Guyton Model: Aldosterone
Catherine
Lloyd
Auckland Bioengineering Institute, University of Auckland
Model Status
This CellML model has been validated. Due to the differences between procedural code (in this case C-code)
and declarative languages (CellML), some aspects of the original model were not able to be encapsulated by
the CellML model (such as the damping of variables). This may effect the transient behaviour of the model,
however the steady-state behaviour would remain the same. The equations in this file and the steady-state
output from the model conform to the results from the MODSIM program.
Model Structure
Arthur Guyton (1919-2003) was an American physiologist who became famous for his 1950s experiments in which he studied
the physiology of cardiac output and its relationship with the peripheral circulation. The results of these experiments
challenged the conventional wisdom that it was the heart itself that controlled cardiac output. Instead Guyton
demonstrated that it was the need of the body tissues for oxygen which was the real regulator of cardiac output.
The "Guyton Curves" describe the relationship between right atrial pressures and cardiac output, and they form a
foundation for understanding the physiology of circulation.
The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model of human circulatory
physiology, capable of simulating a variety of experimental conditions, and contains a number of linked subsystems relating
to circulation and its neuroendocrine control.
This is a CellML translation of the Guyton model of the regulation of the circulatory system. The complete model consists
of separate modules each of which characterise a separate physiological subsystems. The Circulation Dynamics is the primary
system, to which other modules/blocks are connected. The other modules characterise the dynamics of the kidney,
electrolytes and cell water, thirst and drinking, hormone regulation, autonomic regulation, cardiovascular system etc,
and these feedback on the central circulation model. The CellML code in these modules is based on the C code from the
programme C-MODSIM created by Dr Jean-Pierre Montani.
This particular CellML model describes how aldosterone and its feedback control functions to modify the circulation.
Two inputs are used for controlling aldosterone secretion, the potassium concentration in the extracellular fluids (CKE)
and the effect of angiotensin (ANM) on aldosterone secretion. In turn, multiplier effects for aldosterone control of
potassium (AMK) and sodium (AMNA) transport through cell membranes, especially through the kidney tubule membranes are calculated.
model diagram
A systems analysis diagram for the full Guyton model describing circulation regulation.
model diagram
A schematic diagram of the components and processes described in the current CellML model.
There are several publications referring to the Guyton model. One of these papers is cited below:
Circulation: Overall Regulation, A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972,
Annual Review of Physiology
, 34, 13-44. PubMed ID: 4334846
Terkildsen
Jonna
j.terkildsen@auckland.ac.nz
The University of Auckland
The Bioengineering Institute
2008-04-03
The University of Auckland, Bioengineering Institute
Guyton
Aldosterone
Description of Guyton aldosterone module
2008-00-00 00:00
keyword
physiology
organ systems
cardiovascular circulation
aldosterone
Guyton
ALDOSTERONE AND ITS FEEDBACK CONTROL FUNCTIONS FOR MODIFICATION OF THE CIRCULATION
Two inputs are used for controlling aldosterone secretion, the potassium concentration in the
extracellular fluids (CKE) and the effect of angiotensin (ANM) on aldosterone secretion.
In turn, multiplier effects for aldosterone control of potassium (AMK) and sodium (AMNA) transport
through cell membranes, especially through the kidney tubule membranes are calculated.
Encapsulation grouping component containing all the components in the Aldosterone Model. The inputs and
outputs of the Aldosterone Model must be passed by this component.
AL1, AL2, and AL3:
Calculation of the partial effect of angiotensin on aldosterone secretion (ANMAL)
based on the general angiotensin multiplier (ANM). The sensitivity of this effect
is controlled by the sensitivity control variable (ANMALD) in Block AL2.
AL1, AL2, and AL3:
Calculation of the partial effect of angiotensin on aldosterone secretion (ANMAL)
based on the general angiotensin multiplier (ANM). The sensitivity of this effect
is controlled by the sensitivity control variable (ANMALD) in Block AL2.
$\mathrm{ANMAL}=\mathrm{ANM}\mathrm{ANMALD}+1$
AL4:
Calculation of the driving force of potassium extracellular fluid concentration (CKE)
on aldosterone secretion by subtracting the constant 3.3 from CKE.
AL4:
Calculation of the driving force of potassium extracellular fluid concentration (CKE)
on aldosterone secretion by subtracting the constant 3.3 from CKE.
$\mathrm{OSMAL}=\frac{\mathrm{CKE}-3.3}{1.0}$
AL5:
Calculation of the basic rate of secretion of aldosterone (AMRBSC) by multiplying
the potassium drive for secretion from Block AL4 times the angiotensin drive for
aldosterone secretion (ANMAL).
AL6, AL7, AL8, and AL9:
These blocks calculate the aldosterone secretion rate (AMR). Blocks AL6, AL7,
and AL8 represent a sensitivity controller for the control of aldosterone secretion rate.
The sensitivity control variable is AMKMUL in Block AL7. Block AL9 sets a lower limit
to the aldosterone secretion equal to zero.
AL9A:
Provision is made here for infusion of aldosterone to perform infusion experiments (ALDINF).
AL9B:
Provision is made here to set the rate of aldosterone entering the circulatory system (AMR1)
to a constant value (ALDKNS) irrespective of all other changes at earlier stages in this
calculation.
AL5:
Calculation of the basic rate of secretion of aldosterone (AMRBSC) by multiplying
the potassium drive for secretion from Block AL4 times the angiotensin drive for
aldosterone secretion (ANMAL).
AL6, AL7, AL8:
These blocks calculate the aldosterone secretion rate (AMR). Blocks AL6, AL7,
and AL8 represent a sensitivity controller for the control of aldosterone secretion rate.
The sensitivity control variable is AMKMUL in Block AL7.
AL9:
Block AL9 sets a lower limit to the aldosterone secretion equal to zero.
AL9A:
Provision is made here for infusion of aldosterone to perform infusion experiments (ALDINF).
AL9B:
Provision is made here to set the rate of aldosterone entering the circulatory system (AMR1)
to a constant value (ALDKNS) irrespective of all other changes at earlier stages in this
calculation.
$\mathrm{AMRBSC}=\mathrm{ANMAL}\times 0.909\mathrm{OSMAL}\mathrm{AMRT}=\mathrm{AMRBSC}\mathrm{AMKMUL}+1\mathrm{AMR}=\begin{cases}0 & \text{if $\mathrm{AMRT}< 0$}\\ \mathrm{AMRT} & \text{otherwise}\end{cases}\mathrm{AMR1}=\begin{cases}\mathrm{ALDKNS} & \text{if $\mathrm{ALDKNS}> 0$}\\ \mathrm{AMR}+\mathrm{ALDINF} & \text{otherwise}\end{cases}$
AL10, AL11, and AL12:
Calculation of aldosterone concentration (AMC), allowing for a time delay in the
build-up of the aldosterone. The time constant for the time delay is AMT in Block AL12.
AL10, AL11, and AL12:
Calculation of aldosterone concentration (AMC), allowing for a time delay in the
build-up of the aldosterone. The time constant for the time delay is AMT in Block AL12.
$\frac{d \mathrm{AMC}}{d \mathrm{time}}=\frac{\mathrm{AMR1}-\mathrm{AMC}}{\mathrm{AMT}}$
AL13:
This block calculates, based on the input of aldosterone concentration (AMC),
an output factor (AM1) for the physiological multiplying effect of aldosterone
on different physiological mechanisms. This is a temporary aldosterone multiplier
effect. It is calculated as shown in the block, with AM1LL equal to the lower
limit of AM1 and AM1UL equal to the upper limit.
AL14, AL15, and AL16:
These are a sensitivity controller; the control variable for sensitivity is ALDMM in
Block AL15, and the output AM is a general aldosterone multiplier.
AL13:
This block calculates, based on the input of aldosterone concentration (AMC),
an output factor (AM1) for the physiological multiplying effect of aldosterone
on different physiological mechanisms. This is a temporary aldosterone multiplier
effect. It is calculated as shown in the block, with AM1LL equal to the lower
limit of AM1 and AM1UL equal to the upper limit.
AL14, AL15, and AL16:
These are a sensitivity controller; the control variable for sensitivity is ALDMM in
Block AL15, and the output AM is a general aldosterone multiplier.
$\mathrm{AM1}=\mathrm{AM1UL}-\frac{\mathrm{AM1UL}-1}{\frac{\mathrm{AM1LL}-1}{\mathrm{AM1LL}-\mathrm{AM1UL}}(\mathrm{AMC}-1)\mathrm{AMCSNS}+1}\mathrm{AM}=\mathrm{AM1}\mathrm{ALDMM}+1$
AL17, AL18, AL19, and AL20:
This is an additional sensitivity control circuit for controlling the aldosterone
multiplier effect on potassium transport through cell membranes (AMK), especially
in the kidney tubules. The input to this system is the general aldosterone multiplier (AM),
and the sensitivity controller is the variable AMKM in Block AL18. The lower limit to
AMK is set by Block AL20.
AL17, AL18 and AL19:
This is an additional sensitivity control circuit for controlling the aldosterone
multiplier effect on potassium transport through cell membranes (AMK), especially
in the kidney tubules. The input to this system is the general aldosterone multiplier (AM),
and the sensitivity controller is the variable AMKM in Block AL18.
AL20:
The lower limit to AMK is set by Block AL20.
$\mathrm{AMKT}=\mathrm{AM}\mathrm{AMKM}+1\mathrm{AMK}=\begin{cases}0.2 & \text{if $\mathrm{AMKT}< 0.2$}\\ \mathrm{AMKT} & \text{otherwise}\end{cases}$
AL21, AL22, AL23, AL24, and AL25:
This circuit calculates an aldosterone multiplier factor for control of sodium
transport through cell membranes (AMNA), with the input to the circuit equal to
the generalized aldosterone multiplier (AM) and a sensitivity controller (AMNAM)
in Block AL22. The upper and lower limits for the controlling effect on sodium
transport are set by variables AMNAUL and AMNALL in Blocks AL24 and AL25 respectively.
AL21, AL22 and AL23:
This circuit calculates an aldosterone multiplier factor for control of sodium
transport through cell membranes (AMNA), with the input to the circuit equal to
the generalized aldosterone multiplier (AM) and a sensitivity controller (AMNAM)
in Block AL22.
AL24, and AL25:
The upper and lower limits for the controlling effect on sodium
transport are set by variables AMNAUL and AMNALL in Blocks AL24 and AL25 respectively.
$\mathrm{AMNAT}=\mathrm{AM}\mathrm{AMNAM}+1\mathrm{AMNA}=\begin{cases}\mathrm{AMNALL} & \text{if $\mathrm{AMNAT}< \mathrm{AMNALL}$}\\ \mathrm{AMNAUL} & \text{if $\mathrm{AMNAT}> \mathrm{AMNAUL}$}\\ \mathrm{AMNAT} & \text{otherwise}\end{cases}$