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SEMISTER VI BIOMEDICAL ENGINEERING

Solutions

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*For complete understanding of the subject one must refer to the prescribedreference books.

BMS SOLUTIONS


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1. Explain voltage clamp mechanism in detail

The voltage clamp was the technique introduced by Hodgkin and Huxley and was crucialto the task of separating the capacitive, sodium and potassium components of

membrane current in their measurements on the squid axon.

It is basically a feedback arrangement where the transmembrane potential is held

electronically during an action potential or sub threshold response.

The sodium-potassium pump active transport mechanism in cell membranes that moves

ions from one side to other side of the membrane.

Their energy source is Adenosine Triphosphate (ATP) and they can be blocked by

chemical ovabain and slowed by low temperatures.

The reaction to low temperatures is due to increased utilization of ATP. This effectchanges the resting potential of about 2mV/C.

The ion pumps may be electrogenic, where there is a net transfer of charge or non-

electrogenic where no charge is transferred.

Na+ concentration is high in extracellular fluid and low in cytosol. The K+

concentration

is high in cytosol and low in extracellular fluid.

The Na+ in the cytosol finds to pump protein. This finding triggers breaking down of ATP

to ADP and attachment of high energy phosphate group to the pump proteins.

This changes the shape of pump protein so that Na+ is pushed to the membranes and

expelled into extracellular fluid. K+ binding triggers opposite reaction which again changes the shape of pump protein.

As pump pretends to original shape, K+ ions are pushed through the membrane into

cytosol.

At this moment pump is ready to again bind Na+ in cytosol and the cycle repeats. This is

known as voltage clam mechanism.

2. Define a Model .Mention the steps for modelling. (5mrks)

Ans: Models are simplified representation of objects and systems. They are used to help,

configure and evaluate computer systems. Biological modelling is the process of representing a

body (system) of biological hypothesis as theory in mathematical form.

The steps involved in formation of model are as follows:

1. understand the given problem


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2. define the parameter

3. understand the performance criteria

4. make small parts of the system

5. simulate each part

6. test each parameter separately7. test the complete system

8. evaluate the complete system

9. Quantitative assessment with validity criterias.

10. Check accuracy in application point of view.

11. Check does it require manageable set equation; also check whether simplification of

equation is possible or necessary.

12. Check either equation simply describes the system.

13. Prepare documentation.

3. Write expression for Goldmans Equation and explain its significance.

Ans: the Goldman equation is written as:

= lnPk[K +]o + PNa[Na +]o + PCl[Cl ]iPk[K +]i + PNa[Na +] +PCl[Cl ]i

This equation is also called as Constant field equation. Since constant field, equation is used as

an assumption. Its significance here is a biological membrane can be modelled as having a

constant electric field within it. Model will be accurate if the permeable ions are univalent and

total ionic concentrations on each side of membrane are equal and membrane is thin. The

significance of Goldman expression is that it can be used to explain variations in membrane

permeability changes. It is also use to determine relative permeabilitys of ions.

4. Mention any two industrial application of thermoregulatory system and explain any one in

detail.

Bio heat transfer is the study of the transport of thermal energy in living systems.

Because biochemical processes are temperature dependent, heat transfer plays a major

role in living systems.

Thermoregulation is an elaborate control system, used by mammals, to maintain

internal body temperatures near a physiological set point under a large spectrum of


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environmental conditions and metabolic rate activities. Even though there have been

many years of research, many remains unknown about the human thermoregulatory

system.

There are many applications of thermoregulatory systems in the industries:

1. Thermoregulation system in space suits used by astronauts since human bodycannot use perspiration as defence against overheating because water vapour

cannot escape from body.

2. Organ transplantation, blood banks and animal husbandry are the tree

applications that require the long term cryopreservation of biological tissue.

The drawback of earlier space suits were :

1. Cooling water coils were installed in the suit to remove heat generated

by exercise or work.

2. Problem of controlling the cooling.

3. Manual control by the subject did not work because subject oftenreacted too late or overheated indicating there were different

physiological and psychological temperature sensors.

Hence, thermoregulatory models were used to design the automatic control systems for

these space suits.

System consisted of cooling device with closed loop controller utilizing physiological

input feedback.

Cooling water is circulated by a pump from inside the suit where it absorbs heat to an

external thermoelectric cooler where it is cooled.

A constant water flow of 2.5x10

-6

m/sec kept a resting subject comfortable at atemperature of 26-32C, yet it could not remove all metabolic heat a man bought to his

surface during work.

The two methods that worked are:

1. Measuring the oxygen consumption which is proportional to metabolic

activity. The difficulty in this method was that O2 consumption change

rapidly but water inlet temperature requires a longer time to change.

There is human body thermal mass which slows the rate of change of

body temperature upon initiation of activity.

2. The second method operates by matching heat removal by the coolingwater to maintain thermal equilibrium from the skin. This is used a direct

feedback control principle than first method.

The temperature of inlet and outlet manifolds of the water cooled suit are used to

obtain total amount of heat removed.

Average skin temperature is derived from four thermistors placed inside the suit over

the thigh, muscle biceps, lower abdomen, and kidney. When this average temperature


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increases, inlet water temperature decreases to increase heat removal. This is how

thermoregulatory system is used in space suits.

5. Draw and explain electrical equivalent model of biological membrane in short.

1. Membrane potential depends on the concentration ratios and the related Nernst

potential. The above figure shows a model of a small patch of a nerve or muscle

membrane.

2. The batteries are the Nernst potential for Sodium (ENa) potassium (EK) and leakage

(EL)ions. EK and EL have negative value. The leakage channel is primarily that of chlorine

ions.

3. Current flowing out of the cell is defined to be positive current. The sodium and

potassium are very slow compared to the time course of a voltage spike.

Applying Kirchhoffs voltage law around the loop containing the sodium elements,

+ = 0

= +

But ENa is Nernst potential which is due to the concentration difference of sodium ions.

=

+ ln[ ]2[ ]1

Applying Kirchhoffs Law around the loop containing the potassium elements

= 0

=

But Ek is Nernst potential which is due to the concentration difference of potassium ions

= ln[ ]

[ ]

There is a drift component that depends upon the ionic concentration ratio. In general,

Vm ENa


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Hence, the net sodium flow is not zero. The sodium-potassium pumps are included in the

model to remove the sodium that leak into the cell. Therefore the total flow of sodium should

be,

=

+

Similarly, for simplicity assume that JPNa=JPK

=

+

4. In cell membranes, the Nernst potential for sodium is quite different from the resting

membrane potential. This means that sodium pump must work very hard to maintain

the concentration difference.

5. The Nernst potential for chlorine is just about the same as the resting membranepotential. The Cl

-ions are in electrochemical equilibrium and no direct energy

expenditure is required to maintain the steady state concentration ratios. Therefore,

there is no chlorine pump available.

6. Neglecting leakage channel RL and EL and ignoring the sodium and potassium pumps. In

steady state iK=iNa , by Kirchhoffs voltage law:

= = +

+ 10

( ) = 0

( ) = 90

This is the value that is typical for biological cells. Now for Vm(reversal) i.e. calculation with ACH

gates open; Vm(reversal)=-20mV

This is a typical value for reversal potential at a neuromuscular junction.


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6. Explain Biophysics tool with related laws and expressions.

Ans:- the four basic mathematical tools are needed to calculate voltages across membrane:

1. Ficks law for diffusion of particles

2. Ohms law for drift of charged particles in electric field

3. Einstein relationship

4. Space-charge neutrality

1. FICKS LAW-

It states that diffusion takes place down the concentration gradient and is everywhere directly

proportional to the magnitude of that gradient. The equation for Ficks law is given by:

= [ ]

Where Jc= diffusion flux

D= constant of proportionality called diffusivity (cm2/sec)

2. OHMS LAW-

It states that drift of positively charged particles takes place down the electric potential

gradient and is everywhere directly proportional to the magnitude of that gradient. And it also


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states that negatively charged particles drift up the potential gradient in proportion to gradient

magnitude.

= [ ]

Where C= ion species under consideration

Z= no. of electric charges

=mobility

dV/dx= gradient of voltage potential.

3. EINSTEIN RELATIONSHIP-

The relation between the diffusion and drift process is called Einsteins relationship. The

mobility and diffusion constant D, both depend upon the ability of the ion to move though

the solution. Hence, a relationship exists between D and .

=

4. SPACE CHARGE NEUTRALITY-

It states that the number of positive ionic charges in a given volume is equal to the number of

negative ionic charges.

=

7. Derive Nernst equation and give its significance.

Ans: The simplest system for studying the ionic flow would be a system where only one ion can

flow. Hence, we consider a system where only potassium can pass through the membrane. The

potassium flow has two components: drift and diffusion. The sum of two must be zero for

equilibrium.


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The tank is divided by a membrane that is permeable only to potassium ions and water. The

concentration of KCl is different on each side. This will produce a voltage potential across the

membrane.

From the Ficks law the diffusion flow from left to right is

[ ] = [ ]

By Ohms law

[ ] [ ]

The total potassium flow is

[ ] = [ ]

[ ]

From Einsteins relationship,

=

( ) = [ ]

[ ]

Thus for equilibrium,


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( ) = 0

[ ]

[ ] = 0

[ ]

= [ ]

= 1

[ ][ ]

Now integrating from left to right across the membrane

= 1

[ ]

[ ]

Changing the variables of integration yields

= [ ][ ]

[ ]

2 1 =

{ln[ ] 2 ln[ ]1}

2 1 =

ln[ ]2

[ ]1

Nernst equation expresses the voltage difference required to balance potassium with equal but

opposite potassium drift, thus making the net flow of potassium zero.

8. Draw and explain reciprocal innervations model of eye movement in short.

Ans: the following fig. shows the nonlinear reciprocal innervations model of Hsu, Bahil and

Stark. The top fig. (a) Shows the Descartes basic concept, which states that muscles were like

balloons; when inflated they would be short and flat, when drained of fluid they would be long

and skinny.

The pipes were to pump fluid reciprocally in and out of the muscles. Shortening of the agonist

together with the lengthening of the antagonist muscles produces eye movement.


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The bottom figure shows the ideal mechanical elements used for the modelling the plant. The

globe and surrounding tissues were modelled by the inertia (J), a viscous element (BP) and a

passive elasticity (KP).

Each muscle was modelled by an active state tension generator (FAG and FANT), a nonlinear

dashpot (BAG and BANT) representing the non linear force velocity relationship, a series elasticity

(KA) and a parallel elasticity that was combined with passive elasticity of the globe to form (KP).

The active-state generator converts motor neuronal firing into force through a first order

activation-deactivation process.

The controller signals (CSAG and CSANT) represent the aggregate activity of all the motor neurons

in the agonist and antagonist motor neuronal pools.

The system equation of the model is-

= ( ) +

= ( )

( ) ( ) = + + --------(1)

FAG is the muscle force exerted on the agonist. FANT is the muscle force exerted by the

antagonist.1 is eye position; 2 and 3 are the nodal positions separated from 1 by the series

elasticities of the agonist and antagonist muscle as shown in figure.

. , .

The Newtonian equation is given by;

= + + + + +

This is a sixth order non-linear system.

The antagonist activity circumscribes the agonist activity.EMG studies shows that antagonist

activity resumes its activity after the agonist ceases its burst of activity.

It has been reported that the pause of the antagonist motor neuronal pool starts before theagonist motor neuronal pool begins its high frequency burst of firing in human lateral and

medial rectus muscles.


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9. Explain four types of eye movement model and mention the name of eye muscles

responsible for eye movement.

Ans: The eye movement system is ideal for studying human control of movements. The muscle

controlling the eye movements are defined by the following muscles.

Medial and lateral rectus: they contract to move the eyes side to side.

Superior and inferior rectus: they move the eyes upward and downwards.

Inferior rectus moves the eyes downward by adduction whereas the superior

rectus moves the eyeball upwards by abduction.

The oblique muscles function is to rotate the eyeball and to keep the visual field

in the upright position.

There are four types of eye movements:

1. Saccadic eye movement

2. Smooth pursuit eye movement

3. Vergence eye movement

4. Vestibular eye movement

Saccadic Eye movement

Rapid jerky movement from one fixation point to another allows sweeping

search. During this movement, the high resolution fovea centers the retina

which is focussed on important feature seen by using information from the

periphery of the retina to direct the movement.

The purpose of the saccadic eye movement is to move the fovea of the eyes to

facilitate efficient information processing. However, one does not see well

during saccadic and therefore we do not want our eyes to be constantly

producing saccadic eye movement. Therefore we have a process called Saccadic suppression that suppresses our

visual path during saccadic movement which is specific for saccadic size and

direction.

Smooth Pursuit movement


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It is a tracking movement of the eye while following the moving objects. This

movement is controlled by Occipital cortex and superior colliculus.

Vergence Eye movement

It brings visual axis towards each other as the object moves towards the

observer.

This movement is controlled by occipital cortex and superior colliculus.

Vestibular eye movement

This movement of the eye is to maintain the visual fixation as the head moves. it

is controlled by the vestibular systems, cerebellum and superior colliculus.

Consider an example of duck hunter sitting in a rowboat on a lake. He scans the sky using

saccadic eye movement. When he spots a duck, he tracks its movement using smooth pursuit

eye movement. When the ducks come closer to him, his eyes move towards each other using

Vergence eye movement. While he is doing all this, the boat is rocking which requirescompensatory vestibular ocular movements.

10. Write mathematical expression of cable equation and mention its significance.

Ans: Application of Kirchhoffs laws (for electrical circuits) to the core-conductor model network

leads to the cable equations. These equations are the basic mathematical relationships used to

study the electrical response of a uniform fibre to subthreshold and transthreshold stimuli.

The mathematical expression of cable equation is given as follows:

=

The significance of the cable expression is as follows:

Cable expression is important for analyzing the data collected from intracellular microelectrode

recordings and for analyzing the electrical properties of neuronal dendrites.

11. Explain the role of spindle receptor and Golgi tendon organ in modelling of

neuromuscular system.


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1. Most biological control system is closed loop systems. To gain an appreciation for such

systems, we study a small part of the neuromuscular system. Neuromuscular systems

seem unnecessarily complex for the task they perform.

2. We first consider the study of biceps muscle, which bends the elbow, this muscle with

its associated sensory fibers and motor neurons acts as feedback control system. Thestretching of a muscle results in prompt contraction of that muscle which tends to

restore its former length.

3. They showed that this response depended upon afferent signals from the muscle to the

spinal cord and upon efferent signals that were sent from the spinal cord to the muscle.

This reflex is called the stretch reflex.

4. The following figure shows only a single spindle receptor, a single motor neuron (mn)

and single afferent neuron and efferent nerve fibers. E stands for excitatory synaptic

connection. The controlled output of the above fig. is the position of load which is

directly related to the length of the muscle.

5. The length of the muscle shortens because it can only contract. However, it is

convenient to put negative sign into the muscle dynamics and call the control output

length. This negative sign is required in the loop for a negative feedback control system.

6. The transducers that measure muscle length are called muscle spindle organs. These

sensory organs are located within the belly of the muscle and are connected in parallel

with the other muscle fibers so that they are stretched whenever the muscle is

stretched. These nerve fibers increase their rate of firing when they are stretched.

7. The neuromuscular control system also contains another sensory organ called the Golgi

tendon organ. In contrast to the muscle spindles that lie in the parallel with the main

muscle fibers, tendon organs are located at the junction between the tendon and the

muscle fibers and are in series with the contractile elements.

8. Tendon organs are insensitive to passive stretch of the muscle. Also, the contractile

element absorbs most of the stretch and prevents elongation of the tendonous organ.

Therefore, it has very little effect on tendon organs.

9. If contraction occurs when the muscle is lengthened and its ends are fixed, the

shortening of the muscles contractile part necessarily lengthens the non contractile

regions where the tendon organs are located and vigorous firing results.

10. A particular tension may be developed at various muscle lengths. By virtue of their

location, tendon organs measure this tension regardless their of length.

11. The outputs of tendon organs are fed back to the alpha motor neurons through

interneurons. They inhibit of the alpha motor neurons and are a part of negative

feedback loop.


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12. Parameter estimation

In developing a model of system, the parameters of the model must be assigned

numerical values. Sometimes the assignment can be based upon knowledge of physical

system. For example. The mass of an object being controlled is often known.

However, some physical parameters such as the viscosities in the reciprocal innervations

model can only be estimated. Choosing parameters can be done manually or under

computer control. For example in the case of experimental passive length tension diagram was

approximated with a hand drawn straight line. this approximation was then used in the

construction of model.

Other parameters such as agonist activation time constant were adjusted after the

model was constructed.

The model was run and the output was visually compared to human eye movements.

Then the time constant was changed and the model was rum again.

After many iterations, a satisfactory value of the parameter was obtained. This

estimation was done manually therefore probability of error occurrence was more. A digital computer could perform this parameter estimation more efficiently. The

following figure shows the estimation scheme.


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The criterion function is the mean squared error between the model and and plant

outputs. It is a function of parameter values, .

( ) = ( ) ( )

Where the T- the matrix transpose and G-a weighting matrix.

The purpose of algorithm is to adjust the parameters so as to minimize the criterion

function. Parameter estimation by minimizing the difference between the model

behaviour and the behaviour of the physical system is an important step in building a

model.

13. Explain with a neat diagram sliding filament theory.

The idea that muscular contraction is a consequence of the contraction of protein units

patterned after that of a helical spring had to be abandoned when measurements

revealed that the A band does not change length during contraction or lengthening.

In fact, in frog muscle, as the sarcomere length is varied from 2.2 to 3.8 m, the I

filaments remain essentially at 2.05 m in length and the A filaments at around 1.6 m.

As a consequence of the above, the sliding-filament model was advanced. According to

this idea, contraction involves the relative movement of the thin and thick filaments, as


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illustrated in fig., where contraction yields a reduced sarcomere length while the

filaments are unchanged in length.

Fig 1.sliding-filament model: (a) the muscle is elongated ;( b) the muscle is contracted.The lengths of the thick and thin filaments are unchanged.

The sliding itself is thought to be produced by reactions between the projections on the

myosin filaments and active sites on the thin filament.

Each projection first attaches itself to the actin filament to form a cross-bridge, then

pulls on it, causing the sliding of the actin, then releases it, and finally moves to attach

to another site which is further along the thin filament.

The sliding filament theory is generally (though not universally) accepted.

Accordingly, one expects isometric tension to depend on the degree of overlap in thethin and thick filaments.

This result is supported by the study illustrated in Fig.2 and fig.3 and can be understood

in the following discussion.


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Fig. 2. Isometric Tension of a Frog Muscle Fiber, measured as a percentage of itsmaximum value at different sarcomere lengths. The numbers 16 refer to the

myofilament positions illustrated in Fig.3.

Fig. 3. Myofilament Arrangements at Different Lengths. a=thick filament length; b=thin

filament length including z line.

c=thick filament region base of projections, z=z line width

Stage 1 (in Fig. 2 and 3) refers to full extension of the myofibril. Using the dimensions

given above for the thin and thick filament lengths, the sarcomere length is 2.05 +1.60 =


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3.65 m, which is the sum of the length of the thin plus thick filament. There can be no

cross-bridges and the observed zero tension is explained on this account.

As the myofibril shortens so that the sarcomere diminishes from 3.6 to 2.22.25 m

(stage 2), the number of cross-bridges increases linearly with decreasing length.

Therefore, the isometric tension should show a similar increase. In fact, such an increasein tension with decreased length is seen in Figure 11.12. This linear behaviour ends at

stage 2, when the ZZ distance equals 2.05 m plus the L zone width ( 0.15 m), or

2.20 m.

With further shortening, the number of cross-bridges remains unchanged and a plateau

in tension is both expected and observed. Stage 3 is reached when the thin filaments

touch. The sarcomere equals the length of the thin filament, namely, 2.05 m at this

point.

From stage 3 to stage 4, one anticipates some internal resistance to shortening to

develop, since actin filaments now overlap. Beyond stage 4, this overlap not only constitutes a frictional impediment, but it also

interferes with cross-bridge formation. When stage 5 (1.65 m) is reached, the myosin

filaments hit the Z line and a further increase in resistance is associated with the

deformation that results beyond this point.

The curve in Fig. 2 shows a break point at stage 5 and a rapid decrease in tension with

further shortening. Zero tension is reached at a sarcomere length of 1.3m, which

designates stage 6.

This is sliding filament theory.

14. Explain two control mechanism neuromuscular systems.

Ans>>>

The higher level of CNS can control the output position with either of two strategies.

The open loop control strategies uses the alpha motorneurons and holds the

innervations to the muscles spindles, via the gamma fibres, constant.

If elbow angle were decreased, the CNS innervations to the biceps motorneurons

would increase and the innervations to the triceps motorneurons would decrease. This

strategy is fast and it is used for larger or fast movements.

The second strategy, the closed loop control strategy, uses gamma fibers.


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To decrease the elbow angle the innervations to the gamma fibers of the biceps

muscles is increased and at the same time the innervations to the gamma fibers of

triceps muscle is decreased.

The increased firing will cause the biceps spindle fibers contract, this in turn will stretch

the central region of spindle where the sensory fibers are. Therefore the biceps sensory fibers will increase their rate of firing. This in turn will

stimulate the motorneurons of the biceps muscle and cause it to contract.

Analogous changes will allow the triceps to relax. Gamma control fibre may be used for

very fine movements and for postural control, but most movements are probably made

with a combination of alpha and gamma control.

This is the two control mechanism for neuromuscular system.

15. With reference to the thermoregulatory system explain controller action for:

a) Low average skin and brain temperature

The primary defense against overheat is perspirations. Consider the following

fig(a).

= ( 36.6)( 34.1)Where THC is head core temperature

Where TS is skin temperature

K2 =80W/C2

Take THC=37C , EV1=3.2 and so on.

Even though there is a wide fluctuation in environmental temperature. Homeostatic

mechanism can maintain a normal range for internal body temperature.

If there is heat production or heat loss then a constant temperature near 37C is

maintained. Core temperature in body structures below skin and subcutaneous

tissues temperature at surface i.e skin and subcutaneous skin.

If heat producing mechanism gives off more heat than heat generated, core

temperature falls. Too high core temperature denatures the body proteins. Below a

core, temperature causes arrhythmias that result in death.

b) High average skin and brain temperature

Consider the following fig(b).

= ( . )( . )Where K3=70 W/C

2, take THC=35C, M1=11.2, M2=112,M3=224,M4=448.


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If TS is kept constant , THC is varied from 36.6 to 37.6, EV goes on increasing but

maximum EV is very less for low skin temperature.

As TS goes on increasing for particular value for of head core temperature EV

goes on increasing. Both temperature are losses than the set points.

The person will undergo shivering. As we go towards the righthand side of thegraph, M goes on decreasing. As 36.6C,M and EV both are equal. Further on

increasing EV indicating the person perspiring.

Hence the person is either shivering or perspiring except for dead band or dead

zone.

16. Explain Hodgkin-Huxley conductance equation in short.

The Hodgkin-Huxley model is used to explain neuronal voltage spikes.

The experiments that formed the basis of the model were performed on the squid giant

axon. Because of the large diameter of the axon, silver wire could be pushed through

the end of the axon and into its axoplasm.

This electrode extended the entire length of the axon. The voltage potential on this wire

and thus inside the axon was carefully controlled.

They could hold the voltage across the membrane constant while measuring the current

passing through the membrane. This current is a good indicator of the inductance.

The voltage clamp technique included a guard system with cylindrical electrodes which

enabled the extracellular solution to be kept isopotential.

This eliminated all axial components of the current, leaving only radial components in

the voltage clamped portion of the axon.

It allowed the voltage clamp to be applied to a large area of the membrane. When

Hodgkin-Huxley applied a step depolarization to a voltage clamp membrane, they

observed three phases of current.

Based on the model, it was concluded that the inward current was due to sodium ions

and the delayed outward current was due to potassium.

When a step depolarization was applied to a voltage clamp membrane the potassium

conductance increased gradually, with an inflection to its final value.

In response to a step repolarisation or hyperpolarisation, the potassium conductance

decreased without an inflection towards its final, lower value.

Hodgkin-Huxley found a mathematical function for the inflected rise and a non-inflected

fall which is given by:-


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=

=

Where m= mass number of ion

n=number of sample related to potassium

= constants for gK and gNa respectively

Neglecting the sodium-potassium pumps, total membrane current i is given by

= + ( ) ( ) + ( )

Where V= voltage across membrane

Cm= membrane capacitance

gK=potassium conductance

gNa= sodium conductance

gL=leakage conductance

EK=Nernst potential for K+

ions

ENa=Nernst potential for Na+

ions

EL= Nernst potential for leaking currents

17. For thermoregulatory system explain the following:-

Draw block diag. of thermoregulatory system and explain it in short.

Ans:>>>

Thermoregulatory system is the system which controls the changes in body temperature

with respect to atmosphere and regulates it to a constant value.

There is a need for thermoregulatory system because of of the following reasons:

a) All biochemical and biological reactions are temperature dependent


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b) Species with good thermoregulatory systems have a competitive advantage over

other species.

c) For a thermo regulated body:

0C-37C thyroxin controls the temperatur37C-45Cproteins control the

temperature

Fig. thermoregulatory system B.D

It is a closed loop system where the heat is exchanged between the body and the

environment.

Temperature sensors are located primarily in the skin and hypothalamus and the

receptors are located in spinal cord, medulla, abdominal muscles and respiratory

track.

There are separate sensors for warmth and cold. The summing junction and the

controller CNS are located in particular regions of hypothalamus. CNS is the main controller which gives decision to the temperature controller. Three

basic principle mechanisms are as follows:

a) Metabolism which produces 86W of power in the body

b) Exercise which produces 1000W of power in the body.

c) Shivering produces 100 W of power in the body.


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Heat is exchanged between the body and environment. Heat is lost to the environment

by conduction, convection and radiation which is not CNS controlled.

About 20% of heat loss occurs during conduction and convection. Heat loss through

these processes depends upon the temperature of surrounding atmosphere.

About 55% heat loss occurs by radiation due to temperature difference between bodyenvironment and takes place through the skin.

About 25% heat loss occurs by evaporation, sweat is vaporised from the skin thus

decreasing its temperature.

In cold conditions, the arteries constrict to avoid transfer of heat by convection,

whereas in hot conditions they dilated to remove excess to remove excess heat by

convection of blood flow.

Heat loss is proportional to ventilation rate, which is proportional to oxygen

consumption and metabolic rate. There is less heat loss by breathing through nose than

by breathing through mouth. The equation used to derive Wind-chill factor is:

= 1.16 100 + 10.45 (33 )(1)

Where, HA=power loss in watts due to convection

A= exposed surface area

W=wind speed in m/s

Ta=air temperature in C.

The body radiates energy into the environment according to equation:

= ..(2)

Where, HRAD= radiated power in watts

A=effective area

Ts=temperature of skin K

Ta= ambient temperature in K

The body also loses heat by conduction with chairs and walls.

18. Explain validation model for thermoregulatory system in detail.(2 fig. needed)


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Ans:>>>

After a model is formed, it is very much necessary to validate that model. In order to

validate that model we should compare the behaviour of the model with that of real human

being subjected to step changes in ambient temperatures as shown in fig.

The temperature of the tympanic membrane in the ear was measured for an approximation

of THC .

The subjects weight loss was used to determine the amount of perspiration that

evaporated. The results of the model compared well with the physiological data.

The next step for the validation of model was to carry out ice cream experiment test. In

this test, an abrupt change in trunk core temperature was produced rapidly eating 420 gm

of ice-cream.

The results adequately represented the desired physiological data. Stolwijk and Hardys

original model was implemented on an analog computer.

After the model was rewritten in FORTRAN in general purpose digital computers, scientists

ran a series of dry-ice cooling experiments which found a good match between their

implementation of model and their new physiological data.

This is how validation model is created or defined for thermoregulatory system.


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19 .GibbsDonnan effect

The GibbsDonnan effect (also known as the Donnan effect, Donnan law, Donnan equilibrium,

or GibbsDonnan equilibrium) is a name for the behavior of charged particles near a semi-

permeable membrane that sometimes fail to distribute evenly across the two sides of the

membrane.

The usual cause is the presence of a different charged substance that is unable to pass through

the membrane and thus creates an uneven electrical charge.

For example, the large anionic proteins in blood plasma are not permeable to capillary walls.

Because small cations are attracted, but are not bound to the proteins, small anions will cross

capillary walls away from the anionic proteins more readily than small cations.

Some ionic species can pass through the barrier while others cannot. The solutions may be gels

or colloids as well as solutions of electrolytes, and as such the phase boundary between gels, or

a gel and a liquid, can also act as a selective barrier. The electric potential arising between two

such solutions is called the Donnan potential.

The Donnan equilibrium is prominent in the triphasic model for articular cartilage proposed by

Mow and Lai, as well as in electrochemical fuel cells and dialysis.

The Donnan effect is extra osmotic pressure attributable to cations (Na+ and K+) attached to

dissolved plasma proteins.


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20. Draw an explain working of thermoregulatory plant model.

1. This is a simplified version of Stolwijk and Hardys model.

2. Resting state values of metabolic heat production (M0), thermal conductance between

compartments (resistors between the units), thermal conductance between skin

segments and environment (at temperature TA) and insensible evaporative heat loss (EV)

are given.

3. The left half of the figure shows the blood flow in litres per hour. The brain is perfused

at 45litre/hr and the core of the trunk at 210litre/hour.

4. All the other blood flows change according to the demand. The extra arrows to the coreof the head, muscles of the trunk and extremities indicate that extra heat inputs occur in

shivering and in exercise.

5. The body is modelled as a series of compartments. The head and the trunk are modelled

by cylinders and the aggregate of the extremities is modelled by another cylinder.

6. These cylinders are subdivided into coaxial shells representing the skins, fat, muscle and

viscera. The central blood volume contained by the heart and the large arteries and

veins is a separate compartment.

7. The dimensions of the cylinders were chosen so that their mass /surface ratio

corresponds to that of an average person. Heat exchange occurs only radially withineach cylinder.

8. This conductive heat must flow through the thermal resistance indicated by long

resistors symbols. It is assumed that there is no conduction between the cylinders.

9. Heat is transferred between the cylinders by convection of blood flow. This flow is under

the control of the vasomotor centers and varies significantly. These pathways are


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represented by short resistor symbols. Only the flow to the brain and viscera is not

variable.

10. Basal metabolic heat sources and heat sources caused by muscular activity or shivering

are shown with arrows into the appropriate compartments. Heat losses resulting from

evaporation are shown with arrows out of the compartments.

21. Compartmental modelling

A model consisting of a finite number of compartments with specific

interconnections among the compartments.

Compartmental modelling results from the requirements to simplify the structure as

much as possible.

When analyzing the systems of the body characterized by a transfer of solute from

one compartment to another, such as the respiratory and circulatory systems, it is

convenient to describe the systems as a series of compartments.

This is particularly useful when analyzing complex systems. Compartmental

modelling also has a solid theoretical foundation since it is based on conservation of

mass.

The system to describe with the compartmental approach is subdivided into a finite

number of states interconnected among them. The interconnections can represent

transport fluxes or chemical transformations.

Compartmental models can be linear or non-linear and an extensive literature exists

on methodological aspects connected with their formulations, identifications and

validation.


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The figure above shows two substances A and B, both exist in plasma and

liver. Thus, the plasma concentration of A and plasma concentration of B are

both compartments, similarly the liver concentration of A and the liver

concentration of B are also compartments.

A can be irreversibly lost from plasma, no exchange in plasma can occur

between A and B.

Both A can exchange between plasma and liver similarly both B can also

exchange. B can be lost in the liver and not in plasma.

22. Parkinsons Syndrome

Parkinsons syndrome is Central nervous system disease afflicting elderly persons

and is well known in the neurological literature. The muscles and the peripheral

nerves of patient are generally not affected by the diseases until late secondarychanges occur.

This the interruption of stretch reflex reduces the rigidity of muscles which is a

prominent sign of the syndrome.

Stark and his colleagues performed the experiments on a group of 20 patients. They

were asked to rotate the handle back and forth as rapidly as possible, the patients


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could not attain frequencies as high as the normal human, which implies that they

could not open the loop on muscle spindle system.

This explains the essential nature of rigidity of Parkinsons syndrome. In these

patients the spindle length regulator is always on full gain, (except in sleep), and

thus opposes and weakens corticospinal inputs. They then had normals and patients track unpredictable target movements and

recorded their responses and constructed Bode diagrams.

As seen in figure, the patients had much lower gains at high frequencies. These

results explained that patients could not turn off their muscle spindle systems and

allow unimpeded(without any block) fast control by cortical-motorneuronal

pathways.

It also implies that the feedback control system of patients should be more stable

than in normal. This brings up the most puzzled symptom of this disease.

Parkinson patients often have a tremor of the limbs. In starks patients theoscillations were about 10 in amplitude and ranged from 3 to 10Hz. The cause of

oscillations probably resides in the higher levels of the CNS, which could not be

explained on the feedback control model of fig.

Thus, both inability to turn off the muscle spindle system and the parkinsonian

tremor are caused by disturbances in CNS rather than in peripheral nervous system.

23. Explain validation model for thermoregulatory system in detail.

Ans:>>>

After a model is formed, it is very much necessary to validate that model. In order to

validate that model we should compare the behaviour of the model with that of real human

being subjected to step changes in ambient temperatures as shown in fig.

The temperature of the tympanic membrane in the ear was measured for an approximation

of THC .

The subjects weight loss was used to determine the amount of perspiration that

evaporated. The results of the model compared well with the physiological data.

The next step for the validation of model was to carry out ice cream experiment test. In

this test, an abrupt change in trunk core temperature was produced rapidly eating 420 gm

of ice-cream.


31/31

The results adequately represented the desired physiological data. Stolwijk and Hardys

original model was implemented on an analog computer.

After the model was rewritten in FORTRAN in general purpose digital computers, scientists

ran a series of dry-ice cooling experiments which found a good match between their

implementation of model and their new physiological data.

This is how validation model is created or defined for thermoregulatory system.

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