/*
 * Guyton Model: Angiotensin
 * 
 * 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 the control functions
 * of angiotensin, beginning with the control of angiotensin formation
 * by the kidneys in response to changes in the rate of flow of
 * fluid in the renal tubules at the macula densa (MDFLW), and
 * extending through a series of curve-fitting and sensitivity
 * controlled equations to determine the multiple feedback effects
 * of angiotensin to control the various aspects of circulatory
 * function.
 * 
 * model diagram
 * 
 * [[Image file: full_model.png]]
 * 
 * A systems analysis diagram for the full Guyton model describing
 * circulation regulation.
 * 
 * model diagram
 * 
 * [[Image file: angiotensin.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 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 MDFLW L_per_minute;
	MDFLW=1.00051;
	real ANGSCR dimensionless;
	real MDFLW3 L_per_minute;
	real ANX1(time) dimensionless;
	when(time=time.min) ANX1=0.0;
	real ANXM dimensionless;
	ANXM=0;
	real ANV minute;
	ANV=5000;
	real ANX dimensionless;
	real ANPR(time) dimensionless;
	real REK dimensionless;
	REK=1;
	real ANPRT(time) dimensionless;
	real ANPR1(time) dimensionless;
	real ANGKNS dimensionless;
	ANGKNS=0;
	real ANGINF dimensionless;
	ANGINF=0;
	real ANC(time) dimensionless;
	when(time=time.min) ANC=0.859476;
	real ANT minute;
	ANT=12;
	real ANM(time) dimensionless;
	real ANMUL dimensionless;
	ANMUL=1.8;
	real ANMLL dimensionless;
	ANMLL=0.7;
	real ANCSNS dimensionless;
	ANCSNS=0.4;
	real ANU(time) dimensionless;
	real ANUM dimensionless;
	ANUM=6;
	real ANULL dimensionless;
	ANULL=0.8;
	real ANU1(time) dimensionless;
	real ANUVN(time) dimensionless;
	real ANUVM dimensionless;
	ANUVM=0;
	real Z12 dimensionless;
	Z12=5;

	// <component name="environment">

	// <component name="angiotensin">

	// <component name="instantaneous_angiotensin_formation">
	MDFLW3=MDFLW;
	ANGSCR=(if (MDFLW3>(1 L_per_minute)) (1 L_per_minute)/((1 L_per_minute)+(MDFLW3-(1 L_per_minute))*72) else 10-(9 L_per_minute)/((1 L_per_minute)+((1 L_per_minute)-MDFLW3)*8));

	// <component name="time_delayed_angiotensin_formation">
	ANX=((ANGSCR-1)*ANXM);
	ANX1:time=((ANX-ANX1)/ANV);

	// <component name="total_angiotensin_formation">
	ANPRT=((ANGSCR+ANX1)*REK);
	ANPR=(if (ANPRT<1E-5) 1E-5 else ANPRT);

	// <component name="artificial_angiotensin_formation">
	ANPR1=(if (ANGKNS>0) ANGKNS else ANPR+ANGINF);

	// <component name="angiotensin_concentration">
	ANC:time=((ANPR1-ANC)/ANT);

	// <component name="general_angiotensin_multiplier">
	ANM=(ANMUL-(ANMUL-1)/((ANMLL-1)/(ANMLL-ANMUL)*(ANC-1)*ANCSNS+1));

	// <component name="angiotensin_effect_on_circulation">
	ANU1=((ANM-1)*ANUM+1);
	ANU=(if (ANU1<ANULL) ANULL else ANU1);

	// <component name="angiotensin_effect_on_venous_constriction">
	ANUVN=((ANU-1)*ANUVM+1);

	// <component name="parameter_values">
}