Biocybernetics

Dr. Fragoon Ahmed

CONTROL IN PHYSIOLOGICAL
SYSTEMS

 The study of control in physiological systems reveals

a range of manifestations of complexity.
 A central feature is homeostasis at various levels in
the hierarchy from intracellular mechanisms to
mechanisms operating at the level of the whole
organism.
 Much of the major focus is related to the internal
environment of the intact physiological organism, but
control systems also feature prominently in relation
to the way we deal with externally sensed
information (via the eyes, ears, etc.).
CONTROL IN PHYSIOLOGICAL
SYSTEMS

 The patterns of regulation and control occurring within

physiological systems are many and varied. Static and dynamic
equilibrium, linear and nonlinear regulation, weak and highly
stable rhythmicity (oscillating systems) – all are instrumental in
the maintenance of the living state.
 In most engineering applications of feedback control, the focus
is temporal control, studying and seeking to minimize transient
errors in the approach to a goal value.
 In the physiological state, however, in addition to such temporal
aspects, control also involves geometric or functional patterns
(in the context of neural control) and the minimization of their
deviations from normal resting values.
CONTROL IN PHYSIOLOGICAL
SYSTEMS

 Let us return now to chemical regulation and control within the

physiological system and examine some of its dynamic features.
 A range of regulatory mechanisms is involved, both in the
maintenance of the environment within the individual cell and in their
aggregation into the behavioral patterns of the entire organism.
 Control is evident at each level. For example, at the lowest level there
is both transcriptional and translational control involved in protein
synthesis, incorporating genetic effects transmitted via RNA.
 Feedback features in all these control mechanisms.
 Proteins may either be incorporated into the cellular structure or may,
as enzymes, be involved in subsequent chemical reactions occurring
within the cell.
Enzymes

 The rate of chemical changes in physiological

systems is generally controlled by such enzymes,
which act as biological catalysts.
 In the simplest enzyme controlled reaction, an
enzyme E and chemical substrate S form an
enzyme-substrate complex X which in turn
decomposes into the original enzyme E and the
product of the reaction P.
 This system of reactions can be represented by the
equation:
 Assuming first order reactions, such that rate of
change is directly proportional to the concentration of
the ingredients of the reaction, the mass transfer
equations for the system are given by:
 where E, S, X and P are the quantities of free
enzyme, substrate, complex and product
respectively.
 The k values are the rate constants for the
appropriate reactions, so that for instance
kXP is the rate constant relating rate of
production of product to the quantity of
complex.
Hormones

 Hormones are powerful chemical agents secreted by endocrine

glands such as the pancreas and the thyroid gland.
 Control in such chemical reactions, however, is not confined to
the action of enzyme systems.
 For example, there is a large number of chemical reactions that
form a part of glucose metabolism taking place in the lever that
are under enzyme control.
 However, this set of reactions is also controlled by a range of
hormones, including insulin, glucagon, adrenalin, growth
hormone and the thyroid hormones.
 Three types of hormonal action are evident from a control perspective.
 The first type of action is associated with hormones that act on smooth
muscle or other cells to stimulate an effect such as muscle contraction .
 These are sometimes referred to as kinetic hormones.
 The consequence of this action is perceived by a neural detector.
 For example, arterial baroreceptors monitor changes in blood pressure
following the secretion of adrenalin from the adrenal medulla.
 The fact that neural transmission is involved in the feedback pathway
from the site of the kinetic action to the particular endocrine gland
ensures that within seconds the appropriate changes in hormonal
output can occur.
 The second type of hormonal action manifests itself in the
change in blood concentration of a particular chemical.
 Hormones bringing about such action are sometimes referred
to as metabolic hormones.
 For example, insulin secreted in the pancreas brings about a
decrease in the level of blood glucose.
 The feedback in this case is chemical, the lower level of blood
glucose in the blood perfusing the pancreas being recognized
and inhibiting further insulin secretion.
 The limitation of this type of control stems from the fact that this
local chemical feedback has an effective time constant which is
typically of the order of tens of minutes.
 The third type of hormonal control involves endocrino-kinetic or trophic
hormones (sometimes also known as endocrine-kinetic hormones).
 These are produced by one gland which, in turn, controls the activity of
another .
 For example, ACTH is a trophic hormone secreted by the anterior
pituitary which, in turn, acts upon the adrenal cortex in controlling the
rate of secretion of cortico-steroids.
 The actions of such target gland hormones are complex, multiple and
slow. The effects of cortico-steroids, for instance, are such that their
actions on peripheral tissues cannot be monitored by changes in a
single blood constituent.
 It is therefore the concentration of the steroid itself that is used as the
feedback signal.
 Also it can be seen that the feedback effects are more complex for this
type of hormone.
 The overall control of the chemical processes of physiology involves the
nervous system as well as hormones.
 Many of these are still not very well understood, though considerable advances
in understanding have taken place in some areas; for instance, relating to the
vagal control of breathing.
 Nevertheless, it is clear that a complex array of control actions is involved in the
totality of chemical processes to be found in the intact physiological organism.
 At a simple level there is strong local control action.
 This enables many of the chemical processes to be regulated without recourse
to higher levels of control. This is due to the fact that chemical reaction rates
are generally concentration-dependent, giving rise to inherent negative
feedback.
 This, together with the sophisticated array of enzymic, hormonal and nervous
system mechanisms involving both chemical and neural transmission, provides
a degree of flexibility and adaptability that constitutes
 an excellent example of effectively functioning control.
HIERARCHY

 The structure of the overall human organism offers

itself to analysis in hierarchical terms; from genes,
through cellular subsystems, cells, organelles,
organs to the intact physiological organism.
 At each level there is feedback and control action of
a variety of modes.
 Equally each level of organization is aggregated into
the next level up in this organizational hierarchy (e.g.
cellular subsystems aggregate into cells and organs
into the intact organism).
 Examining the control of organ systems a number of
mechanisms are evident.
 As we have already seen, in many processes there is strong,
local low level chemical control.
 This is particularly appropriate for the situation in which
disturbances to the metabolic process are unlikely to be large in
magnitude.
 On the other hand, for the likes of carbohydrate metabolism
where gross perturbations occur daily, through the feeding
process, hormonal mechanisms form an integral component of
the regulatory process.
REDUNDANCY

 One more feature that characterizes the complexity of human

physiology is redundancy.
 The most obvious examples of redundancy relate to the provision of
pairs of organs: two eyes, ears, lungs and kidneys.
 In the case of the sensory organs, this permits an increased
sophistication in sensory perception, such as binocular vision.
 The duplication of lung and kidney function provides the ability to cope
with extremes of operating conditions that would tax the single organ.
 Moreover, the kidney, whilst of prime importance in the regulation of
the body’s water balance, also has a limited capacity to act as a
chemical plant and can therefore provide a limited degree of back-up
for the major chemical plant – the liver.
 A degree of redundancy is also apparent in the organ control systems.
 For example, a number of hormonal control loops are involved in the
maintenance of blood glucose levels.
 Glucagon, adrenalin, growth hormone and the cortico-steroids are all
capable in their several ways of remedying low glucose levels.
 This is not to say that all these hormones are specific in their action,
for many hormones mediate a variety of metabolic effects.
 Nevertheless, a high level of reliability is afforded in the correction of a
deficiency in blood glucose.
 On the other hand there is only a single control loop capable of
lowering elevated glucose levels – the insulin controller.
 This is, however, a robust controller in the healthy individual, thus
offsetting to a degree the absence of any back-up system from a
system design perspective
 Redundancy is also apparent in the nervous system.
 In many instances a small fraction of the available information needing to be
transmitted is carried by each of a large number of units.
 In this way immunity to large scale loss of information is provided, even though
small numbers of the central neurons are dying each and every day.
 Organisms with a higher nervous system are capable of responding selectively
to a vast number of specific combinations of sensory stimuli.
 This ability has led to the hypothesis that information from the dense organs is
progressively re-coded to higher levels in a less redundant form. Since the
transmission lines – the number of fibers in a sensory pathway – is fairly
constant, this reduction process would occur in terms of reduced average
activity in the sensory centers, that is economy of pulses.
 Great economy can be achieved by this recoding, providing of course that it
occurs with the minimum sacrifice of information.
FUNCTION AND BEHAVIOR AND
THEIR MEASUREMENT

 From the foregoing sections it is clear that physiological

systems exhibit complexity in a variety of forms.
 The integration of the system components, the manner in which
 they are inter-connected and the mechanisms by means of
which they are regulated and controlled gives rise to the
functional and behavioral patterns that are to be found in the
functioning physiological organism.
 Figure 2.1 provided us with one simplified representation of
some of this overall physiological complexity.
 It is these functional and behavioral patterns which are of
interest to us as physiological modelers.
 However, in order to be able to quantify the dynamic processes and effects that
are occurring within the complexity of our physiological systems, we must be
able to make measurements.
 This is where many challenges lay; there are limits as to what can be measured
in living organisms.
 There are constraints, both practical and ethical.
 For example, it is generally not possible to make invasive measurements on the
organs, nor in the tissues, nor of the secretion of the glands of the intact
physiological organism.
 This has traditionally meant that, in terms of chemical variables in the body,
measurements have been limited to those that could be derived from blood,
urine or breath samples.
 More is now possible, however, due to technological advance.
 Making use of advanced imaging modalities it is now possible to derive
measurements of say glucose in the brain, assuming that the organ in question,
brain, liver or kidneys for example, can be precisely identified from the images
in question.
 So, at an experimental level, our ability to access
and hence potentially understand physiological
complexity is limited.
 We are constrained by measurement technology and
methodology as to what may be measured directly
(in vivo).
 As far as accessing information regarding other
quantities is concerned, the only way forward is by
using indirect or inferential methods.
 This means using models as will be explained below.