/*
 * Guyton Model: Aldosterone
 * 
 * Model Status
 * 
 * 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.
 * 
 * Model Structure
 * 
 * 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.
 * 
 * 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.
 * 
 * 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.
 * 
 * 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.
 * 
 * model diagram
 * 
 * [[Image file: full_model.png]]
 * 
 * A systems analysis diagram for the full Guyton model describing
 * circulation regulation.
 * 
 * model diagram
 * 
 * [[Image file: aldosterone.png]]
 * 
 * A schematic diagram of the components and processes described
 * in the current CellML model.
 * 
 * There are several publications referring to the Guyton model.
 * One of these papers is cited below:
 * 
 * Circulation: Overall Regulation, A.C. Guyton, T.G. Coleman,
 * and H.J. Granger, 1972, Annual Review of Physiology , 34, 13-44.
 * PubMed ID: 4334846
 */

import nsrunit;
unit conversion on;
unit minute=60 second^1;
unit monovalent_mEq=.001 mole^1;
unit monovalent_mEq_per_minute=1.6666667E-5 second^(-1)*mole^1;
unit monovalent_mEq_per_litre=1 meter^(-3)*mole^1;
unit monovalent_mEq_per_litre_per_minute=.01666667 meter^(-3)*second^(-1)*mole^1;
unit litre2_per_monovalent_mEq_per_minute=1.6666667E-5 meter^6*second^(-1)*mole^(-1);
unit L_per_minute=1.6666667E-5 meter^3*second^(-1);

math main {
	realDomain time minute;
	time.min=0;
	extern time.max;
	extern time.delta;
	real ANM dimensionless;
	ANM=0.987545;
	real CKE monovalent_mEq_per_litre;
	CKE=4.44092;
	real ANMAL dimensionless;
	real ANMALD dimensionless;
	ANMALD=2.5;
	real OSMAL dimensionless;
	real AMR1 dimensionless;
	real AMKMUL dimensionless;
	AMKMUL=12;
	real ALDINF dimensionless;
	ALDINF=0;
	real ALDKNS dimensionless;
	ALDKNS=0;
	real AMRBSC dimensionless;
	real AMRT dimensionless;
	real AMR dimensionless;
	real AMC(time) dimensionless;
	when(time=time.min) AMC=1.0;
	real AMT minute;
	AMT=60;
	real AM(time) dimensionless;
	real AM1UL dimensionless;
	AM1UL=5;
	real AM1LL dimensionless;
	AM1LL=0;
	real AMCSNS dimensionless;
	AMCSNS=0.65;
	real ALDMM dimensionless;
	ALDMM=2.5;
	real AM1(time) dimensionless;
	real AMK(time) dimensionless;
	real AMKM dimensionless;
	AMKM=0.5;
	real AMKT(time) dimensionless;
	real AMNA(time) dimensionless;
	real AMNAM dimensionless;
	AMNAM=0.8;
	real AMNAUL dimensionless;
	AMNAUL=15;
	real AMNALL dimensionless;
	AMNALL=0.04;
	real AMNAT(time) dimensionless;

	// <component name="environment">

	// <component name="aldosterone">

	// <component name="angiotensin_control_of_aldosterone_secretion">
	ANMAL=((ANM-1)*ANMALD+1);

	// <component name="osmotic_control_of_aldosterone_secretion">
	OSMAL=((CKE-(3.3 monovalent_mEq_per_litre))/(1 monovalent_mEq_per_litre));

	// <component name="aldosterone_secretion">
	AMRBSC=(ANMAL*.909*OSMAL);
	AMRT=((AMRBSC-1)*AMKMUL+1);
	AMR=(if (AMRT<0) 0 else AMRT);
	AMR1=(if (ALDKNS>0) ALDKNS else AMR+ALDINF);

	// <component name="aldosterone_concentration">
	AMC:time=((AMR1-AMC)/AMT);

	// <component name="general_aldosterone_multiplier">
	AM1=(AM1UL-(AM1UL-1)/((AM1LL-1)/(AM1LL-AM1UL)*(AMC-1)*AMCSNS+1));
	AM=((AM1-1)*ALDMM+1);

	// <component name="aldosterone_effect_on_cell_membrane_K_transport">
	AMKT=((AM-1)*AMKM+1);
	AMK=(if (AMKT<.2) .2 else AMKT);

	// <component name="aldosterone_effect_on_cell_membrane_Na_transport">
	AMNAT=((AM-1)*AMNAM+1);
	AMNA=(if (AMNAT<AMNALL) AMNALL else if (AMNAT>AMNAUL) AMNAUL else AMNAT);

	// <component name="parameter_values">
}