<?xml version="1.0" encoding="utf-8"?>
<model
name="thirst_drinking_and_salt_appetite_CellML1_0_model"
cmeta:id="thirst_drinking_and_salt_appetite_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: thirst_drinking_and_salt_appetite</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 affect 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 mechanisms underlying salt appetite and thirst. The salt appetite is considered in this
model to be related to the adequacy of body metabolism, as measured by the PO2 level in the non-muscle tissue cells (POT). Also when
the concentration of angiotensin increases (ANM), this too increases salt intake. For instance in circulatory shock, when the adequacy
of metabolism falls, the person develops a salt appetite. Due to a lack of information, no control function of salt concentration per
se has been assumed, merely that when the body salt falls, circulatory effectiveness falls, angiotensin increases, and a salt appetite
develops. Regarding thirst, three separate factors are assumed to drive the thirst mechanism: first, the concentration of antidiuretic
hormone, which in turn is driven by changes in electrolyte composition (as detailed in another model); second, the effect of
angiotensin on thirst, and; thirdly, the effect of the salt appetite stimulation on thirst.
</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="thirst_drinking_and_salt_appetite_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="thirst.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="#thirst_drinking_and_salt_appetite_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>Thirst, Drinking and Salt Appetite</vCard:Family>
<vCard:Given></vCard:Given>
<vCard:Other></vCard:Other>
</vCard:N>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>Description of guyton thirst, drinking and salt appetite 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>thirst, drinking and salt appetite</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="per_minute">
<unit units="minute" exponent="-1"/>
</units>
<units name="mmHg">
<unit multiplier="133.322" units="newton"/>
<unit units="metre" exponent="-2"/>
</units>
<units name="per_mmHg2">
<unit units="mmHg" exponent="-2"/>
</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>
<units name="L_per_minute_per_mmHg">
<unit units="litre"/>
<unit units="minute" exponent="-1"/>
<unit units="mmHg" exponent="-1"/>
</units>
<!-- ===================================================================================================================== -->
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#thirst_drinking_and_salt_appetite_CellML1_0_model">
<rdf:value>
The salt appetite is considered in this model to be related to the adequacy
of body metabolism, as measured by the PO2 level in the non-muscle tissue
cells (POT). Also, when the concentration of angiotensin increases (ANM),
this, too, increases salt intake. For instance, in circulatory shock, when
the adequacy of metabolism falls, the person develops a salt appetite. For
lack of information, no control function of salt concentration per se has
been assumed, merely that when the body salt falls, circulatory effectiveness
falls, angiotensin increases, and a salt appetite develops.
Three separate factors are assumed to drive the thirst mechanism, the
concentration of antidiuretic hormone, which in turn is driven by changes
in electrolyte composition (as detailed in another section) and second, the
effect of angiotensin on thirst, and third, the effect of the salt appetite
stimulation on thirst.
</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>
<!-- ======================================== THIRST DRINKING AND SALT APPETITE TOP-LEVEL COMPONENT ============================================= -->
<component name="thirst_drinking_and_salt_appetite"
cmeta:id="thirst_drinking_and_salt_appetite">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#thirst_drinking_and_salt_appetite">
<rdf:value>
Encapsulation grouping component containing all the components in the Thirst, Drinking and Salt Appetite Model.
The inputs and outputs of the Thirst, Drinking and Salt Appetite 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="ADHC" initial_value="1.0" units="dimensionless" private_interface="out" public_interface="none"/>
<variable name="ANM" initial_value="0.987545" units="dimensionless" private_interface="out" public_interface="none"/>
<variable name="POT" initial_value="35.1148" units="mmHg" private_interface="out" public_interface="none"/>
</component>
<!-- OUTPUT CONNECTIONS -->
<connection>
<map_components component_1="thirst_drinking_and_salt_appetite" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- ======================================== EFFECT OF SALT APPETITE STIMULATION ON THIRST ============================================= -->
<component name="effect_of_salt_appetite_stimulation_on_thirst"
cmeta:id="effect_of_salt_appetite_stimulation_on_thirst">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#effect_of_salt_appetite_stimulation_on_thirst">
<rdf:value>
TS1, TS1A, TS2, TS2A, TS2B, TS2C, TS3, and TS4:
These are curve-fitting blocks to derive a value for salt appetite and for partial control of
thirst (STH) based on the input values of PO2 in the non-muscle tissue cells (POT) and the
angiotensin multiplier effect (ANM). The constant ANMSLT sets the sensitivity of salt appetite
to angiotensin, and the constant Z10 sets the PO2 level below which POT exerts its effects.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS2_TS2A_and_TS2B">
<rdf:value>
TS1, TS1A, TS2, TS2A, TS2B, TS2C, TS3, and TS4:
These are curve-fitting blocks to derive a value for salt appetite and for partial control of
thirst (STH) based on the input values of PO2 in the non-muscle tissue cells (POT) and the
angiotensin multiplier effect (ANM). The constant ANMSLT sets the sensitivity of salt appetite
to angiotensin, and the constant Z10 sets the PO2 level below which POT exerts its effects.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS1_TS1A_and_TS2C">
<rdf:value>
TS1, TS1A, TS2, TS2A, TS2B, TS2C, TS3, and TS4:
These are curve-fitting blocks to derive a value for salt appetite and for partial control of
thirst (STH) based on the input values of PO2 in the non-muscle tissue cells (POT) and the
angiotensin multiplier effect (ANM). The constant ANMSLT sets the sensitivity of salt appetite
to angiotensin, and the constant Z10 sets the PO2 level below which POT exerts its effects.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS3_and_TS4">
<rdf:value>
TS1, TS1A, TS2, TS2A, TS2B, TS2C, TS3, and TS4:
These are curve-fitting blocks to derive a value for salt appetite and for partial control of
thirst (STH) based on the input values of PO2 in the non-muscle tissue cells (POT) and the
angiotensin multiplier effect (ANM). The constant ANMSLT sets the sensitivity of salt appetite
to angiotensin, and the constant Z10 sets the PO2 level below which POT exerts its effects.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANM" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="POT" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="effect_of_salt_appetite_stimulation_on_thirst_STH"
name="STH" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANMSLT" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="Z10" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="Z11" units="per_mmHg2" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="ANMSML" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="STH1" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="TS2_TS2A_and_TS2B">
<eq/>
<ci>ANMSML</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>ANM</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ANMSLT</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="TS1_TS1A_and_TS2C">
<eq/>
<ci>STH1</ci>
<apply>
<times/>
<apply>
<power/>
<apply>
<minus/>
<ci>Z10</ci>
<ci>POT</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>Z11</ci>
<ci>ANMSML</ci>
</apply>
</apply>
<apply id="TS3_and_TS4">
<eq/>
<ci>STH</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0.8</cn>
<apply>
<lt/>
<ci>STH1</ci>
<cn cellml:units="dimensionless">0.8</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">8</cn>
<apply>
<gt/>
<ci>STH1</ci>
<cn cellml:units="dimensionless">8</cn>
</apply>
</piece>
<otherwise>
<ci>STH1</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="effect_of_salt_appetite_stimulation_on_thirst" component_2="thirst_drinking_and_salt_appetite"/>
<map_variables variable_1="ANM" variable_2="ANM"/>
<map_variables variable_1="POT" variable_2="POT"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="effect_of_salt_appetite_stimulation_on_thirst" component_2="parameter_values"/>
<map_variables variable_1="ANMSLT" variable_2="ANMSLT"/>
<map_variables variable_1="Z10" variable_2="Z10"/>
<map_variables variable_1="Z11" variable_2="Z11"/>
</connection>
<!-- ============================================== EFFECT OF ANTIDIURETIC HOMONE ON THIRST =============================================== -->
<component name="effect_of_antidiuretic_hormone_on_thirst"
cmeta:id="effect_of_antidiuretic_hormone_on_thirst">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#effect_of_antidiuretic_hormone_on_thirst">
<rdf:value>
TS5, TS6, and TS7:
These blocks are a sensitivity controller for calculating a multiplier effect
of antidiuretic hormone on thirst (AHCM) from an antidiuretic hormone
concentration factor in the circulating body fluids (ADHC). The sensitivity is
controlled by the control factor (AHTHM).
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS5_to_TS7">
<rdf:value>
TS5, TS6, and TS7:
These blocks are a sensitivity controller for calculating a multiplier effect
of antidiuretic hormone on thirst (AHCM) from an antidiuretic hormone
concentration factor in the circulating body fluids (ADHC). The sensitivity is
controlled by the control factor (AHTHM).
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ADHC" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AHCM" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AHTHM" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="TS5_to_TS7">
<eq/>
<ci>AHCM</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>ADHC</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AHTHM</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="effect_of_antidiuretic_hormone_on_thirst" component_2="thirst_drinking_and_salt_appetite"/>
<map_variables variable_1="ADHC" variable_2="ADHC"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="effect_of_antidiuretic_hormone_on_thirst" component_2="parameter_values"/>
<map_variables variable_1="AHTHM" variable_2="AHTHM"/>
</connection>
<!-- ========================================= EFFECT OF ANGIOTENSIN ON THIRST ============================================================== -->
<component name="effect_of_angiotensin_on_thirst"
cmeta:id="effect_of_angiotensin_on_thirst">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#effect_of_angiotensin_on_thirst">
<rdf:value>
TS10 and TS11:
Calculation of the drive to stimulate thirst caused by angiotensin (ANMH) from
the generalized angiotensin multiplier (ANM). The sensitivity of this calculation
is controlled by the angiotensin-thirst sensitivity control variable (ANMTM).
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS10_and_TS11">
<rdf:value>
TS10 and TS11:
Calculation of the drive to stimulate thirst caused by angiotensin (ANMH) from
the generalized angiotensin multiplier (ANM). The sensitivity of this calculation
is controlled by the angiotensin-thirst sensitivity control variable (ANMTM).
</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="ANMTH" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANMTM" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="TS10_and_TS11">
<eq/>
<ci>ANMTH</ci>
<apply>
<times/>
<apply>
<minus/>
<ci>ANM</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>ANMTM</ci>
<cn cellml:units="dimensionless">0.001</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="effect_of_angiotensin_on_thirst" component_2="thirst_drinking_and_salt_appetite"/>
<map_variables variable_1="ANM" variable_2="ANM"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="effect_of_angiotensin_on_thirst" component_2="parameter_values"/>
<map_variables variable_1="ANMTM" variable_2="ANMTM"/>
</connection>
<!-- ================================================ RATE OF FLUID INTAKE =============================================================== -->
<component name="rate_of_fluid_intake"
cmeta:id="rate_of_fluid_intake">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#rate_of_fluid_intake">
<rdf:value>
TS8 and TS9:
Calculation of a thirst drive (AHTH) based on antidiuretic hormone and salt
appetite by multiplying three factors, the salt appetite drive (STH), the antidiuretic
hormone concentration multiplier (AHCM), and a constant. Block TS9 sets a lower limit
to AHTH equal to zero.
TS12 and TS13:
A temporary calculation for rate of intake of fluid by the body (TVZ) is equal to the
drinking drive (AHTH) caused by the product of the salt appetite drive (STH) and the
antidiuretic-thirst drive (AHTH), plus the angiotensin-thirst drive (ANMTH). Block
TS13 sets the lower limit of (TVZ) to zero.
TS14, TS15, and TS16:
This is a delay circuit which causes the actual rate of fluid intake (TVD) to be delayed
with respect to changes in the temporarily calculated rate of fluid intake (TVZ) by a
time constant TVDLL. Also shown in Block TS14 is a variable (DR) that can be used for
forced input of water over and above the natural drinking desires; this can be used for
intravenous infusion of water as well.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS8">
<rdf:value>
TS8:
Calculation of a thirst drive (AHTH) based on antidiuretic hormone and salt
appetite by multiplying three factors, the salt appetite drive (STH), the antidiuretic
hormone concentration multiplier (AHCM), and a constant.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS9">
<rdf:value>
TS9:
Block TS9 sets a lower limit to AHTH equal to zero.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS12">
<rdf:value>
TS12:
A temporary calculation for rate of intake of fluid by the body (TVZ) is equal to the
drinking drive (AHTH) caused by the product of the salt appetite drive (STH) and the
antidiuretic-thirst drive (AHTH), plus the angiotensin-thirst drive (ANMTH).
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS13">
<rdf:value>
TS13:
Block TS13 sets the lower limit of (TVZ) to zero.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#TS14_to_TS16">
<rdf:value>
TS14, TS15, and TS16:
This is a delay circuit which causes the actual rate of fluid intake (TVD) to be delayed
with respect to changes in the temporarily calculated rate of fluid intake (TVZ) by a
time constant TVDLL. Also shown in Block TS14 is a variable (DR) that can be used for
forced input of water over and above the natural drinking desires; this can be used for
intravenous infusion of water as well.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="STH" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AHCM" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANMTH" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="time" units="minute" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="rate_of_fluid_intake_TVD"
name="TVD" initial_value="0.000980838" units="L_per_minute" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="DR" units="L_per_minute" private_interface="none" public_interface="in"/>
<variable name="TVDDL" units="minute" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AHTH" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="AHTH1" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="TVZ" units="L_per_minute" private_interface="none" public_interface="none"/>
<variable name="TVZ1" units="L_per_minute" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="TS8">
<eq/>
<ci>AHTH1</ci>
<apply>
<times/>
<ci>AHCM</ci>
<ci>STH</ci>
<cn cellml:units="dimensionless">0.001</cn>
</apply>
</apply>
<apply id="TS9">
<eq/>
<ci>AHTH</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>AHTH1</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<ci>AHTH1</ci>
</otherwise>
</piecewise>
</apply>
<apply id="TS12">
<eq/>
<ci>TVZ1</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>ANMTH</ci>
<ci>AHTH</ci>
</apply>
<cn cellml:units="L_per_minute">1</cn>
</apply>
</apply>
<apply id="TS13">
<eq/>
<ci>TVZ</ci>
<piecewise>
<piece>
<cn cellml:units="L_per_minute">0</cn>
<apply>
<lt/>
<ci>TVZ1</ci>
<cn cellml:units="L_per_minute">0</cn>
</apply>
</piece>
<otherwise>
<ci>TVZ1</ci>
</otherwise>
</piecewise>
</apply>
<apply id="TS14_to_TS16">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>TVD</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>TVZ</ci>
<ci>DR</ci>
</apply>
<ci>TVD</ci>
</apply>
<ci>TVDDL</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="rate_of_fluid_intake" component_2="effect_of_antidiuretic_hormone_on_thirst"/>
<map_variables variable_1="AHCM" variable_2="AHCM"/>
</connection>
<connection>
<map_components component_1="rate_of_fluid_intake" component_2="effect_of_salt_appetite_stimulation_on_thirst"/>
<map_variables variable_1="STH" variable_2="STH"/>
</connection>
<connection>
<map_components component_1="rate_of_fluid_intake" component_2="effect_of_angiotensin_on_thirst"/>
<map_variables variable_1="ANMTH" variable_2="ANMTH"/>
</connection>
<connection>
<map_components component_1="rate_of_fluid_intake" component_2="thirst_drinking_and_salt_appetite"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="rate_of_fluid_intake" component_2="parameter_values"/>
<map_variables variable_1="DR" variable_2="DR"/>
<map_variables variable_1="TVDDL" variable_2="TVDDL"/>
</connection>
<!-- ========================================================== PARAMETER VALUES ================================================================ -->
<component name="parameter_values"
cmeta:id="parameter_values">
<variable name="Z10" units="mmHg" initial_value="45" private_interface="none" public_interface="out"/> <!-- damping factor, STH [P] -->
<variable name="Z11" units="per_mmHg2" initial_value="0.01" private_interface="none" public_interface="out"/> <!-- damping factor, STH [P] -->
<variable name="ANMSLT" units="dimensionless" initial_value="2" private_interface="none" public_interface="out"/> <!-- sensitivity controller ANMSML [P] -->
<variable name="AHTHM" units="dimensionless" initial_value="2" private_interface="none" public_interface="out"/> <!-- sensitivity controller, effect of ADH on thirst [P] -->
<variable name="ANMTM" units="dimensionless" initial_value="1.5" private_interface="none" public_interface="out"/> <!-- sensitivity controller of ANMTH [P] -->
<variable name="DR" units="L_per_minute" initial_value="0" private_interface="none" public_interface="out"/> <!-- rate of water drinking (in addition of thirst) -->
<variable name="TVDDL" units="minute" initial_value="30" private_interface="none" public_interface="out"/> <!-- TVD damping coefficient [P] -->
</component>
<!-- ============================================================ GROUPING =============================================================== -->
<group>
<relationship_ref relationship="containment"/>
<component_ref component="thirst_drinking_and_salt_appetite">
<component_ref component="effect_of_salt_appetite_stimulation_on_thirst"/>
<component_ref component="effect_of_antidiuretic_hormone_on_thirst"/>
<component_ref component="effect_of_angiotensin_on_thirst"/>
<component_ref component="rate_of_fluid_intake"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="thirst_drinking_and_salt_appetite">
<component_ref component="parameter_values"/>
<component_ref component="effect_of_salt_appetite_stimulation_on_thirst"/>
<component_ref component="effect_of_antidiuretic_hormone_on_thirst"/>
<component_ref component="effect_of_angiotensin_on_thirst"/>
<component_ref component="rate_of_fluid_intake"/>
</component_ref>
</group>
<!-- SIMULATION METADATA -->
<RDF:RDF xmlns:RDF="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<RDF:Description RDF:about="#thirst_drinking_and_salt_appetite_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:#$4SdBX3"/>
</RDF:Description>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$SQv43" NS1:endingValue="300" NS1:nonstandard-pointDensity="1000"/>
<RDF:Description RDF:about="#thirst_drinking_and_salt_appetite_CellML1_0_model#LfY7zdZ%60EYs">
<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>
