CAUSAL OR ACAUSAL MODELLING: LABOUR FOR

HUMANS OR LABOUR FOR MACHINES

J. Kofránek, M. Mateják, P. Privitzer, M. Tribula

Laboratory of Biocybernetics, Institute of Pathological Physiology, First Faculty of Medicine, Charles
University in Prague

Abstract
Models designed using classical Simulink networks provide a clear graphic
visualization of individual mathematical relationships. Signals flow in connections
between individual blocks, transmitting values of individual variables from the
output of one block to inputs of other blocks. Processing of input information to
output information takes place in the blocks. Interconnection of the blocks in
Simulink thus reflects rather the calculation procedure than the very structure of the
modelled reality. This is the so called causal modelling. However, it is important in
designing and especially presenting and describing the model that the very structure
of the model, rather than the very algorithm of the simulation calculation, captures
well especially the physical essence of the modelled reality. Therefore, declarative
(acausal) notation of models is starting to be used in a growing extent in modern
simulation environments; this means that individual components of the model
describe the equations directly and not the algorithm of their solution. By
interconnecting individual components, the systems of equations become connected
with each other. Interconnection of the components does not define the calculation
procedure but the modelled reality. The way of solving the equations is then “left up
to the machines”. Application of acausal approach has been made possible by new
Simulink libraries Simscape, and linked domain libraries SimElectronics,
SimHydraulics, SimMechanics etc. Modelica is a modern simulation language built
directly on acausal notation of models. Implementation of this language of the
company Dynasim is interesting for Mathworks products users as it allows for direct
connection with Simulink and Matlab (Modelica is implemented under the name
Dymola in this case).

1 Introduction
An article was published in the journal Annual Review of Physiology [3] 36 years ago, whose form
surpassed at the very first sight the accustomed form of the then physiological articles. It was
introduced by a large diagram pasted in as an attachment (Fig. 1). At the first sight, the diagram full of
lines and mutually connected elements remotely resembled a drawing of some electrotechnical device.
However, instead of tubes or other electrotechnical parts, computational blocks were shown in the
diagram (multiplication, division, summation, integration, functional blocks), symbolizing
mathematical operations performed with physiological quantities. Bunches of connecting conductors
between the blocks seemed at the first sight to express complex feedback interconnection of
physiological quantities. The blocks were grouped in 18 groups, representing individual
interconnected physiological subsystems.
The very article gave a quantitative description of physiological regulation of the circulation
system in a manner absolutely new in the then medical professional literature, as well as its connexion
with and linkage to other subsystems of the organism – the kidneys, regulation of volumetric and
electrolyte equilibrium etc. Instead of writing a set of mathematical equations, the article made use of
graphic depiction of mathematical relationships. This syntax made it possible to provide a graphic
depiction of connexions among individual physiological quantities in the form of interconnected
blocks representing mathematical operations. These elements are very similar to Simulink blocks;
there is a difference only in their graphic shape.

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Figure 1: Extensive diagram of the physiological circulatory regulations according to A. C. Guyton et

al from 1972

This resemblance inspired us to bring the old classical Guyton’s diagram back to life using
Simulink, and to transform it into the shape of a functional simulation model. We developed an effort
to preserve the outside appearance of the Simulink model quite the same as that of the original graphic
diagram – the layout, placement of conductors, quantity names as well as block numbers. We reported
on this implementation last year [10].

2 Web of Physiological Relationships in Simulink

Simulation visualization of the old diagram was not quite easy – there are namely mistakes in the
original image diagram of the model! This is no problem in a drawn picture; however, upon
attempting at bringing it to life in Simulink, the model collapses as a whole immediately. Not many
mistakes were found – switched signs, a division block instead of a multiplication one, switched
connection between blocks, missing decimal point in a constant etc. However, they were enough to
make sure the model did not function (Fig. 2). Some mistakes could be seen at the first sight (even
without any physiological knowledge) – it is apparent from the diagram that during the run of the
model, value of some quantities in some integrators (due to wrongly indicated feedback) would rise
quickly to the infinite and the model would collapse. However, with knowledge of physiology and
system analysis, all the mistakes could be found upon exerting some effort. For a detailed description
of the mistakes and their corrections see [10].
It is interesting that the Guyton’s diagram as a complex image has been reprinted many times in
various publications (recently, see for example [5, 12]). However, no one called attention to the
mistakes and took the trouble to remove them. This was understandable in the times the image-based
diagram was being created. No drawing programs existed – the image was created as a complex
manual drawing – and manual redrawing of the complex diagram was not easy. However, it is also
possible that the model authors themselves did not really want to correct the mistakes perhaps – those
who took the trouble analyzing the model revealed the image “spelling mistakes”; those who wanted

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nothing but copy the diagram mindlessly had bad luck. After all, in those times, the authors also
mailed out source program codes of their model in the Fortran programming language – thus if
somebody wanted only to test the model behaviour, there was no need to program anything (perhaps
only to perform a routine conversion from Fortran to another programming language at the
maximum).
Our Simulink implementation of the (corrected) Guyton’s model (Fig. 3) is available to those
interested at www.physiome.cz/guyton. On this website, our Simulink implementation of a much more
complex model version of Guyton et al from subsequent years can be found, as well. At the same time,
very detailed description of all the mathematical relationships applied is presented together with the
reasons.

Figure 2: Correction of the most significant errors in the model of A. C. Guyton et al.

3 Block-Oriented Simulation Networks

The Guyton’s block diagram augured occurrence of block-oriented simulation languages. However, in
the year 1972, Guyton himself and his collaborators implemented the model in Fortran – Simulink
version 1 was not marketed until 18 years later (in 1990). Block-oriented simulation languages,
Simulink being one of their typical representatives, make it possible to set up computer models using
individual hierarchically arranged blocks with defined inputs and outputs. It is apparent from such a
hierarchically arranged block-oriented description how the values of individual variables are
calculated in the model – i.e. the computational algorithm. The blocks can be grouped into individual
subsystems, which communicate with the surrounding environment through defined input and output
“pins”, thus representing something like “simulation chips”. A simulation chip hides the simulation
network structure from the user, similarly as an electronic chip hides the interconnection of individual
transistors and other electronic elements. The user can thus be concerned only with the chip behaviour,
without having to take care of its inner structure and the computational algorithm. Behaviour of a
simulation chip can be thus tested by observing the outputs on connected virtual displays or virtual

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oscilloscopes. This is very advantageous especially in testing the model behaviour and to express
mutual dependencies among variables. The entire complex model can be then displayed as
interconnected simulation chips, while it is clear from the structure of their mutual connections what
effects are taken into account in the model and how.

NON-MUSCLE OXYGEN DELIVERY MUSCLE BLOOD FLOW CONTROL AND PO2

260
228 240 PM3
1 1 BFM PK2 245
57.14
02M OSV s xo 259 PMO AU 254
0.7 800 AMM
1
168 1
269 AOM 261 227 1
229 lower limit .001
s xo
1 POV 5 239 237 02A
270 RMO
5 PK1 PK3 0.15
258 1 1
2500 PM1^2 u^2 253

226 246
268 262
POT 40 230 5
236
POV OVA 238 QOM PM4
257 0.25
RDO 40 198.7 -1
2688 BFM 1
s x 252
512 o 247
267 lower limit 50 263 P2O AOM
5 0.7 1
OVA 231 2400 8
x 235 POE
u^3 P40^3 225 200 1 o Xo P2O 1
upper limit 8
s
DOB 7.983 lower limit .005
256
264
266 P4O 5 DVS 248 251
MO2 241
1
8.0001 RMO 8.0001
265 2400 232 57.14
224 OSA 60
271 234
u^3 POT^3 HM 255
xo 1
271 P3O
1 242 250
s PVO 244
BFN OVA
40 223 P3O^3 u^3 1
272 233 POM
upper limit 8
QO2 200
P1O POT 0.00333 0.08
PM5 PDO
243
122
2.8 PMO 249
2.859 0.5 8
8 512 EXC
VPF 40
HM 1
POT 0.0125
40 PVO
8

0.9999
AOM

1 0.9864
AMM

NON-MUSCLE OXYGEN DELIVERY MUSCLE BLOOD FLOW CONTROL AND PO2 VASCULAR KIDNEY DYNAMICS AND EXCRETION
260
STRESS THIRST AND DRINKING
228 240 PM3
1 1 BFM PK2 245 RR GFN
02M
57.14
OSV
s xo 0.7 259 800
PMO AU 254 AMM
RELAXATION 206 218
8 POT
192 193 194
1 205 GFR VUD STH
168 1
269 AOM 261 227 200
1
229 lower limit .001 65 VUD 1
s xo lower limit 0.0003 STH TVD
POV 239 237 02A 0.125 0.001 8.25 4
1 270 5 1 0.001022 lower limit 0
RMO PK1 PK3 208 1
5 0.15 s Z10 Z11
258 1 1 0.00781 0
2500 PM1^2 u^2 253
EVR PFL 190 191
226 246 199 AHM
268 0.8 TRR 1
262 64 AAR
POT 40 230 5
236 VV7 212 TVD
OVA 238 QOM PM4 1000 0.01
POV
257 0.25 0 AAR 0.0009964
RDO -1 198 PPC 209 219
40 198.7 BFM 1 SRK 51.66 0.009
2688 217
s xo 252 33 18 1
512 247 GLP
267 lower limit 50 263 AOM
0.7 P2O VV6 63
5 OVA 231 2400 8 1 5
u^3 xo 235 Xo POE VV7 31.67 203 GF4 210
P40^3 225 200 1 P2O
upper limit 8 1 VV2 VV7 algebraic
s VIM
AM
DOB 7.983 lower limit .005 GF3 loop
256 0.01028 1 188
264 61 breaking 186
VV1 GF3 220 189
266 P4O DVS 248 251 62 197 AHM AH4 6
5 1 211
MO2 241 216 AHC
1 1 s xo 1 0.0785 185
VIM
8.0001 RMO 8.0001 1 0.1 0.9996
265 2400 232 AH2 187 AH1
57.14 0.301 1
224 OSA
60 6 s
271 234 215 AHM 10u
u^3 POT^3 HM 255 APD
xo 1 VVE 202 GP3
271 P3O 196
1 242 250 0.5 158A
PVO 244 221 NOD
s BFN 1 CNZ 183
OVA upper limit 15.0
40 u^3 1 AM 6 1 176 182
223 P3O^3 lower limit 0.4 175
272 233 POM AAR RFN AHM 0.3333
upper limit 8 CNY NOD
QO2 200 CNA CN8
POT 1.5 142 0.14
P1O 0.00333 0.08 1.2 0.1024 AH
PM5 PDO 195 ARF 184
243 0.3 201 207 213 214 222 lower limit 3
122 CNR
2.8 PMO 249 1
0.5 1.2
2.859 8 139
8 512 EXC lower limit 0
VPF 40
HM RFN RBF 0.001 177 178
POT 1 0.025 2.5
0.0125 PRA 179 180 AHY
PVO lower limit 0.35 RBF 1.2 0
40 CNX AHZ
8
1
RFN AH7 s
AUM 100
0.9999 1.2 1 AHM CNE
AOM 0.0007
10 2
REK 181
1 1 28 AM
0.9864 PPC 1 AU AH8
AMM
1

1
lower_limit_0
1
NON-MUSCLE LOCAL BLOOD FLOW CONTROL 40
POV
POB
278 277 276 275 274 POD 273
ARM
1 ANM 40
algebraic
loop 2.9 CAPILLARY MEMBRANE DYNAMICS ANTIDIURECTIC HORMONE CONTROL
1 breaking RVS
0.9387 AVE
1 lower limit 0.95 66
42 41A DP0
s AK1 lower limit 0.2 POK 1 1 79
xo 1 ARM 1.6379 0.007
POR 38 s xo PPD
1 0.06 36 CN7 0 PVG
1 40 1 1 ANU 1.79 BFN 0
AR1 43 RV1 67 DPL
0.0212 0.2
AMM 2.8 78
290 3.7 PVS 77
VIM RVS 41 39 DLP
RAM RSM RV1 CN2 85
96.3 0.04
17 17 PC LPK
AUM CPR DPP 162
POA 279 35 RAM ANM 1 163
281 280 1.6 ANU 1 2.9 17 0.00047
285 282 ARM 3 AN5 3.3
AR3 VB
AR1 37 BFM PC 5 PC
VIM PGS 5.002
1 VIM 1 RAR 2.781 16.79 1.004 160
80 lower limit 0.7 161
s A2K lower limit 0.5 PON 30.5 17 70 AN3
xo 1 AUM PAM VB 68
PAM 1.011 RVS 61 PRP AN2 0.042
20 RAR VRC 62 CPP 1 ANM 4.0 10u
1 0.1 1.2
AR2 VVE s xo
34 BFM 2 210
AUM AUM
VV7 72 VP REK
100 RBF 0.3216 VP 159
0 CFC
1 4 69 PPC 153b
PIF 0.007 28 0.4 153a 1
284 PA BFN QAO PVS
CPP 1.2 RFN s xo
-6.3 (1.2/u)^3 ANC 1
POC 283 100 5 6 VVR 3.774 16.79
287 286 POJ 2.859 69.76
284b 0.495 0.00355 VBD DVS 2.95 (1.2/RFN)^3
VTC 10
31 7 8 9 CNE
2 1 VVS VV8 PTC 73 PPC 10
33 RSN 0.002 74 CPP
0.33 1 s 154 155 156 157 158
288 11520 32 BFN PVS
lower limit 0.3 PA PGS 3.25 xo 5 CNA CNE
1 VAS VAE u^3 142 AN1
A3K 0.3 if (POD<0) {POJ=PODx3.3} 0.3 VVE lower limit 0.0001 75 ANM
s QVO 0.0825
1 0.85 xo 2.8 VVS 3.7 0.001879 CP1
POZ VTC PC^3
289 100 QVO CV
74
PVS 1.6283e-007
AR3 VAS3 152 0.1 15
1 CPK
s DAS CPI ANT
1 xo 60
TVD DPC
0.001 70 0.04
VAS VVS 71
PA 0.001 VPD
VUD VP
59 VB 1 0.03824
5
29 HSL
LVM
1
1.4 58 VLA
5 DFP
3 xo s ANGIOTENSIN CONTROL
30 3 20
QAO VPA VRA DPC
QLN
0
PA2 3.002
HMD LVM VTL
QLO PVS
HPL
PLA 0.002 VP
5.07 45 10
QLO 46 QLO
0.01453 PR1
291 POT 0
292 POQ 1 0 260 0.6 PVS 0.9984 20.039
PLA 173
QLN AM 174 172
8 LVM = f(PA2) QRF
1 AM AM5 19.8
8 upper limit 8 10u
PA 44
lower limit 4
0 1 ANM AM2
100 RVG
27 47 AM3
28 2.738 164 171
294 POQ 8 15
4
3 293 P2O 0.1 VLE 1
CPA
RVM 1 -0.017
295 11 167 168
296 8 0.4 PLA 54 PA
298 297 53 49 AMP AM1
QLN 100
EXE 26
48 AUH
VLA sqrt HSR
1.24 25 0.03791
EXC 0 RPA 1 QVO 0.001879 DPL
Z12 20 50 AMT
QLO -4 107 169
1 PP1 1.4 HPR 0 AMR
1 QLN = f(PLA) VTL VTL PLD 0 200 60
VLA 1
AUC CALCULATION s 106 AMP = f(PA)
56 HMD HMD 0.004
1 55 PIF 0.00352
12 5.045 165 166
AUC xo 7.8
PA1 when PA1<40: AUC=1.2 RVM QRO 0.002 lower limit 5
PA1 AUC RPV CKE KN1 1
when 40>PA1<80: AUC=0.03*(80-PA1) 20.18 5
lower limit 0 PTC 108 s
when PA1>=80: AUC=0 170
xo
307 DPL AMC
1 0.4 0.0357 16 DRA 5 CPI
302 303 20 52 15 CNA lower limit 6
0.1 142
AUC calculation DLA 0
AU6 57 PP2 0 50 13 PTC 0.04
24 105 9 1
PL1 1
PLA RVM = f(PP2) xo
A1B 301 DAU CPI 109
51 QRN PRA -6.334
RPT 0.026 AUH PTT
AUK AU2

AUB CALCULATION
u^3 AUB^3
0.0005
304
308
PPA VRA
1
s PIF
20 ALDOSTERONE CONTROL
305 AUH PR1
0.25 104
AUB 0
when PA1<40: AUB=1.85718 1 20 lower limit 4
PA1 AUB -4 DPC GP1
when 40>PA1<170: AUB=0.014286*(170-PA1) 1 0.04
s QRN = f(PRA) VRA
when PA1>=170: AUB=0 QPO 102 103
xo PPA DPI IFP
Z8 19 18 15 VIF
15.18 1
309 23 PLA 20 QRO 14 DPL
AUB calculation 0 6 PRA 0.005 s
RPT 12 xo 8.154e-006
22 21 PRA
QPO VPE VPA 1 0.1 110
AU8 PGL PPA s
0.09477 GPD VID 0
xo 0.38 0
AUZ CKI 133 CCD 134 135
0.30625 VTL
AUN CALCULATION 15 GP2 VID
VPA 132
1 0.0048 VIC
310 1
when PA1<50: AUN=6 AUN 111
PA1 AUN 1 0.002 0.0005 0.01 s
311 CNA 25 xo
when 20>PA1<50: AUN=0.2*(50-PA1) 83
AUJ 1 VTC 87
when PA1>=50: AUC=0 AU VIC
u
v s xo 1
CIRCULATORY DYNAMICS VID
20
0 PIF
AUN calculation GPD 131
AUJ^AUZ
316 VTD 12 VIF PTS -6.3 KI
317 0.21 0.9993 VV9 171
AUM AU9 84 xo 112 1
AUV 312 AUL 3.159 s
0.85 AU 1 xo
314 xo 128
1 313 VVR s 130 129
0.3 88 1 KIR
PLA 0 KCD KIE
0.15 s 3550 2850
0.999 0 10
AUD 2.95 0 8 POT VIM
12 PTS = f(VIF)
VVR KE1
0.7 70 339 VIM GPR
2.949 PPA 150 PO1 329 86 127
315 0.4667 1 VTS 0.013
CPP CPN CKE
8.25 VG
136 28 VG 5
0.9998 15 146 8
AUH AUH PPR PO2 338 11.98 113
1 149 100 15 101 140
PPC PA AM
1 AUY 1 VPF 0.333 1
319 1.5 VTS
320 0.9994 0.55 137 PPA KCD
318 0.5 1 0.4 151 HSR 85 1 0.00014
AUM lower limit 0.2375 HSL POT 121 122
0.000225 s 100 15 s 5
VIE 337 1 350 xo KED 123 124
xo 1 0.0028 KE CKE
1 POY PTT = (VTS/12)^2 (u/12)^2 1
AVE 138 147 340 345
0.9997 6 KID 75 xo s
AVE
0.375 464e-7 PTT 11.4
PPD 330
-9.648e-008 97
148 125
PPN
AUTONOMIC CONTROL PPD POS
0.5333
341
PPA4
346
PP3
351
0.0025
100
VGD 0.013332
120 126
PCP 0 RC1 HM2 0.00042
u^0.625 PP3^0.1 KOD
u^0.625 PA4^0.625
336 98
PPC 331 HMK HPL DHM 96
PLF 90 1 V2D REK
POS 1
139 352
0.07026
SVO PLF 145 0.0003 HPR 0.1 u^2 CHY^2 117 CNA
PPI 152 RCD 2 336b xo 118
32 322 347 NOD
342 1 1 NED 119
SVO 327 323 332 CNA 142.1
328 2 PPO xo s 93 1 NAE
HR 94 95 PG2
CPF 1 0.25 xo s
PGR PGC 99 2130
PRA 0 s 0.4 0.1
0.0003 144
140 116
HM
QLO 11 PIF 142
321 2 57600
324 335 HM 57600 348 upper limit 1
326 325 343 PGP
40 40 NID
VRC PTC
HMD PFI PGH STH 0.1
1 PPI 40 HMD
AU 1
5 143 0.0000058 VIC
PTS PIF
0.5 1 141 DFP 1 VG 89 VPF 114 115
PLF 333 RKC 90 91 92 0.0125
1 1 2-(0.15/u) PPI = 2 - (0.15/VPF) VEC
-1.154e-008 334 39.97
100 344 349 1 57 CHY
VB PRM VTW
DFP HYL VTW
VPF 5 HMD -5.9 3 VP
142 0.01252 VRC
VPF VRC 1 1
1 RC2 24.2
HEART RATE AND STROKE VOLUME 0
0.0125 xo s 2
1 xo s
HPL
1 1 xo s
HPR
1
12
VTS
0.0125

PULMONARY DYNAMICS AND FLUIDS RED CELLS AND VISCOSITY HEART HYPERTROPHY OR DETERIORATION TISSUE FLUIDS, PRESSURES AND GEL ELECTROLYTES AND CELL WATER

Figure 3: Implementation of the model of A. C. Guyton et al in Simulink

This means a high advantage for multidisciplinary cooperation – especially in borderline areas
such as, for example, biomedical systems modelling [9]. An experimental physiologist is not forced to
examine in detail what mathematical relationships are hidden “inside” the simulation chip; however,
based on interconnection of individual simulation chips with each other he or she can understand the
model structure and can verify its behaviour in an appropriate simulation visualization environment.
Hierarchical block-oriented simulation tools have therefore found their significant application in
description of complex regulation systems, which can be seen in physiology. The international project
PHYSIOME is devoted to formalized description of physiological systems; it is the successor of

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GENOME project. GENOME project output was represented by detailed description of the human
genome; PHYSIOME is aimed at formalized description of physiological functions. Computer models
are used as the methodological tool [2, 7].
Several block-oriented simulation tools were designed as part of PHYSIOME project, serving as
a reference database for formalized description of the structure of complex physiological models. They
include JSIM [11] (http://www.physiome.org/model/doku.php) and also the CEllML language
(http://www.cellml.org/). Disciples and followers of Prof. Guyton expanded the original extensive
simulator of the circulatory system (Quantitative Circulatory Physiology [1]) by an integrated
connection of all important physiological systems. The simulator Quantitative Human Physiology is
the most recent result, which describes the currently most complex and most extensive model of
physiological functions. The model can be downloaded from
http://physiology.umc.edu/themodelingworkshop/. In order to express the complex structure of the
model, its authors created a special, block-oriented simulation system, QHP.

4 Causal and Acausal Approach

Block-oriented tools use hierarchical connected blocks. Signals are transmitted through links between
individual blocks; the signals serve to transfer values of individual variables from the output of one
block to inputs of other blocks. Input information is processed in the blocks to output information.
Interconnection of blocks therefore reflects rather the calculation procedure than the very structure of
the modelled reality.
In complex systems, physical reality of the modelled system slowly disappears under the
computation structure thanks to this approach.
That is why in recent times, such tools are starting to be used in modelling complex systems, in
which individual parts of the model are directly described as equations and not as an algorithm of the
solution of such equations. This is the so called declarative (acausal) notation of models, unlike
causal notation in block-oriented languages where the (causal) description of the way of calculating
individual model variables must be (for example, also visually using graphic connection of individual
computational elements) expressed.
Acausal approach is made possible by the new Simulink libraries Simscape and linked domain
libraries SimElectronics, SimHydraulics, SimMechanics etc.
A modern simulation language built directly on acausal notation of models is the programming
language Modelica [4]. Originally, it was developed in Sweden and now is available both as an open-
source version (developed under the auspices of the international organization Modelica Association,
http://www.modelica.org/), and in two commercial implementations. One of them is the commercial
implementation of the company Dynasim AB – purchased recently by the supranational concern
Dassault Systemes (marketed under the name Dymola, currently version 7.1) and the other one is
offered by MathCore (marketed as MathModelica). Dynasim Modelica provides good linkage to
Matlab and Simulink while MathModelica can connect with the Mathematica environment supplied by
the company Wolfram.
Modelica utilizes mutually connected components, which represent instances of individual
classes. Unlike implementation of classes in other object-oriented languages (such as jw C#, Java etc.),
classes in Modelica have a special section in addition, in which equations are defined. The equations
do not express assignment (i.e. saving of the calculation result of an assigned statement into a given
variable) but a definition of relationships among variables (as is the custom in mathematics and
physics).
In Modelica, components (instances of classes) can be connected through exactly defined
interfaces – connectors. Connectors are instances of connector classes in which variables used for
connection are defined. Connectors falling in the same connector classes can be connected (while in
these classes, variables of equivalent types can be connected). In other words – in the connection, the
type of plugs must correspond exactly to the socket types.

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The important thing is that by connecting the components, connection of sets of equations in
individual components with each other occurs actually. in cases an identical variable is defined in the
connector of connected components (and if it does not represent the flow – see further), by
establishing the connection it is defined that the value of this variable should be the same in all
components. When the variable is a part of equations in the connected components, by means of
connection we also define interconnection of the equations in which the given variable is found. At the
point where multiple components are connected, values of the variables connected through the
common point must be the same (similarly to voltage on the common terminal in electric circuits,
which must correspond to Kirchhoff’s first law). And not only that. In the connector, it is possible to
define that some connected variables shall represent the flow – in such a case, this means that values
of all variables marked in this way shall be set in all components interconnected at the same point to
such a value so that their algebraic sum is equal to zero (similarly to the sum of currents on the
common terminal in electric circuits, which must correspond to Kirchhoff’s second law).
If a variable marked in this way is a part of equations in interconnected components, another
equation is thus added to the connected set of equations, which defines the requirement of the zero
value of the algebraic sum of this variable’s values).
By means of connecting Modelica components, we thus do not define the computation
procedure but the modelled reality. The way of solving the equations is then “left up to the
machines”.

5 Generalized System Properties

e

e=Rf C
q=Ce

p R
q
p=Lf

L
f
Figure 4: Relationships among generalized system properties:
 e means generalized effort – matched by force in mechanics, voltage in electric
diagrams, pressure in hydraulics etc.
 f is generalized flow – matched by velocity in mechanics, current in electric
diagrams, flow in hydraulics, temperature flow in thermodynamics etc.
 q is generalized accumulation or deflection, represented by the generalized flow
integral. It is matched, for example, by spring stretching in mechanics, liquid
volume in hydraulics, charge in electric diagram, accumulated heat in
thermodynamics etc.
 p represents generalized inertance – generalized effort integral, representing
kinetic energy; matched by the flow velocity change proportional to pressure
difference (inertance of flow) in hydraulics, potential needed to change electric
current (induction) in electric circuits etc.
 R, C and L represent constants of proportionality among individual generalized
system properties. Matched, for example, by resistance, capacitance or mass.

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Depiction of the model in the acausal simulation environment thus resembles the physical reality of
the modelled world more than classical interconnected block schemata in Simulink or QHP. This is
related to generalized system properties of the real world (Fig. 4) in which generalized efforts (to
which the force, pressure, voltage etc. correspond in real world) and generalized flow (to which the
current, flow etc. correspond in real world) play an important role.
Provided that the reality is depicted in Modelica by means of connected components, then as for
flow variables, the value at the connection point must correspond to Kirchhoff’s second law (the
current cannot accumulate or be lost at the connection point), and equality must hold true for other
variables at the common connecting point (according to Kirchhoff’s first law).
In Modelica, there is a standard library of varied classes to model electric, mechanical,
hydraulic objects of the real world. Mathworks, too, has responded to development trends of acausal
modelling by creating Simscape toolboxes and linked application libraries to model electric circuits,
mechanical and hydraulic systems.
We shall illustrate the difference between modelling in block-oriented simulation tools and in
Modelica on two examples of modelling physiological reality: On the model of simple mechanics of
pulmonary ventilation and on implementation of a classical model of cellular membrane of the
neurone pursuant to Hodgkin-Huxley [6].

6 Pulmonary Ventilation Mechanics Model

Let us consider a simple model of pulmonary mechanics, shown schematically in Fig. 5. Upon
applying significant simplification, the lungs can be viewed as three bags connected using two tubes.
The lungs are connected to the ventilator of artificial pulmonary ventilation, which blows air into the
lungs periodically under the pressure PAO. P0 is the pressure of ambient atmosphere. The air flow Q
flows through upper respiratory tract whose resistance is RC. From the upper respiratory tract, air
struggles through the lower respiratory tract into alveoli. The resistance of the lower respiratory tract is
RP, the pressure in central parts of the respiratory tract (at the borderline of the upper and lower
respiratory tract) is PAW, pressure in alveoli is PA.

CW
CL
RC RP
PAO Q PAW QA PA PPL P0
Q-QA
P0
CS
Q QA
PAW
PAO RC RP PA

CL
Q-QA CS
PPL
CW
P0

Figure 5: Simple model of pulmonary mechanics (hydraulic and electric similarity)

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The air expands pulmonary alveoli whose elasticity is CL (as total pulmonary elasticity). The
interpleural cavity is found between the lungs and the chest. The pressure in the chest is PPL. In
artificial pulmonary ventilation in which case the air is blown into the lungs under pressure, the chest
must expand in addition – chest elasticity is CW. A small part of air, which does not reach all the way
to the alveoli only expands the respiratory tract – its elasticity is CS (the so called dead space
breathing).
Now the equations can be set up. According to Ohm’s law the following must hold true:

PAW  PA  RP QA
PAO  PAW  RC Q (1)

The relationship between elasticity, pressure gradient and volume (expressed as the flow integral) is
expressed by the equations:

1
CL 
PA  PPL  QA dt

1
CW 
PPL  P 0  QA dt

1
Q  QA  dt
CS 
PAW  P 0 
(2)

According to the generalized Kirchhoff’s law, the sum of all pressures (voltages) along a closed loop
must be equal to zero, i.e. the following must hold true in the loop along the PAW node and along the
PA0 node:

( PAW  PA)  ( PA  PPL)  ( PPL  P0)  ( P0  PAW )  0

( PAO  PAW )  ( PAW  P0)  ( PO  PAO )  0

And upon substitution using Ohm’s law and elasticity equations:

  1 1  1
 RP QA  

 
 QA dt 
 CL CW  CS 
(Q  QA) dt  0

Q RC  1 (Q  QA) dt  ( P0  PAO)  0
 CS  (3)

6.1 Implementation of the Pulmonary Ventilation Mechanics Model in Simulink

When setting up the model in Simulink, the computation procedure from input variables to the output
ones must be exactly defined. If we want to calculate the reaction of air flow to/from the lungs (Q) to
the input – i.e. pressure changes at the initial point of the respiratory tract (PAO) caused by the
artificial pulmonary ventilation apparatus – the Simulink model shall be similar to that in Fig. 6.
The Simulink model can also be expressed in a simpler form. At first, from Equation (3) we
shall derive the differential equation (input variable PAO, output variable Q):

d 2 PAO 1 dPAO d 2Q  1 RC  dQ 1  1 1 
  RC        Q
dt 2 RP CT dt dt 2  CS RP CT  dt RP CS  CL CW  (4)

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Mux respm2.mat

Mux To File

1/s
Integrator Volume vs time

Pao vs time Q vs time

Pao Q
1 QA
Ventilator 1/s
Sum 1/Rc
Integrator1
Sum1

Qs

-K- du/dt
Paw dPaw/dt
Memory CS

PA
0.5

Rp 1/0.2

PAW 1/CL

Sum3 Sum2
1/0.2

1/Cw

Figure 6: Implementation of the model in Simulink according to Equations (3)

Upon entering the following numerical parameters of resistances (in the units: cm H2O/L/sec) and
elasticities (in the units: L/cmH2O) [8]:
RC  1; RP  0.5; CL  0.2; CW  0.2; CS  0.005
Equation (4) becomes simplified:

d 2 PAO dPAO d 2 Q dQ
2
 420  2  620  4000 Q
dt dt dt dt (5)
Upon Laplace transform of Equation (5) we obtain:

Q( s) s 2  420s

PAO( s ) s 2  620s  4000 (6)
This gives us the possibility to simplify the Simulink model (Fig. 7):

PAO vs time

Mux respm1.mat

Mux To File

1/s
s2 +420s
Integrator
PAO s2 +620s+4000 Volume vs time
Ventilator

Respiratory Mechanics
Q
Q vs time

Figure 7: Implementation of the model in Simulink using Laplace transform according to

Equation (6)

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However, when the parameter values change, the transformation function (6) must be
recalculated and the Simulink model changes. Now let us make the model slightly more complicated
by taking into account inertia of air in the upper respiratory tract (Fig. 8).
Now we shall moreover include the inertial element LC=0.01 cm H2O s2 L-1:
P
LC 
dQ
dt
dQ
where P is the pressure gradient and dt is flow acceleration, or:
dQ
P  LC
dt (7)

CW
CL
RC LC RP
PAO Q PAW QA PA PPL P0
Q-QA
P0
CS
Q QA
PAW
RC=1 RP=0,5 PA
LC=0,01
CL=0,2
Q-QA CS=0,005
PPL
CW=0,2
P0

Figure 8: Simple model of pulmonary mechanics taking inertia into account (hydraulic and electric
similarity)
Then instead of the Set of Equations (3) we shall obtain:
 dQA  1 1  1
 RP dt   CL  CW  QA  CS Q  QA  0
 
 2
 RC dQ  LC d Q  1 Q  QA  dP 0  dPAO  0
 dt dt 2 CS dt dt (8)
And instead of Equation (5):

d 2 PAO dPAO d 3Q d 2Q dQ
2
 420  0,01 3
 5, 2 2
 620  4000 Q
dt dt dt dt dt (9)
And finally, upon Laplace transform:

Q( s ) s 2  420s

PAO( s ) 0,01s 3  5,2s 2  620s  4000
(10)
The Simulink model shall change (Fig. 9):

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PAO vs time

Mux respm1.mat

Mux To File

1/s
s 2 +420s
Integrator
PAO 0.01s 3 +5.2s 2 +620s+4000 Volume vs time
Ventilator

Respiratory Mechanics
Q
Flow vs time

Figure 9: Implementation of the model in Simulink using Laplace transform according to

Equation (10)
Thanks to the fact that the computational direction must be always taken into account in
Simulink, the very Simulink diagram is quite distant from the actual physical reality of the system
described. Even a small change in the model, such as addition of the inertial element, causes the need
of careful calculation and change of the model structure. An essential change of the model occurs also
in the case that spontaneous breathing is considered instead of artificial pulmonary ventilation. The
model input shall not be represented by the pressure PAO created by the artificial pulmonary
ventilation respirator but, for example, the thoracic wall elasticity CW (function of the breathing
muscles can be modelled by cyclic change of elasticity).
Connection of blocks in Simulink reflects rather the calculation procedure and not the
modelled reality structure.
6.2 Implementation of the Pulmonary Ventilation Mechanics Model in Modelica
In Modelica (or even in the Simulink library Simscape), the situation is different (source codes of the
example can be downloaded from http://patf-biokyb.lf1.cuni.cz/wiki/objekty_2008). Instead of blocks,
Modelica operates with connected components, which represent instances of individual classes, in
Modelica moreover equipped with a special section in which equations are defined. By connecting
Modelica components, not the calculation procedure but the modelled reality is defined. The way of
solving the equations is thus “left up to the machines”.
The model representation in Modelica thus resembles rather the physical reality of the modelled
world than connected block diagrams in Simulink. The simple ventilation mechanics model according
to Fig. 3 can be expressed in a very straightforward way in Modelica. We shall make use of the fact
that Modelica includes libraries of various classes to model electric, mechanical and hydraulic objects
of the real world. Representation of the relationships of resistance, pressure gradient and flow
according to Equation (1) and relationships of elasticity, pressure and flow according to Equation (2)
thus takes the following form in Modelica:
Making the model more complex by adding the inertial element - pursuant to Equation (7) and
Fig. 7 is easy (see Figure 11).
In the given case, we have used visual components of electric circuits for quick setting up of the
model; however, nothing prevents us from creating a different shape of icons representing individual
resistance, capacity and inertial elements in the lungs. These are far more than picture icons. Modelica
is an object language and there is no obstruction in creating a special class using which it is possible,
for example, to model oxygen and carbon dioxide flows (considering the oxygen bond to hemoglobin,
CO2 conversion to bicarbonate, acidobasic equilibrium effect on blood gases transport etc.).
Formation of the physiological relationships library is one of our future aims. We are planning
to transfer (and extend further in Modelica) our Simulink library of physiological relationships,
Physiology Blockset (www.physiome.cz/simchips).
In respect of the fact that there are numerous relationships in physiological models (leading to
solution of implicit equations in Simulink), acausal description of modelled relationships applied in
Modelica provides a great advantage. Acausal description describes much better the essence of

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modelled reality and the simulation models are much more legible, and thus much less prone to
mistakes, as well. Modelica is therefore a very suitable environment to model physiological systems.

Figure 10: Simple model of pulmonary mechanics according to Fig. 5 in Modelica

Figure 11: Modified model of pulmonary mechanics upon adding the inertia element in
Modelica

7 Excitable Membrane of the Neuron according to Hodgkin and Huxley

In 1963, Alan Lloyd Hodgkin and Andrew Huxley were awarded the Nobel Prize for physiology and
the mathematical model of the action membrane potential. Precisely their article [6] has become the
foundation of many models describing the membrane potentials behaviour in varied cell types.

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Primarily, the model provides explanation of the nervous impulse spreading by depolarization of the
cellular membrane using the connection of two physical domains – the electric and chemical one.
Thanks to the conductivity study of membrane channels, in dependence on time and current membrane
voltage, the model describes the course of electric current that is formed by the flow of sodium and
potassium ions through the membrane.
This electric current subsequently affects the current electric voltage. At rest, the inside of the
cellular membrane has a negative charge. Proteins with the negative charge cannot pass through the
cellular membrane and remain on the inside of the membrane. Potassium and sodium ions are (thanks
to the sodium-potassium pump) distributed non-uniformly between the cell and its surroundings –
inside the cell, there is a high potassium concentration and low sodium concentration in respect of the
surroundings of the cell. Transfer of the ions can take place only through ionic channels. The
concentration and electric gradient has an impact on the ions movement – at rest, the cellular
membrane has a negative charge and sodium concentration outside the cell is much higher than inside.
Sodium is pushed into the cell both by the electric and concentration gradient. As for potassium, both
gradients act against each other; however, the concentration gradient prevails (and potassium thus
shows the tendency to leave the cell).
Nernst equation describes how the chemical and concentration gradients can be compared.
Differences in concentrations are transformed using this equation to the membrane voltage needed to
maintain their different concentrations on both sides of the membrane. These concentration differences
in the model form a kind of power supplies for specific ions. When the difference of the Nernst minus
current voltage for the cation is greater than zero, the cation is pushed into the cell. The sodium-
potassium pump (Na-K-ATPasis) takes care, from the long-term point of view, of maintaining the
concentration differences of potassium and sodium in the cell and outside the cell; this pump keeps
pumping sodium from the cell and potassium into the cell constantly. However, its functionality and
change of sodium and potassium concentrations is disregarded in this model and the concentrations are
considered constant, and the concentration differences (thanks to the Nernst equation) form a power
supply of +40 mV for sodium and -87 mV for potassium.
Charge accumulation on the membrane is a typical example of a capacitor, where the non-
conductive cellular membrane acts as a medium, which separates two charged surfaces.
However, sodium and potassium flows through appropriate channels depend on the channels
permeability (much lower for sodium than for potassium at rest). The channels permeability depends
on the membrane voltage. If the membrane voltage rises from the rest (negative) voltage to a certain
boundary value, sodium channels start to open for a very short moment and the current of sodium ions
breaks into the cell and “discharges the negatively charged membrane capacitor” – and even charges it
to the opposite (positive) value – we speak of depolarization and occurrence of the action potential. At
the same time, sodium channels start to close again due to the change of the voltage (and thus make
sure that the concentration of ions in the cell virtually does not change). At the same time,
permeability for potassium channels changes, potassium starts to leave the cell more rapidly (and the
current of positive potassium ions flowing out of the cell recharges the “membrane capacitor” again to
the rest negative value).
7.1 Implementation of the Model according to Hodgkin and Huxley in Modelica
The model implementation in Modelica corresponds to an electric diagram (Fig. 12). Source codes can
be downloaded from http://patf-biokyb.lf1.cuni.cz/wiki/objekty_2008. Special components are
represented by membrane channels for sodium (or potassium, respectively). These behave as a power
supply with changing inner resistance. Its constant voltage is given by the chemical gradient of sodium
(or potassium, respectively) according to the Nernst equation, while their inner resistance corresponds
to the open state (permeability) of the channels. Only potassium cations can pass through potassium
channels and only sodium ones through sodium channels. Other electrically charged atoms that can
pass through the membrane are implemented using a constant power supply and constant resistance,
not changing in dependence on time and voltage.

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Figure 12: Diagram of the Hodgkin-Huxley’s model in Modelica (in the Dymola environment)

Figure 13: Model simulation outputs. Time units are given in ms.
 capacitor.v is current voltage of the cellular membrane in mV
 k_channels.G is electric conductivity for potassium channels
 na_channels.G is electric conductivity for sodium channels
 na_channels.R is electric resistance for sodium channels = 1/(1000*G)
When implementing the model in Modelica, basic electric components from the standard library
can be used: We shall thus use models of a constant voltage supply, a capacitor. Afterwards, it is only
necessary to define the membrane channel classes and connect all elements visually.
Membrane channels can be modelled as special components. Using the empirically confirmed
relationships (equations) from the Hodgkin’s and Huxley’s article [6], we shall create a new type of an
electric component describing the behaviour of membrane channels as constant voltage sources

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(pursuant to the Nernst equation) with changing inner resistance dependent on the membrane voltage.
And finally, it only remains to connect all the elements visually.
Upon running the simulation of the entire circuit actuated by electric current pulses, the required
course of the action potential and conductivity of the channels during an impulse is obtained (Fig. 13).
7.2 Implementation of the Model according to Hodgkin and Huxley in Simulink
In implementation of the model in Simulink, the model structure corresponds more to the calculation
process than the physical structure of the modelled system. Comparison of the model implementation
in Simulink (Fig. 14) and Modelica (Figs. 12 and 13) is very eloquent.

Figure 14: The Hodgkin-Huxley’s model [6] can also be implemented using the block-oriented
Matlab/Simulink environment; however, this environment remains tied to the calculation procedure.

8 Conclusion
New technologies provide new opportunities and challenges in simulation models creation. One of
such technologies is represented by acausal simulation environments, such as the library Simscape in
Simulink and especially the new object simulation language Modelica, which shall make modelling of
complicated and complex systems such as physiological systems considerably easier.
In respect of the fact that numerous relationships are found in physiological models (leading to
solution of implicit equations in block-oriented languages), the acausal description of modelled
relationships used in Modelica (but also in Simscape) provides a great advantage. Acausal description
captures the essence of the modelled reality much better, and the simulation models are much more
legible and thus also less prone to mistakes. Acausal simulation tools therefore represent a very
suitable environment in physiological systems modelling.
References

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Acknowledgments
This work has been supported by research MSM 0021620806 and by the aid grant MŠMT 2C06031,
and by Creative Connections s.r.o.

Jiří Kofránek, M.D., Ph.D.

Laboratory of Biocybernetics,
Institute of Pathological Physiology, First Faculty of Medicine,
Charles University in Prague
U Nemocnice 5
128 53 Praha 2
e-mail: kofranek@gmail.com
Tel.: 777 68 68 68

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