- Author:
- Tommy Yu <tommy.yu@auckland.ac.nz>
- Date:
- 2015-02-12 17:26:11+13:00
- Desc:
- Merge in that extra head
- Keeping Joanna's version of RDF as she was original author.
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/guyton_aldosterone_2008/rawfile/4e79c5a5e51ee4e94aef801059d796d2278014c0/guyton_aldosterone_2008.cellml
<?xml version="1.0" encoding="utf-8"?>
<model
name="aldosterone_CellML1_0_model"
cmeta:id="aldosterone_CellML1_0_model"
xmlns="http://www.cellml.org/cellml/1.0#"
xmlns:cellml="http://www.cellml.org/cellml/1.0#"
xmlns:cmeta="http://www.cellml.org/metadata/1.0#"
xmlns:xlink="http://www.w3.org/1999/xlink">
<!-- ======================================== DOCUMENTATION ============================================= -->
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Guyton Model: Aldosterone</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
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.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
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.
</para>
<para>
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.
</para>
<para>
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.
</para>
<para>
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.
</para>
<informalfigure float="0" id="full_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="full_model.png"/>
</imageobject>
</mediaobject>
<caption>A systems analysis diagram for the full Guyton model describing circulation regulation.</caption>
</informalfigure>
<informalfigure float="0" id="aldosterone_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="aldosterone.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the components and processes described in the current CellML model.</caption>
</informalfigure>
<para>
There are several publications referring to the Guyton model. One of these papers is cited below:
</para>
<para>
Circulation: Overall Regulation, A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972,
<emphasis>Annual Review of Physiology</emphasis>
, 34, 13-44. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=4334846&query_hl=1&itool=pubmed_docsum">PubMed ID: 4334846</ulink>
</para>
</sect1>
</article>
</documentation>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
<!--
The following RDF block contains metadata that applies to this document
as a whole, as indicated by the empty about attribute on the
<rdf:Description> element.
-->
<rdf:Description rdf:about="">
<!--
The Model Builder Metadata. The Dublin Core "creator" element is used
to indicate the person who translated the model into CellML.
-->
<dc:title>Description of Guyton aldosterone module (CellML 1.0)</dc:title>
<dc:creator rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Terkildsen</vCard:Family>
<vCard:Given>Jonna</vCard:Given>
</vCard:N>
<vCard:EMAIL rdf:parseType="Resource">
<rdf:value>j.terkildsen@auckland.ac.nz</rdf:value>
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet" />
</vCard:EMAIL>
<vCard:ORG rdf:parseType="Resource">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</vCard:ORG>
</dc:creator>
<!--
The Creation Date metadata. This is the date on which the model
was translated into CellML.
-->
<dcterms:created rdf:parseType="Resource">
<dcterms:W3CDTF>2008-04-03</dcterms:W3CDTF>
</dcterms:created>
<!--
The Modification History metadata. This lists the changes that have been
made to the document, who made the changes, and when they were made.
-->
<!-- The Publisher metadata. -->
<dc:publisher>
The University of Auckland, Bioengineering Institute
</dc:publisher>
</rdf:Description>
</rdf:RDF>
<!-- ======================================================= CITATION AND KEYWORD METADATA ================================================== -->
<rdf:RDF
xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
xmlns:bqs="http://www.cellml.org/bqs/1.0#"
xmlns:dc="http://purl.org/dc/elements/1.1/"
xmlns:dcterms="http://purl.org/dc/terms/"
xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
<rdf:Description rdf:about="#aldosterone_CellML1_0_model">
<bqs:reference rdf:parseType="Resource">
<bqs:JournalArticle rdf:parseType="Resource">
<dc:creator>
<rdf:Seq>
<rdf:li rdf:parseType="Resource">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
<vCard:N rdf:parseType="Resource">
<vCard:Family>Guyton</vCard:Family>
<vCard:Given></vCard:Given>
<vCard:Other></vCard:Other>
</vCard:N>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
<vCard:N rdf:parseType="Resource">
<vCard:Family>Aldosterone</vCard:Family>
<vCard:Given></vCard:Given>
<vCard:Other></vCard:Other>
</vCard:N>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>Description of Guyton aldosterone module</dc:title>
<bqs:volume />
<bqs:first_page />
<bqs:last_page />
<bqs:Journal rdf:parseType="Resource">
<dc:title></dc:title>
</bqs:Journal>
<dcterms:issued rdf:parseType="Resource">
<dcterms:W3CDTF>2008-00-00 00:00</dcterms:W3CDTF>
</dcterms:issued>
</bqs:JournalArticle>
</bqs:reference>
<bqs:reference rdf:parseType="Resource">
<dc:subject rdf:parseType="Resource">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>
<rdf:Bag>
<rdf:li>physiology</rdf:li>
<rdf:li>organ systems</rdf:li>
<rdf:li>cardiovascular circulation</rdf:li>
<rdf:li>aldosterone</rdf:li>
<rdf:li>Guyton</rdf:li>
</rdf:Bag>
</rdf:value>
</dc:subject>
</bqs:reference>
</rdf:Description>
</rdf:RDF>
<!-- ======================================================= UNITS ================================================== -->
<units name="minute">
<unit multiplier="60" units="second"/>
</units>
<units name="monovalent_mEq">
<unit units="mole" prefix="milli"/>
</units>
<units name="monovalent_mEq_per_minute">
<unit units="mole" prefix="milli"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="monovalent_mEq_per_litre">
<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="monovalent_mEq_per_litre_per_minute">
<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="litre2_per_monovalent_mEq_per_minute">
<unit units="litre" exponent="2"/>
<unit units="mole" prefix="milli" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="L_per_minute">
<unit units="litre"/>
<unit units="minute" exponent="-1"/>
</units>
<!-- =================================================================================================================================== -->
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#aldosterone_CellML1_0_model">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- ======================================== ENVIRONMENT COMPONENT ============================================= -->
<component name="environment">
<variable cmeta:id="environment_time"
name="time" units="minute" private_interface="none" public_interface="out"/>
</component>
<!-- ======================================== ALDOSTERONE TOP-LEVEL COMPONENT ============================================= -->
<component name="aldosterone"
cmeta:id="aldosterone">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#aldosterone">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<variable name="time" units="minute" private_interface="out" public_interface="in"/>
<!-- Inputs from components in other models -->
<variable name="ANM" initial_value="0.987545" units="dimensionless" private_interface="out" public_interface="none"/>
<variable name="CKE" initial_value="4.44092" units="monovalent_mEq_per_litre" private_interface="out" public_interface="none"/>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="aldosterone" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- ======================================== ANGIOTENSIN CONTOL OF ALDOSTERONE SECRETION ============================================= -->
<component name="angiotensin_control_of_aldosterone_secretion"
cmeta:id="angiotensin_control_of_aldosterone_secretion">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#angiotensin_control_of_aldosterone_secretion">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL1_to_AL3">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANM" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANMAL" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANMALD" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AL1_to_AL3">
<eq/>
<ci>ANMAL</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>ANM</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ANMALD</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_control_of_aldosterone_secretion" component_2="aldosterone"/>
<map_variables variable_1="ANM" variable_2="ANM"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_control_of_aldosterone_secretion" component_2="parameter_values"/>
<map_variables variable_1="ANMALD" variable_2="ANMALD"/>
</connection>
<!-- ======================================== OSMOTIC CONTROL OF ALDOSTERONE SECRETION ============================================= -->
<component name="osmotic_control_of_aldosterone_secretion"
cmeta:id="osmotic_control_of_aldosterone_secretion">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#osmotic_control_of_aldosterone_secretion">
<rdf:value>
AL4:
Calculation of the driving force of potassium extracellular fluid concentration (CKE)
on aldosterone secretion by subtracting the constant 3.3 from CKE.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL4">
<rdf:value>
AL4:
Calculation of the driving force of potassium extracellular fluid concentration (CKE)
on aldosterone secretion by subtracting the constant 3.3 from CKE.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="CKE" units="monovalent_mEq_per_litre" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="OSMAL" units="dimensionless" private_interface="none" public_interface="out"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AL4">
<eq/>
<ci>OSMAL</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>CKE</ci>
<cn cellml:units="monovalent_mEq_per_litre">3.3</cn>
</apply>
<cn cellml:units="monovalent_mEq_per_litre">1.0</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="osmotic_control_of_aldosterone_secretion" component_2="aldosterone"/>
<map_variables variable_1="CKE" variable_2="CKE"/>
</connection>
<!-- ======================================== ALDOSTERONE SECRETION ============================================= -->
<component name="aldosterone_secretion"
cmeta:id="aldosterone_secretion">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#aldosterone_secretion">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL5">
<rdf:value>
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).
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL6_to_AL8">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL9">
<rdf:value>
AL9:
Block AL9 sets a lower limit to the aldosterone secretion equal to zero.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL9A_and_AL9B">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANMAL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="OSMAL" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AMR1" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AMKMUL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ALDINF" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ALDKNS" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AMRBSC" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="AMRT" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="AMR" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AL5">
<eq/>
<ci>AMRBSC</ci>
<apply>
<times/>
<ci>ANMAL</ci>
<cn cellml:units="dimensionless">0.909</cn>
<ci>OSMAL</ci>
</apply>
</apply>
<apply id="AL6_to_AL8">
<eq/>
<ci>AMRT</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>AMRBSC</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AMKMUL</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AL9">
<eq/>
<ci>AMR</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>AMRT</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<ci>AMRT</ci>
</otherwise>
</piecewise>
</apply>
<apply id="AL9A_and_AL9B">
<eq/>
<ci>AMR1</ci>
<piecewise>
<piece>
<ci>ALDKNS</ci>
<apply>
<gt/>
<ci>ALDKNS</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<plus/>
<ci>AMR</ci>
<ci>ALDINF</ci>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_secretion" component_2="angiotensin_control_of_aldosterone_secretion"/>
<map_variables variable_1="ANMAL" variable_2="ANMAL"/>
</connection>
<connection>
<map_components component_1="aldosterone_secretion" component_2="osmotic_control_of_aldosterone_secretion"/>
<map_variables variable_1="OSMAL" variable_2="OSMAL"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_secretion" component_2="parameter_values"/>
<map_variables variable_1="AMKMUL" variable_2="AMKMUL"/>
<map_variables variable_1="ALDINF" variable_2="ALDINF"/>
<map_variables variable_1="ALDKNS" variable_2="ALDKNS"/>
</connection>
<!-- ======================================== ALDOSTERONE CONCENTRATION ============================================= -->
<component name="aldosterone_concentration"
cmeta:id="aldosterone_concentration">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#aldosterone_concentration">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL10_to_AL12">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AMR1" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="time" units="minute" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AMC" initial_value="1.0" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AMT" units="minute" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AL10_to_AL12">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AMC</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>AMR1</ci>
<ci>AMC</ci>
</apply>
<ci>AMT</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_concentration" component_2="aldosterone_secretion"/>
<map_variables variable_1="AMR1" variable_2="AMR1"/>
</connection>
<connection>
<map_components component_1="aldosterone_concentration" component_2="aldosterone"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_concentration" component_2="parameter_values"/>
<map_variables variable_1="AMT" variable_2="AMT"/>
</connection>
<!-- ======================================== GENERAL ALDOSTERONE MULTIPLIER ============================================= -->
<component name="general_aldosterone_multiplier"
cmeta:id="general_aldosterone_multiplier">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#general_aldosterone_multiplier">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL13">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL14_to_AL16">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AMC" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AM" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AM1UL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AM1LL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AMCSNS" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ALDMM" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AM1" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AL13">
<eq/>
<ci>AM1</ci>
<apply>
<minus/>
<ci>AM1UL</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>AM1UL</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<ci>AM1LL</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<minus/>
<ci>AM1LL</ci>
<ci>AM1UL</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>AMC</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AMCSNS</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
<apply id="AL14_to_AL16">
<eq/>
<ci>AM</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>AM1</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ALDMM</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="general_aldosterone_multiplier" component_2="aldosterone_concentration"/>
<map_variables variable_1="AMC" variable_2="AMC"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="general_aldosterone_multiplier" component_2="parameter_values"/>
<map_variables variable_1="AM1UL" variable_2="AM1UL"/>
<map_variables variable_1="AM1LL" variable_2="AM1LL"/>
<map_variables variable_1="AMCSNS" variable_2="AMCSNS"/>
<map_variables variable_1="ALDMM" variable_2="ALDMM"/>
</connection>
<!-- ======================================== ALDOSTERONE EFFECT ON CELL MEMBRANE POTASSIUM TRANSPORT ============================================= -->
<component name="aldosterone_effect_on_cell_membrane_K_transport"
cmeta:id="aldosterone_effect_on_cell_membrane_K_transport">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#aldosterone_effect_on_cell_membrane_K_transport">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL17_to_AL19">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL20">
<rdf:value>
AL20:
The lower limit to AMK is set by Block AL20.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AM" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="aldosterone_effect_on_cell_membrane_K_transport_AMK"
name="AMK" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AMKM" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AMKT" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AL17_to_AL19">
<eq/>
<ci>AMKT</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>AM</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AMKM</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AL20">
<eq/>
<ci>AMK</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0.2</cn>
<apply>
<lt/>
<ci>AMKT</ci>
<cn cellml:units="dimensionless">0.2</cn>
</apply>
</piece>
<otherwise>
<ci>AMKT</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_effect_on_cell_membrane_K_transport" component_2="general_aldosterone_multiplier"/>
<map_variables variable_1="AM" variable_2="AM"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_effect_on_cell_membrane_K_transport" component_2="parameter_values"/>
<map_variables variable_1="AMKM" variable_2="AMKM"/>
</connection>
<!-- ======================================== ALDOSTERONE EFFECT ON CELL MEMBRANE SODIUM TRANSPORT ============================================= -->
<component name="aldosterone_effect_on_cell_membrane_Na_transport"
cmeta:id="aldosterone_effect_on_cell_membrane_Na_transport">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#aldosterone_effect_on_cell_membrane_Na_transport">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL21_to_AL23">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AL24_and_AL25">
<rdf:value>
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.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AM" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="aldosterone_effect_on_cell_membrane_Na_transport_AMNA"
name="AMNA" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AMNAM" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AMNAUL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AMNALL" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AMNAT" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AL21_to_AL23">
<eq/>
<ci>AMNAT</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>AM</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AMNAM</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AL24_and_AL25">
<eq/>
<ci>AMNA</ci>
<piecewise>
<piece>
<ci>AMNALL</ci>
<apply>
<lt/>
<ci>AMNAT</ci>
<ci>AMNALL</ci>
</apply>
</piece>
<piece>
<ci>AMNAUL</ci>
<apply>
<gt/>
<ci>AMNAT</ci>
<ci>AMNAUL</ci>
</apply>
</piece>
<otherwise>
<ci>AMNAT</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_effect_on_cell_membrane_Na_transport" component_2="general_aldosterone_multiplier"/>
<map_variables variable_1="AM" variable_2="AM"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="aldosterone_effect_on_cell_membrane_Na_transport" component_2="parameter_values"/>
<map_variables variable_1="AMNAM" variable_2="AMNAM"/>
<map_variables variable_1="AMNAUL" variable_2="AMNAUL"/>
<map_variables variable_1="AMNALL" variable_2="AMNALL"/>
</connection>
<!-- ========================================================== PARAMETER VALUES ================================================================ -->
<component name="parameter_values"
cmeta:id="parameter_values">
<variable name="ANMALD" units="dimensionless" initial_value="2.5" private_interface="none" public_interface="out"/> <!-- sensitivity controller, angiotensin effect on aldo secretion [P] -->
<variable name="AMKMUL" units="dimensionless" initial_value="12" private_interface="none" public_interface="out"/> <!-- sensitivity controller of AMR [P] -->
<variable name="ALDINF" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- rate of exogenous aldosterone infusion [P] -->
<variable name="ALDKNS" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- overriding value for aldosterone secretion [P] -->
<variable name="AMT" units="minute" initial_value="60" private_interface="none" public_interface="out"/> <!-- time constant, aldo accumulation and destruction [P] -->
<variable name="AM1UL" units="dimensionless" initial_value="5" private_interface="none" public_interface="out"/> <!-- AM1 upper limit [P] -->
<variable name="AM1LL" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- AM1 lower limit [P] -->
<variable name="AMCSNS" units="dimensionless" initial_value="0.65" private_interface="none" public_interface="out"/> <!-- sensitivity controller, aldosterone secretion [P] -->
<variable name="ALDMM" units="dimensionless" initial_value="2.5" private_interface="none" public_interface="out"/> <!-- sensitivity controller of aldosterone multiplier [P] -->
<variable name="AMKM" units="dimensionless" initial_value="0.5" private_interface="none" public_interface="out"/> <!-- sensitivity controller of AMK [P] -->
<variable name="AMNAM" units="dimensionless" initial_value="0.8" private_interface="none" public_interface="out"/> <!-- sensitivity controller of AMNA [P] -->
<variable name="AMNAUL" units="dimensionless" initial_value="15" private_interface="none" public_interface="out"/> <!-- AMNA upper limit [P] -->
<variable name="AMNALL" units="dimensionless" initial_value="0.04" private_interface="none" public_interface="out"/> <!-- AMNA lower limit [P] -->
</component>
<!-- ============================================================ GROUPING =============================================================== -->
<group>
<relationship_ref relationship="containment"/>
<component_ref component="aldosterone">
<component_ref component="angiotensin_control_of_aldosterone_secretion"/>
<component_ref component="osmotic_control_of_aldosterone_secretion"/>
<component_ref component="aldosterone_secretion"/>
<component_ref component="aldosterone_concentration"/>
<component_ref component="general_aldosterone_multiplier"/>
<component_ref component="aldosterone_effect_on_cell_membrane_K_transport"/>
<component_ref component="aldosterone_effect_on_cell_membrane_Na_transport"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="aldosterone">
<component_ref component="parameter_values"/>
<component_ref component="angiotensin_control_of_aldosterone_secretion"/>
<component_ref component="osmotic_control_of_aldosterone_secretion"/>
<component_ref component="aldosterone_secretion"/>
<component_ref component="aldosterone_concentration"/>
<component_ref component="general_aldosterone_multiplier"/>
<component_ref component="aldosterone_effect_on_cell_membrane_K_transport"/>
<component_ref component="aldosterone_effect_on_cell_membrane_Na_transport"/>
</component_ref>
</group>
<!-- SIMULATION METADATA -->
<RDF:RDF xmlns:RDF="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<RDF:Description RDF:about="#aldosterone_CellML1_0_model">
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$QQv43"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$4SdBX3">
<RDF:first RDF:resource="rdf:#$5SdBX3"/>
<RDF:rest RDF:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$3SdBX3">
<NS1:boundIntervals xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$4SdBX3"/>
</RDF:Description>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$5SdBX3" NS1:endingValue="1000"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$SQv43" NS1:endingValue="1000" NS1:nonstandard-pointDensity="100000"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$d2Cb93" NS1:nonstandard-pointDensity="100000"/>
<RDF:Description RDF:about="#aldosterone_CellML1_0_model">
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$b2Cb93"/>
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$3SdBX3"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$QQv43">
<NS1:boundIntervals xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$RQv43"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$RQv43">
<RDF:first RDF:resource="rdf:#$SQv43"/>
<RDF:rest RDF:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$b2Cb93">
<NS1:boundIntervals xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$c2Cb93"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$c2Cb93">
<RDF:first RDF:resource="rdf:#$d2Cb93"/>
<RDF:rest RDF:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
</RDF:Description>
</RDF:RDF>
</model>
