Flashcards in Regulation of Cardiac Output Deck (44):
What is the eqn for arterial pressure?
= CO x resistance (TPR)
What is arterial resistance mainly determined by?
radius of the vessel
What two major things regulate cardiac output/functio?
- cardiac function
- vascular function
What does a cardiac function curve define?
ventricular output as a function of atrial (not arterial) pressure
What does a vascular function curve define?
venous return as a function of atrial pressure, independent of cardiac output
The cardiac function curve defines an dependent variable, ventricular output, as a function of an independent variable, atrial function. However, in the intact system atrial pressure is not fully independent and is determined by:
simultaneous activity of the ventricles and the blood vessels
What is atrial pressure determined by?
volume of fluid in the atria (which is in turn determined by vascular and ventricular function)
Describe the shape of a cardiac function curve.
The greater the atrial pressure (representing greater end diastolic volume, since atrial volume becomes ventricular volume once the volume has moved down from atria into ventricles) the greater is the ventricular output (SV x HR), up to a physiological limit represented by the flat part of the curve.
Why is increased atrial pressure associated with increased ventricular output (to a certain point)?
Increased atrial stretch activates Ca channels, thus inducing a greater heart rate. (SA node stretch sensitive calcium channels are activated due to stretch)
Moreover, increased atrial stretch also activates the Bainbridge reflex which further increases heart rate via sympathetics
The third factor involved in increased ventricular output via the classical Frank-Starling mechanism (increased EDV= increased SV).
What are some factors that directly set the cardiac function curve?
- sym/para activity
- intrinsic ventricular effectiveness
- afterload (aortic pressure)
- intrapleural (intrathoracic) pressure
How does afterload affect the cardiac function curve?
increased afterload shifts the cardiac function curve downward, via a reduction of stroke volume.
The net stretch imposed on a ventricle is determined by what?
the intraventricular end diastolic pressure MINUS the extraventricular pressure (intrapleural or intrathoracic pressure), that is the pressure surrounding the ventricles.
How does breathing affect net ventricular stretch?
As the outside pressure becomes more negative (normal= -4 mm Hg), as with deep breathing, the net stretch is also increased which results in greater ventricular output, as represented by a shift of the cardiac function curve to the left.
Note that in this case (or any time the intrathoracic pressure changes) the flat portion of the curves remains the same.
Describe a vascular function curve.
- plateau phase where venous return (VR) remains constant with increasing atrial pressure
- transitional zone at atrial pressure from ~-4 to 0 mm Hg
- down slope where VR decreases as atrial pressure increases until reaching:
-mean systemic filling pressure where venous return reaches zero
What does the slope of venous return curve represent?
resistance to venous return
The pressure gradient driving venous flow is the difference between the mean systemic filling pressure (x-intercept) and the arbitrarily set right atrial pressure. This is true until the curve reaches the plateau level. Why does the curve level out at the plateau?
Because of venous collapse, due to the fact that venous pressure becomes more negative than the pressure surrounding veins and veins are floppy. Thus, as the veins collapse, their resistance starts going up in parallel with the increase in the pressure gradient and therefore there is no further increase of venous return.
What is filling pressure?
the pressure that is required to fill the blood vessels beyond their intrinsic (air) volume with heart input
the pressure that is measured in the blood vessels with flow stopped so that the pressures are equal in all compartments of the circulatory system
T or F. The filling pressure can only be measured at zero cardiac output
T, because in the functioning system with a greater than zero cardiac output, there is no unique vascular pressure and the various pressures reflect the function of both ventricular output and venous return
What things determine filling pressure?
-unstressed volume, -compliance of blood vessels and
What is unstressed volume?
Unstressed volume is that volume of blood that just fills the blood vessels without stretching them beyond their intrinsic capacity, so that the filling pressure at that point is zero.
Any additional blood volume greater than the unstressed volume causes stretch and increases the pressure to greater than zero, i.e. the filling pressure
Describe the relationship between filling pressure and blood volume.
Linear. The x-intercept represents the unstressed volume whereas the slope represents the inverse of the compliance of the circulatory system. The greater the sympathetic activity, the lesser the unstressed volume (due to smaller blood vessels constricted under the influence of increased sympathetic activity) and the lesser the compliance, represented by the greater slope (due to less compliant blood vessels, also under the influence of increased sympathetic activity). Decreasing sympathetic activity will decrease systemic filling pressure, both by increasing unstressed volume and increasing compliance, i.e, decreasing the slope of the volume pressure line.
At “normal” sympathetic activity, unstressed volume is 4000 ml and at a blood volume of 5000 ml, filling pressure is 7 mm Hg. With increased sympathetic activity, unstressed volume is now 3200 ml and filling pressure is 14.5 mm Hg. Conversely, with decreased sympathetic activity, unstressed volume is 4600 ml and filling pressure is 2 mm Hg.
Eqn for VR.
RVR= slope of the curve (same as peripheral resistance)
What are some normal numbers for a vascular function curve?
In the “normal” condition, the curve intersects the x-axis at 7 mm and has a slope such that at zero right atrial pressure, the curve predicts 5 L/min venous return
How does RVR affect the VR curve?
A decrease of resistance causes the vascular function curve to rotate clockwise whereas an increase of resistance causes a counterclockwise rotation.
Based on the “normal” curve, we read a venous return of 5 L/min at arbitrarily assumed zero atrial pressure. Decreasing the resistance by half causes a clockwise rotation, and increases the slope by a factor of 2, thus causing a doubling of flow (recall that numerically, flow equals delta P divided by resistance and if resistance is halved, then flow will double). The opposite will be the case for a 2-fold increased resistance where flow will be 2.5 L/min, i.e., half of “normal”.
Steady state CO, VR, and atrial pressure (end diastolic volume) are determined by what?
the point of intersection of the cardiac function curve and the vascular function curve
How is steady state maintained?
In this example, the steady state atrial pressure is about 1.2 mm Hg and the steady state ventricular output/venous return is about 5.5 L/min. Now, let us arbitrarily assume an atrial pressure different than the steady state one, say zero. At atrial pressure zero, the ventricular function curve predicts a ventricular output of about 3.2 L/min (point 3) and a venous return of about 6.8 L/min (point 2). Thus, venous return is more than double ventricular output and this circumstance will result in an increase in atrial volume since more volume is coming into atria via venous return than is leaving via ventricular output. Consequently, atrial pressure will rise due to increased atrial blood volume. Therefore, in the next heart beat, let us assume that atrial pressure has risen to about 0.8 mm. At this atrial pressure, ventricular output is now about 4.5 L/min (point 5) and venous return is about 6.1 L/min (point 4). Thus, returning volume is still greater than outgoing volume and therefore atrial pressure will continue to rise, until output is exactly equal to return which is the values determined by point 1, i.e. the steady state.
What does sympathetic activity do to steady state?
if we assume the sympathetics only act on the heart, then the VR curve is unchanged and the cardiac function curve move up, making SS atrial pressure lead and SS VO and VR greater
Moreover, because cardiac output has increased and TPR is arbitrarily unchanged, arterial pressure has increased (recall that arterial pressure is cardiac output multiplied by TPR).
T or F. Atrial pressure reflects venous pressure.
T. Thus, as atrial pressure increases or decreases, so does venous pressure in parallel.
How does hypervolemia affect SS?
Hypervolemia (increase in blood volume) moves the vascular function curve to the right on the x-axis due to the increase in blood volume (increased filling pressure), without changing the slope of the line, i.e. TPR is assumed to remain constant.
This increase in the x-intercept occurs because there is greater blood volume in the system without a change of unstressed volume.
Furthermore, no change in the cardiac function curve is assumed because blood volume does not directly influence the cardiac function curve.
The move results in increased CO and increased atrial pressure (end diastolic pressure, preload). This is a very important set of curves because it will eventually allow us to link the role of the kidneys to excrete fluid to the regulation of long term regulation of arterial pressure.
What changes occur during exercise?
At rest, based on the “normal” curves, we read a cardiac output of about 5 L/min and an atrial pressure of about 0 mm Hg.
Exercise imposes independent changes on both cardiac function and vascular function curves.
How does the cardiac function curve change during exercise?
First, increased sympathetic activity/decreased parasympathetic activity associated with exercise moves the cardiac function curve upward. The curve is also moved upward/left because of a more negative intrathoracic pressure, associated with deeper breathing
How does the venous return curve change during exercise?
Sympathetic drive to the veins is also increased which causes smaller and stiffer veins and thus, increased systemic filling pressure. Moreover, mechanical compression of veins by active skeletal muscles induces a further increase of systemic filling pressure
Due to the large decrease of skeletal muscle blood vessel resistance, TPR decreases dramatically via local dilators to increase blood flow. This causes rotation of the vascular function curve in a clockwise direction. (Recall that the cardiac function curve is not directly influenced by TPR). In this system arterial pressure stays the same because even though CO is increased by 4x, resistance is decreased
Take home from the exercised induced changes?
The take home message is that when we impose appropriate changes on the curves, they predict a large increase of cardiac output with little or no increase in atrial pressure (aka end diastolic pressure or preload)
Both of these features are beneficial as the increase in cardiac output is necessary to sustain physical activity and the lack of a major increase in atrial or end diastolic pressure prevents a decrease in cardiac perfusion that would occur if the end diastolic pressure were to increase significantly. (Recall that especially the left side of the heart undergoes major perfusion during diastole and an increase of end diastolic pressure would tend to compromise such perfusion)
T or F. An increase in left heart end diastolic pressure would manifest as pulmonary edema if sufficiently elevated
T. Edema (in lungs) formation becomes significant when atrial pressure rises above 20 mm Hg. Prevention of edema at lower atrial pressures is due to so-called edema safety factors.
How does arterial pressure change in exercise?
Here we have a situation of increased cardiac output together with decreased TPR. Since arterial pressure is numerically determined by the product of these variables, it is unlikely that there will be a large increase in arterial pressure and indeed, in healthy persons, exercise induces either no increase of arterial pressure or a small increase.
How does hemorrhage affect steady state via the VR curve?
Curve 1 to 2: Hemorrhage involves hypovolemia (loss of blood) and therefore filling pressure decreases (FP2), leading to decreased CO(2) and therefore reduced arterial and atrial pressure (AP2)
What happens to the VR curve following these initial changes during hemorrhage?
increased systemic filling pressure (FP2'- still less than FP1 but more then FP2) and counterclockwise rotation of the curve because of increased TPR. These actions are the result of activation of sympathetic system due to baroreceptor inactivation, accompanied by inverse stress relaxation, increased capillary reabsorption and increased renin-angiotensin levels.
Potentially, chemoreceptors and CNS ischemic response may be activated as well.
Together, these slightly increase CO- called CO2' (below CO1 and above CO2), resulting in an increase of arterial pressure (partial or complete compensation of original decrease in arterial pressure, depending on the magnitude of the decrease and the capacity of homeostatic mechanisms to compensate) and atrial pressure increases above AP2 but still less than AP1.
How does hemorrhage affect steady state via the cardiac function curve?
- increased sympathetic activity raises the curve (from the end pt of the VR changes-2')
At the point of intersection of curves B and 2’ (point delta), cardiac output (CO3) is still lower than normal (but higher than CO2') but TPR is higher than normal (the latter due to increased sympathetic activity);
arterial pressure may be lower than normal or normal (partial or complete compensation of original decrease in pressure).
However, atrial pressure (AP3)(central venous pressure) will be below normal (below AP2') , leading to events in the following slide.
Last steps in hemorrhage?
Going from curve 2’ to curve 3 involves increasing systemic filling pressure over several days but not much further change of TPR (thus, not much change in slope).
Increased filling pressure is due to decreased stretch receptor activity because of lower than normal atrial pressure (inactivation of the atrial reflex thus causing increased renal sympathetic activity), increasing the release of vasopressin. angiotensin II, aldosterone and decreasing the release of atrial natriuretic peptide.
These, together with continuing generally increased sympathetic activity, induce fluid retention, over several days, due to renal function curve moving to the right on the x-axis (not shown here). Also, sensation of thirst will be increased (due to increased angiotensin II), further augmenting the increase in blood volume.
Thus, we go from CO3 to CO4 (point delta to point epsilon). Eventual going back to original curves and cardiac output (CO1) will involve restoration of blood volume loss over time, both by increased drinking and renal fluid retention and eventual normalization of blood pressure controlling mechanisms.
End result: In the intermediate term, somewhat reduced cardiac output, somewhat elevated TPR, partially compensated or normal blood pressure. In the long term, return to original curves and original cardiac output/arterial pressure.
Sequence of events in MI
1) Decreased cardiac output (from CO1 to CO2) induces decreased arterial pressure and inactivation of baroreceptors, potential activation of chemoreceptors and CNS ischemic response, thus inducing strong increase of sympathetic activity.
Sequence of events in MI
Due to decreased arterial pressure, all short term and intermediate term homeostatic pressure regulating mechanisms will be activated (except for cardiorenal reflex and atrial natriuretic peptide- reason: increased rather than decreased atrial pressure), causing an increase of filling pressure and movement of the vascular function curve to the right . These responses are homeostatic as they will tend to increase cardiac output (from CO2 to CO3).
Moreover, increased sympathetic activity will cause the vascular function curve to rotate counter-clockwise due to increased TPR (effect of increased TPR exaggerated here, for emphasis). Note that counterclockwise rotation is anti-homeostatic towards an increase of cardiac output; nevertheless, recall that increased TPR will independently contribute to increasing arterial pressure via Ohm’s Law and together with increased cardiac output, there will be an increase of arterial pressure.
Sequence of events in MI
Increased sympathetic activity may also move the cardiac function curve up, slightly, from curve B to curve C (even in a sick heart). This will induce a further increase of cardiac output (from CO3 to CO4).
End result of MI
End result: At this point, cardiac output is below optimal and blood pressure is likely to be lower than normal.