Location: Guyton, Aldosterone, 2008 @ 905fc7293bea / guyton_aldosterone_2008.cellml

Author:
James Lawson <j.lawson@auckland.ac.nz>
Date:
2009-07-13 16:23:06+12:00
Desc:
added model name using bqs citation paper name metadata, added keyword
Permanent Source URI:
http://models.cellml.org/workspace/guyton_aldosterone_2008/rawfile/905fc7293bea6845c21ceb3856be7be9f1a2ed95/guyton_aldosterone_2008.cellml

<?xml version='1.0' encoding='utf-8'?>
<model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:RDF="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#" cmeta:id="aldosterone_CellML1_0_model" name="aldosterone_CellML1_0_model">

<!-- ========================================	DOCUMENTATION	============================================= -->

<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Guyton Model: Aldosterone</title>
  <author>
    <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
    <affiliation>
      <shortaffil>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>
<ulink url="http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.ph.34.030172.000305">Circulation: Overall Regulation</ulink>,  A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972, <ulink url="http://www.biophysj.org/">
            <emphasis>Annual Review of Physiology</emphasis>
          </ulink>, 34, 13-44.  (A <ulink url="http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.ph.34.030172.000305?cookieSet=1">PDF</ulink> version of the article are available to journal subscribers on the <emphasis>Annual Review of Physiology</emphasis> website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=4334846&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 4334846</ulink>
</para>

</sect1>
</article>
</documentation> 



  
<!-- =================================================================================================================================== -->
    
	

<!-- ========================================	ENVIRONMENT COMPONENT	============================================= -->
   <component name="environment">
      <variable units="second" public_interface="out" private_interface="none" cmeta:id="environment_time" name="time"/>
   </component>

<!-- ========================================	ALDOSTERONE TOP-LEVEL COMPONENT	============================================= -->
	<component name="aldosterone" cmeta:id="aldosterone">
		

		<variable units="second" public_interface="in" private_interface="out" name="time"/>

<!-- Inputs from components in other models -->
		<variable units="dimensionless" public_interface="none" private_interface="out" name="ANM" initial_value="0.987545"/>
		<variable units="dimensionless" public_interface="none" private_interface="out" name="CKE" initial_value="4.44092"/>

	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_2="environment" component_1="aldosterone"/>
		<map_variables variable_2="time" variable_1="time"/>
	</connection>

<!-- ========================================	ANGIOTENSIN CONTOL OF ALDOSTERONE SECRETION	============================================= -->
	<component name="angiotensin_control_of_aldosterone_secretion" cmeta:id="angiotensin_control_of_aldosterone_secretion">
		
		
<!-- Inputs from other components -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="ANM"/>

<!-- Outputs to other components -->
		<variable units="dimensionless" public_interface="out" private_interface="none" name="ANMAL"/>

<!-- Parameters from parameter_file -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="ANMALD"/>

		<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_2="aldosterone" component_1="angiotensin_control_of_aldosterone_secretion"/>
		<map_variables variable_2="ANM" variable_1="ANM"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_2="parameter_values" component_1="angiotensin_control_of_aldosterone_secretion"/>
		<map_variables variable_2="ANMALD" variable_1="ANMALD"/>
	</connection>

<!-- ========================================	OSMOTIC CONTROL OF ALDOSTERONE SECRETION	============================================= -->
	<component name="osmotic_control_of_aldosterone_secretion" cmeta:id="osmotic_control_of_aldosterone_secretion">
		
		
<!-- Inputs from other components -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="CKE"/>

<!-- Outputs to other components -->
		<variable units="dimensionless" public_interface="out" private_interface="none" name="OSMAL"/>

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL4">
				<eq/>
				<ci>OSMAL</ci>
				<apply>
					<minus/>
					<ci>CKE</ci>
					<cn cellml:units="dimensionless">3.3</cn>
				</apply>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_2="aldosterone" component_1="osmotic_control_of_aldosterone_secretion"/>
		<map_variables variable_2="CKE" variable_1="CKE"/>
	</connection>

<!-- ========================================	ALDOSTERONE SECRETION	============================================= -->
	<component name="aldosterone_secretion" cmeta:id="aldosterone_secretion">
		
		
<!-- Inputs from other components -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="ANMAL"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="OSMAL"/>

<!-- Outputs to other components -->
		<variable units="dimensionless" public_interface="out" private_interface="none" name="AMR1"/>

<!-- Parameters from parameter_file -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMKMUL"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="ALDINF"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="ALDKNS"/>

<!-- Internal variables -->
		<variable units="dimensionless" public_interface="none" private_interface="none" name="AMRBSC"/>
		<variable units="dimensionless" public_interface="none" private_interface="none" name="AMRT"/>
		<variable units="dimensionless" public_interface="none" private_interface="none" name="AMR"/>

		<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_2="angiotensin_control_of_aldosterone_secretion" component_1="aldosterone_secretion"/>
		<map_variables variable_2="ANMAL" variable_1="ANMAL"/>
	</connection>
	<connection>
		<map_components component_2="osmotic_control_of_aldosterone_secretion" component_1="aldosterone_secretion"/>
		<map_variables variable_2="OSMAL" variable_1="OSMAL"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_2="parameter_values" component_1="aldosterone_secretion"/>
		<map_variables variable_2="AMKMUL" variable_1="AMKMUL"/>
		<map_variables variable_2="ALDINF" variable_1="ALDINF"/>
		<map_variables variable_2="ALDKNS" variable_1="ALDKNS"/>
	</connection>

<!-- ========================================	ALDOSTERONE CONCENTRATION		============================================= -->
	<component name="aldosterone_concentration" cmeta:id="aldosterone_concentration">
		
		
<!-- Inputs from other components -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMR1"/>
		<variable units="second" public_interface="in" private_interface="none" name="time"/>

<!-- Outputs to other components -->
		<variable units="dimensionless" public_interface="out" private_interface="none" name="AMC" initial_value="1.0"/>

<!-- Parameters from parameter_file -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMT"/>

		<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_2="aldosterone_secretion" component_1="aldosterone_concentration"/>
		<map_variables variable_2="AMR1" variable_1="AMR1"/>
	</connection>
	<connection>
		<map_components component_2="aldosterone" component_1="aldosterone_concentration"/>
		<map_variables variable_2="time" variable_1="time"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_2="parameter_values" component_1="aldosterone_concentration"/>
		<map_variables variable_2="AMT" variable_1="AMT"/>
	</connection>

<!-- ========================================	GENERAL ALDOSTERONE MULTIPLIER	============================================= -->
	<component name="general_aldosterone_multiplier" cmeta:id="general_aldosterone_multiplier">
		
		
<!-- Inputs from other components -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMC"/>

<!-- Outputs to other components -->
		<variable units="dimensionless" public_interface="out" private_interface="none" name="AM"/>

<!-- Parameters from parameter_file -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AM1UL"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AM1LL"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMCSNS"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="ALDMM"/>

<!-- Internal variables -->
		<variable units="dimensionless" public_interface="none" private_interface="none" name="AM1"/>

		<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_2="aldosterone_concentration" component_1="general_aldosterone_multiplier"/>
		<map_variables variable_2="AMC" variable_1="AMC"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_2="parameter_values" component_1="general_aldosterone_multiplier"/>
		<map_variables variable_2="AM1UL" variable_1="AM1UL"/>
		<map_variables variable_2="AM1LL" variable_1="AM1LL"/>
		<map_variables variable_2="AMCSNS" variable_1="AMCSNS"/>
		<map_variables variable_2="ALDMM" variable_1="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">
		
		
<!-- Inputs from other components -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AM"/>

<!-- Outputs to other components -->
		<variable units="dimensionless" public_interface="out" private_interface="none" cmeta:id="aldosterone_effect_on_cell_membrane_K_transport_AMK" name="AMK"/>

<!-- Parameters from parameter_file -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMKM"/>

<!-- Internal variables -->
		<variable units="dimensionless" public_interface="none" private_interface="none" name="AMKT"/>

		<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_2="general_aldosterone_multiplier" component_1="aldosterone_effect_on_cell_membrane_K_transport"/>
		<map_variables variable_2="AM" variable_1="AM"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_2="parameter_values" component_1="aldosterone_effect_on_cell_membrane_K_transport"/>
		<map_variables variable_2="AMKM" variable_1="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">
		
		
<!-- Inputs from other components -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AM"/>

<!-- Outputs to other components -->
		<variable units="dimensionless" public_interface="out" private_interface="none" cmeta:id="aldosterone_effect_on_cell_membrane_Na_transport_AMNA" name="AMNA"/>

<!-- Parameters from parameter_file -->
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMNAM"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMNAUL"/>
		<variable units="dimensionless" public_interface="in" private_interface="none" name="AMNALL"/>

<!-- Internal variables -->
		<variable units="dimensionless" public_interface="none" private_interface="none" name="AMNAT"/>

		<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_2="general_aldosterone_multiplier" component_1="aldosterone_effect_on_cell_membrane_Na_transport"/>
		<map_variables variable_2="AM" variable_1="AM"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_2="parameter_values" component_1="aldosterone_effect_on_cell_membrane_Na_transport"/>
		<map_variables variable_2="AMNAM" variable_1="AMNAM"/>
		<map_variables variable_2="AMNAUL" variable_1="AMNAUL"/>
		<map_variables variable_2="AMNALL" variable_1="AMNALL"/>
	</connection>

<!-- ==========================================================	PARAMETER VALUES	================================================================ -->
	<component name="parameter_values" cmeta:id="parameter_values">

	  <variable units="dimensionless" public_interface="out" private_interface="none" name="ANMALD" initial_value="2.5"/>	<!-- sensitivity controller, angiotensin effect on aldo secretion [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AMKMUL" initial_value="12"/>	<!-- sensitivity controller of AMR [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="ALDINF" initial_value="0"/>	<!-- rate of exogenous aldosterone infusion [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="ALDKNS" initial_value="0"/>	<!-- overriding value for aldosterone secretion [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AMT" initial_value="60"/>	<!-- time constant, aldo accumulation and destruction [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AM1UL" initial_value="5"/>	<!-- AM1 upper limit [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AM1LL" initial_value="0"/>	<!-- AM1 lower limit [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AMCSNS" initial_value="0.65"/>	<!-- sensitivity controller, aldosterone secretion [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="ALDMM" initial_value="2.5"/>	<!-- sensitivity controller of aldosterone multiplier [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AMKM" initial_value="0.5"/>	<!-- sensitivity controller of AMK [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AMNAM" initial_value="0.8"/>	<!-- sensitivity controller of AMNA [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AMNAUL" initial_value="15"/>	<!-- AMNA upper limit [P] -->
      <variable units="dimensionless" public_interface="out" private_interface="none" name="AMNALL" initial_value="0.04"/>	<!-- 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 -->


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  <rdf:Description rdf:about="">
    <dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
    <cmeta:comment rdf:resource="rdf:#9a70ea36-bf46-423d-98ed-878bf355fe69" />
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  </rdf:Description>
  <rdf:Description rdf:about="rdf:#9a70ea36-bf46-423d-98ed-878bf355fe69">
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  </rdf:Description>
  <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="rdf:#32d54a09-8494-4a32-a4dc-f143cb295de2">
    <bqs:Pubmed_id />
    <bqs:JournalArticle rdf:resource="rdf:#8165353a-32bc-4215-b592-5c9eebba19e7" />
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#d204634a-c636-4a5a-9cfa-6b93f7015c5a">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
    <vCard:N rdf:resource="rdf:#65e44fd5-e430-4101-9827-0bfd07f4a384" />
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#e386ddfa-7d48-4b76-9634-8405d5d83e42">
    <dcterms:W3CDTF>2008-04-03T00:00:00+00:00</dcterms:W3CDTF>
  </rdf:Description>
  <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="http://www.cellml.org/models/guyton_aldosterone_2008_version02/download#aldosterone_CellML1_0_model#LfY7zdZ%60EYs">
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    <ns7:simulation rdf:resource="rdf:#$b2Cb93" />
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#$RQv43">
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  <rdf:Description rdf:about="rdf:#8165353a-32bc-4215-b592-5c9eebba19e7">
    <dc:creator rdf:resource="rdf:#0ed41fb2-8b42-4bae-92de-0a801335dd86" />
    <dc:title>Description of Guyton aldosterone module</dc:title>
    <bqs:volume />
    <bqs:first_page />
    <bqs:Journal rdf:resource="rdf:#92beded5-a6f8-493e-b688-971e8447a536" />
    <dcterms:issued rdf:resource="rdf:#5444eb0f-d2f3-4608-bcd6-674023b4fe64" />
    <bqs:last_page />
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#75a07b91-9ba8-4714-914e-42c51cfa2f55">
    <vCard:Orgname>The University of Auckland</vCard:Orgname>
    <vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#8c71bd4a-eae9-4c93-9be7-127dcbea2d9c">
    <vCard:Given>Jonna</vCard:Given>
    <vCard:Family>Terkildsen</vCard:Family>
    <vCard:Other />
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#$3SdBX3">
    <ns7:boundIntervals rdf:resource="rdf:#$4SdBX3" />
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#7fdb2812-6704-46c2-aab0-da64a81fa93f">
    <vCard:Given />
    <vCard:Family>Guyton</vCard:Family>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#65e44fd5-e430-4101-9827-0bfd07f4a384">
    <vCard:Given />
    <vCard:Family>Aldosterone</vCard:Family>
  </rdf:Description>
  <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="#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="rdf:#6b483995-ab55-4b20-85a3-10aa81cfa1e8">
    <dc:creator rdf:resource="rdf:#5c2e7819-71bd-4ab1-b82e-7445930ac12a" />
    <rdf:value />
  </rdf:Description>
  <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="rdf:#27ec91fc-1a76-411d-b815-5927b7c135ca">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
    <vCard:N rdf:resource="rdf:#7fdb2812-6704-46c2-aab0-da64a81fa93f" />
  </rdf:Description>
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    <vCard:FN />
  </rdf:Description>
  <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="#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:Description rdf:about="#aldosterone_CellML1_0_model">
    <ns7:simulation rdf:resource="rdf:#$QQv43" />
    <bqs:reference rdf:resource="rdf:#32d54a09-8494-4a32-a4dc-f143cb295de2" />
<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>aldosterone</rdf:li>
        <rdf:li>Guyton</rdf:li>
      </rdf:Bag>
    </rdf:value>
  </dc:subject>
</bqs:reference>

    <cmeta:comment rdf:resource="rdf:#6b483995-ab55-4b20-85a3-10aa81cfa1e8" />
    <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:Description rdf:about="rdf:#298675f8-2e34-453d-97ba-dad23404461d">
    <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet" />
    <rdf:value>j.terkildsen@auckland.ac.nz</rdf:value>
  </rdf:Description>
  <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="rdf:#$SQv43">
    <ns7:endingValue>1000</ns7:endingValue>
    <ns7:nonstandard-pointDensity>100000</ns7:nonstandard-pointDensity>
  </rdf:Description>
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  </rdf:Description>
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    <vCard:FN />
  </rdf:Description>
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    <vCard:ORG rdf:resource="rdf:#75a07b91-9ba8-4714-914e-42c51cfa2f55" />
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  </rdf:Description>
  <rdf:Description rdf:about="rdf:#$4SdBX3">
    <rdf:rest rdf:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil" />
    <rdf:first rdf:resource="rdf:#$5SdBX3" />
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#5444eb0f-d2f3-4608-bcd6-674023b4fe64">
    <dcterms:W3CDTF>2008-00-00 00:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#92beded5-a6f8-493e-b688-971e8447a536">
    <dc:title />
  </rdf:Description>
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    <ns7:nonstandard-pointDensity>100000</ns7:nonstandard-pointDensity>
  </rdf:Description>
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</model>