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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.

sigmoidal shape


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
-blood volume


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.

delta(P)/RVR, where

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.