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Statická analýza fyziologických systémů Obecné systémové vlastnosti

Statická analýza fyziologických systémů

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Statická analýza fyziologických systémů. Obecné systémové vlastnosti. Studijní materiály. Studijní materiály. Chapter 2. Mathematical Modeling. Chapter 3. Static analysis of Physiological Systems. Modelování a simulace. Modelování. Blokové modelovací jazyky ( např. Simulink , ...). - PowerPoint PPT Presentation

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Statická analýza fyziologických systémů

Obecné systémové vlastnosti

Studijní materiály

Studijní materiály

Chapter 2. Mathematical Modeling

Chapter 3. Static analysis of Physiological Systems

Proprietární kód klasických programovacích jazyků (např. Ada, Fortran, C,...)

Proprietární kód

Definice systému

Dekompozice systému

Modelování subsystémů Odvození kauzality výpočtu

(manuální odvození

vstupně/výstupních vztahů) Implementace Simulace

Modelování

Blokové modelovací jazyky

Blokové modelovací jazyky (např. Simulink, ...)

……

Vstupy do bloku jsou vnější vstupy nebo výstupy z jiných bloků

Výstupy z bloku jsou vnější výstupy nebo vstupy do dalších bloků

Modelování a simulace

Formalizace (modelování)

Počítačová simulace

Softwarové nástroje pro tvorbu modelů

VECml

DistNaFlow

200

Venous conductance[ml/min/torr]

7

Vena renalis pressure [torr]

-C-

Totasl body water content [ml]

Scope1 Scope

0

Renal artery pressure clamp

drop [torr]

0.07

Plasma protein cnoncentration

[g/ml]

6.25

Normal proximal tubule conductance

[ml/min/torr]

1

Normal macula densafeedback signal

16

Normal glomerular fi ltration coeffitient

[ml/min/torr]

0.5

Normal distalfractional reabsorbtion for Na

25

Normal conductanceof Efferent artery

[ml/min/torr]

30

Normal conductanceof Afferent artery

[ml/min/torr]

0.93

Normal collecting duct fractional reabsorbtion for Na

0.8

Normal Na proximal fractional reabsorbtion

0.125

NaDiet [mmol/min]

MDNaFlow

LogA2

MDNorm

MDSig

M A C U L A D E N S A

INPUTS :MDNaFlow - Macula densa sodium flow [mmol/min]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]MDNorm - Normal macula densa feedback signal [ x Normal]

OUTPUT :MDSig - Macula densa feedback signal [ x Normal]

Macula densa feedback signal calculation based on macula densa sodium flow and angiotensin concentration

0.44

Hematocrit

NaDiet

NaUrine

VECml

ZNAE

PNa

S I M P L E S O D I U M B A L A N C E

INPUTS :NaDIet - Dietary sodium intake [mmol/min]

NaUrine - Sodium urine outflow [mmol/min]VECml - Extracellular fluid volume [ml]

OUTPUT :ZNAE - ECF sodium content [mmol]

PNa - Plasma sodium concentration [mmol/ml]

Extracellular sodium quantity is the integral over time dietary sodium intake minus urinary sodium loss

15000

Extracellular fluid volume[mmol/min]1

0.5086

1.855

18.84

1.275

6.846

0.144

2159

125.1

3.648

14.37

0.7975

0.1248

0.9999

99.65

1182

662.1

29.83

25.1

99.651.006

0.9418

1.792

0.9304

1.668

1

Converting Enzyme Activity

ZNAE

LogA2

APNorm

AP

A R T E R I A L P R E S S U R E

INPUTS :ZNAE - ECF sodium content [mmol]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]APNorm - Normal value of arterial pressurel [torr]

OUTPUT :AP Arterial pressure [torr]

Control of arterial pressure by angiotensin and extracellular sodium content

RAP Af f My o1

M Y O G E N I C R E S P O N S E

INPUT :RAP - Renal artery pressure [torr]

OUTPUT :AffC - Myogenic effect [ x Normal]

Calculation of the myogenic response to changes in renal perfusion pressure(afferent conductance responds to changes in perfusion pressure,

with pressure increases causing vasoconstriction)

Af f C

Ef f C

RenVenC

AP

VP

Hct

Clamp

RAP

RBF

RPF

R E N A L P E R F U S I O N

INPUTS :AffC - Afferent artery conductance [ml/min/torr]EffC Efferent artery conductance [ml/min/torr]

RenVenC - Renal venous conductance [ml/min/torr]AP - Arterial pressure [torr]

VP - Vena renalis pressure [torr]Hct - Hematocrit [relative number]

Clamp - Renal artery pressure drop caused by renal artery clamp [torr]

OUTPUTS :RAP - Renal artery pressure [torr]

RBF - Renal blood flow rate[ml/min]RPF - Renal plasma flow rate[ml/min]

Calculation of renal artery pressure and renal blood flow rate

PNa

GFR

LogA2

PrxFNaNorm

MDNaFlow

PdxNaReab

PrxFNa

N A T R I U M - P R O X I M A L T U B U L E

INPUTS :PNa - Plasma sodium concentration [mmol/ml]

GFR - GLomerulal fi ltration rate [ml/min]LogA2 - Logarithm of plasma angiotensin concentration

[pg/ml]PrxFNaNorm - Normal value of sodium proximal

fractional reabsorbtion [relative number]

OUTPUTS :MDNaFlow - Sodium outflow [mmol/min]

PdxNaReab - Proximal sodium reabsorbrtion [mmol/l]PrxFNa - Proximal fractional sodium reabsorbtion

[relative number]

Calculation of proximal tubule sodium reabsorbtion

MDSig

VECml

PRA

R E N I N

INPUTS :MDSig - Macula densa feedback signal [ x Normal]

VECml - Ectracellular fluid volume

OUTPUT :PRA - Plasma renin activity [ Units/ml]

Calculation of plasma renin activity

PRA

CEAct

A2Inf

A2

logA2

A N G I O T E N S I N

INPUTS :PRA - Plasma renin activity [ Units/ml]

CEAct - Converting enzyme activity [x Normal]A2Inf Angiotensin 2 infusion rate [nG/min]

OUTPUTS :A2 - Plasma angiotensin 2 concentration [ pG/ml]

LogA2 - logarithm of plasma angiotensin concentration [ pG/ml])

Calculation of plasma angiotensin concentration and logarithm of plasma angiotensin concentration (most of the action of angiotensin are logarithmic in nature: concentration changes at higher concentrations produce less of an

effect than changes of the same size at lower concentrations)

logA2

AldoInf

VTWml

Aldo

A L D O S T E R O N E

INPUTS :logA2 - Logarithm of plasma angiotensin concentration [pG/ml]

AldoInf - Aldosterone infusion rate [nG/min]VTW - Total body water content [ml]

OUTPUT :Aldo - Plasma aldosterone concentration [ nG/dl]

Calculation of plasma aldosterone concentration

RAP

Af f C

TubC

RBF

RPF

APr

GKf

GFR

G L O M E R U L A R F I L T R A T I O N

INPUTS :RAP - Renal artery pressure[torr]

Affc - Afferent artery conductance [mll/min/torr]TubC - Proximal tubule conductaqnce [ml/min/torr]

RBF - Renal blood flow [ml/min]RPF - Renal plasma flow

APr - Plasma protein concentration (in afferent artery) [g/ml]GKf - Glomerular fi ltration coeffitient [ml/min/torr]

OUTPUT :GFR - Glomerular fi ltration rate [ml/min]

Calculation of glomerular fi ltration rate1

MDNaFlow

Aldo

DisFNaNorm

DisNaFlow

DisNaReab

DisFNa

N A T R I U M - D I S T A L T U B U L E

INPUTS :MDNaFlow - Sodium inflow [mmol/min]Aldo - Plasma aldosterone level [pg/ml]

DisFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :DisNaFlow - Sodium outflow [mmol/min]

DisNaReab - Distal sodium reabsorbrtion [mmol/min]DisFNa - Distal fractional sodium reabsorbtion

[relative number]

Calculation of distal tubule sodium reabsorbtion

DisNaFlow

CDFNaNorm

NaUrine

CDNaReab

CDFNa

N A T R I U M - C O L L E C T I N G D U C T

INPUTS :DisNaFlow - Sodium inflow [mmol/min]

CDFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :NaUrine - Sodium urine outflow [mmol/min]

CDNaReab - Collecting duct sodium reabsorbrtion [mmol/min]

CDFNa - Collecting duct fractional sodium reabsorbtion [relative number]

Calculation of collecing duct sodium reabsorbtion

logA2

MDSig

Ef f Norm

Ef f C

E F F E R E N T A R T E R Y

INPUTS :logA2 - logarithm of angiotensin concentration

MDSig - Macula densa feedback signal [ x Normal]EffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :EffC - Vascular conductance [ml/min/torr]

Calculates conductance of efferent artery

Af f My o

MDSig

Af f Norm

Af f C

A F F E R E N T A R T E R Y

INPUTS :AffMyo - Myogenic effect [ x Nomal]

MDSig - Macula densa feedback signal [ x Normal]AffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :AffC - Vascular conductance [ml/min/torr]

Calculates conductance of afferent artery

0

Angiotensin Infusion Rate

0

Aldosteron Infusion Rate

100

APNorm [torr]

Ef f C

AP

AP

Aldo

LogA2

LogA2

LogA2

Matlab/Simulink

Softwarové nástroje pro tvorbu modelů

VECml

DistNaFlow

200

Venous conductance[ml/min/torr]

7

Vena renalis pressure [torr]

-C-

Totasl body water content [ml]

Scope1 Scope

0

Renal artery pressure clamp

drop [torr]

0.07

Plasma protein cnoncentration

[g/ml]

6.25

Normal proximal tubule conductance

[ml/min/torr]

1

Normal macula densafeedback signal

16

Normal glomerular filtration coeffitient

[ml/min/torr]

0.5

Normal distalfractional reabsorbtion for Na

25

Normal conductanceof Efferent artery

[ml/min/torr]

30

Normal conductanceof Afferent artery

[ml/min/torr]

0.93

Normal collecting duct fractional reabsorbtion for Na

0.8

Normal Na proximal fractional reabsorbtion

0.125

NaDiet [mmol/min]

MDNaFlow

LogA2

MDNorm

MDSig

M A C U L A D E N S A

INPUTS :MDNaFlow - Macula densa sodium flow [mmol/min]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]MDNorm - Normal macula densa feedback signal [ x Normal]

OUTPUT :MDSig - Macula densa feedback signal [ x Normal]

Macula densa feedback signal calculation based on macula densa sodium flow and angiotensin concentration

0.44

Hematocrit

NaDiet

NaUrine

VECml

ZNAE

PNa

S I M P L E S O D I U M B A L A N C E

INPUTS :NaDIet - Dietary sodium intake [mmol/min]

NaUrine - Sodium urine outflow [mmol/min]VECml - Extracellular fluid volume [ml]

OUTPUT :ZNAE - ECF sodium content [mmol]

PNa - Plasma sodium concentration [mmol/ml]

Extracellular sodium quantity is the integral over time dietary sodium intake minus urinary sodium loss

15000

Extracellular fluid volume[mmol/min]1

0.5086

1.855

18.84

1.275

6.846

0.144

2159

125.1

3.648

14.37

0.7975

0.1248

0.9999

99.65

1182

662.1

29.83

25.1

99.651.006

0.9418

1.792

0.9304

1.668

1

Converting Enzyme Activity

ZNAE

LogA2

APNorm

AP

A R T E R I A L P R E S S U R E

INPUTS :ZNAE - ECF sodium content [mmol]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]APNorm - Normal value of arterial pressurel [torr]

OUTPUT :AP Arterial pressure [torr]

Control of arterial pressure by angiotensin and extracellular sodium content

RAP Af f My o1

M Y O G E N I C R E S P O N S E

INPUT :RAP - Renal artery pressure [torr]

OUTPUT :AffC - Myogenic effect [ x Normal]

Calculation of the myogenic response to changes in renal perfusion pressure(afferent conductance responds to changes in perfusion pressure,

with pressure increases causing vasoconstriction)

Af f C

Ef f C

RenVenC

AP

VP

Hct

Clamp

RAP

RBF

RPF

R E N A L P E R F U S I O N

INPUTS :AffC - Afferent artery conductance [ml/min/torr]EffC Efferent artery conductance [ml/min/torr]

RenVenC - Renal venous conductance [ml/min/torr]AP - Arterial pressure [torr]

VP - Vena renalis pressure [torr]Hct - Hematocrit [relative number]

Clamp - Renal artery pressure drop caused by renal artery clamp [torr]

OUTPUTS :RAP - Renal artery pressure [torr]

RBF - Renal blood flow rate[ml/min]RPF - Renal plasma flow rate[ml/min]

Calculation of renal artery pressure and renal blood flow rate

PNa

GFR

LogA2

PrxFNaNorm

MDNaFlow

PdxNaReab

PrxFNa

N A T R I U M - P R O X I M A L T U B U L E

INPUTS :PNa - Plasma sodium concentration [mmol/ml]

GFR - GLomerulal filtration rate [ml/min]LogA2 - Logarithm of plasma angiotensin concentration

[pg/ml]PrxFNaNorm - Normal value of sodium proximal

fractional reabsorbtion [relative number]

OUTPUTS :MDNaFlow - Sodium outflow [mmol/min]

PdxNaReab - Proximal sodium reabsorbrtion [mmol/l]PrxFNa - Proximal fractional sodium reabsorbtion

[relative number]

Calculation of proximal tubule sodium reabsorbtion

MDSig

VECml

PRA

R E N I N

INPUTS :MDSig - Macula densa feedback signal [ x Normal]

VECml - Ectracellular fluid volume

OUTPUT :PRA - Plasma renin activity [ Units/ml]

Calculation of plasma renin activity

PRA

CEAct

A2Inf

A2

logA2

A N G I O T E N S I N

INPUTS :PRA - Plasma renin activity [ Units/ml]

CEAct - Converting enzyme activity [x Normal]A2Inf Angiotensin 2 infusion rate [nG/min]

OUTPUTS :A2 - Plasma angiotensin 2 concentration [ pG/ml]

LogA2 - logarithm of plasma angiotensin concentration [ pG/ml])

Calculation of plasma angiotensin concentration and logarithm of plasma angiotensin concentration (most of the action of angiotensin are logarithmic in nature: concentration changes at higher concentrations produce less of an

effect than changes of the same size at lower concentrations)

logA2

AldoInf

VTWml

Aldo

A L D O S T E R O N E

INPUTS :logA2 - Logarithm of plasma angiotensin concentration [pG/ml]

AldoInf - Aldosterone infusion rate [nG/min]VTW - Total body water content [ml]

OUTPUT :Aldo - Plasma aldosterone concentration [ nG/dl]

Calculation of plasma aldosterone concentration

RAP

Af f C

TubC

RBF

RPF

APr

GKf

GFR

G L O M E R U L A R F I L T R A T I O N

INPUTS :RAP - Renal artery pressure[torr]

Affc - Afferent artery conductance [mll/min/torr]TubC - Proximal tubule conductaqnce [ml/min/torr]

RBF - Renal blood flow [ml/min]RPF - Renal plasma flow

APr - Plasma protein concentration (in afferent artery) [g/ml]GKf - Glomerular filtration coeffitient [ml/min/torr]

OUTPUT :GFR - Glomerular filtration rate [ml/min]

Calculation of glomerular filtration rate1

MDNaFlow

Aldo

DisFNaNorm

DisNaFlow

DisNaReab

DisFNa

N A T R I U M - D I S T A L T U B U L E

INPUTS :MDNaFlow - Sodium inflow [mmol/min]Aldo - Plasma aldosterone level [pg/ml]

DisFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :DisNaFlow - Sodium outflow [mmol/min]

DisNaReab - Distal sodium reabsorbrtion [mmol/min]DisFNa - Distal fractional sodium reabsorbtion

[relative number]

Calculation of distal tubule sodium reabsorbtion

DisNaFlow

CDFNaNorm

NaUrine

CDNaReab

CDFNa

N A T R I U M - C O L L E C T I N G D U C T

INPUTS :DisNaFlow - Sodium inflow [mmol/min]

CDFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :NaUrine - Sodium urine outflow [mmol/min]

CDNaReab - Collecting duct sodium reabsorbrtion [mmol/min]

CDFNa - Collecting duct fractional sodium reabsorbtion [relative number]

Calculation of collecing duct sodium reabsorbtion

logA2

MDSig

Ef f Norm

Ef f C

E F F E R E N T A R T E R Y

INPUTS :logA2 - logarithm of angiotensin concentration

MDSig - Macula densa feedback signal [ x Normal]EffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :EffC - Vascular conductance [ml/min/torr]

Calculates conductance of efferent artery

Af f My o

MDSig

Af f Norm

Af f C

A F F E R E N T A R T E R Y

INPUTS :AffMyo - Myogenic effect [ x Nomal]

MDSig - Macula densa feedback signal [ x Normal]AffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :AffC - Vascular conductance [ml/min/torr]

Calculates conductance of afferent artery

0

Angiotensin Infusion Rate

0

Aldosteron Infusion Rate

100

APNorm [torr]

Ef f C

AP

AP

Aldo

LogA2

LogA2

LogA2

Matlab/Simulink

Softwarové nástroje pro tvorbu modelů

VECml

DistNaFlow

200

Venous conductance[ml/min/torr]

7

Vena renalis pressure [torr]

-C-

Totasl body water content [ml]

Scope1 Scope

0

Renal artery pressure clamp

drop [torr]

0.07

Plasma protein cnoncentration

[g/ml]

6.25

Normal proximal tubule conductance

[ml/min/torr]

1

Normal macula densafeedback signal

16

Normal glomerular filtration coeffitient

[ml/min/torr]

0.5

Normal distalfractional reabsorbtion for Na

25

Normal conductanceof Efferent artery

[ml/min/torr]

30

Normal conductanceof Afferent artery

[ml/min/torr]

0.93

Normal collecting duct fractional reabsorbtion for Na

0.8

Normal Na proximal fractional reabsorbtion

0.125

NaDiet [mmol/min]

MDNaFlow

LogA2

MDNorm

MDSig

M A C U L A D E N S A

INPUTS :MDNaFlow - Macula densa sodium flow [mmol/min]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]MDNorm - Normal macula densa feedback signal [ x Normal]

OUTPUT :MDSig - Macula densa feedback signal [ x Normal]

Macula densa feedback signal calculation based on macula densa sodium flow and angiotensin concentration

0.44

Hematocrit

NaDiet

NaUrine

VECml

ZNAE

PNa

S I M P L E S O D I U M B A L A N C E

INPUTS :NaDIet - Dietary sodium intake [mmol/min]

NaUrine - Sodium urine outflow [mmol/min]VECml - Extracellular fluid volume [ml]

OUTPUT :ZNAE - ECF sodium content [mmol]

PNa - Plasma sodium concentration [mmol/ml]

Extracellular sodium quantity is the integral over time dietary sodium intake minus urinary sodium loss

15000

Extracellular fluid volume[mmol/min]1

0.5086

1.855

18.84

1.275

6.846

0.144

2159

125.1

3.648

14.37

0.7975

0.1248

0.9999

99.65

1182

662.1

29.83

25.1

99.651.006

0.9418

1.792

0.9304

1.668

1

Converting Enzyme Activity

ZNAE

LogA2

APNorm

AP

A R T E R I A L P R E S S U R E

INPUTS :ZNAE - ECF sodium content [mmol]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]APNorm - Normal value of arterial pressurel [torr]

OUTPUT :AP Arterial pressure [torr]

Control of arterial pressure by angiotensin and extracellular sodium content

RAP Af f My o1

M Y O G E N I C R E S P O N S E

INPUT :RAP - Renal artery pressure [torr]

OUTPUT :AffC - Myogenic effect [ x Normal]

Calculation of the myogenic response to changes in renal perfusion pressure(afferent conductance responds to changes in perfusion pressure,

with pressure increases causing vasoconstriction)

Af f C

Ef f C

RenVenC

AP

VP

Hct

Clamp

RAP

RBF

RPF

R E N A L P E R F U S I O N

INPUTS :AffC - Afferent artery conductance [ml/min/torr]EffC Efferent artery conductance [ml/min/torr]

RenVenC - Renal venous conductance [ml/min/torr]AP - Arterial pressure [torr]

VP - Vena renalis pressure [torr]Hct - Hematocrit [relative number]

Clamp - Renal artery pressure drop caused by renal artery clamp [torr]

OUTPUTS :RAP - Renal artery pressure [torr]

RBF - Renal blood flow rate[ml/min]RPF - Renal plasma flow rate[ml/min]

Calculation of renal artery pressure and renal blood flow rate

PNa

GFR

LogA2

PrxFNaNorm

MDNaFlow

PdxNaReab

PrxFNa

N A T R I U M - P R O X I M A L T U B U L E

INPUTS :PNa - Plasma sodium concentration [mmol/ml]

GFR - GLomerulal fi ltration rate [ml/min]LogA2 - Logarithm of plasma angiotensin concentration

[pg/ml]PrxFNaNorm - Normal value of sodium proximal

fractional reabsorbtion [relative number]

OUTPUTS :MDNaFlow - Sodium outflow [mmol/min]

PdxNaReab - Proximal sodium reabsorbrtion [mmol/l]PrxFNa - Proximal fractional sodium reabsorbtion

[relative number]

Calculation of proximal tubule sodium reabsorbtion

MDSig

VECml

PRA

R E N I N

INPUTS :MDSig - Macula densa feedback signal [ x Normal]

VECml - Ectracellular fluid volume

OUTPUT :PRA - Plasma renin activity [ Units/ml]

Calculation of plasma renin activity

PRA

CEAct

A2Inf

A2

logA2

A N G I O T E N S I N

INPUTS :PRA - Plasma renin activity [ Units/ml]

CEAct - Converting enzyme activity [x Normal]A2Inf Angiotensin 2 infusion rate [nG/min]

OUTPUTS :A2 - Plasma angiotensin 2 concentration [ pG/ml]

LogA2 - logarithm of plasma angiotensin concentration [ pG/ml])

Calculation of plasma angiotensin concentration and logarithm of plasma angiotensin concentration (most of the action of angiotensin are logarithmic in nature: concentration changes at higher concentrations produce less of an

effect than changes of the same size at lower concentrations)

logA2

AldoInf

VTWml

Aldo

A L D O S T E R O N E

INPUTS :logA2 - Logarithm of plasma angiotensin concentration [pG/ml]

AldoInf - Aldosterone infusion rate [nG/min]VTW - Total body water content [ml]

OUTPUT :Aldo - Plasma aldosterone concentration [ nG/dl]

Calculation of plasma aldosterone concentration

RAP

Af f C

TubC

RBF

RPF

APr

GKf

GFR

G L O M E R U L A R F I L T R A T I O N

INPUTS :RAP - Renal artery pressure[torr]

Affc - Afferent artery conductance [mll/min/torr]TubC - Proximal tubule conductaqnce [ml/min/torr]

RBF - Renal blood flow [ml/min]RPF - Renal plasma flow

APr - Plasma protein concentration (in afferent artery) [g/ml]GKf - Glomerular filtration coeffitient [ml/min/torr]

OUTPUT :GFR - Glomerular filtration rate [ml/min]

Calculation of glomerular filtration rate1

MDNaFlow

Aldo

DisFNaNorm

DisNaFlow

DisNaReab

DisFNa

N A T R I U M - D I S T A L T U B U L E

INPUTS :MDNaFlow - Sodium inflow [mmol/min]Aldo - Plasma aldosterone level [pg/ml]

DisFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :DisNaFlow - Sodium outflow [mmol/min]

DisNaReab - Distal sodium reabsorbrtion [mmol/min]DisFNa - Distal fractional sodium reabsorbtion

[relative number]

Calculation of distal tubule sodium reabsorbtion

DisNaFlow

CDFNaNorm

NaUrine

CDNaReab

CDFNa

N A T R I U M - C O L L E C T I N G D U C T

INPUTS :DisNaFlow - Sodium inflow [mmol/min]

CDFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :NaUrine - Sodium urine outflow [mmol/min]

CDNaReab - Collecting duct sodium reabsorbrtion [mmol/min]

CDFNa - Collecting duct fractional sodium reabsorbtion [relative number]

Calculation of collecing duct sodium reabsorbtion

logA2

MDSig

Ef f Norm

Ef f C

E F F E R E N T A R T E R Y

INPUTS :logA2 - logarithm of angiotensin concentration

MDSig - Macula densa feedback signal [ x Normal]EffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :EffC - Vascular conductance [ml/min/torr]

Calculates conductance of efferent artery

Af f My o

MDSig

Af f Norm

Af f C

A F F E R E N T A R T E R Y

INPUTS :AffMyo - Myogenic effect [ x Nomal]

MDSig - Macula densa feedback signal [ x Normal]AffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :AffC - Vascular conductance [ml/min/torr]

Calculates conductance of afferent artery

0

Angiotensin Infusion Rate

0

Aldosteron Infusion Rate

100

APNorm [torr]

Ef f C

AP

AP

Aldo

LogA2

LogA2

LogA2

Matlab/Simulink

RPF - Renal plasma flow [ml/min]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

GFR - Glomerular fi ltration rate [ml/min]

AVeCOP - Average colloid osmotic pressure [torr]

ECOP - Efferent colloid osmotic pressure [torr]

APr - Afferent protein concentration [g/ml]

EPr - Efferent protein concentration [g/ml]

GFR - Glomerular fi ltration rate [ml/min]

PTP - Proximal tubule pressure [torr]TubC - Tubule conductance [ml/min/torr]

FF - Filtration fraction [relative number]

AffC - Afferent artery conductance [ml/min/torr]

RBF - Renal blood flow [ml/min]

ACOP - Afferent colloid osmotic pressure [torr]

GFR - Glomerular fi ltration rate [ml/min]

RAP - Renal artery pressure [torr]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

NETP - Net pressure gradient in glomerulus [torr]

PAff - Afferent artery pressure [torr]

GP - Glomerulal pressure [torr]

simulation chip: G L O M E R U L A R F I L T R A T I O N

1

GFR

PTP = GFR/TubC

PAff=RBF*AffC

NetP = GP - PTP - AVECOP

GP = RAP - PAff

GFR = NETP*GKf

FF = GFR/RPF

EPr = APr / (1-FF)

ECOP = A*Epr + B*(EPr)^2

1160

B - Landis-Pappenheimer coeffitient [torr/g/ml]1

B * (Epr)^2

B * (Apr)^2

AVeCOP = (ACOP+ECOP)/2

ACOP+ECOP

ACOP = A*Apr + B*(APr)^2

A*Epr

A*Apr

320

A - Landis-Pappenheimer coeffitient [torr/g/ml]

1 - FF

u2

(EPr)^2

u2

(APr)^2

2

1

7

GKf

6

APr

5

RPF

4

RBF

3

TubC

2

AffC

1

RAP

GP

PAf f

RAP

GKf

Matlab/Simulink

Grafické zobrazení matematických vztahů?

RPF - Renal plasma flow [ml/min]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

GFR - Glomerular fi ltration rate [ml/min]

AVeCOP - Average colloid osmotic pressure [torr]

ECOP - Efferent colloid osmotic pressure [torr]

APr - Afferent protein concentration [g/ml]

EPr - Efferent protein concentration [g/ml]

GFR - Glomerular fi ltration rate [ml/min]

PTP - Proximal tubule pressure [torr]TubC - Tubule conductance [ml/min/torr]

FF - Filtration fraction [relative number]

AffC - Afferent artery conductance [ml/min/torr]

RBF - Renal blood flow [ml/min]

ACOP - Afferent colloid osmotic pressure [torr]

GFR - Glomerular fi ltration rate [ml/min]

RAP - Renal artery pressure [torr]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

NETP - Net pressure gradient in glomerulus [torr]

PAff - Afferent artery pressure [torr]

GP - Glomerulal pressure [torr]

simulation chip: G L O M E R U L A R F I L T R A T I O N

1

GFR

PTP = GFR/TubC

PAff=RBF*AffC

NetP = GP - PTP - AVECOP

GP = RAP - PAff

GFR = NETP*GKf

FF = GFR/RPF

EPr = APr / (1-FF)

ECOP = A*Epr + B*(EPr)^2

1160

B - Landis-Pappenheimer coeffitient [torr/g/ml]1

B * (Epr)^2

B * (Apr)^2

AVeCOP = (ACOP+ECOP)/2

ACOP+ECOP

ACOP = A*Apr + B*(APr)^2

A*Epr

A*Apr

320

A - Landis-Pappenheimer coeffitient [torr/g/ml]

1 - FF

u2

(EPr)^2

u2

(APr)^2

2

1

7

GKf

6

APr

5

RPF

4

RBF

3

TubC

2

AffC

1

RAP

GP

PAf f

RAP

GKf

FF=GFR/RPF

GFR

RPFRPF

APrAPr

BA

RBF

AffC

TubC

RAP

GFR=NETP*GKf

NETP=GP-PTP-AVeCOP

PTP=GFR/TubC

PAff=RBF/AffCGP=RAP-PAff

ACOP=A*Apr+B*(APr)^2A*Apr

B*(APr)^2(APr)^2

EPr=APr/(1-FF)

(1-FF)

EPr^2

A*EPr

B*EPr^2

ECOP=A*EPr+B*EPr^2

ACOP+ECOP

AVeCOP=(ACOP+ECOP)/2

AVeCOPPTP

GP

GFR

TubC

GFRGKf

GKf

Matlab/Simulink

Grafické zobrazení matematických vztahů?

RPF - Renal plasma flow [ml/min]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

GFR - Glomerular fi ltration rate [ml/min]

AVeCOP - Average colloid osmotic pressure [torr]

ECOP - Efferent colloid osmotic pressure [torr]

APr - Afferent protein concentration [g/ml]

EPr - Efferent protein concentration [g/ml]

GFR - Glomerular fi ltration rate [ml/min]

PTP - Proximal tubule pressure [torr]TubC - Tubule conductance [ml/min/torr]

FF - Filtration fraction [relative number]

AffC - Afferent artery conductance [ml/min/torr]

RBF - Renal blood flow [ml/min]

ACOP - Afferent colloid osmotic pressure [torr]

GFR - Glomerular fi ltration rate [ml/min]

RAP - Renal artery pressure [torr]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

NETP - Net pressure gradient in glomerulus [torr]

PAff - Afferent artery pressure [torr]

GP - Glomerulal pressure [torr]

simulation chip: G L O M E R U L A R F I L T R A T I O N

1

GFR

PTP = GFR/TubC

PAff=RBF*AffC

NetP = GP - PTP - AVECOP

GP = RAP - PAff

GFR = NETP*GKf

FF = GFR/RPF

EPr = APr / (1-FF)

ECOP = A*Epr + B*(EPr)^2

1160

B - Landis-Pappenheimer coeffitient [torr/g/ml]1

B * (Epr)^2

B * (Apr)^2

AVeCOP = (ACOP+ECOP)/2

ACOP+ECOP

ACOP = A*Apr + B*(APr)^2

A*Epr

A*Apr

320

A - Landis-Pappenheimer coeffitient [torr/g/ml]

1 - FF

u2

(EPr)^2

u2

(APr)^2

2

1

7

GKf

6

APr

5

RPF

4

RBF

3

TubC

2

AffC

1

RAP

GP

PAf f

RAP

GKf

FF=GFR/RPF

GFR

RPFRPF

APrAPr

BA

RBF

AffC

TubC

RAP

GFR=NETP*GKf

NETP=GP-PTP-AVeCOP

PTP=GFR/TubC

PAff=RBF/AffCGP=RAP-PAff

ACOP=A*Apr+B*(APr)^2A*Apr

B*(APr)^2(APr)^2

EPr=APr/(1-FF)

(1-FF)

EPr^2

A*EPr

B*EPr^2

ECOP=A*EPr+B*EPr^2

ACOP+ECOP

AVeCOP=(ACOP+ECOP)/2

AVeCOPPTP

GP

GFR

TubC

GFRGKf

GKf

Matlab/Simulink

Grafické zobrazení matematických vztahů?

RPF - Renal plasma flow [ml/min]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

GFR - Glomerular fi ltration rate [ml/min]

AVeCOP - Average colloid osmotic pressure [torr]

ECOP - Efferent colloid osmotic pressure [torr]

APr - Afferent protein concentration [g/ml]

EPr - Efferent protein concentration [g/ml]

GFR - Glomerular fi ltration rate [ml/min]

PTP - Proximal tubule pressure [torr]TubC - Tubule conductance [ml/min/torr]

FF - Filtration fraction [relative number]

AffC - Afferent artery conductance [ml/min/torr]

RBF - Renal blood flow [ml/min]

ACOP - Afferent colloid osmotic pressure [torr]

GFR - Glomerular fi ltration rate [ml/min]

RAP - Renal artery pressure [torr]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

NETP - Net pressure gradient in glomerulus [torr]

PAff - Afferent artery pressure [torr]

GP - Glomerulal pressure [torr]

simulation chip: G L O M E R U L A R F I L T R A T I O N

1

GFR

PTP = GFR/TubC

PAff=RBF*AffC

NetP = GP - PTP - AVECOP

GP = RAP - PAff

GFRold - GFRnew

GFR = NETP*GKf

FF = GFR/RPF

EPr = APr / (1-FF)

ECOP = A*Epr + B*(EPr)^2

1160

B - Landis-Pappenheimer coeffitient [torr/g/ml]1

B * (Epr)^2

B * (Apr)^2

f (z) zSolve

f(z) = 0

Algebraic Constraint

AVeCOP = (ACOP+ECOP)/2

ACOP+ECOP

ACOP = A*Apr + B*(APr)^2

A*Epr

A*Apr

320

A - Landis-Pappenheimer coeffitient [torr/g/ml]

1 - FF

u2

(EPr)^2

u2

(APr)^2

2

1

7

GKf

6

APr

5

RPF

4

RBF

3

TubC

2

AffC

1

RAP

GP

PAf f

RAP

GKf

FF=GFR/RPF

GFR

RPFRPF

APrAPr

BA

RBF

AffC

TubC

RAP

GFR=NETP*GKf

NETP=GP-PTP-AVeCOP

PTP=GFR/TubC

PAff=RBF/AffCGP=RAP-PAff

ACOP=A*Apr+B*(APr)^2A*Apr

B*(APr)^2(APr)^2

EPr=APr/(1-FF)

(1-FF)

EPr^2

A*EPr

B*EPr^2

ECOP=A*EPr+B*EPr^2

ACOP+ECOP

AVeCOP=(ACOP+ECOP)/2

AVeCOPPTP

GP

GFR

TubC

GFRGKf

GKf

GFRold-GFRnew

Algebraic Constraint

Matlab/Simulink

Grafické zobrazení matematických vztahů?

RPF - Renal plasma flow [ml/min]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

GFR - Glomerular fi ltration rate [ml/min]

AVeCOP - Average colloid osmotic pressure [torr]

ECOP - Efferent colloid osmotic pressure [torr]

APr - Afferent protein concentration [g/ml]

EPr - Efferent protein concentration [g/ml]

GFR - Glomerular fi ltration rate [ml/min]

PTP - Proximal tubule pressure [torr]TubC - Tubule conductance [ml/min/torr]

FF - Filtration fraction [relative number]

AffC - Afferent artery conductance [ml/min/torr]

RBF - Renal blood flow [ml/min]

ACOP - Afferent colloid osmotic pressure [torr]

GFR - Glomerular fi ltration rate [ml/min]

RAP - Renal artery pressure [torr]

GKf - Glomerular fi ltration coeffitient [ml/min/torr]

NETP - Net pressure gradient in glomerulus [torr]

PAff - Afferent artery pressure [torr]

GP - Glomerulal pressure [torr]

simulation chip: G L O M E R U L A R F I L T R A T I O N

1

GFR

PTP = GFR/TubC

PAff=RBF*AffC

NetP = GP - PTP - AVECOP

GP = RAP - PAff

GFRold - GFRnew

GFR = NETP*GKf

FF = GFR/RPF

EPr = APr / (1-FF)

ECOP = A*Epr + B*(EPr)^2

1160

B - Landis-Pappenheimer coeffitient [torr/g/ml]1

B * (Epr)^2

B * (Apr)^2

f (z) zSolve

f(z) = 0

Algebraic Constraint

AVeCOP = (ACOP+ECOP)/2

ACOP+ECOP

ACOP = A*Apr + B*(APr)^2

A*Epr

A*Apr

320

A - Landis-Pappenheimer coeffitient [torr/g/ml]

1 - FF

u2

(EPr)^2

u2

(APr)^2

2

1

7

GKf

6

APr

5

RPF

4

RBF

3

TubC

2

AffC

1

RAP

GP

PAf f

RAP

GKf

Matlab/Simulink

Grafické zobrazení matematických vztahů?

Grafické zobrazení transformace

vstupních hodnot na výstupní

Ne!

Softwarové nástroje pro tvorbu modelů

VECml

DistNaFlow

200

Venous conductance[ml/min/torr]

7

Vena renalis pressure [torr]

-C-

Totasl body water content [ml]

Scope1 Scope

0

Renal artery pressure clamp

drop [torr]

0.07

Plasma protein cnoncentration

[g/ml]

6.25

Normal proximal tubule conductance

[ml/min/torr]

1

Normal macula densafeedback signal

16

Normal glomerular filtration coeffitient

[ml/min/torr]

0.5

Normal distalfractional reabsorbtion for Na

25

Normal conductanceof Efferent artery

[ml/min/torr]

30

Normal conductanceof Afferent artery

[ml/min/torr]

0.93

Normal collecting duct fractional reabsorbtion for Na

0.8

Normal Na proximal fractional reabsorbtion

0.125

NaDiet [mmol/min]

MDNaFlow

LogA2

MDNorm

MDSig

M A C U L A D E N S A

INPUTS :MDNaFlow - Macula densa sodium flow [mmol/min]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]MDNorm - Normal macula densa feedback signal [ x Normal]

OUTPUT :MDSig - Macula densa feedback signal [ x Normal]

Macula densa feedback signal calculation based on macula densa sodium flow and angiotensin concentration

0.44

Hematocrit

NaDiet

NaUrine

VECml

ZNAE

PNa

S I M P L E S O D I U M B A L A N C E

INPUTS :NaDIet - Dietary sodium intake [mmol/min]

NaUrine - Sodium urine outflow [mmol/min]VECml - Extracellular fluid volume [ml]

OUTPUT :ZNAE - ECF sodium content [mmol]

PNa - Plasma sodium concentration [mmol/ml]

Extracellular sodium quantity is the integral over time dietary sodium intake minus urinary sodium loss

15000

Extracellular fluid volume[mmol/min]1

0.5086

1.855

18.84

1.275

6.846

0.144

2159

125.1

3.648

14.37

0.7975

0.1248

0.9999

99.65

1182

662.1

29.83

25.1

99.651.006

0.9418

1.792

0.9304

1.668

1

Converting Enzyme Activity

ZNAE

LogA2

APNorm

AP

A R T E R I A L P R E S S U R E

INPUTS :ZNAE - ECF sodium content [mmol]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]APNorm - Normal value of arterial pressurel [torr]

OUTPUT :AP Arterial pressure [torr]

Control of arterial pressure by angiotensin and extracellular sodium content

RAP Af f My o1

M Y O G E N I C R E S P O N S E

INPUT :RAP - Renal artery pressure [torr]

OUTPUT :AffC - Myogenic effect [ x Normal]

Calculation of the myogenic response to changes in renal perfusion pressure(afferent conductance responds to changes in perfusion pressure,

with pressure increases causing vasoconstriction)

Af f C

Ef f C

RenVenC

AP

VP

Hct

Clamp

RAP

RBF

RPF

R E N A L P E R F U S I O N

INPUTS :AffC - Afferent artery conductance [ml/min/torr]EffC Efferent artery conductance [ml/min/torr]

RenVenC - Renal venous conductance [ml/min/torr]AP - Arterial pressure [torr]

VP - Vena renalis pressure [torr]Hct - Hematocrit [relative number]

Clamp - Renal artery pressure drop caused by renal artery clamp [torr]

OUTPUTS :RAP - Renal artery pressure [torr]

RBF - Renal blood flow rate[ml/min]RPF - Renal plasma flow rate[ml/min]

Calculation of renal artery pressure and renal blood flow rate

PNa

GFR

LogA2

PrxFNaNorm

MDNaFlow

PdxNaReab

PrxFNa

N A T R I U M - P R O X I M A L T U B U L E

INPUTS :PNa - Plasma sodium concentration [mmol/ml]

GFR - GLomerulal filtration rate [ml/min]LogA2 - Logarithm of plasma angiotensin concentration

[pg/ml]PrxFNaNorm - Normal value of sodium proximal

fractional reabsorbtion [relative number]

OUTPUTS :MDNaFlow - Sodium outflow [mmol/min]

PdxNaReab - Proximal sodium reabsorbrtion [mmol/l]PrxFNa - Proximal fractional sodium reabsorbtion

[relative number]

Calculation of proximal tubule sodium reabsorbtion

MDSig

VECml

PRA

R E N I N

INPUTS :MDSig - Macula densa feedback signal [ x Normal]

VECml - Ectracellular fluid volume

OUTPUT :PRA - Plasma renin activity [ Units/ml]

Calculation of plasma renin activity

PRA

CEAct

A2Inf

A2

logA2

A N G I O T E N S I N

INPUTS :PRA - Plasma renin activity [ Units/ml]

CEAct - Converting enzyme activity [x Normal]A2Inf Angiotensin 2 infusion rate [nG/min]

OUTPUTS :A2 - Plasma angiotensin 2 concentration [ pG/ml]

LogA2 - logarithm of plasma angiotensin concentration [ pG/ml])

Calculation of plasma angiotensin concentration and logarithm of plasma angiotensin concentration (most of the action of angiotensin are logarithmic in nature: concentration changes at higher concentrations produce less of an

effect than changes of the same size at lower concentrations)

logA2

AldoInf

VTWml

Aldo

A L D O S T E R O N E

INPUTS :logA2 - Logarithm of plasma angiotensin concentration [pG/ml]

AldoInf - Aldosterone infusion rate [nG/min]VTW - Total body water content [ml]

OUTPUT :Aldo - Plasma aldosterone concentration [ nG/dl]

Calculation of plasma aldosterone concentration

RAP

Af f C

TubC

RBF

RPF

APr

GKf

GFR

G L O M E R U L A R F I L T R A T I O N

INPUTS :RAP - Renal artery pressure[torr]

Affc - Afferent artery conductance [mll/min/torr]TubC - Proximal tubule conductaqnce [ml/min/torr]

RBF - Renal blood flow [ml/min]RPF - Renal plasma flow

APr - Plasma protein concentration (in afferent artery) [g/ml]GKf - Glomerular filtration coeffitient [ml/min/torr]

OUTPUT :GFR - Glomerular filtration rate [ml/min]

Calculation of glomerular filtration rate1

MDNaFlow

Aldo

DisFNaNorm

DisNaFlow

DisNaReab

DisFNa

N A T R I U M - D I S T A L T U B U L E

INPUTS :MDNaFlow - Sodium inflow [mmol/min]Aldo - Plasma aldosterone level [pg/ml]

DisFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :DisNaFlow - Sodium outflow [mmol/min]

DisNaReab - Distal sodium reabsorbrtion [mmol/min]DisFNa - Distal fractional sodium reabsorbtion

[relative number]

Calculation of distal tubule sodium reabsorbtion

DisNaFlow

CDFNaNorm

NaUrine

CDNaReab

CDFNa

N A T R I U M - C O L L E C T I N G D U C T

INPUTS :DisNaFlow - Sodium inflow [mmol/min]

CDFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :NaUrine - Sodium urine outflow [mmol/min]

CDNaReab - Collecting duct sodium reabsorbrtion [mmol/min]

CDFNa - Collecting duct fractional sodium reabsorbtion [relative number]

Calculation of collecing duct sodium reabsorbtion

logA2

MDSig

Ef f Norm

Ef f C

E F F E R E N T A R T E R Y

INPUTS :logA2 - logarithm of angiotensin concentration

MDSig - Macula densa feedback signal [ x Normal]EffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :EffC - Vascular conductance [ml/min/torr]

Calculates conductance of efferent artery

Af f My o

MDSig

Af f Norm

Af f C

A F F E R E N T A R T E R Y

INPUTS :AffMyo - Myogenic effect [ x Nomal]

MDSig - Macula densa feedback signal [ x Normal]AffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :AffC - Vascular conductance [ml/min/torr]

Calculates conductance of afferent artery

0

Angiotensin Infusion Rate

0

Aldosteron Infusion Rate

100

APNorm [torr]

Ef f C

AP

AP

Aldo

LogA2

LogA2

LogA2

Matlab/Simulink

Blokově orientované modelovací nástroje

VECml

DistNaFlow

200

Venous conductance[ml/min/torr]

7

Vena renalis pressure [torr]

-C-

Totasl body water content [ml]

Scope1 Scope

0

Renal artery pressure clamp

drop [torr]

0.07

Plasma protein cnoncentration

[g/ml]

6.25

Normal proximal tubule conductance

[ml/min/torr]

1

Normal macula densafeedback signal

16

Normal glomerular fi ltration coeffitient

[ml/min/torr]

0.5

Normal distalfractional reabsorbtion for Na

25

Normal conductanceof Efferent artery

[ml/min/torr]

30

Normal conductanceof Afferent artery

[ml/min/torr]

0.93

Normal collecting duct fractional reabsorbtion for Na

0.8

Normal Na proximal fractional reabsorbtion

0.125

NaDiet [mmol/min]

MDNaFlow

LogA2

MDNorm

MDSig

M A C U L A D E N S A

INPUTS :MDNaFlow - Macula densa sodium flow [mmol/min]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]MDNorm - Normal macula densa feedback signal [ x Normal]

OUTPUT :MDSig - Macula densa feedback signal [ x Normal]

Macula densa feedback signal calculation based on macula densa sodium flow and angiotensin concentration

0.44

Hematocrit

NaDiet

NaUrine

VECml

ZNAE

PNa

S I M P L E S O D I U M B A L A N C E

INPUTS :NaDIet - Dietary sodium intake [mmol/min]

NaUrine - Sodium urine outflow [mmol/min]VECml - Extracellular fluid volume [ml]

OUTPUT :ZNAE - ECF sodium content [mmol]

PNa - Plasma sodium concentration [mmol/ml]

Extracellular sodium quantity is the integral over time dietary sodium intake minus urinary sodium loss

15000

Extracellular fluid volume[mmol/min]1

0.5086

1.855

18.84

1.275

6.846

0.144

2159

125.1

3.648

14.37

0.7975

0.1248

0.9999

99.65

1182

662.1

29.83

25.1

99.651.006

0.9418

1.792

0.9304

1.668

1

Converting Enzyme Activity

ZNAE

LogA2

APNorm

AP

A R T E R I A L P R E S S U R E

INPUTS :ZNAE - ECF sodium content [mmol]

logA2 - Logarithm of plasma angiotensin concentration [pG/ml]APNorm - Normal value of arterial pressurel [torr]

OUTPUT :AP Arterial pressure [torr]

Control of arterial pressure by angiotensin and extracellular sodium content

RAP Af f My o1

M Y O G E N I C R E S P O N S E

INPUT :RAP - Renal artery pressure [torr]

OUTPUT :AffC - Myogenic effect [ x Normal]

Calculation of the myogenic response to changes in renal perfusion pressure(afferent conductance responds to changes in perfusion pressure,

with pressure increases causing vasoconstriction)

Af f C

Ef f C

RenVenC

AP

VP

Hct

Clamp

RAP

RBF

RPF

R E N A L P E R F U S I O N

INPUTS :AffC - Afferent artery conductance [ml/min/torr]EffC Efferent artery conductance [ml/min/torr]

RenVenC - Renal venous conductance [ml/min/torr]AP - Arterial pressure [torr]

VP - Vena renalis pressure [torr]Hct - Hematocrit [relative number]

Clamp - Renal artery pressure drop caused by renal artery clamp [torr]

OUTPUTS :RAP - Renal artery pressure [torr]

RBF - Renal blood flow rate[ml/min]RPF - Renal plasma flow rate[ml/min]

Calculation of renal artery pressure and renal blood flow rate

PNa

GFR

LogA2

PrxFNaNorm

MDNaFlow

PdxNaReab

PrxFNa

N A T R I U M - P R O X I M A L T U B U L E

INPUTS :PNa - Plasma sodium concentration [mmol/ml]

GFR - GLomerulal fi ltration rate [ml/min]LogA2 - Logarithm of plasma angiotensin concentration

[pg/ml]PrxFNaNorm - Normal value of sodium proximal

fractional reabsorbtion [relative number]

OUTPUTS :MDNaFlow - Sodium outflow [mmol/min]

PdxNaReab - Proximal sodium reabsorbrtion [mmol/l]PrxFNa - Proximal fractional sodium reabsorbtion

[relative number]

Calculation of proximal tubule sodium reabsorbtion

MDSig

VECml

PRA

R E N I N

INPUTS :MDSig - Macula densa feedback signal [ x Normal]

VECml - Ectracellular fluid volume

OUTPUT :PRA - Plasma renin activity [ Units/ml]

Calculation of plasma renin activity

PRA

CEAct

A2Inf

A2

logA2

A N G I O T E N S I N

INPUTS :PRA - Plasma renin activity [ Units/ml]

CEAct - Converting enzyme activity [x Normal]A2Inf Angiotensin 2 infusion rate [nG/min]

OUTPUTS :A2 - Plasma angiotensin 2 concentration [ pG/ml]

LogA2 - logarithm of plasma angiotensin concentration [ pG/ml])

Calculation of plasma angiotensin concentration and logarithm of plasma angiotensin concentration (most of the action of angiotensin are logarithmic in nature: concentration changes at higher concentrations produce less of an

effect than changes of the same size at lower concentrations)

logA2

AldoInf

VTWml

Aldo

A L D O S T E R O N E

INPUTS :logA2 - Logarithm of plasma angiotensin concentration [pG/ml]

AldoInf - Aldosterone infusion rate [nG/min]VTW - Total body water content [ml]

OUTPUT :Aldo - Plasma aldosterone concentration [ nG/dl]

Calculation of plasma aldosterone concentration

RAP

Af f C

TubC

RBF

RPF

APr

GKf

GFR

G L O M E R U L A R F I L T R A T I O N

INPUTS :RAP - Renal artery pressure[torr]

Affc - Afferent artery conductance [mll/min/torr]TubC - Proximal tubule conductaqnce [ml/min/torr]

RBF - Renal blood flow [ml/min]RPF - Renal plasma flow

APr - Plasma protein concentration (in afferent artery) [g/ml]GKf - Glomerular fi ltration coeffitient [ml/min/torr]

OUTPUT :GFR - Glomerular fi ltration rate [ml/min]

Calculation of glomerular fi ltration rate1

MDNaFlow

Aldo

DisFNaNorm

DisNaFlow

DisNaReab

DisFNa

N A T R I U M - D I S T A L T U B U L E

INPUTS :MDNaFlow - Sodium inflow [mmol/min]Aldo - Plasma aldosterone level [pg/ml]

DisFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :DisNaFlow - Sodium outflow [mmol/min]

DisNaReab - Distal sodium reabsorbrtion [mmol/min]DisFNa - Distal fractional sodium reabsorbtion

[relative number]

Calculation of distal tubule sodium reabsorbtion

DisNaFlow

CDFNaNorm

NaUrine

CDNaReab

CDFNa

N A T R I U M - C O L L E C T I N G D U C T

INPUTS :DisNaFlow - Sodium inflow [mmol/min]

CDFNaNorm - Normal value of sodium distal fractional reabsorbtion [relative number]

OUTPUTS :NaUrine - Sodium urine outflow [mmol/min]

CDNaReab - Collecting duct sodium reabsorbrtion [mmol/min]

CDFNa - Collecting duct fractional sodium reabsorbtion [relative number]

Calculation of collecing duct sodium reabsorbtion

logA2

MDSig

Ef f Norm

Ef f C

E F F E R E N T A R T E R Y

INPUTS :logA2 - logarithm of angiotensin concentration

MDSig - Macula densa feedback signal [ x Normal]EffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :EffC - Vascular conductance [ml/min/torr]

Calculates conductance of efferent artery

Af f My o

MDSig

Af f Norm

Af f C

A F F E R E N T A R T E R Y

INPUTS :AffMyo - Myogenic effect [ x Nomal]

MDSig - Macula densa feedback signal [ x Normal]AffNorm - Normal conductance in afferent artery [ml/min/torr]

OUTPUT :AffC - Vascular conductance [ml/min/torr]

Calculates conductance of afferent artery

0

Angiotensin Infusion Rate

0

Aldosteron Infusion Rate

100

APNorm [torr]

Ef f C

AP

AP

Aldo

LogA2

LogA2

LogA2

Matlab/Simulink

Model v Simulinku vyjadřuje spíše

způsob výpočtu než strukturu

modelované reality

Musíme definovat

postup výpočtu

Proprietární kód klasických programovacích jazyků (např. Ada, Fortran, C,...)

Proprietární kód

Definice systému

Dekompozice systému

Modelování subsystémů Odvození kauzality výpočtu

(manuální odvození

vstupně/výstupních vztahů) Implementace Simulace

Modelování

Blokové modelovací jazyky

Blokové modelovací jazyky (např. Simulink, ...)

……

Vstupy do bloku jsou vnější vstupy nebo výstupy z jiných bloků

Výstupy z bloku jsou vnější výstupy nebo vstupy do dalších bloků

Modelování a simulace

d

Zobecněné systémové vlastnosti

formalizace

Zobecněné systémové vlastnosti

F = vRm

dP = QR1

dT = QR1

dc = QRc

Mechanická doménaF

v

Q

dP = P1-P2

P1 P2

Termodynamická doména

dT= t°1-t°2

Q

Chemická doménaQ

dc = c1-c2 c1 c2

Hydraulická doména

Elektrická doména R uR = iRRur = u1-u2

u1 u2 iR

Zobecněné úsilí „e“Zobecněný tok „f“

e=rf

Zobecněné systémové vlastnostiElektrická doména

Q=C *uC

1uC = Q

C = iC dt C

1

Mechanická doména

pružinaF

x

x=C *F 1

F = x C = vC dt

C

1

v - rychlost)

Hydraulická doména1

P = V C = fC dt

C

1V=C *P

přítok fc P

V

Termodynamická doména

q=C *dT dT= t°1-t°2

Q - skladované teplo

1 dT = q

C = fq dt C

1fq - tepelný tok

q

fq

t°1

t°2

Zobecněné úsilí „e“Zobecněný tok „f“

e=1/c * f dt

e

f

p q

Zobecnělé úsilí (effort)

Zobecnělý tok (flow)

R

e=Rf

Zobecnělá akumulace (quantity)

ò

Cq=Ce

Zobecnělá hybnost

ò

Lp=Lf

Zobecněné systémové vlastnosti

Zobecněné systémové vlastnosti

e

f

p q

Zobecnělé úsilí (effort)

Zobecnělý tok (flow)

R

e=Rf

Zobecnělá akumulace (quantity)

ò

Cq=Ce

Zobecnělá hybnost

ò

Lp=Lf

úsilí hybnost tok akumulace

e fp

q

úsilí hybnost tok akumulace

napětí proud nábojindukční tok

síla rychlost polohaimpuls síly

moment úhlová rychlost úhelimpuls momentu síly

tlak objemový průtok objemprůtočná hybnost

koncentrace molární průtok množství

teplota tepelný tok teplo

teplota entropický průtokentropie

òò

Obecné systémové vlastnosti

e fp

q

úsilí hybnost tok akumulace

napětí proud nábojindukční tok

síla rychlost polohaimpuls síly

moment úhlová rychlost úhelimpuls momentu síly

tlak objemový průtok objemprůtočná hybnost

koncentrace molární průtok množství

teplota tepelný tok teplo

teplota entropický průtokentropie

energie

òò

Obecné systémové vlastnosti

e

f

p q

Zobecnělé úsilí (effort)

Zobecnělý tok (flow)

R

e=Rf

Zobecnělá akumulace (quantity)

ò

Cq=Ce

Zobecnělá hybnost

ò

Lp=Lf

energie

Obecné systémové vlastnosti

Bond Graphs - Výkonové grafy

prvek prvekf (flow)e (effort)

Přenos energie

prvekprvekf (flow)

e (flow)

Přenos energie

bránabrána

bránabrána

Bond Graphs - Výkonové grafyEnergie do prvku

floweffort

Energie z prvku

floweffort

Bond Graphs - Výkonové grafy

1

R:R

l:LSr:us

C:C

i

i

i

i

us

ur

ul

ucStejný tok = uzel typu „1“

Bond Graphs - Výkonové grafy

Bond Graphs - Výkonové grafy

1

R:R

l:LSr:us

C:C

i

i

i

i

us

ur

ul

ucStejný tok =uzeltypu „1“

R

us

L

C

Bond Graphs - Výkonové grafy

0

R:R

l:LSr:us

C:C

i

i

i

i

us

ur

ul

ucStejné úsilí = uzel typu „0“,

suma toků nulová

R

us

L

C

Bond Graphs - Výkonové grafy

f (flow)e (effort)

Přenos energie

e - směr výpočtu

f - směr výpočtu

prvek prvek

f (flow)e (effort)

e - směr výpočtu

f - směr výpočtu

prvek prvek

Bond Graphs - Výkonové grafy

Přenos energie

f e

f e

Přenos energie

f e

f e

Přenos energie

Přenos energie

e - směr výpočtu

e - směr výpočtu

e - směr výpočtu

e - směr výpočtu

Bond Graphs - Výkonové grafy

f e

SE

Ideální zdroj

Zdroj úsilířízení

FSEřízení e

f e

SF

Zdroj tokuřízení

F-1SFřízení f

Bond Graphs - Výkonové grafy

Jednobran typu rezistor

f

f e R

FRee=Rf

f e R

F-1Re

f

f=(1/R)e

R

Q

Bond Graphs - Výkonové grafy

Jednobran typu akumulátor (kapacitor)

f

f e C

FCe

dq/dt

q

f

f e C

F-1Ce

q

ò

Bond Graphs - Výkonové grafy

Jednobran typu induktor

f

f e I

e

F-1I

pF-1IF-1IF-1I

f

f

e I

dq/dte

p

FI

Bond Graphs - Výkonové grafy

Jednobran typu induktor

f

f e I

e

F-1I

pF-1IF-1IF-1I

f

f

e I

dq/dte

p

FI

Transformátory

Gyrátory

Gyrátory

Využití výkonových grafů k určení kauzálního směru výpočtu

Využití výkonových grafů k určení kauzálního směru výpočtu

• Podrobnosti v článku „Introduction to Physical System Modeling with Bond Graphs

https://cw.felk.cvut.cz/lib/exe/fetch.php/courses/a6m33mos/intro_bondgraphs.pdf

Využití výkonových grafů k určení kauzálního směru výpočtu

Proprietární kód klasických programovacích jazyků (např. Ada, Fortran, C,...)

Proprietární kód

Definice systému

Dekompozice systému

Modelování subsystémů Odvození kauzality výpočtu

(manuální odvození

vstupně/výstupních vztahů) Implementace Simulace

Modelování

Blokové modelovací jazyky

Blokové modelovací jazyky (např. Simulink, ...)

……

Vstupy do bloku jsou vnější vstupy nebo výstupy z jiných bloků

Výstupy z bloku jsou vnější výstupy nebo vstupy do dalších bloků

Modelování a simulace

d

Zobecněné systémové vlastnosti

formalizace

Proprietární kód klasických programovacích jazyků (např. Ada, Fortran, C,...)

Proprietární kód

Definice systému

Dekompozice systému

Modelování subsystémů Odvození kauzality výpočtu

(manuální odvození

vstupně/výstupních vztahů) Implementace Simulace

Modelování

Blokové modelovací jazyky

Blokové modelovací jazyky (např. Simulink, ...)

……

Vstupy do bloku jsou vnější vstupy nebo výstupy z jiných bloků

Výstupy z bloku jsou vnější výstupy nebo vstupy do dalších bloků

Modelování a simulace

Zobecněné systémové vlastnosti

formalizace

Modelica

Blokové schéma systému

S xs

x1

x2

.

.

.

xm

u

u1

u2

un

.

.

.

vstupy

y1

y2

y

yr

výstupy

.

.

.

Stavové proměnné xs

Separabilita systému

Podmínka separability systému - systém je separabilní, jestliže jeho výstupy zpětně vlivem prostředí neovlivňují podstatně vstupy.

Příklad:

·  termoregulační systém živého organismu - systém můžeme považovat za separabilní, pokud organismus svou tepelnou energií významně neovlivňuje teplotu prostředí, ve kterém se nachází;

·

S Xu y

u1u2

un

x1

x2

.

.

.

xm

y1y2

yr

.

.

.

!!! Výstupy nesmí ovlivňovat vstupy pře okolí systému !!!!

Základní atributy systému

Stav systému - souhrn přesně definovaných podmínek nebo vlastností daného systému, které lze v daném časovém okamžiku rozpoznat. Stavu systému lze v libovolném časovém okamžiku t (z nějakého zvoleného časového intervalu) přiřadit vektor hodnot x(t)  , který nazýváme stavovým vektorem, složky xi vektoru x nazýváme

stavovými veličinami (proměnnými) a prostor všech možných hodnot stavových veličin nazýváme stavovým prostorem.

S Xu

y

u1

u2

un

x1

x2

.

.

.

xm

y1

y2

yr

.

.

.

.

.

.

Blokové schéma systému

S xs

x1

x2

.

.

.

xm

u

u1

u2

un

.

.

.

vstupy

y1

y2

y

yr

výstupy

.

.

.

Stavové proměnné xs

Blokové schéma systému

S xs

x1

x2

.

.

.

xm

u

u1

u2

un

.

.

.

vstupy

y1

y2

y

yr

výstupy

.

.

.

Stavové proměnné xs

(vnitřní) nestavové proměnné xs

xn

Stavové proměnnéAlgebrodiferenciální rovnice v Modelice

g(x(t), x‘(t), y(t), u(t))=0

h1(x(t), y(t), u(t))=0

x‘(t) = f (x(t), u(t))

y(t)=h2(x(t), u(t))=0

x(t) - dynamické proměnné

u(t) - vstupní proměnné

y(t) - výstupní proměnné

ODE

Algebr. Eq.

xs(t)

xn(t)x(t)

stavové proměnné (vzájemně nezávislé)

nestavové proměnné (vypočítatelné ze stavových a vstupních proměnných)

xs(t)

xn(t)x(t)

stavové proměnné (vzájemně nezávislé)

nestavové proměnné (vypočítatelné ze stavových a vstupních proměnných)

StateSelect.default - nech to na Modelice,

StateSelect.never – nikdy to nebude stavová, vypočítej vždy z ostatních

StateSelect.avoid – použij ji jako stavovou, jen když to už jinak nejde

StateSelect.prefer - preferuj ji jako stavovou před default

StateSelect.alwais – vždy ji ber jako srtavovou

Real x (min=0, max = 100, … StateSelect.prefer)

Stavové proměnnéAlgebrodiferenciální rovnice v Modelice

Statická analýzy fyziologických systémů

PříkladRegulace srdečního výdeje

Regulace srdečního výdeje

Regulace srdečního výdejeNa konci diastoly:

Na konci systoly:

Systolický objem:

Minutový objem:

Qc>=0

Regulace srdečního výdejeSympaticus - parasympaticus

Diastolická dysfunkce

Regulace srdečního výdejeSympaticus - parasympaticus

Diastolická dysfunkce

Intrapleurální tlak

Regulace srdečního výdejeVenózní návrat

Mean systemic pressure Pms

Regulace srdečního výdejeVenózní návrat

Mean systemic pressure Pms

CV=18 CA

Regulace srdečního výdejeUzavřená smyčka

Sympatikus f

Vasodilatace, RA

venokonstrikce CV CA

cvičení

Regulace srdečního výdejeUzavřená smyčka

Sympatikus f

Vasodilatace, RA

venokonstrikce CV CA

cvičení infarkt

CS CD

Vv VA