~~e study ~~~~~~~tol System: •

Physiolog·
h man body that ~ystems in the
omeostasis. maintain
Introduction
a Example: Blood sugar regulation

High blood glucose level

• Pancreas releases insulin.

• Insulin allows cells to receive Glucose GI-~

by Alpha Cells
d Pancreu
lndnRele-
by Beta Cella
of Pancreu
Low blood glucose level
• Pancreas releases Glucagon. ,,
Liver Rel111111
Glucoee Int> Blood
~
Fat Cella Teke In
Glucoee from Blood
• Liver releases Glucose into blood
Introduction

• System:
- When a number of elements or components are connected in a sequence
to perform a specific function, the group formed is called a system.

• Control system:
- A collection of interconnected components that can be made to achieve a
desired response in the face of external disturbances.
Introduction
Introduction

• Applications of Feedback Control

Evolved as an engineering discipline and has been extended to various fields like
economics, sociology, biology, medicine etc.
Played a vital role in the advancement of engineering and science.
- Become an integral part of the modern manufacturing and industrial processes.

• Why Biomedical Engineers Should Study Control theory?

- Human body has many control systems that can be analyzed using control
theory
- Modeling physiological processes require understanding of control theory
Inventing devices for curing dysfunctional physiological control mechanisms
Introduction

• Are the study of Physiological and Engineering control the same?

The methodology of system analysis can be applied to both type of systems.
During the first part of the course we focus on the methodology of systems analysis
In the second part we will study physiological systems in depth.

• Differences between Physiological and Engineering control system:

Engineering control systems Physiological control systems
An engineering control system is designed Physiological systems are versatile and
to accomplish a given task capable of serving different functions

I Has components that are generally known

to the designer
Usually consists of components that are
unknown and difficult to analyze
-

May not be adaptive Are adaptive

May not have cross coupling Have a high degree of cross coupling
Control System: Engineering vs. Physiological~

Sotpolnt

•• ••
Angles

,., : • cmd• .,..__-..i cmds engles

•• I
teferenco Angle
Test Vectors
Controller 6 OOF Robot Arm

Physiological control system: Engineering control system:

Blood glucose regulation Robotic arm
The Big Picture
Chemical
Engineering

Biomaterials Hlcrofluld cs
Tissue engineering Point-of-care diagnostics
Medical imaging Molecular b1omechanks
Co D onal an lvs s

lli1•1llicll--

BME 305 Physiological

Control Systems (Control
theory)
NMolt<h
Blapll,siol &..awls
dlenlhlry
Sllfnsdeta
BME 305 Physiological Control <'I,~
Systems (Computational ~ 8;0c 11>istry
~tnistry
Physiology)
Course Overview
• Goals:
Understand the fundamental concepts of classical contro l system theo ry
Learn the different control systems in the human body
• Outcomes:
Gain a fundamental insight into variou s physiological control systems
Understand the fundamentals of (feedback) control system s.
Express and solve system equations in the state-variab le form
Determine the time/frequency-domain responses of 1st and 2nd order systems
Determine the (abso lute) sta bility of a closed-loop control system
Levels of organization +

Atoms
- Mo~ IH - ~~
Cella
Tiasues
(e.g. epithelium) Organ
(e.g. stomach) Organ System
(e.g. digestive system)

Organism

• Atoms: the smallest particle of a chemical element that can exist.

• Molecules: atoms of elements link together to form molecules
• Cells: Collections of molecules in living organisms form cells, the smallest un it of structure capable of carrying out all
life processes.
• Tissues: Collections of cells that carry out related functions are called tissues.
• Organs: Tissues form structural and functional units known as organs
• Organ systems: gro ups of organs integrate their functions to create organ systems
• Organism: a collection of organ systems create an organism (e.g. human)
Physiological Models: Example +
• Electrical analogue circuit of rigid and flexible tubes

a Rigid tube b Flexible tube

t ····--···'""ty"·-·----,..

P,Q~·.~- - - ~~------:.'..~P,
J_.

Iv. V, l L

Many physiological systems can be represented as electrical circuits.

We will analyze such systems and analyze their characteristics. But focus in this
course will be on feedback control systems.
Fundamental Concepts +
A. Open loop control system
Plant is affected by controller
action and disturbance (a) Disturbance
"
Controller input does not have Conlroller
action
Output
lnpu t Plant y
r u
any knowledge of output - Controller -. (controlled -
.
system)
Output is affected by
disturbance
(b) Disturt>ance

Controller
,. "
Output
lnput
B. Closed loop control system r +
Error
e
action Plant y
.
-'/
.. -- Controller
u -. (controlled --
Controller input changes system)

Feedback
according to feedback signal signal
z
from o utput
Feedback
Effect of disturbance can be sensor
-
minimized
Negative vs. positive feedback.
Physiological Control: Negative Feedback ExamJ31-le

• Knee Jerk Reflex:

Sharp tap to the patellar tendon in the knee
Abrupt stretching of the muscle of the thigh to
which the tendon is attached
Activation of the muscle spindles (stretch S~n1ory
ncuroo

receptors)
Neural impulses sent along afferent nerve fibers to
t he spinal cord that is in synapse with a motor-
neuron
The motor-neurons get activated and send efferent
neural impulses back to the same thigh muscle.
Contraction of the muscle to straighten t he lower
leg
• Observations:
Closed loop regulation of muscle system.
Negative feedback.
Physiological Control: Negative Feedback Exam~e
• Terminology:
Reflex centerr = Controller Tap-induced
Thigh extensor muscle= Plant stretch, x
(disturbance)
v
Tap/ stretch= Disturbance
-
Change in
Musclespindle = Feedback sensor Reflex efferent neural
center frequency, u Thigh
• Negative feeclliack: . (spinal .- extensor
(Controller muscle
The disturbance stretches the thigh cord)
action)

extensor muscle
The reflex system results in opposing
Controller

/
Pia/
this stretch by contracting the muscle.
• Importance: Feedback sensor
When standing, gravity may cause the
Muscle
knee to bend slightly and make (Feedback signal)
spindle
(System output)
.
~

someone fa ll Change In afferent Change In muscle

neural frequency, z spindle length, y
The knee (or deep tendon) reflex acts as - -

a protective mechanism to straighten V

the knee and keep the person standing
upright.
Physiological Control: Positive Feedback Example
• Positive feedback: cannot maintain homeostasis as the Baby drops lowe< In
uterus to inltlate lahot.
response reinforces the stimu lus. Regulated variable moves
away from t he set point.
• Example: Control of uterine contractions during childbirth.
- Baby is ready to be delivered and it drops lower in the uterus
- Pressure applied on t he cervix (opening of the uterus).
- Sensory signals from the cervix sent to the brain
- Release of the hormone oxytoci n that causes uterus
contraction
- Contraction pushes the baby t oward the cervix and stretch it
- Increased stretch causes more oxytocin release
- More contractions push the baby harder against t he cervix.
- The cycle continues until t he baby is delivered , releasing the
stretch on t he cervix and stopping the positive feedback
loop.
Research on Physiological Modeling +
• Research: Sleep stage classification
- Sleep research uses many sensors: EEG, ECG, PPG, respiration, etc.
- Difficult to sleep with all these sensors attached. Need EEG for ground truth.
- A physiological model can benefit such research.
2.1 GENERALIZED SYSTEM PROPERTIES

® Ohm'5 lt1i.v
v==- Dr1v·,n ~ potentiOi '7\C. ro s.s K
0 .!;---+~ J: :::,. <.4YY0'11 -f{owlri.5 ---lhrolJ,j h tZ
-t V -
R ~ 'Res·1sl-c.rnce
V= ~1
(iem9'f0\i'~ed {o rm ;
' { .:::: O\o o .s s: var ic-,bl e / e--fl<r< t
j :: -fhl'Ovj va.,,ioi.!ile.
R ==- Ye ~j >r~n&
 F = vRm
f ---, --{orc:e_ [ ~fJ-o..-t / o..n o<; '.> ~I,~

• Rni--,. d~·,n :, CtJ <~ c:, e.tt- /Resi'r-flre

(a) rri~c"hoin·, c~ v
V -? vebc,)j [/4tt1V:;h ~~1t']

4f ~ f're>JvY./! ~e'l)C,(_
_ _ _ _ _4.....Olllllllla_ _ 6P
,.- • OR•1
(b) AP=P,-P2
~ -1:, -f lV?<1 -(lo v0 Rt o<_, L-
~/lJ)d --tt'C)t.v R'- -,. veJJ.flvvnc e. _L
~"" o( A"'-
lf3 -= ~a-fvre J;:fter <¼>re
Q = -ftaw ~ hQ~
(C)
f<i ::::. ~vn~ res))f-o--t)e,e_

(d)
@± 2) PY~j o-f ~ore\~
l\Glr\ e;r~ Ii?e cl -{or YTJ
J' lf c. o '\~cv
-,. V -
'P = ~ 1~ di
vi C ~ Cf/v
V-=-
I
CJ I
l:
dt-
~L O)
0 V"h1..!olt. --lhr<!IV)i
Vt-l~~ltl.
(a)
--:l=-d-15~~
X
-:f -:: : -for re
< C..m;: C()n,~iO\nCe..
F X = F Cm

X= &I dt

6. V (volume change)
~\J ~ \loJurvu.. chor<l 5 e.
(b)
/~ :: ~<.:>5v'Ye: ~7e_

,--
flV = aP C1
- C-f =. com))oince_

q :::. CimDv..A ~ V'\2.J--

~cl <A~ ~ UVYl
Heat stored, q = 6.IJ C 1
pe;r UYJ n;- J;,ff-M.tmc.A.. -'11~,
1

~ _:. ~- ditlt·
Ci -= ~~ l<K>'fH ~nc e '
(d)

Mass of
./ l/olvML
It-
9~ Y'r)d\S5 o..J- _-fw c.NlJh1l~
chemical
species
-
q = rt, Cc
_ __ ~ -;: u>h ~~ 01) I

Conau,tration, rt, 37
Property of Inertia
TABLE 2.4 Force-velocity. force-displacement, and impedance translational relationships
for springs, viscous dampers, and mass

lmpedence
Component Force-velocity Force-displacement Z.w (s) = F (s)/X (s)
Spring
T \'(I)

/(I)
f(t) = K J~ v(r)dr f (t) = Kx(t) K

Viscous damper
-+-- .\(/)
f(t) = f vv(t ) / (/) = f V ~~l)

Mass
- - x(I)
f (t) = M dv(t) Ms2
dt
M f(t)

Note: The following set of symbols and units is used throughout this book: f (t) = N (newtons),
x(t) = .m (meters), v(t) = mis (meters/second ), K = Nim (newtons/meter), / 1 =N-s/m(newton-seconds/
meter). M =kg (4ograms = newton-seconds2/meter).
2.2 MODELS WITH COMBINATIONS OF SYSTEM ELEMENTS

E1
c;; , "'b v E2 \<VL :
a b

('1/~-'fh)--t- ('t'l,-L)
E3 -+ ( 0 - '-\Ji:,) = 0

----
/(CL

Fig:re 2.3 Simple model consisting of a network of generalized sysiem elements.-z; + (- 'S'°)T (-~ ?;,)
J

.:::::. 0
a b a b

R, C1 -.::

0 0
1 1 )_,
(a) R= ( R, + R2 (c)

a b

0 0
1
1 1 )-
(b) R=R1+R2 (d) C=( c, + C°;
Figure 2.4 Mode] properties that emerge from simple networks of system elements in
+ electrical, ftuidic, thermal, and chemical systems.
 Rm2
1
1 1 )-
(a) R= Rm1 + Rm2 (C) C= ( Cm,+ Cm2

(b)
1
R= ( - + -
1 )-
Rm1 Rm2
1
~ (d) C= Cm1 + Cm2

Figure 2.S Models of parallel and series combinations of mechanical dashpots (resis-
+ tances) and springs (compliances).
Example: Bubble CPAP

' ....
~
~

t 7
f Opening for
escaping air J I l ~ t~
,--
Patient
0

r~
interface

- Column of
water
~Air/o,
_ lender
J
o, Concentrator 7
which delivers
f G.S~ B\d. t"lfit~j air/oxygenmix ___
1 1
Vres.s0, a. ( PE.£ f)
Flow is generated by a concentrator ana delivered to the patient and exhaled into a column of water. The length of the
immersed pipe determines the level of pressure. An opening allows ai r to escape from the bottle. The air-oxygen blender
allows titration of oxygen.
 a
f1'e,J l,1"(l, f(? .:::. r61stt>v')i ct
CL, Cw ":::tt t/Jf cem¾~
Ol1.rwtAj ~pert;)~
Com~rance ~ __ cs I

lAlt~~ .
lv"'~ ~ che5r wlilM Pp1

Ct>tvfl)
pf\ =- f ~(S.~lj'f../ at'
~\veo\,
Cw
 ~ -\- .A al. :::. 1) d~v + e._ dj_ + i) ~
dt'V" dki dl_'l/ ~

-G-t ·{'i-C5l +Asi--l?'J-= -g~-yt~+cs'/(;;+D'1<'0

-v

--
s -+ A:>
 / 3-:::.~ C ~ -::, t ~ 3-
\V c5
R
c.,,.,.. - fo ::. -{ovt<2 da,ve,I or,c?c) bj '11\Q tilcfiv e.
x, - x
_::. con¾ tAcli,e. e ) e ~ ~ ,11,tt rnusc{.e,
X

f -::: O\C~~ rtr H,4~Y)V -(o-, e .

K. .::: V '15 (OJ s A.,..Wlf ;Tl O ~ t) --w -+is 51.A £.
C..p = ?~r~n d -<-,vt> e\a5h( ~
) )
))

'A\
Cs
-
-
-----®i
 Fascicle Sarcolemma

Perimysium Musclle fiber (cell)

Tendon Epimysium

neurt>n
Deep fascia

Blood vessels Endomysium Blood capillary

 ~ == ~ '>-', ev, Yef, f}-an<e. ~
1<.m of /4¼- -t)5.)v1e..
verr 1 CrY\'°V c ~o.S, .s PCh ~
OYe~
i
~ -::. veriJ~V\)lcl.
h') 01° V\ fY ,t,
rne.~Y~/1 e_

~ (~fJ{C-1f Pfl(L
~ Membrane
of nenve,
'Yt1 e. m b~"n e
 ~?'-

~
ox
'
)II, +
R.tV
J
-
~

•
/+ SI
v~1R

~
1
t I
-t-
-- v
Figure 2.8 Relationship between the lumped-parameter and distributed-parameter
models of the passive cable characteristics of an unmyelinated nerve fiber.
 SV / inc re 111e <3-f volru._se_
~ o;, a 8 '1{_

fJ\~),'f t?t'f\.l- C(_/Yr~ 61 9

OI = - V - 2..:n .:l\ 6--J... + c rv,
( ..,IV) 2'7f °' cS ~ V
"1-

Li) .JG :::p ?J '7.--70 :P

'3· .5t~~ -. r-",l')'is of phj1;a10.,;,~ >jJf'etYi)

Non· pi~v\o~...., <V< 01"1/ le ~ {An J.-t"'1-df"

Open loop vs Closed Loop systems

Disturbance
6x

Reference Heat output , . - - - - - Room Temperture

Input Fan-Heater
>----1~ u Room y = y ~ 6y
Input Ge (Controller Gp
(Output)
Voltage-----.J Action)
(Controller) (Plant)
 0~ -1o~.p ~'j>~~
~-~£
~
R•ence - - . Heal QU1pU1 - - - - - - Room Temo«1ur1
_

Y" 1 • &y
1~
x0 •
•
1~
Fan HNI•
Ge
~age~----'
11

(Controler
Adlon)
Room
Gp (OulplJI) ~o ::::: G~c;p'Ao /
(Conlrolllf)

--
(Planl)

~f\(fl' bO\n<c? ~ ===P'

= 0°c 'j :=. Ge Cf ( ~ + ~}
-
 Disturbance
6X
Reference ~ f Room Tempert ure
Heat output y = y + 6y
Input + +
Xe
- -~
~
/
l
X

Input
--
~
Fan-Heater
Ge
u
(Controller
--
--
Room
Gp
o,..__
--
(Outp ut)
Voltage Action)
(Controller) (Plant)
Feedback
z

Temperture ...,,,
(b) Sensor
..
~

H
(Feedback
sensor)
 J>·,Jv1' b ~WP 6 'l ;
'j c:::: C.cG.f ( ')e i 8-;i)
/ t ~c Gptt __-.,.,---:----------
(b)

. - - t Cp s...,__
\ (I'\ ,- 'j-'1o-~j- ~G
UO -:: CC c~c - -=2_ ) c..,.l;Se< ' ) / -t c. P-H
jo -=. C, c Ctp ( Ac -i:J (voon _!:::,) fJl'.j~"< --feeJ bcc:ck. ~ ~
JW ~Ule +o J;,Jti.frb ~,re
 Tap-induced
',
Stretch, x
)
(Disturbance)

1 ~

Change in
Efferent Neural
REFLEX Frequency, u THIGH
-... CENTER
(SPINAL
,- EXTENSOR
(Controller MUSCLE
CORD) Action)

FEEDBACK SENSOR

(Feedback Signal) (System Output)

MUSCLE -
SPINDLE "' Change ln Muscle
Change in Afferent
Neural Frequency, z Spindle Length, y

Figure 1.3 Block diagram re-presentation of the muscle stretch reflex.

5pi~ \ (Ol" J\ Gttle-r,..,,.J Y)(' LA ro-l &IS" (_~ t,~,e.
f <1711 e11(j -f C\ ~ ~ .?.eAYld c l»JVe-r fed +O Hi,,,.~ Jir ch i?tr,-e
f<~~v ~ ·,
{e_ = c:;c f °' ---(i)

L ::: L<3 - ~~~ - - @

( 0>1:)e_d6R6 Y\e5°'°1vt -{-eed b&;(}.) .

f~ -=- ~s L . 0
SPINAL CORD (CONTROLLER) MUSCLE (PLANT)

Efferent Neural L Gain= -GM

Frequency
fe

----- ,.
Gain = Gs

'· L

Afferent Neural Muscle Spindle

Frequency Length

SPINDLE (FEEDBACK ELEMENT)

Figure 3.2 Block diagram displaying the steady-state characteristics of the muscle stretch
reflex model components.
L (011e-5por, ¾ {1/\'3, 1 --( Q_
1
f ~, c=.. ~5 Lo
J -+ l;' !Y\ LAC~ 5

1eJ -::: c:;-c. c:;5 Lo

) -t- CM ~c. Cis

L -:::. Lo_ lM (LCAcGi~

Lo _
::t, L -:::. I--:, :::::. J + t;l'VI ~c Gs
1
.- ~:\: Cl6f 1vJ \~ i
ext ~qv·1\,~r\Um
 L
MUSCLE (PLANT)

'
- - ~ L3 - - - - -:- ---
•
' --- -•------
L, ----- --~--
,

,.

'
'
'•3 '
'

--------- - -- - - -· -- ----- -- ;;,- -- -- . -- - -- . - . -. -- --

SPINDLE (FEEDBACK}
,. SPINAL CORD (CONTROLLER)

Figure 3.3 Graphical detennination of the steady-state operating point.

Regulation of glucose
II Example: Blood sugar regulation

High blood glucose level

• Pancreas releases insulin.

• Insulin allows cells to receive Glucose

Low blood glucose level

~ ;1
by Alpha Cells
otP•oeu
lneulnR8'eued
by Beta Cells
of Pancreea

• Pancreas releases Glucagon. r, Fa! eels Take In

Glucoee from Blood
• Liver releases Glucose into blood
 I

CD -f~ Vo/'-fW.. &-{- IJood-+ ·,nre,r.rliho,j -fu',d ~) f;)\e.::1· Cffel-f~

~
® S1evi½-St.4"e. ccrice-,rlr-W(if) ~ . rv ISL
a\1..A(O.fe_ -==: ?(_ (YYlj/L)
1 () .ke.tlf ~ ~)-~ ~
gltA{a.£€. i1)-{rokJ -= 5/ l,f core. o vJ fio v0
 ?erw loss vk ~ _?- ( ,x_- G)·, ~ )G
= 0 ; '/-~G
::. 0

@
 - Renal Loss Rate

Glucose Input Glucose

Flow Rate - - ____ Concentration
P~sma
L
r- -
.
+
Tissue Utilization Rate

,, .... .... -- _ -;
,
x
,'1:lL_
(Insulin-dependent)
.....__ __,.Tissue Utilization Rate

I
I
/
/
/

I
I
,
/
.
•

I
I
(Insulin-dependent)

I I

Pancreas
' I
I
I
t
I
I

I
I
I
I
I

I I
I I
•
I I
I

I I
I I
I •
I
I

• Plasma , I
Insulin
Pancreatic Insulin '
Concentration
\j
Insulin Destruction
Rate
Production Rate ,-,
-
Figure 3.12 Schematic representation of the processes involved in the regulation of
glucose and insulin.
 Jl)>lJin prod-v<~O"YJ -Y~e. ::= 0 +
- ~ ~ - P)

:., ~ -= 0

=: r~-cb) -

\.J
I
4>
4l1ACoJe conce,dr-~cM
(~J19
Diabetes
+
• Healthy Pancreas:
Blood sugar level high.
Healthy
Glucose
Insulin
receptor

Pancreas releases insulin. Insulin

Insulin allows cells to receive
Glucose

• Diabetes Type 1: (less common)

Blood sugar level high.
Type 1

X
Glucose

Pancreas fails to produce insulin. Pancreas failure to

produce Insulin
Glucose cannot enter cell

• Diabetes Type 2: (more common)

Blood sugar level high.
Type2
Glucose
Insulin
receptor

Pancreas releases insulin.

Insulin
• Cells fail to
Cell fails to respond to insulin respond to
Insulin property
 Jl1>c.J1'n proc}-v(~O'f) -y~e == 0
== _t_(~ -~)
:{.-,5<.fl,n d.esfrvcl-i<JYJ y-ork_ -=:
- Cl\ 6

:., "1 -:= 0 -:;ic ~cp

= p (,z-cb) -?( '?~
~ -
-

I
 ?erw los.s .,~ .::::. _)A ( "A-- G) ~ ?-- >0
-:=: 0 -; -7-~G

® -f;55 lAe 1.-1 ri1~~~'1Y) -v4e..

CiY)5lA"1.Yl- ,1 ) ~
q>
c;1uc0Je COY\CUlYN1loY1
(-rvi::J19
0.15

0.10 +
0.05

0.05
(c)

0.'4 0.8 1.2 1.6 2.0 f11u,. 3.13 Stcady-siate analysis of glucose
0.0
regulation under (a) nonNI conditions; (b)
Glucose Concentration (mg ml-1) Type- I diabe1c:s; and (c) Type-2 diabc1cs.
 CT-2
Chapter : 4 & 5