricle
Lft atrium
systemic circulation
systemic veins
Rt atrium
Rt ventricle
pulmonary arteries
pulmonary capillaries
pulmonary veins
Left ventricular failure produces symptoms related to increased pulmonary venous volume & pressureRight ventricular failure produces symptoms related to increased systemic venous volume and pressure
Effect of moderate heart failure on equilibrium point
The combination of decreased CO and increased CVP is a sign of heart failure
Heart failure is the inability of the heart to pump blood sufficient to meet the metabolic demands of the body or to do so only with abnormally high filling pressures.
B: Cardiac output
Arterial pressure
Arterial blood volume
venous blood volume
C: CVP
A: normal equilibrium point
Heart failure
2 4 60 8
Central venous pressure, mm Hg
A
Car
diac
out
put,
L/m
in
2
4
6
8Normal
CB
Effect of severe heart failure
Severe heart failure
The increase in blood volume shifts the vascular function curve upward.This increase is a compensation that ameliorates the decrease in CO.
A: Cardiac output
Arterial pressure Arterial blood volume
venous blood volume
B: CVP
CV Reflexes
Retain NaCl & H2O
blood volume
+
Effect of severe heart failure
Severe heart failure
Central venous pressure, mm Hg
Car
diac
out
put,
L/m
in
2 4 60 8 10
2
4
6
8
10
Normal
B
A C
A B represents the decrease in CO due to myocardial failureB C represents the increase in CVP due to the increase in total blood volume & the compensatory increase in CO (Frank - Starling mechanism)
Venous pressure in heart failure
In right heart failure superficial neck veins are distended & venous pressure waves may be visible.
Pulmonary capillary pressure
Pulmonary edema
dyspnea
Dependent edema
Left ventricular failure
CO
Left atrial pressure
Pulmonary venous, capillary, arterial pressure
Systemic venous pressure
Rt. Ventricular failure
afterload to Rt. ventricle
Cardiac output & vascular function
SERCA = sarcoplasmic reticulum Ca++ ATPaseANS = autonomic nervous system
Ventricular compliance
Filling time (heart rate) Preload
Passive relaxation
Active relaxation (SERCA)
Venous return
Blood volume
Venomotor tone
Muscle pump
Respiratory pump
Contractility (Sympathetic activity)
Afterload
Cardiac output = heart ratestroke volume x
End systolic volumeEnd diastolic ventricular volume
ANS
ANP & BNP inhibit the renin angiotensin system & decrease afterload (total peripheral resistance)
Increasing plasma BNP concentration is a sign of worsening heart failure.The kidneys become insensitive to natriuretic peptides in heart failure so renin secretion from the kidneys continues despite increased plasma ANP & BNP.Consequently the beneficial effect on decreasing afterload is limited.
Left ventricular failure
CO
Left atrial pressure (preload)
stroke volume
formation of angiotensin II
secretion of ANP from atria
secretion of BNP from ventricles
TPR (afterload)
renin secretion from kidney
cardiac work
CO
Positive feedback