Polytechnic University of Puerto Rico, San Juan Campus

Biomedical Engineering Department

Physiological Modeling and Control Systems
BME 3020-80
FA-21

Final Project: Mathematical Model of Circulatory System

Ivanette Cubero Muñoz 120696

Sheila Vázquez 111851
Joshua Ruiz 134519

Prof. Juan B. Valera Márquez

Activity submitted: October 27, 2021

Abstract

The circulatory system is the system that contains the heart and blood vessels and moves
blood throughout the body. This system helps tissues get enough oxygen and nutrients,
and it helps them get rid of waste products. [1] A mathematical model is developed to
describe the pressure, volume, and slow dynamics of the systemic circulatory system.
Mathematical representations for the autonomic and central nervous system are
presented. This model shows an approach to modelling the pressure-volume relationship
in a vessel with smooth muscle contractions. Simulations of cardiac arrest and
hemorrhagic situations were conducted, and results were compared with clinical
observations. [2] Graphs shows different relationships with pressure being a variable in
most of them.

i
Table of Contents

Abstract ................................................................................................... i

List of Figures ....................................................................................... iii

Introduction ............................................................................................ 1

Analysis .................................................................................................. 2

Discussion .............................................. Error! Bookmark not defined.

Conclusion .............................................. Error! Bookmark not defined.

References ........................................................................................... 14

ii
List of Figures

Figure 1. The two-compartment model ..................................................................................... 3

Figure 2: The Q1 multiplier function.. ........................................................................................ 4
Figure 3: The OVP multiplier of cardiac uptake ...................................................................... 6
Figure 4: The ANS0 Multiplier of cardiac uptake .................................................................... 7
Figure 5: The ANSz multiplier of the Qz fluidity ...................................................................... 7
Figure 6: The CNS0 multiplier of cardiac uptake .................................................................. 10
Figure 7: The CNSz factor of the Z2 fluidity ........................................................................... 10

ii
Introduction

In this modelling approach, a physiological system is subdivided by constituent into

several linked interacting subunits called compartments. Each compartment contains a
single physical constituent, such as blood. A constituent can appear in more than one
compartment if it is further subdivided based on location in the body or residence in a
subsystem, such as blood in the arteries or veins. Each dynamic found on the
compartment are specified by “lumped” time independent compartmental pressure
functions. Compartmental functions are obtained from the physical pressure associated
with its contents by taking a spatial average over the physical extent of the compartment
and temporal average over one cardiac cycle. The model is the formulated in terms of
differential equations. Changes in volume and flow can be obtained from associating
resistance and compliance parameters with compartments. Volume adjustments are
done in the membrane at the interface. The model described for this project is a
hydrodynamic analogy of an electronic circuit model where voltage, current and charge
are replaced by pressure, flow, and volume respectively. This model captures the
physiological responses instigated by the central and autonomic systems to regulate
cardiac output, arterial pressure, and maintain blood flow to the intracranial system to
preserve brain function. The representations of the model of the autonomic nervous
system (ANS) and central nervous system (CNS) involve functions with maximum and
minimum effect.

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Analysis

Mathematical Model for Circulatory System

In this model developed by Stevens and Lakin they incorporated a more accurate way to
capture circulatory system responses, and that is by modelling the autonomic and the
central nervous system.

The present model was developed of two compartments, the arteries compartment (A)
and the veins compartment (V). The compartments have a time dependent function which
is denoted by PA and PV both measured by the standard unit of pressure mmHg. This
function is spatially averaged over the whole subunit and temporally averaged over one
cardiac cycle. This model also possesses a heart pump for which cardiac uptake equals
cardiac output (QVH = QHA). In the model each compartment also has an associated
volume function denoted as VA and VV. The model considers two pathways for blood flow
and that is between arteries and veins. The model also denotes cerebral blood flow as
Q1, and all other flow is denoted by Q2. The authors make this distinction due to the fact
that cerebral blood flow is well regulated and remains mostly constant. Lastly, the model
includes flow terms QAM and QVM to allow simulations of a hemorrhage and represent
blood flow into a non-vascular region. The diagram of the model explained above is shown
below (Figure 1). The model is governed by the following equations,

(1)

(2)

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 Figure 1. The two-compartment model

Is important to note that this model describes a dynamic behavior that involves a response
bounded by a minimum and a maximum value with a smooth logistic transition between
both values.

According to the authors, normal blood flow through the brain is governed by the pressure
gradient between the cerebral arteries and the brain and it is termed as perfusion
pressure. The authors noted that the model presented above does not have an explicit
brain compartment, the pressure difference PA – PV, denoted by PAV, will act as a
replacement for perfusion pressure. For this context PAV will be termed by “systemic
indicative pressure”. The data indicates that Q1 remains almost constant for arterial
pressures between 60 and 150 mmHg. Thus, Q1 is defined as,

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 (3)

Where PAV is the mean systemic indicative pressure and Q1 is the mean cerebral blood
flow. The Q1 multiplier function Linc is shown in figure 2.

Figure 2: The Q1 multiplier function. The full circle is located at the mean systemic indicative pressure.

As the venous pressure remains near zero, this threshold corresponds to an arterial
pressure that is also near 60 mmHg.

As the author mentions the non-cerebral flow is depicted by Q2, is also governed by a
pressure difference PAV however, unlike Q1, it will not be modelled by an expression
such as (3). Instead, it will be represented by the hydrodynamic version of the Ohm’s
law.

(4)

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In equation number 4 Z2, termed the fluidity or conductance is the inverse of resistance
R2. According to Stevens and Lakin, many mathematical models, fluidities are taken to
be constant in a linearization of the governing equations. In the case of this model, Z2 will
be allowed to vary with both pressures and time. Thus, the governing differential
equations (1) and (2) will be nonlinear. Z2 contains three factors,

Where Z2 = Q2 / PAV and the factors ANSZ and CNSz will vary in such a way that they
maintain arterial pressure. The functions describing ANSZ and CNSz will be explained later
in this analysis.

Since cardiac output plays a major role in the regulation of arterial blood pressure with
below-normal arterial pressures causing an increase in cardiac output, and above-normal
pressures causing a decrease in cardiac output. In this model, cardiac output depicted as
QHA has been set equal to cardiac uptake QVH. It is important to note that cardiac uptake
in this model is modelled in terms of venous return Q1 + Q2 – QVM and a regulatory
multiplier M which is based on central venous pressure and nervous system regulation.

(5)

Authors state that the dependence of QVH on the venous return is thus explicit in equation
5 and when M = 1 which is consistent with the Frank-Starling mechanism of the heart,
then cardiac output is equal to venous return. The effect of venous pressure on cardiac
uptake is included in the model as output versus pressure (OVP) in the cardiac uptake
multiplier M, which is defined to be M = OVP ANS0 CNS0 where OVP is represented by
the logistic function
𝑂𝑉𝑃 (𝑃𝑉 ) = 𝐿𝑖𝑛𝑐 (𝑃𝑉 − 𝑃̅𝑉 , 0.5, 2.5, 0) (6)

It is important to know that the behavior of OVP is depicted in figure 3.

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 Figure 3: The OVP multiplier of cardiac uptake. The full circle is located at the mean venous pressure.

Is known that cardiac output and arterial pressure are well regulated. There are two levels
of regulation in the presented model. The first level represents the ANS, which is provide
a regulatory response based on changes in arterial blood pressure, transmitted via the
baroreceptors located in the walls of the carotid arteries and arch of the aorta. The second
level represents the ischemic response of the CNS, which is triggered by a significant
reduction in cerebral blood flow.

The autonomic nervous system effects on cardiac output (ANS0) helps determine how
the cardiac output differs from the venous return. This is depicted in figure 4 and is defined
by the equation

𝐴𝑁𝑆0 = 𝐿𝑑𝑒𝑐 (𝑃𝐴 − 𝑃̅𝐴 , 0.1, 2, 0) (7)

Where PA is the normal mean arterial pressure.

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 Figure 4: The ANS0 Multiplier of cardiac uptake. The full circle is located at the mean arterial pressure of 96 mmHg.

The autonomic nervous system effects on non-cerebral blood flow (ANSZ) represents the
vasoconstriction or vasodilation of the arterioles based on changes in arterial pressure.
This is defined by
𝐴𝑁𝑆𝑍 = 𝐿𝑖𝑛𝑐 (𝑃𝐴 − 𝑃̅𝐴 , 0.3, 1.1, .7) (8)

This function is depicted in figure 5

Figure 5: The ANSz multiplier of the Qz fluidity. The full circle is located at the mean arterial pressure of 96 mmHg.

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 The authors mentioned that it is clear that a constant pressure, smooth muscle

contraction decreases vessel volume while, at a constant volume, smooth muscle

contraction increases pressure. Given this the authors developed an equation describing
the pressure-volume relationship in a compliant vessel with smooth muscle contraction
may be derived from a few basic assumptions. They assumed that each vessel has a
maximum volume Vmax and a minimum volume of zero, and that the transition between
these extreme values will be logistic in nature. This can be defined as
𝑉 𝑚𝑎𝑥
𝑉(𝑃) = (9)
1+ 𝑒 −𝑟(𝑃−𝑃∗)

Where P is the pressure inside the vessel, P* is the pressure outside the vessel and r >
0. The maximum slope occurs at P = P*. In the present model, the ambient pressure P*
(mmHg).

The authors assume that the curve defined by V(P) shift to the right during smooth muscle
contraction. This is equivalent to a decrease in volume at a given pressure, or alternatively
an increase in pressure at a given volume. This shift is a pressure increment that will be
denoted by f. The authors also assumed that in the resting state, the pressure generated
by smooth muscle contraction is zero. Including the shift f due to smooth muscle
contractions, the expression for V now becomes
𝑉 𝑚𝑎𝑥
𝑉= (10)
1+𝑒 −𝑟[𝑃−(∅+𝑃∗)]

Where f increases as the smooth muscle contracts. Assuming that r and Vmax are
constants, V can be differentiated with respect to time to give.
𝑉̇ = 𝐶[𝑃̇ − (∅̇ + 𝑃 ∗)]
̇
where
𝑟𝑉 𝑚𝑎𝑥 𝑒 −𝑟[𝑃−(∅+𝑃∗)]
𝐶=
(1 + 𝑒 −𝑟[𝑃−(∅+𝑃∗)] )2

The dot on V again denotes a time derivative. Here, C represent a type of compliance
which varies depending on internal pressure, external pressure and the pressure
generated from smooth muscle contraction. It will refer to as an active.

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In compartmental models which do not include smooth muscle contraction, volume
adjustment is directly related to pressure change through the equations dV/dt = C dP/dt,
where C is a traditional compliance. Thus, parameter calibration can be accomplished in
accordance with clinical results where there is no change due to smooth muscle
contraction. For the purpose of this analysis, we are not going to go further the following
constraint and equations:

Central nervous system regulation, the ischemic response. When blood flow through the
intracranial region is diminished significantly, the brain can become ischemic, and
responses are rapidly instigated by the CNS to restore arterial pressure. The factor

CNS0 in the M multiplier defined by equation M = OVP ANS0 CNS0 is associated with the

severe change in heart rate triggered by significant reductions in the cerebral blood flow
Q1. This is defined logistically by
𝐶𝑁𝑆0 = 𝐿𝑑𝑒𝑐 (𝑄1 − 𝑄̅1 , 0.01, 5, 0.9)

Where Q1 is the mean cerebral blood flow. CNS0 is depicted with respect to the
percentage change in Q1 from the original value mean Q1.

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 Figure 6: The CNS0 multiplier of cardiac uptake. The large full circle indicates mean values.

CNSz is associated with the severe vasoconstriction in the arterioles of the non-vital
tissues based on changes in cerebral blood flow. This effect is included in the model as
the final factor of Z2 and is defined by
𝐶𝑁𝑆Z = 𝐿𝑖𝑛𝑐 (𝑄1 − 𝑄̅1 , 0.01, 1.01, 0.1)
Figure 7 depicts CNSz with respect to the percentage change in Q1 from the original mean
Q1.

Figure 7: The CNSz factor of the Z2 fluidity. The full circle indicates mean values.

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Here are the detailed governing equations.

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Conclusion

In this model developed by Stevens and Lakin they incorporated a more accurate way to
capture circulatory system responses, and that is by modelling the autonomic and the
central nervous system.

The present model was developed of two compartments, the arteries compartment (A)
and the veins compartment (V). Each compartment contains a single physical constituent,
such as blood. The compartments have a time dependent function which is denoted by
PA and PV both measured by the standard unit of pressure mmHg. This function is
spatially averaged over the whole subunit and temporally averaged over one cardiac
cycle. This model also possesses a heart pump for which cardiac uptake equals cardiac
output (QVH = QHA). In the model each compartment also has an associated volume
function denoted as VA and VV. The model considers two pathways for blood flow and
that is between arteries and veins. The model also denotes cerebral blood flow as Q1,
and all other flow is denoted by Q2. The authors make this distinction due to the fact that
cerebral blood flow is well regulated and remains mostly constant. Lastly, the model
includes flow terms QAM and QVM to allow simulations of a hemorrhage and represent
blood flow into a non-vascular region.

Despite its relative simplicity, the mathematical model developed for this study is capable
of accurately describing the pressure, volume and flow dynamics of the systemic
circulatory system over the full physiological range of human pressures and volumes.
This is in large part due to new mathematical representations for the ANS and CNS
reflexes which maintain arterial pressure, cardiac output and cerebral blood flow as well
as a new approach to modelling the pressure – volume relationship in a vessel with
smooth muscle contraction. In applications of the model to pathology, near-perfect
agreement is obtained between predicted and observed values of the mean circulatory
filling pressure, cardiac output and arterial pressure decay in the face of hemorrhage and,
in the case of significant hemorrhage, the critical values delineating progressive and non-

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progressive hypovolemic shock. Simulations further indicate that the Frank – Starling ‘law
of the heart’ is relatively accurate, but small deviations from the case in which cardiac
uptake equals venous return must be allowed for the maintenance of cardiac output and
arterial pressure during hemorrhage. Smooth muscle contraction is also found to play a
major role in determining survival following hemorrhage.

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References

[1]National Cancer Institute. (2021). Retrieved from Circulatory System:

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/circulatory-
system
[2] Scott A. Stevens & William D. Lakin (2006) A mathematical model of the systemic
circulatory system with logistically defined nervous system regulatory mechanisms,
Mathematical and Computer Modelling of Dynamical Systems, 12:6, 555-576, DOI:
10.1080/13873950500064343

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