YEREVAN STATE MEDICAL UNIVERSITY AFTER M.

HERATSI

NORMAL PHYSIOLOGY
HANDOUT FOR FOREIGN STUDENTS

YEREVAN – 2008
YEREVAN STATE MEDICAL UNIVERSITY AFTER M. HERATSI

Ter-Markosyan A.S., Harutunyan K.R.,

Arakelyan K.P., Avetisyan K.A.

NORMAL PHYSIOLOGY
HANDOUT FOR FOREIGN STUDENTS

Editor: professor Khudaverdyan D.N.

YEREVAN
Publishing house of the Yerevan State Medical
University after M. Heratsi
2008
 UDC 612 (07)

Normal Physiology (Handout for Foreign Students) / Ter-

Markosyan A.S., Harutunyan K.R., Arakelyan K.P., Avetisyan K.A.
-Yerevan, YMSU, 2008 - 330 pp.

Editor: professor Khudaverdyan D.N.

Reviewers:
Khanbabyan M.V., Professor of the Human and
Animals’ Physiology Department of
the Yerevan State Pedagogical
University after Kh. Abovyan,
Doctor of Medical Sciences
Hakobyan N.S., Professor of the Human and
Animals’ Physiology Department of
the Yerevan State University, Doctor
of Biological Sciences
English language editor: Bisharyan M.N.
In the handout are represented the main parts of physiology,
which correspond to the syllabus of the normal physiology course. It
will be useful for foreign students of medical and biological high
schools.

The handout is adopted by Methodical Comission for Foreign

Students of theYerevan State Medical University after M. Heratsi.

ISBN 978-9994-40-78-7 © Dpt. of Physiology of YSMU, 2008

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ISBN 978-99941-40-78-7 © ºä´Ð ýǽÇáÉá·Ç³ÛÇ ³ÙµÇáÝ, 2008
 CONTENTS

Introduction 10
Chapter 1. Physiology of Excitable Tissues 16
1.1.General Physiology of Excitable Tissues 16
Bioelectrical phenomena. Historical outline 17
Resting potential 19
Action potential 22
Passive and active transport of ions 25
Changes of excitability during excitation 27
Comparative characteristics of the local (LP)
and action (AP) potentials 28
Parameters of excitation 29
The effect of direct current on excitable tissues.
The law of stimulation polarity.
Physiological electrotone 32
1.2.Physiology of Nerve Fibre 34
Classification of nerve fibres 34
Laws of excitation conduction in the nerve 36
Mechanism of impulse conduction in the nerve fibres 37
1.3.Physiology of Neuromuscular Transmission 39
Mechanism of excitation transmission
in neuromuscular synapse 40
The properties of the neuromuscular (chemical) synapse 42
1.4.Physiology of Muscles 43
Skeletal Muscles 44
Types of the muscle contraction 45
Muscle single contraction 45
Tetanus and summation of contractions 46
Ultrastructure of myofibrils 47
Mechanisms of muscle contraction and relaxation 49
Work and force of the muscle 51
Some peculiarities of smooth muscles 52
Chapter 2. Physiology of the Central Nervous System 53
2.1.General Physiology of the Central Nervous System 53
Structural and functional elements of the CNS.
Neuron and glia 53

6
 Interneuronal communications 59
Reflector character of the CNS activity 62
Inhibition in the CNS 64
Nervous centre’s properties 69
Principles of coordination in the CNS 73
2.2.Special Physiology of the Central Nervous System 79
Spinal cord 79
Hindbrain 84
Midbrain 87
Cerebellum 89
Diencephalon. Thalamus and hypothalamus 92
Chapter 3. Higher Nervous Activity 97
3.1.Conditional and Unconditional Reflexes 97
Rules for building conditional reflexes 99
Components of unconditional and conditional reflexes 99
Mechanisms of conditional reflex producing 100
3.2.Cortical Inhibition 102
Analysis and synthesis 104
Mutual induction of excitation and inhibition 105
3.3. Types of the Higher Nervous Activity 105
3.4. Sleep 107
Chapter 4. Physiology of the Vegetative Nervous System 115
General characteristics of the vegetative nervous system 116
Comparative analysis of the somatic and the vegetative
nervous systems 120
Properties of the vegetative ganglia (synapses) 121
Mechanism of impulse conduction in vegetative synapses,
their mediators 123
Vegetative reflexes 127
Chapter 5. Physiology of the Endocrine System 128
5.1. General Characteristics of the Endocrine Glands 129
Structure, properties and action mechanism
of hormones 131
5.2. The Hypothalamo-hypophysial System 136
The hypothalamo – extrahypophysial system 139
The hypothalamo- neurohypophysial system 140
The hypothalamo-adenohypophysial system 141
5.3. Special Physiology of the Endocrine Glands 146

7
 Physiology of the thyroid gland 145
Physiology of the parathyroid glands 148
Physiology of the adrenal glands 150
Physiology of the sex glands (gonads) 154
Physiology of the pancreas 159
Chapter 6. Physiology of the Blood System 162
6.1. Internal Medium of the Body 162
Composition and properties of blood 162
Composition and properties of lymph 166
6.2. Blood Formed Elements 168
Erythrocytes 168
Leucocytes 172
Thrombocytes (platelets) 176
6.3. Blood Coagulation 177
Vascular-platelet hemostasis 178
Coagulation hemostasis 179
After-phase of hemostasis 180
Anticoagulation mechanisms 180
Regulation of blood clotting 181
6.4. Blood Groups and Rh-factor 183
Blood groups 183
Rhesus-factor 185
Chapter 7. Physiology of the Cardio-vascular System 187
7.1. Physiology of the Heart 187
The heart conductive system and automatism 188
The phase analysis of the heart cycle 194
Methods of investigation of the heart activity 196
Cardiac muscle physiological peculiarities 201
Regulation of the heart functional activity 204
7.2. Physiology of the Vascular System 217
General principles of the structure and functioning
of the vascular system. 217
The main indices of hemodynamics 220
Arterial pulse 226
Regulation of blood circulation 229
Chapter 8. Physiology of the Respiratory System 235
External respiration 235
Lung volumes 241

8
 Lung ventilation 243
Gas exchange in alveoli and tissues 244
Gas transport by the blood 249
Regulation of respiration 252
Respiration under various circumstances 260
Chapter 9. Physiology of the Digestive System 266
Functions of the digestive system and types
of digestive processes 266
Digestion in the mouth 268
Digestion in the stomach 273
Digestion in the small intestine 280
Digestion in the large intestine 288
Absorption 291
Motor activity of the gastro-intestinal tract 293
Periodic activity of the digestive organs 298
Chapter 10. Metabolism of Energy and Thermoregulation 301
10.1. Metabolism of Energy 301
10.2. Thermoregulation 307
Chapter 11. Physiology of the Excretory System 311
Morpho-functional characteristics of the kidneys 311
Kidney blood supply 314
Formation of urine 316
Urine excretion and micturition 325
Endocrine function of the kidney 325
Regulation of kidney function 327
Literature 329

9
Introduction

The term “Physiology” generates from the Greek words

– physics (nature) and logy (studying). Physiology studies the
main processes of alive organism’s activity, its organs, tissues,
cells and their structural elements in conjunction with external
environment.
So the goal of physiology is to reveal the organs’
functions, intra-organic connections, and interactions between
the organism and surrounding medium which is the necessary
condition for its existence.
Physiology and other disciplines. Physiology is in close
connection with other sciences and firstly with such
morphological disciplines as anatomy, histology, cytology,
since structure and function are interconnected and determine
each other.
As during the activity of cells the convection of
substances and energy proceeds, physiology is based on the
rules of physics and chemistry that brings to the development
of separate disciplines – biophysics and biochemistry.
Physiology is the theoretical base of general pathology
and clinical medicine. Without deep comprehension of the
heart, lungs, digestive system and other organs’ function it is
impossible to reveal the pathology. Achievements of
physiology are of great use in medicine, e.g. Pavlov’s works on
the physiology of the digestive tract organs serve as a basis for
gastroenterology and dietology. In its turn medicine gives a
clinical material for physiological study, e.g. different clinical
manifestations of endocrine impairments enable the further
study of the inner secretion glands’ function.

10
 The connection of physiology and cybernetics is the
point of interest and helps to reveal the general principles of
function regulation of their interaction using artificial
modelling of biological phenomenon.
Physiology is an experimental science. The investigator
intervenes artificially in organism function. In 1628 English
physician William Harvey using the experimental method of
investigation, published the data of his observations in the
small booklet “Anatomical investigations of the heart and
blood motion in animals” and settled the basis for the great
science - Physiology. Harvey is considered to be the founder of
Physiology.
The main methods of physiological investigations.
The main methods are the observations and experiment.
Experimental methods are divided into two types – acute,
that was widely used by Harvey at the beginning of the 17th
century; and the chronic one, that was deeply worked out in
Pavlov’s investigations.
Acute method or vivisection is performed in immobilized
animal by means of narcotic preparations or otherwise, during
which they perform section and the further investigation of the
interesting organ. But this method has its disadvantages. First,
it is impossible to carry out the experiment for a long time, as
well as to use that animal repeatedly; second, the organ activity
is studied beyond its connection with other ones and out of
normal physiological conditions. It is the analytical method of
investigation. But, in spite of these disadvantages, all the main
information about functions of majority of organs has been
gained with the help of this method, and up to now it has
remained as one of the main investigation methods.

11
 In case of chronic method the animal undergoes different
surgical operations in the aseptic and antiseptic conditions.
After recovering under the normal physiological conditions the
function of the organ in the whole organism is studied using
the adequate stimulus. The opportunity of multiple repeating of
the experiment on the same animal is an advantage of the
chronic method. The chronic method is a synthetic one.
Clinical and functional tests, as well as the control of human
functions in space also refer to the chronic method.
The most implementing methodical ways are the
extirpation of an organ, transplantation, denervation (cutting of
the nerves) or the pharmaceutical inhibition of the organ
activity by different types of solutions, the content of which is
chosen by the investigator.
Owing to the scientific achievements in the field of
physics, the electrophysiological methods, the registration of
bioelectrical phenomena in alive cells (ECG, EEG, evoked
potentials and others) have been developed. That is a rather
subtle type of investigation.
Along with them graphical registration of experimental
data that have been used since the 19th century
(mechanocardiography, pneumography, miography etc.) also
remain applicable.
The main physiological regularities. From the
physiological point of view, the organism is an independent
unit of the organic world that is capable to regulate its
functions and to react on different changes of external
environment.
Adaptation of the organism to altering conditions of
external environment or to its own requests is carried out by

12
physiological functions and particularly by regulation or self-
regulation processes.
The self-regulation of the organism function, as well as
interconnection between organs and systems take place in two
ways, humoral and neuronal.
Humoral mechanism is phylogenetically older one and is
propagated by chemical substances, hormones, as well as
biological active substances and metabolic products. The main
property of the chemical stimulus is the absence of the specific
address and it influences on all the cells. But in spite of it the
sensibility of cells may be diverse, i.e. the pancreatic hormone
insulin acts on the diversity of cells, changing (increasing) the
permeability of membranes to glucose, especially in fatty tissue
and muscles. The hormone of the thyroid glands, thyroxin,
evokes the energy changes in the cells of the organism,
particularly in the heart and CNS.
Neuronal mechanism is the most important way of
regulation. The neuronal impulse has an appropriate address,
i.e. from the motoneurons of the definite segments of the spinal
cord thoracic part the impulse passes along the nerves to the
intercostal muscles; from the cervical segments to the
diaphragm, etc. Reaction is got faster by the neuronal way,
than by the humoral one. The both regulation types are
interconnected; the chemical substances influence on the
neuronal cells, altering their functional state (CO2 – on the
respiratory centre), on the other hand, the function of the
respiration regulating nervous centres ensures the certain
concentration of O2 and CO2 in blood.
The higher the evolution level of animal, the more is the
neuronal mechanism part in regulation.

13
 Self-regulation of physiological functions is realized
automatically by means of the feedback mechanisms. It means,
that regulated organ itself stimulates the regulatory mechanism
keeping on its own function of the definite optimal for the
organism level. An increased level of glucose in blood causes
enhanced production of insulin, that regulates the glucose level
in blood.
According to Claud Bernard “All vital processes have
only purpose to maintain the constancy of the internal medium,
that is the necessary element for the beneficial life” (1878). In
1929 by American physiologist Cannon the assumption of the
internal medium constancy was developed and introduced in
physiology as “homeostasis” notion.
Homeostasis is a relative constancy of the internal
medium and several physiological functions of organisms
(blood circulation, composition of blood, metabolism,
thermoregulation, etc.).
Maintenance of the blood content constancy, which
together with the lymph and the intercellular fluid makes up the
internal medium of organism, is of a crucial importance.
Among the parameters of the internal medium the more stable
are: blood pH – 7.36 – 7.4; the osmotic pressure - 7.6 atm,
ionic interrelations (Ca – 9-11 mg/% , Na – 0.8%; P – 3-4
mg%); the inter-products and the final metabolic product
concentration (nitrogen – 40 – 60mg%; urea – 30mg%, etc.)
the nutritional substances concentration (glucose – 80 –
120mg%, proteins – 7.2%, etc). In such a manner in spite of
continual income into organism from outside and produced
during metabolism osmotic active products, the osmotic
pressure value remains at a definite level (7.6 atm.). It occurs

14
due to regulation mechanisms and is changed only in
pathology.
The mechanisms providing homeostasis are called
homeokinetic ones: e.g. in salt content increase special
osmoreceptors send the impulses flow to the supraoptic nucleus
of hypothalamus stimulating the antidiuretic hormone’s (ADH)
production. Influence of ADH on the kidneys stimulates the
H20 reabsorption to the blood, restoring the Posm. In case of
H20 content increase in blood, i.e. Posm. decrease, the impulse
flow to the hypothalamus is reduced and ADH is produced in
less amount, and consequently the kidneys excrete water from
plasma, re-establishing the Posm. value.
In impairment of the homeostasis constants the
pathological state develops.

15
CHAPTER 1.
PHYSIOLOGY OF EXCITABLE TISSUES

1.1. GENERAL PHYSIOLOGY OF EXCITABLE TISSUES

All cells of alive organism possess irritability, but only

definite cells of alive organism possess excitability. Irritability
is the property of the tissue to pass from physiologically resting
state into the active state under internal or external influences.
This process is called irritation and correspondingly the
influences are called irritants or stimuli.
Classification of stimuli. They are classified by the
following criteria: 1) by nature, e.g. physical (mechanical,
electrical, light, etc.), chemical (salts, acids, bases, etc.),
biological (bacteria, viruses, their toxins, etc.). Of these stimuli
the electrical stimulus is the most preferable in physiological
experiments, because it is universal for all excitable tissues; it
has a short latent period of action, does not evoke postreaction
and can be dozed; 2) by strength (threshold, subthreshold,
superthreshold). The threshold is the lowest strength of
stimulus required to give a response by tissue. The
subthreshold stimulus is lower than the threshold one; the
superthreshold stimulus is higher than the threshold one. The
superthreshold stimulus can be maximal, optimal, pessimal; 3)
by location (external and internal), but this subdivision is
relative, e.g. CO2 and HCl can be external as well as internal
stimuli; 4) by biological significance (adequate and
inadequate). The adequate stimulus is accepted by the tissue

16
adapted during the evolution process to definite one (e.g. light
is the adequate stimulus for photoreceptors). Inadequate
stimulus is not specific for the given receptor, but can influence
on it (e.g. the mechanical stimulus brings to the light sensation
in photoreceptors).
Excitability is the capacity of the tissue to respond to the
action of stimuli by definite reactions. Excitation is manifested
by a number of common and specific processes. The common
processes are the following: generation of local and action
potentials, increased utilization of O2 by cells, intensification of
energetic and metabolic processes, changes of viscosity and pH
in cytoplasm and so on. The specific ones are: specific
reactions for the given excitable tissue, and are represented by
contraction of the muscle, the secretion process in the glandular
tissue, impulse conduction in the nerve fibre. The classical
excitable tissues are nervous, muscular and glandular.

Bioelectrical phenomena. Historical outline

The theory of “animal electricity” arose in the middle of

the 18th century. There were represented data that some fishes
(electrical rays) strung their preys with a strong electrical
shock. The founder of “animal electricity” theory was Italian
scientist Galvani (1791).
The first experiment of Galvani. To study the
physiological influence of electrical discharges of lightning on
the alive tissue Galvani used a preparation of frog hind legs
linked with the spine (Figure 1, A).

17
A. B.
Figure 1. Bioelectrical phenomena.
A) Galvani`s first and second experiments; B) Matteucci’s
secondary tetanus experiment.

After suspending this preparation on a copper hook from

an iron railing of a balcony, he noticed that the muscles of the
frog’s legs, swinging under the influence of the wind, were
contracting each time they touched the railing. He concluded
that this phenomenon was caused by the “animal electricity”,
being generated in the spinal cord and transmitted through the
chain, formed in a result of the leg being touched the railing.
This conclusion was opposed by Volta, who found that the
source of electricity were two different metals (copper and
iron).
The second experiment of Galvani. To deny Volta’s
objections Galvani carried out the second experiment using the
neuromuscular preparation contented of n. ishiadicus and m.
gastrocnemius. During preparing the neuromuscular
preparation he refused metal instruments and used the glass
ones. When he threw the nerve along the muscle, the muscle
18
contracted. Thus he proved that electricity could arise in the
tissue. Galvani’s second experiment is the classical experiment
of electrophysiology.
The next experiment of this field was Matteucci’s
experiment.
Matteucci’s secondary tetanus experiment. He used
two neuromuscular preparations (Figure 1, B). He contacted
the nerve of the second preparation with the muscle of the first
one and excited with rhythmical stimuli of the first preparation
nerve. In this case the contraction of the first preparation as
well as of the second one occurred. For the first time it was
shown that excitation (action potential) was capable to be
spread through alive tissue.

Resting potential

It is known that in physiological resting conditions the

inner side of membrane is charged negatively and the outside
one, positively, i.e. the living cell membrane is polarized. This
difference of potentials is called resting potential, which is
equal to -60 - -90 mV. The resting potential is measured by
means of micro- or macro-electrode techniques. The
microelectrode is micropipette, filled with 3 M solution of KCl.
The microelectrode is input into the cell and another,
indifferent electrode is applied to the surface of membrane.
Both electrodes are connected with register apparatus,
oscillograph or voltmeter (Figure 2). As soon as the
microelectrode pierces the cell membrane the register apparatus
registers the resting potential. In macroelectrode registration

19
the definite part of membrane is damaged, to which the
electrode is applied. The indifferent electrode is applied to the
membrane of intact surface. But the potential, being measured
by this method usually does not exceed -30 - -50 mV, because
the liquid flowing out from the tissue shunts the recording
system.

Figure 2.
Мeasurement of the resting
potential by means of micro-
electrode technique.

The origin of resting potential. Some scientists, e.g.

Osvald, Chagovets tried to explain the origin of resting
potential using Arrenius electrolytic dissociation theory. But
only in 1902 Bernstein gave the complete ionic theory, which
was proved experimentally by Hodgkin, Huxley and Katz in
1952. In compliance with this theory two factors are
responsible for the arising of resting potential: membrane
selective permeability for K+ and ionic asymmetry between
exterior and interior media of the cell. In the cell cytoplasm K+
concentration is 40-50 times higher than that in the extra-
cellular liquid. In contrast to it the extra-cellular Na+
concentration (in 10-12 times) and Cl- concentration (in 30-40
20
times) exceed the intracellular Na+ and Cl- concentration. The
permeability of the membrane to these ions is represented by
the following relation: K+: Na+: Cl- = 1 : 0,04 : 0,45. If the
resting membrane is permeable to potassium ions alone the
resting potential would correspond to the equilibrium potential
for potassium, as defined by Nernst’s equation:
RT K 0
E0 = In = −97.5 mV,
nF K i
where E0 is the resting potential;
R is the gas constant;
T is the absolute temperature;
F is Faraday number;
K0 and KI are the cell outer and inner concentrations of
potassium, respectively.
The experimentally obtained value of the resting
potential is lower than that calculated by Nernst’s equation,
which is explained by the fact, that the membrane is permeable
not only to K+ but to Na+ and Cl- though to a lesser degree.
The following model experiment explains the resting
potential origin. The vessel is divided by an artificial
membrane, which is selectively permeable to K+, but
impermeable to anions, e.g. SO42-. Both parts of the vessel are
filled with K2SO4 solution. But the concentration of this
solution in the right part is higher than that in the left one.
Owing to the existence of the concentration gradient potassium
ions begin to diffuse from the right part to the left one. The
negative anions, to which the membrane is impermeable, are

21
accumulated at the membrane surface in the right part of the
vessel. By their negative charge they keep potassium ions
electro-statically on the membrane surface in the left part of the
vessel, which causes polarization of the membrane, i.e. the
resting potential.
The direct evidence of the competent of Bernstein’s
theory was obtained by Hodgkin and his co-workers on a squid
giant axon. The cytoplasm was squeezed out of the axon and
the collapsed membrane was filled with an artificial saline
solution. In cases, when the concentration of potassium in the
solution was close to the cellular concentration, the normal
value (-60 - -90mV) of resting potential was established
across the membrane. A reduction of potassium concentration
in the internal solution led to reduce of the membrane potential.
These experiments demonstrate that K+ concentration
gradient is the principal factor that determines the value of the
resting potential in a cell.

Action potential

A rapid variation of the excitable tissue membrane

potential during excitation is called an action potential. The
action potential can be also registered by micro- and macro-
electrode methods, i.e. by the intra- and extra-cellular leads.
For a long time physiologists supposed that the action potential
is the disappearance of the resting potential. But detail
investigations showed that the amplitude of the action potential
exceeds the value of the resting potential by 30-50 mV. During
the development of the action potential the resting potential

22
does not simply disappear, as it was previously believed, but
the membrane potential is reversed, so the inner surface of
membrane becomes positively charged in relation to its outer
side. The action potential can arise under the threshold and
superthreshold strength action. The main property of the action
potential is the capacity to propagate along the excitable tissue
without decrement.
Phases of action potential. On the curve of the action
potential we can differentiate the local potential (Figure 3,
phase 1), which is the first phase of excitation. If the local
potential reaches to the critical level of depolarization (Ecr.), the
action potential arises. Ecr. = E 0 + ∆V,
where E0 is the resting potential;
∆V is the excitation threshold.
The first phase of the action potential is the
depolarization (ascending part of the curve), during which the
membrane potential reduces to 0 (Figure 3, phase 2), and then
reappears (Figure 3, phase 3), but by an opposite sign, i.e.
reverts, reaching to +30 mV (peak of the curve or spike). This
part of action potential curve is called overshoot. After
reaching the spike (Figure 3, phase 4) the membrane potential
returns to its initial level. On the curve of the action potential it
is represented as the repolarization phase (Figure 3, phase 5;
descending part of the curve).
Sometimes the action potential is accompanied by after-
potentials. Two types of after-potentials are distinguished:
depolarizing (Figure 3, phase 6) (negative) and hyperpolarizing
(Figure 3, phase 7), positive after-potentials, after which the
23
membrane potential finally returns to its initial level (Figure 3,
phase 8).

3 5

1 6
8
7

Figure 3. Phases of action potential.

Ion mechanism of the action potential origin. The

reason for the action potential appearance is the changes of ion
permeability of the membrane (Figure 4). In excitation the
membrane permeability to sodium sharply increases, which is
considered as the depolarization phase. The inflow of sodium
ions is the auto-regenerative process. Na-channels are the
potential-dependent ones. Sodium ions inflowing the cell
change the membrane potential, and more sodium channels
open, i.e. sodium provides self-regulation. Afterwards the
inactivation of sodium channels, as well as activation of Na-K–

24
pump and K-channels are observed (spike). The repolarization
phase of the action potential is conditioned by K-channel
activation, which is reduced during the negative after-potential
phase and reactivated during the positive after-potential phase.

Figure 4. The ionic mechanisms of action potential.

Passive and active transport of ions

During the discussion of ionic mechanisms of resting and

action potentials’ origin mechanisms it could be noticed that
across the membrane the passive and active transport of ions
took place: the passive outflow of K+ brings to arising of the

25
resting potential, and the inflow of Na+, to generation of the
action potential. The passive flow of ions occurs along the
concentration gradient by the potential-activated ionic
channels. We distinguish Na-, K- and Ca ion-selective
channels. K-channels possess the greatest selectivity. Their
diameter is 0.3 nm and they can transfer only K ions, but Na
channels transfer Na, as well as K ions, so they have less
selectivity, than K ones. All ionic channels consist of the
transport system of the protein nature and the so-called gate
mechanism. The gates assume two positions: they are either
fully closed or fully open. The gates are of two types:
activating and inactivating, the function of which is controlled
by the membrane potential. When the activating gates are open,
the channel is in an active state, in closure of the inactivating
gates, the channel is inactivated. Potential-dependent channels
are characterized by definite kinetics. Activation kinetics of
Na-channels is faster than that of K ones. The activation of Ca-
channels as well as their inactivation takes place very slowly.
The ionic channels have specific inhibitors, e.g. K-channel
inhibitor is amino-pyridine and tetra-ethyl-ammonium, Na-
channel inhibitor is tetrodotoxin, Ca-channel inhibitor is
verapamil.
The ion active transport is realized opposite to ionic
gradient with the energy expenditure. This type of ion transport
is performed by ion pumps, e.g. Na-K-pump provides the
exchange of Na+ and K+ against the concentration gradients of
these ions. Na-K-pump is activated at action potential
generation, when the intracellular concentration of Na+
26
increases. But it functions also in resting state and keeps the
ion asymmetry between the interior and exterior cell medium.
Due to this pump the outflow of 3 Na ions and inflow of 2 K
ions are observed, so this pump is electro-genic and
participates in resting potential arising. This pump is inhibited
by ouabain.

Changes of excitability during excitation

The excitability of the tissue is changed during the

excitation development (Figure 5). There is a certain relation
between the action potential phases and excitability. At the
development of a local potential the excitability rises (Figure 5
a), because the membrane potential approaches a critical
depolarization level. The depolarization phase of the action
potential coincides with the so-called absolute refractory
period, when the tissue loses excitability. In this phase the
tissue does not respond to any maximal stimulus (Figure 5, b).
During the repolarization phase of the action potential the
excitability is gradually recovered. This period is known as the
relative refractory period (Figure 5, c), during which the tissue
can respond to a superthreshold stimulus.
The after-depolarization phase is accompanied by the
increased excitability (supernormal excitability or exaltation,
Figure 5, d), since the membrane potential is closer to the
critical level, than in the resting state. In this phase the tissue
can respond to the subthreshold stimulus (∆V1<∆V).

27
 -70

Figure 5. Changes of excitability during excitation

In contrast, the after-hyperpolarization phase is

accompanied by the decreased excitability (subnormal
excitability), because of the deviation of the membrane
potential from the critical level (Figure 5, e). In this phase the
tissue can respond to the superthreshold stimulus (∆V2 > ∆V).

Comparative characteristics of the local (LP)

and action (AP) potentials
1. The AP arises in response to the threshold strength
stimulus; the LP appears under the influence of the
subthreshold stimulus (stimuli, which account for 50-75% of
the threshold value).
2. The AP is propagated in an unlimited distance
without decrement; the LP can spread only on 2-3 mm.
3. The AP obeys the “all or none” law, i.e. the same
amplitudes of AP to response of threshold and superthreshold

28
stimuli occur; the LP obeys the “strength’s relation” law, i.e.
the more is the strength, the more is response.
4. The AP is accompanied with the excitability
decrease, the LP, with the excitability increase.
5. The AP can’t be summed; the LP is summed.
6. The AP generation is conditioned by the regenerative
process of sodium inflow the cell; at arising of LP the initial
increase in the permeability to sodium is not sufficiently high
to induce fast regenerative process.
7. The AP evokes specific visual effects: contraction,
excretion, impulse conduction, etc.; the LP is invisible.

Parameters of excitation

In order to evoke excitation it is necessary to have an

alive tissue and stimulus. But the stimulus might be
characterized by the strength, action duration and steepness of
the strength’s increase. The main condition of excitation is the
stimulation of tissue by the threshold strength stimulus and
only after the membrane depolarization till the critical level the
action potential can be generated. If the steepness of the
strength’s rise reduces, the action potential amplitude
decreases, or no action potential appears at all. The reason of
this phenomenon is an increase of the depolarization critical
level, as a function of the ionic inactivation processes
development in tissue. This phenomenon is called an
accommodation or adaptation of tissue to stimulus.
In 1863 during the mollusk’s smooth muscle excitation
Fick noted that besides the strength its action duration is also
29
very important. The threshold strength of any stimulus within
certain limits is inversely proportional to its duration.
Mathematical dependence between the threshold and the
duration of excitation is inferred, which is described by the
empirical formula, determined by the properties of the tissue:
a
i = + b,
t
where i is the current strength;
t is its duration;
a and b are constants.
This dependence can be expressed by the curve, which
has been studied in detail in experiments on various excitable
tissues by Hoorweg, Weiss and Lapicque (1892-1909). The
curve has a form of an equilateral hyperbola (Figure 6). The
values of strength are along the ordinate axis and the values of
its duration along the abscissa. The threshold strength of the
current expressed in millivolts or milliampers is called
rheobase. The minimal time during which the current equal to
the rheobase must act to induce an action potential is
designated by the term “utilization time”. It implies that further
prolongation of the influence of the current has no effect, so it
is called “useless time”.

30
 I

b time
a

Figure 6. The curve of Hoorweg, Weiss, Lapicque. 1- rheobase,

2 - double rheobase; a- utilization time; b- chronaxie.

Due to the inverse dependence between the strength

value and its duration intensification of the current leads to a
shortening of the minimal time of stimulation, but not without
limits. As we can see, the stimulation by very short-termed
stimuli, the strength-time curve becomes parallel to the axis of
ordinates. It means that they produce no excitation, however
strong they may be. In practice it is difficult to determine the
utilization time. For that reason, Lapicque proposed the term
chronaxie, the least time, required for the current equal to
double rheobase to evoke excitation. Chronaxie shows the
excitation generating speed. There are constitutional and
subordinary chronaxies. The constitutional one is the property
of the isolated tissue, while the subordinary one is governed by
organism's regulating influence, particularly CNS.

31
 The measure of the chronaxie is widely used not only in
experimental research, but also in clinical practice and it has a
diagnostic significance.
Lability. It means functional mobility. It is the velocity of
elementary reactions underlying the excitation. It is also the
parameter of excitability. The criterion of lability is the
maximum number of the action potentials, that can be
reproduced by tissue in the unite time correspondingly to the
excitation rate. It can be expressed by the formula:
1
L= ,
R
where R is the absolute refractory period (refractoriness).
It is an inversely dependence between L and R.
The values of the lability of some excitable tissues are:
Lnerve = 500imp/sec, Rnerve= 1/500 = 0.002 sec;
Lmuscle= 200imp/sec, Rmuscle= 1/200 = 0.005sec;
Lsynapse= 100imp/sec, Rsynapse = 1/100 = 0.01sec.

The effect of direct current on excitable tissues.

The law of stimulation polarity. Physiological electrotone

An electrical generator with two electrodes, anode and

cathode can serve as a source of the direct current. When an
excitable tissue is stimulated by the direct current, excitation
arises only at the cathode at the moment the circuit is closed;
while at the moment of the circuit is open, excitation arises at
the anode. These facts are united under the law of polarity that
was discovered by Pfluger in 1859. The phenomena developed
at the cathode and anode are explained by the passive changes
32
of the membrane. At the moment the circuit is closed at the
side where the cathode is applied to the tissue, the negative
charge on the outer surface of the membrane appears, i.e. the
membrane passive depolarization occurs, which leads to the
excitability increase and even action potential generation. In
contrast, in this case at the anode the membrane is
hyperpolarized and the excitability decreases. At the moment
the circuit is open the local electrical current rises between the
depolarized and hyperpolarized membrane parts, which causes
an increase of excitability (depolarization) at the anode and
decrease of excitability (hyperpolarization) at the cathode. The
phenomena developed at the cathode and anode is called
cathelectrotone and anelectrotone and generally physiological
electrotone. There is a neutral point between cathode and
anode, where the membrane charge is not changed and is called
an isoelectric point. All these phenomena are the result of the
passive processes, which is proven by the experiments with
using ionic blockers. The latters are not effective in the
development of cathelectrotonic and anelectrotonic processes.
All these phenomena are observed during the short action
of cathode and anode. During the prolonged action of cathode
the excitability decreases, although the depolarization of
membrane occurs. It is conditioned by the depolarization
critical level increase (more than depolarization degree),
connected with the sodium inactivation process. This
phenomenon is called cathodic depression.

33
 1.2. PHYSIOLOGY OF NERVE FIBRE

Nerve fibre is the axon of the neuron, which diameter

makes up 10-20 µm and length above 1 m. The main function
of the nerve fibre is the transduction of a nerve impulse. But
due to microtubules, neurofilaments transporting fibres,
included into cytoplasm, the nerve fibres can perform the
transporting function realizing the convey of mediators,
enzymes from the soma to the nerve ending, or in the opposite
direction, from periphery to the soma.

Classification of nerve fibres

Nerve fibres are divided into two groups: myelinated and

unmyelinated ones. The unmyelinated fibre consists of an axis
cylinder, which encloses axoplasm with microtubules,
neurofilaments, mitochondria and so on. The myelinated nerve
fibre has the same structure, but its axis cylinder is covered by
the myelin sheath, which is produced by Schwann cells.
Schwann cell wraps itself in many times around the cylinder.
But the myelin sheath is interrupted at regular intervals, leaving
uncovered some parts of the axis cylinder membrane, which
are called Ranvier’s nodes.
In 1937 Erlanger and Gasser classified the nerve fibres
into 3 types by their excitability, impulse conduction velocity,
duration of the action potential, diameter: A, B and C. A type
in its turn is divided into 4 groups: Aα, Aβ, Aγ and Aδ. All the
nerves of A type are myelinated. Aα is the motor nerve fibre,
innervating the skeletal muscle (d=12-22µm, velocity of

34
impulse conduction, v= 70-120m/sec). Aβ, Aγ and Aδ are the
afferent fibres, which start from the pressure-, pain- and
thermo- receptors. Aγ also innervates an intrafusal muscle
fibres of muscle spindles. B type fibres are slightly myelinated
and serve as preganglionic fibres of the vegetative nervous
system. Their conduction velocity is 3-18 m/sec, diameter is 1-
3µm. A distinctive feature of these fibres is the absence of the
after-depolarization phase: the repolarization phase of the
action potential passes directly to the after-hyperpolarization. C
type fibres are unmyelinated fibres (d=1 µm, v=0.5-3 m/sec.).
These fibres are the postganglionic fibres of the sympathetic
nervous system. They have a long-lasting after-depolarization,
accompanied by still more prolonged after hyperpolarization.
Action potential of nerve trunk. The above mentioned
classification was made in a result of a detailed study of the
nerve trunk action potential properties. This action potential
depends on the strength of the stimulus applied. A weak
stimulus causes a weak response, as the stimulation is
augmented, the potential amplitude increases reaching the
maximal value. In contrast, the action potential of the isolated
nerve fibre belongs to the law “all or none”, i.e. it does not
depend on the stimulus strength. These regularities are
observed, when recording electrodes are applied to the nerve
near stimulating electrodes. The increase of the distance
between these electrodes up to 10-15 cm is accompanied by the
breaking up of the total action potential into several separate
potentials of the nerve fibres, which have different parameters.

35
This phenomenon is observed, because the velocity of different
nerve fibres’ conduction is dissimilar and arrivals of impulse to
the recording electrodes via these fibres are not simultaneous.
At first the stimulus arrives at the record apparatus via A type
fibre. On the nerve trunk action potential curve several spikes
differ that are the spikes of A, B, C nerve fibres action potential
spikes. So the electric response of the nerve trunk is the
algebraic sum of the action potentials of its individual fibres.

Laws of excitation conduction in the nerve

The propagation of impulse along the nerve belongs to

some rules or laws.
1. Anatomical and physiological continuity of a nerve.
Impulse conduction is feasible in anatomical and physiological
intactness of the nerve. That is why cutting, crushing of the
nerve, as well as some inhibitors’ influence on the nerve, lead
to the complete or partial disturbance of conduction.
2. Two-way conduction. Upon stimulation excitation is
propagated along the nerve fibre in both directions. This could
be proved by the following experiment. Two recording
instruments are applied on the nerve, which register the action
potential, arising in excitation of the nerve’s certain part
between them.
3. Isolated conduction. Conduction of impulse along the
nerve fibres, included into the same nerve trunk, is realized
separately. This phenomenon is elucidated by the fact that the
resistance of nerve fibre membrane is more than that of the
inter-fibre liquid. So the action potential can’t jump from one
36
fibre to another. Due to this phenomenon the impulse acts only
on that organ, which is innervated by the given nerve fibre,
providing normal functioning of the whole organism.
4. Conduction without decrement. Nerve impulse
(action potential) is conveyed along the nerve fibre without
decrement (attenuation), because the action potential is
generated newly in all points or certain parts of the nerve fibre.

Mechanism of impulse conduction in the nerve fibres

In unmyelinated nerve fibres an excitation is propagated

continuously point by point (Figure 7). Excitation of the certain
part of the fibre leads to depolarization of the membrane and
action potential generation. Local current arises between the
excited and unexcited parts, which causes the generation of the
action potential in unexcited part of the nerve fibre. In
myelinated nerve fibres the mechanism of impulse conduction
is the same (by the local currents). But the local current arises
between excited and unexcited Ranvier’s nodes and the action
potential can be generated only in these nodes, because the
sodium channels are located only in these parts of the nerve
fibre membrane. The density of Na-channels is very high,
10000 channels per 1 µm2 of the membrane. So the action
potential can be conducted by the saltatory manner, by
jumping. The reliability factor is very important in this
mechanism.
A
R f = AP = 5 − 6,
∆V

37
where AAP is the action potential amplitude;
∆V is the excitation threshold.
In this condition (when Rf =5-6) the impulse can jump
over 1-2 nodes and provide normal conduction even when
some anesthetics or Na-channel inhibitors act on these nodes.
D P

D P

D P

D P
Figure 7. The mechanism of impulse conduction in myelinated and
unmyelinated nerve fibres
(“P”- polarization and “D” – depolarization of the membrane).

Myelinated nerve fibre has some advantages in

comparison with unmyelinated one: 1) the conduction velocity
of myelinated fibre is higher and is proportional to its diameter,
whereas, the conduction velocity of unmyelinated fibre is
proportional to square root of its diameter; 2) it is more
economical in energetic aspect (energy saving), because only
in Ranvier’s nodes Na-K pump functions; 3) fatigue of
myelinated nerve could be observed rarely, because of the
lower energetic expenditure.

38
 1.3. PHYSIOLOGY OF NEUROMUSCULAR TRANSMISSION
NEUROMUSCULAR SYNAPSE
The term synapse means connection (junction). This term
was proposed by Sherrington. The structural formation
ensuring the transmission of impulses from the motor nerve
fibre to the muscle is called neuromuscular synapse. It is a
classical chemical synapse, because the specific chemical
substance, transmitter (mediator) provides the transmission of
excitation. In 1936 Dale demonstrated, that this transmitter was
acetylcholine. Synapse consists of three main elements: the
presynaptic membrane, the postsynaptic membrane and the
synaptic cleft (Figure 8).

Figure 8. Structure of
neuro-muscular synapse.
1- nerve ending;2-vesicles
of acetylcholine;
3-mytochondria;
4-synaptic cleft;
5-postsynaptic membrane;
6-cholinoreceptors;
7-sarcoplasmatic
reticulum; 8-myofibrils.

The presynaptic
membrane is electro-excitable, where the potential-dependent
Ca-channels are located. In contrast, the postsynaptic
membrane is chemo-sensitive. There are chemo-excitable
39
channels, which are coupled with the specific choline-
receptors. There is also a huge amount of cholinesterase
enzyme, breaking down acetylcholine. The presynaptic
membrane is the membrane covering the nerve ending, which
is represented as a specific neurosecretory apparatus, enclosed
the acetylcholine vesicles. In the neurosecretory apparatus the
electrosecretory coupling process occurs. The postsynaptic
membrane is related to the muscle fibres. The synaptic cleft
makes up 20-50 nm and filled with a liquid, which composition
is close to the blood plasma.

Mechanism of excitation transmission

in neuromuscular synapse

The action potential arriving at the presynaptic ending

evokes presynaptic membrane depolarization, in result of
which Ca-channels become open and Ca ions enter the nerve
ending. These ions are bound with calmodulin and the formed
complex activates the Ca-calmodulin dependent proteinkinase,
which provides the phosphorylation of vesicle and presynaptic
membrane proteins, ensuring the activation of these structures.
Due to the interaction of the vesicles and the presynaptic
membrane acetylcholine is released into the synaptic cleft and
interacts with the choline-receptors.
Owing to this interaction the chemo-sensitive channels
become open and sodium ions pass into the muscle, evoking
the depolarization of the postsynaptic membrane and formation

40
of so-called end-plate potential (EPP) or excitatory
postsynaptic potential (EPSP).
The properties of EPP are similar to the local response: it
depends on the amount of a linked acetylcholine (the more the
acetylcholine the more open channels are and the more is the
membrane depolarization level); it could be summed; it is not
propagated.
Afterwards local current arises between the postsynaptic
membrane and the neighboring part of electro-sensitive
membrane of the skeletal muscle, which leads to
depolarization. When the latter reaches the critical level, the
action potential arises. Thus the action potential (electrical
stimulus) of the motor nerve fibre, which has been transformed
into the chemical stimulus in the synapse, is newly
retransformed into the action potential of the skeletal muscle.
In case of successive nerve impulses it is necessary to remove
the preceding portion of acetylcholine before the arrival of each
next impulse to produce normal stimulation. This function is
accomplished by cholinesterase. Choline formed in the
breakdown of acetylcholine is brought back to the nerve ending
by a special transport mechanism. This portion of choline is
used for re-synthesis of acetylcholine.
Miniature potentials. It is known that a weak
depolarization of the postsynaptic membrane occurs not only
upon stimulation, but also at resting state. Depolarization leads
to arising of the so-called miniature potential. Its amplitude
(0.5 mV) is 50-80 times smaller, than EPP generated by a
single impulse. At rest acetylcholine is released from 1-2
41
vesicles. Each vesicle (quantum) contains 2000 acetylcholine
molecules. The miniature potentials usually arise at the
frequency of about one per second.
Inhibition of the neuro-muscular synapse. The
inhibition of the neuromuscular synapse can be realized in the
pre- and postsynaptic membranes. The inhibitors of Ca-
channels (e.g. verapamil) inhibit release of acetylcholine. On
the level of the postsynaptic membrane the inhibition occurs
upon the influence of inhibitors of acetylcholine receptors, e.g.
curare (poison). The acetylcholine-receptor has a higher
affinity to this poison, than to acetylcholine. In case of this
interaction synaptic transmission is blocked. Curare-like
substances (ditilinium, diplacin) are widely used in clinics,
when it is necessary to switch off the respiratory muscles and
ensure an artificial respiration. The next group of synaptic
inhibitors is the group of substances blocking the
cholinesterase. Upon the action of these inhibitors (eserine,
proserine, prostigmine) acetylcholine remains bound with the
receptors and the new impulses couldn’t pass across the
synapse.

The properties of the neuromuscular

(chemical) synapse

All the chemical synapses, including the neuromuscular

synapse, have the following properties:
1. One-way conduction, which is explained by the
presence of a large synaptic cleft and electrically unexcitable
postsynaptic membrane.

42
 2. Synaptic delay. It makes up 0.2-0.5 msec, which is
connected with the low mobility of chemical processes,
occurred in the synapse.
3. Rhythm transformation. It is conditioned by the fact,
that the lability of the synapse (100 imp/sec) is less, than that in
the motor nerve (500 imp/sec).
4. Synaptic facilitation. Each impulse conduction across
the synapse is easier, than the previous one, because each
impulse leaves a trace both on the presynaptic- and
postsynaptic membrane, exactly on the ion channels.
5. Synapse fatigue. In a frequent and long-term
stimulation of the synapse inhibition of conductivity is
observed, which is explained by weakening of acetylcholine
resources and decrease of acetylcholine receptors’ sensitivity.
6. High sensitivity to temperature, hypoxia and chemical
factors.

1.4. PHYSIOLOGY OF MUSCLES

Vertebrates and humans have three types of muscles:

striated muscles of the skeleton, cardiac muscle and smooth
muscles of the internal organs, vessels and skin. Cardiac
muscle has many differences compared to skeletal muscle,
although it is also striated.
Skeletal muscles
Functions and properties of striated muscles. Skeletal
muscles constitute an active part of the supporting system and
ensure the following functions:
1) posture support;

43
 2) they provide movements of separate parts of the body
relative to each other;
3) owing to them the body movement occurs in a space;
4) heat production. They produce 60% of the organism’s
total heat.
Skeletal muscles possess three very important properties:
excitability, conductivity and contractility.
In comparison with the motor nerve fibre the skeletal
muscle fibre excitability is less, therefore although the critical
level of depolarisation in the muscle and nerve fibres is nearly
equal (-50mV), the RP in muscle fibre is more negative (-90
mV), than that in nerve fibre (-70 mV). So the excitation
threshold (40 mV) in muscle fibres is higher than in nerve ones
(20 mV). This comparative electronegativity of the RP in
muscle fibres is explained by higher permeability of their
membranes to Cl-.
The AP amplitude in the muscle fibres is 120-130 mV,
and its duration, 2-3 msec. Excitation spreading velocity along
the muscle fibres makes up 3-5 m/sec.
The skeletal muscle obeys the law “strengths’ relation”.
It is conditioned by the fact, that the muscle consists of
enormous separate muscular fibres of different excitability and
as the stimulus strength grows up more amounts of myofibrils
involve into the contraction process. In result the muscle
response gradually increases. If the stimulus strength achieves
such a value, when all the fibres are excited, the maximal
contractile response occurs and the further strength increase

44
does not matter. Unlike the whole muscle, the isolated muscle
fibre obeys the “all or none” law.

Types of the muscle contraction

There are two types:

1. Isotonic, in which myofibrils are shortened, but the tension
is not changed. It occurs when only one end of the muscle is
fixed.
2. Isometric, in which the length of myofibrils remains
constant, but their tension increases. It occurs when both ends
of the muscle are fixed.
Altogether natural contractions in the organism are never
purely isotonic or purely isometric, since the muscle is shorted
under the load, but simultaneously change its tension.
Exceptionally the isometric is the contraction of the heart
ventricles. Mixed type of contraction is called auxotonic, that
can be concentric, when the muscle length is reduced, while its
tension is increased; and excentric, that is characterized by
increase of length and tension.

Muscle single contraction

Stimulation of the muscle or the motor nerve fibre by a

single stimulus evokes the single muscle contraction. But the
muscle reacts to the individual stimulus not immediately. There
is a latent period of 0.01 sec that is followed by the mechanical
response of the muscle that can be registered. The latent period
corresponds to the term of the AP inducing. In this period the
muscle is in refractory period, during which the processes of

45
preparing contraction, excitation conduction and
physicochemical alterations of the muscle occur. Beginning
with the middle of the contraction (shortening) period (it lasts
0.04 sec) up to the final of the muscle relaxation (that lasts
0.05 sec) the muscle is in the phase of exaltation (increased
excitability). Totally the single contraction duration is 0.1 sec.

Tetanus and summation of contractions

In natural conditions in the organism a skeletal muscle

usually receives number of impulses from the nervous system.
Stimulation of the muscle by rhythmic stimuli leads to a strong
and long-term contraction, known as tetanic contraction or
tetanus. Amplitude of the tetanic contraction exceeds the
maximal value of a single contraction in several times. Tetanus
can be of 2 types: complete (smooth) and incomplete (toothed).
Tetanic contractions of the muscle are the result of the
summation of individual contractions that can occur in two
possible ways. If the second stimulus is applied before the first
contraction has reached its peak, the second contraction will
fully merge with the first, forming a single summation peak
(so-called complete summation, smooth tetanus). If the second
stimulus is applied when the muscle has already begun to relax
after the first contraction, the peak of the second contraction
will be separated from that of the first (incomplete summation,
toothed tetanus). At complete summation the interval between
the first and second stimuli must be less than 0.05 sec, while
for the second type (incomplete summation), it must be longer
than 0.05sec. To produce tetanus artificially the muscle is
46
subjected to a great number of stimuli following one another at
the frequency required for summation. With a relatively low
frequency incomplete tetanus (toothed tetanus, Figure 9,a) is
obtained, and with a higher frequency, complete tetanus
(smooth tetanus, Figure 9,b). Generally tetanus can be
observed if the interval between stimuli is longer than the
refractory period and shorter than the whole duration of the
contraction response, so that the second stimulus will act on the
muscle before it has relaxed after the first stimulation. After
termination of the tetanic stimulation muscle fibres do not relax
completely and their initial length recovers but some time later.
This phenomenon is called post-tetanic or residual contraction.

Figure 9. Toothed (a) and smooth (b) tetanus.

Ultrastructure of myofibrils

The muscle fibre is a multinuclear formation that has

special contractile organelles, myofibrils. The myofibril
consists of 2500 protofibrils that are polymerized molecules of
actin and myosin proteins. Actin is a thin filament (d=5nm)
and consists of two twisted strands. Tropomyosin is located
between strands. Tropomyosin is bound with troponin, which
has high affinity to Ca2+. Myosin is a large, complex molecule

47
consisting of the tail, neck and head regions. Its diameter is 10
nm. Each head possesses ATP-ase activity. The structural and
functional unit of the muscle is sarcomere, limited by Z-
membranes (Figure 10). Actin is supported on the Z-membrane
and its ends enter spaces between myosin thick filaments.

A Band

Figure 10. Ultrastructure of myofibrils.

The area of the myofibril containing only actin filaments
and Z-membrane is called I-band (isotropic). This band is light
upon the light microscope. The region of both thin and thick
filaments possesses polarized light double refraction. It is dark
and is called A-band (anisotropic). In the middle of A-band
there is a light line H, where are only myosin filaments. So
under the light microscope in the skeletal muscle regular
altering dark and light striations are apparent, which give
striated appearance to the skeletal muscle.
48
 Conductive system of the muscle. Myofibril membrane
at Z-membrane level is invaginated, forming so-called T-
tubules (T-system) (Figure 11). On the both sides of the T
tubule there are cisterns of the sarcoplasmic reticulum. T-
tubule with two adjacent cisterns composes triad. Ca2+
concentration in the cisterns makes up 10-4M.
Mechanisms of muscle contraction and relaxation
The initiator of the muscle contraction is an AP. It
spreads along the membrane and into the depth of T-tubule.
Ca2+-channels of the cisterns are open and Ca2+ ions pass to the
myoplasm (Figure 11). Ca2+ concentration in the myoplasm
becomes 10-6M (at rest 10-8 M) and Ca2+ ions interact with
troponin. Troponin alters its configuration promoting the
tropomyosin displacement into the depth of the space between
the actin strands, which enables interaction of actin and
myosin. The heads of myosin are attached to the actin, forming
cross-bridges, which due to the neck hinge special mechanism
provide the displacement of actin towards the middle of the
sarcomere for the distance equal to 1 per cent of its length.
Then the heads step aside from the actin and are reattached to
the next region of the actin, providing its further displacement.
The head detachment from the actin occurs in the presence of
ATP and ATP-ase of myosin’s head. This mechanism of
contraction is called the “mechanism of filament sliding”. In
contraction the I-band and the H-line are reduced, while the A-
band remains constant (Figure 10).

49
 Figure 11. Conductive system of muscle and mechanisms
of muscle contraction.
After contraction of the muscle its relaxation comes. This
process is opposite to contraction. Owing to the Ca2+-ATP-ase
Ca2+ ions return into the cisterns against their concentration
gradient in result of which Ca2+ is detached from troponin and
tropomyosin is lifted up on the strand surface between the actin
filaments. The actin and myosin interaction desists.
As it is seen energy is required both for contraction and
relaxation of the muscle. The third way of ATP consumption in
the muscle is for the Na-K-pump work provision.

50
 Work and force of the muscle

In contraction the muscle, overcoming the load, fulfils

work equal to:
A=F× h,
where F is the strength;
h is the muscle shortening degree.
The strength of contraction depends on the peculiarities
of the given muscle, particularly on its cross section. There are
maximal and absolute muscle strengths.
A measure of maximal strength is the value of maximal
load that could be lifted up by the muscle, or the value of
maximal strength that could be developed by the muscle during
isometric contraction.
Muscle absolute strength is the maximal strength, which
acts on the unit area of its physiological section.
The physiological section is the section that is
perpendicular to all myofibrils (Figure 12).

Figure 12. Cross

sections of various
muscles.

51
 Work fulfilled by the muscle is governed by the
regularity named as a “rule of average loads”. Pursuant to this
rule the maximal work is carried out in average loads.

Some peculiarities of smooth muscles

In comparison with the skeletal muscles in the smooth

muscles troponin – tropomyosin complex is absent. During the
muscle contraction the actin and myosin interaction is provided
by phosphorylation of the myosin head through the calcium -
calmoduline complex. Relaxation of muscle is realized due to
dephosphorylation of the myosin heads. Herein, the Ca-ATP-
ase is weakly exhibited and the Ca2+ back into the cisterns
thereby Na-Ca exchange occurs. The energy expenditure here
is about 300 times less than that in the skeletal muscles.

52
CHAPTER 2.
PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM

2.1. GENERAL PHYSIOLOGY

OF THE CENTRAL NERVOUS SYSTEM

It is known that the main condition for existence and for

providing integrity of the organism and environment is the
organism’s ability to be adapted to the external medium
conditions. The important role in this providing belongs to the
neuronal system. In general, the main functions of the central
nervous system (CNS) are: the regulation and coordination of
all the organs’ and systems’ activity, the organism’s effective
adaptation to the continuously altering external medium
conditions and, as a result, the living organisms’ aimed
behaviour formation. Strictness of these regulatory influences
is due to the existence of a two-way circular connection
between the nerve centres and the peripheral organs.
The neuronal system owing to its neuronal principle of
the structure and the reflector mechanism of activity differs
from other regulatory systems by very high promptness of
reactions and preciseness of signals that provides a great
effectiveness of the organism’s reactions.

Structural and functional elements of the CNS.

Neuron and glia

The base of the present conception of the neuronal

system structure and function is the neuronal theory of Ramon

53
y Cajal and Charles Sherrington. This theory considers the
brain as a functional unity of neurons that are separate
structures and only contact to each other. So, the morpho-
functional unit of this system is the neuron. The main function
of neurons is perception of the afferent signals, their
elaboration, and transmission to other neuronal cells and to the
executive organs.
Structure of neuron. Each neuron consists of a body
(soma) and special processes: one long, the axon, and
numerous short ramifying ones, the dendrites (Figure 13). The
soma is covered with the protoplasmatic membrane and
contains all necessary cellular organelles (nucleus, ribosomes,
Golgi apparatus, mitochondria, etc.). The soma performs
synthetic function (e.g. synthesis of neuromediators). The
function of the axon is to convey impulses from the soma to
other cells or to other peripheral organs. The axon is an alone
long process that does not give collaterals at the beginning and
ramifies only at the contact site with the innervating cell or
organ. The axon has the following compartments:
1. Axon hillock (the site of its origin from the soma) and the
initial part of the axon, which over the 50-150 µm has no
myelin sheath. The initial part with the axon hillock is called
the initial segment. The specific feature of this segment is its
high excitability and an ability to generate the action potential.
2. Axon’s cylinder, which performs the conductive and
transport (e.g. synthesized in the soma neuromediator is
conveyed by the axon) functions.

54
 Figure 13. Structure of neuron.

3. Presynaptic terminal, in which the mediator vesicles are

located.
4. Dendrites are numerous ramifying processes, which
function is the reception of impulses arriving from other
neurons and their conduction to the soma. Dendrites with a
large amount of contacting endings and a big perception
surface fulfil the leading role in the neuron’s perception of
information.
Classification of neurons and their electro-
physiological properties. Neurons are classified by their
55
different properties. All neurons differ by their shape, structure,
size and function. By shape they can be round, oval,
multangular, pyramidal, etc. By size they vary from 5 µm to
150 µm. By amount of processes they can be unipolar, bipolar,
pseudo-unipolar and multipolar. By their significance
(physiological role) they are subdivided into: 1) afferent, or
sensory, or receptory neurons; 2) intercalated, or contact, or
interneurons, 3) efferent or motor neurons.
The afferent or sensory neurons in vertebrates are
represented in the spinal ganglia as pseudounipolar round cells.
The afferent neurons ensure the signal perception and
conduction from periphery to the centres, and are named as
centripetal ones. The afferent neurons are divided into
primary-afferent and secondary-afferent ones. The primary-
afferent neuron precepts the excitation by its receptors, in
which due to the changes of their ion permeability and
membrane depolarization the receptory potential (RP) arises.
The latter provides the generation of spreading action potential
(AP). The secondary-afferent neuron obtains the excitation
from the special sensitive neuron, in which RP arises. This
potential promotes the mediator release, providing the
generation of so-called generatory potential (GP) in the
secondary-afferent neuron ending. This potential getting a
definite critical value generates the spreading AP. RP and GP
on their physiological significance are similar to the local
potentials and give the similar effects of summation, relief,
they can’t be spread, etc.

56
 The effector or motor neurons give rise to an axon that
goes out of the CNS and finishes in the effector structures (for
example muscles, glands). These neurons have a lot of
ramifying dendrites. Impulses arising in the effector neuron
spread mainly centrifugally and provide the realization of
different final reactions. Among these motoneurons of the
spinal cord are studied more detailed. They are characterized
by efferent discharges of low frequency. This ability has an
important physiological significance. It is enough for the allied
peripheral effect (e.g. the muscle group general contraction),
maximally economical and excludes the opportunity to block
the peripheral effect due to the pessimum phenomenon (e.g.
pessimum in this rate does not arise). This low intensity arises
because of the prolonged hyperpolarization (positive after
potential) of the soma followed by each AP generation. Its
duration for the spinal motoneurons is about 100-150 msec.
The intercalated neurons are characterized by a huge
number (90% of all neurons) and small sizes. Moreover, their
processes do not leave the CNS. They are located between the
afferent and the efferent neurons. Interneurons can be divided
into the excitatory and inhibitory by evoked effects on other
neurons. The critical level of depolarization a little prevails its
resting potential and the threshold is low. The AP duration is
rather short (0.5 msec), the hyperpolarization is not significant
and is of a short duration. All this determines the characteristic
specificity of interneurons, the ability to generate discharges of
high frequency. The characteristic feature of the interneurons is
their ability to rhythmical and spontaneous activity.
57
 Systemic interaction of all the mentioned neuronal
populations provides the regulation, coordination and
realization of motor acts in a living organism.
AP of neuron. At first the AP arises in the axon hillock.
It is connected with the fact that the excitation threshold is
different in different parts of the neuron: it is the lowest in the
axon hillock region (due to a big amount of Na+ channels); it is
the highest in the soma and dendrites. In direct excitation of the
neuron its AP has two peaks: 1) the peak of the initial segment
(IS) and 2) the peak of the soma and dendrites. In the condition
of antidromic excitation the AP has three peaks: 1) the peak of
the myelin; 2) the peak of the IS and 3) the peak of the soma
and dendrites.
Glia. The main types of glia are: olygodendroglia,
astroglia and microglia. The glia is another compartment of the
CNS and consists of the glial cells, which like neurons have a
soma and many processes, but they have other specialization.
They make a network, matrix, in hinges of which the neuronal
cells are located. They make generally the main mass of the
brain. On the one side the processes of the glial tissue attach to
the neurons and on the other side to the vessels. So, it is
supposed, that the glial cells have not only the support
function, but also provide the transport of nutrients to the
neuronal cell, as well as remove the waste products from it
(metabolic function). Glial cells have also other functions: the
buffer (due to the high permeability to K+ ions they regulate K+
concentration in intercellular liquid), the isolating (Schwann

58
cells compose the myelin sheath), the defensive (microglia
performs the phagocytosis).

Interneuronal communications

The process of transduction of the neuronal impulse from

one neuron to another or organ proceeds by means of the
asserting contact (synapse) between them. All synapses are
classified by the mechanism of impulse transmission
(electrical, chemical and mixed), structure (axosomatic,
axodendritic, dendrodendritic, axoaxonic, etc.) and functional
specialization (excitatory, inhibitory). The electrical synapses
in general are represented in invertebrates and partly in
vertebrates, but the chemical synapses compose the main part
of synapses in the CNS of higher animals and humans. In
electrical type of synapses the synaptic cleft is practically
absent (it makes up 2-4 nm), inside which the protein bridges
are situated. The impulse transduction, realizing along these
bridges, in general resembles the conduction mechanism in
nerve fibre. This type of structure determines also the
peculiarities of their functioning:
1) the synaptic delay is practically absent;
2) the two-way conduction;
3) the generator for current arising in the postsynaptic
membrane is located in the presynaptic membrane, from which
it spreads on the postsynaptic membrane electrotonically
(passively). In this connection these electrical synapses are
called electrotonical ones.

59
 There are also mixed synaptic contacts in the CNS that
combine both chemical and electrical synaptic elements.
Chemical transmission of excitation. This mechanism
of transmission in the chemical synapses of CNS is similar to
that of the neuromuscular synapse. The neuromediator’s
extrusion is carried out by the special electrosecretory
mechanism in compulsory participation of Ca2+.
The electrosecretory mechanism includes: a) the
presynaptic ending depolarization by AP arriving; b) activation
and opening of the potential-dependent calcium channels; c)
Ca2+ ions entrance into the ending; d) interaction of Ca2+ ions
with neuromediator vesicles and their activation; e) interaction
of the vesicles with membrane, their rupture and the mediator
pouring out into the synaptic cleft.
The mediator interacting with the postsynaptic membrane
receptors causes postsynaptic membrane depolarization. The
investigations of English physiologist Katz have shown that
this depolarization (excitatory postsynaptic potential - EPSP) is
connected with Na+ and K+ ion permeability strict increase
(more for Na+). The EPSP is a basis for the AP generation and
neuronal impulse spreading. If the mediator evokes the
hyperpolarization of the postsynaptic membrane, conditioned
by K+ or Cl- permeability increase, the inhibitory postsynaptic
potential (IPSP) arises.
The main functional properties of the chemical synapse,
by which it is distinguished from the electrical synapse, are:
1) relatively long-lasting synaptic delay (0.2-0.5 msec); 2) one-
way conduction; 3) development of active postsynaptic
60
potential on the postsynaptic membrane (i.e. the neuronal
impulse generator arises on the postsynaptic membrane); 4)
postsynaptic potentials in the chemical synapses can be both
excitatory and inhibitory, while in the electrical synapses –
only excitatory; 5) rhythm transformation; 6) synaptic fatigue;
7) high sensitivity to temperature changes.
Chemical mediators (transmitters). In the neuronal
system many chemical substances have a mediator role. The
basic criteria of the mediator function of substances are: a)
their synthesis and accumulation in the presynaptic terminals
(vesicles); b)capacity for being released under the influence of
a nerve impulse; c) the similar molecular and ionic
mechanisms of action on the postsynaptic membrane of a
substance which is released by a nerve impulse and that of
artificially applied to the postsynaptic membrane; d)existence
of the special mechanism of their removal from the
postsynaptic membrane and synaptic cleft.
The same mediator can react with various receptors.
Different cholinoreceptors being combined with acetylcholine
give rise to different effects (excitatory or inhibitory). There
are different receptors to catecholamines (α− excitatory and
β − inhibitory). The ability of the same mediator to evoke
various changes of permeability in various postsynaptic
membranes is a reason for EPSP and IPSP arising in neurons.
Simultaneously the same neuron can serve as a site of
attachment for both inhibitory and excitatory mediators and so
generates the IPSP or EPSP. But glycine and γ- amino-butyric

61
– acid (GABA) are classical inhibitory mediators that evoke
only IPSP.
Principle of Dale. In all endings of the same neuron the
same mediator is secreted. Therefore the cholinergic,
serotonergic, dopaminergic, adrenergic and GABA-ergic
neurons are denominated.

Reflector character of the CNS activity

A reflex is a regular reaction of the organism to a change

in its external or internal environment effected through the
CNS.
Classification of reflexes. Reflexes can be classified
according to a number of attributes. According to biological
importance (nutritional, defence, sexual, orientation), to the
location of the reflexogenic receptors (exteroceptive,
interoceptive, proprioceptive), to the parts of the CNS,
involved in their performance (spinal, bulbar, mesencephalic,
cortical, etc.), to the character of response, or organs involved
(motor, secretor, vasomotor), etc.
Reflex arc. The reflex arc (Figure 14) involves receptors
(1), afferent nerve fibre (2), nervous centre (3), efferent nerve
fibre (4), effector organ (5).
The simplest reflex arc can be represented schematically
as formed by two neurons only, an afferent and an efferent,
with a synapse between them. Such a reflex is called
bineuronal or monosynaptic reflex. Monosynaptic reflexes
occur very rarely.

62
 1

13

Figure 14. Spinal reflex arc.

They may be exemplified by myotatic reflexes (knee jerk,

Achilles-tendon reflex, etc). The reflex arcs of most reflexes
include not only two neurons (afferent and efferent) but also
one or more interneurons. These reflexes are known as
multineuronal or polysynaptic. Excitation is conducted
considerably more slowly in nerve centres (because of the
presence of synapses and the synaptic delay) compared with
the nerve fibres. The reflex time or latent period of reflex, i.e.
the period between stimulation and response, consists of:
excitation of receptors (A), conduction of excitation by the
afferent nerve (B), transfer of excitation to the effector neuron

63
(C), conduction of excitation by the efferent nerve (D),
conduction of excitation from the nerve to the effector organ,
and its latent period (E). Thus, the reflex time R is the sum of
the time of all these processes: R=A+B+C+D+E. Period C is
called true or reflex central time. In man the quickest reflexes
are the tendon reflexes (monosynaptic reflexes), e.g. the knee
reflex takes only 20 -23 msec, the central time of this reflex is
3 msec. But the winking reflex takes rather longer, 50-200
msec, its central time is 36-186 msec (polysynaptic reflex).

Inhibition in the CNS

The phenomenon of the central inhibition was discovered

by Sechenov in 1863. It was shown, that incision of the frog
brain at the thalamus level and NaCl crystals application on
that site lead to spinal reflex time significant prolongation or
reflex entire eradication. It was determined by Turck’s method
(measuring of the reflex time for withdrawing the hind legs
from a solution of sulfuric acid by frog) (Figure 15). He made
the conclusion about existence of specific neuronal centres in
the thalamic region producing an inhibitory influence on the
spinal centres. Afterwards new facts of inhibition in the CNS
were discovered. Goltz showed that the reflex of the frog leg
withdrawal in response to immersion in an acid solution could
be inhibited by simultaneously strong mechanical stimulation
of the other leg by squeezing with pincers even after removal
of thalamus.

64
 Figure 15. Sechenov`s experiment (central inhibition).

Facts of the central inhibition were out of doubt and got a

common acceptance, but concerning to the mechanism of its
derivation there were contradictory views. Some researchers
(Sechenov) supposed that there were special structures in the
central nervous system performing the function of inhibition.
Others (Goltz, Sherrington) opposed this maintaining that
inhibition resulted from a conflict between several excitations.
Only owing to the electrophysiological research methods rapid
development of the cellular mechanisms underlying the
inhibition process became clear. Inhibition is an independent
nervous process, which is caused by excitation and manifested
by the suppression of another excitation. In distinct from the
excitation process, which is manifested in a view of the local

65
potentials and spreading action potentials, the inhibition
process is manifested only in a local form that never spreads.
There are two principally different ways of neuronal
activity inhibition:
1. The inhibition is a result of special inhibitory synapses
activation (primary inhibition).
2. The inhibition arisen in the neuron is secondary as a
sequence of its excitation. This type of inhibition appears in a
high rate (pessimal rate) stimulation of the cell or it may be
connected with the hyperpolarization processes followed by
excitation.
Primary inhibition. By means of the microelectrode
examination, it has been established, that the primary inhibition
of neuron activity could be a result of the postsynaptic
membrane’s property changing, as well as a result of a special
mechanism blocking excitatory synapses at the level of the
presynaptic structures. We differentiate two types of inhibition
- the postsynaptic and the presynaptic.
Postsynaptic inhibition. It is most common in the CNS.
It has been established that there are so-called inhibitory
neurons in the CNS, e.g. Renshaw’s, Wilson’s cells (spinal
cord) and Purkinje’s cells (cerebellum). The axons of the
inhibitory neurons secrete inhibitory transmitters, glycine or
GABA. These mediators cause postsynaptic membrane
hyperpolarization and IPSP arising (direct inhibition). The
ionic mechanism of the above-mentioned inhibitory action on
the postsynaptic membrane consists in the following: the
inhibitory mediator brings about the postsynaptic membrane
66
permeability increase for K+ (outflow) or Cl- (inflow) ions that
finally lead to hyperpolarization.
Another type of the postsynaptic inhibition is the
recurrent inhibition (Figure 16) that can be studied on α-
motoneurons. α-motoneuron being excited sends stimuli not
only to periphery (muscle), but also by collateral branch to
Renshaw’s cell, which forms the inhibitory synapse on the
body of motoneuron. Renshaw’s cell secretes the inhibitory
mediator (GABA) that acting on the motoneuron through the
synaptic contact, inhibits it. This phenomenon is of importance,
since it prevents the motoneuron from strong excitation. The
particular case of this phenomenon is the inhibition of
inhibition. In this case Renshaw’s cell contacts with another
inhibitory neuron – Wilson’s cell, which in its turn contacts
with α-motoneuron. Wilson’s cell has a background
(spontaneous) activity, by means of which it keeps the
motoneuron in an inhibited state. Renshaw’s cell being excited
(by motoneuron collateral) causes the inhibition of Wilson’s
cell and α-motoneuron will escape from the inhibited state
(inhibition of inhibition or facilitation).
Presynaptic inhibition. As its name implies, this type of
inhibition is localized in the presynaptic elements and realized
in the axoaxonic synapses (Figure 17).

67
 Figure 16. The recurrent Figure 17. The presynaptic
postsynaptic inhibition. inhibition.

The mediator secreted in these synapses evokes the axon

membrane depolarization because of Cl- - pump activation. The
formed state results in a partial or complete block of
conduction of impulses (decrease of the spreading AP
amplitude) to the nerve endings. On the other hand the
inhibitory mediator can disturb the Ca2+ ions entry into the
presynaptic membrane, which can inhibit the secretion of
excitatory mediator.

Secondary inhibition.

Pessimal inhibition. The activity of a nerve cell can be

inhibited without participation of special inhibitory structures.
In that case, inhibition develops in the excitatory synapses as a
result of a strong and prolonged depolarization of the post
synaptic membrane under the influence of nerve impulses
arriving too frequently. So a state similar to Werigo’s cathodal
depression in the cell develops.

68
 Inhibition following the strong excitation. A discrete
type of inhibition is the one developing in a nerve cell after
termination of excitation and which appears when excitation is
followed by a strong after-hyperpolarization of the cell
membrane. The excitatory postsynaptic potential arising under
these conditions proves to be insufficient to depolarize the
membrane, so that spreading of excitation does not occur.

Nervous centres’ properties

The nervous centre is integrity of neurons, which implies

a definite reflex or regulates a particular function. It is located
in a certain part of the CNS. The localization of nervous
centres is determined through experiments with stimulation, or
with limited destruction, extirpation, or section of different
parts of the brain or spinal cord. Since in the nervous centre
neurons are interconnected to each other by means of synapses,
the nervous centres first are to have all that properties intrinsic
to the synapses particularly. They are the following:
1. One-way conduction of stimuli. It can be illustrated by
the following experiment. At stimulation of the dorsal roots of
the spinal cord (the afferent nerve fibres) the action potentials
will be registered in the ventral roots (the efferent nerve fibres).
On the other hand, if the ventral roots are stimulated in the
dorsal roots no action potential will be registered.
2. Central delay. Excitation is conducted considerably
more slowly in the neuronal centres than in nerve fibres, which
accounts for the relatively long duration of reflex time, i.e. the
period between stimulation and response. Slow transmission of
69
excitation is consequent to the peculiarities of the impulse
conduction across the synapses. The more synapses are
involved in the reflex response; the more is the central delay.
3. Fatigue of the nervous centres. In prolonged and more
frequent stimulation of the nervous centre, considerably
weakened responses or gradually ceased responses will be
registered on the efferent way of the reflex. The reason is that
the intensive stimuli cause the mediator resources full
consumption, as well as decrease of the postsynaptic receptors’
sensitivity. The definite time period is required for the mediator
resynthesis and the energetic resources recovering.
4. Transformation of rhythm excitation. In response to an
isolated stimulus applied to an afferent nerve the centre sends
along efferent nerve fibres a series of impulses following each
other in a definite rhythm. Figurally said, they respond to “an
isolated rifle shot with a burst of machine–gunfire”. In certain
cases it is due to the EPSP long duration, which triggers the
second, third, etc. action potentials after the termination of the
first.
5. Summation of excitation. Its essence is that a
combination of two or more stimulations of peripheral
receptors of afferent nerves arises a reflex, whereas each taken
separately is not sufficient to elicit the response. Two types of
summation are determined:
1) spatial (or simultaneous);
2) temporal (or consecutive).
The spatial summation of impulses occurs, when two or
more weak (subthreshold) stimuli are acting simultaneously on
70
different receptors belonging to the same receptive field. Either
stimulus acting alone will not induce the given reflex, but in
combination they will. This phenomenon is explained by
summation of EPSPs evoked by subthreshold stimuli.
Consecutive summation is the interaction of impulses coming
to the neuronal centre one after another at short intervals along
the same afferent nerve fibres. It can be induced by applying a
series of rhythmic stimuli to an afferent nerve or to the
receptive field of a reflex. If each of the stimuli is strong
enough to elicit a reflex, their rhythmic application will
increase it. If the strength of the stimulus is so calculated to be
not enough to cause a reflex when acting alone, the reflex can
be elicited by a succession of them.
The difference between these two types of summation is
that with simultaneous excitation of several neighbouring
synapses the EPSPs are summed up spatially, whereas with
consecutive stimulation they are summed up in time.
6. Occlusion. It is like to be contradictory to the
summation phenomenon represented above. It consists in
simultaneous stimulation of two afferent nerve fibres (each of
which gives a strong response), producing an effect which
magnitude is less than the arythmetical sum of those taken
separately. Reason for this phenomenon is the summation
bringing about the process of cathodal depression.
7. Posttetanic potentiation. It is a phenomenon of
response increase of production in case of preliminarily given
tetanic impulses. For example, we give stimuli in time interval
of 2-3 sec. and take responses accordingly to this rhythm. The
71
following intensifying of stimuli brings about intensified
responses. It can be continued up to 200-600 impulses per
second. But in case of immediate returning to the initial rate of
stimuli, the intensified responses will be kept. The reason is
that the presynaptic ending acquires a property to cumulate
much more amount of the mobilized mediator.
8. After-action. Essence of this is the following. Reflex
acts do not end simultaneously with the cessation of the stimuli
causing them, but after a certain, sometimes comparatively
long interval. This phenomenon can be explained by the
circulation of nerve impulses through the closed neuron chains
of the reflex centre. With links of that kind between neurons
excitation of one is conveyed to another (or others) and returns
again to the first cell, through the collateral’s of their axons,
and so on. Owing to existence of such circular connections the
excitation can circulate in a nerve centre for some time until the
onset of fatigue in one of the synapses or the neuronal activity
arrest by the arrival of an inhibitory impulse.
9. Tone of neuronal centres. Electrophysiological
researches have shown that the nervous centres are constantly
in state of limited excitation, in tone. It is sustained by the
afferent impulses continuously conveyed from peripheral
receptors to the nervous centre, as well as by various humoral
stimulants (hormones, CO2, etc). The role of afferent impulses
in maintaining the tone of neuronal centres is demonstrated by
Bronjest’s experiment. Section of the sensory roots of the
spinal cord innervating the hind leg of a frog causes a decline
of the muscular tone, almost identical with that seen with
72
damage of the motor nerve. In result the leg with decreased
tone becomes longer than the other one.
10. High sensitivity of the neuronal centres to oxygen
supply and to certain poisons. The brain cells are marked by
intensive consumption of oxygen (twice more than the skeletal
muscles). Because they consume large amount of oxygen,
neurons are highly sensitive to its deficit (hypoxia), so a
decrease in oxygen supply to the CNS leads to functional
disturbances in the nervous centres. That is why complete or
partial cessation of the cerebral circulation (e.g. in thrombosis)
entails severe impairments in the neuronal system and the
death of nerve elements. Besides, nervous centres possess a
selective sensitivity to certain poisons, which are known as
nerve poisons. For example, strychnine serves as an inhibitor
of the central inhibitory synapses, thereby causes a sharp
increase in the excitability of the CNS, particularly of the
spinal cord; apomorphine stimulates excessively the vomiting
centre; lobeline acts on the respiratory centre and abruptly
stimulates it, etc.

Principles of coordination in the CNS

Every reflex is a reaction of the entire central nervous

system and is realized by the definite nervous centre. It
depends on the CNS condition at the given moment and on the
whole aggregation of intercentral relationships and
interactions, which in turn encounter through the neuronal and
synaptic chains. The same reflex could have a number of

73
components – motor, secretor, vascular and so on; and all these
centres act in a coordination way.
The main principles of coordination are:
1. Convergence. Impulses reaching the central nervous
system along various afferent fibres may converge upon the
same inter- and effector neurons. In the spinal and medullar
centres convergence is comparatively limited; only stimuli
coming from the same reflexogenic field can converge. In
contrast, in the higher parts of the CNS (e.g. in subcortical
nuclei and the cerebral cortex) there is a convergence of
impulses issuing from different receptive zones, for instance,
acoustic, optic, the smell and skin receptors.
2. Divergence. It is an opposite phenomenon to
convergence. The afferent nerve entering into the nervous
centre can form synaptic contacts with several neurons.
3. Irradiation. Impulses arriving at the CNS can induce
excitation not only in the neurons of a given reflex centre but
also in those of other centres. It occurs mostly in case of strong
and prolonged stimulation. To illustrate this phenomenon let us
consider the results of the following experiment. A weak
stimulus applied to the pads of the animal’s hind leg causes
flexion of that leg only, at the talocrural joint. Intensified
stimulation causes flexion at the knee joint, in addition, and
still stronger stimulation at the hip joint. Further increase in
stimulus strength entails in addition to the above mentioned
flexion, the extension of the hind leg on the opposite side.
Irradiation could be endless and strong if the inhibitory
synapses don’t exist. Irradiation is obstructed by numerous
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inhibitory neurons in various reflex centres. Importance of
inhibition is clearly illustrated by injecting 0,1% solution of
strychnine. Strychnine blocks the inhibitory synapses and
evokes hyperexcitation. Even insignificant touch or another
stimulus can induce the most intensive general excitation of the
CNS accompanied by convulsions of all the skeletal muscles.
4. Reciprocal innervations. Flexion reflex is
accompanied by inhibition of extension reflex, simultaneously
the contraction of the extensor muscle and the relaxation of the
flexor muscle of the opposite side are observed. This
phenomenon is explained as stimulation of the flexion centre
causing inhibition of the extensor centre. Afferent nerve
exciting the flexor motor centre simultaneously sends the
impulses by collateral branch to Renshaw’s cell. The latter
being excited brings about the extensor α-motoneuron
inhibition. The flexor centre could evoke an excitatory
influence on the extensor centre of the opposite side (opposite
leg), as well as an inhibitory influence on the flexor centre.
5. Principal of the dominant. Activity of the nervous
system is characterized in the natural conditions of the
organism by the existence of dominant foci of excitation,
which change the action of all other nerve centres and
subordinate them to themselves. If during the act of defecation
a strong pain stimulus is applied, the flexion reflex of the leg
that is normally evoked by this stimulation will not occur.
Instead, the defecation reflex will be quicken and intensified.
Dominant centres fulfil the most important for that moment
reflex.
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 Dominant foci are characterized by the following basic
peculiarities: a) increased excitability; b) stability of the
excitation; c) capacity to summate excitation; d) inertia,
capacity to remain excited for a period after the stimulus has
ended.
6. The common final pathway. The same reflex may be
caused by a great number of different stimuli acting on various
receptors. For example, the scratching reflex may be caused by
stimulation of the skin receptors, of the flexor muscle
proprioceptors, of the extensor muscle proprioceptors on the
contrary side, or even by acoustic or visual action, if they have
been previously combined with the scratching reflex
(conditional reflex). So, in this experiment stimuli from
different reflector arcs get the same motoneuron (final common
pathway). Reflexes which arcs have a final common pathway
may be divided into allied and antagonistic.
Reflexes coming to compete for the final common path
are antagonistic ones. Example for antagonistic reflex is the
following: if during the scratching reflex a strong pain stimulus
is applied, the scratching reflex will cease, since the final
common path for these two reflexes is the same.
Those reflexes coming into collaboration with each other
and so intensify the final common path are synergistic (allied)
ones, e.g. the reflex of saliva excretion is accompanied by
excitation both of the taste and the tactile receptors. If these
two types’ receptors are excited at the same time, the main
reflex (saliva excretion) will be more intensified.

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 7. The excitation replacement by inhibition, and vice
versa (induction). Inhibition is always followed by excitation
and this is called consecutive positive induction. Similarly,
excitation is followed by inhibition (that will be negative
consecutive induction). It is shown, that if the animal’s skin is
excited by a weak stimulus, a weak scratching reflex will be
produced, which in turn will be inhibited if at this moment the
strong electrical stimulus is applied at that site of the skin. But,
if we remove that strong stimulus, the scratching reflex will be
expressed more intensively.
Pavlov studied induction interrelations during the
functioning of the conditional reflex, and named these
phenomena as the cerebral positive and the negative induction.
8. The”rebound’’ phenomenon. It consists in the
following: one reflex could be replaced by another reflex of the
contrary meaning. Termination of stimulation causing a strong
flexion reflex is followed by a sharp extension of the flexed
leg. The reason is that, the extensor centre being in reciprocal
relations with the flexor centre becomes excited now. Actually,
the flexor centre excitation brings to the extensor centre
inhibition, and vice versa. All this is connected with realization
of the successive rhythmic reflex.
9. The principle of ,,feedback’’. Not only basic stimuli,
but also the so-called secondary afferent stimuli come into the
CNS. Any motor act induced by an afferent stimulus is
accompanied with the stimulation of the receptors of the
muscles, tendons, etc., i.e. of the proprioceptors, from which
nerve impulses are conducted to the CNS. When a movement
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is being performed by a human being under the guidance of
vision, or hearing, the proprioceptor impulses are joined by
visual or acoustic signal.
The significance of secondary afferent impulses for
reflex realization and of its coordination is very great. It is
successfully shown both by experiments on animals and by
clinical observations of patients who have lost one or other of
the senses. Patients with impaired proprioceptive sensibility no
longer have smooth and accurate movements (their movements
become abrupt, uncoordinated). Section of afferent nerve
fibres, deafferentiation, results in abnormal reflex performing.
In this case intensified irradiation of the nerve impulse will be
also observed. For example, the leg deprived of sensibility
performs rhythmical movements coinciding with the
respiratory rhythm.
This type of connection (secondary afferentation) persists
in the whole organism between all the organs and systems.
Owing to this ,,feedback’’ between the nerve centres and the
effector organs the intensity of the excitation of neurons in the
centre and the sequence of excitation of its demands are strictly
coordinated.
This ,,feedback’’ could be positive in case of
strengthening of the basic reflex; and negative in case of
weakening of the basic reflex. Very often they turn over
together, e.g. secondary afferent impulses during the muscular
contraction on the one hand excite one centre of motoneurons
and on the other hand, inhibit another centre of motoneurons.

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 2.2. SPECIAL PHYSIOLOGY OF THE
CENTRAL NERVOUS SYSTEM

Spinal cord

The spinal cord is phylogenetically the oldest part of the

CNS. It is logged in the vertebral canal. The typical feature of
the spinal cord is its segmental structure, which reflects the
segmental structure of the vertebrate body. Each spinal
segment gives rise to two pairs of the ventral and dorsal roots.
The dorsal roots form afferent inputs of the spinal cord. They
are formed by central processes of the fibres of first afferent
neurons which bodies are located on the periphery in the spinal
ganglia. The ventral roots form efferent outputs of the spinal
cord. They contain axons of the α- and γ-motoneurons. This
distribution of afferent and efferent roots is known as Bell-
Magendie’s law. All the neuronal elements of the spinal cord
are classified into four principal groups: efferent neurons,
interneurons, ascending tract neurons, and intraspinal fibres of
sensory afferent neurons. The spinal cord performs the
following functions: conducting, reflectory and elementary
analysis.
The neuronal organization of the spinal cord. Motor
neurons are located in the anterior horns. The α-motoneurons
innervate skeletal muscle fibres (so-called extrafusal fibres)
and ensure muscle contraction. The γ - motoneurons innervate
muscle intrafusal fibres, contraction of which causes the
excitation of muscle stretch receptors. Combined activity of
these two types of neurons provides the motor coordination. In
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decreased tone of the skeletal muscle the γ- motoneurons cause
contraction of intrafusal fibres, ensuring the excitation of
stretch receptors, which are located in the nucleus of the fuse.
The impulses, coming from these receptors to the spinal cord,
activate the α−motoneurons. The latters provide the contraction
of muscles (extrafusal fibres), causing the increase of muscle
tone.
The preganglionic neurons of the vegetative nervous
system make up a special group of efferent neurons of the
spinal cord. They are located in the lateral horns of the gray
matter. Axons of these neurons pass to the ganglion cells of the
sympathetic chain, where they are interrupted forming
synapses with the second neurons. The latters innervate the
internal organs.
The interneurons of the spinal cord form rather a
heterogenous group of nerve cells, which processes lie within
the spinal cord. The interneurons can be excitatory, as well as
inhibitory. The Renshaw cells which are excited by the muscle
receptor afferent fibres belong to the group of inhibitory
interneurons. They participate in reciprocal inhibition of the
motor neurons of antagonistic muscles. They take place in
postsynaptic (direct and indirect) and presynaptic inhibition.
The conducting tracts of spinal cord. As is noted
above, the spinal cord contains neurons, which give rise to long
ascending pathways to various brain structures. The main
ascending pathways of the spinal cord are the fasciculus of
Goll and the fasciculus of Burdach. They are included in the
composition of the posterior funiculus of the white matter and
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end in the medulla oblongata. These pathways are responsible
for the perception of skin mechanical stimuli. The other
ascending pathways begin from the neurons of the grey matter
of the spinal cord. Since these neurons are supplied by the
synaptic inputs from the first afferent neurons, it was accepted
to designate them as the secondary afferent neurons. The main
bulk of secondary afferent fibres pass as part of the lateral
funiculus of the white matter. Here the spinothalamic tract is
located. The axons of the spinothalamic neurons are decussated
and through the medulla oblongata and midbrain reach
uninterruptedly the thalamic nuclei to form synapses with the
thalamic neurons. This tract transmits the impulses from skin
receptors. The lateral funiculi contain fibres of the
spinocerebellar, posterior and anterior tracts, which transmit
impulses from the skin and muscle receptors to the cortex. The
pathway of pain sensation is located in the anterior funiculi.
Тhe posterior, lateral and anterior funiculi contain
propriospinal tracts which provide the functional integration
and reflex activity of the spinal cord centres.
The spinal cord also receives many descending pathways,
which are formed by the axons of nerve cells located in the
cerebral cortex, mid-brain and medulla oblongata. The main
among them are reticulospinal and vestibulospinal tracts
(phylogenetically older). The reticulospinal tract is formed by
axons of the brainstem reticular formation neurons, which
terminate on the neurons of the grey matter, including
motoneurons. The vestibulospinal tract is composed by the

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axons of the neurons of the lateral vestibular nucleus, Deiters
nucleus. These two tracts do not decussate.
The evolutionary younger rubrospinal tract begins from
the red nucleus of the mid-brain. After decussating, the
rubrospinal tract is included in the composition of the lateral
white funiculi. The neurons of corticospinal or pyramidal tract
(evolutionary the youngest) lie in the motor cortex. The fibres
of this tract decussate and as a part of the dorsolateral funiculi
pass above the rubrospinal tract. Pyramidal axons make direct
contacts with motor neurons.
Reflex activity of the spinal cord. The centres of
number of reflexes are located in the spinal cord. The tendon
and stretch reflexes are the simplest spinal reflexes. The
afferent pathway of these reflexes begins from stretch receptors
forming synapses directly with the motoneurons. Thus, the arc
of these reflexes is monosynaptic and the reflex time is very
short. The estimation of reflex time has an important diagnostic
significance for nervous diseases. Among these reflexes the
patellar, the Achilles reflex, the knee reflex are the most
important.
The reflexes of the body position have a more complex
character. They are polysynaptic reflexes. For that reason the
tonic neck postural reflex has been especially distinguished.
The proprioceptors of muscles of the neck and fascia covering
the spinal cervical segment are the receptive field of the tonic
reflexes. The reflex reaction involves the muscles of the trunk
and limbs. Tonic neck reflexes arise when the head is turned or

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bent, which causes stretching of the neck muscles and
excitation of the receptive fields.
The spinal cord also plays a major role in the reflex
regulation of the internal organs and contains of the centres of
numerous visceral reflexes. The preganglionic neurons of the
vegetative nervous system take part in these reflexes. The
axons of these neurons leave the spinal cord through the
anterior roots and are interrupted in ganglia. The ganglion
neurons, in turn, send axons to the visceral organs (intestine,
urinary bladder, vessels, heart, etc.). The centres of defecation
and diuresis are also located in the spinal cord.
Descending control of the spinal cord activity. The
activity of the spinal cord is subjected to the strict control of
the overlying parts of the CNS. The impulses arriving at the
spinal cord via the descending tracts can exert direct action on
the spinal motor centres. That is why in partial, and moreover,
in total section of the spinal cord, the activity of the spinal
centres caudally to the site of trans-section is sharply disrupted
(spinal shock). A unilateral affection of the spinal cord due to
trauma or various diseases of the CNS causes the development
of a symptom complex which is known as the Brown-
Sequard’s syndrome. It is characterized by the disturbed
muscle tone and sensitivity, paralysis and vasomotor disorders
on the site of affection. Further the reflex activity is gradually
restored, and the higher the organization of the nervous system
the slower this restoration process is. First, the motor reflexes
are restored. Reflexes connected with the activity of internal
organs are restored later. Sometimes spinal reflexes are
83
expressed more strongly, than in the norm (hypereflexia),
which demonstrates that overlying structures have also an
inhibition effect on the spinal cord activity.

Hindbrain

The medulla oblongata and the pons varolii compose the

hindbrain. This part performs reflectory and conducting
functions. The nuclei of the fifth-twelfth pairs of cranial nerves
are located in the hindbrain.
The neuronal organization of hindbrain. Similar to
the spinal cord, it has efferent neurons, interneurons, neurons
of ascending and descending tracts, primary sensory fibres and
fibres of conducting tracts passing through the hindbrain in the
ascending (rostral) and descending (caudal) directions.
Nuclei of the cranial nerves receive afferent impulses
from the periphery and send efferent impulses to the muscles,
organs thus resembling the spinal neuron centres. The eleventh
pair (n.accessorius) and twelfth pair (n. hypoglossus) nerves
are purely motor nerves. The tenth pair (n. vagus) and ninth
pair (n. glossopharyngeus) nerves are mixed. The eighth pair of
nerves is sensory (n. vestibulocochlearis). It consists of two
branches, the vestibular and cochlear nerves. The vestibular
nerve is formed by the afferent fibres running from the
receptors of the semicircular canals. Some of these fibres pass
to the cerebellum. The vestibular neurons give rise to the
vestibulocerebellar and vestibulospinal tracts. The reticular
formation is situated in the medial part of the medulla
oblongata. Cells of the reticular formation give rise to the
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ascending and descending tracts, which form numerous
collaterals whose endings make synaptic contacts with various
nuclei of the CNS.
The pons varolii, which is a continuation of the medulla
oblongata, connects the medulla with the midbrain. It consists
of nuclei of the seventh pair (n. facialis), sixth pair
(n.abducens) and fifth pair (n. trigeminus) nerves. The facial
and trigeminal nerves are mixed. The abducent nerve is motor.
The medial nuclei of the reticular formation of the pons give
rise to the ascending fibres to the midbrain and diencephalons.
Reflex activity of hindbrain. The hindbrain is
responsible for numerous functions, such as respiration, heart
activity, digestion, vasomotor activity, etc., which are vitally
important for the body. The hindbrain realizes static reflexes,
which are subdivided into the postural and righting reflexes
and statokinetic ones. The postural reflexes ensure changes in
the muscle tone, when the body position in space is changed.
The righting reflexes govern the redistribution of the muscle
tone, owning to which the natural posture can be restored in
case it has been changed. The vestibular afferent fibres and
neurons of the lateral vestibular nucleus, whose axons pass to
the spinal cord as a component of the vestibulospinal tract,
take part in the performance of these reflexes. The excitation
of vestibular receptors causes postural reflexes, i. e. the
activation of extensor muscles and inhibition of flexor muscles.
The righting reflexes are responsible for the normal position of
the head.

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 The statokinetic reflexes are the most complex. They
provide the maintenance of posture and orientation in space
when the speed of movements is changed. For example, during
the sudden halt of bus or car, the muscles contract to overcome
the force acting on a human body. The statokinetic reflexes
involve almost all body musculature. They are pronounced in
the muscles of the eye. Movement of eye muscles mediates the
normal visual orientation during acceleration or slowing down
of movement.
Along with motor reflexes, activation of the vestibular
apparatus causes excitation of the autonomic centres, including
the nucleus of the n. vagus. The formation of vestibule-
autonomic reflexes cause changes in respiration, heart rate,
gastro-intestinal activity, etc. In turn, many motor reflexes are
associated with the food intake, chewing and swallowing.
Damage to other parts of the CNS may have no
symptoms due to great compensatory capacities of the brain,
while a minor trauma to hindbrain immediately has a grave or
even fatal consequence.
Descending and ascending influences. The medulla
oblongata and the pons send fibres to the spinal cord, which
cause more diffuse non-specific influence on the spinal cord
motor centres. Electrical stimulation of the medulla oblongata
medial reticular formation causes inhibition of all the spinal
motor reflexes owning to the development of postsynaptic
inhibition with the help of inhibitory interneurons. It has been
concluded that this zone functions as a non-specific inhibitory
centre.
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 The hindbrain reticular formation can have a positive
effect on the cerebral cortex, which is associated with
involvement of the reticular formation not only of the
hindbrain but of the midbrain and the diencephalon. This
complex of the reticular nuclei and pathways makes up a
functionally united system.

Midbrain

The midbrain or mesencephalon consists of two main

parts: the dorsal part known as the tegmentum of the midbrain
and the ventral part, the cerebral peduncles. The midbrain
contains also the substantia nigra, the quadrigeminal bodies,
the red nucleus, the nuclei of the cranial nerves, and the
reticular formation. Various ascending pathways pass through
the midbrain to the thalamus and cerebellum; the descending
pathways from the cerebellum hemispheres, corpus striatum
and hypothalamus run to the midbrain neurons and to the
nuclei of the medulla oblongata and the spinal cord.
Neuronal organization of midbrain. The nuclei of the
trochlear (forth pair, n. trochlearis) and oculomotor (third pair,
n. oculomotorius) are located in the midbrain. Neurons, which
receive signals via the auditory tracts (the primary auditory
centre), are situated in the inferior colliculus. The superior
colliculus contains cells, which are relay stations for the
impulses arriving along the optic tracts (the primary optic
centre).
The red nucleus contains cells of different sizes. The
thickest and having higher conduction velocity axons of the
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rubrospinal tract arise from the large neurons, which receive
signals from the motor area of the cerebral cortex, the nucleus
interpositus of the cerebellum and from the nerve cells of the
subtantia nigra. The red nucleus gives rise to cells, which
axons innervate the spinal centres controlling the upper and
lower limb musculature.
The substantia nigra is the integrity of nerve cells
containing pigment melanin, which imparts the typical dark
color to this nucleus. These neurons are dopaminergic. They
are lodged in the zona compacta. The other part of the
substantia nigra is zona reticulata, which consists of target
cells for the projections of the basal ganglia. The latters in turn
form synaptic inhibitory contacts with the nuclei of the
thalamus, pons, and superior colliculus.
Functions of midbrain nuclei. The arcs of orientation,
visual and auditory reflexes are closed in the midbrain (inferior
and superior colliculi). The nuclei of the quadrigeminal bodies
participate in the performance of the guarding reflex. The
substantia nigra participates in the complex coordination of
movements. The dopaminergic neurons of the substantia nigra
send axons to the nuclei of the corpus striatum, where the
dopamine controls the complicated motor acts. Damage to the
substantia nigra leads to degeneration of dopaminergic fibres
causing disorders of movements of fingers and development of
muscular rigidity and tremor (Parkinson’s disease).
Trans-section of the brainstem below the red nucleus in
animals causes significant changes in the distribution of muscle
tone of the body. The tone of the extensor muscles is sharply
88
increased. The animal’s limbs are strongly extended, the head
is tilted back, and the tail is raised. This condition is known as
decerebrative rigidity. This phenomenon is explained by
interruption of signal transmission to the spinal cord via the
corticospinal and rubrospinal tract activating the motor neurons
of the flexor muscles and inhibition of the extensor muscles.
As a result, the activity of the vestibulospinal system, which
increases the tone of the motor neurons of the extensor
muscles, becomes dominating.

Cerebellum

The cerebellum is located posteriorly to the cerebral

hemispheres, above the medulla oblongata and the pons. The
cerebellar hemispheres consist of anterior and posterior lobs,
which are covered by cortex. The cerebellum is connected with
other parts of CNS by three pairs of peduncles.
Neuronal organization of cerebellum. The cerebellar
cortex consists of three layers. The superficial or molecular
layer has ramifications of the flask-like or Purkinje cells, which
are inhibitory neurons. It has been established that one Purkinje
cell forms nearly 200000 synapses due to a huge amount of
dendrites. The molecular layer has also parallel fibres, which
are the axons of intercalary neurons. The lower part of the
molecular layer contains basket cell bodies, the axons of which
make synapses with Purkinje cell bodies. The molecular layer
also contains a certain number of stellate cells.
The second layer is ganglionic layer, which is
represented by Purkinje cell bodies. The third layer is granular

89
layer, which contains intercalary neuron bodies. Axons of these
cells ascend to the molecular layer where they divide in a T–
pattern. The Golgi cells, which axons project to the molecular
layer, are also located in the granular layer.
The cerebellar cortex receives only two types of afferent
fibres: climbing and mossy. They supply the cerebellum with
all sensory influences. The climbing fibres, which are axons of
the neurons lying in the inferior olives, make synapses with the
dendrites of the Purkinje cells. Each Purkinje cell is reached by
only one climbing fibres. The characteristic feature of these
fibres is the formation of plural synapses with intercalary
neurons, which axons reach to the molecular layer form the
system of parallel fibres. The latters are in the synaptic contacts
with the Purkinje cell dendrites. These synapses are excitatory.
Mossy fibres make synapses with the basket cells. The
synapses between the basket cell axons and Purkinje cell
bodies are inhibitory. They provide effective inhibition of
excitatory influences exerted on the Purkinje cells through the
axodendritic synapses formed by climbed fibres and intercalary
neuron bodies.
The mossy fibres make synapses also with the Golgi cells
and stellate cells, which like the basket cells are inhibitory
neurons.
Two types of afferent fibres (climbing and mossy) enter
the cerebellar cortex, but only one type of efferent fibres, i.e.
axons of the Purkinje cells, leave it.
The cerebellum receives information from various
sensory systems. Afferent signals reach the cerebellum from
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the spinal cord, vestibular receptors, inferior olive and reticular
formation of the hind-brain. The spinocerebellar tract supplies
the cerebellum with information about the muscular apparatus,
skin and deeper lying tissues.
Neurons of the nucleus interpositus (the globosus and
emboliform nuclei) send fibres to the cells of the red nucleus.
Synapses formed by these fibres on the rubrospinal neurons are
excitatory. Thus, responses arising in spinal motor neurons on
stimulation of the nucleus interpositus resemble those arising
on stimulation of the red nucleus. Neurons of other nuclei of
the cerebellum establish excitatory synapses on the
reticulospinal neurons of the medulla oblongata and the pons.
Thus, the whole information supplied to the cerebellum is
transmitted to the Purkinje cells, which, in turn exert inhibitory
influences on the cerebellar nuclei, as well as on the neurons of
the lateral vestibular (Deiters) nucleus. Therefore, Purkinje
cells through cerebellar nuclei inhibit the activity of the
reticulospinal and rubrospinal neurons.
Thus, the cerebellum can effectively control most signals
transmitted to the spinal cord via the main descending tracts.
Functions of cerebellum. Clinical manifestations
attendant to disturbances of the cerebellum as well as the
effects caused by its stimulation or extirpation testify to the
important role played by the cerebellum in static and
statokinetic reflexes and other processes involved in the control
of motor activity. Their main manifestations are impaired
equilibration and muscle tone, tremor, ataxia, asynergy and
astasia. Muscular atonia is an inability to maintain posture.
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The tremor is characterized by small amplitudes of oscillations,
which occur synchronously in various body segments. Ataxia
is described by less precise of movement range, speed and
direction. Motor reactions lose their smoothness and
steadiness. The goal-directed movement (e.g. an attempt to
take an object) becomes rough and jerky. In asynergy, the
interaction between motor centres of various muscles is
deranged. Adiadochocinesia is a variant of asynergy and
manifested in the derangement of correct of antagonistic
movements, e.g. finger flexion and extension. In astasia
movements are swinging and jerky.
Total excision of the cerebellum or its anterior lobe in
animals increases the tone of extensors; on stimulation of the
anterior lobe, the tone decreases.
The cerebellum performs a significant role in the
regulation of the vegetative functions due to its numerous
synapses with the brainstem reticular formation.

Diencephalon. Thalamus and hypothalamus

The diencephalon consists of thalamus and

hypothalamus.
Neuronal organization of thalamus. The number of
thalamus nuclei is forty. They are classified topographically
into the following main groups: anterior, intralaminar, medial
and posterior. According to their function, non-specific and
specific nuclei are distinguished. Axons of the specific nuclei
make contacts only with the cells of specific cortical areas.
Neurons of the non-specific nuclei first transmit signals into
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the subcortical structures from where impulses pass to different
cortical areas. The non-specific nuclei are a continuation of the
reticular formation of the midbrain and by nature they resemble
the functions of reticular formation.
Fibres of various ascending tracts end on the neurons of
the specific nuclei. Axons of these neurons make direct
monosynaptic contacts with the neurons of the sensory and
association cortex. Cells of the nuclei of the lateral group of the
thalamus receive impulses from receptors of the skin, motor
apparatus, and from the cerebellothalamic tract. The other
group of the specific nuclei is a component of the posterior
group and forms the medial and lateral geniculate bodies. The
neurons of the lateral geniculate body receive impulses from
the primary visual centre of the anterior quadrigeminal bodies.
The medial geniculate body neurons receive signals from the
auditory nuclei of posterior quadrigeminal bodies.
Neurons of the specific nuclei send axons, which are
almost devoid of collaterals to the cortex. In contrast, axons of
the non-specific nuclei form numerous collaterals. At the same
time, fibres passing from the cortex to the neurons of the
specific nuclei have exact topography of their endings unlike
the widely ramified system of fibres ending diffusely in the
non-specific nuclei.
Functions of thalamus. All sensory signals, except those
arising in the olfactory tract, reach the cerebral cortex only via
the thalamocortical projections. The thalamus may be regarded
as a kind of a gateway through which the main information
about the external and internal environment and status of the
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body passes to the cortex. Thalamic neurons are relay stations
for the afferent signals on the way to the cerebral cortex. In
turn, the thalamus receives inhibitory signals from the cortex.
The ascending activating influences from the brainstem
reticular formation enter the cerebral cortex through the non-
specific thalamic nuclei. The system of non-specific thalamic
nuclei is involved in the control of rhythmic activity of the
cerebral cortex and performs as the intrathalamic integrative
system. The cortex reaction is marked by prolonged latent
period and intensifies on repeated stimulation. This reaction
differs from specific responses of the cerebral cortex by
generalized pattern, when extensive cortical areas become
activated. Damage of non-specific thalamic nuclei causes
disorders of consciousness and emotions. Pain signals cause
strong activation of the thalamic nuclei. Latent period of
thalamic responses is prolonged and variable. The thalamus is
the higher centre of pain sensitivity.
Certain thalamic nuclei (dorsal group) exert regulatory
influences on the subcortical structures. Thus, the thalamus can
play a significant role of a suprasegmentary centre of reflex
activity. The talamus is responsible for the locomotion and
complex motor reflex control (swallowing, chewing, sucking,
etc.).
Neuronal organization of hypothalamus. The
hypothalamic nuclei are the higher subcortical centres of the
vegetative nervous system and governing all vitally important
body functions. The preoptic, anterior, medial lateral and
posterior areas are distinguished. The preoptic area comprises
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the medial and lateral preoptic nuclei. The anterior part
includes the supraoptic, suprachiasmatic and paraventricular
nuclei. The lateral area consists of lateral groups of nuclei. The
posterior hypothalamus has the posterior hypothalamic and a
large group of mamillary nuclei.
The hypothalamus is characterized by extensive and
highly complicated afferent and efferent connections. Afferent
signals are supplied from the cerebral cortex, thalamic
structures and basal ganglia. Main efferent pathways pass to
the midbrain and thalamic and subthalamic areas. There is a
direct connection between anterior hypothalamus and posterior
pituitary, which provides the transport of synthesized hormones
(oxytocin and ADH).
Functions of hypothalamus. The lateral and dorsal
groups of hypothalamic nuclei increase the tone of the
sympathetic nervous system. Stimulation of the medial nuclei
decreases the sympathetic tone. Experimental evidence
suggests the existence of sleep and wakefulness centres in the
hypothalamus.
The hypothalamus plays a significant role in the
thermoregulation. Stimulation of the posterior part causes
hyperthermia due to increased heat production (intensification
of metabolism). It is the centre of chemical thermoregulation.
The anterior part of the hypothalamus is responsible for the
physical thermoregulation.
The medial area is considered as the centre of satiety and
the lateral one, hunger. The activity of these areas is stimulated
or inhibited by changes in the chemical composition of the
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supplied blood. The sensation of thirst is conditioned by
activity of the area, located dorsolaterally of the supraoptic
nucleus. Destruction of this area causes absence of thirst.
It has been established that the emotional and pleasure
centres are located in the hypothalamus.
The posterior hypothalamus, which is connected with the
anterior pituitary, regulates the secretion of adenohypophyseal
hormones by means of liberins and statins.

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CHAPTER 3.
HIGHER NERVOUS ACTIVITY

The conception of higher nervous activity was first

suggested by Pavlov distinct from the lowest neuronal activity
and is represented by the brain hemisphere cortex activity, as
well as the closest subcortex, which together provide normal
complex interrelations of the whole organism and the internal
and external media.

3.1.CONDITIONAL AND UNCONDITIONAL REFLEXES

The whole integrity of reflector reactions is the

convention to divide into the conditional and unconditional
reflexes.
Unconditional reflexes are congenital and strictly
connected with the structure and are functioning from the birth
moment, afterwards depending on the given structure
maturation and have an adaptation significance to the
environment constancy.
Conditional reflexes are being obtained during
ontogenesis and are connected with acting stimulus. They are
individual and have adaptation significance to the altering
environment.
Differences:
I. Unconditional reflexes are congenital; conditional
ones are obtained.
2. Unconditional reflexes become stable during
phylogenesis; conditional ones arise during ontogenesis.

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 3. Unconditional ones are connected with structure;
conditional ones are connected with acting stimulus.
4. Unconditional reflexes are typical; conditional ones
are individual.
5. Unconditional reflexes are constant; conditional ones
are temporary.
6. Unconditional stimulus is adequate; conditional
stimulus is not adequate.
7. Unconditional reflexes have an adaptation significance
to the constant environment; conditional ones – to the
environment changes.
Classification of reflexes. According to their biological
significance the whole totality of unconditional reflexes are
divided into: feeding, defence, sexual, orientation reaction
(,,what is it?’’ reflex) and parental reflexes.
Another interesting classification was suggested by
Slonin:
1) reflexes for the internal environment constancy
sustain (feeding, maintaining homeostasis);
2) reflexes for the external environment altering
(defence, situational);
3) reflexes sustaining the type (sexual and defence);
Conditional reflexes are divided into natural (that are
worked out on the natural stimulus action, smell and other
natural features), artificial (light, bell ringing, geometrical
figures, i.e. features not intrinsic to the acting stimulus).

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 Rules for building conditional reflexes

1. Conditional reflex can be produced in time when the

beginning of the indifferent (conditional) signal precedes the
beginning of unconditional stimulation.
2. Conditional and unconditional signals have to cohere
in time.
3. Stimulus, which will become conditional must not
produce a significant unconditional reaction, i.e. physical
strength of conditional one must not exceed the strength of
unconditional stimulation.
4. The cortex must be active.
5. The cortex must be free from other types of activity.
6. Motivation.
7. Attribute factors.
8. The animal has to be healthy.

Components of unconditional and conditional reflexes

Each reflector reaction is accompanied by vegetative and

motor components. For example, unconditional defence reflex
on the pain stimulation is manifested by defence motor
reaction, changes in breathing, cardiac activity, arterial
pressure, blood content, etc. The conditional reflex produced
on the unconditional base also serves as a multi component
reaction. Herein they differentiate the main specific and
secondary non-specific components. In the defence reaction the
main component is the movement component, the vegetative
changes are secondary. In feeding the main component will be

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secretion and motor activity of the digestive tract; whereas all
the rest components will be secondary ones and they have just
a serving role, forming optimal conditions for the main
component realization.

Mechanisms of conditional reflex producing

According to Hasratyan, any unconditional reflex is

multistage and each unconditional reflex has a cortical
representation. With the cortex removal the unconditional
reflex does not disappear, but changes in its character take
place. In case of acting of two signals having similar strength
and producing feeding and defence reflexes, then altering them
timely we can work out doubled conditional reflex: upon the
feeding reflex not only saliva excretion, but also paw’s pulling
off take place. So, between two unconditional reflexes a
connection arises. But decortications interrupt this connection.
In the conditional reaction forming, e.g. on light signal,
first the orientation reaction arises, and on reply to alimentary
signal the feeding reflex produces. Multiple combinations in
time of these signals create a temporary functional connection
between the visual and the feeding centres. Closing of this
connection takes place by the dominant principle. Stronger
feeding centre (there is a feeding motivation) being excited
more impulses attract from the visual centre, and the
summation expense becomes more intensive. Now just in case
of conditional signal acting (e.g. light) impulses through the
existing pathway will arrive from the visual centre to the
feeding centre, exciting the latter.
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 Ecckles considered that repeated passing of impulses
through the neuron system enhances effectiveness of synapses
and intensifies the synaptic transmission (synaptic relief).
Pavlov previously suggested that the conditional reflector
connection was realized transcortically: cortex-cortex. But
Hasratyan and other researchers showed, that the vertical
dissection of the grey matter does not affect on the conditional
reflex producing. Hasratyan proposed the vertical closing of
connection: cortex-subcortex-cortex. The afferent impulses
arrive by specific and non-specific pathways to the sensory
zone of the cortex, and after being worked off there they return
to the reticular formation by the efferent ways, and then to the
cortical centre of the unconditional reflex. Afterwards this
version was ascertained electro-physiologically.
An issue of long-term keeping of the worked out
conditional reflexes even nowadays remains not solved. The
short-term memory is considered to be connected with the
neurons functional characteristics augmentation, as well as
with the neuronal traps. As for the long-term memory the
version of morphological changes in the neurons is suggested:
the development of the presynaptic terminals, increasing in
number of synapses, changes in the nucleic acids, particularly
in RNA contents. But the update knowledge level does not
allow submitting a certain hypothesis regarding the memory
problem.

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 3.2. CORTICAL INHIBITION

No conditional reflex is possible to work out just by

stimulation. Herein inhibition is necessary and very important.
The orientation is the reaction previously arisen by the light
stimulation then inhibited and lets the feeding reflex be
produced. Without inhibition the existing excitation will
irradiate over the whole cortex. Inhibition is characterized by
ceasing or weakening of that or other reflector activity. There
are two types of cortical inhibition: conditional and
unconditional.
Unconditional inhibition. Unconditional inhibition
arises since the first display: the feeding reflex becomes
inhibited and the orientation reaction arises. This inhibition is
called external, because it is formed under the influence of
external, non-significant for the given reflector activity stimuli
from the other neuronal centres, out of the given reflector arc.
In multiple repetitions the orientation reaction disappears and
the signal’s inhibitory influence weakens. Such stimuli were
called by Pavlov “extinguishing inhibitors’’. External
inhibition is explained by the negative spatial induction.
Another type of unconditional inhibition is the
transmarginal inhibition. The excessive increase in strength or
in action duration of conditional stimulus gives an opposite
result, leading to weakening and inhibition of the conditional
reflex. It has a protective significance and protects neuronal
cells from the exhausting influence of strong and prolonged
stimuli.

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 Both of these types of inhibition are connected with the
neuronal system’s natural congenital properties.
Conditional inhibition. Conditional inhibition is based
on the conditional reflex and appears in those neuronal
structures, which participate in the given conditional reflex
realization, i.e. within the given reflector arch. So, it is called
an internal inhibition.
Conditional inhibition arises during ontogenesis and
needs processing.
Types of internal inhibition. There are 4 types of
internal inhibition, depending on conditions expediting the
conditional reflex to be not sustained: extinguishing inhibition,
differential inhibition, conditional inhibition and delayed
inhibition.
1. Extinguishing inhibition. A conditional signal is
accompanied and reinforced by an unconditional stimulus, but
if a conditional reflex is used alone and is not reinforced by an
unconditional stimulus, the stable conditional reflex, previously
established, gradually weakens after several applications and
finally extinguishes.
2. Differential inhibition. If a conditional reflex is
developed to the note ,,re’’, similar sounds (do, re, mi) will
also be capable of eliciting a conditional positive reaction. But
in case of reinforcing only the ,,re’’ note, generalization of the
conditional reflex declines and differentiation of stimuli takes
place. The closer parameters of stimuli, the more difficult to
develop a conditional reflex.

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 3. Conditioned inhibitor. It develops in case, when the
stimulus A (light) is constantly sustained, but A+B (light +
sound) - not. Previously both A and (A+B) combination evoke
a conditional reflex. Further, the (A+B) combination loses its
positive significance. ,,B’’ serves as a conditional inhibitor. It
contributes additional information to the conditional
stimulation and obtains an inhibitory significance.
4. Delayed conditional reflex. If the unconditional
stimulus (food) is constantly delayed for a short span after the
beginning of the conditional stimulus (1-5 sec), the secretion
begins just after the conditional stimulus action onset. If the
reinforcement lags behind for 2-3 min, the secretion is delayed
by 1-3min. The conditional stimulus first has really an
inhibitory significance, but afterwards- a positive one. Deeply
delayed stimulus loses its positive significance.
The role of internal inhibition is:
a) to divide all conditional signals into 2 categories: the
positive, which evokes conditional reflex reactions and the
negative, causing inhibition;
b) to have an adaptation importance making the
organism’s reactions more economic and purposeful;
c) to bring to inhibition and excitation processes
underlying the analysis and synthesis of the cortex activity.

Analysis and synthesis

Analysis is an investigation of specific discrete sides of a

whole process. In physiological meaning it is a reaction of the
organism to discrete components of a complex stimulus and
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consists in discrimination between different signals and
divisions of (complex phenomenon) its components. Analysis
is achieved through the internal inhibition.
Synthesis is a common reaction of the organism on
several stimuli, and is expressed in the association,
generalization and unification of excitations. Synthesis is
manifested by the formation of a temporary connection on
which every conditional reflex is built.

Mutual induction of excitation and inhibition

Excitation and inhibition may intensify each other, which
is called induction. First this phenomenon was discovered by
Vvedensky in the spinal cord. Then it was studied by
Sherrington, and finally, Pavlov, who found out induction in
the cortex. After the concentration of excitation or inhibition,
they induct contrary phenomenon on the periphery.
Pavlov differed two phases of induction:
1) positive (inhibition intensifies excitation);
2) negative (excitation intensifies inhibition).

3.3. TYPES OF THE HIGHER NERVOUS ACTIVITY

Integrity of the main individual properties of the neuronal

system is called the type of the higher nervous activity (HNA).
In Pavlov's laboratory it was revealed, that being in the same
conditions not in all animals it was possible to develop
conditional reflexes, which depended on individual
peculiarities of the HNA. As a criterion of the HNA assessment

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the force mobility and balance of the excitation and inhibition
processes were elected.
According to these criteria Pavlov elected 4 types of
HNA:
I type is strong-balanced-moveable (sanguine);
II type is strong- balanced-inert (phlegmatic);
III type is strong-unbalanced (choleric);
IV type is weak (melancholic).
Pavlov’s this classification coincides with the
temperaments submitted by Hippocrates: sanguine, phlegmatic,
choleric, melancholic. There are many other intermediate types
of HNA, making variants of these main ones.
Type of HNA is built up based on congenital and
acquired characteristics during all life. The integrity of the
congenital characteristics is named as genotype; of the acquired
ones as a result of life experience – as phenotype. In man the
significance of genotype and phenotype in forming HNA are
approximately equal, since man is a social being. Different
conditions during life may change not only behaviour, but all
the psychological habits. In any type of HNA it is possible to
work out socially useful features of character. Thus, even a
weak type being in favourable conditions can attain much and
become a more useful member of a society, than a
representative of a strong type deprived of constant purpose
(e.g. outstanding composer Chaykovsky was melancholic).
In Pavlov’s laboratory puppies from the same family
were taken and placed into two different conditions – with a
poor care and with a good one. They respectively were grown
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up of a weak and a strong types of HNA. Excessive
guardianship and limitation of independence lead to weak, non-
initiative people’s appearance.

3.4. SLEEP

Sleep is a period of relative rest for the body and mind,

which arises in definite spans of time, and is accompanied by
decrease of the work ability level of discrete organs and
functions. Sleep is an indispensable requirement for the
organism, especially higher animals and man. This requirement
is different in different periods of life. Grown up man spends
third of his life in a state of periodically recurring sleep. But for
every man duration of sleep is individual and depends on habits
and temperament. Napoleon and Peter I slept only 5 hours a
day, Edison – 2 hours, Kant –7 hours. Sleep has a crucial role
in normal physiological activity. Without meal man can not
live more than 1 month, but without sleep - more than 1 week.
Sleep is a primary state of the organism and wakefulness is the
following state. Wakefulness is developed in the evolution
process, and the higher organization of matter the completer
process of wakefulness. As an evidence of it is the fact of
development of wakefulness in child during his growth.
Types of sleep. There are several types of sleep:
1) periodic diurnal sleep;
2) periodic seasonal sleep (winter and summer hibernation
in animals);
3) narcotic sleep induced by different chemical or physical
agents;
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 4) hypnotic sleep;
5) pathological sleep, connected with the brain blood
supply disorders and affection of its several parts.
The first two types are the variants of physiological
sleep, and the remaining three occur due to special non-
physiological effects on the organism.
The objective indices of sleep.
1) loss of active connections between the organism and
environment;
2) change in muscular tone;
3) change in vegetative functions depending on the sleep
phases (heart activity, arterial pressure, redistribution of blood,
metabolism, the body temperature, etc.).
Electric activity of the cerebral cortex. Record of
electrical potentials from the cortex is called
electroencephalography (EEG), which was submitted by
Berger. There are 4 main types of oscillations:
Frequency Amplitude
β 13 Hz 20-25 mV vivacity (eyes are
open, man is
thinking)
α 13-8 Hz 50 mV rest (man is
awaken with close
eyes)
θ 8-4 Hz 100-150 mV sleep
δ 4-0.5 Hz 50–300 mV deep sleep

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 In synchronic excitation the waves’ amplitude is high; in
vivacity desynchronization of waves (activation of cortex) is
observed and the β rhythm of vivacity arises.
Phases of sleep. According to the contemporary
classification sleep has got two phases: the slow and the fast
ones. The slow phase of sleep or the orthodoxal sleep lasts 1-
1.5 hours. It is characterized by θ and δ rhythms on EEG, as
well as by pattern of synchronous work of neurons. But EEG of
different cerebral structures brings about a conclusion, that
sleep is not a passive process, but rather active. In experiments
on cats it was revealed that even in wakefulness one part of
neurons is in active state, and another part, in passive (is
inhibited). Some neurons in sleep even intensify their
spontaneous activity, but work in another rhythm synchrony.
The fast phase of sleep or paradoxal sleep was
established in 1952 by the post-graduate of Chicago
University, Yujin Azerinsky. It is characterized in EEG by
desynchronization and by arising of β−rhythm. A rapid motion
of eyeballs occurs. It is called rapid eye movement (REM-
phase). After 1.5 hour sleep (slow phase) the REM-phase
comes, which lasts 6-10 min and alters by the slow phase
again. In such a manner it occurs 4-6 times over the night.
Herein, close to waking up this phase is prolonged up to 0.5
hour. In REM-phase man is in deep sleep and to wake up him
is more difficult, than in the phase of slow sleep. This period is
called fast because in EEG we have a rapid rhythm. That’s why
it is called also paradoxal for that although it is deep sleep, the

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β−rhythm of wakefulness occurs. Thus sleep during all night is
summed up by the slow and fast cycles of sleep. In man fast
sleep makes up 25% of the whole sleep. It is interesting, that in
various animals the duration of the REM-phase is different. In
rabbits – 3%, in cats – 30%, Cat is a cousin of beast prey, but
the latter has not any rights to sleep much, otherwise it will be
eaten.
The vegetative and the motor components of sleep.
Abrupt decrease of the muscular tone (neck, face) during the
REM-phase, the blood supply of the brain increases, muscular
small contractions, oscillations of the heart activity rhythm,
breathing, the metabolism increase, etc. appear. Most
interesting is the fact, that fast sleep is connected with dreams
accompanied by emotional experience. A waken up person in
the fast phase of sleep can retell the dream, but in the slow
phase of sleep he can’t, because the slow phase sweeps off the
dreams.
The vegetative changes in the fast phase are accompanied
by the dreams’ vision. If one continuously wakes up an
experimental animal in REM- phase, the different disorders
will arise: excitation, lack of appetite, fear, hallucinations up to
the conscience impediments. If in this case it’s allowed to have
a sleep, all disturbances will disappear. Wakening up in the
slow phase of sleep does not influence on overall condition.
In the slow phase of sleep the motor activity decreases,
but in the fast phase it increases. People can speak, cry, etc.
during the sleep. Some of them with an increased excitation
can go for a walk; they are called somnambulists or
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sleepwalkers. This arises in the fast phase of sleep. In medicine
a whole family of somnambulists is described (6 persons).
During nights they gathered together in the dining room to
have tea and went separately, but in the mornings they couldn’t
remember anything. The somnambulist’s movements are
distinguished by easiness. It is considered to be a compound of
normal and pathology and refers to sleep anomalies.
Physiological mechanisms of sleep. At the beginning of
this century a number of theories explaining the sleep nature
were proposed. They are the follows: circular, anemic, and
hyperthermic. All these vascular theories articulate sleep with
the brain blood flow changes. French scientists Legendre and
Pueron conducted an interesting experiment trying to explain
sleep as a result of special chemical substances’ production
(“the poisons”) that by humoral way evoke sleep. The
following experiment was performed on a dog. During some
days the dog was not allowed to sleep; and on the 10-th day it
was killed, after which its brain was studied. It was ascertained
that something horrible had happened to the frontal lobe of the
brain: the neurons’ shape was altered and their membranes
were eaten by leukocytes. Introduction of the spinal liquid of a
dog not permitted to sleep for a long time to the awaken dog,
evoked the same changes in the brain of the latter. Ten-year
investigations of these French scientists, as well as their
humoral theory of sleep without any doubt were accepted,
although hypnotoxin was not managed to get. Russian scientist
Anokhin observing the twins Sasha and Pasha revealed that

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twins slept at different times in spite of their common blood
supply. It was a quite serious fact against the humoral theory.
The next stage in the sleep mechanisms’ studying was the
theory of subcortical nuclei. During the World War I
encephalitis epidemic burst off, the characteristic feature of
which was sleepiness. Austrian neuropathologist Economo
observing the patients and performing sections and histological
studies of the dead bodies’ brains proved and testified that the
reason for this pathology was a virus having affinity to the hind
parts of the hypothalamus and the upper parts of the brain. This
type of encephalitis was named as Economo’s encephalitis.
Afterwards it was established, that affection of the mentioned
part of the hypothalamus leads to the sleepy condition
development. Brazil singer Maria-Luisa-Santes after a car
accident was in sleep condition during seven years due to the
affection of the upper parts of the brainstem.
Further investigations of the Swiss physiologist Hess on
the cat’s hypothalamus, as well as Russian neuropathologist
Grastchenkov on the patient’s hypothalamus asserted
Economo’s conclusion consisting of presence of the sleep and
wakefulness centres in the hypothalamus. Pavlov appreciated
of the data obtained by Hess, but referred to them with
criticism. According to Pavlov, excitation of these subcortical
structures brings about sharp reduction of the inflow of afferent
signals to the cortex, supporting the latter in a tone
(wakefulness). Thus, a cortical theory of sleep was proposed by
Pavlov. In his laboratory it was revealed, that a dog fell asleep
during the conditional reflex or its inhibition development.
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Pavlov suggested the inhibition and sleep were the same. Weak
monotone excitation brought to sleep, and the inhibition
irradiated over the whole cortex and even the subcortical
structures. But there were some situations, when the inhibition
did not capture all the cortex and some “guard centres”
remained, by means of which contact with environment took
place. Pavlov differentiated two types of sleep: active or
internal inhibition; and passive, when the cortex tone decreases
after removing afferent impulses. The law of strength relations
changes upon the parabiosis type.
Botkin was observing lass, who was deprived of vision,
hearing and touch feeling and always slept. German
neuropathologist Shtrompel described a boy, who was blind in
one eye and deaf in one ear and did not feel any pain, when
pricking the skin. When they covered his capable eye and
capable ear he immediately fell asleep. All these facts prove the
functional significance of afferent impulses in the cortex tone
maintenance. But, Pavlov’s theory is not universal and can’t
explain all types of sleep. A modern theory of sleep, cortico-
subcortical theory, was proposed by Anokhin. Independent of
the sleep type’s reasons it is arranged on a unique scheme.
Discovery of the reticular formation proved Anokhin’s
hypothesis. According to Anokhin 3 main structures take part
in the sleep formation: the reticular formation (RF), the
limbico-hypothalamic centres of sleep and the cerebral cortex.
Between the reticular formation and the hypothalamus
reciprocal interrelations exist. It is established, that in presence
of ascending influence from the RF the cortex inhibits the
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hypothalamus activity. In the passive sleep fewer impulses
come from the RF and the cortex activity weakens. Inhibition
of the cortex removes the hypothalamus inhibition (activation
of hypothalamus). In this case the RF also becomes inhibited,
which causes strong inhibition of the cortex. Another trunk
structures (hypnotic zones) take part in the sleep development,
too, but the main role here belongs to the thalamus-cortical
system. Other zones evoke the regulatory effect on the latter
depending on humoral factors and on physiological systems’
activity. All these zones correspond to the slow sleep, but the
fast sleep is connected with the reticular nuclei of the pons. In
their destruction the fast sleep disappears and the slow one
remains. Ideal sleep is accessed when the RF all ascending
influences become as less as it is possible. In the RF partial
blockage non-deep sleep occurs. Dreams are considered to be
the cortex activity without the RF ascending influences; they
take place at the limbic system’s and hormones’ expense.

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CHAPTER 4.
PHYSIOLOGY OF THE VEGETATIVE NERVOUS SYSTEM

Vegetative functions are the functions performed by the

internal organs, blood and lymphatic vessels, blood formed
elements and are directed to provide metabolism, growth,
development, as well as reproduction of the organism.
This term (vegetative) was proposed by French
physiologist Bichat in 1800. All functions of the organism have
been divided into animal, or somatic, and vegetative. In
accordance with this distribution of functions somatic and
vegetative regulating nervous systems are distinguished. The
somatic nervous system is responsible for the sensory and
motor functions of the organism; the vegetative system
provides the efferent innervations of all the viscera. Vegetative
functions are characteristic both to plants and animals, i.e. they
comprise nourishment, reproduction, respiration, etc. Animal
functions are intrinsic to animals only. They mostly comprise
the moving functions. In 1883 Gaskell proposed another term,
the visceral nervous system that was renamed later as the
autonomic nervous system by Langley. The meaning of this
term was in the independence of this system from the central
nervous system. But the concept of “autonomy” is quite
conventional. Later it has been shown that this system
innervates skeletal muscles providing their trophy. Besides, the
centres of vegetative system are located in the CNS and
numerous somatic reflexes have vegetative components.

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 General characteristics of the vegetative nervous system

In the structural and functional point of view the

vegetative nervous system consists of two parts: sympathetic
and parasympathetic (Figure 18).
Both of them have central and peripheral parts. The
central part is located in the CNS. The peripheral part consists
of ganglia and nerve fibres.
The sympathetic centres are situated in the thoracolumbar
part of the spinal cord, in T1-L5 segments. Their neurons’
bodies are located in the lateral horns, but the axons extend
from the spinal cord through the anterior horns, forming the
white rami communicantes. They are interrupted in the
sympathetic ganglia, where the second neurons are located.
The axons of postganglionic neurons extend from the ganglia
to the peripheral organs either via individual pathways or as
part of somatic nerves’ trunk. They extend from the ganglia as
delicate grey rami communicantes (their colour is due to lack
of myelin sheaths). Summarizing in contrast to somatic
nervous system the vegetative system’s efferent pathway
consists of two successive neurons, i.e. the preganglionic fibres
terminate in the vegetative ganglion and form the synaptic
contact with the main effector neurons. The axons of these
neurons are called postganglionic fibres. So, the vegetative
ganglia serve as migrated neurons from the nervous centres,
which were turning out from the CNS during evolution. The
true effector neurons are located in the ganglia, but the
interneurons are still in the CNS.

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 Figure 18. The structural characteristics of the vegetative
nervous system.

Depending on localization all the sympathetic ganglia are

divided into the paravertebral and prevertebral. The
paravertebral ganglia are arranged on both sides of the spinal
cord, forming two sympathetic trunks. The prevertebral ganglia
are situated further away from the spinal cord, than the ganglia
of sympathetic trunk.
The majority of sympathetic preganglionic fibres are
interrupted in the ganglia of the sympathetic trunk, but some of

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them pass through the trunk without interruption and are
broken in prevertebral ganglia. The sympathetic nerves supply
actually all organs and tissue. In contrast, the parasympathetic
nerves do not innervate the skeletal muscle, the CNS, most of
the blood vessels, and the uterus. The upper centres of the
sympathetic system realize the innervations of the organs of the
head (via superior cervical sympathetic ganglion), several
thoracic segments send the fibres through ganglion stellatum to
the chest organs (heart, bronchi), through the solar plexus and
superior mesenteric ganglion to the abdominal organs; from
the lumbar segments fibres pass through the inferior mesenteric
ganglion to the organs of the pelvis.
The parasympathetic centres have craniosacral
localization. The cranial part is represented by the midbrain,
pons and the medulla oblongata. Its neurons respectively are
situated in the III pair of craniocerebral nerve nucleus; in the
VII, IX, and X pair of nerve nuclei. The parasympathetic fibres
extended from these centres form the part of n. oculomotorius
(innervation of the pupil), n. facialis (innervation of the
sublingual and submaxillary glands) n. glossopharyngeus
(innervation of the parotid gland) and n. vagus (innervation of
all the thoracic and abdominal organs). The sacral centres’
fibres form the part of the pelvic nerve (innervation of large
intestine, urinary bladder, genitals).
Parasympathetic ganglia are located within the organs
(intramural ganglia) or are close to them (ciliary ganglion, otic
ganglion, etc.). The parasympathetic efferent pathway has also
bineuronal structure, i.e. the first neuron axon is interrupted in
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the parasympathetic ganglion, forming synaptic contact with
the second neuron. Moreover, the parasympathetic
preganglionic nerve fibres are longer than the postganglionic
ones. In contrast, the sympathetic preganglionic nerve fibres
are shorter than the postganglionic ones.
The vegetative innervation of the above mentioned
organs is bineuronal.
But there are some exceptions:
1. The medulla of the adrenal glands. The sympathetic
efferent pathway of this one has one-neuronal structure. The
role of the postganglionic fibres is performed by the
chromaffine cells of the adrenal medulla, which secrete
catecholamines into blood. So, the chromaffine cells produce
adrenaline and like the sympathetic postganglionic nerve
ending they are able to produce noradrenaline.
2. The metasympathetic nervous system is characteristic
for some internal organs (intestine, ureter) that possess
automatism. These organs due to own reflex arc (reflexogenic
field, the afferent way, the centre (ganglion) and deriving from
it the efferent pathway) have in fact three-neuronal
innervation, since the outer vegetative part provides the two-
neuronal innervation.
Afferent pathway of vegetative reflex. The afferent
pathways begin from the reflexogenic fields and appropriate
receptors. The latters are localized in the internal and external
organs. The afferent nerve fibres may pass with somatic nerves
or independently. The impulses coming by those pathways
reach not only the vegetative centres, but also the
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hypothalamus and the cortex. All levels of the autonomic
nervous system are subordinated to the higher autonomic
centres located in the hypothalamus and corpus striatum, which
coordinate the functions of many organs and systems of the
body and, in turn are subordinated to the cerebral cortex. So,
the cerebral cortex is responsible for an integrated body
reaction by combining its somatic and vegetative functions into
single behavioural acts.

Comparative analysis of the somatic and the vegetative

nervous systems

1. The vegetative nervous centres are located in foci, but the

somatic centres are situated in all spinal segments.
2. In the vegetative system the effector neuron is located out
of the CNS and only the interneuron is in the CNS. In the
somatic nerve centres both the effector and the interneuron are
in the CNS (Figure 19).
3. The vegetative neurons are situated in the lateral horns of
the spinal cord, while the somatic neurons are in the anterior
horns (Figure 19).
4. The vegetative innervation is not of metameric pattern in
distinct from the somatic one.
5. The conductivity of impulses in the vegetative nerve
system is low, because the preganglionic nerve fibres are
represented by the B-type very weak myelinated fibres, and the
conductivity speed of impulses is 3-18m/sec. The
postganglionic nerve fibres belong to the C-type: they are
unmyelinated nerve fibres, and the conductivity speed of
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impulses is 1-3 m/sec. In contrast, all the somatic nerve fibres
belong to A-type and their conductivity speed of impulses
makes up 70-120 m/sec.
6. The action potential (AP) of the vegetative nervous system
is long-term. The AP of postganglionic nerve fibres has
negative after-potential that turns into positive after-potential
of 300 msec duration.
7. The vegetative nerves possess low lability and excitability,
compared with the somatic fibres.

Figure 19. Comparative analysis of the somatic and the

vegetative reflector arcs.

Properties of the vegetative ganglia (synapses)

The vegetative ganglia play a significant role in the

distribution and propagation of the impulses passing through
them. The vegetative ganglia could be represented as neuronal

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centres and perform peripheral reflexes, e.g. in the cardiac
activity. The number of nerve cells in ganglia is much larger
(2-30 times) than the number of preganglionic fibres entering
them. Each fibre forms synapses with many ganglionic cells
(divergence of impulses). It is rather important, because the
zone of influence of preganglionic fibre is extended. The same
neuron could get impulses from different nerve fibres, so there
is also convergence phenomenon. The latter provides reliability
of the impulse transmitting. Since ganglia are neuronal unites,
some properties of nervous centres have to be intrinsic to them.
For example, one-way conduction of impulses, fatigue, spatial
and temporal summation, occlusion and so on.
Along with this, the vegetative ganglia have also a
number of specific features:
1) long synaptic delay (1.5-30 msec), while the synaptic
delay in the CNS is only 0.5 msec;
2) long duration of excitatory postsynaptic potential;
3) long-term after-hyperpolarization that results in
inhibition after the excitation;
4) rhythm transformation. The rhythm of excitation of
preganglionic fibres exceeding the natural frequency of
impulses is partially blocked in the synapses, and the
postganglionic neuron is excited at a slower rhythm;
5) low lability of the ganglionic synapses. The maximal
rhythm of impulse conduction along the postganglionic nerve
fibres is 15 imp /sec. In contrast to this, in the motor nerve
fibres it makes 500 imp/sec.

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 Mechanism of impulse conduction in vegetative synapses,
their mediators

It has been revealed that in the preganglionic nerve

endings (both for the sympathetic and the parasympathetic) the
same mediator, acetylcholine, is produced, and the impulse
transmission is realized by means of acetylcholine. This
phenomenon was discovered by Kibyakov in 1933 during the
experiment with perfusion of the superior sympathetic
ganglion. He determined acetylcholine in the perfusion liquid.
Being produced acetylcholine bounds to the cholinoreceptors,
which could be blocked by curare-like substances (for example
ditillinum, etc.), and could be activated by nicotine. So, this
type of receptors is called N-type of cholinoreceptors.
The mediator of the postganglionic parasympathetic
nerve fibre is also acetylcholine. In this case it interacts with
another type of receptors, so called M-type cholinoreceptors
(the muscarinic ones). They can be blocked by atropine. M-
cholinoreceptors have their subdivision too. It has been
revealed, that acetylcholine can activate Na+ - chemo-excitatory
channels resulting in the excitatory postsynaptic potential
formation. These synapses are present in the smooth muscles:
intestine, urinary bladder, bronchi. Another type of the M-
cholinoreceptors results in activation of K+-channels and
hyperpolarization of the postsynaptic membrane, so the
inhibitory postsynaptic potential is formed. This type of M-
cholinoreceptors is present in the heart, excitation of which

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causes inhibition of the heart activity (negative chronotropic,
negative dromotropic, negative inotropic effects, etc).
The mediator of the sympathetic postganglionic fibre is
noradrenaline. But there are some exceptions: the cholinergic
sympathetic nerve fibres, innervating the sweat glands and the
skeletal muscle vessels. However, the majority of the
sympathetic nerve fibres are adrenergic ones. There are two
types of adrenoreceptors: α and β, which in their turn are
divided into α1-and α2-, β1- and β2 -groups. Depending on the
type of adrenoreceptor the mediator is combined with, different
effects could be observed. In case of binding with α1-
adrenoreceptors, which are abundant in the arterioles of the
internal organs, the vasoconstrictor (excitatory) effect occurs.
The α2-adrenoreceptors are localized in the presynaptic
membrane. In case of noradrenaline binding to these receptors
its further production is inhibited. If noradrenaline interacts
with β1-adrenoreceptors, which are available preferably in the
cardiac muscle, the excitatory effect (positive chronotropic,
positive dromotropic, positive inotropic, etc.) is observed. β2-
adrenoreceptors are available in the coronary vessels of the
heart. In case of binding of adrenaline to these receptors, the
inhibitory (vasodilative) effect takes place (it prevents heart
attack during the sympathetic over-stimulation).
Comparative characteristics of sympathetic and
parasympathetic influences. The sympathetic nervous system
has a crucial importance in all extreme situations and provides
ergotropic regulation (mobilization of all the organ-systems).

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The parasympathetic nervous system performs the regulation
of current activities of organs and systems (trophotropic
regulation). Stimulation of the sympathetic nerves of a
fatigued skeletal muscle restores its working capacity
(experiment of Orbeli and Ginetsinsky), so the sympathetic
system also possesses a trophotropic function. We can assert
that the sympathetic and parasympathetic nerve systems are in
close interconnection. But simultaneously they have opposite
effects, which are expressed in the regulation of different
organs’ and tissues’ activity (Figure 20).
1. The smooth muscles of internal organs. The sympathetic
nervous system has an inhibitory influence on the gastro-
intestinal tract motor and secretory activity, urinary bladder,
bronchi (relaxation because of the stimulation of the β2-
adrenoreceptors). Conversely, the parasympathetic nervous
system has an excitatory influence on the above-mentioned
organs (the effect of M-cholinoreceptors, combined with Na-
channels).
2. Sphincters of digestive organs and urinary bladder. The
sympathetic nervous system causes contraction of the
sphyncters; the parasympathetic one evokes their relaxation.
3. The vascular smooth muscles of the internal organs. The
sympathetic nervous system stimulates contraction of the
smooth muscle layer in the vessels of the skin and internal
organs (the effect of α1-adrenoreceptors). The parasympathetic
nervous system causes dilation of salivary gland and tongue
vessels (the effect of M-cholinoreceptors combined with K-
channels).
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 4. The heart activity. The sympathetic nervous system
stimulates the heart function (the effect of β1-adrenoreceptors).
The parasympathetic nervous system inhibits the cardiac
activity (the effect of M-cholinoreceptors combined with K-
channels).

Figure 20. The sympathetic and parasympathetic influences

on the organs.

The antagonistic effects of sympathetic and

parasympathetic systems are also expressed in their action on
the pupil. The excitation of sympathetic nervous system leads
to dilation of pupil, parasympathetic – to narrowing.
Nevertheless in some conditions the sympathetic and the
parasympathetic nervous systems are synergists (in stress

126
reaction development, in blood clotting process, etc.).
Generally, the sympathetic nervous system inhibits the
peristaltic movements of the intestine, but in a very strong
stimulation (e.g. during stress reaction) it acts like the
parasympathetic system (so-called nervous diarrhea). Both the
sympathetic and parasympathetic nervous systems lead to the
activation of blood clotting.

Vegetative reflexes

In connection with the given reflex reflexogenic field and

effector organ localization all the vegetative reflexes are
divided into:
1) viscero-visceral reflexes (the regulation of the heart
activity is performed by excitation of the receptors in the aorta,
a. carotid, vena cava, etc.);
2) somato-visceral reflexes (decrease of the heart rate
when pressure is applied to the eyeballs (Danini-Aschner’s
reflex or oculocardiac reflex);
3) viscero-somatic reflexes (the activation of respiratory
muscles (breathing) at blood composition changes and
chemoreceptors’ excitation);
4) viscero-sensory reflexes (hypoxia in cardiac muscle
causes a pain in the subscapular or pectoral region);
5) senso-visceral reflexes (the stimulation of the skin
definite areas leads to appearance of vascular reactions in
visceral organs. Certain therapeutic methods (acupuncture and
physiotherapeutic procedures) are based on this phenomenon.

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CHAPTER 5.
PHYSIOLOGY OF THE ENDOCRINE SYSTEM

Alive organism is an integral system that is ensured by

the coordinated activity of various regulatory systems.
Evolution of organisms occurs in close interconnection with
evolution of the regulatory systems. For example, in the
simplest organisms (viruses, unicellular organisms) regulation
was carried out by diverse chemical products, inter-
metabolites. Later, when the multi-cellular organisms
appeared, the neuronal system arose. With appearing of
vertebrates some part of the neuronal cells obtain the capacity
to secrete biologically active substances, i.e. neurosecretory
cells appear. Finally, at the recent stages of the development of
vertebrates, the endocrine glands appeared which along with
the neuronal system fulfilled the regulation of the organism
that leads to the organism integrity. Thus, evolution of the
regulatory systems goes on in the following direction:
intralcellular mechanisms→neuronal cells→neurosecretory
cells→endocrine glands. The endocrine glands, being
submitted to the neuronal influences, themselves influence
actively on the neuronal system and are a compound part of the
nervous-endocrine regulation general system.

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5.1. GENERAL CHARACTERISTICS OF THE ENDOCRINE GLANDS

The properties, functions and the biological importance

of the endocrine glands are an issue of endocrinology. The
term endocrine derives from Greek words: endo – inside and
crineum secrete. So endocrine glands, or the glands of inner
secretion, are specialized organs or a group of cells having a
main function to secrete specific biologically active substances
into the internal medium of the organism.
Properties of the endocrine glands:
1. They are of very small size (from some mg to 25-35 g).
2. They have an abundant blood supply.
3. They don’t have ducts. The endocrine glands excrete
their secret immediately into the blood (Figure 21).

Figure 21. An exocrine gland (left) and an endocrine gland

compared by their respective paths of secretion.

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 The endocrine glands of humans and higher animals are
follows: pituitary (hypophysis), pineal gland (epiphysis),
thyroid gland, parathyroid glands, thymus, adrenal glands,
pancreas (islets of Langerhans), sex glands, the temporal
gland - placenta.

Figure 22. Endocrine glands of humans.

Some organs (kidney, heart and digestive tract) consist of

endocrine cells, which are included into the APUD (amine

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precursor uptake and decarboxylation) system and produce
some hormones. The hypothalamus, “endocrine brain”
simultaneously is a neuronal and endocrine structure.

Structure, properties and action mechanism of hormones

The specific product of the endocrine gland secretion is

called hormone (from the Greek word horma – excitation).
By their biochemical structure all hormones are classified
into three principle groups:
1) protein–peptide compounds (pituitary hormones,
insulin, thyrocalcitonin, parathyroid hormone, glucagon and
the hypothalamic releasing factors);
2) steroids (adrenal cortical hormones, sex hormones);
3) amino-acid derivatives (thyroxin, thriiodothyronine,
renin, epinephrine and norepinephrine (adrenaline and
noradrenaline)).
This classification is very important, since the hormone
action mechanism depends on their chemical structures.
Hormone properties. The most important properties of
hormones are:
1. High specificity. It is a unique property, which is
conditioned by the hormone chemical structure, function and
site of production. Every hormone evokes a definite and
specific biological action. Another hormone cannot replace the
deficiency of a certain hormone. Every hormone influences on
the corresponding organ, tissue or cell, which are named as
targets. Along with this it is known, that several biologically
active substances – histamine, serotonin, bradykinin,
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prostaglandins, etc also have a specific action. But these are not
called hormones due to their production in different organs and
different tissues. Catecholamines (epinephrine, norepinephrine
and dopamine) together with the main site of their production
have also other sites (peripheral synapses of the neuronal
system, some structures of peripheral organs) and cannot be
considered as true hormones, so they are usually called
hormonoids.
2. High biological activity. Their quite insignificant
amounts can sharply change functions of the organs.
3. Distant action. The hormones can act on the organs
and tissues being located at a distance from the gland, by which
they are secreted.
4. Secretion (property to be secreted). Ahead of being
released hormone has to be synthesized. The peptide hormone
synthesis proceeds in ribosomes, after which hormone passes
and is accumulated in Golgi’s complex. The steroid hormones’
and catecholamines’ synthesis takes place in the cytoplasm and
mitochondria. All synthesized hormones are accumulated in the
vesicles, which move to the cytoplasmic membrane with the
help of microtubules and extrude their composition into the
blood. The secreted hormone passes into the inner medium of
the organism (blood and lymph). One part of it circulates in the
active form (free state), and another, in a combined state with
the proteins specific for the given hormone (transcortin for the
hormones of adrenal cortex), or with nonspecific plasma
proteins (albumins, globulins), or with formed elements
(erythrocytes). The complex part with proteins and the part in
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free state are in dynamic equilibrium and easily convert into
each other, if necessary. The combined state of the hormone
has a significant physiological benefit: 1) prevents the
organism from the abundant accumulation of free state
hormones in the blood and protects tissues from their action; 2)
serves as a reserve and, if needed, can be decomposed and
converted into a free state; 3) protects the hormones’ from the
destructive action of enzymes; 4) prevents the low molecular
hormones’ filtration through the kidneys.
Two factors are effective to increase or decrease the
concentration of a hormone in blood. One of these is a rate of
hormone secretion into blood; the second one is a rate of
removal of the hormone from the blood, which is called the
metabolic clearance rate. This is usually expressed in terms of
millilitres of plasma cleared out of the hormone per minute.
The biological half-life of hormone (T1/2) is the time,
during which the blood concentration of hormone is reduced
by half. That could be used to estimate the intensity of hormone
consumption.
Mechanism of hormone action. The mechanism of
hormone action on the target-cell is conditioned by the
chemical origin of the hormone.
1. The membrane type of hormone action (Figure 23). It
is suitable for hormones with a high molecular mass (protein-
peptide hormones) and catecholamines. The high molecular
mass of the hormone hurdles its passage into the cell. In this
case the hormone action takes place through the hormone-
receptor conjunction. The hormone is being combined with a
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receptor on the outer membrane, forming so-called hormone-
receptor complex, which can act on certain intracellular
structures only with the help of the intracellular mediators –
messengers (cAMP, cGMP, Ca2+ ions, products of the
membrane phospholipid decomposition (diacylglycerol,
inositoltriphosphate)).
The sequence of events in proteinic hormone action is
essentially the following:
1. The hormone binds with the membrane specific
receptor.
2. The combined receptor-hormone complex activates
synthesis of the secondary messenger.
3. The messenger activates the appropriative
proteinkynase with the phosphorylation and activation of
intracellular proteins.

Figure 23. Membrane and cytoplasmatic mechanisms

of hormones’ action.
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 2. The cytoplasmic type of hormone action (Figure 23). It
begins with the hormone penetration through the membrane,
conjunction with the cytoplasmic protein-receptor and the
signal transmitting from the originated complex to the nuclear
structures that are responsible for the protein synthesis. That is
the way of steroid and thyroid hormones’ action.
The sequence of events in steroid hormone action is
essentially the following:
1. The hormone enters the cytoplasm of the cell, where it
binds with a specific receptor.
2. The combined receptor-hormone complex is
transported into the nucleus.
3. The receptor-hormone complex acts on the
transcription process of the RNA messenger.
4. The RNA messenger diffuses into the cytoplasm,
where it promotes the translation process in the ribosomes.
Summarizing the issue of hormone action mechanisms it
is necessary to note, that the hormone action can be of two
ways: functional and morphogenetic.
1. The functional action can be:
a) metabolic, changes of metabolic processes in the
target-organ;
b) kinetic, some functions of organs or processes are
expressed only by action of the given hormone;
c) corrective, changes of function intensity in organs or
tissues;

135
 d) reactogenic or permissive, changes of the tissue
susceptibility to the given hormone action in the presence of
another hormone.
2. Morphogenetic action.
The morphogenetic action is the stimulation of
differentiation, growth and metamorphosis processes in the
organism.
Methods of study of the endocrine glands’ activity are:
1. Clinical examination of the patients with endocrine
hypo- or hyper-functions.
2. Gland removal.
3. Gland transplantation.
4. Determination of hormone in the organism liquid
medium. Estimation of the blood or urine concentration of a
specific hormone using biological or physiological techniques.
5. Introduction of glandular extracts or pure hormones.
6. Selective damage of gland.
7. Parabiotic method.
8. Comparative assessment of the biological activity of
the glandular inflowing and out- flowing blood content.
9. Method of indicated radioactive isotopes.
10. Method of fluorescent antibodies.

5.2. THE HYPOTHALAMO-HYPOPHYSIAL SYSTEM

A close anatomical and functional connection between

the hypothalamus and hypophysis is a base for their uniting in
the entire hypothalamo–hypophysial system. For
comprehension of the physiological mechanisms of functioning
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of this system it is necessary to imagine its anatomic –
histological characteristics.
The hypothalamus, containing 32 pairs of nuclei
conditionally is divided into 3 parts: anterior, medial,
posterior; and thanks to its special neuro-secretory cells it is
conjoined with the pituitary functionally. There are two main
conjunctions between the hypothalamus and hypophysis
(Figure 24).

Figure 24. Hypothalamo-hypophysial system.

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 I. The hypothalamo-neurohypophysial system. The
anterior hypothalamus, where two types of neurosecretory
cells (nuclei) are, the supraoptic nucleus (SON) and
paraventricular nucleus (PVN), is connected with the posterior
pituitary (neurohypophysis) through the nerve cells’ axons.
Posterior pituitary consists of pituicytes that resemble the glial
cells and are named as Herring’s bodies. They serve as a
reservoir and only two hypothalamic hormones accumulate:
anti-diuretic hormone (ADH) and oxytocin. So
neurohypophysis is connected with the hypothalamus by nerve
cells’ axons.
II. The hypothalamo-adenohypophysial system.
Hypothalamic posterior and medial parts’ conjunction with the
anterior pituitary (which is known as adenohypohysis) and is
realized through the abundant vascular (arterial) ramifications
that compose so called marvelous network (primary capillary
plexus). In the hypothalamic region the nervous network,
consisting of the nerve cells’ axons, forms peculiar neuron-
capillary synapses on the capillary plexus. Through these
structures, the products of neurosecretion of the hypothalamic
cells enter the blood and with its flow are conveyed to the
anterior pituitary cells to change their function. The blood out-
flowing from the capillaries of the hypothalamic region enters
the so-called portal vessels of the pituitary. These vessels
compose the pituitary secondary capillary plexus, from which
the blood outflows into the vein. Pituitary consists of uncolored
principal or chromophobe cells (60%) and the colored
chromophil cells (40%). In turn the chromophil cells are
138
divided into the acidophil (30-35%) and the basophile cells (5-
10%). It is considered that the main producers of hormones are
the chromophil cells, and the principal cells are only their
precursors.
III. Recent data evident about the presence of the third
hormonal system, the hypothalamo-extrahypophysial system of
neuroregulatory peptides (encephalin, endorphins, vasoactive
intestinal peptide (VIP), substance P, etc.). These
neuropeptides partially are produced in the digestive system
and other tissues.

The hypothalamo – extrahypophysial system

It includes neurosecretory cells’ axons, that continue into

the medulla oblongata, thalamus, hypophysis, limbic system
and by secreting neuropeptides (endorphin, encephalin,
dinorphin, substance P, vasoactive intestinal peptide (VIP),
somatostatin) realize their activity. A more characteristic action
of endorphin, encephalin, dinorphin is a morphine-like action.
It is considered they are bound with the same receptors of the
neuron membrane that provides the morphine (opium) action.
That’s why they are named “endogen opiates”.
Correspondingly, the morphine antagonists, particularly
naloxone, inhibit the endorphin action. The endorphins and the
P- substance have a direct relation to pain. They take part in the
realization of pain reflex: P-substance is a mediator of pain and
promotes the pain perception, whereas endorphins and
encephalin mitigate the pain sensitivity. The stronger is the
pain, the more are endorphins. Secretion of endorphins and
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encephalin increases during stress, labor, surgical operations,
etc.

The hypothalamo-neurohypophysial system

There are two peptide hormones in this system: ADH and

oxytocin, which are secreted in the SON and PVN, but ADH is
secreted mainly by SON, and oxytocin - secreted mainly by
PVN. Normal, physiological doses of ADH exert antidiuretic
action and regulate water reabsorption. The mechanism of the
antidiuretic action consists in intensifying water facultative
reabsorption by the walls of the renal distal and collecting
tubules. The initiator of the ADH secretion is the excitation of
the osmoreceptors, which are represented by vacuolated cells.
ADH transfers to the neurohypophisis by axons and thereafter
is released into blood. ADH circulating in blood influences on
its target (renal distal and collecting tubules) and activates the
enzymes that destroy cell membrane with creating pores
through which water reabsorption is facilitated. In this way the
water balance of the organism is regulated. Thus, impairment
of the neurohypophisis function brings to diabetes insipidus
development. ADH is also called vasopressin, because it causes
contraction of the smooth muscles of the vessels (especially of
the arterioles) and raises arterial pressure. But this pressing
effect is observed only in artificial administration of the
hormone large dozes or its hypersecretion.
Oxytocin stimulates contraction of the uterus smooth
muscles, especially in near-term pregnancy. The presence of
this hormone is indispensable for the normal course of labour.
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It also influences on the extruding of already produced milk.
There are some data that oxytocin has a stimulating influence
on the smooth muscles of vessels and sex ducts and evokes
their contraction. Pursuant to recent data in male oxytocin in
parallel with ADH participates in the water–salt balance
regulation.
Natural stimulus for the oxytocin secretion is the
irritation of receptors of the nipple and uterus. The way of the
reflex is: mechano-sensory afferent impulses from the nipple
and uterus → SON and PVN→ neurosecretion of oxytocin →
milk secretion or uterus contraction. So the hypothalamo-
neurohypophysial system function is submitted to the reflector
regulation.

The hypothalamo-adenohypophysial system

In the mediobasal shallow cell nuclei and the posterior

hypothalamus regions produce substances or factors, which
stimulate or inhibit the release of the hypophysial tropic
hormones. Correspondingly these parts are named
hypophysotropic zones, and the hormones released there -
releasing factors. Herein the hormone production releasing
factors of adenohypophysis are called liberins, and the factors,
inhibiting the production - statins.
Liberins are the followings:
1.Thyroliberin (TL), stimulates the thyrotropic (or
thyrotropin) hormone (TTH) production (according to some
data the prolactin production too) by adenohypophysis.

141
 2.Corticoliberin (CL), stimulates the adrenocortico-
tropic hormone (ACTH) secretion.
3.Gonadoliberin (GL), stimulates the luteinizing (LH)
and the follicle stimulating (FSH) hormone secretion.
4.Somatoliberin (STL), stimulates the growth
(somatotropic) hormone (STH) secretion.
5.Prolactoliberin (PLL), stimulates the prolactin (PL)
secretion..
6.Melanoliberin (ML), stimulates the melanocyte-
stimulating hormone (MCSH) secretion.
Statins are the followings:
1. Somatostatin (SS), inhibits the STH secretion.
2. Melanostatin (MS), inhibits the MCSH secretion.
3. Prolactostatin (PS), inhibits the PL secretion.
All hormones of adenohypophysis are divided into
glandotropic hormones, which directly act on the peripheral
gland activity, and effector ones, which alter some organs’
functions.
The glandotropic hormones are: ACTH, TTH, LH, FSH.
The effector hormones are: STH, PL, MCSH.
Effector hormones. STH is produced by the acidophil
cells of adenohypopyisis. It promotes protein synthesis in
organs and tissues, especially in tubular bones, and so causes
growth in children and younger. STH activates RNA synthesis,
which is an essential link in the protein synthesis and
intensifies the amino-acid transportation from the blood to the
cells. It is of importance to note that STH performs its protein
synthesis stimulating action only in the presence of
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somatomedins, synthesized in the liver, and insulin, as well as
carbohydrates. This action is inhibited after removal of the
pancreas in animals or exclusion of carbohydrates from food.
Large doses of STH activate insulin secretion in young
animals, but in adults the pancreatic islets are degenerated and
diabetes mellitus develops. Owing to the intensified protein
synthesis the blood content of amino-acids is reduced.
Retention of nitrogen in the body takes place, as well as that of
phosphorus, calcium and sodium. STH mobilizes fats from
depots and activates their utilization by tissues.
Secretion of STH continues throughout the organism’s
life. It is stimulated by the STH – releasing factor and is
inhibited by somatostatin. In early childhood hypoproduction
of STH brings to sharp retardation of growth, what is called
hypophysial dwarfism (nanism). Overproduction of STH in
childhood leads to gigantism. Hyperproduction of STH in adult
life, when the growth has already been completed altogether,
causes enlargement of the body parts, which are still capable to
grow. This state is called acromegalia. It is also characterized
by insufficiency of the pancreatic insular apparatus, leading to
diabetes mellitus.
Hypoproduction of STH in adults leads to
panhypopituitarism. Panhypopituitarism is expressed by
suppression of thyroid and adrenal glands’ function, which
leads to dysfunction of sex glands.
MCSH or intermedin immediately acts on the skin and
retina pigment metabolism. It activates the melanin pigment
synthesis in the melanophores. Besides, it promotes the
143
melanophores’ enlargement and the pigment synthesis and
distribution throughout the cytoplasm. Melanin pigment in
retina or skin has a protective function against direct sun light.
Reduced production of the hormone leads to the skin
depigmentation. Hyperproduction of it, observed in pregnancy,
brings to hyperpigmentation in separate parts of the skin.
PL or luteotropic hormone (product of the acidophil
cells) has a property to strengthen milk production by the
mammalian glands, as well as to stimulate the corpus luteum of
pregnancy development. Parenteral administration of this
hormone induces intensification of the milk extrusion not only
in feeding females, but also in non feeding individuals. PL
decreases the utilization of carbohydrates by tissues, but
facilitates the glucose transport to the mammary glands. This
hormone regulates the water-salt balance. It also is responsible
for the mother’s instinct development. In males prolactin
regulates activity of spermatozoa, formation of LH-sensitive
receptors in sex glands and secretion of androgens.
Glandotropic hormones. ACTH is produced by the
basophile cells of the anterior hypophysis. It has a direct
relation to the adrenal glands’ incretory function regulation.
Mostly it refers to the fascicular zone of the adrenal cortex, but
ACTH has insignificant action on the glomerular and reticular
zones. Secretion of ACTH by the pituitary is augmented in
stress. Hypersecretion of ACTH leads to Cushing’s syndrome
(moon face, buffalo torso and hirsutism) development, but
hyposecretion of it, to Addison’s disease (bronze disease,
which is accompanied by metabolic disorders).
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 TTH is produced by the basophile cells. It regulates the
iodine-containing hormones’ synthesis and secretion by thyroid
gland in the following ways: 1) it activates the iodine pump
and accumulation of iodine by thyroid tissue; 2) it increases
iodination of tyrosine; 3) it intensifies thyroglobulin
breakdown in the thyroid gland, which leads to enhanced
secretion of thyroxin and triiodothyronine into the blood.
Hypersecretion of TTH evokes Grave’s syndrome.
GTHs are produced by the basophile cells. They regulate
the sex glands’ activity. The FSH stimulates the follicle
maturation and estrogens’ secretion in female ovaries and
spermatogenesis in male testes Sertoli’s cells. The LH
stimulates the ovulation process, corpus luteum formation and
progesterone secretion in the ovaries, as well as androgens’
secretion by the interstitial Leydig’s cells in the testes.
The regulation of functional activity of the endocrine
glands is realized by so-called positive and negative feedback
mechanisms mainly at the level of hypothalamus (liberins and
statins), and also of hypophysis.
Endocrine glands that are not under the regulating
influence of the hypothalamo-hypophysial system are
parathyroid glands, C-cells of the thyroid gland, pancreas, and
the medullar part of the adrenal glands.

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 5.3. SPECIAL PHYSIOLOGY OF ENDOCRINE GLANDS
Physiology of the thyroid gland

Iodine-containing hormones. The thyroid gland

(Figure 25) consists of follicular and parafollicular tissues.
The follicular tissue contains of glandular cells, which are
characterized by the capacity to absorb iodine from blood by
the iodine pump. Their intercellular concentration of iodine
exceeds 300 times than that in the blood plasma. Owing to the
accumulation of iodine the iodinated monoiodotyrosine (MIT),
diiodotyrosine (DIT) and active hormones triiodotyronine (T3)
and tetraiodotyronine (thyroxin, T4) are synthesized in the
gland. They form a complex with the protein thyroglobulin. T3
and T4 are released into the blood, when thyroglobulin is
hydrolyzed by protease produced by the gland cells. In the
blood these hormones bind to the specific proteins, carriers
(thyroxin-binding globulin, thyroxin-binding prealbumin). But
only the free form of hormone is capable to produce
physiological action.

Figure 25. Structure of thyroid gland.

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 T4-protein complex serves as a reserve from which new
active portions of hormone are liberated. T3 is physiologically
more active than T4. But T3 effect is observed only during 6-12
hours, while the duration of T4 effect is 12 days. The active
agent of T3 and T4 is the triiodothyroacetic acid which is
formed in the tissues from T3 more quickly than from T4.
Physiological effects of iodine-containing hormones.
The characteristic action of these hormones are: 1) metabolism
intensification (facilitation of carbohydrates’, fats’ and
proteins’ breakdown with increase of oxygen consumption); 2)
calorigenic action (decoupling of oxidative phosphorylation,
diminish of ATP synthesis, release of the energy in a form of
heat and increase of the body temperature); 3) stimulation of
the growth and development processes; 4) activation of the
CNS function, particularly of the cerebral cortex (mediated by
stimulation of the reticular formation); 5) increase of the
tissues’ excitability and receptors’ sensitivity to the
catecholamines.
The regulation of thyroid gland function (production of
iodine-containing hormones) is realized by the hypothalamo-
adenohypophysial system (thyroliberin, thyrotrophic hormone)
by feedback mechanism.
Disorders of thyroid function. Malfunction of the
thyroid gland (hypothyroidism), developed in childhood leads
to cretinism, which is characterized by retarded growth,
disproportion of the body, delay of sexual and mental
development. This disorder in adulthood causes myxedema,
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which is accompanied by diminished metabolism, slow
thinking and speech, apathy, sexual dysfunction and the body
temperature drop. Due to derangement of protein metabolism,
the oncotic pressure increases in the tissue, causing retention of
water and the body weight increase. When there is a deficiency
of iodine required for the thyroid hormones’ synthesis the
gland tissue proliferates and goiter develops (endemic goiter).
In hyperfunction of thyroid gland Basedow’s or Graves’s
disease (thyrotoxicosis) develops which is characterized by the
goiter, exophthalmoses, acceleration of the heart rate, high
basal metabolic rate and temperature, enhanced consumption of
oxygen and food, hyperexcitability of the nervous system and
tremor.
Thyrocalcitonin (TCT). TCT hormone is a calcium-
regulating hormone. It is produced by C cells of the
parafollicular tissue. It decreases the concentration of Ca2+ in
the blood, because it activates the function of osteoblasts,
which promote formation of the bone tissue. TCT also reduces
the reabsorption of Ca2+ in kidney and its absorption in small
intestine. So, the targets of the TCT action are the kidneys,
bones and intestine. It also reduces the reabsorption of
phosphate in the kidneys. The regulation of the C-cells’
function is realized by the feedback mechanism regarding the
blood Ca2+ concentration.

Physiology of the parathyroid glands

Parathyroid glands (two pairs in man, Figure 26)

produce parathyroid hormone (PTH), which is the main
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calcium-phosphate-regulating hormone. Its targets are the
kidney, bone and intestine (the same as that for TCT). But in
contrast to TCT, PTH activates the osteoclasts (causes
destruction of bone), stimulates the reabsorption of Ca2+ in the
kidney and its absorption in intestine. All these processes lead
to increase of Ca2+ level in the blood. PTH reduces the
reabsorption of phosphate in kidney. So in this function PTH
and TCT are synergists. The regulation of the parathyroid
glands’ function is realized by the negative feedback
mechanism, which is determined by the blood Ca2+
concentration.

Figure 26. Thyroid and parathyroid glands.

Parathyroid glands are vital glands and their

hypofunction is accompanied by so-called hypoparathyroidism.
The latter is characterized by convulsions of the skeletal
muscles (parathyroprival tetany). Parathyroprival tetany
develops because of a low calcium level in the blood.

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Parathyroidectomy leads to death, the reason for which is the
spasm of the respiratory muscles. Parathyroid hyperfunction
(hyperparathyroidism) is accompanied by muscular weakness
and destruction of bones (osteoporosis) and teeth.

Physiology of the adrenal glands

The adrenal glands consist of two parts: the medulla and

the cortex (Figure 27). The cortex forms three zones: an
external glomerular zone (zona glomerulosa), a middle
fascicular zone (zona fasciculata) and an internal reticular
zone (zona reticularis). The cortical part of this gland produces
more than fifty corticosteroids, but only eight of them are
physiologically active.

Figure 27. Adrenal glands.

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 The glomerular zone secretes mineralocorticoids:
aldosterone, corticosterone and desoxycorticosterone.
Hormones of the fascicular zone are the glucocorticoids:
cortisone, hydrocortisone and corticosterone. The reticular
zone produces sex hormones: androgens, estrogens and
progesterone.
Mineralocorticoids regulate the mineral metabolism. The
most active of the mineralocorticoids is aldosterone, which
promotes sodium reabsorption in the renal tubules and increases
sodium content in the blood. Simultaneously aldosterone inhibits
potassium reabsorption in the renal tubules, which leads to
potassium decrease in the blood.
Secretion of aldosterone is directly dependent upon the
level of sodium and potassium in the blood and is regulated by
the feedback mechanism (by concentration of sodium and
potassium ions). The control of aldosterone release is also
realized by the renin-angiotensin system. In decreased blood
supply and pressure in the kidney, it produces renin, which
activates plasma angiotensinogen, transforming it into
angiotensin I. The latter is converted into angiotensin II, which
possesses vasoconstrictive effect. Constriction of the vessels
leads to the normalization of blood supply and pressure. On the
other hand the renin-angiotensin system stimulates secretion of
aldosterone with further reabsorption of sodium and water that
causes the blood volume and pressure increase. In this point of
view renin, angiotensin and aldosterone are included into one
integral system: renin-angiotensin-aldosterone system.

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Overproduction of aldosterone causes hypernatriemia and
hypokalemia, hypertension, increase of water content in the
organism, promotes edema and inflammatory process
development in tissues, etc. Hyposecretion of aldosterone
evokes hypotension, disorders of mineral metabolism
(hyponatriemia and hyperkalemia) and further death of the
organism.
Glucocorticoids regulate carbohydrate, protein and fat
metabolism. Glucocorticoids owe their name to their ability to
raise the blood sugar level, which is conditioned by
acceleration of the deamination of aminoacids and conversion
of their nitrogen-free residues to carbohydrates
(gluconeogenesis). They also decrease the glucose utilization in
tissues and receptors’ sensitivity to insulin, thereby the glucose
level in blood increases. But in the liver they stimulate
glycogen synthesis. Glucocorticoids intensify the mobilization
of fat from its depots and its utilization in the energy
metabolism. They weaken the inflammatory and allergic
reactions by inhibiting lymphocytes and eosinophils production
and reducing capillaries’ wall permeability. At the same time
they inhibit phagocytosis although the amount of neutrophils in
this case increases. Glucocorticois are used in clinical practice
for treating some chronic diseases due to their anti-
inflammatory action. Concentration of glucocorticoids
increases in stress reactions. The function of fascicular zone is
regulated by the hypothalamo-hypophysial system, particularly
by ACTH of adenohypophysis (negative feedback mechanism).
Hypersecretion of glucocorticoids leads to hyperglycemia and
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inhibition of the organism’s immune reaction. The same
symptoms are observed in Cushing’s syndrome. Hyposecretion
of hormones evokes Addison’s disease, hypersensitivity to
stress factors.
The sex hormones of adrenal reticular zone perform a
very important role in formation of the secondary sex
characters in teenage period of ontogenesis, when the function
of sex glands is still insufficient. In old age when the function
of sex glands has ceased the reticular zone of adrenal cortex
again becomes the source of androgens and estrogens.
Hypersecretion of sex hormones in girls causes virilism, but in
boys, pre-term sexual maturation.
The adrenal medulla is composed of the chromaffin cells
embryogenically related to the cells of the sympathetic nervous
system. The adrenal medulla produces adrenaline
(epinephrine) and dimethylated adrenaline – noradrenaline
(norepinephrine). Adrenaline and noradrenaline are referred as
cathecolamines, because they are derivatives of cathecol. They
are also called sympathomimetics, because their effect is
similar to that of the sympathetic nerves. Adrenaline realizes
several effects: 1. It activates the glycogenolysis in the liver
and muscles, increasing the blood glucose level. Glucose is the
main source for the energetic metabolism of the muscles and
other tissues. 2. Adrenaline stimulates cardiac muscle
contraction, has constrictive effect on the arterioles, but causes
dilation of the heart coronary vessels. 3. It reduces the
functional activity of the digestive system (secretor and motor)
and the kidneys. 4. Adrenaline causes contraction of some
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muscles (radial muscle with dilation of pupil and skin smooth
muscle with increase of pilomotor activity) and relaxation of
the bronchial muscles. 5. Adrenaline increases the excitability
of receptors, which promotes perception of external stimuli by
the organism. It also activates CNS. 6. Adrenaline provides
trophic function of the skeletal muscle.
The effect of noradrenaline is similar to that of
adrenaline, but there are some exceptions, e.g. adrenaline
relaxes the uterus in pregnancy, while noradrenaline stimulates
the uterus contraction, noradrenaline increases the blood
systolic and diastolic pressure, but adrenaline increases only
the systolic pressure.
Thus cathecolamines can bring about an urgent
reorganization of functions in order to mobilise the working
capacity of the organism in extraordinary circumstances –
stress.
The function of medullar part of adrenals is regulated by
a nervous way, particularly by the sympathetic nervous system.
That is why in extraordinary circumstances, when the
sympathetic nervous system is excited, the concentration of
adrenaline and noradrenaline increases in the blood, which
leads to the functional reorganization for a long time.

Physiology of the sex glands (gonads)

The sex glands (Figure 22) are mixed glands, because

they perform excretory (formation of spermatozoa and ova)
and incretory (synthesis of sex hormones) functions. Sex
hormones are divided into two groups: male sex hormones,
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androgens and female sex hormones, estrogens. Androgens
(testosterone, androsterone and dehydro-3-epiandrosterone)
are formed in the interstitial tissue of Leidig’s cells. This tissue
in the testes is known as the puberty gland. Estrogens (estrone,
estriol and estradiol) are formed in the ovaries in the granular
layer of the follicles and graafian vesicles and their internal
sheath. Progesterone, the hormone responsible for the normal
course of pregnancy is produced in the ovarian corpus luteum,
which develops in place of the ruptured graafian vesicle (after
it has ruptured and discharged its ova). It is also produced by
placenta.
Sex hormones are responsible for the sexual activity of
the organism. They are necessary for sexual maturation and
reproduction function, a normal course of pregnancy. They
provide development of the secondary sexual characters,
specific features distinguishing the male and female organisms.
Besides, they have a significant role in the regulation of
metabolism of proteins and fats. They stimulate the ossification
of the cartilaginous zones in the long bones. Male and female
sex hormones have a different action on hemopoiesis. The
androgens stimulate the RBC formation, while estrogens
inhibit this process.
The function of the sex glands is regulated by the
nervous and humoral ways. Stress and strong emotions may
impair the female sex cycle (emotional amenorrhea). But the
most important regulation is realized by the hypothalamo-
hypophysial system via feedback mechanism. The
adenohypophysial hormones, follicle-stimulating and
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luteinizing hormones take participation in this regulation. In
females the follicle-stimulating hormone promotes the
development and maturation of graafian vesicles and secretion
of estrogens, in males it provides the development of
seminiferous tubules and accelerates spermatogenesis in
Sertoli’s cells. The luteinizing hormone stimulates the
formation of sex hormones. In females it determines the
ovulation and formation of the corpus luteum, which produces
progesterone. In males it stimulates Leidig’s cells activity and
hormone production.
The pineal gland also has a certain effect on the sex
maturation. It prevents the organism from the pre-term sex
maturation.
Menstrual cycle. Puberty describes the series of
events in which a child matures into a young adult. These
changes include the development of secondary sex
characteristics, the growth spurt (peak height velocity) and
achievement of fertility.
With the onset of puberty in women, menstrual cycle
occurs periodically, which is the result of maturation of the
hypothalamic-pituitary-ovarian axis and is the cyclic pattern of
activity of the hypothalamus, pituitary, ovary and uterus. The
produced hormones include gonadotropin-releasing hormone
(GRH) or GL from the hypothalamus, which stimulates FSH
and LH from the anterior pituitary. The latter stimulates the
estrogen and progesterone production from the ovarian follicle.
The menstrual cycle lasts for 27-28 days and may be divided

156
into several phases (Table 1, Figure 28) and duration of each
phase varies from woman to woman and cycle to cycle.

Table 1.
Phases of menstrual cycle.
Name of phase Days
Menstruation 1-4
Follicular phase (also known as proliferative or pre-
5-13
ovulatory phase)
Ovulation (not a phase, but an event dividing
14
phases)
Luteal phase (also known as secretory or post-
ovulatory phase) 15-28

During the follicular phase release of FSH from the

pituitary results in development of a primary ovarian follicle
(graafian vesicle). The ovarian follicle produces estrogen,
which causes the uterine lining vaginal mucosa to proliferate.
Estrogen promotes also the contraction of the uterus and
fallopian tubes.
At the midcycle, approximately day 14, there is an LH
spike in response to a preceding estrogen surge, which
stimulates ovulation. Ovulation is the process in the menstrual
cycle, by which a mature ovarian follicle ruptures and
discharges an ovum, which moves along the fallopian tube into
the uterus. After ovulation the luteal phase begins. The
remnants of the follicle left behind in the ovary, develop into

157
the corpus luteum, under stimulation by LH. It is responsible
for the secretion of estrogen and significant quantities of
progesterone, which causes the endometrium to become more
glandular and secretory in preparation for implantation of a
fertilized ovum. If fertilization occurs, the developing
trophoblast synthesizes human chorionic gonadotropin (hCG),
which maintains the corpus luteum so that it can continue
production of estrogen and progesterone to support the
endometrium until the placenta develops its synthetic function.
If fertilization, with its concomitant rise in hCG, does not
occur, the corpus luteum degenerates and progesterone level

Figure 28. Menstrual cycle.

falls. Without progesterone, the endometrial lining is not

maintained and sloughed off resulting in menstrual flow. This
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phase is known as menstruation. At the same time, FSH level
begins to rise slowly, in the absence of negative feedback and
the follicular phase starts again.

Physiology of the pancreas

Pancreas is a mixed gland (Figure 29). It performs

excretory and internal secretion functions. Due to excretory
function it participates in digestive process by means of the
digestive enzymes’ secretion. Besides, it comprises special
clumps of cells, which are called the islets of Langerhans. The
islets participate in secretion of hormones (direct secretion into
the blood without any ducts). The islets consist of three types
of cells: alpha, beta and gamma. Alpha cells produce
glucagon, beta - insulin and gamma - somatostatin. The
epithelium of small pancreatic ducts secrets lipocain, vagotonin
and centropnein.

Figure 29. Pancres.

The targets of insulin are muscle and fatty tissues, in

which insulin drastically increases the glucose permeability of
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the cell membrane. Insulin promotes the utilization of glucose
and formation of glycogen in liver cells. Insulin also increases
the amino-acid permeability of cells. It stimulates the synthesis
of RNA messenger and facilitates protein synthesis. The
insulin large doses cause passage of the glucose large amounts
from the blood plasma into the skeletal, heart muscles and the
fatty tissues. As a result, the blood glucose level decreases,
which leads to insufficiency of glucose in the nervous system
cells. But insulin doesn’t act on the nervous cells’ membrane
permeability to glucose. The accumulation of glucose in nerve
cells is realized by concentration gradient. Therefore the brain
and the spinal cord experience an acute lack of glucose, which
is the main source of energy for the nerve cells. This state
(hypoglycemic coma) is characterized by the acute disturbance
of the cerebral activity, loss of consciousness, attacks of
convulsions, decreased muscle tone and low body temperature.
Insufficient function of beta-cells brings about sharp
increase of glucose in blood (hyperglycemia). Diabetes mellitus
develops, which is characterized by glucosuria, polyuria,
polydipsia and polyphagia. Owing to glucosuria, the
expenditure of proteins and fats providing energy metabolism
sharply increases. Products of the fats’ incomplete oxidation
are accumulated in the organism leading to severe functional
disorders, e.g. acidosis.
The secretion of insulin is regulated by the blood glucose
level (feedback mechanism).
Glucagon is an antagonist of insulin and provides the
glucose level increase in the blood. It stimulates glycogenolysis
160
due to the activation of phosphorylation. But glucagon
simultaneously activates glycogen synthesis from aminoacids
(glyconeogenesis), inhibits fatty acid synthesis in the liver and
facilitates the function of the myocardium. Its secretion is
regulated by the blood glucose level.
Somatatostatin inhibits the secretion of insulin and
glucagon, lipocain participates in lipids’ metabolism,
centropnein activates the respiratory centre and vagotonin
increases the tone of vagus centre.

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CHAPTER 6.
PHYSIOLOGY OF THE BLOOD SYSTEM

6.1. INTERNAL MEDIUM OF THE BODY

Blood system consists of four parts: blood proper,

hemopoietic organs, organs of blood destruction, and
regulatory neurohumoral mechanisms.
Blood, lymph and intercellular liquid compose the
internal medium of the organism. The blood performs the
following functions: transport (including respiratory,
nutritional, excretory functions, humoral regulation and
creator connections), thermoregulation and defence function.

Composition and properties of blood

The total amount of blood in the body of an adult is

normally 6 to 8 % of the body weight, i.e. 4.5-6 l. Blood
consists of plasma (55-60%) and formed elements (40-45%).
Plasma consists of water (90-92%) and dry residue (8-10%).
The latter contains organic and inorganic substances. The main
organic substances are: proteins (albumins – 4%, globulins –
2.8%, fibrinogen – 0.4%), carbohydrates (glucose – 0.08-
0.12%), lipids (cholesterine – 0.7%). The inorganic micro- and
macro-elements are distinguished. The main inorganic
substances are: NaCl (0.8%), Ca (9-11 mg%), P (3.00 – 4.00
mg%). There are also some anions: HCO3-, HPO42-. The
microelements are Co, Ni, Cu, Mg, Mn, etc.

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 The formed elements are: erythrocytes (4.5-6 mln/ mm3),
leucocytes (4000-9000/mm3) and thrombocytes (blood
platelets) (200000 - 400000/mm3).
The composition of blood is relatively constant. The
relative constancy of internal medium of the organism is called
homeostasis. The mechanisms supporting the homeostasis are
called homeokinesis.
The main constants of blood are the followings: osmotic
pressure (7.6 atm.), oncotic pressure (25-30 mm Hg, which is a
1/200 part of osmotic pressure), temperature (37oC), viscosity
(5 in relation to distilled water), pH (7.35-7.4), hematocrit
(percentage of the volume of a blood sample occupied by cells,
40-45%).
Osmotic pressure is the pressure by which the molecules
of dissolved substance act on the unit surface of the semi-
permeable membrane, or the force, which provides the entering
of dissolvent through semi permeable membrane from the
medium with less concentration to the medium with the high
concentration. The osmotic pressure is conditioned mainly by
inorganic substances (salts). The maintenance of osmotic
pressure is realized by a special mechanism, which includes the
following phases: excitation of osmo-receptors in increased
osmotic pressure; production of ADH from hypothalamus and
its transport to the posterior pituitary; release of the ADH to the
blood and its action on the kidney tubules providing the
reabsorption of water to the blood with the normalization of
osmotic pressure. Those solutions which have the osmotic
pressure like blood are called isotonic. The 0.9% solution of
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NaCl is called physiological solution. Other physiological
solutions are Ringer’s solution (for cold-blooded animals),
Locke-Ringer’s solution and Tyrode’s solution (for warm-
blooded animals). The solutions, which osmotic pressure is less
than that of blood are called hypotonic once. The solutions,
which osmotic pressure is more than that of the blood are
called hypertonic once.
Erythrocytes and other blood formed elements are
destroyed in the hypotonic solution. This phenomenon is called
osmotic hemolysis. In hypertonic solution the erythrocytes are
squeezed, which is called plasmolysis.
There are other types of hemolysis. Chemical hemolysis
is caused by the action of chemical agents (alcohol, acids and
bases). Physical hemolysis occurs in action of physical factors
(temperature, mechanical agents, ultraviolet and other rays).
Biological hemolysis is observed in transfusion of the
incompatible blood, under the action of poisons of snakes or in
presence of microbes and viruses. Physiological hemolysis is
the result of the destroy of old erythrocytes (the span of
erythrocytes is 120 days).
The oncotic pressure is the part of osmotic pressure. It is
conditioned by the protein molecules.
Taking the viscosity of distilled water as unity, the
viscosity of whole blood is about 5.0, the viscosity of plasma is
1.7-2.2.
The pH of blood is weak alkaline. A shift of the normal
pH in man even by 0.1-0.2 may be fatal. During metabolism
blood is continuously supplied with carbon dioxide, lactic acid
164
and other metabolites which change the concentration of
hydrogen ions. However, blood pH is supported at a constant
level owing to the buffer systems.
The buffer systems are: the hemoglobin (HHb/KHb)
buffer system, the carbonate buffer system (H2CO3/NaHCO3),
the phosphate buffer system (NaH2PO4/Na2HPO4), the plasma
protein buffer system. The most active is the hemoglobin
buffer system, which accounts for 75% of the buffer capacity
of blood. Plasma proteins play the role of a buffer system due
to their amphoteric properties (COOH and NH2 groups of
aminoacids).
Plasma proteins. The significance of plasma proteins is
multiform: 1) they are responsible for oncotic pressure, the
level of which is important for regulating water exchange
between blood and tissue; 2) they maintain the acid-base
balance of blood; 3) they ensure a definite viscosity; 4) they
prevent sedimentation of erythrocytes; 5) proteins participate in
blood coagulation; 6) they provide an immunity; 7) proteins are
carriers of a number of hormones, mineral and organic
substances; 8) they serve as a reserve for building up tissue
proteins; 9) accomplish intercellular or creative interactions,
i.e. transmission of information influencing the genetic cell
apparatus and ensuring processes of growth, development,
differentiation, and maintenance of the body structure (the
nerve growth factor, erythropoietins, etc.).
Blood plasma proteins are divided into three main
groups: albumins, globulins (α1, α2, β and γ) and fibrinogen.
These fractions are separated by electrophoresis, a method
165
based on different moving velocity of various proteins with
different molecular mass in an electric field.

Composition and properties of lymph

In addition to the system of blood vessels the body

contains a system of lymphatic vessels, which begins with a
branching network of closed capillaries, which walls are
extremely permeable and capable of absorbing colloidal
solutions and suspensions. The lymphatic capillaries drain into
lymphatic vessels along which a fluid, lymph, flows toward
two large lymphatic ducts, the cervical and thoracic, which in
turn empty into the subclavian veins. The lymphatic vessels
serve to drain off lymph, i.e. to return the blood fluid exuded
into the tissue. They are, thus, a type of drainage system that
removes excess tissue, or interstitial fluid accumulating in the
organs. The lymph flowing from the tissues passes to the veins
via biological filters, the lymph nodes, performing defence
function.
The lymph collected from lymphatic ducts during fasting,
or after a meal poor in fats, is a colorless, almost transparent.
Lymph obtained from the thoracic duct and from the intestinal
lymphatic tissues six to eight hours after a meal rich in fats is
cloudy and milky because it contains emulsified fats. Lymph
contains less protein, than blood, its viscosity is lower. Lymph
has an alkaline reaction and contains fibrinogen, due to which
it is capable of coagulation forming a loose, slightly yellowish
clot. The lymph in the lymphatic vessels of the endocrine
glands contains hormones. The lymph of the thoracic duct

166
contains a large number of lymphocytes, since they are
produced in the lymph nodes and are carried to the blood with
the lymph flow.
Thus the main functions of lymph are: participation in
regulation of water-salt, nutrient balance and performance of
defence function.
The production of lymph is connected with the passage
of water and certain substances dissolved in blood plasma from
the blood capillaries into the tissues and from there into the
lymphatic capillaries. The filtration pressure is the result of
difference of hydrostatic pressure (Ph) and oncotic pressure
(Ponc) of blood. In arterial part of capillary Ph= 40 mm Hg and
Ponc =30 mm Hg, i.e. Pf = 40 – 30 = 10 mm Hg. Pf provides the
transport of water and diluted substances from the capillary
into the tissue and then into the lymphatic capillary. In venous
part the hydrostatic pressure is 20 mm Hg, therefore Pf= 20 -30
= -10 mm Hg. This negative pressure provides the transport of
water and substances from the lymphatic capillary to the tissue
and then into the blood capillary. Filtration process is
facilitated by the action of 2 factors: 1) periodic pressure
variations in tissues that occur due to pulsation of tissue
arteries and regular contractions of skeletal and smooth
muscles of the viscera causing periodic compression of the
lymphatic vessels; 2) the presence of valves in the lymphatic
vessels, owing to their periodic compression lymph is forced in
the central direction, i.e. it is sucked off from the tissue.
Mechanism of lymph movement. Under normal
conditions there is equilibrium in the organism between the
167
rate of lymph formation and the rate of lymph flow from the
tissues. Rhythmic contractions of the walls of certain
lymphatic vessels play a definite role in the flow of lymph.
Contraction of skeletal muscles and sucking property of the
chest are also very important for lymph flow. Owing to the
presence of valves in the lymphatic vessels the lymph flow
takes place in one direction.
The sympathetic nervous system evokes spasm of
lymphatic vessels, which is accompanied by lymph flow
velocity decrease.

6.2. BLOOD FORMED ELEMENTS

Erythrocytes

Erythrocytes or red blood cells (RBC) of humans and

mammals are non-nucleated cells, which perform the following
functions: 1) gas transport; 2) they are ideal carriers realizing
intercellular or creator connections; 3) formation of blood
groups and Rh-factor due to localisation of agglutinogenes on
the erythrocyte membrane. Their number in blood is 4-5
million/mm3. Their number in blood can vary: erythrocytosis is
increase in the number of erythrocytes and erythropenia is their
decrease. These variations may be absolute and relative.
Absolute erythrocytosis is encountered in hypoxia (low
atmospheric pressure or chronic pulmonary and heart diseases).
Relative erythrocytosis (increased erythrocyte number
per unit of blood without its total increase) occurs in blood
condensation (in profuse sweating, burns, cholera and

168
dysentery) and during hard muscular exertion when
erythrocytes are discharged from blood depot.
Absolute erythropenia develops due to decreased
formation, augmented breakdown of erythrocytes or after blood
loss.
Relative erythropenia (decreased erythrocyte number per
unit of blood without its total decrease) occurs in blood
liquefaction at the expense of a rapidly increasing volume of
liquid in the body.
The diameter of erythrocyte is 7.2-7.5 µm, thickness is
2.2 µm. Erythrocyte has a shape of a biconcave disc and in
cross section resembles dumb-bells. With this shape no point of
the cell is located further than 0.85 µm from its surface, which
promotes the easier transport of oxygen and its interaction with
hemoglobin. Since erythrocytes are non-nucleated cells, they
consume oxygen 200 times less, than their nucleated pre-
stages. Erythrocytes supply oxygen to the whole body spending
on themselves its negligible part during oxygen transport.
Besides, loss of nucleus makes the space opening for
hemoglobin possible.
The erythrocyte membrane consists of a phospholipid
bilayer covered by the monomolecular protein layers inside and
outside. The erythrocyte membrane is poorly permeable to Na+
and K+ and readily permeable to HCO3-, Cl- and to O2, CO2, H+
and OH-. Human erythrocytes contain more potassium than
sodium.

169
 Formation of erythrocytes is activated by erythropoietins,
which are produced mainly by the kidneys in hypoxia and
blood loss. Vitamins B12, B6, B2 and C are also necessary for
normal hemopoiesis. Hemopoiesis is activated by male sex
hormones and inhibited by female hormones. That is why the
number of erythrocytes in women is less than that in men.
Erythrocyte sedimentation rate (ESR). Blood to
which anticoagulant has been added will settle in a certain
time, the erythrocytes will be deposited as a sediment. In norm
ESR in males is 2-9 mm/h; in females 6-15 mm/h, in newborns
0.5-1.0 mm/h. The estimation of ESR has a prognostic
significance. ESR can be increased in different inflammatory
processes, cancer-genesis, during pregnancy, etc. The value of
ESR depends on the properties of plasma, primarily on the
proteins (albumins, globulins and fibrinogen). Globulins and
fibrinogen decrease the negative charge on the surface of
erythrocytes, providing the interaction of these formed
elements and due to it the increase of ESR. In contrast, the
albumins decrease ESR. So, ESR depends on albumin/globulin
coefficient. Sometimes in anemia ESR also can be accelerated.
Hemoglobin. Hemoglobin is located inside the
erythrocytes and not in the plasma due to which 1) blood
viscosity is reduced; 2) the oncotic pressure of blood is
decreased; 3) loss of hemoglobin by filtration in the renal
tubules is prevented.
Hemoglobin is the chromoprotein consisting of the
protein, globin and hem. One hemoglobin molecule contains
one molecule of globin and four molecules of hem. The latter
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contains bivalent iron. Human blood contains 14.5 g/100ml
hemoglobin. The saturation of erythrocytes with hemoglobin is
called color index. In norm, it is equal to 0.8-1.00. Erythrocytes
that have this index are called normochromic; erythrocytes
with an index more than 1.00 are called hyperchromic and
those with a value below 0.8, hypochromic. This index has
diagnostic significance, particularly in estimating anemia.
According to color index three types of anemia are differed:
hyperchromic (in insufficiency of B12), hypochromic (in deficit
of iron) and normochromic (in loss of blood, hemorrhages).
Hemoglobin is synthesized in the marrow. In degradation of
erythrocytes in the liver the hemoglobin is converted into bile
pigment bilirubin, which passes into the intestine and is
transformed into stercobilin and urobilin, eliminated from the
body by the faces and urine correspondingly.
The human hemoglobin has various types: HbP
(primitive, hemoglobin of embryo of 7-12 weeks); HbF (fetal,
hemoglobin of embryo from the beginning of 9th week); HbA
(adult, which appears in child’s blood prior to birth). During
the first three years of life, HbF is almost fully replaced by
HbA. HbP and HbF have a higher affinity to oxygen, than
HbA. Different types of hemoglobin have identical hem;
globins differ in their aminoacid composition and properties.
Hemoglobin has two types of physiological compounds:
HbO2 (oxyhemoglobin) and HbCO2 (carbohemoglobin).
Hemoglobin can also form pathologic compounds: HbCO
(carboxyhemoglobin) and MetHb (methemoglobin). The
affinity of hemoglobin to CO exceeds that to O2; therefore,
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even 0.1% of CO in air leads to conversion of 80% of
hemoglobin into HbCO which is unable to add oxygen. This
causes hypoxia, intoxication and is dangerous for life. MetHb
is formed under the influence of strong oxidizing agents
(ferricyanide, potassium permanganate, aniline, atomic
oxygen). In this compound, the bivalent iron is converted into
the trivalent.
Myoglobin. Mioglobin is present in muscles and
myocardium. Its hem is identical to blood hemoglobin hem, but
globin has a lower molecular mass. Myoglobin binds up to
14% of the total oxygen, which is important for the supply of
oxygen to the working muscles. When the blood capillaries are
compressed in contracted muscles, blood flow either decreases
or ceases. However, owing to the presence of oxygen
combined with myoglobin oxygen to the muscles is maintained
for some time.

Leucocytes

Leucocytes or white blood corpuscles play an important

role in body defence against micro-organisms, viruses, foreign
substances, i.e. they insure immunity. In norm, their number is
4000-9000/mm3. The increase of number of leucocytes is
called leucocytosis. Two types of leucocytosis are differed:
reactive (in inflammation, several infectious, non-infectious
diseases) and physiological (in emotional stress, physical
exertion, etc.) The decrease of number of leucocytes is called
leucopenia. It is observed under the action of X-rays and cell
poisons.
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 According to the presence of granules in the cytoplasm of
leucocytes they are classified as granulocytes and
agranulocytes. The granulocytes are neutrophils (45-70%),
eosinophils (1-5%) and basophils (0-1%). The agranulocytes
are monocytes (2-10%) and lymphocytes (20-40%). The
percentage relation between different types of leucocytes is
called differential count or leucogram.
Neutrophils are stained readily with neutral dyes.
Depending on the shape of their nucleus, the neurtrophils are
classified into myelocytes (0%), juvenile or metamyelocytes (0-
1%), stab (1-5%) and segmented (45-70%). The content of the
first three types of neutrophils rises in a number of diseases.
Shift to the left of leucogram indicates the increase of
myelocytes’, juveniles’ and stabs’ forms proportion to the
number of segmented ones. This name implies that the
neutrophils in the leucogram are arranged from the left to right
by the degree of their maturity. This proportion is called
regeneration index, which in norm is equal to 0.05-0.1 and can
reach 1-2 in severe infections and inflammatory diseases.
Neutrophils are the first to appear at the site of tissue
injury and are, so to say, the leucocyte “vanguard”.
Neutrophils put out their pseudopodia, pass through the
capillary walls and actively move in the tissues to the site of
bacteria penetration. The main function of neutrophils is
phagocytosis. One neutrophil is capable to ingest 20-30
bacteria. The neutrophils are also called microphages.
Eosinophils are stained with the acid dyes (eosin), hence,
the name. They have a capacity to phagocytosis, but their role
173
in this process is insignificant because of small blood content.
The main function of eosinophils is detoxication and
destruction of toxins of protein origin. They produce enzyme
histaminase which destroys histamine. The number of
eosinophils increases in allergic reactions.
Basophils are stained with basic dyes. Like the mast
cells, they produce histamine and heparin. Heparin interferes
with blood clotting at the site of the inflammation focus, and
histamine causes vasodilation to promote resorption and
healing of a lesion. The role of basophils is increased in various
allergic reactions. Under the effect of the antigen-antibody
complex basophils and mast cells release histamine that
determines the clinical manifestations of urticaria, bronchial
asthma, anaphylactic shock and other allergic reactions.
Monocytes are capable of phagocytic activity. They
ingest up to 100 bacteria and are called macrophages. At the
inflammatory lesion monocytes ingest bacteria and abnormal
cells of the inflamed tissue, clear the lesion and prepare it for
regeneration. For that function monocytes are called “body
scavengers”. Monocytes in contrast to neutrophils keep their
activity in acidic medium.
Lymphocytes unlike other leucocytes cannot only
penetrate through the tissues, but also return into the blood.
Their lifespan is 20 and more years. The lymphocytes are
divided into three groups: T-lymphocytes (thymus-dependent),
B-lymphocytes (bursa-dependent) and 0-lymphocytes. T-
lymphocytes are formed in the marrow and differentiated in the
thymus. They have a few forms. T-helpers help B lymphocytes
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to convert them into plasmatic cells. T-suppressors block hyper
reaction of B lymphocytes. T-killers interact with foreign
(internal and external) cells and destroy them. They kill tumor
cells, cells of foreign transplants and cell- mutants to preserve
genetic homeostasis. T-killers release immunity mediators or
lymphokins which kill foreign cells by activating their
lysosomal enzymes. T-amplifiers activate T-killers. T-
lymphocytes ensure specific cellular immunity.
B-lymphocytes are produced in the marrow and
differentiated in the bursa gland (in birds) and lymphoid tissue
of the gut, appendix, palatine and pharyngeal tonsils (in
mammals). B-lymphocytes play a major role in specific
humoral immunity by producing antibodies. After the contact
with antigens they recognize the given antigen due to the
receptors located on their membrane. Then the B lymphocytes
migrate into the lymphatic nodes, where they are transformed
into the plasmatic cells, which produce antibodies. B-
lymphocytes are very specific. Their each group reacts with
one antigen and is responsible for antibody production only
against it.
0-lymphocytes are not differentiated and can be
transformed into B- as well as T-lymphocytes
Immunity is the natural body resistance to
microorganisms, viruses and genetically foreign cells. Various
mechanisms that are classified as non-specific and specific are
involved in its realization.
The non-specific mechanisms are provided by the skin,
mucous membranes, intestine, kidney, liver and lymph nodes.
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The non-specific mechanisms are also effected by defence
substances (interferon, γ-globulins, lysozyme, properdin and
the complement system) of blood plasma. The complement
system consists of 11 enzymatic components, which are
produced by monocytes and macrophages. Cellular
mechanisms are also responsible for non-specific body
defence. One of them is phagocytosis. In 1973 the World
Health Organization (WHO) adopted a decision according to
which all phagocyting mononuclear cells were united into the
mononuclear phagocyte system (MPS).
The specific mechanisms of immunity are ensured by
lymphocytes that create specific immunity, i.e. production of
defence proteins – antibodies and immunoglobulins, and
cellular immunity, i.e. production of immune lymphocytes.

Thrombocytes (platelets)

Thrombocytes (platelets) are colorless biconvex

structures 0.5 to 4 µm in diameter. Their content in blood is
200000-400000/mm3. Emotions, physical exertion and food
intake change their number. In vessel damage platelets perform
an important role in blood coagulation. They contain a number
of enzymes, biologically active substances, including
adrenaline, noradrenaline, serotonin, as well as coagulation
factors.
Blood platelets, along with their participation in
hemostasis, are responsible for the transport of creative
substances which are essential for the maintenance of the
vessel wall structure.
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 6.3. BLOOD COAGULATION

The liquid state of blood is the principle condition for the

organism functioning. It is provided by the system of blood
coagulation, which also restores the wholeness of the pathways
of its circulation by forming thrombi (clots) in the damaged
vessels. The process of coagulation or hemostasis involves
three components: vessels, blood plasma and formed elements
coagulation factors.
Blood plasma coagulation factors are designated by
Roman numerals in the chronological order of their discovery.
Factor I, fibrinogen; Factor II, prothrombin; Factor III,
thromboplastin; Factor IV, calcium ions; Factors V and VI,
proaccelerin and accelerin; Factor VII, proconvertin, Factor
VIII, antihemophilic globulin A; Factor IX, Christmas factor or
antihemophilic globulin B; Factor X, Stuart-Prower factor;
Factor XI, plasma thromboplastin antecedent; Factor XII,
Hageman factor; Factor XIII, fibrin-stabilizing factor.
Platelets’ coagulation factors are designated by Arabic
numerals:
Factor 3, thrombocytic thromboplastin; Factor 4,
intracellular protein component (antiheparin); Factor 5,
clotting factor (determines platelet adhesion and aggregation);
Factor 6, thrombostenin; Factor 10, vasoconstrictive factor
(serotonin); Factor 11, aggregation factor (ADP).
Three processes are involved in blood clotting: primary
or vascular-platelet hemostasis (pre-phase of hemostasis);
coagulation hemostasis; after-phase of hemostasis.

177
 Vascular-platelet hemostasis

Bleeding from the microcirculatory vessels with low

arterial pressure commonly subjected to damage can be
arrested by the mechanisms underlying hemostasis which
consists of a number of sequential processes:
1. Spasm of the damaged vessels by reflex is insured by
vasoconstrictive substances released from the platelets
(serotonin, adrenalin and nor-adrenalin).
2. Platelet adhesion to the site of trauma is associated
with the fact that a negative electric charge of the vessel at the
site of damage is altered to the positive one. Negatively
charged platelets adhere to the bare collagen fibres of the basal
membrane.
3. The reversal platelet aggregation begins nearly
simultaneously with adhesion. ADP released from the damaged
vessel and from the platelets and erythrocytes is the main
stimulator of this process.
4. The irreversible platelet aggregation is accompanied
by the loss of the structural pattern of platelets with the
formation of homogenous mass. All the platelet factors and the
new amounts of ADP are released to increase the size of a
platelet thrombus. The release of the platelet factor 3
(thromboplastin) gives rise to the production of platelet
prothrombinase promoting the mechanism of coagulation
hemostasis.
5. Retraction of a platelet thrombus implies its thickening
and fixation at the side of damage at the expense of

178
thrombostenin contraction. As a result of platelet clot
formation, bleeding from microcirculatory vessels is arrested.

Coagulation hemostasis

Hemostasis is ensured by the vascular- platelet reaction

only in microcirculatory vessels with low blood pressure. The
same reaction initiates it in large vessels but the platelet
thrombus cannot endure high pressure and is washed out.
Hemostasis in such vessels can be achieved only if a fibrin
thrombus (a more solid plug) is formed. Its formation is
effected by enzymatic coagulation mechanisms which involve
three phases.
Phase I. Formation of prothrombinase from extrinsic (of
damaged vessel tissue) and intrinsic (of platelet and
erythrocyte) thromboplastin (phospolipid). Tissue
prothrombinase takes 5-10 sec for its formation and blood
prothrombinase - 5-10 min. Formation of prothrombinase is
triggered by V-XII factors and calcium ions (factor IV) of
blood plasma.
Phase II. Formation of thrombin from prothrombin,
which is initiated by prothrombinase, factors V, X and calcium
ions. Duration of this phase is 2-5 sec.
Phase III. Formation of fibrin from fibrinogen. At first
fibrinogen is converted into the fibrin monomer under the
action of thrombin. Then fibrin monomers are polymerized
under the action of calcium ions with the formation of fibrin
polymer (soluble fibrin S). And finally S fibrin is converted
into fibrin I (insoluble) with the help of factor XIII.
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 After-phase of hemostasis

Formation of a fibrin is followed by an after-phase of

blood clotting, which consists of two processes: retraction and
fibrinolysis.
Retraction ensures thickening of a thrombus and its
attachment to the walls of the damaged vessel. This process
occurs due to contractile protein thrombostenin. Retraction is
completed 2-3 hours after clot formation.
Fibrinolysis or decomposition of fibrin is directed to
restoration of vessel lumen (recanalization) that was stopped
with a clot. Fibrin breakdown is effected by the proteolytic
enzyme plasmin, which is present in the plasma as proenzyme
plasminogen. Blood and tissue activators are required for the
conversion of plasminogen into plasmin. The stimulants of
fibrinolysis are lysokinase, urokinase, trypsin, streptokinase,
kallikrein-kinin system and complement C1.

Anticoagulation mechanisms

Circulating blood contains all the necessary components

for coagulation but remains fluid. The fluidity of blood is
preserved due to the action of numerous mechanisms: 1)
smooth surface of vascular endothelium, which prevents
activation of Hageman factor; 2) the vessel walls and formed
elements have negative charges owing to which blood cells
are pushed away from the vascular walls; 3) vessel walls are
covered with a thin layer of soluble fibrin that adsorbs active
coagulation factors, especially thrombin; 4) high velocity of

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blood flow which prevents the accumulation of coagulation
factors in one place; 5) natural anticoagulants.
The anticoagulants are divided into two groups: pre-
existing anticoagulants (primary) and those which are
produced during coagulation and fibrinolysis (secondary). The
main primary anticoagulants are antithromboplastins,
antithrombin III and antithrombin IV, heparin. Secondary
anticoagulants are fibrin (adsorbs and neutralizes thrombin,
hence fibrin is called antithrombin I), peptides which are
cleaved from fibrinogen by thrombin, anticoagulants formed in
fibrinolysis, which inhibit the action of thrombin.
For blood conservation, synthetic anticoagulants are
used. Among them pelentan, dicumarin are well known.
Taking into consideration the important role of calcium ions in
all phases of hemocoagulation, they are used as anticoagulant
those substances which can combine calcium ions, e.g. sodium
citrate.

Regulation of blood clotting

It can be realized by nervous and humoral pathways.

Acceleration of the clotting time is known as
hypercoagulaemia and its slowing down as hypocoagulaemia.
Stimulation of pain, sensation of fright and anger, i.e. the states
accompanied by excitation of the sympathetic part of the
vegetative nervous system accelerate blood coagulation, from
5-10 min to 3-4 min. The development of hypercoagulaemia
upon activation of the sympathetic system and stress-reactions
are brought about by the action of adrenaline and
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noradrenaline. Adrenaline promotes the release of
thromboplastin from vessel walls, which is rapidly converted
into tissue prothrombinase, as well as activates Hageman
factor. Prostaglandins released by the kidneys or gastro-
intestinal tract are the activators of hemocoagulation.
Stimulation of the vagus nerve (or intravenous
administration of acetylcholine) causes release from the vessel
walls of the same substances that are released due to adrenalin
action. Thus, only one defence-adaptive reaction has been
formed during evolution in the blood coagulation system. I.e.
hypercoagulation directed at urgent stoppage of bleeding. It
confirms the fact that primary hypocoagulation does not exist.
It is always secondary and develops after primary
hypercoagulation at the expense of utilization of some blood
coagulation factors. Acceleration of blood coagulation causes
secondary stimulation of fibrinolysis. Fibrinolysis is activated
in physical effort, emotions and pain.
The blood coagulation is subjected to influence of the
cerebral cortex and those endocrine glands that secrete
vasoactive hormones. Owing to the dilation and narrowing of
vessels, their walls release thromboplastin, natural
anticoagulants and fibrinolysis activators.
Blood coagulation system ensures maintenance of the
fluid blood state and restoration of properties possessed by the
vessel walls that undergo changes even during their normal
functioning; it also keeps the content of blood coagulation
factors at the optimal level in case of emergency: damage to
the vessels, organs and tissues.
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 6.4 BLOOD GROUPS AND RH-FACTOR
BLOOD GROUPS

Medical practice is often faced with the need to replace

the blood lost in hemorrhages, certain cases of poisoning,
chronic infection as well as for other medical indications. In
the past the attempts to transfuse blood not infrequently caused
severe reactions, even lethal.
In 1901 K.Landsteiner and in 1903 J. Jansky found that
erythrocytes glue together when the blood of different persons
is mixed. This phenomenon known as agglutination depends
on the presence of erythrocytes of agglutinable factors or
agglutinogens A and B on the membrane. In erythrocytes they
can be found to occur either separately or together or be absent
at all. It has simultaneously been established that plasma
contains agglutinating agents, which agglutinate erythrocytes.
They are called agglutinins α and β. Agglutination of
erythrocytes occurs when agglutinogens of the donor are
combined with the same agglutinins of the recipient (Table 2).
Hence, the blood of each individual has dissimilar
agglutinogen and agglutinin. The human groups are four (in the
ABO system) according to four combinations of agglutinogens
and agglutinins. They are designated as follows: I(0)-α,β;
II(A)-A,β; III(B)-B,α; IV(AB)-AB. Agglutinogen A has more
than 10 variants. The difference between them is that A1 is the
strongest, while A2–A7 and other variants have weak
agglutination properties. For this reason, blood of such
individuals can be erroneously included in group I.
183
Agglutinogen B also has a few variants which activity
diminishes in the order of their numeration. Blood groups are
inherited according to genetic principles and remain unchanged
throughout life. Individuals belonging to group I can be
transfused by the blood of the same group. Blood group I can
be transfused to individuals of any blood group. Persons with
blood group I are known as universal donors. But 10-20% of
individuals with blood group I contain anti-A and anti-B
agglutinins, therefore individuals with blood group I,
containing anti-A and anti-B agglutinins are considered as
“hazardous” universal donors. Individuals with blood group
IV can be transfused by the blood of all groups and are known
as universal recipients. Transfusion of this blood to individuals
with other blood groups causes severe reactions (Table 2).

Table 2.
The agglutination after mixing of serum and erythrocytes
of different blood groups.
Groups of agglutinins Groups of agglutinogens
I (0) II A III B IV AB
I (αβ) - + + +
II (β) - - + +
III (α) - + - +
IV (0) - - - -

Blood group IV can be transfused to persons with the

same blood group. Blood of persons belonging to groups II and
III can be transfused to those with the identical group and to
group IV individuals.
184
 Principles of hemotransfusion. Two main principles of
blood transfusion have been formulated. 1. Blood should be
crossmatched so as to prevent combination of identical
agglutinogens of the donor with identical agglutinins of the
recipient. 2. The donor agglutinins are disregarded; this is so-
called the rule of dilution which is used in transfusion of small
quantities of blood. They lose their activity in dilution. The
agglutinins should be diluted 10-15 times.
Transfusion of incompatible blood may cause
hemotransfusion (clotting) shock which often ends death. The
mechanism underlying its development is that the agglutinated
erythrocytes on destruction secrete their coagulation factors
including thromboplastin. The latter causes intravascular
clotting and blockade of the microcirculatory vessels in all
organs and tissues by fibrin and platelet thrombi.
Study of the blood groups in different countries has
shown their percentage distribution: group I – 40-50%; group
II – 30-40%; group III – 10-20%; group IV – 5 %.

Rhesus-factor

Among the agglutinogens not included in the ABO

system, rhesus-factor or rhesus agglutinogen was first
discovered in macaca rhesus monkeys in 1940 by K.
Lansteiner and A.Weiner. This agglutinogen is present in 85%
of people (rhesus positive) and is absent in 15% (rhesus
negative). Rh-factor - agglutinogen has several variants, D, C
and E among which D is the most active.

185
 If Rh+ blood is transfused into the blood of a Rh-
individual, immune anti-Rh agglutinins will form. Repeated
transfusion of Rh+ blood may lead to the development of post-
transfusion complications. If a Rh+ man marries a Rh- woman,
there is a fair chance that their baby will be Rh+. The blood of
the fetus penetrates (in case of damaged placental barrier) in
the maternal body to cause production of anti-Rh agglutinins.
They diffuse into the fetus blood causing erythrocyte
destruction and intravascular blood clotting. If the
concentration of anti-Rh- agglutinins is high, death of the fetus
or miscarriage may ensure. In mild forms of Rh-incompatibility
the baby will be born alive, but with hemolytic jaundice. The
Rh-conflict occurs with a high concentration of anti-Rh
agglutinins. The first baby is commonly born normal but
during next pregnancies the hazard of the Rh-conflict increases
due to the formation of new portions of anti-Rh agglutinins.

186
CHAPTER 7.
PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEM

7.1. PHYSIOLOGY OF THE HEART

The heart is the central organ of the cardio-vascular

system. It performs the following functions: pump, reserve and
endocrine functions. It’s a muscular organ composed of three
layers; internal endocardium, external epicardium and between
these two layers the myocardium. The heart consists of four
chambers: two atria and two ventricles (Figure 30).

Figure 30.
Structure of the
heart.

The left part contains only arterial blood and the right
one only venous blood. Pursuing to the main anatomical
classification the arteries are the vessels that begin from the
heart and the veins are the vessels that enter the heart. There
187
are four one-way valves in the heart. Two of them lie between
the ventricles and the great arteries and are called semilunar
valves. The aortic semilunar valve prevents blood backward
leakage from the aorta into the left ventricle. The pulmonary
trunk valve performs a similar function between the pulmonary
artery and the right ventricle. Two other valves, called
atrioventricular (AV) valves, prevent blood backward leakage
from the ventricles into the atria when the ventricles are
contracting.
The two-leaflet mitral valve is located between the left
ventricle and left atrium and the three-leaflet tricuspid valve is
located between the right ventricle and the right atrium. AV
valves are represented by the endothelial structures that are
attached to the papillary muscles by the tendinous cords. The
semilunar valves are also derivatives of the endothelial tissue.

The heart conductive system and automatism

The functional element of the heart is the muscular fibre.

Depending on the morphological and functional peculiarities
there are two types of cells, myocytes and cardiomyocytes.
Myocytes are atypical cells and resemble the embryonic
muscle tissue, which are poor in myofibrils and mitochondria,
rich in sarcoplasm and glycogen and glycogenic enzymes.
These cells, contrary to the cardiomyocytes having a
contraction function, are more stable towards O2 starvation.
Myocytes don’t contract and are specialized on the impulse
generation and its conduction, so they compose the conductive

188
system of the heart. Cardiomyocytes don’t have such ability
and serve as a contractile system of the heart.
Principal physiological properties of the cardiac muscle
like other muscles are the following: excitability, contractility
and conductivity. But the heart possesses also specific
capacity, automatism. The capacity of the heart to respond to
stimulus arisen within the heart without any exogenous
influence by contraction is called automatism. It means the
working ability under the influence of impulses originating
directly in the myocyte system of the heart without the
interference of external factors. To prove this given
characteristics, the heart is removed from the organism and
placed in a physiological solution, where the heart continues its
contraction. The automatism of the heart is conditioned by the
conductive system. The following nodes and bundles are
differentiated in the conductive system (Figure 31): 1. The
sinoatrial node (described by Keith and Flack and often called
after them), which is found in the right atrium, at the opening
of the vena cava superior. 2. The atrioventricular (AV) node or
Aschoff - Tawara’s node is found at the AV border. 3. The
bundle of His, beginning from the latter node, passes through
the septum. Here it is divided into right and left roots
(branches), which in turn passing through the respective
ventricles give final branches. The terminal branches of the
conductive system are represented by the network of Purkinje’s
fibres. The impulse passes along all the branches of the
conductive system, reaching the whole myocardium and
causing its contraction.
189
 Figure 31. Heart conductive system.

Contraction of the cardiomyocytes (working myocardial

cells) is realized due to impulses arising in the sinoatrial node.
The cardiomyocites are not characterized by automatism. If the
apex is separated from the heart, which does not contain
elements of the conductive system and placed it in
physiological solution, the contraction will be absent, while the
other parts of the heart due to containing elements of the
conducting system continue their contraction in physiological
solution by different rates. This means that all the parts of the
conductive system are characterized by automatism, but their
ability to produce impulses is suppressed by the impulses
originated from the sinus node. In normal physiological
conditions the heart works under the influence of the impulses
originating from the sinoatrial node, because of this the sinus

190
node is called the primary node or the pacemaker. The
frequency of impulses in it is about 70-75 imp/min. For this
reason the parts of this system, except the sinus node, have the
capacity of latent automatism. These parts reveal their
automatism in cases when the function of the sinus node is
impaired. In this case the AV node becomes a primary one.
The rate of the impulses originated in it is 40-50 imp/min.
When its function is also impaired or obstructed the His’s
bundle takes upon itself the function of the primary node,
which produces 30-40 imp/min. The rate of the impulses
produced in Purkinje`s fibres is 20 imp/min. The impulses
produced by the last two parts are not enough to satisfy the
pump-function of the heart and tissue supply by blood.
Therefore Gaskell formulated the “automatism gradient” law
according to which the further we move out from the sinoatrial
node, the more the automatism of the conductive system
decreases. It can be proved by application of Stannius`s
ligatures on the frog’s heart (there are two nodes: Remak’s
sinus node and the AV Bidder’s node). The first ligature is put
on the site between the sinus venosus and the right atrium, in
result of which asystolia comes up. Some time later the heart
renovates its contractions, but slower twice. This restore is
connected with the second node having automatism capacity
two times lesser than that of the sinus node. If the second
ligature is put on just after the first ligature between the atria
and the ventricles, the heart starts contracting afterwards, as the
second ligature is a mechanical stimulus for the second node.
There can be 3 variants: 1) when the ligature passes through
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the middle of the AV node both atria and ventricles are
contracted; 2) when it passes on the upper border of the AV
node, only the ventricles are contracted; 3) when it passes on
the lower border of the AV node, only the atria are contracted.
The third ligature is put on the apex of the contracting heart,
and the apex does not contract due to the absence of the
conducting elements.
The nature of the heart’s automatism. The cells of the
conductive system are characterized by a resting potential,
which if compared with other muscular cells has a lower value,
it is equal to -60 mV. The level of the critical depolarization is
-50 mV. This small difference in the potentials (10 mV)
assures high excitability. The resting potential is unstable
because of the high permeability to the Na+ and Ca2+ ions. So,
for these reasons the myocytes are able to produce action
potential (AP) by themselves. We determine the following
phases in AP (Figure 32, I):
1) slow diastolic depolarization (SDD);
2) depolarization;
3) repolarization.
The first stage is based on the uniqueness of the myocyte
membrane, which is conditioned by the fact, that its
permeability towards Na+ and Ca2+ is very high being low
towards K+ ions at the same time. Another reason is the high
density of the fast activating T-type of, Ca2+-channels. By the
inflow of Ca2+ ions the advance of the SDD is assured.

192
 1.slow diastolic
2 3

mv
depolarization
1 (SDD);
2.depolarization;
3.repolarization.

2 3
20 1. rapid
0 depolarization;
2. initial (fast)
-40
mv
4 repolarization;
1 3. slow repolarization
or plateau;
-90 4. final rapid
repolarisation.

msec

Figure 32. The AP- phases of myocytes (I)

and cardiomyocytes (II).

The main characteristics of the myocyte AP are:

1) the small steepness;
2) the weak manifestation or the absence of overshoot. The
maximal value of it is 0-10 mV, so the amplitude of AP is 60-
70 mV;
3) the absence of a constant resting potential. As soon as the
potential reaches -60 mV, the SDD stage begins immediately.
The rate of the heart contraction greatly depends on the
appearing of the SDD, on which the sympathetic and
parasympathetic nervous systems have an effect. Under the
sympathetic mediator (noradrenaline) influence the Ca2+-
permeability increases and K+-permeability decreases, bringing
to the facilitation of the SDD steepness, so that, to increase the

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heart rate. The opposite effect happens under the influence of
parasympathetic mediator acetylcholine.
Summarizing, the significance of the conductive system
assures:
1. Heart automatism causing its contractions.
2. Coordinated contractions of the atria and the
ventricles. This is realized because in the conductive system
impulses spread at a speed of 1.0 m/sec and reaching the AV
node continue at a speed of 0.2 m/sec, which is conditioned by
the structural peculiarities of the AV node. This fact allows
ventricles to be contracted afterwards the atria contraction. It is
called AV retention or delay.
3. The synchronous contraction of myofibrils.

The phase analysis of the heart cycle

The function of the heart is based upon consequent

replacing contraction and relaxation (systole and diastole). If
the heart gives 75 contractions/min, the duration of 1 cycle is
0,8 sec.
The heart cycle consists of:
1) atria systole, lasts 0.1 sec;
2) ventricular systole, lasts 0.33 sec;
3) general diastole, lasts 0.37 sec.
The atria systole is the simplest one, during which the
blood from the atria is pumped into the ventricles. Pumping of
the blood is possible because of the open state of the AV
valves. At that time the pressure in the left atrium is equal to 5-
8 mm Hg in the right atrium 2-4 mm Hg. In this phase the atria

194
don’t receive blood because the circular muscles of the veins
are contracted and the blood is collected in the ventricles due to
the closed semilunar valves. In the ventricular systole they
differentiate 2 periods: period of tension and that of ejection.
The tension period is divided into 2 phases: 1)
asynchronous contraction phase lasts 0.05 sec and 2) isometric
contraction phase lasts 0.03 sec. During the asynchronous
contraction phase the wave of excitation is propagated along
the ventricular myocardium causing contraction of the
ventricles. At the end of this phase all myocardial fibres are
involved into contraction and pressure in the ventricles rapidly
rises, which leads to AV valves closure. The isometric
contraction phase begins at the very moment, when the AV
valves and the semilunar valves are closed. The ventricles
represent as hermetically closed reservoir, which are filled
with practically incompressible liquid, blood. This means, that
during the contraction process the length of the muscle fibres
do not change (hence is the “isometric” term), but the tension
grows; in the left ventricle the pressure reaches 70-80 mm Hg
and in the right, 15-20 mm Hg. This pressure is enough to open
the semilunar valves, which occurs at the end of the isometric
contraction phase and the ejection period begins.
They differentiate two phases of ejection – rapid
ejection, lasting 0.12 sec and the slow ejection lasting 0.13 sec.
The pressure in the ventricles exceeds that in the aorta and in
the pulmonary trunk, reaching in the left ventricle 130-140 mm
Hg and in the right ventricle 25-30 mm Hg. At first the rapid

195
ejection occurs. Then it becomes slow while rushing out the
blood.
Then as blood ejection occurs and pressure in the aorta
becomes more, the aortic and lung trunk valves begin to close
and snaps shut, as soon as the ventricular pressure falls below
that in the aorta and lung trunk. This phase is termed as
protodiastole, which lasts 0.04 sec. Then the ventricular
pressure continues to fall rapidly. This phase of the cardiac
cycle is called isometric relaxation (0.08 sec.). In this phase
there is no inflow to or outflow from the ventricles. As the
pressure in the ventricles eventually becomes lower than that in
the atria, the AV valves open and blood flows across AV
commences. With the onset of the flow from the atria into the
ventricles the period of ventricular filling commences. The
flow from the atria into the ventricles at first is rapid (phase of
rapid filling – 0.08 sec.), then it slows somewhat (phase of
slow filling – 0.17 sec). Then a new cardiac cycle begins, in
which the ventricles continue diastole, and the atria contract
resulting in ventricular final filling and its further contraction.

Methods of investigation of the heart activity

Auscultation. The work of the heart is accompanied by

sound manifestations known as heart sounds (tones) which can
be heard by means of auscultation or can be recorded by
phonograph. There are 4 tones. The first tone arises at the
beginning of the ventricles’ isometric contraction, so it is a
systolic tone. It can be heard rather well in the fifth intercostal
span. It is dull and prolonged (0.12sec) and stands for a result

196
of ventricular contraction, the AV valves closure, vibration of
the stretched cusps of the AV valves, their tendinous cords and
ventricular walls, as well as of the blood fast ejection. The
second tone is heard at the beginning of the ventricular
diastole, so it is a diastolic tone. It is high, short (0.08 sec) and
simple and is a result of the semilunar valves’ closure. It can be
heard in the II intercostal span (in the left the valve of a.
pulmonalis (pulmonary trunk) and in the right the valve of
aorta). The third tone occurs after the second one as a result of
vibrations of the ventricle walls during the maximal (rapid)
filling. It can’t be heard by auscultation. It can be detected only
by phonocardiography method. Throbbing of the ventricle
walls caused by atrium contraction and the additional blood
flow into the ventricle leads to the appearance of the fourth
tone, which also can be recorded by phonocardiography
method.
In heart diseases with structural defects of the valves
(insufficiency of valves or stenosis) the normal blood flow
through the heart is impaired and murmurs are heard along
with the tones. The murmur, which is connected with the AV
valves, is named systolic; and the one which is because of the
semilunar valves, is the diastolic murmur. It is the result of
blood contrary turbulent movement.
Electrocardiography (ECG) method is based on the
heart bioelectrical phenomena arising. It is the registration
method of electrical changes on the body surface as a result of
cardiac activity. This method was introduced into practice by
Einthoven.
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 A B
Figure 33. The electrocardiograms (B) registrated by 3
standard leads proposed by Einthoven (A).

In excitation certain parts of the heart obtain

electronegative charge, i.e. the potential difference between the
excited and non-excited areas arises, the electrical field is
formed nearby the heart and lines of electrical force spread
over the entire body. Consequently, typical tracings reflecting
the oscillations of potentials can be registered by applying
electrodes to certain points on the body. The record got by
means of this method is named electrocardiogram. There are 3
standard leads proposed by Einthoven (Figure 33, A): I - right
arm and left arm; II- right arm and left leg; III-left arm and left
leg. As the pacemaker is placed in sinoatrial node, excitation
arising here firstly spreads over the atria and is reflected on

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ECG as a P-wave (Figure 33, B). It’s a result of the atria
excitation and represents the algebraic sum of the electric
potentials arising on excitation of the both atria and lasts 0.08
sec. Then excitation is conducted by the conducting system
upon the ventricles. Then QRST-ventricle complex comes. The
Q, R and S waves characterize the initial period of the
excitation (depolarization) of ventricles, and the T-wave, its
end. The interval P-Q (0.12-0.18 sec) shows the time required
for excitation to spread from the atria to the ventricles. Q-wave
corresponds to the ventricle internal surface excitation, as well
as the right papillary muscle and the heart apex. R–wave is the
biggest and corresponds to the excitation of the external
surface and base of both ventricles. By the end of the S-wave
both ventricles are involved into excitation and there is no
potential difference between their various areas. Therefore, the
S-T interval is on the isoelectric line. As many scientists assert,
T- wave is a result of the ventricle excitation finishing and it
reflects the process of repolarisation. It is the most variable
ingredient of an ECG. Its duration and amplitude have
diagnostic significance. By veering it conversely we can
evaluate the heart muscle trophic disorders (e.g. in the
myocardial infarction). On the ECG we can determine
arrhythmia, blockades of different degrees (prolongation of P-
Q interval or lying on of P and QRST waves), hypertrophy of
left (R1 S3) and right ventricles (R3 S1) etc.
The minute volume and the systolic (stroke) volume. It
is known that the main function of the heart is its pump
function. For that reason, the amount of blood expelled from
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the ventricle is an essential index of the functional state of the
heart. We differentiate the blood circulation minute volume
(BCMV) and the heart systolic volume (HSV). The minute
volume or cardiac output – is the quantity of the blood expelled
into the vascular system by left ventricle per minute. The mean
cardiac output in man at rest is 4.5-5 l. It is the same in both
ventricles. Dividing the BCMV by the number of heart beats
per minute, we can determine the HSV (5 l : 75 = 65 –70 ml).
The BCMV is measured in clinical conditions.
1. Fick’s method consists of an indirect estimation of
BCMV from the following values: 1) the difference between
the O2 content in the arterial and venous blood; 2) the volume
of O2 (400 ml) utilized by the individual per minute.
O 2 / min 400ml 40000
BCMV = × 100% = × 100% = = 5 l in rest
O 2a − O 2 v 20% − 12% 8

2. A number of other methods have been elaborated to

determine the BCMY and HSV. Some of them are based on the
indicator dilution technique. The latter consists in the
evaluation of the dilution and the rate of circulation of an
indicator administered into the vein.
3. Integrative rheography technique is the method for
registering the resistance of tissues. Resistance of blood is
lower than that of tissues. Registration of electric resistance of
the chest shows its periodic sharp decrease which occurs at the
moment of expulsion by the heart of systolic blood volume.
The value of the resistance decrease is proportional to the HSV
value.

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 The BCMV and HSV values are not constant and they
can be altered under various conditions. In trained men the
BCMV increases mainly due to the HSV increase; in untrained
men, due to the heart rate increase. In muscular loading the
BCMV may increase up to 20-30 l.
There are many other clinical methods of investigating
the heart’s functional activity: echocardiography,
dynamocardiography, ballistocardiography, etc.

Cardiac muscle physiological peculiarities

These are those properties of the cardiac muscle by

which it differs from the skeletal muscle. As the other muscles,
the cardiac one also has excitability, conductivity and
contractility. But compared with the skeletal muscle here are
some differences:
1. Conductivity of the cardiac muscle is different in its
different parts (e.g. in the atria the impulse transferring velocity
makes up 1m/sec; near the AV node, it becomes 0.2 m/sec, i.e.
there is an AV delay; along the His’s bundle and Purkinje`s
fibres it composes 2 - 4 m /sec; and finally, in the ventricular
myocardium it is 0.8-0.9 m/sec. The AV delay depends on the
structural features of the AV node and contributes to the
consecutive contractions of the atria formerly and of the
ventricles lastly, so the AV delay provides the coordination of
the consequence of the atrial and ventricular contractions.
2. “All–or-none” law. This law was formulated by
Bowditch in 1871. It means, that to weak, subthreshold stimuli
the heart doesn’t respond, but to the threshold and

201
suprathreshold stimuli the heart responds by a maximum force
of contraction. While the skeletal muscle gives response
according to the law of “strength’s relation”, i.e. as the stimuli
strength increases, the response also increases. It is explained,
that this comes from the anatomical structure of the cardiac and
the skeletal muscles. In skeletal muscle excitation by weak
stimuli, the most excitable fibres respond. As the excitation
increases, the amount of the reactive fibres increases. The
cardiac muscle has a syncytial structure, as each fibre is
connected with other ones thereby nexuses, so the excitation
threshold is similar. Further it was revealed, that this law is not
absolute, but relative. In conditional changes, depending on the
temperature, fatigue, the composition of the nutrient solution,
hypoxia, etc. the cardiac muscle does not always respond with
an equal force to stimuli of different strength (relativity of
“all”). This assertion also is done by Bowditch and is known
as ,,Bowditch staircase phenomenon’’. Besides, the heart can
respond to rhythmic irritation by subthreshold stimuli, because
the local potentials, arising in these conditions can be summed
by revealing visual effect (relativity of ”none”).
3. Refractoriness. The heart absolute refractoriness is the
absence of the response to the stimulus during its systole. It
lasts 0.27 sec. If the heart is stimulated in diastole, an
extraordinary premature contraction – extrasystole arises. It
may be got only by superthreshold stimuli. This period
coincides with the relative refractoriness period (0.03 sec).
The whole refractoriness period is 0.27 + 0.03 = 0.3 sec.
Refractoriness of the skeletal muscle and the nerve is less: in
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the skeletal muscle 0.01 sec, in the nerve 0.008 sec. Such long-
term refractoriness is connected with cardiomyocytes’ AP
features (Figure 32, II). The cardiomyocyte AP has the
following phases: 1) rapid depolarization; 2) initial (fast)
repolarization; 3) slow repolarization or plateau; 4) final rapid
repolarisation. Depolarization phase in the cardiomyocyte is a
result of the Na+ and Ca2+ influx. The phase of initial
repolarization occurs due to the increased K+ efflux. Plateau is
conditioned by the equilibrium of Na+ and Ca2+ influx with K+
efflux. Then Na+ and Ca2+ channels gradually close and final
repolarization occurs because of K+ outflow.
The heart absolute refractoriness coincides with the 1, 2,
3 phases and nearly half duration of 4th phase. The next half
duration of 4th phase corresponds to heart’s relative
refractoriness period (0.03sec.) and super-excitatory
(exaltation) period (0.03sec.). The amplitude of the
cardiomyocytes AP is 120 mV (the resting potential is -90mV,
reversal potential or overshoot is +30 mV). The presence of
long refractoriness in the cardiac muscle explains the fact, that
the heart never gives tetanus, meanwhile the skeletal muscle
gives that contraction. Although in some poisonings the
refractoriness of the cardiac muscle shortens and it can give
tetanus leading to serious impairments of hemodynamics.
4. Extrasystole can be ventricular and supraventricular.
In ventricular extrasystole extraordinary stimulus arises in the
ventricles. After the extrasystole the compensatory pause
comes and the following contraction becomes more expressive
on its amplitude, which is explained by Starling’s law (the
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“Heart law”). The compensatory pause is a result of the fact,
that coming from the sinus node stimulus during extrasystole
finds the ventricles in refractoriness so the ventricles don’t
respond to impulse and one cycle is lost. In supraventricular
extrasystole the compensatory pause does not occur.
5. The Starling’s law. The more the diastole, the stronger
the systole is, i. e. the more the fibre’s initial length, the
stronger its contraction is (e. g. contraction after the
compensatory pause at ventricular extrasystole). This law is
known as the “Heart law”, since it underlies the heart work
self-regulation.

Regulation of the heart functional activity

The regulatory mechanisms are divided into intracardiac

and extracardiac mechanisms.
Intracardiac regulatory mechanisms of cardiac
activity. Intracardiac regulatory mechanisms of the heart
activity are divided into intracellular, intercellular and
mechanisms that are realized by peripheral reflexes.
Intracellular mechanisms of regulation. As it is known
the myocardium is a functional syncytium, i.e. consists of
separate cells, connected between themselves by intercalated
discs. In each cell there are mechanisms involved in the
regulation of the proteins’ synthesis maintaining cell structure
and function. The increased activity of the heart brings to
enhanced synthesis of contractile proteins to ensure this
activity. The so-called working (physiological) hypertrophy of
myocardium appears.

204
 Myogenic self-regulation of the heart work also belongs
to this type of regulation. There are two types of myogenic
self-regulation:
1. Heterometric, i.e. regulation connected with the
cardiomyocyte length (Starling’s law).
2. Homometric autoregulation is revealed without
changes in cardiomyocyte length. It is Anrep’s phenomenon. If
the blood pressure increases in the aorta, the heart contraction
might be enough to overcome the increased pressure in the
aorta. This phenomenon is based on improved nourishment of
the heart by coronary vessels during the increased pressure in
the aorta, as well as on Ca2+- mechanism.
Intercellular mechanism of regulation. Some of the
intercalated discs perform only mechanical function. Others
ensure transport of necessary substances. They supply the
myocardial contractile cells with certain complex high-
molecular products that are necessary for maintenance of their
structure and function (creative interactions); still others i.e.
nexuses, provide the one-way transmission of excitation cell-to-
cell. Impairment of this transmission causes discoordinated
excitation of cardiac muscle cells and appearance of the heart
arrhythmia.
Peripheral reflexes. Observations of American
physiologists Donald and Cooper concerning to the dogs with
auto-transplanted hearts had shown that in muscular work,
emotional tension, the auto-transplanted heart in all respects
corresponded to the organism’s demands and did not differ
from the intact dogs’ hearts. Kositsky electrophysiologically
205
and histologically asserted his own hypothesis about the
intracardiac neuronal mechanisms that functioned out in a
reflector way.
After degeneration of extracardiac nerves in the auto-
transplanted hearts the following neurons were established:
afferent neurons (Dogiel’s II type neurons), reacting on the
pressure changes within the cavities; interneurons (Dogiel’s III
type neurons) and efferent ones (Dogiel’s I type neurons),
endings of which terminate on the cardiac muscle and coronary
vessels. And the reflex “from part to part” was asserted. The
pressure increase in the right atrium leads to the strength
contraction of the left ventricle. It is asserted, that the heart is
rich in the receptors reacting on the pressure changes
(pressoreceptors). Kositsky asserted also, that arising effects,
when the heart pressoreceptors were being excited, are not
equal. This reaction occurs only when the initial blood filling is
low and the pressure in the aortic orifice and coronary vessels
is not high. If the chambers of the heart are overfilled with
blood and the pressure in the aortic orifice and coronary vessels
is high, the stretch of mechanoreceptors of the right atrium
causes suppression of myocardial contraction with the result
that less blood is expelled into the aorta. Hence, it is clear that
intracardial neuronal regulation provides adaptation of the
heart activity to various hemodynamic situations and regulates
not only the function of the heart, but also the hemodynamics.
If the blood inflow into the heart increases the cardiac output
also increases according to Starling’s law. So, intracardiac
neuronal system is the additional and extremely subtle
206
regulator of the cardiac activity on extracardiac impulses’
background.
Extracardiac regulatory mechanisms of cardiac
activity. Like the other organs, the heart is submitted to the
neuronal and humoral regulation.
The neuronal regulation of cardiac activity. The heart
receives an innervation by vagus and sympathetic nerves
(Figure 34).

Figure 34. Innervation of the heart.

The vagus first neuron fibre, originating from the centre

that is located in the medulla oblongata, terminates in the
intramural cardiac ganglion. The second neuron is located
there and its processes extend to the sinoatrial node (right-
vagus), to the muscle fibres of the atria and to the
atrioventricular node (left-vagus).The first neurons of the
sympathetic nerves are located in the lateral horns of five
upper thoracic spinal segments. Their processes terminate in
the cervical and upper thoracic sympathetic ganglia, where the

207
second neurons lie in. Most of the sympathetic nerve fibres
innervating the heart arise from the ganglion stellatum.
In 1838 Folkman irritating the medulla oblongata (n.
vagus) asserted deceleration and even stoppage of the cardiac
activity. In 1846 Weber brothers were the first to demonstrate
the vagus influence on the heart. They revealed that stimulation
of these nerves inhibited the cardiac activity to the point of
complete stoppage during a diastole (Figure 35, I).

A B C

II

D E
Figure 35. Effects of parasympathetic (I) and sympathetic (II)
nerves on the heart. A- negative chronotropic effect; B- negative
inotropic effect; C- complete stoppage during a diastole; D-
positive inotropic effect; E- positive chronotropic effect.

In 1902 Engelmann found out the vagus’s 5 negative

effects on the heart:
1. Negative inotropic effect, consisting in diminishing the
cardiac contraction amplitude.
2. Negative chronotropic effect, i.e. deceleration of the
cardiac contraction rate.

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 3. Negative dromotropic effect, weakening of the
conductivity during stimulation of the vagus nerve. On the
ECG the prolonged PQ interval is encountered.
4. Negative bathmotropic effect, reduction of excitability
that causes increase of the stimulation threshold.
5. Negative tonotropic effect, decreasing the cardiac
muscle tone. The latter effect is observed only in cold-blooded
animals.
The vagus effects are explained by the increase of
membrane permeability to K+ and decrease to Na+ and Ca 2+.
With prolonged stimulation of the vagus nerve, cardiac
performance, at first arrested, begins again to inspire persisting
stimulation. This phenomenon is known as “escape”, i.e.
release of the heart from the influence of the vagus nerve.
Some authors assume that this phenomenon is connected with:
1. Sympathetic nerve excitation, that is in the same stem with
the vagus nerve. In the vago-sympathetic trunk stimulation the
vagus-effect is observed first and the sympathetic effect
afterwards. It can be explained by the fact that n. vagus has a
short latent period and the vagus effect lasts for a very short
period, but the sympathetic nerve has also an after-action.
2. A fatigue develops in the vagal endings.
3. The second nodal automatism appears, since the first one is
inhibited by the vagus.
The influence of the sympathetic nerve on the heart was
first studied in 1867 by Zion brothers. They revealed that in
stimulation of the sympathetic fibres innervating the heart

209
causes intensification of the cardiac activity. The nerve was
named cardiac accelerator.
Later, Engelmann asserted 5 positive effects of the
sympathetic nerve on the heart:
1) positive inotropic;
2) positive chronotropic;
3) positive dromotropic;
4) positive bathmotropic;
5) positive tonotropic.
The sympathetic nerve effects are explained by the
increase of membrane permeability to Na+ and Ca2+ and
decrease to K+.
The mechanism of nerve impulse transmission in the
heart. In 1921 Otto Loewi performed an experiment on the
isolated hearts of frogs. He stimulated the vagus of the isolated
heart and then transfered nutritious fluid (Ringer’s solution)
from the first heart to another, which had not been subjected to
nerve stimulation. The reaction of second isolated heart was
identical to that produced in response to stimulation of the
nerve (vagus effect). The same pattern was observed in the
sympathetic nerve stimulation (sympathetic effect). Hence O.
Loewi made a conclusion that under the stimulation of the
cardiac nerves their endings produce chemically active
substances causing inhibition or intensification of the cardiac
activity. For that reason he named these substances as vagus-
shtoff or sympathetic-shtoff substances. Later it was found out
that the vagus mediator is acetylcholine, and the sympathetic
mediator is noradrenaline, mediating the corresponding effects
210
on the heart. Loewi’s experiment serves as a base for the fact,
that the heart regulation can be realized also by humoral way.
Humoral regulation of heart activity. Similarly to n.
vagus the K+ ions also evoke negative effects up to stoppage of
the heart, as well as the bile acids (in jaundice bradycardia
appears). These substances are called parasympathicotrop ones
(parasympathomimetic). Sympathicotrop substances
2+
(sympathomimetics) are: Ca , adrenaline, thyroid hormones,
glucagon, etc. Activation or depression of cardiac activity by
these substances is realized by facilitation or suppression of
SDD (positive or negative chronotropic effects), increase of
concentration of cAMP and activation of cAMP-dependent
phosphorylase with decomposing of glycogen and producing of
glucose. The latter improves the nutrition of cardiac muscle
and brings to positive inotropic effect. The positive or negative
bathmotropic and dromotropic effects of these substances on
the heart connect with changes of resting potential and critical
level of depolarization.
Interaction of intracardiac and extracardiac neural
mechanisms. The intramural nodes and originating from them
efferent neurons are the final link for the realization of the
vagus effect as well as intracardiac reflexes. Thus they are the
final common pathway through which influences of extra- and
intracardiac origin are realized. There are cholinergic and
adrenergic efferent neurons. It is known that adrenergic
neurons are more excitable than cholinergic ones. As a result,
the impulses of low intensity (both of extra- and intracardiac
origin) lead to the excitation of adrenergic neurons, so to the
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increase of force and rate of heart contraction. Augmentation of
impulses brings about excitation of cholinergic neurons and
correspondingly about inhibition of cardiac activity. That is
why the same stimulation intensity of the vagus nerve as well
as excitation of intracardiac stretch receptors can produce an
opposite effect on the heart, depending on the degree of the
heart and coronary vessels blood filling. As a result, the
constancy of arterial blood filling is regulated not only by
reflex reactions of the intracardiac nervous system, but by the
vagus nerve as well. Here the doubling of the regulatory
mechanisms takes place, which is essential to maintain the
stability of arterial filling. Thus, the interaction of the vagus
nerve with intracardiac mechanisms can both suppress and
stimulate cardiac activity ensuring regulation of the required
level of arterial filling.
Tone of centres that control cardiac activity. The
vagus influence is emphasized more than the sympathetic one.
The proof is: after dissection of the n. vagus, the cardiac rate
becomes twice as more, but after dissection of the n.
sympathicus (or removal of both ganglia stellate) it becomes
15% as less. These phenomena are connected with the tone of
the corresponding neuronal centres. The vagus centre tone
exceeds the sympathetic one.
The vagus tone is weak in newborns (120-150 heart beats
per minute), and is increasing by the first year of age.
The tone is a condition of continuous limited excitation
that is not accompanied by fatigue. The vagus tone is supported
by three pathways: 1) mechanical; 2) humoral; 3) reflector.
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 The mechanical (pressure) pathway. As the nucleus n.
vagus is situated in the medulla oblongata, the pressure of the
craniocerebral liquid acts on the nucleus. This can be proved
by the orthoclinostatic probe. In lying position the cardiac
activity is decelerated because of the reduce of blood outflow
from the head and increase of intra-cranial pressure. In
standing position the blood outflow increases causing the
pressure decrease and the cardiac activity intensification.
The humoral way. The vagus centre tone is supported
also in the humoral way. It was proved by Heimans on his
experiment with cross blood circulation, which consists in
joining the blood vessels of two dogs in such a manner that the
blood of A dog flows into the head of B dog. After joining the
vessels, B’s head is isolated from its body with only the vagus
nerve left intact. Introduction of adrenaline into A’s blood
causes cardiac activity stimulation but stoppage in B dog.
Adrenaline through joint vessels reaches the B’s head resulting
in excitation of the nucleus n. vagus and the stoppage of the
cardiac activity thereafter. So, adrenaline evokes positive
influence on the heart directly, while by central way it acts
negatively. Identical to adrenaline the Ca2+ ions act.
The reflector way. The nucleus n. vagus constantly gets
signals from various reflexogenic zones of the organism, and at
first of all the vascular reflexogenic zones. Particularly in this
respect the afferent impulses that reach from the receptors
lying in the aortic arch and carotid sinus are very important.
The cardiac afferent nerves depending on their effects on
stimulation are divided into the depressor and the presser ones.
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The depressor proceeds from the baro-receptors, reacting on
the arterial pressure changes in the aortic arch and carotid
sinus. Impulses are transmitted by the Ludwig-Zion’s nerve
from the aorta and by the Herring’s nerve from the carotid
sinus, and being reached the nucleus of n. vagus increase the
latter’s tone. As a result the cardiac activity weakens and the
arterial pressure drops. The analogical reflexogenic zone is
located in the lung trunk, the reflex is beginning from which is
called Parin’s reflex. But in arterial pressure decrease
insufficient impulses come into vagus centre, and its tone is
suppressed, which brings to the heart functional activity
activation.
The presser nerve begins from the pressoreceptors,
situated in the vena cava and particularly in the right atrium.
They are stimulated by an increase in blood pressure in the
vena cava because of the heart insufficiency. Presser nerve
originating from these receptors causes reflector decrease of
the vagus centre tone and appearance of the sympathetic effect,
as a result of which heart beats become more frequent and
intensive. The heart pumps more blood into the arteries, due to
which the venous return increases and pressure in the vena
cava falls to normal. This phenomenon is known as Bainbridge
reflex.
The heart regulation is also completed by other
mechanisms realizing by different parts of the CNS. Such
structures as the cerebral cortex, hypothalamus and cerebellum
also take part in the cardiac regulation. The cortex participation
has been proved by the conditional reflexes’ formation. The
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hypothalamus takes part as a higher centre of vegetative
functions.
Reflexes on the heart. Changes of the cardiac activity
can be caused by reflector way. Depending on the nerve
realizing changes of cardiac activity, the reflexes are divided
into the vagal and the sympathetic ones. The vagal reflexes are:
1. Goltz’s classic reflex (Figure 36, A). Essence of this
reflex is a light blow on frog’s gut causing cardiac arrest of
long duration. Cardiac arrest resulting from a blow on the belly
is also encountered in humans. The afferent pathways of this
reflex extend from the intestine to the spinal cord along the
splanchnic nerve and reach the nucleus of the vagus nerve in
the medulla oblongata, where the reflex efferent pathway
begins, formed by the branches of the vagus nerve passing to
the heart.
2. Ortoclinostatic test: in lying position the cardiac
activity weakens, and in standing position it intensifies.
3. Dagnini-Aschner’s oculocardiac reflex (Figure 36, B):
slowing of the heart beats to ten per minute when pressure is
exerted on the eyeball.
4. Chermak’s reflex: pushing on the medial part of m.
sternocleidomastoideus can cause cardiac arrest in result of
mechanical irritation of the receptors, from which the impulses
pass to the vagus centre.
5. The divers’ reflex; in excitation of cold-sensitive skin
receptors the cardiac activity slows.
6. Respiratory arrhythmia. N. vague is an extremely
sensitive nerve for the lungs. So in breathing, during
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inspiration and expiration the heart work changes: in the
inspiration onset it becomes faster, and in the expiration
slower. This reflex is expressed better in children and
teenagers.

A. B.
Figure 36. Goltz’s reflex (A ),
Dagnini-Ashner’s oculocardiac reflex (B).

Cardiac activity can be altered by stimulation of

receptors in the blood vessels of many internal organs
(Cherningovsky’s reflex).
Sympathetic reflexes are realized by sympathetic nerve.
Reflex of acceleration and intensification of the cardiac activity
is encountered in response to pain or in emotional states (anger,
fright, joy) and with muscular exercise.

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 The endocrine function of heart. In 1964 Jewisson and
Palade revealed some granules in the right atrium. Then other
scientist De’Bold proved that these granules possess natriuretic
action and the substance, obtained from the granules was called
natriuretic hormone or atriopeptide. It has properties, which
are antagonist to aldosterone, i.e. it inhibits the sodium
reabsorption in the renal distal tubules increasing the sodium
concentration in the final urea and possesses vasodilator
activity.

7.2. PHYSIOLOGY OF THE VASCULAR SYSTEM

General principles of the structure and functioning

of the vascular system

The cardio-vascular system is represented by the big

(systemic) and the small (pulmonary) circulations that are
successively joint to each other.
The systemic circulation starts from the left ventricle of
the heart. The blood passes to the aorta and originating from its
arteries also to all their branches, thence to the arterioles,
capillaries and the veins of the whole body and finally to the
two main veins (venae cavae), which enter the right atrium.
The pulmonary circulation begins from the right
ventricle, continues along the pulmonary artery and all its
branches, then along the pulmonary arterioles, capillaries, and
veins, and terminates in the pulmonary four veins which enter
the left atrium. The blood circulation time is 23 - 25 sec. The
pulmonary circulation is realized during 5 sec and the systemic

217
one during 20 sec. There is a difference between these two
circulations. The systemic circulation supplies all organs and
tissues with blood and is regulated by a number of
mechanisms. The vessels of pulmonary circulation, i.e. the
pulmonary vessels fulfil just the functions of gas exchange and
thermoregulation. That’s why the regulation of this circulation
is less complex if compared with the systemic circulation,
where the powerful regulation is realized.
The functional classification of the vascular system. In
connection with the functional specificity all the vessels are
divided into several groups:
1. Springing (amortizing) vessels are the aorta,
pulmonary and other big arteries. In their walls a lot of elastic
fibres are available, due to which they retain strong hits of the
blood and during the systolic pressure increase.
2. Resistive vessels. It concerns in general to the
peripheral arteries and arterioles. They have maximal
resistance to the blood flow, i.e. have big length and relatively
small diameter. Besides, they have a thick layer of smooth
muscles in the walls capable to constrict and narrow the
vessels’ lumen.
3. Vessels-sphincters. These are the terminal parts of the
precapillary arterioles that contain circular layer of muscles,
that makes the capillary lumen become smaller in contraction,
which leads to the arterial pressure increase. In relaxation of
the circular muscles the capillary lumen becomes larger
improving a better blood supply in the working tissues. So this
type of vessels performs a very important role in the regulation
218
of arterial pressure, as well as of the blood supply in the given
organ.
4. Metabolic (exchange) vessels are the capillaries owing
to some peculiarities: the capillary walls are thin with one
endothelial layer and the blood flow is very slow there. They
realize gas and substance exchange.
5. Volume vessels. These are the veins. Their walls
contain muscular layer and that’s why can enlarge at a great
extent. The big and middle veins have valves, which provide
one-way blood flow. Big veins have a significance of blood
depots.
6. Shunt-vessels. These are the artery-venous
anastomoses. Along these vessels the blood from the arterioles
enters directly into the venules, eluding the capillary network.
They are located in the lungs, skin and participate in the
thermoregulatory processes.
The main principles of the blood flow along the
vessels (hemodynamics). The main principles of
hemodynamics are: 1) blood continuous flow and 2) one-way
blood flow.
Blood continuous flow. Despite the fact that the blood is
pumped out only in systole, it flows by continuous stream both
in systole and in diastole. It occurs due to the aorta’s and large
arteries’ elasticity. When the blood is expelled from the
ventricles into the aorta or pulmonary trunk, their elastic walls
are distended, obtaining the blood pumped out from the heart.
The heart energy partly is expended on the vascular wall
distension, and partly on propelling the blood along the vessels.
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During diastole, when the blood is not expelled from the heart
and the pressure in the aorta drops, the aorta’s and artery’s
walls collapse and propel the blood along the vessels.
One-way blood flow. It is contributed by intra- and
extracardiac factors.
The intracardiac factors are:
1) successive contractions of the atria and ventricles;
2) the valve apparatus of the heart;
The extracardiac factors are:
1) the pressure difference between the initial and the
terminal parts of the vascular system;
2) the contraction of the skeletal muscles, surrounding
the vessels (veins);
3) the valve apparatus in the veins;
4) the sucking property of the atria in diastole;
5) the sucking property of the chest, promoting the blood
flow in the vena cava, especially during inspiration.

The main indices of hemodynamics

These are: the volume (Q), linear (v) velocities,

peripheral resistance (R) and blood pressure (P).
The volume velocity (Q) is an amount of blood that
passes through the total cross-sectional area of any part of the
vascular network per unit of time. It’s a quantity of blood that
passes through the aorta or all arteries, or all capillaries, or all
veins equally per 1 minute. As much the blood flows out from
the heart, as it returns to the heart. So this value is constant. It
is determined by the formula:
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 P1 − P2
Q= ,
R
where Q is the volume velocity;
P1-P2 is the difference between the pressure at
the beginning and at the end of the vessels;
R is the resistance to the flow.
Since the beginning of the vascular network is the aorta
and the end is vena cava, where the blood pressure is about 0,
P
the formula can be represented as: Q = .
R
The linear velocity (v) is a velocity of the motion of blood
particles along the vessel, i.e. distance passed per unite time. It
equals to the volume flow divided by the cross- sectional area
Q
of the blood vessel: v= .
πr 2
Hence, the larger the total cross-sectional area of the
vessels, the lower linear velocity of blood flow is. The
narrowest point in the cardiovascular system is the aorta (5 - 10
cm2) and the linear velocity is 50 cm/sec. The capillaries
constitute the most extensive vascular area because the total of
all capillary lumen is about 700-800 times more than the size
of the aortic lumen. So, the linear velocity of blood flow in
capillaries is the least (0.05 cm/sec). The cross-section of the
veins is 1.5-2 times less than the size of the aorta, and so the
linear velocity is 25 cm/sec.

221
 According to the laws of hydrodynamics, two forces
determine the flow of fluid along the tube:
1) the difference between the pressures at the beginning and
at the end of any part of the vascular network, that
promotes the blood passage;
2) the peripheral resistance, which is conditioned by the
blood viscosity, length and lumen of the vessel. In its turn
the viscosity is determined by the friction of blood
corpuscles with the vessel walls and blood turbulence.
The total peripheral resistance is summed from a
number of discrete resistances of vessels. Resistance in each
discrete vessel can be calculated according to Poiseuille`s
equation:
8η1
R= 4,
πr
where η is the viscosity of the fluid;
l is the length;
r is the radius of tube.
This formula is used in hydrodynamics for hard tubes and
does not consider the vessels’ elastic properties, the changes in
vascular diameters with changes in the blood pressure, etc.
Nevertheless, this equation reflects the dependence of the
resistance on the width and length of the vessels and on the
viscosity of the blood. It shows that maximum resistance to
blood flow is encountered in the narrowest blood vessels,
capillaries. But, in reality, the total periphery resistance is the
most in the arterioles, which depends on the way of their
conjunction. The vessels are interconnected successively or
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parallel. The arterioles are connected to each other by
successive way and the total resistance of them will be:
Rtot = R1+R2+R3+ … Rn
The capillaries are connected parallel, so their total
length is less and the total resistance will be:
1
R=
1 / R 1 + 1 / R 2 + 1 / R 3 .....1 / R n
Hence, the total resistance is the most in the arterioles.
It’s contributed also to the thick muscular layer inside their
walls, which contraction brings to the resistance increase. This
condition hinders the blood outflow from the arteries and the
arterial pressure level increases. Just for this reason the
arterioles are the arterial pressure regulators. According to
Sechenov they also are called the “taps of the cardio-vascular
system”. Opening of these taps improves the organ’s blood
supply, but closure causes its disorder. The arterial pressure
drop in different vessels is an evidence of the resistance inside
them. Thus, the arterial pressure in the big and middle-sized
arteries drops by 10%, but in the arterioles and capillaries – by
85%.
The blood pressure is the force that blood influences on
the vessel wall’s unit surface. The factors ensuring blood
pressure are the follows:
1) the heart contraction force and rate;
2) the circulating blood volume;
3) the resistance or viscosity of the blood.

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 There are some types of blood pressure: 1) systolic or
maximal; 2) diastolic or minimal; 3) pulse or stroke blood
pressure is the difference between systolic and diastolic
pressures; 4) mean pressure, that ensures the blood flow
without systolic and diastolic pressures’oscillations (i.e. the
force of continuous blood flow) and produces the same
haemodynamic effect as that observed in case of the natural
fluctuating blood pressure.
The maximal blood pressure is in the aorta and the
arteries lying near to the heart 120-130 mm Hg c, the minimal
pressure is 70-80 mm Hg c. The blood pressure in the
arterioles is 70 mm Hg c; in the capillaries 30-40 mm Hg c.; in
the venules 8-12 mm Hg c.; in the veins 2-4 mm Hg c.; in the
vena cava about 0.
In newborns the systolic pressure is 50 mm Hg c., but by
the end of the first month it rises to 80 mm Hg c.
Deviations from the normal arterial pressure (AP) value
are called hypertension (increase) and hypotension (decrease).
Methods of the blood pressure measuring. There are two
methods – acute and chronic.
Acute method is the direct one, when the AP is measured
by inserting into an artery a needle connected to a manometer
by tubule and recording apparatus. It is used in animals and
was proposed by Ludwig in 1843 (Figure 37). The needle and
connecting glass tubule are filled with anticoagulant to prevent
the blood coagulation in them. Intra-arterial pressure is not
constant, but it displays continuous fluctuations, rising above
and dropping below a certain mean level, which produce three
224
types of waves on the blood pressure curve (plethysmogram).
Waves of the first type are most frequent and arise from the
heart contraction. A certain amount of blood enters the arteries
with each systole and increases their elastic distension. During
diastole the ejection of blood from the ventricles into the
arterial system ceases and only the outflow of blood from the
large arteries continues; their walls become less distended and
the pressure falls.

Figure 37. Acute method of the blood pressure measuring.

I - waves of the first type; II - waves of the second type
(respiratory waves); III - waves of the third type.

Apart from these oscillations, the blood pressure curve

shows the waves of the second type, which correspond to
respiratory movements; because of that they are known as
respiratory waves. Inspiration is accompanied by a decrease in
blood pressure, and expiration by an increase. It is explained by
the fact, that in inspiration due to the increase of the negative
pressure in the pleural cleft, the walls of veins (vena cava) are

225
stretched, bringing to the blood pressure decrease in them and
promoting the easy passing of the blood from arterial system to
the venous one.
Waves of the third type are also encountered as slower
rises and falls in pressure, each comprises a few of respiratory
waves. They are caused by a periodic increase and decrease in
the tone of the vasomotor centre, and are most frequently
associated with O2 deficiency in the brain, low atmospheric
pressure or intoxication by certain poisons, etc. Other methods,
namely indirect, are used to measure blood pressure in humans.

Arterial pulse

The rhythmical expansion of the arterial walls (aortal)

caused by the systolic rise in pressure is called the arterial
pulse. Arterial pulsation can easily be felt on any artery
accessible to palpation, as the radial and temporal arteries, the
dorsal artery of the foot, etc.

c
a
b

Figure 38. The sphygmograms of carotid artery (1), radial

artery (2), finger artery (3).

226
 A pulse wave arises in the aorta at the moment of blood
ejection from the ventricle, when the pressure in the aorta rises
sharply and distends its walls. The wave of increased pressure
and expansion of the arterial walls spreads from the aorta to the
arterioles and capillaries, dying out in the capillaries.
The velocity of blood flow does not influence on the rate
at which the pulse wave spreads. The maximum linear velocity
of arterial blood flow does not exceed 0.5 m/sec, while the
pulse wave spreads with 5.5–8 m/sec velocity in the aorta. The
pulse wave velocity increases with age, as the vessels lose their
elasticity.
Graphically the pulse wave can be represented in
sphygmogram as a pulse curve. The curve recorded from the
aorta or big vessels branching directly from it, is called the
central pulse; that from the peripheral arteries - the peripheral
pulse.
On the peripheral pulse curve two main parts are
distinguished:
1) an anacrotic, the ascending part of the curve (Figure
38, a);
2) a catacrotic, the descending part of the curve (Figure
38, b).
The anacrotic rise results from the increase in arterial
pressure and caused distension of the arterial walls at the
beginning of the ejection phase. The catacrotic descent of the
curve occurs at the end of the systole, as pressure in the
ventricle begins to fall. At the start of ventricle relaxation the
blood discharged into the arterial system rushes back toward
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the ventricle. Pressure in the arteries falls sharply and a deep
notch or incisura, appears on pulse curves recorded from the
main arteries. The blood return to the heart is checked by the
semilunar valves, which are pushed shut by the backward flow.
The return stream of blood rebounds against the valves and
gives rise to a secondary wave of increased pressure, which
again distends the arterial walls. As a result, a secondary or
dicrotic rise (Figure 38, c) appears on the sphygmogram. The
central pulse sphygmogram besides these waves has two
additional ones, connected with atrium systole and ventricle
isometric contraction that lead to additional oscillation of
aorta’s or big arteries’ walls. These waves are not registered in
the vessels far from the heart.
The pulse properties are: rate, velocity, amplitude, tone
(hardness) and rhythm. Pulse rate is characterised by the rate
of cardiac contractions. The pulse velocity is determined by the
speed with which pressure rises in the arteries during the
anacrotic ascend and declines during the catacrotic descend. On
this base there are normal pulse, pulsus celer (a quick pulse)
and pulsus tardus (abnormally slow pulse). Pulsus celer occurs
in aortic valve insufficiency. Pulsus tardus occurs with stenosis
of the aorta, when the blood is pushed into the aorta more
slowly than normal. The pulse amplitude is characterized by
the arterial wall expansion during pulse thrust. The pulse
hardness is determined by the pressure required to compress
the artery for the pulse disappearance. Pulse rhythm depends
on the heart rhythm, but sometimes the heart’s normal rhythm
can be accompanied by arrhythmic pulse. “Pulse deficit” is
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sometimes encountered, when occasional wave of ventricular
excitation is not attended with the blood discharge into the
vascular system and by a pulse thrust. Some systoles are so
weak, owing to a small systolic discharge, that they do not give
rise to a pulse wave. Pulse rhythm then becomes irregular
(arrhythmic pulse).

Regulation of the blood circulation

Activity of each organ is conditioned by adaptation of its

blood supply to the given circumstances. It is possible due to
change of the vessels’ lumen, which in turn proceeds by means
of the central and the peripheral mechanisms. The central
mechanisms regulate systemic hemodynamics, but the
peripheral ones are responsible for the given organ’s blood
supply. The central mechanisms can be realized by the
neuronal and the humoral pathways.
The neuronal regulation. It is realized by the nerves
innervating the vessels. These nerves are divided into two
groups: vasoconstrictor and vasodilator.
Those causing spasm of the vessels are vasoconstrictor
nerves and those causing dilatation – vasodilator nerves.
The vasoconstrictor nerves exclusively are of sympathetic
nature. Their existence was first revealed in 1842 by Walther
in experiments on frogs. Walther observed the frog’s
swimming membrane’s vessels’ dilatation in cutting of n.
ischiadicus. Irritation of the cutting nerve causes the vessel
constriction. In 1852 Claude Bernard once again got such a
result in experiments on the ear of a rabbit. Removal of the
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neck sympathetic ganglion or cutting of the sympathetic nerve
on one side of the rabbit leads to its ear’s vasodilatation
(turning red and temperature rise) on this side. Stimulation of
the sympathetic nerve on the rabbit’s neck causes the
corresponding ear to become pale, owing to constriction of its
arterioles and arteries. The experiments described show that the
blood vessels are under the continuous constrictive influence of
sympathetic nerves, which maintain the arterial tone.
The parasympathetic part of the nervous system is
distinguished by realization of vasodilative effect. For instance,
stimulation of chorda tympani causes vasodilatation in the
submandibular salivary gland and the tongue.
But some sympathetic nerves (cholinergic), innervating
the skeletal muscle and the sweat gland vessels possess a
vasodilative effect.
Dilatation, mainly in the vessels of the skin, can be
observed in stimulation of the peripheral endings of the
posterior spinal roots. This fact was explained by Bayliss in the
seventies of the 19th century. In accordance with Bayliss’s
theory, in irritation of the afferent neuronal way the impulses
are transmitted to the spinal cord, as well as to the skin through
the collateral branches, leading to a vasodilation effect.
According to another point of view, dilatation of the skin
vessels at stimulation of the posterior roots results from the
production of acetylcholine and histamine in the receptor
endings.
Vasomotor centre. By means of transversal sections at
various levels of the brainstem Ovsyannikov revealed existence
230
of the tonically active vasomotor centre in the medulla
oblongata. Cutting above the midbrain causes no changes in
arterial pressure, but a section made between medulla
oblongata and spinal cord leads to the fall of systolic pressure
to 60-70 mm Hg c., but it has a temporary character because of
the presence of the other vasomotor (vasoconstrictor) centres
(e.g. sympathetic spinal centres). The main vasomotor centre of
the medulla oblongata lies on the floor of the fourth ventricle
and consists of two parts: the presser and the depressor. These
parts are in reciprocal relations. The sympathetic
vasoconstrictor centres are located in the lateral horns of the
thoracic segments of the spinal cord. Besides, there are nervous
centres in the hypothalamus, cerebral hemispheres that also
regulate the vessel lumen, so the blood pressure.
Regulation of vascular tone. The main vasomotor centre
is activated by signals coming from the mechanoreceptors of
the cardio-vascular system. The afferent system is divided into
two receptive (reflexogenic) fields. Signals of one of them arise
in the cardio-vascular system, forming proper cardio-vascular
reflexes; signals of the other field come from all the other parts
of the organism, forming coupled (conjugated) reflexes. The
main reflexogenic zones that give rise of proper reflexes are the
aortic arch, carotid sinus and a. pulmonaris. In arterial pressure
increase the baroreceptors located in these areas are excited and
the excitation is transferred through Ludwig-Zion’s (branch of
n. vague, from the arch of aorta) and Herring’s (branch of n.
glossopharingeus, from the carotid sinus) nerves activating the
depressor part of vasomotor centre. The latter promotes
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arterial pressure decrease by the inhibition in the tone of the
presser centre (cardiac performance is inhibited, while vessels
of the internal organs are dilated). The increase of blood
pressure in the vena cava and right atrium leads to presser
effect on the vessels (Beinbridge reflex). There is a feedback
mechanism between vasomotor centre and reflexogenic fields.
The tone of vasomotor centre is provided by impulses coming
from the reflexogenic zones.
Another flow of impulses influencing on hemodynamics
comes from the chemoreceptors, located the same sites that the
baroreceptors are in special corpuscles. They are excited by
nicotine, cyanides; they are sensitive to hypoxia and
hypercapnia. Impulses from these receptors coming to the
vasomotor nervous centre evoke the inhibition of its depressor
part, which causes a vasoconstrictive or pressing effect on the
vessels and thus the arterial pressure increases.
The coupled reflexes of the cardio-vascular system are
provided by the impulses coming from the receptive fields out
of the cardio-vascular system and are formed by the afferent
nerves carrying tactile, temperature, pain, chemical and other
sensitivities.
Humoral regulation. It implies the regulation by means
of different biologically active substances: hormones, ions and
metabolites. They are divided into two groups:
vasoconstrictors and vasodilators. Vasoconsrictors are:
1. Catecholamines (adrenaline, noradrenaline) act on the
vessels of all organs, binding with the alpha-receptors;
exclusively, binding with the beta-receptors (they are available
232
in the vessels of the heart, brain, etc.) they exert vasodilative
effect. That’s why in physiological concentrations they cause
blood distribution and as a result the heart, brain and other
organs get more blood than the other regions, where
vasocontriction occurs.
2. The more active from the known vasoconstrictors is the
renin-angiotensine system. The arterial pressure decrease or the
Na+ level decrease in the organism’s liquids causes the renin
secretion in the kidneys, which acting on globulin
angiotensinogen, converts it into angiotensine I. In its turn
angiotensine I is converted into angiotensine II, which causes
1) significant constriction of the peripheral arterioles; 2)
moderate constriction of the veins; 3) constriction of the renal
arterioles, enforcing the kidney to retain the water and salts,
resulting in increase of the blood volume and arterial pressure.
3. Vasopressin, which is secreted in the hypothalamus in
high (pharmacological) dozes, causes significant constriction
of the peripheral arterioles.
4. Serotonin, which is produced in the intestinal cells,
thrombocytes, etc., promotes the vessel spasm and further
bleeding stoppage.
5. Prostaglandins, which are produced in different tissues,
have two types of action: prostaglandin F is a vasoconstrictor,
but prostaglandins A and E are vasodilators.
The vasodilators are:
1. Bradykinin that belongs to the kinins’ group and is
produced by different tissues.

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 2. Histamine evokes the same effect and is produced by
basophiles, the digestive system. Its large concentrations lead
to a shock with arterial pressure decrease.
3. Medullin is secreted by the renal medullar secretor
cells.
4. Acetylcholine, the parasympathetic mediator, action
of which is short and local due to rapid decomposition.
Some ions also participate in regulation of vessel lumen,
e.g. Ca2+ ions evoke vasoconstriction, K+, Mg2+, Na+ ions
cause vasodilatation.
The local mechanism of the vascular regulation. It
occurs in a working organ thereby the accumulation of
metabolites, NO, that causes vasodilatation and increased blood
supply in the given organ. Besides, the endothelial cells of the
vessel produce some biologically active factors, which also
have vasoactive properties. The pacemaker elements of the
vessel smooth muscle wall perform the most important role in
local self-regulation, which is regulated by Ca2+ ions.

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CHAPTER 8.
PHYSIOLOGY OF THE RESPIRATORY SYSTEM

Breathing is integrity of the processes ensuring

continuous entrance of O2 into the organism, its utilization in
oxidative reactions and the CO2 remove from the organism.
The respiratory system ensures the gas content of the
organism, as well as the indices connected with this system
(pH, temperature, excretion, amount of erythrocytes, speaking,
etc).
Breathing consists of several interconnected processes
(phases):
1. External respiration, that results in the lung ventilation (gas
exchange).
2. Gas exchange between the alveolar air and the blood.
3. Gas transport by the blood.
4. Gas exchange between the blood and the tissues.
5. Inner breathing, the O2 uptake and utilization in biological
oxidation by mitochondria of cells. This part is an issue for
biochemical study.

External respiration
Ventilation is the process of gas delivery to the alveoli
and vice versa. It is ensured by periodical changes of
inspiration and expiration that are based on biomechanical
processes. Biomechanics is a part of physiology that studies
respiratory muscles’ movement, changes in the chest and

235
pulmonary volumes as well as the mechanisms of their
realization.
In rest an adult makes 14-18 respiratory movements
per minute. In children it makes up 20-30 per minute, in
newborns, 40-50. With growth breathing becomes rarer.
Breathing rate can be changed because of different reasons:
muscular work, emotions, heat and intensification of
metabolism, which bring to respiratory intensification. In
dreaming it becomes rarer and composes 4/5 from the normal
breathing.
The role of respiratory muscles. In breathing the lungs
have a passive role. They can’t be extended and squeezed
actively, because they have no muscles. Air delivering into the
lung in inspiration and its removal in expiration take place due
to the respiratory muscles’ contraction and relaxation, which
leads to changes of the chest volumes. The lungs follow these
changes. The junction link between the lungs and the chest is
the pleural cleft.
The contractions of respiratory muscles, and respectively
the respiratory act are going on involuntary, without our
consciousness. But they can be regulated voluntarily by
impulses from the big hemisphere neurons. We can breathe
frequently, slowly, or stop our breathing desirably consciously.
Inspiration is an active phase of respiration, in which
main and accessory respiratory muscles take part. The main
muscles are the diaphragm and external oblique intercostal
muscles; the accessory ones are the scalenus, the major and
minor pectoralis, the serratus anterior, the trapezius, the
236
rhomboidei and the levator scapulae. The accessory muscles
participate in forced respiration.
Pleural cleft pressure. As it is known between the
parietal and the visceral pleural sheets there is a cleft
containing a serous liquid that decreases the friction of the
sheets. But the important meaning of intrapleural space is in
the negative pressure in it. Introducing a hollow needle in the
space and attaching it for the manometer it is possible to
measure this negative pressure. It is lower the atmosphere
pressure by 3 mm Hg c., so they say it is negative in respect to
the atmosphere pressure. Considering Patm=760 mm Hg c., the
pleural cleft pressure will make up 757 mm Hg c.
This pressure is conditioned by the elastic recoil of lungs,
i.e. by their property to reduce their volume. The lung elastic
recoil is equal to 3 mm Hg c.
Ppl = Patm – Pelast = 760 – 3=757 mm Hg c.,
or considering 760=0 mm Hg c.
Ppl = Patm – Pelast = 0 – 3= -3 mm Hg c.
This value changes in inspiration and expiration. At the
end of calm inspiration it is lower the Patm by 6-8 mm Hg c.; at
the end of the maximal inspiration by 12-20 mm Hg c.; at the
end of a calm expiration by 3-4 mm Hg c.; in deep expiration
by 0-1 mm Hg c.
In newborns Ppl=0, so in pleural space there is no
negativity. During the human’s individual development the Ppl
value grows up, because the chest grows faster than the lungs.
The elastic force of the lungs is conditioned by 3 factors:

237
 1. The force of the liquid superficial tension (provide 2/3
of the elastic traction). The substance, which covers the inner
surface (by 20-100 nm layers) of alveoli, is called surfactant or
superficial–active substance. It consists of phospholipids and
proteins and is produced by the cells of alveolar epithelium
(pneumocytes of type II). It prevents the alveoli from collapse
that is named atelectasis because it decreases superficial
tension. Besides, surfactant possesses bacteriostatic property. It
also has an important significance in realization of the new-
born’s first breathing.
2. Elastic fibres inside alveoli.
3. The bronchial muscle tone.
The respiration mechanism. The inspiration begins
with the diaphragm, as well as external oblique intercostal
muscles’ contraction. In result the chest volume enhances in
vertical, sagital and frontal directions. It proceeds owing to the
oblique orientation of these intercostal muscle fibres, so the
moment of force that determines level movement is greater for
the lower rib (Figure 39). Because of the chest enlargement, the
pleural cleft also increases, causing an increase of negative
pressure and therefore the passive enlargement of the lungs.
The air pressure falls inside the lungs, which leads to the air
entrance from outside. With this process the inspiration is
completed and the expiration begins.
Expiration is a consequence of processes taking place
during inspiration. During inspiration the inspiratory muscles
have to overcome the following resistances:

238
 a) the abdominal organs’ and the abdominal muscles’
resistance;
b) the weight of the chest being lifted;
c) the elastic pulling of the lungs, as well as the elastic
resistance of rib cartilages and other tissues of the chest.
After inspiration all these forces cause the chest return to
the initial state of rest, extruding air, i.e. expiration arises. So,
for the quiet expiration there is no need in the special muscles’
contraction, and that is why the quiet (usual) expiration is
considered to be a passive process. But in active forced
expiration the muscles of the abdomen press (external and
internal oblique, transversus, rectus abdominis), as well as the
inner intercostal muscles participate. The contraction of the
inner intercostal muscles causes the ribs to descend, their sides
come closer to each other since the moment of force is greater
for the upper than for the lower rib.

Figure 39. The mechanism of inspiration.

239
 So, inspiration and expiration are the results of
consequent and periodic changes of the chest volumes,
connected with filling in and emptying of the lungs.
Interrelations between the chest volume alterations can
be demonstrated by the model supposed by Dutch scientist
Donders in 1880. It is a hermetically closed reservoir with an
elastic rubber bottom. The lungs of animal are located inside
and by the pipe passing through the cork are communicated
with external environment. In drawing off the bottom
downward the imitation of inspiration proceeds: volume of the
reservoir, which imitates the chest, increases and the lungs
passively, enlarge. Return of the rubber bottom to the initial
state imitates expiration with the lung volume decrease.
Pneumothorax. The entrance of air into the pleural cleft
is called pneumothorax. It leads to the lung full collapse.
Pneumothorax may be open and close. In open pneumothorax
the pleural cavity has a direct communication with atmospheric
air. This happens when the thorax is open by wound or during
intrathoracic operations. Close pneumothorax may be external
and internal. Internal pneumothorax is observed mainly in
tuberculosis, in which formation of caverns tears the visceral
pleural sheet and air enters the pleural cleft from alveoli. The
introduced air into the cleft (close external) will restrict the
lung movements temporarily. This type of pneumothorax may
be used for curative purpose, in the cavernous tuberculosis
treatment (in some forms, when the lung movements are not
desirable due to the hurdling for the repairing of the lung). In

240
some time the air gradually is absorbed by pleural cleft sheets
and the lung begins to breathe in the previous rhythm.

Lung volumes

The inspired air volume and the rate of respiratory

movements determine extent of ventilation of the lungs.
There are certain relations between the inspired air
volume and the total air volume in the lungs. In purpose of
quantitative evaluation of these interrelations the total volume
of the lungs is divided into some composites.
At first we have to give quantitative characteristics of the
total volume of the lungs. It is the maximal air volume that can
be contained in the lungs. This volume consists of 2 ones:
1) the lungs’ vital capacity (LVC) is 70-80%;
2) the residual volume is 20-30 %.
LVC is an air volume that may be deeply expired after
the previous maximal inspiration. It is a functional index of the
lungs and the chest, and in its turn it consists of the following
volumes (Figure 40):
1. Respiratory or tidal volume, which is the air volume
that is inspired or expired in quiet breathing and composes 500
ml.
2. Reserve inspiratory air volume that may be
additionally inspired over the respiratory volume, 2500-3000
ml.
3. Reserve expiratory air volume that may be expired
after the quiet expiration, 1300-1500 ml.
Summarized LVC = 500+3000+1300 = 4800ml.
241
 Figure 40. Lung volumes. TV- tidal volume; IRV - reserve
inspiratory air volume; ERV - reserve expiratory air volume;
RV - residual volume; FRC - functional residual capacity;
FVC – forced vital capacity (LVC); TLC – total lung capacity.

Practically LVC is determined by the spirometer. LVC

depends on sex (in men it is more, than in women by 25%), age
(in children and old persons it is less, than in adults),
constitution, presence of different illnesses of the respiratory
and digestive systems. It’s noteworthy, that even after
deepened expiration some air volume (residual volume equal to
1200ml) remains in the lungs. It exits only in pneumothorax.
The sum of the reserve expiratory volume and the residual
volume is called the functional residual capacity (FRC):
1300+1200=2500ml. The air remained in the air transferring
ways (trachea, bronchi, bronchioles, up to alveoli) does not
participate in the gas exchange, so this space is called as
anatomically dead space. It makes up 1/3 of the respiratory
volume (150 ml). Besides, definition of the functional dead

242
space also exists, that comprises all parts of the respiratory
system, where the gas exchange does not occur. Actually it is
the anatomical dead space plus two types of alveoli (that are
not supplied by blood, but ventilated; and that are supplied by
blood, but not ventilated).

Lung ventilation

Having described the mechanisms of inspiration and

expiration, as well as volumes of the lungs, it is necessary to
dwell on the process of ventilation. There are two types of lung
ventilation:
1) minute volume of respiration (MVR);
2) alveolar ventilation.
MVR is a product of the respiratory volume and the
respiratory movements’ frequency. On average MVR makes up
16 x 500 ml = 8000 ml=8 l. MVR gives a certain information of
the lung ventilation, but does not inform about the breathing
efficiency. Efficiency of breathing is judged by that part of
MVR that enters the alveoli and takes part in gas exchange, i.e.
by the alveolar ventilation. So the alveolar ventilation is a part
of MVR. Hence, MVR = (Valveolar + Vdead space) x f (frequency of
breathing). Considering the respiratory volume consisting of
the alveolar volume (350 ml) and the dead space volume (150
ml), and the alveolar volume, or functional residual capacity
(FRV), which is 2500 ml, we can derive that in each
inspiration only 1/7 of alveolar air is renovated, so

243
 RV − Vdead space 500 − 150 1
Alveolar ventilation = = =
FRV 2500 7
The alveolar ventilation is being accounted as a product
of each of these volumes on the breathing rate, so in normal
deep respiration
Vdead space = 150x16=2400ml/min,
Valv=8000–2400=5600 ml/min.
In superficial and frequent respiration
Vdead space=150x32=4800ml/min,
Valv=8000–4800=3200 ml/min.
Since volume of the dead space is constant, the more the
alveolar ventilation, the deeper the breathing is. The breathing
effectiveness is determined by alveolar ventilation, and
effectiveness of the latter is more in deep and rare breathing,
than in frequent and superficial one.

Gas exchange in alveoli and tissues

The next process followed by is diffusion of gases into

the blood, i.e. the alveolar gas exchange. Previous to this it is
necessary to consider the contents of inspired, expired and the
alveolar air.
Inspired Expired Alveolar
O2 20.94% 16.3% 14.5%
CO2 0.03% 4.0% 5.5%
N2 79.03% 79.7% 80.0%
Differences between the gas contents in the expired and
the alveolar airs is explained by the fact that expired air is a
mixture of the alveolar and the dead space airs. There is no
244
change of N2, which indicates N2 does not take part in the
exchange. The alveolar air is an inner medium of the organism
and determines the gas content of the arterial blood. Its content
is relatively constant and does not depend on the phases of
inspiration and expiration in calm breathing. It also is promoted
by special regulatory mechanisms. Only in deep breathing the
alveolar air content may be changed.
It is clear, that for the exchange gases have to pass from
the alveolar air into the blood and be dissolved in it or be
included into certain compounds to be transferred to tissues
and conversely.
Gas passage into the capillaries of the small blood
circulation and vice versa is realized by means of diffusion,
herein in this process only molecules of the dissolved gas take
part. On the other hand diffusion is possible only in the
presence of partial pressures’ difference in the gases of alveolar
air and their tension in the blood.
Gas tension in liquid is the force with which molecules of
the dissolved gas are driven into the gas medium.
The gas partial pressure is a part of the atmosphere
pressure formed by the given gas in the whole mixture. It is
proportional to the content of the given gas in the mixture and
to the total pressure of that; and does not depend on the gas
nature. So the total alveolar air pressure is summed by the
partial pressures of O2, CO2 and N2.
760mm Hg c.= Po2 + Pco2 + PN2

245
 Since water vapours are also present in the alveolar air
(their partial pressure = 47 mm Hg c.), the total pressure of the
alveolar gas will be: 760 – 47 = 713 mm Hg c.
Having percentage of each gas in the alveolar air and
considering the total pressure, it is possible to calculate the
value of the partial pressure for the given gas by the following
formula:
760 − 47
PO 2 = ×14.5% = 102mm Hg c.
100
PC02 =40 mm Hg c.
PN2= 571 mm Hg c.
Determination of the dissolved (in the blood) gas amount
may be done by the next formula:
α×P
g= × 100 ,
760
where g – amount of the dissolved gas;
α – coefficient of solubility for the given gas;
P – its partial pressure in mixture;
100 – the blood volume in cm3 (ml).
Coefficient of gas solubility is the amount of the given
gas, which can be dissolved in 1 ml of solvent in normal
conditions (00 C and 760 mm Hg c.).
Coefficients of solubility for O2 and CO2 are:
αO2 = 0.022 αCO2 = 0.51, α N2=0.011
So, the amount of the dissolved gas in the blood will be:
gO2 =0.3 %, gCO2 = 3%.
g value depends on the: 1) liquid’s composition; 2)
volume and pressure of the gas above the liquid; 3) liquid’s
246
temperature; 4) gas nature. The more is the gas partial
pressure and the lower is the solvent’s temperature, the more
gas is dissolved in the liquid. Dissolving process goes on until
the dynamic equilibrium between the gas partial pressure above
the liquid and its tension of it in the liquid is reached.

Figure 41. Diffusion of gases through the alveolus-capillary

membrane (aerohematic barrier).

At the same time the gas passage through the alveolar

membrane and its following dissolving in the blood depend on
the: 1) diffusion membrane (alveolus-capillary membrane,
containing alveolus epithelium, surfactant layer and capillary
endothelium) thickness (1.2µm) (Figure 41); 2) diffusion

247
surface (90 m2); 3) partial pressure gradient; 4) gas nature
(diffusion capacity). Lung diffusion capacity (DC) is the gas
amount, passing through the membrane of alveoli in 1 min by 1
mm Hg of the pressure gradient. In norm it forms for O2 25
ml/min mm Hg. For CO2 it is 24 times higher than for O2 in
connection with exclusively high solubility of CO2 in the
pulmonary membranes. The importance of the latter for
diffusion is followed from the comparison of values of the
partial pressure and the tension for O2 and CO2 in the lungs,
blood and tissues (Table 3).
Table 3.
Partial pressures or tentions (mm Hg c.) of gases.
Gases Venous Alveolar Arterial Extracellular Cells
blood air blood liquid
O2 40 102 100 20-40 0-1
CO2 46 40 40 46 60

Owing to these differences CO2 exits (46Æ 40) from the

venous blood into the alveoli and the O2 entrance (102Æ40)
from alveoli into the venous blood takes place with its
following transformation into the arterial blood. In the same
way the O2 and CO2 exchange between the blood and tissues
takes place with transformation of the arterial blood into the
venous one (O2 -100Æ20Æ0; CO2 - 60Æ46Æ40). On the other
hand the time of the blood flow in capillaries of the small blood
circulation is important for the O2 and CO2 diffusion process. It
makes up 0.7 sec; and even in intensive physical work it is

248
enough for the O2 and CO2 diffusion. This diffusion theory was
proposed by Krogh in 1909.

Gas transport by the blood

Oxygen transport. O2 is transported in the bound form

of oxyhemoglobin (19.7%) and free form (0.3%). O2 passing
into the blood (erythrocytes) binds to Hb and forms HbO2 with
very high speed (time of a half saturation is 3 ms). So,
transformation of Hb into HbO2 is conditioned by the O2
tension dissolved in the blood.
There is a dependence of these processes that graphically
is expressed by the HbO2 dissociation (S-shaped) curve (Figure
42).
%HbO2

pO2 mmHg c.
Figure 42. The HbO2 dissociation (S-shaped) curve.

Experimentally it has been established that in PO2= 0-10

mm Hg c. the HbO2 formation is going on very slowly because
the Hb affinity to O2 is not significant. With the HbO2
following formation the affinity of Hb to O2 grows up abruptly

249
(in PO2=20mm Hg c., 40% HbO2 and PO2=60mm Hg c., 90%
HbO2). From the beginning PO2 = 80mm Hg c. the curve
becomes parallel to the abscissa axis, that testifies full
saturation of Hb by oxygen.
Some factors, such as temperature, pH, CO2
concentration in the blood, content of diphosphoglycerate in
erythrocytes influence on the duration of this process. Increase
of temperature, of DPG and CO2 content, and decrease of pH
shift the curve to the right that corresponds to the affinity of Hb
to O2 decrease. These processes are common in tissues, where
intensive metabolism occurs, in result of which CO2
concentration increases. The more CO2 concentration in the
blood, the more intensive is dissociation of HbO2 and the lesser
the HbO2 concentration becomes. This effect is called Bohr’s
effect.
The blood oxygen capacity is conditioned by Hb content
in the given blood. This index is determined by the maximal
quantity of O2 in 100 ml blood in condition of the haemoglobin
complete saturation by O2. It is estimated by the following
calculation: 1g Hb can bind to 1.34 ml O2. In case of Hb
concentration 14.7% (100ml of blood contains 14.7g of Hb) the
amount of O2 will be: 1.34 ×14.7=19.7 ml or 19.7v%. So, the
O2 total content in the arterial blood composes approximately
20 v%, in which 0.3 v % is simply solved O2 and 19.7 v% is O2
bound with Hb. The venous blood contains 12 v% O2.
Difference in the gas contents in arterial and venous bloods is
called artery-venous difference and shows the O2 utilization
degree (UDO2) by tissues. Consequently, this value will be:
250
 (20 − 12) × 100
UDO 2 = = 40% .
20
In rest this index varies in terms of 30-40%. In physical
exertion it increases up to 50-60%.
Carbon dioxide transport. CO2 is transported in
dissolved and bound forms. Partial tension of CO2 in tissues
makes up 60 mm and in the arterial blood 40 mm Hg c. This
difference leads to the CO2 diffusion into the blood. In
erythrocytes PCO2=O, so CO2 passing into them binds to H2O
and forms H2CO3. This reaction is catalysed by the enzyme
carboanhydrase. CO2+H2O→H2CO3. Along with it KHbO2→
KHb+O2. O2 enters tissue, H2CO3 reacts with KHb in
erythrocytes: H2CO3 + KHb = KHCO3+HHb.
These reactions occur due to different acidic properties of
the following compounds: HHb<H2CO3 < HHbO2. CO2 binding
with HHb forms HHbCO2 (carbohemoglobin). Some part of
H2CO3 (HCO3-) exits into the plasma and reacts with NaCl.
Then, HCO3-+ NaCl = NaHCO3+Cl-. To support the osmotic
pressure of erythrocytes Cl- enters erythrocyte. So, during
transportation CO2 forms several combinations: KHCO3,
HbCO2, and NaHCO3.
Formation of H2CO3 and its dissociation depend on the
O2 concentration in the blood. This dependence is named
Werigo`s or Holden’s effect. The more O2 concentration is, the
more is H2CO3 dissociation.
The venous blood contains 55-58 v% CO2, from which:
4% HHbCO2; 3% dissolved form of CO2 and 51% carbonates
(KHCO3 and NaHCO3).
251
 Regulation of respiration

The physiological role of the respiration is the O2 supply

provision for the organism and the CO2 removal from it,
connected with its demands at the moment. So, respiration has
to be controlled and regulated, that is realized by means of
complex neuro-humoral pathways. Neuronal regulation is
provided by respiratory centres, located in various parts of the
CNS that are responsible for the coordinated rhythmical
activity of the respiratory muscles, as well as for adaptation of
respiration to the changes occurring in the internal and external
media of the organism. Certain groups of the nerve cells are
indispensable to the rhythmical activity of the respiratory
muscles, and form a respiratory centre (RC). The RC is
situated in the medulla oblongata in the 4-th ventricle, near the
inferior angle of the rhomb-shaped pit. Localization of the RC
first was found out and explained by Flourens by means of
transversal sections of different parts of the CNS. The 1-st
section was done between the cervical and thoracic segments
of the spinal cord, which brought to stoppage of the intercostal
muscles’ activity. The 2-nd section was done between the
cervical spinal segment and the medulla oblongata. In that case
the diaphragm activity also was inhibited. It was assumed that
the RC must be located above section 2. The 3-rd section (in
another animal) was done between the medulla oblongata and
the pons varolii. But it didn’t stop breathing generally, but
caused rhythmical impairments of the process. Consequently,
the RC is located in the medulla oblongata. In destroying this

252
centre, breathing stops. The RC consists of the ventral and
dorsal parts. In the dorsal part inspiratory neurons prevail, and
in the ventral one, both inspiratory and expiratory neurons are
available. Impulses from the dorsal part are mostly sent to the
cervical segments (C3-C4), and thereby to the diaphragm.
Impulses from the inspiratory neurons of ventral part are sent
to the thoracic segments (Th2-Th6), where the motoneurons of
external intercostal muscles are. Impulses from the expiratory
neurons of the ventral part are sent to the Th8-Th10 segments
that realize deep expiration.
There are also groups of cells located in various other
parts of the CNS that can take part in the respiration regulation:
the reticular formation of the medulla oblongata, the pons
varolii that serves as the pneumocontroling centre –
“pneumotaxic centre”, the hypothalamus and cortex.
So, the respiratory centre is an integrity of the
interconnected neurons that ensures the coordinated rhythmic
activity of the respiratory muscles and the breathing adaptation
to the changes of the internal and external media.
Respiratory centre function is supported by:
I. automatism;
II. neuro-humoral way;
III. reflector way.
I. The neurons of the RC are characterized by
automatism, which evident is the fact that rhythmical
oscillations of bioelectric potentials occurring in these neurons
can be recorded. This automatism is much weaker than that of

253
the heart. Apart from this, it differs from the heart automatism
by the follows:
1) not only excitatory, but also inhibitory elements are
localized here;
2) it also submits to the cortex activity, so it is a limited
voluntary process;
3) it is more sensitive to chemical substances;
4) for normal activity it needs getting of nerve impulses
(information) coming from the peripheral reflexogenic zones.
II. The fact, that the RC is controlled by the neuro-
humoral way, was evident by Frederic’s experiment. Two dogs
were anaesthetized and their carotid arteries and jugular veins
were cut and joint, so that the head of each dog was supplied
with the blood not from its own trunk, but from the other.
Compression of the trachea in one of the dogs caused asphyxia,
followed by respiration arrest (apnea) some time afterward,
and was accompanied with severe hyperpnoea in the other dog.
It was explained by the fact that closure of the trachea in the
first dog led to accumulation of CO2 (hypercapnia) in the blood
and to fall in its O2 content (hypoxemia). The blood passed to
the head of the second dog and stimulated its respiratory
centre. As a result, augmentation of respiration
(hyperventilation) occurred in the second dog, leading to
decrease in CO2 tension and increase in O2 tension in the
blood. Blood rich in O2 and poor in CO2 flew from the trunk of
this dog into the head of the first one, causing apnea.
So it was shown, that the activity of the respiratory centre
alters with changes in CO2 and O2 tensions in the blood. At
254
first it was assumed to be just in humoral way, but presently it
is proved to be neuronal too. There are appropriate receptors
for these substances – chemoreceptors. There are two types of
them: central and peripheral. The central ones are localized in
the medulla oblongata in the deepness of ≈ 0.2 mm. These are
sensitive to CO2 and H+ in the blood. The peripheral ones are
localized in the aortal arch, at the site of ramification of a.
carotid and are sensitive both to CO2 content increase and O2
content decrease in the blood. It has been revealed that the
peripheral chemoreceptors are more prompt in their action,
than the central ones. For instance, in CO2 content increase the
excitation, coming from the peripheral chemoreceptors,
appears already in 3-5 sec, but for the central receptors, it
makes up 20-30 sec. It is explained that impulses from the
peripheral chemoreceptors directly stimulate through the
nerves the respiratory neurons, but for the central
chemoreceptors some time for penetration of substances (CO2,
H+) into the brain tissue is required.
The mechanism of the first inspiration in newborns is
connected with these chemoreceptors: fetus in its intra-uterus
life is supplied by O2 from the mother’s blood and its own
lungs don’t act. After the birth, when newborn is off the
mother’s organism, the CO2 content increase in the blood
stimulates the RC that causes the newborn’s first inspiration.
For this process the influences of light, temperature change and
other stimuli (mechanical stimulation from the skin receptors)
are also important.

255
 III. The reflector regulation is commonly conditioned by
impulses arising in different reflexogenic zones, where
mechanoreceptors are available. By their localization, functions
and their final effect they can be:
1) pulmonary stretch receptors;
2) irritant receptors;
3) J-receptors, which derive from the term “juxsta-
capillaries”.
The stretch receptors are the main receptors ensuring
breathing. They are located throughout the pulmonary airways
(in the muscular tissue of the bronchi, trachea) and their
excitation is connected with the lung walls’ inflation. They
adapt very slowly to a sustained stretch and provide
information about the lung volume to the brain. From these
receptors n. vagus derives, so they are considered to be the
terminal parts of n. vagus. Impulses coming from these
receptors provide periodical activity of the RC, i.e. the
rhythmical sequence of inspiration and expiration. Just these
receptors send impulses by the afferent branches of n. vagus to
the RC and provide automatism.
The reflexes considered as Herring – Breuer reflexes
underlie breathing process. They were described in 1868 and
formed the basis for the concept of the respiration reflector
self-regulation. It is displayed as follows: with each inspiration
impulses arise in the lungs, that inhibit inspiration and
stimulate expiration, and with each expiration causes
inspiration process. This point of view was the consequence of
the following reflexes:
256
 1. In inspiration inflation of the lungs with additional air
causes immediate stoppage of inspiration and the expiration
stimulation. It is denoted as “inspiration - inhibitory” reflex.
2. In expiration introduction of additional air into the
lungs brings to the expiration prolongation. It is denoted as
“expiration - facilitating” reflex.
3. In case of a strong inflation of lungs, with excitation of
irritant receptors and additional stimulation of the RC the
convulsive inspiration, “sigh” is observed. It is denoted as
“paradoxal breathing of Hedd”.
By means of these reflexes the recurrent connection
between the RC and the respiratory apparatus is realized.
Inspiration referring neurons are located in the dorsal
part of the RC. They are divided into two groups: inspiration
providing (Iα) and inspiration inhibiting (Iβ). Being excited
from chemoreceptors Iα send impulses to the motoneurons of
the spinal cord cervical and thoracic segments. The
motoneurons innervate the intercostal muscles and diaphragm
and cause contraction of the latters, i.e. provide inspiration.
During inspiration the stretch receptors are excited and
impulses from them flow to Iβ and activate it (Figure 43). Iβ
neuron inhibits Iα one and thereby cause cessation of
contraction of the diaphragm and intercostal muscles, so that
inspiration is arrested transforming into expiration. Herein the
inhibitory influence of Iβ on Iα is mediated by specific
inhibitory neurons. When expiration is already preceded, the
stretch receptors of the lungs are not excited and the impulses

257
do not get to the Iβ, consequently they do not get to the
inspiration inhibitory centre and Iα is rid of inhibition, so they
are able to send impulses to the spinal cord. Cutting of the n.
vagus causes inspiration to become much slower, deeper and
longer and its transition into expiration hurdles. But
nevertheless the inspiration is converted into expiration due to
pneumotaxic centre, which controls activity of the inspiratory
and expiratory centres lying below. It stimulates the expiratory
centre during inspiration and thus ensures rhythmical
alterations of inspiration and expiration by the following
manner. The impulses from the Iα neurons are conducted to the
pneumotaxic centre and pass from it to the expiratory neurons
of the RC with stimulation of expiration.
PTC

+
EC + + IIN
_
_ +
Iβ Iα ChR
+

n. vagus +
MN
+
RM
+
LSR

Figure 43. Reflector regulation of respiration.

Iα − inspiration providing neuron; Iβ − inspiration inhibiting
neuron; ChR – chemoreceptors; MN- motor neurons of spinal
cord; RM – respiratory muscles; LSR – lung stretchreceptors;
EC – expiratory centre; IIN- inhibitory interneurons; PTC –
pneumotaxic centre
258
 Similar respiratory changes are encountered when the
vagus nerves are intact, but the brain stem is cut at the pons,
disconnecting the pneumotaxic centre from the medulla. If
both vagus nerves and the pons varolii are cut, no excitation of
the expiratory centre occurs and breathing ceases at the peak of
inspiration, and the animal dies.
Irritant receptors are located along the trachea, bronchi
in the epithelial and sub-epithelial layers. These receptors can
be excited in great alterations of the lungs’ volume, as well as
in chemical and mechanical irritation of mucous.
J-receptors are located in the intracellular space of
alveoli close to bronchial capillaries. They are excited in
increase of the arterial pressure in the small blood circulation
or when the liquid amount in the intracellular space increases
(in the lung edema, pneumonia). Impulses pass through the
unmyelinated nerves to the RC, distinctly from the stretch
receptors, which send their impulses by the quick myelinated
nerves. In this case breathing intensification takes place.
Defence reflexes. They ensure the removal of various
irritating agents and prevent their entry into the lungs. Dust,
mucus, acids, bases or foreign bodies accumulated in the
respiratory passages, cause spasmodic expiratory movements
by stimulating the nerve endings. The glottis is closed at the
beginning of expiration, but as soon as definite pressure is
produced in the lungs and the respiratory passages, it opens
suddenly and air is expelled with a force from the respiratory
passages. Thus a cough occurs, which is the forcible thrust of

259
air and helps to clear the respiratory tract. If the receptors of the
nasal mucus are stimulated sneezing reflex occurs.
Respiration can be regulated not only by the main
respiratory centre, but also by the other parts of the CNS.
These are the hypothalamus, which is of importance in physical
work, emotional stress, pain influence, and temperature
increase. Herein, the intensification of respiration occurs. The
cortex also influences on the process of respiration. It inhibits
the RC. In case of its removal intensification of respiration is
observed. Owing to the cortex influence respiration may be
voluntary; e.g. divers before diving into water several times
inspire air on purpose to supply tissues by O2.

Respiration under various circumstances

Respiration at reduced atmospheric pressure. The

study of this problem is important, because some people deal
with it by their specialty and work in this condition (alpinists,
pilots, parachute jumpers). The main factor in high altitudes
(reduced atmosphere pressure) is severe hypoxia and
hypocapnia due to decrease of O2 and CO2 partial pressures.
Hypoxia in general can be:
1. Hypoxic hypoxia (at high altitudes).
2. Anemic hypoxia (when the O2 partial pressure is
normal, but the Hb content in erythrocytes is decreased).
3. Circular hypoxia is not connected with the above-
mentioned factors, but circulation impairments are present:
heart troubles, ischemic conditions, etc.

260
 4. Histological (tissue) hypoxia (when the O2 utilization
by tissues is disturbed oxidative phosphorylation).
5. Physiological hypoxia (in hard physical work lack of
O2 may be observed).
6. Hyperoxic hypoxia (in case of damage to the
respiratory centre or in intoxication of tissues).
Hypoxia, observed in certain respiratory and circulatory
changes has an adaptive character. A fall in blood O2 content
stimulates the chemoreceptors of the vascular reflexogenic
zones and produces an increase of the pulmonary ventilation,
accelerates and increases the cardiac output, augments the
amount of circulating blood owing to its discharge from the
spleen and other blood reservoirs and opening the capillaries.
The accumulation in the tissues of incompletely oxidized
metabolites, that stimulate the respiratory nerve centres, also
contributes to the development of these phenomena. If the
factor responsible for hypoxia persists for a long time
(prolonged residence at high altitudes, or certain types of
cardiac disturbance), an adaptive increase in Hb content and in
the number of erythrocytes occur.
At altitudes (1-1.5 km) respiration intensification occurs.
At 2.5-5 km the respiration acceleration is accompanied by the
compensatory mechanisms: 1) increase of the heart rate; 2)
activation of hemopoiesis; 3) formation of 2,3 –
diphosphoglycerate, that reduces the O2 affinity to Hb and so
stimulates the HbO2 dissociation. In this case hypocapnia will
be observed, that will result in the RC inhibition.

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 Starting from 5 km “mountain sickness” can develop, in
which the organism is not capable to cope with the formed
problem, and so fatigue, cyanosis, decreased heart rate,
headache, vomiting and low arterial pressure are manifested.
At the altitudes over 7 km unconsciousness is observed. In
order to elevate at the altitudes from 7 km to 12 km man should
use special balloons, where the gas mixture has to have a
partial pressure more than the external air pressure. In this case
sometimes the CO2 content in balloon is increased to activate
the respiratory centre additionally.
Periodic respiration. A deficient supply of O2 to the
respiratory centre sometimes results in abnormal respiration,
which is called periodic or Cheyne-Stokes respiration (Figure
44). It is connected by decrease of the RC neurons’ functional
activity and characterized by the recurrence of pauses between
groups of respiratory movements. The pauses may last from 5
to 20 seconds; and each pause is followed by weak respiratory
movements and then by rapid strengthened ones. The latter
having reached a maximal volume, gradually, but quite quickly
become weaker until they cease completely. A new pause
occurs, after which the whole cycle is repeated. One cycle lasts
30-60 sec. The main reason for stoppage (pause) of respiration
is hypocapnia, which reduces excitability of the respiratory
centre. The accumulation of CO2 during the periodic pauses
causes strengthening of respiration movements, which increase
the CO2 elimination. Since the CO2 content in this condition
drops below the level required to stimulate the respiratory
centre.
262
 Figure 44. a) Cheyne-Stokes respiration;
b) CO2 tension in the blood.
This respiration is often observed in mountain sickness,
as well as in newborns, prematurely-born babies and different
disorders of CNS: ischemia, haemorrhages and other
conditions of the RC decreased activity.
Respiration in increased atmospheric pressure
conditions. At great depth under the water (in each 10 m the
pressure enhances by 1 atm), where divers have to work, there
could be two hazards: hyperoxic state of the organism that
evokes a toxic effect on tissues; and a great amount of
dissolved gases in the blood and tissue fluids.
Work at depth requires special measure for gradual
decompression. When a diver is brought to the surface slowly
(gradually decompression), gases escape from the body with
expired air, and he is out of danger. But in sudden
decompression, for example, a diver is brought to the surface
too quickly, the gases have no chance to escape and as their
solubility in blood decreases with the fall of pressure to
normal, gas bubbles appear. This can cause embolism of the

263
vessels, blockade of the vessels. As carbon dioxide and oxygen
can form some compounds in the blood they are less hazard
than nitrogen, which is dissolved in fats and lipoids and
accumulated in a great amount in the brain. The condition
caused by rapid decompression is called “caisson disease”. It
is characterized by pains in joints and a number of cerebral
symptoms (dizziness, vomiting, dyspnea and unconsciousness).
A suffer should be treated by being exposed again to the effect
of high pressures so that the gas bubbles can dissolve again. At
present divers working at great depths are given a gas mixture
containing helium instead of nitrogen, as the former is almost
completely insoluble in water and blood.
Respiration during physical effort. Since both
respiration and circulation are concerned in satisfying the
organism’s requirements of O2 and in removing from it the
formed CO2, it is obvious that the intensity of respiration is
closely associated with the intensity of oxidative processes; the
depth and rate of respiratory movements diminish at rest and
increase during work. Thus, the volume of pulmonary
ventilation rises to 50 l per minute. O2 uptake of a resting
individual is 250-350 ml per min, and may reach 4500-5000 ml
in work. The O2 utilization degree increases markedly with
intensive muscular work (in norm – 40%, in work – 60%).
cardiac contractions may be doubled (from 70 to 140 - 150 per
minute); systolic volume can increase from 70 to 220 ml, so the
minute volume from 5-6 l to 20-25 l. Sequence of the processes
may be described as follows: hypoxia→
hyperventilation→hypocapnia (due to the increased removal of
264
eliminated CO2). In this case we can expect that respiration has
to be inhibited, but actually it doesn’t occur, since some
metabolites (lactic acid, etc) formed during strenuous work
accumulate in the blood. The latters are the stimulators of the
RC activity. So, even after breaking of the muscular work the
respiration remains intensified, since concentration of the lactic
acid (H+ ions) is still preserved. Apart from this, a lot of
compensatory mechanisms, like the liberation of erythrocytes
from the blood depots, reduction of the water content through
sweating, which result in a rise in Hb concentration and,
consequently, in an increase blood oxygen capacity. All
contribute to grater carriage of O2 and the O2 supply increase to
the tissues of organism in physical effort.

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CHAPTER 9.
PHYSIOLOGY OF THE DIGESTIVE SYSTEM

The human organism needs various substances and a

considerable amount of energy for its normal functioning. The
human body can uptake organic and inorganic substances,
only after nutrients’ preliminary processing, which is realized
by the digestive system.
Digestion is a complex physiological process during
which food undergoes physical (mechanical) and chemical
changes. Physical changes of food comprise mechanical
processing, fragmentation and swallowing and dissolution.
Chemical changes consist of a sequence of reactions between
the nutrients and the components of digestive gland secretion,
hydrolytic enzymes. The main groups of these enzymes are:
proteases, lipases and carbohydrases.

Functions of the digestive system and types

of digestive processes

The functions of the digestive system are divided into

digestive and indigestive ones. The digestive functions are:
secretor, motor and absorption.
The main stages of digestion are accomplished by
enzymes secreted by the digestive glands, i.e. they are ensured
by secretor function of the digestive tract.
Motor function is performed by muscles of the
alimentary tract and makes possible mastication, food and its

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indigested parts movement through the digestive conveyer,
microvillus contractions. The motor function also promotes
passage of digestive secrets into the gastro-intestinal tract
(opening and closure of the ducts’ sphincters), mixture of food
or chyme with digestive juices.
The simple products of hydrolyzed nutrients are absorbed
in the digestive tract, which condition the absorption function.
Organs of the gastro-intestinal tract take part in other,
indigestive functions: participation in regulation of
homeostasis (water-salt balance), excretory function (excretes
the hard metals’ salts, bile pigments, exogenous substances
including medical preparations), endocrine function (diffuse
endocrine system produces biologically active substances:
gastrin, bombesin, prosecretin, etc.), participation in the
hemopoiesis regulation (it produces internal Castle’s factor
regulating absorption of vit. B12 regulator of the hemopoiesis)
and defence function (saliva and digestive juices contain
antibacterial substances).
According to the origin of digestive enzymes digestion
can be proper (under the action of macroorganism’s digestive
juices), autolytic (under the action of exogenous enzymes
located in the food) and symbiotic (under the action of enzymes
produced by macroorganism’s microflora).
Processes of digestion are classified as intracellular and
extracellular. Two types of digestion, distant (cavital) and
membrane (contact, surface) are distinguished in extracellular
digestion.

267
 Intracellular digestion is accomplished by nutrients
which enter the cells by means of phagocytosis or pinocytosis.
Nutrients are hydrolyzed by cellular (lysosomal) enzymes. In
the human body intracellular digestion occurs in leucocytes and
cells of the lympho- reticular system.
The distant or cavital digestion is realized by enzymes
contained in the juice of the gastro-intestinal tract glands at a
considerable distance from the site of enzyme formation.
Membrane digestion is carried out by membrane-bound
enzymes and simultaneously the hydrolyzed nutrients are
conveyed into the blood and lymph. Structures with bound
enzymes are represented in the small intestine by glycocalyx.
Here membrane digestion takes place to be preceded by gastric
and small intestinal cavital digestion, i.e. the nutrients are
hydrolyzed at first in the small intestine by the pancreatic
enzymes. The formed oligomers undergo hydrolysis by the
adsorbed pancreatic enzymes of glycocalyx. Due to this
hydrolysis the formed dimers are hydrolyzed directly at the
membrane by the membrane-bound intestinal intrinsic
enzymes. The latters are synthesized in enterocytes and are
carried into the membranes of their microvilli.

Digestion in the mouth

The first part of digestive conveyer is the mouth, where

food is broken to small particles and moistened with saliva, its
taste properties are analyzed, and initial hydrolysis of certain
nutrients and formation of the bolus occur. In the mouth the
taste, tactile, temperature and pain receptors are located. Test

268
receptors are divided into the following types: sour, sweet, salt
and bitter receptors. Their location on the tongue is not
proportional. Salt receptors are more at the top of the tongue,
sweet and sour receptors on the sides and bitter, on the root of
the tongue.
The stimulation of receptors is important for the saliva
secretion as well as for mastication and swallowing of bolus.
Mastication. Mastication is a reflex act. Food in the
mouth stimulates the receptors from which signals are
conveyed along the afferent fibres of the trigeminal nerve to
the mastication centre, and from this centre, along the efferent
fibres of the same nerve, to the mastication muscles.
Mastication has the following phases: the rest phase, intake of
food into the mouth, the phase of orientation, the main phase,
formation of the bolus and swallowing.
Salivation. Saliva plays an important role in the initial
stage of digestion. It is secreted by three pairs of large salivary
glands: parotid, sub-maxillary and sublingual. A great number
of small glands are situated on the surface of the tongue and the
mucous membrane of the palate and cheeks. According to the
consistency of saliva produced, three types of salivary glands
are distinguished (Figure 45): serous (parotid gland and small
glands on the sides of the tongue), mucous (small glands of
palate and root of the tongue) and mixed (submaxillary,
sublingual glands and small glands on the tip of the tongue,
cheeks and lips). When food is not taken, saliva is secreted in
man at an average rate of 0.24 ml/min to moisten the oral

269
cavity. During mastication 3-3.5 ml/min of saliva is secreted.
From 0.5 to 2 l of saliva is produced daily.
Composition and properties of saliva. Saliva is a
viscous, slightly opalescent and cloudy fluid with a consistency
of 1.001-1.017. Mixed saliva contains 99.4-99.5% of water; the
remaining part is a dry residue. PH of mixed saliva is 5.8-7.4.
Dry residue consists of organic and inorganic substances. The
inorganic components of saliva are: chlorides, carbonates,
phosphates and other salts of sodium, potassium, calcium,
magnesium and others. The osmotic pressure of saliva is
lower, than that of blood plasma. The organic components of
saliva are: various proteins, free aminoacids, carbohydrates,
urea, ammonia, creatinine and other substances. The
significant viscosity of saliva is conditioned by mucin, included
into the composition of saliva. Saliva is rich in enzymes:
alpha-amylase (destroys polysaccharids with the formation of
dextrins, which are further broken down to form maltose,
disacharide) and maltase (destroys maltose into two particles).
Saliva amylase begins acting in the mouth, but insignificantly
because the food remains here for a short time. Hydrolysis of
carbohydrates by saliva enzymes continues in the stomach only
in the deep layers of bolus. Saliva possesses a bactericidal
property due to enzyme lysozyme. Kallikrein found in saliva
contributes to the formation of kinins which are vasodilators.

270
(parotid gland) (sublingual gland)
Serous gland Mucous gland
(submundibul gland)
Mixed gland

Figure 45. Various secretor cells of the saliva glands.

Control of saliva secretion. The salivary secretion is

realized by reflector mechanism. In intake of food and
excitation of mouth receptors by it the stimuli are transmitted
along the afferent fibres of the trigeminal, facial,
glossopharyngeal and vagus nerves to the main salivation
centre, located in the medulla oblongata. Efferent impulses
come to salivary glands, to submaxillary and sublingual glands
along chorda thympani and to parotid gland along
glossopharyngeal nerve fibres. Parasympathetic innervation of
the salivary glands arises from the nuclei of the medulla
oblongata. Sympathetic innervation of the glands begins from
the lateral horns of the second to fourth thoracic segments of
the spinal cord. Stimulation of the parasympathetic nerve
causes activation of salivary secretion. The sympathetic nerve

271
also activates salivary secretion, but in contrast to the
parasympathetic nerve, when serous saliva is secreted, it
increases secretion of viscous saliva due to high concentration
of organic substances. Besides, salivation can be realized by
conditional reflexes in response to the sight and smell of food.
Methods of studying secretion of saliva. To study the
salivary glands’ activity Pavlov suggested creating a fistula of
the excretory duct. This was accomplished surgically as
follows. The papilla of the duct of the parotid or submaxillary
gland was separated from the surrounding tissues together with
a part of the mucous, brought outside through a wound made in
the cheek and sutured to the skin. Saliva secreted by the
submaxillary or parotid gland can be obtained in man through a
small metal funnel, known as a Lashley-Krasnogorsky capsule,
fastened to the mucous membrane at the opening of the
excretory duct of the examined gland.
Deglutition. Deglutition (swallowing) is a reflex act,
which begins from the tongue root receptors excited by bolus.
The centre of swallowing is located in the medulla oblongata.
The swallowing reflex consists of a series of successive links.
Their strict coordination is effected by a complicated
relationship between various parts of the CNS, from the
medulla oblongata to the cerebral cortex. Stimulation of the
tongue root receptors causes contraction of the muscles that
elevate the soft palate, which prevents the food entering the
nasal cavity. Tongue movements help to push the bolus into the
pharynx; simultaneous contraction of muscles that move the
hyoid bone and raise the larynx causes the epiglottis to close
272
the entrance to the larynx, so that food is prevented from
entering the respiratory passages. As soon as food enters the
pharynx, muscles that cause constriction of its lumen above the
bolus contract, and the bolus passes into the esophagus. The act
of deglutition is separated into three phases: 1) oral
(voluntary); 2) pharyngeal (quick involuntary); 3) esophageal
(slow involuntary).

Digestion in the stomach

The digestive functions of the stomach are as follows:

storage of food, its mechanical and chemical processing and
gradual evacuation of the food contents in portions into the
intestine.
In the stomach we differentiate 3 types of secretor cells:
chief glandulocytes producing inactive enzymes, parietal
glandulocytes, which secret hydrochloric acid and mucocytes
(accessory cells) producing a mucoid secret. There are no
pariental glandulocytes in the pyloric part of the stomach.
From 2 to 2.5 l of gastric juice is secreted daily in the stomach.
It is a colorless clear fluid containing hydrochloric acid (0.3-
0.5 %) and having, therefore, an acid reaction (pH 1.5-1.8).
The chief glandulocytes synthesize and secrete two
groups of pepsinogens. Those of the first group (5 in number)
form in the fundus and pepsinogens of the second group (2 in
numbers) are synthesized in the pyloric part of the stomach.
Pepsinogens are activated in the acid medium by splitting off
the pepsin-inhibiting polypeptide from them. The pepsins
proper are enzymes which hydrolyze proteins at a maximum

273
rate at pH of 1.5-2. Another of their fractions hydrolyses
proteins at maximum pH of 3.2-3.5 and is called gastricsin.
The gastric juice of an adult is marked by mild lipolytic
activity. This activity is important for a breast-fed infant
(breakdown of milk fats that are already emulsified).
The salivary carbohydrases continue to act upon the
carbohydrates in the central part of bolus, where the acid
gastric juice (that arrests the effect of carbohydrases of the
saliva) has not penetrated yet.
Hydrochloric acid of the gastric juice causes denaturation
and swelling of proteins facilitating in this manner their
subsequent breakdown by pepsin, activates pepsinogen and
prosecretine, creates an acid medium which is necessary for the
breakdown of food proteins by pepsins; it also contributes to an
antibacterial effect of the gastric juice and regulation of the
digestive tract motor activity.
Mucoids are an important component of the gastric juice.
They protect the gastric mucosa from mechanical and chemical
irritations. The secretion of mucus is induced by local
stimulation of the mucous membrane and is regulated by the
vagus and splanchnic nerves. Gastromucoprotein (Castle’s
intrinsic factor) is also a mucoid.
Besides these above mentioned components, the gastric
juice consists of other organic (urea, uric and lactic acids,
aminoacids, polypeptides) and inorganic (chlorides, sulphates,
phosphates, bicarbonates of sodium, potassium, calcium and
magnesium and ammonia) substances. The osmotic pressure of
the gastric juice is higher than that of blood plasma.
274
 Control of gastric juice secretion. The gland of the
human stomach secretes a small amount of gastric juice when
digestion is not taking place. The intake of food increases
sharply its secretion by the glands due to their stimulation by
neuronal and humoral mechanisms. The stimulating and
inhibitory factors are responsible for the dependence of gastric
juice secretion on the type of food. The character of the food
determines not only the volume and duration of secretion, but
also its acidity and the pepsin content, e.g. the values of
secretion in response to three food stimuli (meat, bread, milk)
are arranged as follows in a decreasing order:
Volume of juice Meat Bread Milk
Duration of secretion Bread Meat Milk
Acidity of juice Meat Milk Bread
Digesting power of juice Bread Meat Milk

The chief and parietal glandulocytes and the mucocytes

of gastric glands are stimulated by vagus nerve. The
sympathetic nerve has an inhibitory effect on the gastric glands.
Gastrin is a strong stimulator of the gastric glands. It is
released from the G cells. Most of them are located in the
pyloric mucus. Gastric secretion is reduced sharply after
surgical removal of the pylorus. The release of gastrin is
increased by the vagus and by mechanical and chemical
stimulation of this region. Products of protein digestion
(peptides, aminoacids), meat and vegetable extracts are
chemical stimuli of the G cells. The release of gastrin
diminishes when pH of the pyloric part of the stomach reduces

275
(in increased secretion of hydrochloric acid by the gastric
glands) and ceases at pH 1.0. Gastrin, therefore, takes part in
autoregulation of gastric secretion, depending on the pH of the
pyloric contents. Gastrin stimulates the parietal glandulocytes
to the greatest extent, the chief glandulocytes to a lesser extent
and the mucocytes still lesser.
Histamine is also a stimulator of the gastric glands and is
formed in the mucous membrane of the stomach. It stimulates
the parietal glandulocytes, and has a weaker effect on the chief
glandulocytes. The secretion of histamine is activated by n.
vagus.
Products of protein digestion absorbed into the blood
also stimulate gastric secretion.
Bombesin stimulates secretion of the gastric gland
through release of gastrin from the G cells.
The hormone motilin produces a milder stimulating effect
on the stomach secretion.
Secretin and cholecystokinin-pancreozymin inhibit
gastrin and histamine-stimulated hydrochloric acid secretion,
but slightly intensify the secretion of pepsin.
Other intestinal hormones (gastric inhibiting and
vasoactive intestinal peptides, as well as neurotensin,
somatostatin, enterogastrone, bulbogastrone) inhibit the
secretion of hydrochloric acid in the stomach.
Hyperacidity of the duodenal contents inhibits
hydrochloric acid secretion by the gastric glands through reflex
or through duodenal hormones, i.e. autoregulation occurs.

276
 Phases of gastric secretion. In gastric secretion three
phases are differed: “cephalic”, gastric and intestinal.
The first phase (“cephalic”) of secretion begins due to
conditional and unconditional reflexes. Conditional reflexes
originate from the receptors of the eyes, nose and ear by the
sight and smell of food and by the sound and all the
circumstances associated with its intake. Unconditional
reflexes begin from the mouth and pharynx receptors. The
existence of the first phase of gastric secretion has been proved
in experiments with sham feeding esophagostomized dogs with
a gastric fistula. Food given to the dog falls out of the
esophagus and does not reach to the stomach, but secretion of
gastric juice begins. The “cephalic” phase prepares the stomach
in advance for the food.
The gastrin mechanism also contributes to the first phase
of secretion. This is proved by the increase of the blood gastrin
content in dogs during sham feeding. In animals with removed
pyloric part of the stomach in which gastrin is produced,
secretion decreases in the first phase.
Secretion occurs in the “cephalic” phase due to excitation
of the feeding centre located in the medulla oblongata.
The second phase (gastric phase) secretion is realized
owing to irritation of the stomach mucous membrane. This
phase is conditioned by neuro-humoral and local mechanisms.
The neuronal mechanism has reflector nature. The impulses
originated in excitation of mechanoreceptors of the stomach
cause the stimulation of feeding centre and by the vagus the
stomach glands. Simultaneously mechanical excitation of the
277
stomach, its pyloric part, through the intramural nervous
pathways leads to the gastrin release from the G-cells. The
release of gastrin in the gastric phase of secretion is also
augmented by the products of protein hydrolysis, some
aminoacids and by meat and vegetable extracts. Histamine is
of a definite importance in accomplishing the gastric phase of
secretion. It has a stimulating effect on the stomach glands.
The third phase of gastric secretion (intestine phase) is
conditioned by the excitation of intestine mechanoreceptors
with the indigested chyme. The stimuli reaching the feeding
centre by the afferent nerves provide the excitation of stomach
secretion. The products of the nutrients’ hydrolysis,
particularly proteins, which are absorbed into blood, also
contribute to the stimulation of gastric secretion. But later the
gastric secretion is inhibited by the substances of intestinal
contents (products of fat hydrolysis, polypeptides and
aminoacids). The release of the hormones, secretin and
cholecystokinin-pancreazymin inhibits the secretion of
hydrochloric acid. Other intestinal hormones from the group of
gastrones also contribute to inhibition of gastric secretion.
Evacuation of food from the stomach to the duodenum is
due to contraction of muscles of the entire stomach,
particularly to strong contractions of the pyloric muscles, rather
than to opening of the sphincter. It is the contractions of the
pylorus that create a high pressure gradient between the
stomach and duodenum. The evacuation process depends on
the consistency, chemical composition, pH, and volume of the
gastric and intestinal contents.
278
 Methods for investigating functions of the stomach.
The fundamentals of physiology of the digestion system were
elaborated by Pavlov and his school. Before Pavlov, functions
of the digestive organs were mainly studied in acute
experiments in which the organism’s normal condition was
disturbed by an inflicted trauma. At first, Russian surgeon
Basov suggested collecting the gastric contents through a
created “artificial entry into the stomach”, fistula. A fistula is
an artificial communication between a hollow organ or the
duct of a gland and the body surface. But the juice, obtained by
such method was not pure, because it was mixed with the food.
Pure gastric juice was collected from animals with a gastric
fistula and esophagostoma in experiments with sham feeding
(the operation was suggested by Pavlov and Shumova-
Simanovskaya). This operation made it possible to study only
the reflector (neuronal) regulation of gastric secretion, but not
humoral regulation. That problem can be solved to some
extend by experiments, involving the creation of an isolated
miniature stomach or pouch as proposed by Klemensievich and
Heidenhain. A small pouch is formed from a strip of gastric
wall cut (triangle section) from the greater curvature and its
opening is sutured to the skin wound. The intactness of the
stomach is restored by means of sutures. Thus, two stomachs
are formed: one large and normal, though made a little smaller
by the operation, in which normal digestion occurs, and the
other a small or isolated one into which food does not enter,
but the latter secrets the juice, which can be collected with the
help of fistula. The secretion of gastric juice from the isolated
279
pouch begins 30-40 min after the ingestion of food, while in an
esophagotomized dog with a gastric fistula begins after 5-10
min. The regulation of gastric secretion by an isolated small
stomach is realized through humoral pathway, because the
nerve branches (n. vagus) supplying the pouch are cut when it
is created.
Pavlov developed the operation for forming an isolated
miniature stomach or pouch from the greater curvature,
leaving a seromuscular “bridge”. This bridge transmits small
intact branches of the vagus nerve innervating the isolated
miniature stomach, which reflects adequately the dynamics of
changes in the secretory process, the initial reflex phase
included.
All these above mentioned methods are used in
experimental conditions, but in the clinic other methods are
used to examine patients: gastroenteroscopy, X-rays method,
US-gastroscopy, radiotelemetric method by using radiopills.

Digestion in the small intestine

Digestion in the small intestine effects depolymerization

of the nutrients to the stage (monomers for the most part) in
which they are absorbed from the intestine into the blood and
lymph. Two types of digestion (cavital and membrane) are
represented in the small intestine, which are accomplished by
the pancreatic and intestinal juices’ enzymes; bile plays an
important role in intestinal digestion.
Secretor activity of the pancreas. Composition and
properties of pancreatic juice. The pancreas (Figure 46)
280
secrets daily 1.5-2.0 l juice. It is a colorless clear fluid with a
pH of 7.8-8.4. The juice contains bicarbonates, sodium and
potassium chlorides. The juice is rich in enzymes (proteases,
lipases, carbohydrases, nucleases, etc.). Proteases are produced
by the pancreas in the form of zymogens that are activated by
other enzymes.

Figure 46. The opening of the common bile duct

in the duodenum.

Trypsinogen (protease) is converted to trypsin in the

duodenum by its enzyme enterokinase. The formed trypsin also
activates trypsinogen. The second proteolytic enzyme,
chymortypsin is formed from chymotrypsinogen by trypsin.
Trypsin and chymotrypsin (as well as pancreatopeptidase E or
elastase) split the internal peptide bonds of the proteins. They
also exert an action on the high-molecular polypeptides, due to
which low-molecular peptides and aminoacids form.

281
 The pancreas secrets procarboxypeptidase A and B,
proelastase and prophospholipase A. They are activated by
trypsin with the formation of the corresponding enzymes:
carboxypeptidase A and B, elastase and phospholipase.
Carboxypeptidase splits the C-terminal bonds in proteins and
peptides.
Pancreatic juice is rich in a α−amylase, which breaks
down polysaccharides to oligo-, di- and monosaccharides.
Ribo- and desoxyribonucleases of the pancreatic juice act upon
the nucleic acids. Pancreatic lipase breaks down fats to
monoglycerides and fatty acids. Phospholipase A and esterase
also exert an action on the lipids.
Influence of various foodstuffs on the pancreatic juice
secretion. When digestion is not taking place, pancreatic juice
is secreted in small amounts due to the periodic activity of the
digestive tract. Pancreatic secretion increases sharply two to
three minutes after food is taken and lasts from 6-14 hours
depending on the composition of the meal. The higher is the
acidity of the gastric contents entering the duodenum, the more
pancreatic juice is secreted and the greater is the content of
bicarbonates in it. The dynamic of changes in pancreatic
secretion mainly repeats the pattern of gastric secretion.
The ingestion of food induces increased secretion of all
enzymes in the juice, which nature depends on the type of
food. The secretion of amylase increases to the greatest extent
in a carbohydrate diet, more trypsin and chymotrypsin are
secreted in response to a protein diet, while juice with a high
lipolytic activity is secreted when food is rich in fats.
282
 Control of pancreatic secretion. Secretion of the
pancreatic gland is controlled by neuronal and humoral
mechanisms. The initial pancreatic secretion is induced by the
sight and smell of food and by other stimuli (conditional
reflexes), as well as unconditional reflexes, formed from the
mouth and stomach receptors. All these signals reach the
medulla oblongata and then the efferent impulses pass along
the fibres of the vagus nerve to the gland and excite its
secretion. In excitation of sympathetic fibres innervating the
pancreas inhibits its secretor activity, but increases organic
substances’ level in it. Inhibition of pancreatic secretion is
uncounted in stimulation of many centripetal nerves, in pain
reaction, during sleep and in intensive physical and mental
work. Gastro-intestinal hormones possess the principal
significance in the humoral control of pancreatic secretion. It
was shown in Pavlov’s laboratory that administration of
hydrochloric acid into the duodenum excited secretion of
pancreatic juice. In 1902 Bayliss and Starling demonstrated
stimulation of the pancreatic secretion by intravenous infusion
of a hydrochloric acid extract of the duodenal mucosa. The
substance formed in the duodenum under the effect of
hydrochloric acid was named the hormone secretin. Secretin
induces production of a great amount of pancreatic juice which
is rich in bicarbonates, but poor in enzymes because it hardly
acts on the enzyme-secreting acinar cells. The second hormone
that augments pancreatic secretion is cholecystokinin-
pancreozymin. Products of the initial hydrolysis of protein and
fat contained in the food, as well as certain aminoacids,
283
hydrochloric acid and carbohydrates stimulate to a greatest
extent the release of this hormone. Cholecystokinin-
pancreozymin induces secretion of enzyme–rich juice. Gastrin,
serotonin, insulin, bombesin, substance P are also activators of
pancreatic secretion. Glucagon, calcitonin, gastric inhibiting
peptide and somatostatin inhibit it. Vasoactive intestinal
peptide may both stimulate and inhibit pancreatic secretion. In
ingestion of food the neuronal signals merely exert trigger
effects on the gland, whereas the humoral mechanisms play an
important role in the correction of pancreatic secretion.
The phases of pancreatic secretion stimulated by the
intake of food are the same as those of gastric secretion, but the
humoral influences on the pancreas are more marked,
especially in the intestinal phase.
Bile, its composition and participation in digestion.
About 500-1500 ml of bile is produced daily. Its production
occurs continuously, while its ejection or secretion into the
duodenum takes place periodically, mainly in association with
the intake of food. Produced bile flows into the gall bladder
where it is concentrated, therefore hepatic and cystic forms of
bile are distinguished. Bile contains water, mineral salts,
proteins, aminoacids, vitamins, bile acids, bile pigments,
cholesterol, mucin, etc. The bile pigments are the final
products of the breakdown of hemoglobin. The bile pigments
are bilirubin (reddish-yellow) and biliverdin (green).
Primary cholic and xenodeoxycholic acids form in the
human liver, which are converted to several secondary bile
acids in the intestine under the action of enzymes. Most of the
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bile acids and their salts are combined in the bile with glycocoll
and taurine. The human bile contains approximately 80% of
glycocholic and 20 % of taurocholic acids. This ratio changes
under the effect of certain factors. For instance, the content of
glycocholic acid increases in ingestion of food rich in
carbohydrates, while taurocholic acid level grows with a
protein-rich diet. About 85-90 % of bile acids (glycocholic and
taurocholic) ejected into the small intestine are absorbed into
the blood. They again return into the liver and participate in the
formation of the bile.
The bile has an important role in digestion process. Bile
emulsifies fats increasing the surface on which their hydrolysis
by lipase takes place; it dissolves the products of fat hydrolysis
to facilitate their absorption; bile increases the activity of
pancreatic and intestinal enzymes; it neutralizes the acidic
chyme passed from the stomach. Bile salts take part in the
formation of fat particles, which are dispersed, so finely that
can be absorbed from the small intestine in small amounts
without preliminary hydrolysis. Bile also fulfils a controlling
role since it stimulates bile production and ejection, the motor
and secretor activity of the small intestine. Bile also possesses
bacteriostatic properties. Bile plays a very important role in
absorption of fat-soluble vitamins, cholesterol and aminoacids.
Control of bile ejection. Conditional and unconditional
reflex influences on the biliary apparatus are affected with the
participation of numerous reflexogenic zones among which are
the receptors in the mouth, stomach and duodenum. The
regulation of bile production and gall bladder contraction are
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realized by humoral mechanisms: cholecystokinin-
pancreozymin, gastrin, secretin and bombesin are stimulators;
glucagon, calcitonin, anticholecystokinin, vasoactive intestinal
peptide and pancreatic polypeptide are inhibitors.
The secretion of bile and pancreatic juice can be
investigated by operations suggested by Pavlov. He gave
methods of operations for drawing out the common bile duct
and pancreatic duct into the skin wound with the surrounding
them tissue small fragments of duodenum. The intactness of
duodenum was restored by means of sutures.
Intestinal secretion. The intestinal juice is a cloudy and
quite viscous fluid. In centrifugation the intestinal juice
separates into liquid and solid parts. The liquid part consists of
water, inorganic (chlorides, bicarbonates, phosphates of
sodium, potassium and calcium) and organic (mucus, protein,
aminoacids urea, etc.) substances. The solid part of the juice is
a yellow-gray mass of mucous clots made up of undestroyed
epithelial cells. The surface layer of epithelial cells in the small
intestinal mucus is continuously replaced. More than 20
different enzymes which take part in digestion are contained in
the intestinal juice. The main ones among them are:
enterokinase, several peptidases, alkaline phosphatase,
nuclease, lipase, phospholipase, amylase, lactase and
saccharase. Under natural conditions they are attached in the
zone of the brush border and effect surface digestion.
The secretion of the intestinal glands increases during a
meal, in localized mechanical or chemical stimulation of the
intestine, under the effect of some intestinal hormones. Local
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mechanisms are of principal importance, which are realized by
peripheral reflexes. Mechanical stimulation of the small
intestinal mucosa sharply increases the secretion of the liquid
part of the juice. The products of protein and fat digestion,
pancreatic juice, hydrochloric acid (and other acids) are the
chemical stimulators of the small intestine. The local effect of
the products of nutrient digestion induces the secretion of juice
rich in enzymes.
In contrast to the stomach secretion, which is a
morphostatic type, the intestinal secretion is a morphonecrotic
one.
Cavital and membrane hydrolysis of nutrients in the
small intestine. Cavital and membrane or surface digestion
takes place in the small intestine. Digestion in the cavity of the
small intestine is accomplished by pancreatic and intestinal
juices and bile. Macromolecular substances are hydrolyzed
after the cavital digestion. The main products of this process
are oligomers which hydrolysis is completed in the zone of the
striated border of the intestinal epitheliocytes by enzymes
adsorbed on the microvilli (Figure 47) and glycocalyx. The
microvilli increase the effective surface of intestine 300-500-
fold. The final products of oligomer hydrolysis, monomers, are
absorbed into the blood and lymph.
The main intestinal enzymes taking part in surface
hydrolysis of carbohydrates are: maltase, trehalase, lactase
amylase, invertase, etc. Oligo- and dipeptides are hydrolyzed
by several peptidases, phosphoric ethers by alkaline
phosphatase and lipids by lipases.
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 Figure 47. The microvilli of the small intestine.

Intestinal secretion is studied on the isolated segments of

the small intestine. One end (in Thiry’s method) or both ends
(in Thiry-Vella’s method) of the isolated segment are drawn out
into the skin wound.

Digestion in the large intestine

A portion of chyme passes from the small intestine into

the large intestine through the ileocecal sphincter, which acts
as a valve permitting the passage of content only in one
direction. The large intestine plays a small role in the digestion
process, because food is almost completely broken down and
absorbed in the small intestine, except for certain substances,
e.g. plant cellulose. A small amount of food and digestive

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juices are hydrolyzed in the large intestine under the effect of
enzymes, which have entered from the small intestine, as well
as the juice of the large intestine itself. In large intestine juice
the liquid and solid parts are distinguished. This juice has
alkaline reaction (8.5-9.0). The solid part consists of mucous
clumps formed of rejected epithelial cells. Most of enzymes are
contained in the solid part of the juice. Neither enterokinase
nor saccharase is found in it. Alkaline phosphatase is present in
a concentration 15-20 times less than in the small intestine. It
also contains small amounts of cathepsin, peptidases, lipase,
amylase and nucleases.
The secretion of juice in the large intestine is induced by
local mechanisms. Mechanical stimulation increases it 8-10-
fold.
Approximately 400 g of chyme passes daily from the
small intestine into the large intestine. Certain substances are
digested in its proximal part. Water is intensively absorbed in
the large intestine. The chyme is gradually converted to feces,
150-250 g of which is produced and excreted daily. Food rich
in fibres (cellulose, pectin and lignin) increases the amount of
feces due to the presence of undigested fibres in it and
accelerates passage of the chyme, acting like a purgative.
Microflora of large intestine. Bacterial flora of the
gastro-intestinal tract is indispensable for normal body
functioning. The number of microorganisms is minimal in the
stomach, much more in the small intestine and optionally great
in the large intestine, up to tens of billions per kg of contents.

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 The importance of intestinal microflora consists in the
final breakdown of the remnants of undigested food and
components of the digestive juices, the creation of an immune
barrier, suppression of pathogenic microbes, and synthesis of
some vitamins (vit. K and vitamins of B complex), enzymes and
other biologically active substances, participation in
metabolism. The bacterial enzymes break down cellulose fibres
which were not digested in the small intestine. Microflora
participates in the process of carbohydrate fermentation and
protein decay. Unabsorbed aminoacids and other products of
protein digestion are destroyed in the colon by the action of
putrefactive bacteria. In this process a number of toxic
compounds (indole, putrescin, skatole, phenol, etc.) are formed
that are capable to cause intoxication of the organism. They are
detoxified in the liver by formation of coupled complexes with
sulfuric and glucuronic acids. This barrier function of the liver
has been shown by Pavlov-Eck operation by means of liver
portal vein and vena cava anastomosis.
Defecation. Defecation, i.e. evacuation of the large
intestine content, occurs as a result of stimulation of the rectal
receptors by the faecal material, accumulated in it. The urge to
pass stool appears when the pressure in the rectum increases to
the 40-50 cm H2O. The reflex arc of the act of defecation
closes in the lumbosacral segment of the spinal cord. It causes
involuntary defecation. Voluntary defecation occurs with the
participation of centres in the brain, particularly in the cerebral
cortex. As a result of impulses coming from the defecation
centre through motor nerve fibres (parasympathetic pelvic
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nerve) is sphincter ani internus (consisting of smooth muscle
fibres) and sphincter ani externus (made up of striated
muscles) relaxation. Due to peristaltic contraction of the
intestine the feces are pushed out. This is facilitated by
contractions of the abdominal muscles and diaphragm affected
by straining. Contraction of the abdominal muscles causes a
marked increase in intra-abdominal pressure. When defecation
is not taking place, both sphincters are in the state of tonic
contraction which prevents the fecal masses from falling out.
The sympathetic neuronal stimuli raise the tone of sphincters’
muscles and inhibit rectal motor activity.

Absorption

Absorption is a process in which various substances are

transported into the blood and lymph from the surface, cavities,
or from hollow organs of the body through cells, their
membrane or intercellular passages. Transport of macro- and
micromolecules are distinguished. Macromolecules and their
aggregates are transported by means of phagocytosis and
pinocytosis and the process is called endocytosis. A certain
amount of substances may be transported along the
intercellular spaces; this is called persorption. This mechanism
explains the penetration of small amount of proteins
(antibodies, allergens, enzymes, etc.) and other substances
(dyes) and even bacteria into the internal media from the
intestinal cavity.
Micromolecules (monomers of nutrients and ions) are
transported mainly into the internal environment from the

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cavity of the gastrointestinal tract. This transport is divided into
passive transport, facilitated diffusion and active transport.
Passive transport includes diffusion, filtration and osmosis. It
takes place in the direction of concentration, osmotic and
electrochemical gradients of the transported substances.
Facilitated diffusion occurs with the aid of special membrane
carriers. Active transport is the transport of substances through
membranes in the direction opposite to the concentration,
osmotic and electrochemical gradient with expenditure of
energy and the participation of special transport systems:
mobile carriers, conformation carriers, etc.
Absorption in various parts of the digestive tract.
Absorption takes place along the entire length of the digestive
tract, but varies in intensity in its different parts. Absorption
does not actually occur in the mouth, because food remains in
it for a very short time. Besides, the monomer products of
nutrient hydrolysis are still not formed here. Only some
medical preparations can be absorbed in the mouth (cardiac
preparations).
Absorption in the stomach is also limited. Water and
mineral salts, alcohol and glucose are absorbed here to a
somewhat greater extent; aminoacids are absorbed in very
small amounts.
The main process of absorption takes place in the small
intestine. Here the absorption of substances depends on the
contraction of its microvilli. When they contract, the cavity of
their lymph vessels is constricted and the lymph is pressed out,
which creates a sucking action of the central lymph vessels. In
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the small intestine all products (monomers) of hydrolyzed
substances as well as water and electrolytes are absorbed.
The absorption of nutrients in the large intestine is
insignificant under normal physiological conditions, because
they are absorbed mostly in the small intestine. Much water is
absorbed in the large intestine, which is essential in the
formation of feces.

Motor activity of the gastro-intestinal tract

Motor activity of the stomach. Contraction of the

smooth muscles forming the wall of the stomach conditions its
motor activity. The motor function of the stomach consists in
storing the ingested food, mixing it with the gastric juice in the
zone adjacent to the gastric mucosa, moving the gastric
contents to the exit into the intestine and, finally, evacuating
them in portions into the duodenum. During the intake of food
and for some period after the stomach relaxes. This is known as
food receptive relaxation. Some time later, depending on the
type of ingested food, the contractions increase noticeably, the
cardiac part contracting with a lesser force and the pyloric ones
with the greatest force.
There are two types of gastric contractions: phasic and
tonic. The former contractions have a peristaltic character and
maintain the tone of the stomach and promote mixing of the
food with the gastric juice. The latters are propulsive and
characteristic of the pyloric part of the stomach. They
contribute to pushing the contents into the duodenum.

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 The motor activity of the stomach is controlled by
neuronal and humoral mechanisms. Stimuli arriving along the
efferent fibres of the vagus nerve intensify gastric motor
activity (rhythm and force of contractions). Stimuli passing
along the sympathetic nerve reduce the stomach motor activity.
Gastro-intestinal hormones are very important in the
control of gastric motor activity. Gastrin, motilin, serotonin
and insulin intensify motor activity of the stomach. Secretin,
cholecystokinin-pancreozymin, gastric inhibiting peptide,
vasoactive intestinal peptide, bulbogastrone and
enterogastrone inhibit it.
Vomiting. Vomiting is a complex reflex motor act, which
starts with contractions of the small intestine. These
contractions push some of the intestinal contents into the
stomach. In 10-20 sec the stomach contracts, the entrance into
it opens and violent contractions of the muscles of the
abdominal wall and diaphragm occur, as a result of which the
gastric contents are ejected through the esophagus into the
mouth during expiration. Vomiting has a protective importance
and occurs by reflex due to stimulation of the receptors of the
tongue root, pharynx, mucous membrane of the stomach and
intestine, peritoneum and the vestibular apparatus. Vomiting
may be induced by smell and taste stimuli. Signals from the
receptors of the above indicated areas reach the vomiting centre
located in the medulla oblongata along the afferent fibres of
the vagus, glossopharyngeal and some other nerves. The
efferent stimuli, which excite vomiting, pass along the fibres of
the vagus and splanchnic nerves to the esophagus, stomach and
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intestine and along the motor fibres to the muscles of the
abdominal wall and diaphragm.
Motor activity of the small intestine. The motor activity
of the small intestine is responsible for mixing the food
contained in it with the digestive juices, moving the chyme
along the intestine, raising the intra-intestinal pressure to
promote absorption of some of the chyme components from the
intestinal cavity into the blood and lymph.
Contraction of the small intestine results from the
coordinated movements of the longitudinal and circular
smooth muscle fibres. These contractions may be of several
types. According to function all contractions are divided into
two groups: 1) local that mix and grind the contents of the
small intestine; 2) contractions propelling the contents. The
types of contractions are as follows: rhythmic segmentation and
peristaltic (Figure 48, A, B), pendular, and microvilli
contraction.
Rhythmic segmentation is mainly produced by
contraction of the circular muscles, which separate the
intestinal contents into parts. The next contraction forms a new
intestinal segment which contents consist of parts of the former
segment. As a result, the chyme is mixed, and pressure is raised
in every intestinal formed segment. The pendular movements
are produced by contractions of the longitudinal muscles.
These contractions move the chyme forwards and backwards
and propel it slightly.

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 A. B.
Figure 48. Motor activity of small intestine.
A- Rhythmic segmentation; B- peristalsis

Peristaltic consists in the formation of a constriction

above the chyme owing to contraction of the circular layer of
muscles and dilation of the intestine below the chyme due to
contraction of the longitudinal muscles. The constriction and
dilation move along the intestine and propel the portion of
chyme in front of the constriction. Several peristaltic waves
move simultaneously along the length of the intestine.
Antiperistaltic contractions of the small intestine do not occur
in norm. Tonic contractions may be marked by a very low rate
and sometimes may not spread at all causing considerable
constriction of the intestinal lumen for a great distance.
Motor activity of the small intestine is controlled by
neuronal and humoral mechanisms; the role of myogenic
mechanisms, which are based on the automatism of smooth
muscles, is quite important.

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 The control of the motor activity of the small intestine is
effected by the intramural nervous system and signals arriving
from the CNS, as well as humoral factors. The parasympathetic
nerve fibres stimulate, while the sympathetic nerve fibres
inhibit the contractions of the small intestine. Motor activity is
also inhibited in anger, fear and pain. Vigorous peristalsis of
the intestine is sometimes encountered in some strong
emotions, e.g. in fear (“nervous diarrhea”). The intestinal
motor activity depends on the physical and chemical properties
of the chyme. The local, mechanical regulation of the motor
activity of the small intestine is the most important, which is
realized by peripheral reflexes. The humoral substances alter
the intestinal motor activity by acting on the muscle fibres
directly and on the neurons of the intramural ganglia.
Vasopressin, oxytocin, bradykinin, serotonin, histamine,
gastrin, motilin, cholecystokinin-pancreozymin, substance P,
etc increase the motor activity of the small intestine.
Motor activity of the large intestine. The digestive
process in humans lasts one to three days, the propulsion of the
food remnants via the large intestine taking most of the time.
The motor activity of the large intestine is responsible for its
reservoir function: accumulation of the intestinal contents,
absorption of certain substances, mostly water, from it, the
formation of fecal masses and their discharge from the
intestine. The large intestine performs several movements.
Small and large pendular movements mix the contents which
are thickened through absorption of water. Peristaltic and
antiperistaltic movements fulfil the same functions; strong
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propulsive contractions that push the contents caudally occur
three or four times daily.
The large intestine possesses automatism which is,
however, weaker, than that of the small intestine. The large
intestine is supplied with intramural and external innervation
by the sympathetic and parasympathetic parts of vegetative
nervous system. The sympathetic nerve fibres, which inhibit
motor activity, arise from the superior and inferior mesenteric
plexuses, while the parasympathetic fibres stimulating motor
activity run as components of the vagus and pelvic splanchnic
nerves. Local mechanical and chemical stimuli are very
important in exciting contractions of the large intestine.
Serotonin, adrenaline and glucagon inhibit contractions.

Periodic activity of the digestive organs

The motor and secretor activity of the digestive organs

increase in certain periods independent from the food entrance.
This is called periodic activity. A cycle of contractions of an
empty stomach (period of work) and secretion of pepsinogen
rich juice (but not free hydrochloric acid) occurs approximately
20-50 min, the period of rest 45-90 min. The periodic activity
of the digestive tract is also manifested by contractions of the
esophageal wall, increased salivation, production of bile and its
ejection, pancreatic secretion and contractions of the small and
large intestines.
Periodic activity of the digestive tract is attended by
changes in the functions of other systems of the organism: the
heart and respiration rates increase, more blood is supplied to
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the digestive organs, the content of glucose, acetylcholine,
catecholamines and certain enzymes in the blood and the blood
red cell and leukocyte counts are changed. Marked changes are
found on the electroencephalogram. This is an evidence of the
influence of periodic activity on many aspects of metabolism,
on the organism as a whole. On the other hand, periodic
activity of the digestive organs depends on the metabolism in
the body. The principal role in ensuring periodic activity of the
digestive organs belongs to the central nervous system which
stimulates and inhibits their activity by means of
parasympathetic and sympathetic influences. In turn, the
central nervous system is regulated by changes of the content
of certain substances, glucose, aminoacids, etc. in the blood.
Humoral factors (acetylcholine, adrenaline, gastrointestinal
and adrenocortical hormones) have a definite part in the
formation of periodic activity of the digestive organs.
Several hypotheses have been advanced on the
physiological significance of periodic activity of the digestive
organs. According to one of them, periodic activity in the
active phase causes a feeling of hunger and induces the
individual to seek food. Periodic activity is, therefore, called
“hunger periodicity”. Periodicity inhibiting factors reduce the
appetite. According to another view point, digestive juices
contain a great amount of energetically and plastically valuable
substances, proteins among others. They are hydrolyzed in the
digestive tract, absorbed and utilized by the organism’s tissue.
In physiological starvation the organism can utilize its own
substances for nutrition.
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 The feeding centre is located in the hypothalamus, the
lateral nuclei of which are responsible for the sense of hunger
and ventromedial ones for satiety. Stimulation or inhibition of
the feeding centre depends on the chemical composition of the
blood and arrival of various signals from different peripheral
receptors.

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CHAPTER 10.
METABOLISM OF ENERGY AND THERMOREGULATION

10.1. METABOLISM OF ENERGY

Alive organism is an open system, which needs in

continuous energy influx. Energy is spent for the body
temperature maintaining, work performance and plastic
processes. For the humans (heterotrophic organisms) the
energy source is nutrients.
Transformation of energy takes place continuously in the
process of metabolism: the potential energy of the complex
organic compounds in food is transformed into thermal,
mechanical and electrical energy: 75% into thermal; 25% into
mechanical and an insignificant part, into electrical. But all the
energy types eventually turn into thermal energy and leave the
organism. Energetic expenses of the organism are to be
measured in units of heat calories or joules. It is detectable by
means of calorimetry.
Let’s suppose the potential energy of nutrients is A, and
the energy leaving the body is B: so the ratio A/B is the
energetic balance of the organism. In a healthy grown–up
person with constant weight it is equal 1.
When one of these conditions is disturbed, the balance
shifts. It is more than 1, if the cumulative processes prevail
over the expenditure; and is less than 1, in case of exhausterd
organism. For the nutrients’ potential energy (A) determination
we need to detect the caloric indices of nutrients. That is the

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heat quantity, forming in 1 g nutrient’s burning process. The
caloric index of carbohydrates is 4.1 kcal; for fats 9.3 kcal; for
proteins 5.8 kcal. Because of the fact, that proteins of the
organism don’t undergo oxidation completely up to the final
products, their caloric index in the organism is less than 4.1
kcal. For the A determination we also need the examined
person’s diet ratio. It is calculated, that an average loads an
organism takes daily approximately 400-500g of
carbohydrates, 100-120 g of proteins and 90-100g of fats. The
value of A will be: 400× 4.1+ 100× 4.1+90×9.3.
For determinating the energy leaving the body (B), there
are 2 methods: direct calorimetry and indirect calorimetry.
Direct calorimetry is based on immediate measurement
of the heat amount liberated by the organism in a biological
calorimeter chamber. The apparatus is an airtight chamber
with thermal insulation from the external environment. At the
beginning and the end of the tubes, filled with water,
thermometers are installed. Water circulating in the tubes is
warmed by the heat liberated by a person or animal placed in
the chamber. The amount of heat liberated by the body is
calculated from the amount of circulating water and change in
its temperature. This method is expensive. That is why more
often they use the method of indirect calorimetry.
Indirect calorimetry accounts not the liberated heat by
the body immediately, but the amount of O2 consumed in the
heat production, and that of CO2 liberated with the following
calculation of the heat expensed.
For this method 3 values are necessary to know:
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 1) O2 amount consumed during a day, or a definite period
of time;
2) caloric equivalent of O2;
3) the respiratory index.
O2 consumed is determined by the comparative analysis
of the inhaled and exhaled air content (% O2).
The caloric equivalent of O2 is the heat amount generated
after utilization of 1 l O2. For this determination they use the
caloric index in order to calculate the O2 amount consumed.
Oxidation of 1 g of proteins, fats and carbohydrates does not
bring to the same heat amount generation, so is required
different O2 supply. For example, 1g of carbohydrates gives 4.1
kcal of heat (caloric index) and uses for that 0.8 l of O2. The
heat amount when 1 l of O2 is used will be 5.05 kcal (caloric
equivalent of O2).
Caloric equivalent of O2 for proteins is 4.60 kcal, for
fats, 4.69 kcal.
Taking into consideration the amount of consumed
oxygen and O2 caloric equivalent of different substances,
which undergo oxidation, it is possible to determine B. For the
identification of these substances (prevalence of fat, protein or
carbohydrate), and so their caloric equivalents, it is necessary
to know the respiratory index (RI).
The respiratory index, that is ratio of the exhaled CO2

from the organism and the O2 consumed: RI =

[CO 2 ]
[O 2 ]

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 For the CO2 and O2 volumes’ determination the
comparative analysis of the inhaled and exhaled air contents is
needed. In the exhaled air the CO2 is 4.1 %; in the inhaled air,
0.03 %.
[CO2] = 4.1 %-0.03%=4.1%
The O2 consumed is being determined by the %
difference in the inhaled and exhaled airs
[O2] = 20.94 % - 16.4% = 4.5%
RI = 4.1 / 4.5 = 0.85-09
If organism intakes mixed food, the respiratory index
oscillates from 0.85-0.9. The respiratory index differs in fats,
proteins and carbohydrates. In carbohydrates’ prevailing
oxidization it is equal to:
C6H12O6+ 6O2=6H2O+6CO2
RI = 6CO2/6O2 = 1
The amount of the O2 moles consumed is equal to the
CO2 moles. According to Avogadro-Gerard’s law at the same
temperature and the same atmospheric pressure different gases
take the same volume. So the respiratory index for the
carbohydrates is equal to 1. The respiratory index in the fats’
oxidation is equal to 0.7. We can exemplify the mentioned with
tripalmitin:
2C3 H5 (C15H31COO)3+145 O2=102 CO2+98 H2O
RI = 102 CO2/145 O2 = 0.7
For proteins it is 0.8. The respiratory index enables the
determination of caloric equivalent of the corresponding
nutrients. When the respiratory index is equal to 0.7 they use
the corresponding caloric equivalent of O2 (4.69 kcal). By
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multiplying that by the consumed O2 volume we determine the
organism’s energetic expenses.
There is significance as well. It shows what
metabolic pathway prevails, assimilation or dissimilation. If
the assimilation prevails, the respiratory index is more 1. When
fat is getting cumulated at the glucose expense in the organism,
1 molecule of fat is synthesized from 8-9molecules of glucose.
C6H12O6 (8-9)
C51H98O6 (1)
In this case approximately 22 shares of O2 leave free, so
less oxygen is required and the respiratory index becomes more
than 1.
This value is important also for the blood chemical
content reflection. Before physical work this index is 0.85-0.9,
during work it tends to 1 since the main source of energy in
muscles is glucose. Just after work it becomes more than 1,
then decreases lesser than norm and in 50-60 minutes that
comes to norm. All these changes could be explained by
accumulation of the lactic acid which expels carbonic acid
from bicarbonates of the buffer system.
RCOOH + NaHCO3 = RCOONa + H2CO3
The formed CO2 volume increases and the respiratory
index becomes more 1. When carbon dioxide amount decreases
because of the metabolic conversions in the organism the
respiratory index suddenly drops and just after that it comes to
norm.
According to the isodynamic law of Rubner all the
nutrients can substitute each other in the energetic aspect. For
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example energy got from 1 g of fat is equal to that of 2 g of
glucose. But this law is somehow limited since it does not
consider the nutrients’ plastic properties (irreplaceable
aminoacids). Compulsory ratio of different nutrients having not
just nutritional significance is to be considered as well.
Basal metabolism. Energy produced by the organism
cannot be constant because of the functional state of the
organism. In physical work the energy produced daily is 5000-
6000 kcal, in mental work 3000 kcal. Nevertheless, there is
some energy amount which is standard for all the types of the
organism. The energy expenses in standard conditions (t =
18-200C, at fast (in 12-15 hours after the meal intake), in
physical and mental rest state) is a basal exchange. In men
(70kg 165 cm, 35 years) it is equal to 1700 kcal per day. In
women the basal exchange is lesser by 10%.
Due to this the constant temperature is maintained, as
well the vital activity.
The basal exchange can be changed in connection with:
1) meal, especially proteins;
2) medium temperature, if it is low, the metabolism
increases;
3) sex, in men it is more intensive;
4) age, in children that is higher;
5) daily activity, in sleep that decreases by 10%;
6) health state, that increases in hyper-function of thyroid
glands;
7) the state of the neuronal system; in actors, teachers that
is significantly higher.
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 10.2. THERMOREGULATION

In low-organized vertebrates the body temperature is not

constant and can be changed regarding to the environment
temperature. These animals are poikilothermic ones. In birds
and mammalians temperature is constant, and they are
homoiothermic animals.
Constancy of the temperature is isothermia.
Nevertheless, the notion “constant temperature” is relative,
because it varies during a day. At day time (at 4:00 PM) the
highest temperature is 36.5-36.90 C, but at night or early
morning (at 4:00 AM) it becomes by 0.50C lower. Different
parts of the body have different temperature, e.g. the blood
temperature is 370C, in the fossa axillaris that is 36.5-36.90C,
in rectum 37.2-37.5, on the nose 320C. Constancy of the
temperature is maintained by two counteracting and
predetermining processes: heat production and heat loss.
Heat production takes place in mitochondria of the cells.
So, the most heat production occurs in the organs, which are
rich in them, the liver, skeletal muscles, kidneys. This process
is a result of continuous biochemical reactions.
The chemical and physical thermoregulatory mechanisms
are distinguished. The chemical one takes place by means of
changes in the cell metabolism. The physical thermoregulation
encounters by means of changes in the heat emission intensity.
The chemical one takes place continuously and is most
significant, when the temperature of medium becomes lower
than 18-20oC. It is provided in the neuronal and humoral ways.

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The reflexogenic zone for the neuronal regulation is the skin,
where the cold-sensitive and the heat-sensitive receptors are
located. When the body surface temperature decreases the cold-
sensitive receptors are excited, and the impulses go through the
sensory nerves towards the posterior part of hypothalamus,
where the centre of chemical thermoregulation (heat
production) is located. Thereafter, the impulses reach the
muscles, bringing them to chaotic involuntary contractions, in a
type of shivering. Herein, the metabolic processes intensify
markedly, so the heat production increases. Beyond the
muscles, the kidneys and the liver participate in
thermoregulation as well. In cold-perception the heat
production in them increases in reflector way.
There is also a humoral way of thermoregulation. The
latter is provided by the hormones, increasing the metabolic
processes and hence the heat production: the hormones of
thyroid and adrenal glands.
The physical thermoregulation becomes of a special
significance in increase of the environmental temperature and
is realized by the heat emission changes by the organism.
The heat emission takes place in the following ways:
1. Radiation heat loss, the body gives off heat into the
medium.
2. Convection, movement and mixing of air heated by the
body.
3. Heat conduction, the body gives off heat to objects
that are in direct contact with the body surface.

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 4. Evaporation of water from the skin and the lung
surface.
In a human being at rest (the air temperature is equal to
0
+20 C) radiation accounts for 66%, evaporation for 19% and
convection for 15% of the total heat loss of the body. When the
environmental temperature rises to 350 C heats can be lost
mainly by evaporation of water from the surface of the skin
and lungs. The latter share can increase up to 75% in intensive
muscular work. It is calculated that in 1 ml of sweat
evaporation 0.56 kcal of heat is released. Evaporation depends
on the relative humidity of the air. In the air saturated by water
vapours, e. g. in the bath there is excessive sweat production,
but it does not undergo evaporation. This sweat production
does not contribute to the heat loss.
The centre of physical thermoregulation (heat loss) is
located in the anterior part of the hypothalamus.
Heat loss process also is regulated by the neuronal and
humoral pathways. In the environmental temperature increase
the heat-sensitive receptors of the skin are excited, and the
impulses are directed to the heat loss centre, due to which the
skin vessels are dilated in reflector way and the circulating
blood in them increases. This contributes to the heat loss by
radiation and convection. Here, blood will be taken by the
sweat glands as well, and sweat is going to be produced more.
In this case the heat production is inhibited.
At cold the cold-sensitive receptors are excited bringing
to vasoconstriction of the skin arterioles, so the blood enters

309
the abdominal vessels. In result the cutaneous vessels will get
less blood, so the heat loss will decrease.
Endocrine glands, mainly adrenals and thyroid gland also
take part in the regulation of the body temperature. Beyond the
neuronal and humoral regulation the blood temperature itself
has a significant regulatory meaning. The blood, having higher
temperature than normal, excites the heat loss centre and
evokes heat loss. The blood with decreased temperature excites
the heat production centre and brings to increase of metabolic
processes in the organism and the heat production
consequently.
The above-described thermoregulatory mechanisms have
an important significance in the organisms’ adaptation to the
altering circumstances of the external medium.

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CHAPTER 11.
PHYSIOLOGY OF THE EXCRETORY SYSTEM

All organs, the functions of which are directed to the

excretion of the metabolic products, toxic substances, as well
as the excess of water and salts from the organism, belong to
the excretory system. The excretory organs are the lungs
(eliminate the carbon dioxide, water and alcohol vapours,
metabolic products of surfactant), the sweat glands (eliminate
water, salts and urea), the organs of the gastrointestinal tract
(excrete heavy metals, products of haemoglobin metabolism,
excess of hormones) and the kidneys.

Morpho-functional characteristics of the kidneys

1. The basic function of the kidney is the excretory

function, the formation of urine, by which the waste products
of nitrogen exchange like urea, uric acid, creatinine and
ammonia (NH3) are excreted from the organism. Urea is a
waste product of catabolism of proteins, uric acid of purine
bases, creatinin of creatin-phosphoric acid, and NH3 results
from deamination of aminoacids.
2. The kidneys participate in regulation of the
homeostatic constants: a) the water balance of the organism, b)
the ionic composition of the inner medium, c) the pH of blood,
d) the osmotic pressure of blood, e) the content of the organic
substances in blood.
3. The kidneys perform the endocrine function. By
producing a set of biologically active substances (renin,

311
prostaglandins, bradykinin, hemopoietins, calciferol) the
kidneys also take part in the regulation of the blood pressure,
hemopoiesis, calcium metabolism, etc.
4. They provide the synthesis (synthetic function) of
some substances (glucose, NH3).
5. The kidneys also take part in the hemostasis process,
synthesizing prostacyclin, thromboxane and urokinase.
The morpho-functional unit of the kidney is the nephron
(Figure 49), because all processes that bring to the formation of
urine are realized in the nephron. Each kidney of humans
contains 1.2 million nephrons. But all nephrons do not function
simultaneously. Some of them serve as a reserve. But
altogether the functional reduction of the nephrons until 30%
causes kidney failure. The main part of nephron is
Shumlyansky-Bowman’s capsule, which consists of double
walls. The inner wall is covered by the layer of podocytes, the
external wall by one-layer of epithelial cells.

Figure 49. Nephron - the morpho-functional unit of the kidney.

312
 Between the inner and external membranes of the capsule
there is a cavity, which continues as the lumen of the tubule.
The first part of the tubule is the proximal convoluted tubules,
which wall is formed by brush border epithelial cells with
microvilli. Thereafter the tubule straightens and enters the
medullar region of the kidney. In the medulla the tubule turns
by 180O ascends back and up, and at the boundary of the cortex
and the medulla it again forms the convolutions, and this part is
called distal convoluted tubule (Figure 49). The part of tubule,
which is located in the medulla, is called Henle’s loop. In the
loop we differentiate the descending and ascending limbs. The
distal convoluted tube opens in the collecting tubule. The
collecting tubules by origin don’t belong to the nephron but
because they actively take part in the formation of urine, are
considered as a part of it. The collecting tubules of different
nephrons join together and form big extracting channels, which
open into the renal pelvis. Malpighian tuft (capillary
glomerulus) is the most important element of the capsule.
According to their form and location the nephrons are
divided into 3 types: superficial nephrons (malpigian
glomerulus is on the surface of the cortex, Henle’s loop is very
short) and makes up 20-30%; intracortical nephrons
(malpigian glomerulus is in the cortex), 60-70%, they
participate in the filtration process; juxtamedullary nephrons
(malpigian glomerulus is on the boundary between the cortex
and medulla), 10-15%, they have a long Henle’s loop, so they
perform an important significance in the concentration of the
urine.
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 Kidney blood supply

The kidney receives blood from the renal artery, which

originates from the abdominal aorta under 900, and after a
shortcut enters the kidney and separates into many branches:
interlobar, arcuate, interlobular arteries and afferent arteriols
(Figure 50). The latters form afferent vessels (vas afference),
from which a capillary network, nephron’s malpigian
glomerulus originates. The vessel originating from the
glomerulus is not a venous vessel, but is an arteriole which is
called efferent arteriole (vas efference). The diameter of the
efferent vessel is significantly smaller than that of the afferent
vessel. The efferent vessel again separates into secondary
capillary network, which surrounds the tubules. The
peritubular capillaries empty into the vessels of the venous
system and progressively form the interlobular vein, arcuate
vein, interlobar vein and renal vein, which leaves the kidney.
Peculiarities of the kidneys’ blood supply
1. The kidneys, being the 0.43% body’s mass, receive 1/4
of the blood pumped by the heart, therefore they are the most
blood supplied organs (4-5 ml/min/g of tissue).
2. In the capillaries, particularly in the glomerulus of the
kidneys, the hydrostatic pressure is significantly high, which is
equal to 70 mm Hg, while in the other organs this makes up 40
mm Hg. A high hydrostatic pressure is conditioned by two
factors: the renal artery originates from the abdominal aorta
under 90o; the difference between the diameters of the afferent
and efferent vessels.

314
 Figure 50. Kidneys’ blood supply.

3. The capillary pressure is relatively independent from

the common arterial pressure of the organism. The variations in
the arterial pressure by 90-190 mm Hg c. don’t reflect on the
pressure of the kidney capillary pressure. This is explained by
the self-regulating mechanisms.
4. The existence of double capillary network.
5. The difference in volumes between the kidney inflo-
wing and out flowing blood.
6. In the juxstamedullary nephrons, the secondary
capillary network and the difference between the diameters of
the afferent and efferent arterioles are not available.

315
 Formation of urine

According to the recent data the formation of urine is a

complex of processes and it consists of filtration, reabsorption,
secretion and synthesis.
Filtration. It occurs in Shumlyansky-Bowman’s capsule,
into the cavity of which water and different substances that are
dissolved in the blood are filtered. The filtration membrane
(barrier) (Figure 51), through which the filtered substances
pass, consists of 3 sheets. They are: the endothelial and
basement membranes in the glomerulus capillaries and the
capsule podocyte layer. Endothelial and basement membrane
pores’ diameter correspondingly is 100 nm and 10 nm. But the
basement membrane pores have also negative charge and
proteoglycans’ layer, which provides additional restriction to
filtration. The third barrier is composed by podocytes, which
encircle the outer surface of the glomerulus capillaries and
form the specific structure with slit pores (d=3 nm). These
scales limit the passage of substances by high molecular mass
(proteins, blood formed elements). Thus, the ultra-filtrate or
the primary urine, which is formed in the cavity of the capsule,
by its composition, differs from blood plasma only by the
absence of proteins and blood cells.
The ultra-filtrate is formed in a result of 3 different
pressures: 1) the hydrostatic pressure of the renal capillary (70
mm Hg c.), which promotes filtration; 2) the blood oncotic
pressure (30 mm Hg c.), it is the obstructing to filtration

316
pressure; 3) the intracapsular pressure (20 mm Hg c.), it is
also an obstructing pressure.

Figure 51. Structure of the filtration barrier.

Pfilt. = Phyd. – (Ponc. + Pcap.) = 70– (30+20) = 20 mm Hg c.

Changes in these pressures (decrease of Phyd. or increase
of Ponc.) result in urine formation disturbances.

Filtration

mm 20
g

20
20

Figure 52. Filtration mechanism. I – Hydrostatic pressure,

II-oncotic pressure, III- intracapsular pressure, IV- filtration
pressure

317
 Daily 1800 l of blood passes through the kidney, from
which 180 l of primary urine is formed, and from which 1.5-2 l
of the final urine is excreted. In clinical practice, in order to
assess the kidney’s filtration ability, they use an inulin-
cleaning coefficient. For this purpose inulin (polymer of
fructose) is injected into the blood. Inulin has the following
characteristics: 1) it’s not toxic for the organism; 2) it is
completely filtered by the kidneys; 3) during its passage
through tubules it doesn’t undergo any changes; 4) it is not
reabsorbed, secreted or synthesized. So its quantity in the
primary urine is the same as its quantity in the final urine.
Taking this into consideration we can derive the following
equations:
Pin. ×F = Uin. ×V,
where Pin. is the concentration of inulin in the blood,
which is equal to its concentration in the primary urine;
F is the volume of primary urine, formed in a unit
of time;
Uin. is the concentration of inulin in the final urine;
V is the volume of final urine, formed in a unit of
time.
U ×V
F = in
Pin
The value of F in male is 125 ml/min, in female 110
ml/min.
Reabsorption. 180 l of primary urine is formed daily
and 1.5 l of final urine is excreted daily from the organism.

318
Therefore the most amount of the primary urine is reabsorbed
in the tubules. In the composition of primary urine there are not
only waste products, but also substances that are essential for
the organism, like glucose, aminoacids, salts, vitamins,
microelements, hormones, etc. The reabsorption of 2/3 of these
substances occurs in the proximal convoluted tubules. But all
the substances are not reabsorbed. Those substances that can be
reabsorbed are called threshold substances (glucose), and those
that can’t be reabsorbed are called non-threshold (sulfates,
inulin). The non-threshold substances can be used to calculate
the quantity of the filtration.
There is a conception of elimination threshold for the
threshold substances. The elimination threshold is the
concentration of a substance in the blood at which it cannot be
reabsorbed completely and appears in the final urine. The
normal concentration of glucose in blood is 80-120 mg%, and
glucose will not appear in the final urine until its concentration
in the blood does not reach to 160-180 mg%, i.e. its elimination
threshold value is 160-180 mg%.
There are 2 types of reabsorption: obligatory and
facultative. The obligatory reabsorption of the substance is the
reabsorption, which is independent from the blood
concentration of the given substance. This type of reabsorption
mainly occurs in the proximal tubules. The reabsorption
occurring in the distal and collecting tubules of nephron
depends on blood concentration of substances and is called
facultative, which is regulated.

319
 We can differentiate 2 mechanisms of reabsorption,
passive and active. Passive reabsorption is the reabsorption,
when the substance is reabsorbed into the blood in the direction
of the concentration, electrochemical and osmotic gradients.
Water, CO2, some ions (Cl-), and urea are reabsorbed by this
mechanism. By active reabsorption, substances are reabsorbed
against the concentration gradient. There are 2 types of active
transport (reabsorption): primary active and secondary active
transport.
During the primary active reabsorbtion energy obtained
from the cell metabolism is used. The reabsortion of the Na
ions is realized by the primary active transport. This type of
reabsorption is divided into two phases: 1. Na ions pass from
the cavity of the tubule towards the epithelial cell owing to
electrochemical gradient, because sodium is not cumulated by
this cell, and the concentration of Na ions is less than that in
the primary urine; 2. Na ions pass from the epithelial cell into
the intercellular liquid and then into the blood against the
concentration gradient by the energy expenditure. It occurs due
to Na-K-ATP-ase. This enzyme is responsible for transport of
sodium from the cell and simultaneously for entry of potassium
into it.
For the secondary active reabsorption energy is not used
for the given substance, e.g. glucose or aminoacid transport.
At first glucose combines with the carrier and Na ions and this
complex passes from the lumen of the tubules into the
epithelial cells according to the sodium electrochemical
gradient without energy expenditure. Inside the cell the
320
complex is decomposed. The carrier passes back into the tubule
to combine with new portions of glucose. Sodium penetrates
through the basement membrane in a mentioned manner (active
transport) providing the glucose transport (co-transport), so
energy is not needed for the passage of glucose.
Nevertheless, a small amount of proteins (Hb, plasma
albumin) appear in the ultra-filtrate but they are also subjected
to reabsorption. The protein reabsorption mechanism is active
(energy dependent) and is called pinocytosis. The proteins are
engulfed by the epithelial cells forming the vacuole, and are
decomposed by the lysosomal enzymes forming low-molecular
fragments, which are then transported to the blood. The
reabsorption of all the substances necessary for the organism
occurs in the proximal convoluted tubules. In the distal parts,
basically water and salts are reabsorbed. The reabsorption
following percentage relativity exists in different parts of the
tubule. 45% of water and 65% of Na+ ions are reabsorbed in
the proximal convoluted tubules. In Henley’s loop it is 25% for
both and in the distal convoluted tubules it is 10% for water
and 9% for Na+ ions. In the collecting tubules it is 20% for
water and 1% for Na+.
Depending on the organism’s water balance, the kidneys
excrete either dense or dilute urine. The diluting and
concentrating urine occurs in Henley’s loop and also in the
collecting tubules. The medullar tissue is supplied with less
blood than the cortex, so the osmotic density of urine in the
medullar region is higher. When the primary urine flows
through the descending portion of Henley’s loop, which walls
321
are transparent only for water, it loses water and gradually
becomes denser. The density of urine in the descending part of
Henley’s loop is 300 mOsm/l and it is isotonic to plasma, while
in the apex of the loop its density reaches the highest value
(1400 mOsm/l). But if we compare the urine density in two
neighbouring Henle’s loop limbs, a big difference will not be
noticed. Water, by leaving the descending limb dilutes the
liquid of the medullar interstitial tissue, and thus it helps the
passage of Na+ and Cl- from the ascending limb of Henley’s
loop. An increase in the interstitial liquid density results in the
exit of water from the descending limb of Henley’s loop. So
urine advancing through the ascending limb of Henley’s loop
becomes less dense and enters the distal convoluted tube as
hypotonic urine. Its density is 100mOsm/ l. The final
concentrating of urine takes place in the collecting tubules. The
mechanism, which works in Henley’s loop, is called counter-
current multiplier mechanism. By this mechanism the water-
salt balance in the organism is regulated. The mechanism is
called so because in the parallel arranged tubules the urine
flows in opposite direction, and the process which occurs in
one tubule provides the process occurring in the neighbouring
tube and vice versa. In the entrance and exit of each limb of
Henley’s loop the solitary multiplication effect occurs.
Reabsorption is mainly an active process (energy-
dependent), and it might be reduced in cases when energy
synthesis is disturbed, which results in polyuria. In clinical
practice they induce polyuria (when there is excess of water in
the organism) with the help of special pharmacological
322
substances, which have a high osmotic activity and are filtered,
but are not reabsorbed.
In clinical practice to measure the kidney reabsorption
function, they calculate the so-called maximum value of a
substance transportation that can be done by the glucose. For
this purpose they inject enough glucose in the blood so that it
excels the threshold. In this case the most part of the glucose is
reabsorbed according to its threshold; the rest is excreted in the
composition of final urine. The amount that has undergone
reabsorption will be equal to the difference between the filtered
amount and the amount found in the final urine.
Tmaxgl. = Pgl×F– Ugl. ×V,
where Tmaxgl. is the maximal transport of glucose from
the primary urine towards the blood, that is the reabsorbed
amount;
Pgl. is the concentration of glucose in the primary urine
which is equal to its concentration in plasma;
F is the volume of the primary urine, produced in a unit
of time;
Ugl. is the concentration of glucose in the final urine;
V is the volume of the final urine in a unit of time.
Here we have 2 unknowns: Tmaxgl. and F. To calculate
F, besides glucose they also inject inulin in the blood
calculating its clearance coefficient. In the norm the maximal
transport value of glucose is 375 mg/min in male and 303
mg/min in female.
Secretion. The secretion function has a special
significance for the excretory function of the kidney, which is
323
also an active process and occurs in the opposite direction of
reabsorption. The substances useless for the organism, passing
to the interstitial tissue from the blood, are picked up by the
carriers in the epithelial cells of the tubule’s wall. Then the
combination breaks down and the substance is transported to
the cavity of the tubule. Now the carrier returns to the epithelial
cell for a new transportation of the given substance. This
process needs expense of energy. Secretion occurs in the
proximal and also in the distal convoluted tubules. The
substances that are secreted are the following: K+, organic
acids, bases, pigments, different medical preparations,
especially antibiotics (penicillin).
Synthesis. Synthesis appears that the epithelial cells
forming the wall of the tubules are capable of picking up two
different sources of substances and synthesizing a new
substance that doesn’t exist in the blood. For example from
glycocoll and benzoic acid found in blood a hypuric acid is
synthesized. NH3 is also the result of a synthetic process, which
is formed from the deamination of aminoacids.
Thus the substances found in the final urine can be
grouped into 4 categories according to the ways of their
excretion: 1) substances that are only filtered, e.g. inulin,
sulfates, creatinine; 2) substances that are filtered and are
reabsorped, e.g. glucose; 3) substances that are filtered and
undergone the secretion, e.g. paraamino-hypuric acid; 4)
substances that are excreted from the organism by synthetic
ways, e.g. NH3.

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 Urine excretion and micturition
Composition of urine. During a day 1.5 l of final urine
is produced, in which are found urea (25-35g), creatinine (1-
2g), uric acid (till 1g), NH3 (till 1g). There are also
uropigments (urobilin, urochrom), which are formed in the
intestine from bile pigments. In pathologic cases, acetone,
cetonic bodies, proteins, glucose, fatty acids and formed blood
elements also appear in the urine composition.
Urine formed in the renal tubules passes into the renal
pelvis and fills it gradually. When the filling threshold is
reached the signal of which is accepted by the baroreceptors,
the pelvis muscles contract and the uteral lumen opens, and the
urine flows into the urinary bladder. When the volume of the
urine reaches a definite level the mechanoreceptors are excited
and the impulses pass along the afferent nerve to the sacral
part of the spinal cord where the micturition centre is located.
The impulses coming by efferent nerve cause contraction of the
urinary bladder and relaxation of sphincter which promotes the
flow of urine into the urethra and its distension. The spinal
micturition centre is controlled by the cerebral cortex,
midbrain, hypothalamus, etc.

Endocrine function of the kidney

In the kidneys different biologically active substances are

produced, by which different homeostatic constants are
regulated.
1. Renin is produced by the secretor cells that are found
in the walls of the afferent arterioles, in that part where it
325
approaches the distal convoluted tubules, forming the
juxtaglomerular complex.
Renin is a proteolytic enzyme, which by passing to the
blood acts on the angiotensinogen of the blood, detaching from
it a peptide composed of 10 aminoacids, which is called
angiotensin I, the latter is transformed into angiotensin II (a
peptide composed of 8 aminoacids) due to other enzyme
carboxipeptidase. Angiotensin II is one of the most powerful
vasoconstrictor agents, by pressing the vessels; it helps to
increase blood pressure. At the same time angiotensin II
stimulates the production of aldosterone in the cortical part of
adrenal glands. The aldosterone in the kidneys increases the
reabsorption of Na+ which provides the conservation of water
with the increasing of blood volume, and blood pressure. The
production of renin is increased in case the kidneys are not
being supplied well by blood, when the overall blood pressure
is low, when the overall blood volume is decreased, and in case
when the sympathetic nervous system is excited. Renal
pathologies that are accompanied by the kidney’s blood hypo-
supply, bring to hypertension (increase in blood pressure),
because of the renin - angiotensin - aldosterone system
activation.
2. Urokinase by passing to the blood activates the
plasminogen protein, transforming it into plasmine, which
takes part in the hemostasis process, it simulates fibrinolysis.
3. Hemopoietins (erythro-, leuco- thrombopoietins) are
produced in the form of hemopoietinogenes, which after the
activation stimulate hemopoiesis in the bone marrow.
326
 4. Prostaglandins. The representative of this group is
medullin. It regulates the medullar blood supply. It is a
vasodilator agent.
5. Kinins. Bradikinin is a vasodilator agent.
6. Calcipherole. The kidney uptakes Vit. D3 (non active
form) from the blood and activates it, which has a significant
role in Ca2+ metabolism regulating processes.

Regulation of kidney function

The function of the kidneys is regulated by neuronal and

humoral ways. The kidneys receive sympathetic and
parasympathetic nerves; nevertheless the neuronal regulation
does not have a serious significance. This can be proved by
depriving the kidneys from their nerves and monitoring the
formation of urine, even in case of water overloading the
kidneys function properly.

Hormonal regulation.
1. Antidiuretic hormone (ADH) is produced by the neuro-
secretory cells forming supraoptic and paraventricular nuclei
of the hypothalamus. ADH stimulates the reabsorption of water
in the collecting and distal convoluted tubules by the
adenylatecyclase-dependent mechanism, so the volume of final
urine decreases. The production of this hormone is stimulated
when the blood’s osmotic pressure is high, also by nervous
impulses, especially in pain feeling. The pain is accompanied
by anuria.

327
 2. Aldosteron acts on the distal tubules of the nephron
and stimulates the reabsorption of Na+ and the secretion of K+
ions.
3. Parathyroid hormone results in the reabsorption of
2+
Ca in the kidneys, increasing its concentration in the blood,
and also it brings to the excretion of phosphates.
4. Calcitonine is produced in the C-cells of the thyroid
gland, inhibits the reabsorption of Ca2+ and phosphates in the
kidneys.
5. Adrenaline is the hormone of the medulla of the
adrenal glands. In small doses it presses the efferent vessels
increasing the hydrostatic blood pressure in the capillary
glomerulus and activating the filtration process. In large doses
it also presses the afferent vessels, ensuring the opposite effect,
even until anuria.

328
LITERATURE

1. Human Physiology, ed. by G.I.Kositsky, Moscow,

Mir, 1990, I volume, 286 p.
2. Human Physiology, ed. by G.I.Kositsky, Moscow,
Mir,1990, II volume, 447 p.
3. A.C. Guyton and J.E. Hall - Text book of Medical
Physiology, 10th Edition, Harcourt Asia PTE LTD; W.B.
Saunders Company, 2001, 1064p.
4. W.F.Ganong – Review of Medical Physiology, 20th
Edition, McGraw-Hill Companies, 2001, 870 p.
5. L. Praksam Reddy – Fundamentals of Medical
Physiology, second edition, Paras Publishing, 2001, 514 p.
6. Physiology (Editors – Robert M. Berne, Mattew N.
Levi, Bruce M. Koeppen, Bruce A. Stanton), 5th Edition,
Elsevier, Inc., 2004, 1014 p.
7. Robert G.Carroll – Physiology (Elsevier’s
Integrated), Mosby INC., Elsevier Inc., 2007, 239 p.

329
Authors:

1. Anna Ter-Markosyan – Professor of the Department of

Physiology of the Yerevan State Medical University after
M. Heratsi
2. Knarik Harutunyan – Docent of the Department of
Physiology of the Yerevan State Medical University after
M. Heratsi
3. Karen Arakelyan - Docent of the Department of Physiology
of the Yerevan State Medical University after M. Heratsi
4. Karine Avetisyan - Assistant of the Department of
Physiology of the Yerevan State Medical University after
M. Heratsi

Editor:
Drastamat Khudaverdyan – Head of the Department of
Physiology of the Yerevan State Medical University after
M. Heratsi, professor

English language editor:

Meline Bisharyan – Assistant of the Department of Foreign
Languages of the Yerevan State Medical University after
M. Heratsi

330