Location: Guyton, Aldosterone, 2008 @ 0e9ca49cbe92 / aldosterone.cellml

Author:
jonna <devnull@localhost>
Date:
2009-07-16 14:55:58+12:00
Desc:
Added General Files. Changed links of dependencies so can open from web-browser. Added RDF metadata for citation and keywords, removed publication link from documentation.
Permanent Source URI:
http://models.cellml.org/workspace/guyton_aldosterone_2008/rawfile/0e9ca49cbe9242ae31f3c464b0c66b8d0aa2585a/aldosterone.cellml

<?xml version="1.0" encoding="utf-8"?>
<model 
	name="aldosterone_model"
	cmeta:id="aldosterone_model"
	
	xmlns="http://www.cellml.org/cellml/1.1#"
	xmlns:cellml="http://www.cellml.org/cellml/1.1#"
	xmlns:cmeta="http://www.cellml.org/metadata/1.0#"
	xmlns:xlink="http://www.w3.org/1999/xlink">

	<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
		<rdf:Description rdf:about="#aldosterone_model">
			<rdf:value>
			ALDOSTERONE AND ITS FEEDBACK CONTROL FUNCTIONS FOR MODIFICATION OF THE CIRCULATION
			Two inputs are used for controlling aldosterone secretion, the potassium concentration in the 
			extracellular fluids (CKE) and the effect of angiotensin (ANM) on aldosterone secretion.  
			In turn, multiplier effects for aldosterone control of potassium (AMK) and sodium (AMNA) transport 
			through cell membranes, especially through the kidney tubule membranes are calculated.
			</rdf:value>
		</rdf:Description>
	</rdf:RDF>

<!-- =============================================	Import the required units from the Units file	==================================================== -->
	<import xlink:href="units.cellml">
		<units name="minute" units_ref="minute"/>
		<units name="per_minute" units_ref="per_minute"/>
		<units name="beats_per_minute" units_ref="beats_per_minute"/>
		<units name="beats_per_minute_per_mmHg" units_ref="beats_per_minute_per_mmHg"/>
		<units name="minute_per_L" units_ref="minute_per_L"/>
		<units name="mmHg" units_ref="mmHg"/>
		<units name="per_mmHg" units_ref="per_mmHg"/>
		<units name="mmHg_per_mL" units_ref="mmHg_per_mL"/>
		<units name="mmHg_L" units_ref="mmHg_L"/>
		<units name="per_mmHg2" units_ref="per_mmHg2"/>
		<units name="mmHg3" units_ref="mmHg3"/>
		<units name="monovalent_mEq" units_ref="monovalent_mEq"/>
		<units name="monovalent_mEq_per_minute" units_ref="monovalent_mEq_per_minute"/>
		<units name="monovalent_mEq_per_litre" units_ref="monovalent_mEq_per_litre"/>
		<units name="mOsm" units_ref="mOsm"/>
		<units name="mOsm_per_litre" units_ref="mOsm_per_litre"/>
		<units name="mOsm_per_minute" units_ref="mOsm_per_minute"/>
		<units name="monovalent_mEq_per_litre_per_minute" units_ref="monovalent_mEq_per_litre_per_minute"/>
		<units name="litre2_per_monovalent_mEq_per_minute" units_ref="litre2_per_monovalent_mEq_per_minute"/>
		<units name="L_per_minute" units_ref="L_per_minute"/>
		<units name="per_mmHg_per_minute" units_ref="per_mmHg_per_minute"/>
		<units name="mL" units_ref="mL"/>
		<units name="gram_per_L" units_ref="gram_per_L"/>
		<units name="L_mmHg_per_gram" units_ref="L_mmHg_per_gram"/>
		<units name="L2_mmHg_per_gram2" units_ref="L2_mmHg_per_gram2"/>
		<units name="mmHg_minute_per_L" units_ref="mmHg_minute_per_L"/>
		<units name="mmHg_L_per_minute" units_ref="mmHg_L_per_minute"/>
		<units name="gram_per_minute" units_ref="gram_per_minute"/>
		<units name="mL_per_L" units_ref="mL_per_L"/>
		<units name="mL_per_L_per_mmHg" units_ref="mL_per_L_per_mmHg"/>
		<units name="mL_per_L_per_minute" units_ref="mL_per_L_per_minute"/>
		<units name="mL_per_minute_per_mmHg" units_ref="mL_per_minute_per_mmHg"/>
		<units name="L_mL_per_minute_per_mmHg" units_ref="L_mL_per_minute_per_mmHg"/>
		<units name="L_per_mL" units_ref="L_per_mL"/>
		<units name="L_per_mmHg" units_ref="L_per_mmHg"/>
		<units name="mL_per_minute" units_ref="mL_per_minute"/>
		<units name="L_per_minute_per_mmHg" units_ref="L_per_minute_per_mmHg"/>
		<units name="L_per_minute_per_mmHg2" units_ref="L_per_minute_per_mmHg2"/>
	</import>

<!-- =====================================	Import all Parameters and State Variables from the Parameter file	============================================== -->
	<import xlink:href="parameters.cellml">
		<component component_ref="parameter_values" name="parameter_values"/>
		<component component_ref="state_variables" name="state_variables"/>
	</import>


<!-- ========================================	ALDOSTERONE TOP-LEVEL COMPONENT	============================================= -->
	<component 	name="aldosterone" 
				cmeta:id="aldosterone">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#aldosterone">
				<rdf:value>
				Encapsulation grouping component containing all the components in the Aldosterone Model. The inputs and 
				outputs of the Aldosterone Model must be passed by this component.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>

		<variable 	cmeta:id="aldosterone_time"
					name="time"	units="minute"	private_interface="out" public_interface="in"/>

<!-- Inputs from components in other models -->
		<variable name="ANM"	units="dimensionless" private_interface="out" public_interface="in"/>
		<variable name="CKE"	units="monovalent_mEq_per_litre" private_interface="out" public_interface="in"/>

<!-- Outputs to components in other models -->
		<variable 	cmeta:id="aldosterone_AMK"
					name="AMK" 	units="dimensionless" private_interface="in" public_interface="out"/>
		<variable 	cmeta:id="aldosterone_AMNA"
					name="AMNA"	units="dimensionless" private_interface="in" public_interface="out"/>
	</component>

<!-- OUTPUT CONNECTIONS -->
	<connection>
		<map_components component_1="aldosterone" component_2="aldosterone_effect_on_cell_membrane_K_transport"/>
		<map_variables variable_1="AMK" variable_2="AMK"/>
	</connection>
	<connection>
		<map_components component_1="aldosterone" component_2="aldosterone_effect_on_cell_membrane_Na_transport"/>
		<map_variables variable_1="AMNA" variable_2="AMNA"/>
	</connection>

<!-- ========================================	ANGIOTENSIN CONTOL OF ALDOSTERONE SECRETION	============================================= -->
	<component 	name="angiotensin_control_of_aldosterone_secretion" 
				cmeta:id="angiotensin_control_of_aldosterone_secretion">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#angiotensin_control_of_aldosterone_secretion">
				<rdf:value>
				AL1, AL2, and AL3:  
				Calculation of the partial effect of angiotensin on aldosterone secretion (ANMAL) 
				based on the general angiotensin multiplier (ANM).  The sensitivity of this effect
				is controlled by the sensitivity control variable (ANMALD) in Block AL2.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL1_to_AL3">
				<rdf:value>
				AL1, AL2, and AL3:  
				Calculation of the partial effect of angiotensin on aldosterone secretion (ANMAL) 
				based on the general angiotensin multiplier (ANM).  The sensitivity of this effect
				is controlled by the sensitivity control variable (ANMALD) in Block AL2.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="ANM"	units="dimensionless" private_interface="none" public_interface="in"/>

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

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

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL1_to_AL3">
				<eq/>
				<ci>ANMAL</ci>
				<apply>
					<plus/>
					<apply>
						<times/>
						<apply>
							<minus/>
							<ci>ANM</ci>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
						<ci>ANMALD</ci>
					</apply>
					<cn cellml:units="dimensionless">1</cn>
				</apply>
			</apply>
		</math>
	</component>

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

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

<!-- ========================================	OSMOTIC CONTROL OF ALDOSTERONE SECRETION	============================================= -->
	<component 	name="osmotic_control_of_aldosterone_secretion" 
				cmeta:id="osmotic_control_of_aldosterone_secretion">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#osmotic_control_of_aldosterone_secretion">
				<rdf:value>
				AL4:  
				Calculation of the driving force of potassium extracellular fluid concentration (CKE) 
				on aldosterone secretion by subtracting the constant 3.3 from CKE.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL4">
				<rdf:value>
				AL4:  
				Calculation of the driving force of potassium extracellular fluid concentration (CKE) 
				on aldosterone secretion by subtracting the constant 3.3 from CKE.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="CKE"	units="monovalent_mEq_per_litre" private_interface="none" public_interface="in"/>

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

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL4">
				<eq/>
				<ci>OSMAL</ci>
				<apply>
					<divide/>
					<apply>
						<minus/>
						<ci>CKE</ci>
						<cn cellml:units="monovalent_mEq_per_litre">3.3</cn>
					</apply>
					<cn cellml:units="monovalent_mEq_per_litre">1.0</cn>
				</apply>
			</apply>
		</math>
	</component>

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

<!-- ========================================	ALDOSTERONE SECRETION	============================================= -->
	<component 	name="aldosterone_secretion" 
				cmeta:id="aldosterone_secretion">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#aldosterone_secretion">
				<rdf:value>
				AL5:  
				Calculation of the basic rate of secretion of aldosterone (AMRBSC) by multiplying 
				the potassium drive for secretion from Block AL4 times the angiotensin drive for 
				aldosterone secretion (ANMAL).

				AL6, AL7, AL8, and AL9:  
				These blocks calculate the aldosterone secretion rate (AMR).  Blocks AL6, AL7, 
				and AL8 represent a sensitivity controller for the control of aldosterone secretion rate.
				The sensitivity control variable is AMKMUL in Block AL7.  Block AL9 sets a lower limit 
				to the aldosterone secretion equal to zero.

				AL9A:  
				Provision is made here for infusion of aldosterone to perform infusion experiments (ALDINF).

				AL9B:  
				Provision is made here to set the rate of aldosterone entering the circulatory system (AMR1)
				to a constant value (ALDKNS) irrespective of all other changes at earlier stages in this 
				calculation.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL5">
				<rdf:value>
				AL5:  
				Calculation of the basic rate of secretion of aldosterone (AMRBSC) by multiplying 
				the potassium drive for secretion from Block AL4 times the angiotensin drive for 
				aldosterone secretion (ANMAL).
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL6_to_AL8">
				<rdf:value>
				AL6, AL7, AL8:  
				These blocks calculate the aldosterone secretion rate (AMR).  Blocks AL6, AL7, 
				and AL8 represent a sensitivity controller for the control of aldosterone secretion rate.
				The sensitivity control variable is AMKMUL in Block AL7.  
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL9">
				<rdf:value>
				AL9:
				Block AL9 sets a lower limit to the aldosterone secretion equal to zero.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL9A_and_AL9B">
				<rdf:value>
				AL9A:  
				Provision is made here for infusion of aldosterone to perform infusion experiments (ALDINF).

				AL9B:  
				Provision is made here to set the rate of aldosterone entering the circulatory system (AMR1)
				to a constant value (ALDKNS) irrespective of all other changes at earlier stages in this 
				calculation.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="ANMAL"	units="dimensionless" private_interface="none" public_interface="in"/>
		<variable name="OSMAL"	units="dimensionless" private_interface="none" public_interface="in"/>

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

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

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

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL5">
				<eq/>
				<ci>AMRBSC</ci>
				<apply>
					<times/>
					<ci>ANMAL</ci>
					<cn cellml:units="dimensionless">0.909</cn>
					<ci>OSMAL</ci>
				</apply>
			</apply>
			<apply id="AL6_to_AL8">
				<eq/>
				<ci>AMRT</ci>
				<apply>
					<plus/>
					<apply>
						<times/>
						<apply>
							<minus/>
							<ci>AMRBSC</ci>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
						<ci>AMKMUL</ci>
					</apply>
					<cn cellml:units="dimensionless">1</cn>
				</apply>
			</apply>
			<apply id="AL9">
				<eq/>
				<ci>AMR</ci>
				<piecewise>
					<piece>
						<cn cellml:units="dimensionless">0</cn>
						<apply>
							<lt/>
							<ci>AMRT</ci>
							<cn cellml:units="dimensionless">0</cn>
						</apply>
					</piece>
					<otherwise>
						<ci>AMRT</ci>
					</otherwise>
				</piecewise>
			</apply>
			<apply id="AL9A_and_AL9B">
				<eq/>
				<ci>AMR1</ci>
				<piecewise>
					<piece>
						<ci>ALDKNS</ci>
						<apply>
							<gt/>
							<ci>ALDKNS</ci>
							<cn cellml:units="dimensionless">0</cn>
						</apply>
					</piece>
					<otherwise>
						<apply>
							<plus/>
							<ci>AMR</ci>
							<ci>ALDINF</ci>
						</apply>
					</otherwise>
				</piecewise>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="aldosterone_secretion" component_2="angiotensin_control_of_aldosterone_secretion"/>
		<map_variables variable_1="ANMAL" variable_2="ANMAL"/>
	</connection>
	<connection>
		<map_components component_1="aldosterone_secretion" component_2="osmotic_control_of_aldosterone_secretion"/>
		<map_variables variable_1="OSMAL" variable_2="OSMAL"/>
	</connection>

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

<!-- ========================================	ALDOSTERONE CONCENTRATION		============================================= -->
	<component 	name="aldosterone_concentration" 
				cmeta:id="aldosterone_concentration">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#aldosterone_concentration">
				<rdf:value>
				AL10, AL11, and AL12:  
				Calculation of aldosterone concentration (AMC), allowing for a time delay in the
				build-up of the aldosterone.  The time constant for the time delay is AMT in Block AL12.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL10_to_AL12">
				<rdf:value>
				AL10, AL11, and AL12:  
				Calculation of aldosterone concentration (AMC), allowing for a time delay in the
				build-up of the aldosterone.  The time constant for the time delay is AMT in Block AL12.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="AMR1"	units="dimensionless" private_interface="none" public_interface="in"/>
		<variable name="AMC_init"	units="dimensionless" private_interface="none" public_interface="in"/>
		<variable name="time"	units="minute" private_interface="none" public_interface="in"/>
		
<!-- Outputs to other components -->
		<variable name="AMC" 	initial_value="AMC_init"	units="dimensionless" private_interface="none" public_interface="out"/>

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

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL10_to_AL12">
				<eq/>
				<apply>
					<diff/>
					<bvar>
						<ci>time</ci>
					</bvar>
					<ci>AMC</ci>
				</apply>
				<apply>
					<divide/>
					<apply>
						<minus/>
						<ci>AMR1</ci>
						<ci>AMC</ci>
					</apply>
					<ci>AMT</ci>
				</apply>
			</apply>
		</math>
	</component>

<!-- STATE VARIABLES INITIAL VALUE -->
	<connection>
		<map_components component_1="aldosterone_concentration" component_2="state_variables"/>
		<map_variables variable_1="AMC_init" variable_2="AMC_init"/>
	</connection>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="aldosterone_concentration" component_2="aldosterone_secretion"/>
		<map_variables variable_1="AMR1" variable_2="AMR1"/>
	</connection>
	<connection>
		<map_components component_1="aldosterone_concentration" component_2="aldosterone"/>
		<map_variables variable_1="time" variable_2="time"/>
	</connection>

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

<!-- ========================================	GENERAL ALDOSTERONE MULTIPLIER	============================================= -->
	<component 	name="general_aldosterone_multiplier" 
				cmeta:id="general_aldosterone_multiplier">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#general_aldosterone_multiplier">
				<rdf:value>
				AL13:  
				This block calculates, based on the input of aldosterone concentration (AMC), 
				an output factor (AM1) for the physiological multiplying effect of aldosterone 
				on different physiological mechanisms.  This is a temporary aldosterone multiplier
				effect.  It is calculated as shown in the block, with AM1LL equal to the lower 
				limit of AM1 and AM1UL equal to the upper limit.

				AL14, AL15, and AL16:  
				These are a sensitivity controller; the control variable for sensitivity is ALDMM in
				Block AL15, and the output AM is a general aldosterone multiplier.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL13">
				<rdf:value>
				AL13:  
				This block calculates, based on the input of aldosterone concentration (AMC), 
				an output factor (AM1) for the physiological multiplying effect of aldosterone 
				on different physiological mechanisms.  This is a temporary aldosterone multiplier
				effect.  It is calculated as shown in the block, with AM1LL equal to the lower 
				limit of AM1 and AM1UL equal to the upper limit.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL14_to_AL16">
				<rdf:value>
				AL14, AL15, and AL16:  
				These are a sensitivity controller; the control variable for sensitivity is ALDMM in
				Block AL15, and the output AM is a general aldosterone multiplier.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="AMC"	units="dimensionless" private_interface="none" public_interface="in"/>

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

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

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

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL13">
				<eq/>
				<ci>AM1</ci>
				<apply>
					<minus/>
					<ci>AM1UL</ci>
					<apply>
						<divide/>
						<apply>
							<minus/>
							<ci>AM1UL</ci>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
						<apply>
							<plus/>
							<apply>
								<times/>
								<apply>
									<divide/>
									<apply>
										<minus/>
										<ci>AM1LL</ci>
										<cn cellml:units="dimensionless">1</cn>
									</apply>
									<apply>
										<minus/>
										<ci>AM1LL</ci>
										<ci>AM1UL</ci>
									</apply>
								</apply>
								<apply>
									<minus/>
									<ci>AMC</ci>
									<cn cellml:units="dimensionless">1</cn>
								</apply>
								<ci>AMCSNS</ci>
							</apply>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
					</apply>
				</apply>
			</apply>
			<apply id="AL14_to_AL16">
				<eq/>
				<ci>AM</ci>
				<apply>
					<plus/>
					<apply>
						<times/>
						<apply>
							<minus/>
							<ci>AM1</ci>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
						<ci>ALDMM</ci>
					</apply>
					<cn cellml:units="dimensionless">1</cn>
				</apply>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="general_aldosterone_multiplier" component_2="aldosterone_concentration"/>
		<map_variables variable_1="AMC" variable_2="AMC"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_1="general_aldosterone_multiplier" component_2="parameter_values"/>
		<map_variables variable_1="AM1UL" variable_2="AM1UL"/>
		<map_variables variable_1="AM1LL" variable_2="AM1LL"/>
		<map_variables variable_1="AMCSNS" variable_2="AMCSNS"/>
		<map_variables variable_1="ALDMM" variable_2="ALDMM"/>
	</connection>

<!-- ========================================	ALDOSTERONE EFFECT ON CELL MEMBRANE POTASSIUM TRANSPORT	============================================= -->
	<component 	name="aldosterone_effect_on_cell_membrane_K_transport" 
				cmeta:id="aldosterone_effect_on_cell_membrane_K_transport">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#aldosterone_effect_on_cell_membrane_K_transport">
				<rdf:value>
				AL17, AL18, AL19, and AL20:  
				This is an additional sensitivity control circuit for controlling the aldosterone 
				multiplier effect on potassium transport through cell membranes (AMK), especially 
				in the kidney tubules.  The input to this system is the general aldosterone multiplier (AM),
				and the sensitivity controller is the variable AMKM in Block AL18.  The lower limit to 
				AMK is set by Block AL20.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL17_to_AL19">
				<rdf:value>
				AL17, AL18 and AL19:  
				This is an additional sensitivity control circuit for controlling the aldosterone 
				multiplier effect on potassium transport through cell membranes (AMK), especially 
				in the kidney tubules.  The input to this system is the general aldosterone multiplier (AM),
				and the sensitivity controller is the variable AMKM in Block AL18.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL20">
				<rdf:value>
				AL20:  
				The lower limit to AMK is set by Block AL20.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="AM"	units="dimensionless" private_interface="none" public_interface="in"/>

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

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

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

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL17_to_AL19">
				<eq/>
				<ci>AMKT</ci>
				<apply>
					<plus/>
					<apply>
						<times/>
						<apply>
							<minus/>
							<ci>AM</ci>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
						<ci>AMKM</ci>
					</apply>
					<cn cellml:units="dimensionless">1</cn>
				</apply>
			</apply>
			<apply id="AL20">
				<eq/>
				<ci>AMK</ci>
				<piecewise>
					<piece>
						<cn cellml:units="dimensionless">0.2</cn>
						<apply>
							<lt/>
							<ci>AMKT</ci>
							<cn cellml:units="dimensionless">0.2</cn>
						</apply>
					</piece>
					<otherwise>
						<ci>AMKT</ci>
					</otherwise>
				</piecewise>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="aldosterone_effect_on_cell_membrane_K_transport" component_2="general_aldosterone_multiplier"/>
		<map_variables variable_1="AM" variable_2="AM"/>
	</connection>

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

<!-- ========================================	ALDOSTERONE EFFECT ON CELL MEMBRANE SODIUM TRANSPORT	============================================= -->
	<component 	name="aldosterone_effect_on_cell_membrane_Na_transport" 
				cmeta:id="aldosterone_effect_on_cell_membrane_Na_transport">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#aldosterone_effect_on_cell_membrane_Na_transport">
				<rdf:value>
				AL21, AL22, AL23, AL24, and AL25:  
				This circuit calculates an aldosterone multiplier factor for control of sodium 
				transport through cell membranes (AMNA), with the input to the circuit equal to 
				the generalized aldosterone multiplier (AM) and a sensitivity controller (AMNAM) 
				in Block AL22.  The upper and lower limits for the controlling effect on sodium 
				transport are set by variables AMNAUL and AMNALL in Blocks AL24 and AL25 respectively.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL21_to_AL23">
				<rdf:value>
				AL21, AL22 and AL23:  
				This circuit calculates an aldosterone multiplier factor for control of sodium 
				transport through cell membranes (AMNA), with the input to the circuit equal to 
				the generalized aldosterone multiplier (AM) and a sensitivity controller (AMNAM) 
				in Block AL22.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#AL24_and_AL25">
				<rdf:value>
				AL24, and AL25:  
				The upper and lower limits for the controlling effect on sodium 
				transport are set by variables AMNAUL and AMNALL in Blocks AL24 and AL25 respectively.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="AM"	units="dimensionless" private_interface="none" public_interface="in"/>

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

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

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

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="AL21_to_AL23">
				<eq/>
				<ci>AMNAT</ci>
				<apply>
					<plus/>
					<apply>
						<times/>
						<apply>
							<minus/>
							<ci>AM</ci>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
						<ci>AMNAM</ci>
					</apply>
					<cn cellml:units="dimensionless">1</cn>
				</apply>
			</apply>
			<apply id="AL24_and_AL25">
				<eq/>
				<ci>AMNA</ci>
				<piecewise>
					<piece>
						<ci>AMNALL</ci>
						<apply>
							<lt/>
							<ci>AMNAT</ci>
							<ci>AMNALL</ci>
						</apply>
					</piece>
					<piece>
						<ci>AMNAUL</ci>
						<apply>
							<gt/>
							<ci>AMNAT</ci>
							<ci>AMNAUL</ci>
						</apply>
					</piece>
					<otherwise>
						<ci>AMNAT</ci>
					</otherwise>
				</piecewise>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="aldosterone_effect_on_cell_membrane_Na_transport" component_2="general_aldosterone_multiplier"/>
		<map_variables variable_1="AM" variable_2="AM"/>
	</connection>

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

	
<!-- ============================================================		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="state_variables"/>
			<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>


</model>