<?xml version="1.0" encoding="utf-8"?>
<model
name="angiotensin_CellML1_0_model"
cmeta:id="angiotensin_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: Angiotensin</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 the control functions of angiotensin, beginning with the control of angiotensin formation
by the kidneys in response to changes in the rate of flow of fluid in the renal tubules at the macula densa (MDFLW), and extending
through a series of curve-fitting and sensitivity controlled equations to determine the multiple feedback effects of angiotensin
to control the various aspects of circulatory function.
</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="angiotensin_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="angiotensin.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>
<!-- ======================================================= 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="#angiotensin_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>Angiotensin</vCard:Family>
<vCard:Given></vCard:Given>
<vCard:Other></vCard:Other>
</vCard:N>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>Description of Guyton angiotensin 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>angiotensin</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="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="#angiotensin_CellML1_0_model">
<rdf:value>
This section calculates the control functions of angiotensin, beginning with the
control of angiotensin formation by the kidneys in response to changes in the rate
of flow of fluid in the renal tubules at the macula densa (MDFLW), and extending
through a series of curve-fitting and sensitivity controlled equations to determine
the multiple feedback effects of angiotensin to control the various aspects of
circulatory function.
</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>
<!-- ======================================== ANGIOTENSIN TOP-LEVEL COMPONENT ============================================= -->
<component name="angiotensin"
cmeta:id="angiotensin">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#angiotensin">
<rdf:value>
Encapsulation grouping component containing all the components in the Angiotensin Model. The inputs and
outputs of the Angiotensin 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="MDFLW" initial_value="1.00051" units="L_per_minute" private_interface="out" public_interface="none"/>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="angiotensin" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- ======================================== INSTANTANEOUS ANGIONTENSIN FORMATION ============================================= -->
<component name="instantaneous_angiotensin_formation"
cmeta:id="instantaneous_angiotensin_formation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#instantaneous_angiotensin_formation">
<rdf:value>
AN1:
This block damps the variations in rate of fluid flow in the renal tubules at
the macula densa (MDFLW). The damped outflow is the variable MDFLW3.
NB - REMOVED DAMPING FORM AN1!!!!
AN2:
This block calculates the formation rate of angiotensin (ANGSCR) at different
levels of MDFLW3.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN1">
<rdf:value>
AN1:
This block damps the variations in rate of fluid flow in the renal tubules at
the macula densa (MDFLW). The damped outflow is the variable MDFLW3.
NB - REMOVED DAMPING FORM AN1!!!!
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN2">
<rdf:value>
AN2:
This block calculates the formation rate of angiotensin (ANGSCR) at different
levels of MDFLW3.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="MDFLW" units="L_per_minute" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANGSCR" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Internal variables -->
<variable name="MDFLW3" units="L_per_minute" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN1">
<eq/>
<ci>MDFLW3</ci>
<ci>MDFLW</ci>
</apply>
<apply id="AN2">
<eq/>
<ci>ANGSCR</ci>
<piecewise>
<piece>
<apply>
<divide/>
<cn cellml:units="L_per_minute">1</cn>
<apply>
<plus/>
<cn cellml:units="L_per_minute">1</cn>
<apply>
<times/>
<apply>
<minus/>
<ci>MDFLW3</ci>
<cn cellml:units="L_per_minute">1</cn>
</apply>
<cn cellml:units="dimensionless">72</cn>
</apply>
</apply>
</apply>
<apply>
<gt/>
<ci>MDFLW3</ci>
<cn cellml:units="L_per_minute">1</cn>
</apply>
</piece>
<otherwise>
<apply>
<minus/>
<cn cellml:units="dimensionless">10</cn>
<apply>
<divide/>
<cn cellml:units="L_per_minute">9</cn>
<apply>
<plus/>
<cn cellml:units="L_per_minute">1</cn>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="L_per_minute">1</cn>
<ci>MDFLW3</ci>
</apply>
<cn cellml:units="dimensionless">8</cn>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="instantaneous_angiotensin_formation" component_2="angiotensin"/>
<map_variables variable_1="MDFLW" variable_2="MDFLW"/>
</connection>
<!-- ======================================== TIME-DELAYED ANGIOTENSIN FORMATION ============================================= -->
<component name="time_delayed_angiotensin_formation"
cmeta:id="time_delayed_angiotensin_formation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#time_delayed_angiotensin_formation">
<rdf:value>
AN4, AN5, AN6, AN7, and AN8:
Calculation of additional formation of angiotensin caused after a long-term delay.
That is, when the JG cells are stimulated over long periods of time, in addition to
their acute effects on secretion rate of renin and subsequent formation of angiotensin,
there is a long-term increase in numbers of active JG cells to give a long-term delayed
response over a period of days. The variable ANXM adjusts the magnitude of this
delayed response. ANX is the total response without regard to the time delay. ANV is
the time-constant of the time delay. ANX1 is the total extra secretion after factoring
in the time delay effects of blocks 6, 7, and 8.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN4_and_AN5">
<rdf:value>
AN4, AN5, AN6, AN7, and AN8:
Calculation of additional formation of angiotensin caused after a long-term delay.
That is, when the JG cells are stimulated over long periods of time, in addition to
their acute effects on secretion rate of renin and subsequent formation of angiotensin,
there is a long-term increase in numbers of active JG cells to give a long-term delayed
response over a period of days. The variable ANXM adjusts the magnitude of this
delayed response. ANX is the total response without regard to the time delay. ANV is
the time-constant of the time delay. ANX1 is the total extra secretion after factoring
in the time delay effects of blocks 6, 7, and 8.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN6_to_AN8">
<rdf:value>
AN4, AN5, AN6, AN7, and AN8:
Calculation of additional formation of angiotensin caused after a long-term delay.
That is, when the JG cells are stimulated over long periods of time, in addition to
their acute effects on secretion rate of renin and subsequent formation of angiotensin,
there is a long-term increase in numbers of active JG cells to give a long-term delayed
response over a period of days. The variable ANXM adjusts the magnitude of this
delayed response. ANX is the total response without regard to the time delay. ANV is
the time-constant of the time delay. ANX1 is the total extra secretion after factoring
in the time delay effects of blocks 6, 7, and 8.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANGSCR" 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="ANX1" initial_value="0.0" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANXM" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANV" units="minute" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="ANX" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN4_and_AN5">
<eq/>
<ci>ANX</ci>
<apply>
<times/>
<apply>
<minus/>
<ci>ANGSCR</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ANXM</ci>
</apply>
</apply>
<apply id="AN6_to_AN8">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ANX1</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>ANX</ci>
<ci>ANX1</ci>
</apply>
<ci>ANV</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="time_delayed_angiotensin_formation" component_2="instantaneous_angiotensin_formation"/>
<map_variables variable_1="ANGSCR" variable_2="ANGSCR"/>
</connection>
<connection>
<map_components component_1="time_delayed_angiotensin_formation" component_2="angiotensin"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="time_delayed_angiotensin_formation" component_2="parameter_values"/>
<map_variables variable_1="ANXM" variable_2="ANXM"/>
<map_variables variable_1="ANV" variable_2="ANV"/>
</connection>
<!-- ======================================== TOTAL ANGIOTENSIN FORMATION ============================================= -->
<component name="total_angiotensin_formation"
cmeta:id="total_angiotensin_formation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#total_angiotensin_formation">
<rdf:value>
AN9:
Summation of instantaneous formation of angiotensin (ANGSCR) plus the time delayed
formation of angiotensin (ANX1).
AN10:
Calculation of the total rate of formation of angiotensin (ANPR) in case some of
the renal mass (and therefore some of the JG cells) has been removed or destroyed.
Factor REK is equal to the proportion of kidney mass that is still functional.
AN11:
This sets the lower limit of ANPR to a very low level, almost zero, below which
this cannot fall. The reason for this is to prevent a negative value from appearing.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN9_and_AN10">
<rdf:value>
AN9:
Summation of instantaneous formation of angiotensin (ANGSCR) plus the time delayed
formation of angiotensin (ANX1).
AN10:
Calculation of the total rate of formation of angiotensin (ANPR) in case some of
the renal mass (and therefore some of the JG cells) has been removed or destroyed.
Factor REK is equal to the proportion of kidney mass that is still functional.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN11">
<rdf:value>
AN11:
This sets the lower limit of ANPR to a very low level, almost zero, below which
this cannot fall. The reason for this is to prevent a negative value from appearing.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANGSCR" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANX1" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANPR" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="REK" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="ANPRT" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN9_and_AN10">
<eq/>
<ci>ANPRT</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>ANGSCR</ci>
<ci>ANX1</ci>
</apply>
<ci>REK</ci>
</apply>
</apply>
<apply id="AN11">
<eq/>
<ci>ANPR</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0.00001</cn>
<apply>
<lt/>
<ci>ANPRT</ci>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</piece>
<otherwise>
<ci>ANPRT</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="total_angiotensin_formation" component_2="instantaneous_angiotensin_formation"/>
<map_variables variable_1="ANGSCR" variable_2="ANGSCR"/>
</connection>
<connection>
<map_components component_1="total_angiotensin_formation" component_2="time_delayed_angiotensin_formation"/>
<map_variables variable_1="ANX1" variable_2="ANX1"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="total_angiotensin_formation" component_2="parameter_values"/>
<map_variables variable_1="REK" variable_2="REK"/>
</connection>
<!-- ======================================== ARTIFICIAL ANGIOTENSIN FORMATION ============================================= -->
<component name="artificial_angiotensin_formation"
cmeta:id="artificial_angiotensin_formation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#artificial_angiotensin_formation">
<rdf:value>
AN11A:
This block allows the addition of infused angiotensin (ANGINF) to the amount of
angiotensin that is formed in the body (ANPR).
AN11B:
This block allows one to disregard all the previous blocks and to set the total
rate of angiotensin entering the circulatory system (ANPR1) to a constant level, ANGKNS.
When ANGKNS is equal to zero or less, then Block 11B is ineffective.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN11A_and_AN11B">
<rdf:value>
AN11A:
This block allows the addition of infused angiotensin (ANGINF) to the amount of
angiotensin that is formed in the body (ANPR).
AN11B:
This block allows one to disregard all the previous blocks and to set the total
rate of angiotensin entering the circulatory system (ANPR1) to a constant level, ANGKNS.
When ANGKNS is equal to zero or less, then Block 11B is ineffective.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANPR" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANPR1" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANGKNS" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANGINF" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN11A_and_AN11B">
<eq/>
<ci>ANPR1</ci>
<piecewise>
<piece>
<ci>ANGKNS</ci>
<apply>
<gt/>
<ci>ANGKNS</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<plus/>
<ci>ANPR</ci>
<ci>ANGINF</ci>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="artificial_angiotensin_formation" component_2="total_angiotensin_formation"/>
<map_variables variable_1="ANPR" variable_2="ANPR"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="artificial_angiotensin_formation" component_2="parameter_values"/>
<map_variables variable_1="ANGKNS" variable_2="ANGKNS"/>
<map_variables variable_1="ANGINF" variable_2="ANGINF"/>
</connection>
<!-- ======================================== ANGIOTENSIN CONCENTRATION ============================================= -->
<component name="angiotensin_concentration"
cmeta:id="angiotensin_concentration">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#angiotensin_concentration">
<rdf:value>
AN12, AN13, and AN14:
These blocks convert the rate of entry of angiotensin into the body fluids (ANPR1),
into the concentration of angiotensin (ANC) considering the normal value to be the
numeral 1. The value ANT is the time constant for rate of change of angiotensin
concentration in the body fluids. The value Z12 is a damping coefficient to allow
damping of this conversion so that the model can be run faster for long-term simulations.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN12_to_AN14">
<rdf:value>
AN12, AN13, and AN14:
These blocks convert the rate of entry of angiotensin into the body fluids (ANPR1),
into the concentration of angiotensin (ANC) considering the normal value to be the
numeral 1. The value ANT is the time constant for rate of change of angiotensin
concentration in the body fluids. The value Z12 is a damping coefficient to allow
damping of this conversion so that the model can be run faster for long-term simulations.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANPR1" 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="ANC" initial_value="0.859476" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANT" units="minute" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN12_to_AN14">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ANC</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>ANPR1</ci>
<ci>ANC</ci>
</apply>
<ci>ANT</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_concentration" component_2="artificial_angiotensin_formation"/>
<map_variables variable_1="ANPR1" variable_2="ANPR1"/>
</connection>
<connection>
<map_components component_1="angiotensin_concentration" component_2="angiotensin"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_concentration" component_2="parameter_values"/>
<map_variables variable_1="ANT" variable_2="ANT"/>
</connection>
<!-- ======================================== GENERAL ANGIOTENSIN MULTIPLIER ============================================= -->
<component name="general_angiotensin_multiplier"
cmeta:id="general_angiotensin_multiplier">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#general_angiotensin_multiplier">
<rdf:value>
AN15:
This is an equation that allows one to convert the concentration of angiotensin (ANC)
into an angiotensin multiplier (ANM) which describes the multiplicative effect of
angiotensin on various physiological functions, assuming the normal value of ANM
to be 1.0. The value ANMUL is the upper limit to the level of ANM. ANMLL is the
lower limit of ANM. And the value ANCSNS is a sensitivity value for adjusting the
quantitative effect of ANC on ANM.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN15">
<rdf:value>
AN15:
This is an equation that allows one to convert the concentration of angiotensin (ANC)
into an angiotensin multiplier (ANM) which describes the multiplicative effect of
angiotensin on various physiological functions, assuming the normal value of ANM
to be 1.0. The value ANMUL is the upper limit to the level of ANM. ANMLL is the
lower limit of ANM. And the value ANCSNS is a sensitivity value for adjusting the
quantitative effect of ANC on ANM.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANC" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="general_angiotensin_multiplier_ANM"
name="ANM" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANMUL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANMLL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANCSNS" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN15">
<eq/>
<ci>ANM</ci>
<apply>
<minus/>
<ci>ANMUL</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>ANMUL</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<ci>ANMLL</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<minus/>
<ci>ANMLL</ci>
<ci>ANMUL</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>ANC</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ANCSNS</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="general_angiotensin_multiplier" component_2="angiotensin_concentration"/>
<map_variables variable_1="ANC" variable_2="ANC"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="general_angiotensin_multiplier" component_2="parameter_values"/>
<map_variables variable_1="ANMUL" variable_2="ANMUL"/>
<map_variables variable_1="ANMLL" variable_2="ANMLL"/>
<map_variables variable_1="ANCSNS" variable_2="ANCSNS"/>
</connection>
<!-- ======================================== ANGIOTENSIN EFFECT ON CIRCULATION ============================================= -->
<component name="angiotensin_effect_on_circulation"
cmeta:id="angiotensin_effect_on_circulation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#angiotensin_effect_on_circulation">
<rdf:value>
AN16, AN17, and AN18:
These blocks are a sensitivity controller for converting the basic effect of the
angiotensin multiplier (ANM) on other functional systems of the circulation (ANU).
The sensitivity adjustment is the factor ANUM in Block 17.
AN19:
This block sets the lower limit to which ANU can fall (ANULL).
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN16_to_AN18">
<rdf:value>
AN16, AN17, and AN18:
These blocks are a sensitivity controller for converting the basic effect of the
angiotensin multiplier (ANM) on other functional systems of the circulation (ANU).
The sensitivity adjustment is the factor ANUM in Block 17.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN19">
<rdf:value>
AN19:
This block sets the lower limit to which ANU can fall (ANULL).
</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 cmeta:id="angiotensin_effect_on_circulation_ANU"
name="ANU" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANUM" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANULL" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="ANU1" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN16_to_AN18">
<eq/>
<ci>ANU1</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>ANM</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ANUM</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AN19">
<eq/>
<ci>ANU</ci>
<piecewise>
<piece>
<ci>ANULL</ci>
<apply>
<lt/>
<ci>ANU1</ci>
<ci>ANULL</ci>
</apply>
</piece>
<otherwise>
<ci>ANU1</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_effect_on_circulation" component_2="general_angiotensin_multiplier"/>
<map_variables variable_1="ANM" variable_2="ANM"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_effect_on_circulation" component_2="parameter_values"/>
<map_variables variable_1="ANUM" variable_2="ANUM"/>
<map_variables variable_1="ANULL" variable_2="ANULL"/>
</connection>
<!-- ======================================== ANGIOTENSIN EFFECT ON VENOUS CONSTRICTION ============================================= -->
<component name="angiotensin_effect_on_venous_constriction"
cmeta:id="angiotensin_effect_on_venous_constriction">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#angiotensin_effect_on_venous_constriction">
<rdf:value>
AN20, AN21, and AN22:
Calculation of the effect of angiotensin on venous constriction (ANUVN), with
sensitivity controlled by ANUVM in Block 21.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AN20_to_AN22">
<rdf:value>
AN20, AN21, and AN22:
Calculation of the effect of angiotensin on venous constriction (ANUVN), with
sensitivity controlled by ANUVM in Block 21.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANU" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="angiotensin_effect_on_venous_constriction_ANUVN"
name="ANUVN" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANUVM" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AN20_to_AN22">
<eq/>
<ci>ANUVN</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>ANU</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ANUVM</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_effect_on_venous_constriction" component_2="angiotensin_effect_on_circulation"/>
<map_variables variable_1="ANU" variable_2="ANU"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="angiotensin_effect_on_venous_constriction" component_2="parameter_values"/>
<map_variables variable_1="ANUVM" variable_2="ANUVM"/>
</connection>
<!-- ========================================================== PARAMETER VALUES ================================================================ -->
<component name="parameter_values"
cmeta:id="parameter_values">
<variable name="ANXM" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- sensitivity controller of ANX [P] -->
<variable name="ANV" units="minute" initial_value="5000" private_interface="none" public_interface="out"/> <!-- time constant, angiotensin secretion [P] -->
<variable name="REK" units="dimensionless" initial_value="1" private_interface="none" public_interface="out"/> <!-- total functional renal mass, ratio to normal [P] -->
<variable name="ANGINF" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- rate of exogenous angiotensin infusion [P] -->
<variable name="ANGKNS" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- overriding value for angiotensin secretion [P] -->
<variable name="ANT" units="minute" initial_value="12" private_interface="none" public_interface="out"/> <!-- time constant, angiotensin accumulation and destruction [P] -->
<variable name="Z12" units="dimensionless" initial_value="5" private_interface="none" public_interface="out"/> <!-- damping factor, angiotensin system [P] -->
<variable name="ANMUL" units="dimensionless" initial_value="1.8" private_interface="none" public_interface="out"/> <!-- ANM upper limit [P] -->
<variable name="ANMLL" units="dimensionless" initial_value="0.7" private_interface="none" public_interface="out"/> <!-- ANM lower limit [P] -->
<variable name="ANCSNS" units="dimensionless" initial_value="0.4" private_interface="none" public_interface="out"/> <!-- sensitivity controller of ANM [P] -->
<variable name="ANULL" units="dimensionless" initial_value="0.8" private_interface="none" public_interface="out"/> <!-- ANU lower limit [P] -->
<variable name="ANUM" units="dimensionless" initial_value="6" private_interface="none" public_interface="out"/> <!-- sensitivity controller of ANU [P] -->
<variable name="ANUVM" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- sensitivity controller of ANUVN [P] -->
</component>
<!-- ============================================================ GROUPING =============================================================== -->
<group>
<relationship_ref relationship="containment"/>
<component_ref component="angiotensin">
<component_ref component="instantaneous_angiotensin_formation"/>
<component_ref component="time_delayed_angiotensin_formation"/>
<component_ref component="total_angiotensin_formation"/>
<component_ref component="artificial_angiotensin_formation"/>
<component_ref component="angiotensin_concentration"/>
<component_ref component="general_angiotensin_multiplier"/>
<component_ref component="angiotensin_effect_on_circulation"/>
<component_ref component="angiotensin_effect_on_venous_constriction"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="angiotensin">
<component_ref component="parameter_values"/>
<component_ref component="instantaneous_angiotensin_formation"/>
<component_ref component="time_delayed_angiotensin_formation"/>
<component_ref component="total_angiotensin_formation"/>
<component_ref component="artificial_angiotensin_formation"/>
<component_ref component="angiotensin_concentration"/>
<component_ref component="general_angiotensin_multiplier"/>
<component_ref component="angiotensin_effect_on_circulation"/>
<component_ref component="angiotensin_effect_on_venous_constriction"/>
</component_ref>
</group>
<!-- SIMULATION METADATA -->
<RDF:RDF xmlns:RDF="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<RDF:Description RDF:about="#angiotensin_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:#$5SdBX3" NS1:endingValue="100"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$SQv43" NS1:endingValue="100" NS1:nonstandard-pointDensity="10000"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$d2Cb93" NS1:nonstandard-pointDensity="100000"/>
<RDF:Description RDF:about="#angiotensin_CellML1_0_model">
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$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>
