METHODICAL INSTRUCTIONSand notes for practical studies of Normal Physiology

"COMMON PHYSIOLOGY OF EXITABLE TISSUE. NEURAL AND HUMORAL REGULATION OF ORGANISM

Methodical Instructions to Lesson 1 for Students

Theme s : 1. PHYSIOLOGY IS THE THEORETICAL BASES OF MEDICINE.2. BIOELECTRICAL PHENOMENA IN NERVE CELLS.Aim: To know the common characteristic of physiology, method of physiology, history of it development. To know the analyze the mechanisms of beginning the resting membrane potential and membrane potential, methods of their registration in nerves and muscles.

Professional Motivation: The knowledge of physiology is necessary for future physicians to decision the normal and pathological processes. The knowledge of resting membrane potential and membrane potential, methods of their registration in nerves and muscles is necessary for future physicians to value the functional condition of excitable tissues.

Basic Level: 1. History of medicine (History of medicine Course)2. Medical apparatus. Installing of electrical impulses (Physics Course)3. Structure of nerves cells, their membranes (Biology Course)4. Anatomy of nerves (Anatomy Course)

Students’ Practical Activities:

Theme 1Student must become acquainted with

A. The main notion of physiology (After-depolarisation, after-hyperpolarisation, antiport, chemical mediator, electrical synapses, exitation, firing level, inhibition, latent period, local responce, overshoot, period of latent addition, postsynaptic cell, presynaptic cell, refractory period, resting membrane potential, saltatory conduction, spike, stimulator, subnormal period, supernormal period, symport, synapses), find it in book and note in the notebook.B. The functional diagnostic apparatuses (All apparatuses, which are used in physiological investigation, are divosed into 2 main groups: 1) apparatus for irritation of biological structure; 2) apparatus for register of physiological processes which are reflect different function. The stimulators (such as electric stimulators) and irritable electrodes (device which help to pass stimulus on the object which had stimulated) belong to the first group of apparatus. The registers,

corresponding electrodes (device which transform nonelectrical processes on electrical) belong to the second group of apparatus.)C. The scheme of keeping a protocols of practical units

1. Number of protocol, date2. Theme of unit3. Title of students’ practical activities4. Method of students’ practical activities fulfillment5. Receiving results6. Conclusion

Theme 2Definition of speed conduction of excitation by moving nerve

To establish stimulating electrodes over the nervus ulnaris more medial to processus ulnaris. The leading electrodes place over the abducens muscle of fifth finger. Inflict the upper threshold stimulus.

On the electromyograph‘s screen to definite the time from moment of infliction of stimulus to moment of origin the active potential (latent period) – t1. To carry stimulating electrodes in distant place and definite this latent period – t2. The results, which receiving on the electromyograph‘s screen represent in your exercise book.

To measure the distance between the place of stimulating electrodes – S.The speed‘s conduction of excitation which are moving by nerve determine

according to the formula: V=S : (t1-t2) (m/s).In conclusion define whether the speed is within physiology norm. If not, than

explain the reason of this phenomena.

Students’ Independent Study Program

Objectives for Students’ Independent Studies You should prepare for the practical class using the existing textbooks and lectures. Special attention should be paid to the following:

Theme 11. Common characteristic of physiology

a) Defining of “physiology” notion (Physiology is the science about the regularities of organisms‘ vital activity in connection with the external environment.)

b) Tasks of physiological subjects (A deep studying of the mechanisms of vital activity of health man with the matter of expose the causes and characters‘ breaches of this mechanisms in different diseases.)

c) Connection of physiology with other sciences (Connection of physiology with anatomy course – the names, localization, functions of nerves, muscles, bones, vessels, inner organs, endocrine glands; with histology – the structure of nerves, muscles, bones, vessels, inner organs, endocrine glands; with chemistry – osmotic and oncotic pressure, gradient of concentration, with physics – electric

conductivity, with biology – blood groups inheritance. This is the connection of physiology with the subjects which was studied. The physiology is necessary for pathologic physiology, pathologic anatomy, surgery, obstetrics, therapeutics.)

2. Method of physiologya) Observation (This is the method in which the scientists don‘t mix in course

of vital processes. They only make use of vision and description of all changes. On the base of this changes they make conclusions.)

b) Experiment (There are two kinds of experiments: acute and chronic. Acute experiment was doing with the helps of anesthesia. It may be accompanied by cut off the nerves, introduction the different substances. The chronic experiment was doing in vital animals, for example, after the acute experiment scientists can used the observation.)

c) Examination (This is the method of examine the patient with different diseases, for example, with using the different apparatuses.)

d) Simulation (We can simulation different processes as a laboratory simulation or realistic simulation, for example, apparatus of artificial kidney or apparatus of artificial circulation. It may be the simulation the different processes by means of computers.)

3. History of physiology developmenta) Till 17 century (The first medicine used the knowledge about function of

health and ill person and animal, which was based on the observation method. This summarizing of receiving results was doing by Hippocrates, Gallen, Aristotel, Ibn Sina (Avicenna). One of the doctor was Akmean. He come to the conclusion that brain is the organ of consciousness and answer for memory, thought, filling. Empedocl determined that the breathing are doing not only by nose and mouth, but through skin too. Pracsagor distinguished the arterial and venous vessels, but it thought that they have air. Gallen considered that arteries had blood, established the knowledge about the breathing, described the nerves.)

b) In 17-18 centuris (Garvey in 1628 published the work about the small and big circles of blood circulation and about the heart as a engine of blood. Decart was the author of the first text-book “About the Man”, developed the theory of pain, hunger, thirst, digestion, vision, memory. The high of his physiology investigation was the description of the organism‘s reaction on the external irritations. Prokhaska considered that the reflex act may arise in internal and external stimulus. Levenguk and Malpigy described the capillaries. This development widen the vision on blood circulation. Discovering Azelly and Bartolini lymphatic vessels maintain the lymph circulation. Galvani put the bases of electric physiology.)

c) From 19 century to our days (In 19 century physiology separated of anatomy and became the independent science. Majandi studied the physiology of nerves system. Bernar studied the physiology mechanisms of development of digestive juice and their digestion properties, the role of liver in supporting the sugar level in blood, meaning of constant of pupils‘ internal surrounding. Yung

worked out the three component theory of color perception. Gelmgolths developed this theory and creation the theory of hear perception. Phylomaphytsky worked out the theory of cyclic functioning of nerves system. Phylomaphytsky and Basov worked the operation of suturing the gastric fistula on dogs. Phylomaphytsky and Pirogov worked the method of anesthesia intravenous. Gering worked out the theory of the color vision. Gering and Braier described the reflex of nervus vagus, which control the breathing. Boydich formulated the “all or none” low, which say that cardiac muscle can contract in full or noncontract. In 1846 Ludvig described the theory of uropoiesis. Kennon created the doctrine about homeostasis. G.Selye studied the stress-syndrome.)

d) Standing of physiology in Ukraine (In year 1593 was opened the first high medical school near Lviv – Zamoiska academy. In year 1594 this school became the university and it has given the doctor degree. In 1661 was opened the Lviv University with the medical faculty. In 1805 was opened the Charkiv University with the medical faculty. On this the medical faculty studied Danilevsky, who published the important work about the influence of brain on blood circulation and breathing, the text-book from physiology, he was the one science in the world, who register bioelectrical phenomenon of dogs‘ brain. In September 1842 developed the chair of physiology of health people in the medical faculty of Kiev University. In 1842 Valter opened the nerves of vessel constriction and showed that its is the sympathetic. Leontovich was the first in the world who described the nerves cells in the peripheral plexuses and lead that peripheral nerves plexuses resume during the life, worked out the original method of staining which permit study of synapses in nerves system and come to the conclusion that it is the physiological apparatuses between neuronal connection. In 1913 Pravdich-Neminsky register electroencephalogramm in experiment. Voroncov created the common theory about the unity of main physiology processes excitement and inhibition. Bogach was the first who established the regulatory influences of hypothalamus on the pancreatic juice secretion. . In 1865 was opened the Odessa University. Sechenov opened the inhibition in central nerves system. In 1863 Sechenov published the book “Reflexes of brain".)

Key words and phrases: After-depolarisation, after-hyperpolarisation, antiport, chemical mediator, electrical synapses, exitation, firing level, inhibition, latent period, local responce, overshoot, period of latent addition, postsynaptic cell, presynaptic cell, refractory period, resting membrane potential, saltatory conduction, spike, stimulator, subnormal period, supernormal period, symport, synapses, apparatus for irritation of biological structure; apparatus for register of physiological processes, observation, experiment, examination, modeling

Theme 21. Resting membrane potential

a) Common characteristic (There is a potential difference across the membranes of most if not all cells, with the inside of the cells negative to the exterior. By convention, this resting membrane potential (steady potential) is

written with a minus sign, signifying that the inside is negative relative to the exterior. Its magnitude vanes considerably from tissue to tissue, ranging from -9 to –100 mV. When 2 electrodes are connected through a suitable amplifier to a CRO and placed on the surface of a single axon, no potential difference is observed. However, if one electrode is inserted into the interior of the cell, a constant potential difference is observed, with the inside negative relative to the outside of the cell at rest. This resting membrane potential is found in almost all cells. In neurons, it is usually about –70 mV.)

b) Mechanism of development (There are two kind of ion’s transport: active and passive. Active transport is doing due to the energy of ATP. The sodium-potassium pump responsible for the coupled active transport of Na+ out of cells and K+ into cells is a unique protein in the cell membrane. This protein is also an adenosine triphosphatase, ie, an enzyme that catalyzes the hydrolysis of ATP to adenosine diphosphate (ADP), and it is activated by Na+ and K+. Consequently, it is known as sodium-potassium-activated adenosine triphosphatase (Na+-K+

ATPase). The ATP provides the energy for transport. The pump extrudes three Na+

from the cell for each two K+ it takes into the cell, ie, it has a coupling ratio of 3/2. Its activity is inhibited by ouabain and related digitalis glycosides used in the treatment of heart failure. It is made up of two subunits, each with a molecular weight of about 95,000, and two subunits, each with a molecular weight of about 40,000. Separation of the subunits leads to loss of ATPase activity. The subunits contain binding sites for ATP and ouabain, whereas the subunits are glycoproteins. Application of ATP by micropipette to the inside of the membrane increases transport, whereas application of ATP to the outside of the membrane has no effect. Conversely, ouabain inhibits transport when applied to the outside but not to the inside of the membrane. Consequently, the subunits must extend through the cell membrane. The protein could exist in 2 conformational states. In one, three Na+ bind to sites accessible only from the inside of the membrane. This triggers hydrolysis of ATP, and the protein changes its conformation so that the three Na+ are extruded into the ECP. In the second conformation, two K+ bind to sites accessible only from the outside of the membrane. This triggers a return to the original conformation while extruding two K+ into the interior of the cell. It appears that Na+ binding is associated with phosphorylation of the protein and K+

binding with dephosphorylation.)

2. The origin of excitationa) Characteristic of experimental stimulus (For the force it divided on the

under threshold, threshold and upper threshold.)b) Local answer, critical range of depolarization (Local answer is arised only

on under threshold stimulus. Critical range of depolarization is the point from which the action membrane potential can develop.)

c) Genesis of the membrane potential (The stimulus artifact is followed by an isopotential interval (latent period) that ends with the next potential change and corresponds to the time it takes the impulse to travel along the axon from the site of stimulation to the recording electrodes. Its duration is proportionate to the distance between the stimulating and recording electrodes and the speed of conduction of the axon. If the duration of the latent period and the distance between the electrodes are known, the speed of conduction in the axon can be calculated. For example, assume that the distance between the cathode stimulating

electrode and the exterior electrode is 4 cm. The cathode is normally the stimulating electrode. If the latent period is 2 ms long, the speed of conduction is 4 cm/2 ms, or 20 m/s.

The first manifestation of the approaching impulse is a beginning depolarization of the membrane. After an initial 15 mV of depolarization, the rate of depolarization increases. The point at which this change in rate occurs is called the firing level. Thereafter, the tracing on the oscilloscope rapidly reaches and overshoots the isopotential (zero potential) line to approximately +35 mV. It then reverses and falls rapidly toward the resting level. When repolarization is about 70 % completed, the rate of repolarization decreases and the tracing approaches the resting level more slowly. The sharp rise and rapid fall are the spike potential of the axon, and the slower fall at the end of the process is the after-depolarization. After reaching the previous resting level, the tracing overshoots slightly in the hyperpolarizing direction to form the small but prolonged after-hyperpolarization. The after-depolarization is sometimes called the negative after-potential and the after-hyperpolarization the positive after-potential, but the terms are now rarely used. The whole sequence of potential changes is called the action potential. It is a monophasic action potential because it is primarily in one direction. Before electrodes could be inserted in the axons, the response was approximated by recording between an electrode on intact membrane and an electrode on an area of nerve that had been damaged by crushing, destroying the integrity of the membrane. The potential difference between an intact area and such a damaged area is called a demarcation potential.)

d) Changing of excitability in the time of excitation (During the action potential as well as during catelectrotonic and anelectrotonic potentials and the local response, there are changes in the threshold of the neuron to stimulation. Hyperpolarizing anelectrotonic responses elevate the threshold and catelectrotonic potentials lower it as they move the membrane potential closer to the firing level. During the local response the threshold is also lowered, but during the rising and much of the falling phases of the spike potential the neuron is refractory to stimulation. This refractory period is divided into an absolute refractory period, corresponding to the period from the time the firing level is reached until repolarization is about one-third complete; and a relative refractory period, lasting from this point to the start of after-depolarization. During the absolute refractory period no stimulus, no matter how strong, will excite the nerve, but during the relative refractory period stronger than normal stimuli can cause excitation. During after-depolarization the threshold is again decreased, and during after-hyperpolarization it is increased. These changes in threshold are correlated with the phases of the action potential.)

3. Receptor potential (Stimulation of dendrites of nerves cells lead to oscillation of resting membrane potential. This changes called receptor potential. Duration of receptor potential correspond to duration of stimulation. Receptor potential cause by increasing of nerves permeability of dendrites membrane. Receptor potential lead to axon hillock. Spreading of receptor potential depend on diameter of dendrites, resistance of cytoplasm and resistance of cell membrane.

4. Carrying of excitation by axons

a) Condition of carrying (1. Anatomic integrity of nerve‘s filament. 2. Physiological full value.)

b) Laws of carrying (1. Double-sided conduction. 2. Isolated of conducting. 3. Conducting of excitation without attenuation.)

c) Carrying in myelinated nerves (In myelin filaments conducting of excitation is doing from node of Ranvier to node of Ranvier.)

d) Carrying in nonmyelinated nerves (In nonmyelin filaments conducting of excitation is doing uninterrupted.)

Key words and phrases: potential difference, excitability, excitation, local response, refractory period, after-depolarization, membrane potential, stimulation, after-hyperpolarization, absolute refractory period, relative refractory period, local answer, critical range of depolarization, resting membrane potential, zero potential, spike potential, period of latent addition, supernormal period, subnormal period, firing level, propagated action potential, axon hillock

Students must know:Theme 11. Common characteristic of physiology2. Method of physiology3. History of physiology development4. Main notion of physiologyTheme 21. Structure of cell membrane2. Structure of nerves3. Bioelectrical condition of cell membrane4. Origin of excitement and stimulate of excitability

Students should be able to:Theme 11. To define the type of functional diagnostic apparatuses2. To keep protocols of practical units.Theme 21. To estimate bioelectrical phenomenon in excitable tissues2. To master the techniques of biopotential lead

Tests and Assignments for Self-assessmentMultiple Choice.Choose the correct answer/statement:Theme 11. What kind of physiological method doing only on peoples?

a) Observation; b) Acute experiment; c) Chronic experiment; d) Examination; e) Modelling

2. What kind of physiological method doing only on animals with aneasthesia?

a) Observation; b) Acute experiment; c) Chronic experiment; d) Examination; e) Modelling

3. What kind of physiological methods doing only on animals without aneasthesia?a) Observation, acute experiment; b) Acute experiment, chronic experiment; c) Chronic experiment, observation; d) Examination, acute experiment; e) Modelling, chronic experiment

4. Who was study the breathing?a) Gallen, Empedocl; b) Hypocrat, Decart; c) Empedocl, Garvey; d) Akmean, Levenguk; e) Magandy, Galvany

5. Who was study the vessels structure?a) Hypocrat, Empedocl, Aristotel; b) Decart, Gallen, Levenguk; c) Galvany,

Magandy, Aristotel; d) Pracsagor, Gallen, Garvey; e) Hypocrat, Akmean, Aristotel

Real-life situations to be solved:1. Patient D. went to you in therapeutic unit with some complains. What kind of physiological method do you use?2. You want to study the changing of breathing in the different condition of atmospheric pressure. What kind of physiological method do you use?

Answers for the Self-Control1. d; 2. b; 3. c; 4. a; 5. d1 real-life situation – Examination and observation. 2 real-life situation – chronic experiment on animals, may be rats, rabbits or dogs.

Theme 21. In the nerves cells during the resting membrane potential:

a) Na+ and K+ go into the cells; b) Na+ and K+ go from the cells; c) Na+ go into the cells, K+ go from the cells; d) K+ go into the cells, Na+ go from the cells; e) Na+ and K+ don‘t move

2. In the nerves cells during the local response:a) Na+ and K+ go into the cells; b) Na+ and K+ go from the cells; c) Na+ go into the cells, K+ go from the cells; d) K+ go into the cells, Na+ go from the cells; e) Na+ go into the cells

3. In the nerves cells during the depolarization:a) Na+ intensively go into the cells; b) K+ intensively go from the cells; c) Na+

go into the cells, K+ go from the cells; d) K+ go into the cells, Na+ go from the cells; e) Na+ and K+ go into the cells

4. In the nerves cells during the repolarization: a) Na+ intensively go into the cells; b) K+ intensively go from the cells; c) Na+

go into the cells, K+ go from the cells; d) K+ go into the cells, Na+ go from the cells; e) Na+ and K+ go into the cells

5. In the nerves cells during the spike:a) Na+ and K+ go into the cells; b) Na+ intensively go into the cells; c) Na+ and K+ go from the cells; d) K+ intensively go from the cells; e) Na+ and K+ go from the cells

6. In the nerves cells during the after-hyperpolarization:a) Na+ intensively go into the cells; b) Na+ go into the cells, K+ go from the cells; c) K+ go into the cells, Na+ go from the cells; d) Na+ and K+ go into the cells; e) Na+ and K+ go from the cells

Real-life situations to be solved:1. Firing level of membrane cell increased from -60 mV to -50 mV. What and why changing excitability of cell?2. Stimulus caused depolarization of the membrane cell, but the excitability of the cell decreased. What is the cause of this change?

Answers for the Self-Control1. c; 2. e; 3. a; 4. b; 5. e; 6. c1 real-life situation – 1. Excitability of cell decrease, because firing potential of its membrane increase. 2. The excitability of the cell decreased during the increasing of firing level.

References:1. Review of Medical Physiology // W.F.Ganong. – Twentieth edition, 2001. – P. 1-12. 49-58.2. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Tenth edition, 2002. – P. 2-9. 52-65.

Methodical Instructions to Lesson 2 for Students

Theme s : 1. PHYSIOLOGY OF SYNAPSES.2. PHYSIOLOGY OF CONNECTION BETWEEN THE NEURONS.3. ELECTROPHYSIOLOGICAL PHENOMENA IN MUSCLE CELLS.4. PHYSIOLOGY OF SPINAL CORD.

Aim: To know the peculiarities mechanisms of transmission‘s excitation through the synapses in the skeletal and smooth muscles. To know the functioning peculiarities of nervous system. To know the function, physiological properties and processes in skeletal, smooth and cardiac muscles. To know functions, reflectory activity, ascendens and descendens ways of spinal cord, to provoke and estimate tendinous and dermal reflex of spinal cord.

Professional Motivation: The knowledge of the peculiarities mechanisms of transmission‘s excitation through the synapses in the skeletal and smooth muscles is necessary for future physicians for nomination medicine of synaptic effect. The knowledge of the functioning peculiarities of nervous system, peculiarities of excitement transmition in neural chains, inhibition, reflexes is necessary for future physicians for understanding the principles of nervous system working. The knowledge of functions, physiological properties and processes in skeletal, smooth and cardiac muscles is necessary for future physicians to evaluate their functional condition. The knowledge of functions of spinal cord is necessary for future physicians to analyse the mechanisms` status of segmental regulation of organism’s functions in norm and pathology, in clinical diagnosis, in preventive and therapeutic measures.

Basic Level:1. Structure of smooth muscle. Structure of skeletal muscle. Anatomy of spinal cord (Anatomy Course).2. Structure of nervous and neuroglial cells. Ultrastructure of muscles. Ultrastructure of spinal cord (Histology Course) 3. Structure of reflector arc (Biology Course)4. Bioelectrical potential (Physic Course)5. Anatomy of muscle (Anatomy Course)

Students’ Practical Activities:

Theme 1

Evaluation of neuro-muscular transmissionTo establish stimulating electrodes on the forearm (antebrachium) over the

nervus ulnaris. The leading electrodes place over the muscle flexion wrist ulnar. Inflict the upper threshold stimulus with the gradual increasing of frequency to 70 impulses per second. On the electromyograph‘s screen look after the changing of amplitude of active membrane potential. The results, which receiving on the electromyograph‘s screen represent in your exercise book.

In conclusion evaluate the condition of neuro-muscular transmission. To explain the changing of active membrane potential when the frequency of stimulus increased.

Theme 2Space summation of under threshold stimulation

To establish stimulating electrodes on the project of m. flexor carpi radialis in the middle third of antebrachii with the common square 1,2 sm2. To establish level of threshold stimulus, which elicit prolonged contraction of muscle.

After that on this muscle put the electrodes with common square 4,0 sm2. Inflict the under threshold stimulus that was for electrodes with the common square 1,2 sm2.

In conclusion open the mechanism of development of space summation.

Theme 3Single contraction and tetanus of skeletal muscles

To establish stimulating electrodes over the nervus ulnaris more medial to processus ulnaris. To inflict the stimulus with different frequency. Pay attention on the external manifestation of single contraction and tetanus of muscles, which are innervated by nervus ulnaris.

Represent your results (single contraction and tetanuses) in your exercise book.In conclusion define whether development the single contraction and tetanus of

skeletal muscles.Electromyography of volitional conduction of muscles

To establish leading electrodes over the musculus biceps brachii (one electrodes is situated on belly, other – on tendon). Inflict the upper threshold stimulus. To bend slowly arm to maximal tension of musculus biceps brachii.

To calculate the frequency of active potential, which receiving on the electromyograph‘s screen. The results represent in your exercise book.

In conclusion define the type of myogram, which was received.Theme 4

Biceps-reflexMake a stroke by neurologic hammer on the tendon of biceps above radial

bend. The hand of observed person must be semibent and maximally relaxed. With this aim his forearm you must lie on forearm of observer. Call rellexon two hands. Compare reactions. Represent schematically arc of the reflex in conclusion.

Triceps-reflex

Make a stroke by neurologic hammer on the tendon of m. triceps brachii above radial process. The hand of observed person must be relaxed, bend in radial articulation and abducted by observer on the back and outside. Call reflex on two hands. Compare reactions. Represent schematically arc of the reflex in conclusion.

Patellar reflexMake a stroke by neurologic hammer on the tendon of quadriceps of hip under

the patella. Observed person is sitting with compound legs. Muscle must be relaxed. Call reflex on two legs, with and without test of Yendrasyk. Compare reactions. Represent schematically arc of the reflex in conclusion.

Ahill reflex.Offer observed person to stand on chair with freely hanging feet. Make a stroke

by nurologic hammer on Ahill's tendon to legs, with and without test of Yendrasyk. Compare reactions. Represent schematically arc of the reflex in conclusion.

Indicate about what received results testify, from what results and why are they arising these reflexes.

Students’ Independent Study Program

Objectives for Students’ Independent Studies You should prepare for the practical class using the existing textbooks and lectures. Special attention should be paid to the following:

Theme 11. Common characteristic of synaptic and junction transmission (Impulses are transmitted from one nerve cell to another at synapses. These are the junctions where the axon or some other portion of one cell (the presynaptic cell) terminates on the soma, the dendrites, or some other portion of another neuron (the postsynaptic cell). It is worth noting that dendrites as well as axons can be presynaptic or postsynaptic. Transmission at most of the junctions is chemical; the impulse in the presynaptic axon liberates a chemical mediator. The chemical mediator binds to receptors on the surface of the postsynaptic cell, and this triggers intracellular events that alter the permeability of the membrane of the postsynaptic neuron. At some of the junctions, however, transmission is electrical, and at a few conjoint synapses it is both electrical and chemical. In any case, impulses in the presynaptic fibers usually contribute to the initiation of conducted responses in the postsynaptic cell, but transmission is not a simple jumping of one action potential from the presynaptic to the postsynaptic neuron. It is a complex process that permits the grading and modulation of neural activity necessary for normal function.

In the case of electrical synapses, the membranes of the presynaptic and postsynaptic neurons come close together, forming a gap junction. Like the

intercellular junctions in other tissues, these junctions form low-resistance bridges through which ions pass with relative ease. Electrical and conjoint synapses occur in mammals, and there is electrical coupling, for example, between some of the neurons in the lateral vestibular nucleus. However, most synaptic transmission is chemical.

Transmission from nerve to muscle resembles chemical synaptic transmission. The myoneural junction, the specialized area where a motor nerve terminates on a skeletal muscle fiber, is the site of a stereotyped transmission process. The contacts between autonomic neurons and smooth and cardiac muscle are less specialized, and transmission is a more diffuse process.)

a) Classification of synapses (For localization – central (neuro-neuronal) and peripheral (neuro-muscles, neuro-secretion; central synapses may be axo-somatic, axo-dendrites, axo-axonal, dendro-dendrites; for functional meaning – excitatory and inhibitory; for the method of transmission – electrical and chemical.

There is considerable variation in the anatomic structure of synapses in various parts of the mammalian nervous system. The ends of the presynaptic fibers are generally enlarged to form terminal buttons (synaptic knobs). Endings are commonly located on dendritic spines, which are small knobs projecting from dendrites. In some instances, the terminal branches of the axon of the presynaptic neuron form a basket or net around the soma of the postsynaptic cell (“basket cells” of the cerebellum and autonomic ganglia). In other locations, they intertwine with the dendrites of the postsynaptic cell (climbing fibers of the cerebellum) or end on the dendrites directly (apical dendrites of cortical pyramids) or on the axons (axo-axonal endings). In the spinal cord, the presynaptic endings are closely applied to the soma and the proximal portions of the dendrites of the postsynaptic neuron. The number of synaptic knobs varies from one per postsynaptic cell (in the midbrain) to a very large number. The number of synaptic knobs applied to a single spinal motor neuron has been calculated to be about 10,000, with 2000 on the cell body and 8000 on the dendrites. Indeed, there are so many knobs that the neuron appears to be encrusted with them. The portion of the soma membrane covered by any single synaptic knob is small, but the synaptic knobs are so numerous that, in aggregate, the area covered by them all is often 40 % of the total membrane area. In the cerebral cortex, it has been calculated that 98 % of the synapses are on dendrites and only 2 % are on cell bodies.)

b) Structure of synapses (All synapses consist of: presynaptic membrane, postsynaptic membrane, synaptic cleft, subsynaptic membrane.)

c) Excitatory postsynaptic porential (Single stimuli applied to the sensory nerves in the experimental situation described above characteristically do not lead to the formation of a propagated action potential in the postsynaptic neuron. Instead, the stimulation produces either a transient, partial depolarization or a transient hyperpolarization.

The depolarizing response produced by a single stimulus to the proper input begins about 0,5 ms after the afferent impulse enters the spinal cord. It reaches its peak 1-1,5 ms later and then declines exponentially, with a time constant (time required for the response to decay to 1/e, or 1/2,718 of its maximum) of about 4

ms. During this potential, the excitability of the neuron to other stimuli is increased, and consequently the potential is called an excitatory postsynaptic potential (EPSP).

The EPSP is due to depolarization of the postsynaptic cell membrane immediately under the active synaptic knob. The area of inward current flow thus created is so small that it will not drain off enough positive charges to depolarize the whole membrane. Instead, an EPSP is inscribed. The EPSP due to activity in one synaptic knob is small, but the depolarizations produced by each of the active knobs summate.

Summation may be spatial or temporal. When activity is present in more than one synaptic knob at the same time, spatial summation occurs and activity in one synaptic knob is said to facilitate activity in another to approach the firing level. Temporal summation occurs if repeated afferent stimuli cause new EPSPs before previous EPSPs have decayed. The EPSP is therefore not an all or none response but is proportionate in size to the strength of the afferent stimulus. If the EPSP is large enough to reach the firing level of the cell, a full-fledged action potential is produced.)

d) Synaptic delay (When an impulse reaches the presynaptic terminals, there is an interval of at least 0,5 ms, the synaptic delay, before a response is obtained in the postsynaptic neuron. The delay following maximal stimulation of the presynaptic neuron corresponds to the latency of the EPSP and is due to the time it takes for the synaptic mediator to be released and to act on the membrane of the postsynaptic cell. Because of it, conduction along a chain of neurons is slower if there are many synapses in the chain than if there are only a few. This fact is important in comparing, for example, transmission in the lemniscal sensory pathways to the cerebral cortex and transmission in the reticular activating system. Since the minimum time for transmission across one synapse is 0,5 ms, it is also possible to determine whether a given reflex pathway is monosynaptic or polysynaptic (contains more than one synapse) by measuring the delay in transmission from the dorsal to the ventral root across the spinal cord.)

2. Common characteristic of electrical synapses (Electrical synapses is the junctions in which the transmission of information do through the direct passage of bioelectrical signal from cell to cell. This synapses has small synaptic split (to 5 nm), low specific resistance between the presynaptic and postsynaptic membranes. There are the transverse canals in both membranes with the diameter of 1 nm..)

a) Excitatory transmitter (Excitatory impulses go to the synapse and increase permeability of postsynaptic cell membrane to Na+.)

b) Inhibitory transmitter (Inhibitory impulses go to the synapse and increase permeability of postsynaptic cell membrane to Cl-, not to Na+.)

3. Common characteristic of chemical synapses (Chemical synapses is the junctions in which the transmission of information do through the direct passage with chemical substances from cell to cell. These substances named mediators.)

a) Classification of chemical synapses (These synapses named for the type of mediator – cholinergic (mediator – acetylcholine), adrenergic (mediator – epinephrine, norepinephrine), serotonin (mediator – serotonin), dopaminenergic (mediator – dopamin), GABA-ergic (mediator – gamma-aminobutyric acid).

b) Chemical transmission of synaptic activity (Active membrane potential go along the nerve to presynaptic end – presynaptic membrane have depolarilazed – the Ca2+-cannals activated – Ca2+-go to the presynaptic end – Ca2+-activated transport of vesiccles with the mediator along the neurofilaments to presynaptic membrane – the mediator pick out from presynaptic ends to the synaptic split – molecules of mediator diffuse through the synaptic split to postsynaptic membrane – molecules of mediator interact with the receptors on the postsynaptic membrane – this interaction lead to the conformation of receptors and activation of corresponding substances.)

Key words and phrases: synapses, the presynaptic cell, the postsynaptic cell, chemical mediator, electrical synapses, chemical synapses, conjoint synapses, myoneural junction, neuro-neuronal, neuro-muscles, neuro-secretion, axo-somatic, axo-dendrites, axo-axonal, dendro-dendrites, excitatory and inhibitory synapses, terminal buttons, synaptic knobs, dendritic spines, time constant, excitatory postsynaptic potential (EPSP), spatial or temporal summation, facilitate activity, synaptic delay, specific resistance

Theme 21. Functionally-structures peculiarities of nervous system

a) Neuron as a structurally-functional unit (The bases of nervous system are neurons. They have body or soma and axons and dendrites. Physiological role of axons is transmition of neurons impulses from soma to other neurons or organs, the physiological role of dendrites is supplying of information to the neurons body. The axon hillock has a maximal excitability in neurons. Neuron may be in the rest condition (absent change of rest membrane potential) and active condition (may generate active potential), and inhibition condition (stop the impulses activity of the neuron).

Classification of nervous cells according to functioning meaning:1) Sensory or afferent (to perceive irritation and transmit excitement in central

nervous system); 2) Interneurons (to help spreading of excitement in neurons nets or act inhibition); 3) moving (motor or efferent) – to transmit the excitement to working organs.

Mediators help to connect the neurons. There are excitable (glutamine acid, acetylcholine) and inhibitory (gamma-ammino-butiric acid – GABA, glycin) mediators.

b) Axon transport (There are 2 kinds of axon transport: fast and slow. Fast transport provides transmition of mitochondria, vesicles with mediators. It speed is 250-400 mm per day. These transport stop when destroyed microtubules and neurofilaments and if absent in axon ATP and Ca2+. Fast transport may transmit substances from the neurons' body (anterogrades transport) and to body

(retrogrades transport). By help of fast anterogrades transport transmit substances and structures which very important for synaptic action; by help of fast retrogrades transport moving trophogens, which need for nutritient of neurons, and products of axons' metabolism. Slow axon transport is a transmition of all mass of cytoplasm in distal direction. It stops in the case of separation soma from axon. It need to axons' growth and provide trophic in postsynaptic cells.)

c) Role of glia cells (The neurons of the central nervous system are supported by several varieties of non-excitable cells that are called the neuroglia. There are four types of neuroglial cells: astroglia, oligodendroglia, microglia, epindima. They have insulating function, produce myelin, have secretor role, absorbed from intercells fluid K+.)

2. Peculiarities of excitement transmition in neural chaina) Divergence and irradiation (Neurons may to connected by synapses with

different nervous cells. This property has the notion divergence. If it will be an active transmition of excitement it is called irradiation.)

b) Convergence (On the each neuron of central nervous system may come together different afferent impulses. That is why in one neuron coming at the same time different excitement. Later it analyzing and formed in one axon excitement that goes to other chain of nervous net.)

c) Reverberation (In central nervous system are present the nervous chain of own excitement. They arise at the answer of stimulus and excitements in these chains are circulated to the time, when other external stimulus inhibits it or it tired. Reverberation is a base of short-time memory.)

d) Time summation (It is a rise of excitement in the case of action under threshold stimulus. If the frequency of stimulus sufficiently big, excitive postsynaptic potential amount to firing level of depolarization and active potential arise.)

e) Space summation (It is a rise of excitement because of simultaneous action of several under-threshold stimuli. In these case excitive postsynaptic potential amount to the firing level of depolarization or may be more and active potential arise.)

f) Occlusion (On account of divergence one neuron may pass excitive signals on the other neurons. Another neuron may excite several neurons. But if from both neurons which are divergented excitement will be simultaneously the total quantity of excited neurons will be decrease.)

3. Inhibition in the nervous system (Inhibition is an active reaction which add to the oppression or prevention of excitement.)

a) Postsynaptic inhibition (Excitement, which are coming to the inhibitory neuron – Renshow cell of spinal cord, Purkinje cell of cerebellum, astrocites of cortex of big hemisphere – help to produce an inhibitory mediator of this cell (GABA, glycin). According to this act, increase activity of K+ channels of postsynaptic cells, which lead to the hyperpolarization. As result – decrease of

activity of Na+ channels and possibility of development of depolarization in the excitive cell.)

b) Presynaptic inhibition (It may be between axons of excitive and inhibitory neurons. Inhibitory mediator cause hyperpolarization of axon of excitable neuron, prevent arriving of active potential to presynaptic end and as result decrease production of mediator for the development of excitement in postsynaptic cell.)

c) Opposite inhibition (Collaterals of axons of excitive nervous cells are form synaptic connection with inhibitory neurons. These inhibitory neurons have synaptic connection with these excitive neurons. In the case of excitement of excitive neuron activated inhibitory neuron, which produce GABA or glycin in synaptic cleft. As a result, occur hyperpolarization of membrane of excitive neuron and it activity inhibited. Opposite inhibition may be presynaptic or postsynaptic.)

d) Lateral inhibition (If in a neurons' chain, which secure opposite inhibition collaterals of axons of inhibition neurons form synaptic connection with neighboring excitive cells in these cells develop lateral inhibition.)

4. Common characteristic of reflexes (Reflex is a change of functional activity of tissues, organs or whole organism as an answer on stimulus by help of central neural system.)

a) Structure of reflector arc (Reflector arc is a structure base of reflex. It consist of 1. receptors, which are perceive different influences which are act on organism; 2. afferent neurons, which connect receptors with central nervous system; 3. central part of central nervous system, which realize analyses and synthesis of afferent information; 4. efferent chain secure going out of excitement from central nervous system; 5. effector is executive organ; 6. opposite connection.)

b) Classification of reflexes (1. According to the biological meaning: food, defensive, oriental, homeostatic, sex. 2. According to the position of receptors: exteroreceptors (skin, vision, hearing, smell), interoreceptors (visceroreceptors –from inner organs) and proprioreceptors (from muscular, tendons, joints). 3. According to the level of close of reflector arc: spinal, bulbar, mesencephalon, diencephalon, cortex. 4. According to the character of answer: moving, secretory, vessel-moving. 5. According to the duration of answer: fase, tonic. 6. According to the quantity of synapses in central chain: monosynaptic, polisynaptic. 7. According to the kind of efferent part of reflectory arc: somatic, autonomic. 8. According to the position of effector: moving, vessels, heart, secretory, etc. 9. According to the adaptative meaning: physiological, pathological.)

Key words and phrases: sensory or afferent neuron, interneuron, moving (motor or efferent) neuron, gamma-ammino-butiric acid – GABA, glycin, axon transport, fast and slow transport, anterogrades transport, retrogrades transport, neuroglial cells, astroglia, oligodendroglia, microglia, epindima, divergence, irradiation, convergence, reverberation, time summation, space summation, occlusion, inhibition; postsynaptic, presynaptic, opposite, lateral inhibition

Theme 31. Characteristic of skeletal muscles

a) Resting and active potentials of muscle fiber (The electrical events in skeletal muscle and the ionic fluxes underlying them are similar to those in nerve, although there are quantitative differences in timing and magnitude. The resting membrane potential of skeletal muscle is about -90 mV. The action potential lasts 2-4 ms and is conducted along the muscle fiber at about 5 m/s. The absolute refractory period is 1-3 ms long and the after-polarizations, with their related changes in threshold to electrical stimulation, are relatively prolonged. The chronaxie of skeletal muscle is generally somewhat longer than that of nerve.

Although the electrical properties of the individual fibers in a muscle do not differ sufficiently to produce anything resembling a compound action potential, there are slight differences in the thresholds of the various fibers. Furthermore, in any stimulation experiment, some fibers are farther from the stimulating electrodes than others. Therefore, the size of the action potential recorded from a whole muscle preparation is proportionate to the intensity of the stimulating current between threshold and maximal current intensities. The distribution of ions across the muscle fiber membrane is similar to that across the nerve cell membrane. As in nerve, depolarization is a manifestation of Na+ influx, and repolarization is a manifestation of K+ efflux.)

b) Electromyography (Activation of motor units can be studied by electromyography, the process of recording the electrical activity of muscle on a cathode-ray oscilloscope. This may be done in humans by using small metal disks on the skin overlying the muscle as the pick-up electrodes or in un anesthetized humans or animals by using hypodermic needle electrodes. The record obtained with such electrodes is the electromyogram (EMG). With needle electrodes, it is usually possible to pick up the activity of single muscle fibers.)

c) Connection between excitation and contraction (It is important to distinguish between the electrical and mechanical events in muscle. Although oneresponse does not normally occur without the other, their physiologic basis and characteristics are different. Muscle fiber membrane depolarization normally starts at the motor end-plate, the specialized structure under the motor nerve ending.

A single action potential causes a brief contraction followed by relaxation. This response is called a muscle twitch; the action potential and the twitch are plotted on the same time scale. The twitch starts about 2 ms after the start of depolarization of the membrane, before repolanzation is complete. The duration of the twitch varies with the type of muscle being tested. “Fast” muscle fibers, primarily those concerned with fine, rapid, precise movement, have twitch durations as short as 7.5 ms. “Slow” muscle fibers, principally those involved in strong, gross, sustained movements, have twitch durations up to 100ms.)

d) Solitary contraction (The process by which the shortening of the contractile elements in muscle is brought about is a sliding of the thin filaments over the thick filaments. The width of the A bands is constant, whereas the Z lines move closer together when the muscle contracts and farther apart when it is stretched. As the muscle shortens, the thin filaments from the opposite ends of the sarcomere approach each other; when the shortening is marked, these filaments apparently overlap.

The sliding during muscle contraction is produced by breaking and re-forming of the crosslinkages between actin and myosin. The heads of the myosin molecules

link to actin at an angle, produce movement of myosin on actin by swiveling, and then disconnect and reconnect at the next linking site, repeating the process in serial fashion. Each single cycle of attaching, swiveling, and detaching shortens the muscle 1 %.

The immediate source of energy for muscle contraction is ATP. Hydrolysis of the bonds between the phosphate residues of this compound is associated with the release of a large amount of energy, and the bonds are therefore referred to as high-energy phosphate bonds. In muscle, the hydrolysis of ATP to adenosine diphosphate (ADP) is catalyzed by the contractile protein myosin; this adenosine triphosphatase (ATPase) activity is found in the heads of the myosin molecules, where they are in contact with actin.

The process by which depolarization of the muscle fiber initiates contraction is called excitation-contraction coupling. The action potential is transmitted to all the fibrils in the fiber via the T system. It triggers the release of Ca2+ from the terminal cisterns, the lateral sacs of the sarcoplasmic reticulum next to the T system. The Ca2+ initiates contraction. Ca2+ initiates contraction by binding to troponin C. In resting muscle, troponin I is tightly bound to actin, and tropomyosin covers the sites where myosin heads bind to actin. Thus, the troponin-tropomyosin complex constitutes a “relaxing-protein” that inhibits the interaction between actin and myosin. When the Ca2+ released by the action potential binds to troponin C, the binding of troponin I to actin is presumably weakened, and this permits the tropomyosin to move laterally. This movement uncovers binding sites for the myosin heads, so that ATP is split and contraction occurs.

Shortly after releasing Ca2+, the sarcoplasmic reticulum begins to reaccumulate Ca2+. The Ca2+ is actively pumped into longitudinal portions of the reticulum and diffuses from there to the cisterns, where it is stored. Once the Ca2+ concentration outside the reticulum has been lowered sufficiently, chemical interaction between myosin and actin ceases and the muscle relaxes. If the active transport of Ca2+ is inhibited, relaxation does not occur even though there are no more action potentials; the resulting sustained contraction is called a contracture. It should be noted that ATP provides the energy for the active transport of Ca2+ into the sarcoplasmic reticulum. Thus, both contraction and relaxation of muscle require ATP.

e) Types of Contraction (Muscular contraction involves shortening of the contractile elements, but because muscles have elastic and viscous elements in series with the contractile mechanism, it is possible for contraction to occur without an appreciable decrease in the length of the whole muscle. Such a contraction is called isometric (“same measure” or length). Contraction against a constant load, with approximation of the ends of the muscle, is isotonic (“same tension”)).

f) Summation of contraction and tetanus of muscles (The electrical response of a muscle fiber to repeated stimulation is like that of nerve. The fiber is electrically refractory only during the rising and part of the falling phase of the spike potential. At this time, the contraction initiated by the first stimulus is just beginning. However, because the contractile mechanism does not have a refractory period, repeated stimulation before relaxation has occurred produces additional activation of the contractile elements and a response that is added to the contraction already present. This phenomenon is known as summation of contractions. The tension developed during summation is considerably greater than that during the single

muscle twitch. With rapidly repeated stimulation, activation of the contractile mechanism occurs repeatedly before any relaxation has occurred, and the individual responses fuse into one continuous contraction. Such a response is called a tetanus (tetanic contraction). It is a complete tetanus when there is no relaxation between stimuli, and an incomplete tetanus when there are periods of incomplete relaxation between the summated stimuli. During a complete tetanus, the tension developed is about 4 times that developed by the individual twitch contractions.

The stimulation frequency at which summation of contractions occurs is determined by the twitch duration of the particular muscle being studied. For example, if the twitch duration is 10 ms, frequencies less than 1/10 ms (100/s) cause discrete responses interrupted by complete relaxation, and frequencies greater than 100/s cause summation.)

2. Peculiarities of smooth musclesa) Resting membrane (It may be from –50 mV to –60 mV. In this process take

place K+, Na+, Cl-. There are a large concentration of Na+, Cl- in the cells.)b) Active potential (Prolongation of it may be from 20-50 ms to 1 second;

amplitude is less that in skeletal muscles. Active potential end by after-hyperpolarization. The main role in the beginning of it have Ca+.)

c) Elasticity, plasticity and tensility (Another special characteristic of smooth muscle is the variability of the tension it exerts at any given length. If a piece of visceral smooth muscle is stretched, it first exerts increased tension. However, if the muscle is held at the greater length after stretching, the tension gradually decreases. Sometimes the tension falls to or below the level exerted before the muscle was stretched. It is consequently impossible to correlate length and developed tension accurately, and no resting length can be assigned. In some ways, therefore, smooth muscle behaves more like a viscous mass than a rigidly structured tissue, and it is this property that is referred to as the plasticity of smooth muscle.

The consequences of plasticity can be demonstrated in the intact animal. For example, the tension exerted by the smooth muscle walls of the bladder can be measured at varying degrees of distention. After each addition of fluid, the tension was measured for a period of time. Immediately after each increment of fluid, the tension was higher; but after a short period of time, it decreased.)

3. Characteristic of cardiac muscle a) Resting membrane and action potential of cardiac muscle cells (The resting

membrane potential of individual mammalian cardiac muscle cells is about -80 mV (interior negative to exterior). Stimulation produces a propagated action potential that is responsible for initiating contraction. Depolarization proceeds rapidly and an overshoot is present, as in skeletal muscle and nerve, but this is followed by a plateau before the membrane potential returns to the baseline. In mammalian hearts, depolarization lasts about 2 ms, but the plateau phase and repolarization last 200 ms or more. Repolarization is therefore not complete until the contraction is half over.

As in other excitable tissues, changes in the external K+ concentration affect the resting membrane potential of cardiac muscle, whereas changes in the external Na+

concentration affect the magnitude of the action potential. The initial rapid

depolarization and the overshoot are due to a rapid increase in Na+ permeability similar to that occurring in nerve and skeletal muscle, whereas the second plateau phase is due to a slower starting, less intense, and more prolonged increase in Ca2+

permeability. The third phase is the manifestation of a delayed increase in K+

permeability. This increase produces the K+ efflux that completes the repolarization process. The Na+ channel in cardiac muscle is often called the fast channel. It probably has 2 gates, an outer gate that opens at the start of depolarization, at a membrane potential of -60 to -70 mV, and a second inner gate that then closes and precludes further influx until the action potential is over (Na+

channel inactivation). The Ca2+ channel is called the slow channel. It is activated at a membrane potential of -30 to -40 mV and inactivates much more slowly than the fast channel.)

b) Mechanic properties (The contractile response of cardiac muscle begins just after the start of depotanzation and lasts about 1,5 times as long as the action potential. The role of Ca2+ in excitation-contraction coupling is similar to its role in skeletal muscle, except that Ca2+ entering from the ECF as well as Ca2+ from the sarcoplasmic reticulum contributes to contraction. Responses of the muscle are all or none in character, ie, the muscle fibers contract fully if they respond at all. Since cardiac muscle is absolutely refractory during most of the action potential, the contractile response is more than half over by the time a second response can be initiated. Therefore, tetanus of the type seen in skeletal muscle cannot occur. Of course, tetanizalion of cardiac muscle for any length of time would have lethal consequences, and in this sense the fact that cardiac muscle cannot be tetanized is a safety feature. Ventricular muscle is said to be in the “vulnerable period” just at the end of the action potential, because stimulation at this time will sometimes initiate ventricular fibrillation.)

Key words and phrases: elasticity, tensility, tetanus, summation of contraction, electromyography, excitation, contraction, solitary contraction, spontaneous activity, myosin, actin, tropomyosin, troponin, troponin I, troponin T, troponin C, excitation-contraction coupling, the terminal cisterns, contracture, isometric, isotonic, tetanic contraction, complete tetanus, incomplete tetanus, plateau, plasticity

Theme 41. Functionally-structural characteristic of spinal cord.

a) Functions, macroscopic structure (The functions of spinal cord are transmitting the impulses and reflectory function. Spinal cord has segmental structure. It consist of 31-33 segments: 8 cervical, 12 thoracic, 5 lumbal, 5 sacral and from 1 to 3 coccigea. Every segment has two pairs of ventral and dorsal roots: right and left. In outer layer present the white substance, where pass conduction tracts, and in inner layer present grey matter, where present nucleus. Segmental principle of work connects with segmental structure of spinal cord. Spinal reflexes are reflexes, which reflex arc are locked on level of segment of spinal cord. They are tendinous and dermal reflexes. For example, knee reflex is locked on LIII-LIV

level. Reflexes between segments whose reflex arcs are locked on many segments. For example, vessels` reflex – on ThI– LII level.)

b) Property of neurons elements (Body of sensory cell are present outside the spinal cord. Some of them are present in spinal ganglion (they innervate the sceletal muscles). Other are present in extra- and intramural ganglions of autonomic nervous system and provide sensitivity of inner organs. The nervous fibers of sensory cells may be myelinated (v=12-120 m/s) and nonmyelinated (v=2 m/s). They go to spinal cord from pain, chemo- and some mechanoreceptors. 3 % of all neurons are moving, 97 % are interneurons. There are α- and γ-motoneurons. α-motoneurons transmit signals from spinal cord to celetal muscles. γ-motoneurons (30 %) innervate intrausal muscles fibers. Excitement of the fibers lead to the contraction or relaxation of extrafusal muscles fibers.)

c) Interposed of afferent and efferent fibers on peripheral part (Bell-Magandy`s law: in the spinal cord the dorsal are sensory, the ventral roots are motors. Quantity of sensory fibers in posterior roots in 20 time more than moving in arterior.)

2. Reflectory activity of spinal cord.a) Elicity and reflectory arc of miotatic reflexes: elbow, knee, achill (Spinal

somatic reflexes are totally of simple pose and motor acts, which can be realized without participation of higher parts of central nervous system. Stretch reflexes are monosynaptic. Extention, flexor reflexes – polysynaptic, spinal locomotor reflexes are transference. They provide by the help of coordinated movements of limbs. Programated on spinal level It is autonomic movement. Characteristics of elbow, knee, Achilles, plantar and abdominal reflexes. Elbow, knee, Achilles reflexes are monosynaptic, myotatic reflexes. They have segmental character. They are locked on level: elbow – CV– CVI , knee – LII– LIV, Achilles SI– SII.

Plantar and abdominal are dermal monosynaptic reflexe. Are locked on level: plantar – Th12. Superior abdominal Th8 - Th9, medius abdominal Th9–Th10, inferior abdominal – Th11–Th12.

Reflex arcs of tendinous relflex are: knee reflex – intrafusal fibers of m. quadriceps femoris – n. femoralis – LII - LIV – n. femoralis – extrafusal fibers of m. quadriceps femoris.

Achilles reflex – intrafusal fibers of m. gastrocnemius – n. ischiadicus – SI-SII – n. tibialis – extrafusal fibers of m. gastrocnemius.

Elbow flexor reflex – intrafusal fibers of m. biceps brachii – n. musculocutaneus – CV-CVI – n. musculocutaneus – extrafusal fibers of m. biceps brachii.

Elbow extension reflex - intrafusal fibers of m. triceps brachii – n. radialis – CVII-CVIII – n. radialis – extrafusal fibers of m. triceps brachii.

b) Mechanism of development of miotatic reflexes (Muscle spindle consist of nucleus bag (central part) and intrafusal muscles fibers. Spindles connect to the exstrafusal fibers. The quantity of spindles increase in the case of direct muscles' moving. In the nucleus bag present nervous ending (like-spirale), this has receptor function. From begining of afferent fiber, which transmit excitement fast. Nervous ending may excited in the case of cotraction of muscles fibers. γ-motoneurons have the influence on contraction of it too. γ-motoneurons help to contract the intrafusal fibers. These is a course of stretch of nervous ending in nucleus bag. The quantity

of impulses to spinal cord are increase. Sensor neurons end near α-motoneurons, excite them and as result extrafusal fibers are contract. These is a base of myotatic reflexes.)

c) Meaning of invistigation of spinal reflexes (It very important for neurologic department to determing the place of destruction of spinal cord.)

d) Bent and cross-unbend reflexes (Cross-unbend reflexes are in the base of locomotor acts and characterised by inhibition of motoneurons of extensor muscles in the same time of excitement of motoneurons of flexor muscles. At this time on the leg and arm of opposite side present opposite reaction. In the stretch reflexes more high tone are in muscles extensor. They help support the static and pose of body.)

3. Functional meaning of spinal cord' tracts (There are 2 kinds of tracts: ascendens and descendens. Ascendens tract are sensory, descendens are motor.)

a) Ascendens (Ascending tracts are sensory. They conduct information from external environment to the higher situated centers of encephalon. They are conductors of information from enternal surroundings to the higher part of central nervous system. Goll`s tract (fasciculus gracilis), Burdach`s tract (fasciculus cuneatus) are situated in postirior columnus. They are conducters of tactive and proprioceptive (for example, muscles-elbow) sensorities from down and upper part of the body. Tractus spinothalamicus is situated in lateral columnus. They carry pain, temperature – tractus spinothalamicus dorsalis and spinotectalis – and tactil – tractus spinothalamicus ventralis – sensetivities from body to thalamus.)

b) Descendens (Descending tracts are motors. Corticospinal tract (tractus corticospinalis lateralis) is basic motor tract. It is passing in side columns. It is a conductor of impulses to the skeletal muscles, is regulating free movements.

Monacow`s tract (rubrospinalis) – in side columns, regulate tone of skeletal muscles.

Tractus vestibulospinal dorsalis is present in side columns regilate equilibrium and supporting of pose. Olivospinal tract – in side columns – may be takes part in thalamospinal reflexes. Reticulospinal tract – in front columns – is regulating the tone of skeletal muscles, vegetative spinal centers. Vestibulospinal tract – in front columns – regulates equilibrium and supporting of pose.)

Key words and phrases: spinal cord, segments, reflex function, guide function, efferent neurons, afferent neurons, tendinous reflex.

Students must know:Theme 11. Ultrastructure of electrical and chemical synapses2. Excitatory and inhibitory mediatorsTheme 21. Axon transport of substances through the neuron 2. Peculiarities of excitement transmition in neural chain

3. Inhibition in nervous system4. Excitatory and inhibitory mediatorsTheme 31. Ultrastructure of muscles2. Mechanism of muscle‘s energy security Theme 41. The main characteristics of spinal cord.2. All arcs of reflexes.

Students should be able to:Theme 11. To analyze the modern registers about the molecular mechanisms of synaptic transmission in the skeletal and smooth musclesTheme 21. To analyze the mechanism of development of excitement transmition in neural chain2. To analyze the mechanism of development of inhibition in neural chainTheme 3

1. To analyze the peculiarities of physiological properties and physiological processes of skeletal, smooth and cardiac muscles

Theme 31.Call all the reflexes.

Tests and Assignments for Self-assessmentMultiple Choice.Choose the correct answer/statement:

Theme 11. What are the more sensitive to epinephrine kind of receptors?

a) 1-adrenergic; b) 2-adrenergic; c) 1-adrenergic; d) 2-adrenergic; e) M-cholinergic

2. What are sensitive to epinephrine and norepinephrine kind of receptors?a) 1-adrenergic; b) 2-adrenergic; c) 1-adrenergic; d) 2-adrenergic; e) M-cholinergic

3. What are sensitive to acetylcholine kind of receptors?a) -adrenergic; b) -adrenergic; c) nicotinic; d) muscarinic; e) cholinenergic

4. Acetylcholine breaking on … by…:a) on acetyl-CoA and choline, by acetylcholinesterase; b) on acetyl-CoA and choline, by monoamine oxidase; c) on acetyl-CoA and choline, by catechol-O-methyltransferase; d) on dopamine, by dopa decarboxylase; e) on Dopa, by tyrosine hydroxylase

Real-life situations to be solved:1. Neuro-muscles preparation of frog was stimulated with the 250 impulses per

second. What was reduce of muscle‘s frequency?

Answers for the Self-Control1. d; 2. c; 3. e; 4. a1 real-life situation – Reduce of muscle‘s frequency was only 100 impulses per second, because the lability of synapse only 100 impulses per second.

Theme 21. What are the kind of inhibition in the case of increase of potassium ions in outer side of memsrane?

a) Postsynaptic; b) Presynaptic; c) Lateral; d) Opposite 2. You are studying. What are the ways of excitement transmition in neural chain in Your brain?

a) divergence; b) irradiation; c) convergence; d) reverberation; e) time summation3. You are play football. What are the ways of excitement transmition in neural chain in Your brain?

a) divergence; b) irradiation; c) convergence; d) reverberation; e) time summation; f) space summation4. What is the inhibitory mediator of interneurons of spinal cord?

a) glycin; b) acetylcholine; c) epinephrine; d) glutamine acid; e) serotonin5. What is the main excitive mediator of neurons?

a) glycin; b) acetylcholine; c) epinephrine; d) glutamine acid; e) serotonin

Real-life situations to be solved:1. At the morning You stand up by help of alarm-clock after 5 or more signals of it. Why You don't stand up after first signal?

Answers for the Self-Control1. a; 2. all answer are though; 3. all answer are though; 4. a; 5. d1 real-life situation – We stand up after 5 or more signal because in these case will be time summation of under threshold stimulus and after 1 signal we don't may awakening.

Theme 31. What are the peculiarities of the contraction of smooth muscles?

a) Absent of T-system; b) Absent of Ca2+; c) Small quantity of Ca2+; d) Good development of T-system; e) Large concentration of Ca2+

2. What the main ions, which take place in the development of active potential?a) Ca2+; b) Na+; c) K+; d) Cl-; e) H+

Real-life situations to be solved:1. What is the changing of myogram when increase the active potential frequency of individual fibers?2. What is the changing of myogram when increase the quantity of simultaneously

stimulated fibers of muscles?

Answers for the Self-Control1. a; 2. a1 real-life situation – 1. On the myogram increased the frequency and amplitude of summer‘s active potential, which are leading from muscles. 2. On the myogram increased the amplitude of summer‘s active potential, which are leading from musclesTheme 41. Reflex arc of knee reflex is locked on level:

a) LIII – LIV; b) SI – SII; c) LI – LII; d) LIV – SI; e) LIII

2. Reflex arc of albow reflex is locked on level:a) CIV – CV; b) CV – CIV; c) CVII – CVIII; d) ThI – ThII; e) ThV

3. Which tracts of spinal cord are motor:a) Goll`s tract; b) Monakow`s tract; c) Flexig`s tract; d) Gower`s tract; e)

Pyramidal tract.

Real-life situations to be solved:1. Traumatic rupture of person' spinal cord on ThI – ThII arised after automobile

catastrophe. Such symptoms arise after this: free movements disappeared, tactive, temperature, pain sensivities are lost.

a) How can you call this status?b) Explain arising the symptoms?

III. Answers for the Self-Control1. c; 2. b, c; 3. e;

1 real-life situation – a) spinal shock; b) disappearing of free movements can be explained violation of pyramidal tracts; disappearing of sensivity can be explained by violation of spinothalamic tract , Goll`s and Burdach`s tracts.

References:1. Review of Medical Physiology // W.F.Ganong. – Twentieth edition, 2001. – P. 62-84, 90-91, 95-96. 110-113. 123-128. 1302. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Tenth edition, 2002. – P. 67-78, 80-94, 96-99.512-525. 622-632.

Methodical Instructions to Lesson 3 for Students

Theme s : 1. PHYSIOLOGY OF HIND-BRAIN, MESENCEPHALON, AND DIENCEPHALON.2. PHYSIOLOGY OF ENCEPHALON AND CEREBELLUM3. FUNCTIONAL ACTIVITY OF CORTEX OF ENCEPHALON

Aim: To know the peculiarities of regulation of bulbar mesencephalon and diencephalon and to show the specialization each of them which ensure the perfection of central regulation. To realize the peculiarities of regulation subcortical nuclei and cerebellum that reviling the specialization, which provides the perfection of central regulation; to give some reasoning of somatical, sensorial and psychological manifestation of functional asymmetry of the brain of excitable tissues. To define physiological basis of electroencephalography and its possibilities in physiologic anatomy of the cerebral cortex..

Professional Motivation: The knowledge of physiology of metencephalon, mesencephalon and diencephalons is necessary for prospective physicians for diagnosis of different diseases. The knowledge of the physiology of encephalon and cerebellum is necessary for prospective physicians to value the condition of whole organism. The knowledge of cortex of encephalon and methods of its registration is necessary for future physicians to value the functional conditions of encephalon activity.

Basic Level:1.Structure of metencephalon, mesencephalon and diencephalons. Structure of big hemispheres Structure of cerebellum. Structure of cortex of encephalon (Anatomy Course).2.Nuclear composition of metencephalon, mesencephalon. Microstructure of encephalon and cerebellum (Histology Course).

Students` practical Activities:Theme 1

Superciliar reflexMake a light stroke by neurologic hammer on margin of superciliar arc. Call

reflex on both sides. Compare reactions. Represent schematically arc of the reflex in conclusion.

Lid reflexTouch by small piece of cotton wool to the cornea. Compare reactions.

Represent schematically arc of the reflex in conclusion.

Mandibular reflexMake the light stroke on chin (the mouth must be open). Pay attention to the

reaction. Represent schematically arc of reflex in conclusion.Indicate about what received results testify.

Theme 2Displays of functional encephalic asymetry

a) Somatic. Take hand dynamometer, abduct hand from the trunk at right angles. Second hand put down along the trunk. Press with maximum strength fingers and fix the pointer of dynamometer. Do so 5 times with intervals on some minutes. Maximum deflection of the pointer of dynamometer shows maximum strength of the hand’s. Make determination for both hands.b) Psychical. Look attentively on proposed table. Determinate where is smile, and where is grief.

The key to the test: left – hemispherial person on the first picture shows smile, on the second – grief. Right – hemispherial – the other way round.Indicate about what received results testify in conclusion.

Cerebellar testsa) Finger – nasal test. Observed person must touch the end of the nose by index finger. The hand must be straight and abduct to the back. Pay attention to the availability of trembling. Fulfil test with opened and closed eyes.b) Romberg’s test. Offer observed person to stand with put down hands, combined foots and closed eyes. Pay attention is there shaking. If there is no shaking, offer to pick hands up, appraise stability of observed person in present pose.

Indicate what functions of cerebellum this test shows.Theme 3

ElectroencelographyFix electrodes in frontal, temporal and occipital states. Bioelectric activity of

encephalon is registrated when the person is relaxed with eyes closed and later with eyes opened. Define the altitude and frequency of the electroencephalogram. Show it as a scheme in the report.In the conclusion answer what electroencephalogram reflects and what rhythms were registered.

Students’ Independent Study Program

Objectives for Students’ Independent Studies You should prepare for the practical class using the existing textbooks and lectures. Special attention should be paid to the following:Theme 11. Metencephalon (We mean that metencephalon or hind-brain is combain medulla oblongata and pons.)

a) Neuronal composition, nuclei (Medulla oblongata is a continuation of spinal cord. In medulla oblongata are present efferent neurons, interneurons, neurons of asdendens and descendens tracts, ending of afferents neurons. Functions of metencephalon are reflectory, conductive. The grey matter of hind-brain is present in the look of congestion (nucleus). Classification of nucleus of medulla oblongata according to functional properties: moving (n. nervus hypoglossus, n. nervus accessorius), combain (n. nervus vagus, n. nervus glossopharyngeus), substantia formatio reticularis. Classification of nucleus of pons: moving (n. nervus abducens), sensetive (n. nervus vestibulocochlearis), combain (n. nervus facialis, n. nervus trigeminus), substantia formatio reticularis.)

b) Reflexes (1. Chain reflexes are the compound reflector acts, in which one reflexs is a direct cause of rise of future reflexes. In these reactions, take place moving nucleus of medulla oblongata. These reflexes provide chewing and swallowing of food.

2. Reflexes, which are direct on supporting of muscle tone are neck and vestibular. Neck reflexes send up in the case of excitement of proprioreceptors of neck muscles. In these cases change the tone of extensor muscles. If the head throw at backward the tone of muscles extensor of upper extremities increase and tone of muscles extensor of lower extremities decrease. If the head put down the tone of muscles extensor of upper extremities decrease and tone of muscles extensor of lower extremities increase. Turning of the head in right side add to the change of tone of muscles extensor in the side of turhing the head. In this case eyeballs are moving in the opposite side. All neck reflexes are polisynaptic.

Vestibular reflexes are static. Static reflexes of position provide supporting of pose in the space.)

c) Conductive system (All nervous impulses from tracts of Goll's and Burdach's about deep muscle-joint sensitivity transmit to cortex of big hemisphere. Lateral corticospinalis tract begin from the big pyramidal cells of Bets and cross in the hind-brain. To hind-brain go tractus corticobulbaris, which transmit impulses from cortex to mooving nucleus of the cranial nerves. Substantia reticularis of hind-brain give impulses to spinal cord.) 2. Mesencephalon (We mean that that mesencephalon is combain corpora quadrigemina and pedunculi cerebri.)

a) Funtions, nuclei (Functions: reflectory, conductive. Nucleus of mesencephalon: n. nervus oculumotorius, n. nervus trochlearis, substantia nigra, nucleus ruber, nuclei substantia reticularis.)

b) Reflexes (The anterior quadrigeminal bodies are the primary optic centres and involved in certain reflexes responding to light stimuli, including the visual orientation reflexes. Reflex movements of the eyes are induced by impulses

conveyed to the eye musvles from the nuclei of the oculomotor and trochlear nerves. The anterior quadrigeminal bodies take part in the pupillary reflexes. The posterior quadrigeminal bodies are the primary auditory centres. They are involved in the performance of sound orientation reflexes: the pricking up of the ears of animals, turning of the head and body towards a new sound.

Vestibular reflexes are static and statokinetic. Static reflexes of straight provide restore of pose. Statokinetic reflexes direct on supporting of pose in the case of act the change of speed moving. These may be horizontal, vertical (in the lift; increase tone of muscles extensor in the go up mowing and increase tone of muscles flexor in the go down mowing and), angular.)

c) Conductive system (Fibres of the mid-brain connect cortex, mid-brain with hind-brain and spinal cord. If the brain stem of a cat is severed above the medulla oblongata so that the red nuclei are above the incision a special state of the body musculature develops called decerebrate rigidity. This state is characterized by sharply increased tone of the extensor muscles. The extremities are greatly extended; the head is tilted back and the tail raised.)3. Diencephalon (We mean that that diencephalon is combain thalamencephalon and hypothalamus.)

a) Specific nuclei of thalamus (Specific nuclei have connection with the projected zones of cortex. They are sensetive (geniculate bodies; transmit impulses of tractus opticus, sound stimulus proprioreceptors of scin to the cortex) and motor (transmit impulses to moving centres of cortex).

b) Associative nuclei of thalamus (Information are goes to them from periferal parts and specific nuclei of thalamus. There are connections between nuclei and zones. Associative nuclei of thalamus are sensory. For example, nucleus of pillow: it lateral part transmits information about vision to associative zones of occipital part, it medial part transmits information about hearing to associative zones of temporal part of cortex.)

c) Nonspecific nuclei of thalamus (Their neurons are polysensetive. They give the answers of excitement on any stimulus. They have high connection with reticular formation, that's why the answers are in all part of the cortex.)

d) Morpho-funtional peculiarities of hypothalamus (Hypothalamus has 48 pairs of nucleus. According to the functional meaning, it may be divided on 3 parts: anterior, middle and posterior. Anterior part of hypothalamus produced two kinds of substances: liberins and statins. Middle and posterior parts of hypothalamus are zones without hematoencephalic baarrier. In these parts are present neurons, which are sensetive to the change of temperature, chemical components of blood.)

e) Role of hypothalamus in regulation of behavior (Anterior part of hypothalamus is responsible for increase of muscle tone, aggression. Middle part of hypothalamus is responsible for beggining of complex of somatic reactions, which direct at search of water. Posterior part of hypothalamus is responsible for beggining of complex of somatic reactions, which direct at search of food; in this part present the centers of satisfaction.)

4. Physiological role of reticular formation of metecephalon, mesencephalon (Most of the various sensory pathways relay impulses from sense organs via 3- and 4-neuron chains to particular loci in the cerebral cortex. The impulses are responsible for perception and localization of individual sensations. Impulses in these systems also relay via collaterals to the reticular activating system (RAS) in the brain stem reticular formation. Activity in this system produces the conscious, alert state that makes perception possible.

The reticular formation occupies the midventral portion of the medulla and midbrain. It is made up of myriads of small neurons arranged in complex, intertwining nets. Located within it are centers that regulate respiration, blood pressure, heart rate, and other vegetative functions. In addition, it contains ascending and descending components that play important roles in the adjustment of endocrine secretion, the formation of conditioned reflexes, the regulation of sensory input, and consciousness. The reticular activating system is a complex polysynaptic pathway. Collaterals funnel into it not only from the long ascending sensory tracts but also from the trigeminal, auditory, and visual systems and the olfactory system. The complexity of the neuron net and the degree of convergence in it abolish modality specificity, and most reticular neurons are activated with equal facility by different sensory stimuli. The system is therefore nonspecific, whereas the classic sensory pathways are specific in that the fibers in them are activated only by one type of sensory stimulation. Part of the RAS by passes the thalamus to project diffusely to the cortex. Another part of the RAS ends in the intralaminar and related thalamic nuclei, and from them is projected diffusely and nonspecifically to the whole neocortex. The RAS is intimately concerned with the electrical activity of the cortex. It has inhibitory (excitement of the Rentshow cells add to the inhibition of motoneurons; and direct inhibitory influences of motoneurons of spinal cord) and excitive (increase tone of exrensor muscles, contraction of sceletal muscles) influences.)

Key words and phrases: hind-brain, mid-brain, metencephalon, mesencephalon, diencephalons, nuclei of trunk, conductive system, reflex activity, specific associative and nonspecific nuclei of thalamus, reticular formation.Theme 21. Structure-functional characteristic of the subcortical nucleus – basal ganglions

a) Components, functions (Physiologically, the basal ganglia are considered to be comprised of the caudate nucleus, putamen, and globus pallidus. However, the substantia nigra, subthalamus, and important portions of both the thalamus and reticular formation operate in close association with these and therefore are actually part of the basal ganglia system for motor control.

b) Afferent and efferent connection (c) Circulation of excitement in the basal ganglion (cycle of putamen and

nucleus caudatum) (Function of the Caudate Nucleus and Putamen (The Neostriatum). The caudate nucleus and putamen seem to function together to initiate and regulate gross intentional movements of the body. To perform this function they transmit impulses through two different pathways: (1) into the globus

pallidus, thence by way of the thalamus to the cerebral cortex, and finally downward into the spinal cord through the corticospinal pathway; (2) downward through the globus pallidus and the substantia nigra by way of short axons into the reticular formation and finally into the spinal cord mainly through the reticulospinal tracts.

In summary, the neostriatum helps control gross intentional movements that we normally perform subconsciously. However, this control also involves the motor cortex, with which the neostriatum is closely connected.)

d) Notion about extrapyramidal system

2. Functional assymetry of big hemispheresa) Manifestations (somatic, sensory, psychological)b) Methods of investigation c) Practical meaning

3. Structure-functional characteristic of cerebellum (The cerebellum has long been called a silent area of the brain principally because electrical excitation of this structure does not cause any sensation and rarely any motor movement. However, as we shall see, removal of the cerebellum does cause the motor movements to become highly abnormal. The cerebellum is especially vital to the control of very rapid muscular activities such as running, typing, playing the piano, and even talking. Loss of this area of the brain can cause almost total incoordination of these activities even though its loss causes paralysis of no muscles.

But how is it that the cerebellum can be so important when it has no direct capability of causing muscle contraction? The answer to this is that it both helps plan the motor activities and also monitors and makes corrective adjustments in the motor activities elicited by other parts of the brain, It receives continuously updated information on the desired program of muscle contractions from the motor control areas of the other parts of the brain. And it receives continuous information from the peripheral parts of the body to determine the instantaneous status of each part of the body – its position, its rate of movement, forces acting on it, and so forth. It is believed that the cerebellum compares the actual instantaneous status of each part of the body as depicted by the peripheral information with the status that is intended by the motor system. If the two do not compare favorably, then appropriate corrective signals are transmitted instantaneously back into the motor system to increase or decrease the levels of activation of the specific muscles.Since the cerebellum must make major motor corrections extremely rapidly during the course of motor movements, a very extensive and rapidly acting cerebellar input system is required both from the peripheral parts of the body and from the cerebral motor areas. Also, an extensive output system feeding equally as rapidly into the motor system is necessary to provide the necessary corrections of the motor signals.)

a) Afferent system (cells of cortex, afferent fibres, their cooporation)b) Efferent system (nucleus, efferent connection)c) Zones of cerebellum between cortex and nucleus

d) Functions and their neurons securing

FUNCTIONS OF THE BASAL GANGLIABefore attempting to discuss the functions of the basal ganglia in human

beings, we should speak briefly of the better known functions of these ganglia in lower animals. In birds, for instance, the cerebral cortex is poorly developed while the basal ganglia are highly developed. These ganglia perform essentially all the motor functions, even controlling the voluntary movements in much the same manner that the motor cortex of the human being controls voluntary movements. Further more, in the cat, and to a lesser extent in the dog, decortication removes only the discrete types of motor functions and does not interfere with the animal's ability to walk, eat, fight, develop rage, have periodic sleep and wakefulness, and even participate naturally in sexual activities. However, if a major portion of the basal ganglia is destroyed, only gross stereotyped movements remain, which were discussed earlier in relation to the mesencephalic animal.

Finally, in the human being, cortical lesions in very young individuals destroy the discrete movements of the body, particularly of the hands and distal portions of the lower limbs, but do not destroy the person's ability to walk crudely, to control equilibrium, or to perform many other subconscious types of movements. However, simultaneous destruction of a major portion of the caudate nucleus almost totally paralyzes the opposite side of the body except for a few stereotyped reflexes integrated in the cord or brain stem.

With this brief background of the overall function of the basal ganglia, we can attempt to dissect the functions of certain portions of the basal ganglia system, realizing that the system actually operates, along with the motor cortex and cerebellum, as a total unit and that individual functions cannot be ascribed to the different individual parts of the basal ganglia.

Inhibition of Motor Tone by the Basal Ganglia. Though it is wrong to ascribe a single function to all the basal ganglia, nevertheless, one of the general effects of diffuse basal ganglia excitation is to inhibit muscle tone throughout the body. This effect results from inhibitory signals transmitted from the basal ganglia to both the motor cortex and the lower brain stem. Therefore, whenever widespread destruction of the basal ganglia occurs, this causes muscle rigidity throughout the body. For instance, when the brain stem is transected at the mesencephalic level, which removes the inhibitory effects of the basal ganglia, the phenomenon of decerebrate rigidity occurs.

Yet, despite this general inhibitory effect of the basal ganglia, stimulation of certain specific areas within the basal ganglia can elicit positive muscle contractions and at times even complex patterns of movements.

Function of the Globus Pallidus. It is alreadyclear that almost all the outflow of signals from the basal ganglia are channelled through the globus pallidus en route back to the cortex or on their way to lower brain centers. However, in addition to this motor relay function of the globus pallidus, the globus pallidus seems to have still another function that operates in close association with the subthalamus and brain stem to help control the axial and girdle movements of the

body. These movements provide the background positioning of the body and proximal limbs so that the more discrete motor functions of the hands and feet can then be performed. That is, a person wishing to perform an exact function with a hand first positions the body, next positions the legs and arms, and finally tenses all the axial and girdle muscles to provide background positioning and stability of all the proximal portions of the body. These associated tonic contractions are supposedly initiated by circuits in the globus pallidus but operate also through the axial and girdle motor control areas of the brain stem. Lesions of the globus pallidus seriously interfere with the attitudinal movements that are necessary to position the hand and, therefore, make it difficult or impossible for one to use the hand for discrete activities.

Electrical stimulation of the globus pallidus while an animal is performing a gross body movement often will stop the movement in a static position, the animal holding that position for many seconds while the stimulation continues. This fits with the concept that the globus pallidus is involved in some type of servo feedback motor control system that is capable of locking the different parts of the body into specific positions.

THE MOTOR CORTEX—THE PRIMARY AND PREMOTOR AREAS

The posterior part of this area, the somatic sensory cortex, we have already discussed. Lying directly anterior to the somatic sensory area in front of the central sulcus, as illustrated in the figure, and occupying approximately the posterior one half of the frontal lobes is the motor cortex. Nerve signals originating from this region cause muscle contractions in different parts of the body.

The motor cortex is divided into two separate divisions, the primary motor area and the premotor area. The primary area contains very large pyramidal motor neurons that send their fibers all the way to the spinal cord through the corticospinal tract and therefore have almost direct communication with the anterior motor neurons of the cord for control of either individual muscles or small groups of muscles.

This area is frequently called areas VI and VIII because it occupies both these areas in the Brodmann classification of brain topology. The premotor cortex has very few neurons that project nerve fibers directly to the spinal cord. Instead, most of the nerve signals generated in this area cause more complex muscle movements, usually involving groups of muscles performing some specific task, rather than individual muscles. To achieve these results, the premotor area mainly sends its signals into the primary motor cortex to excite multiple groups of muscles. Some of these signals pass directly to the motor cortex through subcortical nerve fibers, but the premotor cortex also has extensive connections with the basal ganglia and cerebellum, both of which transmit signals back by way of the thalamus to the motor cortex. Thus the premotor cortex, the basal ganglia, the cerebellum, and the primary motor cortex constitute a complex overall system for voluntary control of muscle activity.

Key words and phrases: afferent and efferent connections; the circulation of excitation; putamen cycle and the cycle of caudative nucleus; extrapyramidal system; functional asymmetry of hemispheres; cortico-nuclear zones.Theme 3

The functional part of the cerebral cortex is composed mainly of a thin layer of neurons 2 to 5 millimeters in thickness, covering the surface of all the convolutions of the cerebrum and having a total area of about one quarter square meter. The total cerebral cortex probably contains 50 to 100 billion neurons.

Neurohistologists have divided the cerebral cortex into almost 100 different areas, which have slightly different architectural characteristics. Yet in all these different areas except the hippocampal region there still persist representations of all the six major layers of the cortex.

FUNCTIONS OF CERTAIN SPECIFIC CORTICAL AREASStudies in human beings by neurosurgeons have shown that some specific

functions are localized to certain general areas of the cerebral cortex. Now present a map of some of these areas as determined by Penfield and Rasmussen from direct electrical stimulation of the cortex or by neurological examination of patients after portions of the cortex had been removed. The lightly shaded areas are primary sensory areas, while the darkly shaded area is the primary motor area (also called voluntary motor area) from which muscular movements can be elicited with relatively weak electrical stimuli. These primary sensory and motor areas have highly specific functions as we have discussed in previous chapters, whereas other areas of the cortex perform more general functions that we call association or cerebration.

THE SENSORY ASSOCIATION AREASAround the borders of the primary sensory areas are regions called sensory

association areas or secondary sensory areas. In general, these areas extend 1 to 5 centimeters in one or more directions from the primary sensory areas; each time a primary area receives a sensory signal, secondary signals spread, after a delay of a few milliseconds, into the respective association area as well. Part of this spread occurs directly from the primary area through subcortical fiber tracts, but part also occurs in the thalamus, beginning in the sensory relay nuclei, passing next to corresponding thalamic association areas, and then traveling to the association cortex.

The general function of the sensory association areas is to provide a higher level of interpretation of the sensory experiences.

Destruction of the sensory association area greatly reduces the capability of the brain to analyze different characteristics of sensory experiences. For instance, damage in the temporal lobe below and behind the primary auditory area in the "dominant hemisphere" of the brain often causes a person to lose the ability to understand words or other auditory experiences even though they are heard.

Likewise, destruction of the visual association area in Brodmann's areas 18 and 19 of the occipital lobe in the dominant hemisphere, or the presence of a brain tumor or other lesion in these areas, does not cause blindness or prevent normal activation of the primary visual cortex but does greatly reduce the person's ability

to interpret what is seen. Such a person often loses the ability to recognize the meanings of words, a condition that is called word blindness or dyslexia.

Finally, destruction of the somatic sensory association area in the parietal cortex posterior to primary somatic area I causes the person to lose spatial perception for location of the different parts of the body. In the case of the hand that has been "lost," the skills of the hand are greatly reduced. Thus, this area of the cortex seems to be necessary for interpretation of somatic sensory experiences.

Possible Mechanisms for Attention and for Searching the Memory StoreWe are all aware that we can direct our attention toward certain of our mental

activities individually and can also search through our memory store for specific memories. Because of the capability of the generalized thalamocortical system to activate small areas of the cerebral cortex at a time, it is tempting to believe that specific activation of regional portions of the cortex might be the way in which we do indeed direct our attention, and might also be the basis for searching through memory stores.

One other bit of information also suggests that the generalized thalamocortical system might be important in searching for memories: It has been reported that specific lesions in the thalamus are sometimes associated with retrograde amnesia – that is, inability to recall memories that are known to be stored within the brain.

BRAIN WAVESElectrical recordings from the surface of the brain or from the outer surface of

the head demonstrate continuous electrical activity in the brain. Both the intensity and patterns of this electrical activity are determined to a great extent by the overall level of excitation of the brain resulting from functions in the reticular activating system. The undulations in the recorded electrical potentials, are called brain waves, and the entire record is called an electroencephalogram (EEG).

The intensities of the brain waves on the surface of the scalp range from 0 to 300 microvolts, and their frequencies range from once every few seconds to 50 or more per second. The character of the waves is highly dependent on the degree of activity of the cerebral cortex, and the waves change markedly between the states of wakefulness and sleep and coma.

Much of the time, the brain waves are irregular, and no general pattern can be discerned in the EEG. However, at other times, distinct patterns do appear. Some of these are characteristic of specific abnormalities of the brain, such as epilepsy, which is discussed later. Others occur even in normal persons and can be classified as alpha, beta, theta, and delta waves.

Alpha waves are rhythmic waves occurring at a frequency of between 8 and 13 per second and are found in the EEGs of almost all normal adult persons when they are awake in a quiet, resting state of cerebration. These waves occur most intensely in the occipital region but can also be recorded at times from the parietal and frontal regions of the scalp. Their voltage usually is about 50 microvolts. During sleep the alpha waves disappear entirely, and when the awake person's attention is directed to some specific type of mental activity, the alpha waves are replaced by asynchronous, higher frequency but lower voltage beta waves. Note that the visual

sensations cause immediate cessation of the alpha waves and that these are replaced by low voltage, asynchronous beta waves.

Beta waves occur at frequencies of more than 14 cycles per second and as high as 25 and rarely 50 cycles per second. These are most frequently recorded from the parietal and frontal regions of the scalp. Most beta waves appear during activation of the central nervous system or during tension.

Theta waves have frequencies of between 4 and 7 cycles per second. These occur mainly in the parietal and temporal regions in children, but they also occur during emotional stress in some adults, particularly during disappointment and frustration. They can often be brought out in the EEG of a frustrated person by allowing enjoyment of some pleasant experience and then suddenly removing this element of pleasure; this causes approximately 20 seconds of theta waves. These same waves also occur in many brain disorders.

Delta waves include all the waves of the EEG below 3.5 cycles per second and sometimes as low as 1 cycle every 2 to 3 seconds. These occur in deep sleep, in infancy, and in serious organic brain disease. And they occur in the cortex of animals that have had subcortical transections separating the cerebral cortex from the thalamus. Therefore, delta waves can occur strictly in the cortex independently of activities in lower regions of the brain. Physiologic diagnosis of functional state of mechanisms of regulation in general and particular regulative zones, to realize the functions of cortex of encephalon as the highest regulative CNS level.

Key words and phrases: neuron layer, corticolisation of functions, primary zone, motor zone, premotor zone, additional motor zone, somato-sensor zone, optic zone, olfactory zone, zone of taste, associative zones, electrocorticography, electroencephalography.

Students must know:Theme 11. Structure and functions of hind-brain; mesencephalon; thalamus and hypothalamus.2. Physiological role of reticular formation.Theme 21. Morphological and functional characteristics of the Basal Ganglia and

cerebellum. Theme 3

1. Morpho- functional characteristics of cortex of encephalon a) Functions b) Neurons lyers c) Corticalization of functions2. Projective zones a) Primary motor zone b) Premotor zone c) Additive motor zone d) Primary and secondary somatosensor zones

e) Zone of vision f) Hearing, testing, smelling zones j) Column organization3. Associative zone a) Peculiarities b) Physiological meaning4. Investigation of electrical phenomenon in cortex of big hemispheres a) Electrocorticography b) Elecrtoencephalography

Students should be able to:Theme 1To induce: superciliar, lid and mandibular reflexes. Theme 21. Cerebellum tests 2. Displays of functional encephalic asymetry.Theme 31. Register electroencephalogram

Tests and assignments for Self-assessmentMultiple Choice.Choose the correct answer/statement:Theme 11. Where should you make the transaction of the brain to cause the rigidity?

a) upper the red nucleus; b) under the red nucleus; c) under vestibular nucleus;d) under the nucleus of Yakubovych; e) under the nucleus of Deyters.

2.Where are the reflex arcs of orientative reflexes situated?a) the red nucleus; b) quadrigeminal body; c) the black substance;d) nuclei of mesencephalon; e) nucleus of Yacubovych-Vestfal-Triger.

Real-life situation to be solved: 1. It was found that during the intake of pharmacological substances, which

blockade the structures of reticular formation of the trunk of the brain, bioelctric and functional activity of the cortex of brain inhibit intensively. Why does it happen? What is the mechanism relaxation in this case?

Answers for the Self-control1. b; 2. b;1. The transmission of excitation throughout the ascending reticulo-cortical ways which relize an activate influences to the neurons of encephalon cortex.Theme 21. Which layers are present in cerebellum?

a) Molecular, fastigial, Purkinje cell; b) Molecular, stellate, Bets cell; c) Molecular, dentate, Purkinje cell; d) Globose, stellate, Purkinje cell; e) Molecular, stellate, Purkinje cell.

Real-life situations to be solved:1. While studying the functions of different parts of central nervous system, one of the students while extracting the part of brain of a rat, made a wrong move which resulted in disappearing of some right side reflexes, like moving round the circle. Which part of the brain was distroyed?

III. Answers for the Self-Control1. e; 1. Cerebellum.Theme 31. On EEG of patient G. determine alpha-rythm. Which parameters of EEG characterozed alpha rethm?

a) frequency – 18 Gerths, amplitude – 50 mcV; b) frequency – 24 Gerths, amplitude – 25 mcV; c) frequency – 12 Gerths, amplitude – 50 mcV; d) frequency – 9 Gerths, amplitude – 20 mcV; e) frequency – 2 Gerths, amplitude – 25 mcV.2. On EEG of patient P. determine beta-rythm. Which parameters of EEG characterozed beta-rethm?

a) frequency – 18 Gerths, amplitude – 50 mcV; b) frequency – 24 Gerths, amplitude – 25 mcV; c) frequency – 12 Gerths, amplitude – 50 mcV; d) frequency – 9 Gerths, amplitude – 20 mcV; e) frequency – 2 Gerths, amplitude – 25 mcV.

Real-life situation to be solved: 1. While analizing of the EEG of the student the frequency of periodic potential of 12/sec and the altitude of 5 microvolts were found.a) What rhythm do these parameters refer to?b) In what conditions was the student during the registration of EEG?

III. Answers for the Self-control1. c; 2. b;1. a) α–rhythm;b) physical and emotional peace.

References:1. Review of Medical Physiology // W.F.Ganong. – Twentieth edition, 2001. – P. 198-216., 224-225.2. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Tenth edition, 2002. – P. 514, 634. 659, 663-671.

Methodical Instructions to Lesson 10 for Students

Theme: FUNCTIONAL PECULIARITIES OF AUTONOMIC (Vegetative) NERVOUS SYSTEM.

Aim: To know the peculiarities of autonomic nervous system; be able to use this knowledge on practice.

Professional Motivation: The knowledge of physiology of autonomic nervous system is necessary for prospective physicians for diagnosis of different diseases.

Basic Level:1. Structure of autonomic nervous system (Anatomy Course)

Students` practical Activities:Influence of parasympathetic nervous system on the heart activity

To narcotize a rat and fix it on the preparative table. To make the middle cut on the neck. Find and to separate nervus vagus. Registrate the ECG before and after the electric stimulation of the nerve. Compare the frequency of the heart contraction before and after stimulation of the nerve. Show the results of the investigation in your notebooks.

In conclusion define the influence of parasympathetic nervous system on the heart activity.

Students’ Independent Study ProgramI. Objectives for Students’ Independent Studies You should prepare for the practical class the existing textbooks and lectures. Special attention should be paid to the following:

1. Morpho-functional organization of autonomic nervous systema) Sympathetic nervous system (Sympathetic patr of autonomic nervous system

includes paravertebral ganglions, prevertebral ganglions, sympathetic nerves. In the lateral parts of the spinal cord on the thoracic-lumbal level are present sympathetic centre of Yakobson, whose activity regulated by brain stem. Axons of neurons of sympathetic centre go out from the spinal cord in ventral roots and form white branches with the ganglions of sympathetic stems. From these stems go out postganglionic axons and go to the organs of brain, thorax, abdominal cavity and pelvis. Preganglionic axons, which goes out on the level of segments of spinal cord, innerevate a few paravertebral and prevertebral ganglions; that is why provide multiplicative central regulation of different visceral functions.

b) Parasympathetic nervous system (Parasympathetic patr of autonomic nervous system includes ganglions (present near organs-effectors or inside them), parasympathetic nerves. Bodies of the preganglionic parasympathetic neurons are

in the brain stem and in the sacral level of spinal cord. Axons of preganglion neurons go to the postganglion neurons, which are present in ganglions. The parasympathetic fibers are in n.oculomotorius, n.facialis, n.glossopharyngeus, n.vagus, sacral nerves. Parasympathetic nervous system also innervates muscles of vessels, exept sex organs and may be brain.)

c) Metasympathetic nervous system (Metasympathetic patr of autonomic nervous system is intramural ganglions, which are in the organs walls. Reflector arc are present in the wall of organs too. It regulated by sympathetic and parasympathetic system. It has sensory, interneuronal, moving chain and own mediators.)

2. Characteristic of reflector arc of autonomic nervous systema) Sensory part (Receptors are present in inner organs, walls of blood vessels

and lymphatic vessels of skin, muscles. They named interoreceptors. Their stimulus: mechanical, chemical, and temperature irritans. Afferent part of autonomic reflex consists of interoreceptors, dendrites of sensory neurons, which are in autonomic and spinal ganglions.

From interoreceptors afferent informations enter to sensitive neurons, whose body are in autonomic and spinal ganglions. So, in afferent part of autonomic reflex, sensitive information transmit in two ways: 1) from interoreceptors to sensitive neurons of spinal ganglions of dorsal roots of spinal cord; 2) from interoreceptors to sensitive neurons of autonomic ganglions of dorsal, and then to sensitive neurons of spinal ganglion of posterior roots. From spinal ganglions, transmitters of autonomic sensitivity enter in spinal cord. Signal from interoreceptors may enter in brain pass spinal cord. Crossing of afferent signals on interneurons is on spinal' and bulbar' level.)

b) Central part (Spinal level. When the neurons enter in spinal cord one part of the afferent fibers interact with segmental interneurons, which interact with preganglionic neurons. This is polysynaptic arc. Part of the afferent fibers end in grey substance of upper segments and medulla oblongata. Part of the afferent fibers lower and connect by synapses with interneurons of lower segments.

Supraspinal level. Then the afferent signals go to reticular formation of brein stem. Interaction of afferent visceral and somatic signals activates reticular formation. From reticular formation descending signals transmit to preganglion neurons of arc of autonomic reflex. Ascending signals transmited to mid-brain, dyencephalon, cortex.

c) Efferent part. Peculiarities of mediator transmition in efferent part of autonomic nervous system (scheme):

Transmission at the synaptic junctions between pre- and postganglionic neurons and between the postganglionic neurons and the autonomic effectors is chemically mediated. The principal transmitter agents involved are acetylcholine and norepinephrine, although dopamine is also secreted by intemeurons in the sympathetic ganglia.

d) Difference between autonimuc and somatic nervous system (1. Nervous centres in autonimuc nervous system are present in mesencephalon, bulbar part of brain, thoraco-lumbal and sacral part of spinal cord, in somatic – diffuse in all sentral nervous system; 2. Efference ways of reflector arc in autonimuc nervous system consist of two neurons, in somatic – of one; 3. In analysing of information in autonimuc nervous system take part ganglions, in somatic – nervous centres; 4. Exit of nervous fibers from central nervous system autonimuc nervous system is mix, in somatic – segmental; 5. Mediators of autonimuc nervous system are acetylcholine, epinephrine, norepinephrine, ATP, serotonine, gistamine, substance P, of somatic – only acethylcholine; 6. Functions of autonimuc nervous system are growth, work of inner organs, supporting of homeostasis. of somatic – providing moving reactions of sceletal muscles and sensitive outer stimulus; 7. Effect in autonimuc nervous system may be as excitive, as inhibit, in somatic – only excitive.

3. Change of functional condition of organs in the case of stimulation of autonomic nerves

Symptoms Sympathetic effecrs Parasympathetic effecrsPupil of eye Increase Normal or decreaseCardiovascular system: heart beatstrength of cardiac contractility

IncreaseIncrease

DecreaseDecrease

Rate of breathingDiameter of bronchs

Normal or increaseIncrease

Decrease Decrease

Digestive tract:Salivation Increase, viscous saliva Increase, liguid saliva

Preganglionicneuron

Еxtramural ganglion Еffector

Parasympa-thetic nervous system

Аch N-chrАchM-chr

N-chr (sweet glands, vessels of muscles)

Sympathetic nervous system

Аch N-chr

Аch N-chr

Аch N-chr

Catecholamines, AR

EpiNor blood

Adrenal glands

MotilitySecretory functionSphincters

DecreaseDecreaseContract

IncreaseIncreaseRelex

Vessels of sceletal musclesVessels of skinSweet glands

Increase DecreaseSecretion

–––

Key words and phrases: Sympathetic Nervous System, Parasympathetic Nervous System, Metasympathetic Nervous System, sensitive branch, central branch, efferent branch.

Students must know the peculiarities of:1. Sympathetic nervous system2. Parasympathetic nervous system3. Metasympathetic nervous system

Tests and assignments for Self-assessmentMultiple Choice.Choose the correct answer/statement:1. Patient S. has complete on increasing of breathing frequency, heart beat. Which another complets may be in the patient if we know that he has irritation of sympatetic nervous system?

a) Increase salivation, liguid saliva; b) Relaxation of sphincters; c) Increase motility of digestive tract; d) Increase secretion of digestive tract; e) Decrease strength of cardiac contractility.

Real-life situation to be solved: 1. Patient R. has problem in the thoracic level of vertebrum. Which compleate he has?

Answers for the Self-control1. a; 1. He has the problem of irritation of sympathetic nervous system.

References:1. Review of Medical Physiology // W.F.Ganong. – Twentieth edition, 2001. – P. 217-223.2. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Tenth edition, 2002. – P. 697-707.

Methological Instructions to lesson 11 for students

Theme s : 1. ROLE OF THE AUTONOMIC ( VEGETATIVE ) NERVOUS SYSTEM IN REGULATION OF VISCERAL FUNCTIONS.2. CENTRAL REGULATION OF VEGETATIVE FUNCTIONS OF THE ORGANISM.

Aim: To know the role of vegetative nervous system in regulation of homeostasis. To realize the peculiarities of central regulation of vegetative functions of the organism by spinal, bulbar, mesencephal, diencephal, cortical levels.

Professional Motivation: The knowledge of role of vegetative nervous system is necessary for future physicians to value the functional condition of organs. The knowledge of central regulation of vegetative functions of the organism is necessary for future physicians to value the condition of whole organism.

Basic Level: 1. Structure of vegetative nervous system/ Structure of the regulative levels

(Department of Anatomy).2. Microstructure of the regulative levels of CNS (Department of Histology).

Students` Practical Activities:Theme 1

Cold test:Count the frequency of pulse on the one of the hand. Put the arm of another

hand into the лоток of cold water (+14 Co) for 3 minutes and every 30 seconds count the frequency of pulse. After 2 minutes take out the hand. The result of experiment show graphically.

Hot test:Count the frequency of pulse on the one of the hand. Put the arm of another

hand into the лоток of warm water (+45 Co) for 3 minutes and every 30 seconds count the frequency of pulse. After 2 minutes take out the hand. The result of experiment show graphically.In conclusion define, what vegetative reflexes are in base of the tests and what parts of autonomic nervous system dominate in regulation of heart activity.

Theme 2Pilomotor reflex.

To make a thermal (ice) or mechanical stimulus of skin in area of trapezoidal muscle. Pay attention on development of anserine skin on the part of the body. Rise of intensive anserine skin on the whole body testifies of increased of irritation of the sympathetic nervous system (slight anserine skin testifies of normal reaction). It is known, that pileous muscles of head and neck are connected with I-

III thoracic segments, pileous muscles of hands are connected with IV-VII thoracic segments, pileous muscles of trunk are connected with VIII-IX thoracic segments.

In conclusion define, what the results testify.Functional significance of posterior hypothalamus (stereotaxic research).To determine stereotaxic coordinates of posterior hypothalamus. To narcotize a

rat and fix it on a table. Put the identeferentive electrode into the cervic muscles of a rat. The active electrode into the electrodo-holder and lead it into the posterior hypothalamus.

To count a quantity of respiratorical movements during one minute. To make the stimulation and then count a quantity of respiratorical movements once more. Put the results into the chart:

Quantity of respiratorical movementsbefore the stimulation after the stimulation

In conclusion define, why has the respiration been changed during the stimulation of posterior hypothalamus.

Students’ Independent Study ProgramTheme 1Objectives for Students’ Independent Studies You should prepare for the practical class the existing textbooks and lectures. Special attention should be paid to the following:Theme 1RESPONSES OF EFFECTOR ORGANS TO AUTONOMIC NERVE IMPULSESGeneral Principles

The smooth muscle in the walls of the hollow viscera is generally innervated by both noradrenergic and cholinergic fibers, and activity in one of these systems increases the intrinsic activity of the smooth muscle whereas activity in the other decreases it. However, there is no uniform rule about which system stimulates and which inhibits. In the case of sphincter muscles, both noradrenergic and cholinergic innervations are excitatory, but one supplies the constrictor component of the sphincter and the other the dilator.There is usually no acetylcholine in the circulating blood, and the effects of localized cholinergic discharge are generally discrete and of short duration because of the high concentration of acetylcholinesterase at cholinergic nerve endings. Norepinephrine spreads farther and has a more prolonged action than acetylcholine. The epinephrine and some of the dopamine come from the adrenal medulla, but much of the norepinephrine diffuses into the bloodstream from norad-renergic nerve endings.Cholinergic Discharge

In a general way, the functions promoted by activity in the cholinergic division of the autonomic nervous system are those concerned with the vegetative aspects of day-to-day living. For example, cholinergic action favors digestion and absorption of food by increasing the activity of the intestinal musculature, increasing gastric secretion, and relaxing the pyloric sphincter. For this reason, and

to contrast it with the ''catabolic'' noradrenergic division, the cholinergic division is sometimes called the anabolic nervous system.Noradrenergic DischargeThe noradrenergic division discharges as a unit in emergency situations. The effects of this discharge are of considerable value in preparing the individual to cope with the emergency, although it is important to avoid the teleologic fallacy involved in the statement that the system discharges in order to do this. For example, noradrenergic discharge relaxes accommodation and dilates the pupils (letting more light into the eyes), accelerates the heartbeat and raises the blood pressure (providing better perfusion of the vital organs and muscles), and constricts the blood vessels of the skin (which limits bleeding from wounds). Noradrenergic discharge also leads to lower thresholds in the reticular formation (reinforcing the alert, aroused state) and elevated blood glucose and free fatty acid levels (supplying more energy). On the basis of effects like these, Cannon called the emergency-induced discharge of the noradrenergic nervous system the ''preparation for flight or fight.''The emphasis on mass discharge in stressful situations should not obscure the fact that the noradrenergic autonomic fibers also subserve other functions. For example, tonic noradrenergic discharge to the arterioles maintains arterial pressure, and variations in this tonic discharge are the mechanism by which the carotid sinus feedback regulation of blood pressure is effected. In addition, sympathetic discharge is decreased in fasting animals and increased when fasted animals are refed. These changes may explain the decrease in blood pressure and metabolic rate produced by fasting and the opposite changes produced by feeding.

Key words and phrases: vegetative reflexes: viscero-visceral, viscero-dermal, dermato-visceral, tonic activity of vegetative nervous system.

Theme 2MEDULLA OBLONGATAControl of Respiration, Heart Rate, & Blood PressureThe medullary centers for the autonomic reflex control of the circulation, heart,

and lungs are called the vital centers because damage to them is usually fatal. The afferent fibers to these centers originate in a number of instances in highly specialized visceral receptors. The specialized receptors include not only those of the carotid and aortic sinuses and bodies but also receptor cells that are apparently located in the medulla itself. The motor responses are graded and delicately adjusted and include somatic as well as visceral components.

Other Medullary Autonomic ReflexesSwallowing, coughing, sneezing, gagging, and vomiting are also reflex

responses integrated in the medulla oblongata. Coughing is initiated by irritation of the lining of the respiratory passages. The glottis closes and strong contraction of the respiratory muscles builds up intrapulmonary pressure, whereupon the glottis suddenly opens, causing an explosive discharge of air. Sneezing is a somewhat

similar response to irritation of the nasal epithelium. It is initiated by stimulation of pain fibers in the trigeminal nerves.

RELATION OF HYPOTHALAMUS TO AUTONOMIC FUNCTIONMany years ago, Sherrington called the hypothalamus "the head ganglion of the

autonomic system." Stimulation of the hypothalamus produces autonomic responses, but there is little evidence that the hypothalamus is concerned with the regulation of visceral function per se. Rather, the autonomic responses triggered in the hypothalamus are part of more complex phenomena such as rage and other emotions.

"Parasympathetic Center"Stimulation of the superior anterior hypothalamus occasionally causes

contraction of the urinary bladder, a parasympathetic response. Largely on this basis, the statement is often made that there is a "parasympathetic center " in the anterior hypothalamus. However, bladder contraction can also be elicited by stimulation of other parts of the hypothalamus, and hypothalamic stimulation causes very few other parasympathetic responses. Thus, there is very little evidence that a localized "parasympathetic center" exists. Stimulation of the hypothalamus can cause cardiac arrhythmias, and there is reason to believe that these are due to simultaneous activation of vagal and sympathetic nerves to the heart.

Sympathetic ResponsesStimulation of various parts of the hypothalamus, especially the lateral areas,

produces a rise in blood pressure, pupillary dilatation, piloerection, and other signs of diffuse noradrenergic discharge. The stimuli that trigger this pattern of responses in the intact animal are not regulatory impulses from the viscera but emotional stimuli, especially rage and fear. Noradrenergic responses are also triggered as part of the reactions that conserve heat.

Low-voltage electrical stimulation of the middorsal portion of the hypothalamus causes vasodilatation in muscle. Associated vasoconstriction in the skin and elsewhere maintains blood pressure at a fairly constant level. This observation and other evidence support the conclusion that the hypothalamus is a way station on the so-called cholinergic sympathetic vasodilator system, which originates in the cerebral cortex. It may be this system, which is responsible for the dilatation of muscle blood vessels at the start of exercise.

Stimulation of the dorsomedial nuclei and posterior hypothalamic areas produces increased secretion of epinephrine and norepinephrine from the adrenal medulla. Increased adrenal medullary secretion is one of the physical changes associated with rage and fear and may occur when the cholinergic sympathetic vasodilator system is activated. It has been claimed that there are separate hypothalamic centers for the control of epinephrine and norepinephrine secretion. Differential secretion of one or the other of these adrenal medullary catecholamines does occur in certain situations, but the selective increases are small.

ANATOMIC CONSIDERATIONS

The term limbic lobe or limbic system is applied to the part of the brain that consists of a rim of cortical tissue around the hilus of the cerebral hemisphere and a group of associated deep structures – the amygdala, the hippocampus, and the septal nuclei. The region was formerly called the rhinencephalon because of its relation to olfaction, but only a small part of it is actually concerned with smell.

LIMBIC FUNCTIONSStimulation and ablation experiments indicate that in addition to its role in

olfaction, the limbic system is concerned with feeding behavior. Along with the hypothalamus, it is also concerned with sexual behavior, the emotions of rage and fear, and motivation.

Autonomic Responses & Feeding BehaviorLimbic stimulation produces autonomic effects, particularly changes in blood

pressure and respiration. These responses are elicited from many limbic structures, and there is little evidence of localization of autonomic responses. This suggests that the autonomic effects are part of more complex phenomena, particularly emotional and behavioral responses. Stimulation of the amygdaloid nuclei causes movements such as chewing and licking and other activities related to feeding. Lesions in the amygdala cause moderate hyperphagia, with indiscriminate ingestion of all kinds of food.

Key words and phrases: vegetative centers, posterior hypothalamus, anterior hypothalamus, autonomic regulation of diuresis, vegetative regulation of defecation, vegetative regulation of sexual reflexes, limbic system.

Students must know:Theme 11. Vegetative reflexes.2. The importance of sympathetic and parasympathetic nervous systems.3. Autonomic reflexes a) viscero-visceral b) viscero-dermal (viscero-somatic) c) dermato-visceral (somato-visceral)4. Role of autonomic nervous system in supporting of organism' vital activity a) Meaning of sympathetic nervous system b) Role of parasympathetic nervous system c) Meaning of meta sympathetic nervous system d) Tonic activity of autonomic nervous systemTheme 21. Role of spinal cord, hind-brain, mid-brain in regulation of vegetative functions a) Autonomic centers of spinal cord b) Autonomic regulation of micturation c) Autonomic regulation of defecation d) Autonomic regulation of sex reflexes2. Role of hypothalamus in regulation of autonomic functions a) Physiological meaning of posterior hypothalamus

b) Role of anterior hypothalamus c) Meaning of middle hypothalamus3. Role of limbic system and cortex of big hemispheres in regulation of autonomic functions

Students should be able to:1. To make cool and thermal tests.2. To make a pilomotor reflex.

Tests and Assignments for Self-assessmentMultiple Choice.Choose the correct answer/statement:Theme 11. Patient T. has inflamation of appendicular vermiformies. Which somatic manifistation of viscero-somatic reflex he has?

a) Pain and contraction of all abdominal muscles; b) Pain of muscles above place of inflamation; c) Pain and contraction of legs muscles; d) Pain and contraction of muscles above place of inflamation; e) Pain and contraction of all muscles.

Real-life situation to be solved: 1. Student U. after running has increasing of heart beat and pain in right epigastral area. Which kind of autonomic reflex he has?

Answers for the Self-control1. d; 1. This reflex is viscero-visceral.

Theme 21. Patient F. has tumor of anterior stereotaxis. Which heart beart he has?

a) 54 per minute; b) 60 per minute; c) 78 per minute; d) 90 per minute; e) 104 per minute.

Real-life situation to be solved: 1. During the experiment the stimulation of anterior hypotalamus of the rat was held.a) What methods did you use?b) What are reactions of cardiovascular, respiratorical and digestive systems did you see. Explain, please.

Answers for the Self-control1. a; 1. a) Stereotaxis methods.

b) Decreasing of the frequency and power of the contraction of the heart, stenosis of bronchi, motility secretion and absorption in digestive tract. Parasympathetic influences.

References:1. Review of Medical Physiology // W.F.Ganong. – Twentieth edition, 2001. – P. 217-223, 226-229, 232-233, 242.2. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Tenth edition, 2002. – P. 364, 632, 681-684, 697-707, 736.

Methological instruction to lesson 6 for students

Theme s : 1. REGULATION OF PHYSIOLOGICAL FUNCTIONS BY HYPOTHALAMIC-HYPOPHYSIS SYSTEM AND EPINEPHRAL GLANDS.

2. THE ROLE OF GLANDS IN THE REGULATION OF ORGANISM FUNCTIONS3. AGED PECULIARITIES OF NEURAL AND HUMORAL REGULATION.

Aim: To know the mechanism of regulation of physiological functions by hypothalamic-hypophysis system and epinephral glands. To know the peculiarities of regulation of organism functions by glands. To understand the meaning of hormones and their influence on the metabolism of cells and organs. To know the aged peculiarities of neural and endocrine regulation in fetus, newborn, children and old persons.

Professional motivation: The knowledge of these processes is important for physicians in diagnostics of hormonal discharges and treatment of them. The knowledge of hormones role in the organism is necessary for prospective physicians for understanding the changes of organism functions in different situations and for diagnosis of different diseases. The knowledge of aged peculiarities of neural and endocrine regulation in fetus, newborn, children and old persons are necessary for future physicians to value the peculiarities diseases in pediatric and geriatric clinics.

Basic level: 1. Structure of hypothalamus, hypophysis and epinephral glands. Localisation of glands in the human organism (Department of Anatomy).2. Microstructure of hypothalamus, hypophysis and epinephral glands. Microstructure of glands (Department of Histology).3. Hormones of hypothalamic-hypophysis system and epinephral glands (Department of Biology).4. Hormones (department of Biochemistry).

Students` practical Activities:Theme 1

Influence of melanocyte stimulating hormone on pigment cells of swimming membrane of a frog.

Fix a narcotized frog on a table. Stretch the swimming membrane above the hole of the t.able and observe it under the small magnification of a microscope. Pay attention to the condition of pigment cells. Introduce 0,2 ml of melanocyte stimulating hormone into spinal lymphatic sack. Evaluate the color of the animal

and the condiiton of pigment cells in 20 min. Draw what you’ve observed under the microscope before and after the introduction of melanocyte stimulating hormone in your protocols.

In conclusion define what is the influence of melanocyte stimulating hormone.The influence of epinephrine on the size of pupilla

Compare the diameter of pupilla in both eyes of the examinie. Than put 1-2 drops of epinephrine 0,1% into conjuctival sack. Observe the size of pupillas during 20-30 minutes. Picture the observed changes schematically.

In conclusion define the mechanism of observed changes.Theme 2

Evaluation of the parathyroid glands conditiona) Chvostek’s testMake some light knockings by a neurological hammer in front of meatus

acustius externus. If the functions of parathyroid glands are damaged the contraction of the muscles that are innervated by the VII nerve is observed.

b) Veis’ testMake some light knockings on the lateral margin of the orbita where there is a

zygomatical branch of the nervus facialis. If the functions of parathyroid glands are damaged the contraction of the musculus orbicularis oculi is observed.

c) Trusso’s testPress the brachium by turniquet pulse will disappear for 2-3 minutes. If the

functions of parathyroid glands are damaged the titanic contraction of manual muscles is observed.

In conclusion define the functional state of parathyroid glands of the patient.

Influence of the insulin on the glucose adoptionTake two white mice with the same weight. Introduce intraperitoneal 1.5-2.0 ml

of 20 % glucose solution. Give subcutaneal insulin to one mouse. To pick up the urine during one hour.

Make an investigation of the urine for the glucose. Filtrate 3 ml urine. Make a Feling’s reaction for the glucose. Compare the resultates.

In conclusion define the influence of the insulin on the glucose adoption.

Theme 3Age peculiarities of hematoencephalic barrier

There were studied the changes of brain sensitivity to acetylcholine in animals of different age under the influence of hypoxia. Investigations were held on 45 rats of 4-5 months. Control was grown-up rats. In all experiments they registrated electrocorticogram. Acetylcholine was introduces into common jugular vein. On the electrocorticogram they noticed the presence or absense of reaction of cortical biorhythms on the acetylcholine introducing. There was found higher brain sensitivity to acetylcholine in young rats comparing to grown-up rats. It is known that during intraarterial and intraventtricular introduction acetylcholine causes exact changes in EEG. This fact was first described be Bonne and Bremer, Morutsi, and then ensured by many scientific works. The question about activating

influence of acetylcholine during intravenous introduction is not sure, because it is known that acetylcholine goes badly through the hematoencephalic barrier. In our experiments electrocortical reaction in intravenous introduction of acetylcholine was noticed only in 20 % of experiments under grown-up animals. At the same time in young rats it was observed more often – in 78 % of cases. The duration of electrocortical reactions in grown-up rats was shorter than in animals of younger age. More often appearance of brain cortex reaction in young rats in comparison to grown-ups can be explained by higher penetration of hematoencephalic barrier in young rats. Grashchenkov and Kassil noticed that due to high penetration of hematoencephalic barrier in young age hemoreactivic brain formations in children react on changes in composition and properties of internal environment easier and faster than in adults.

Students’ Independent Study Program

І Objectives for Students` Independent Studies: You should prepare for the practical class the existing textbooks and lectures. Theme 1Anterior Pituitary Hormones.

(1) Growth hormone: causes growth of almost all cells and tissues of the body.(2) Adrenocorticotropin: causes the adrenal cortex to secrete adrenocortical

hormones.(3) Thyroid-stimulating hormone: causes the thyroid gland to secrete thyroxine

and triiodothyronine.(4) Follicle-stimulating hormone: causes growth of follicles in the ovaries prior

to ovulation, promotes the formation of sperm in the testes.(5) Luteinizing hormone: plays an important role in causing ovulation; also

causes secretion of female sex hormones by the ovaries and testosterone by the testes.

(6) Prolactin: promotes development of the breasts and secretion of milk. Posterior Pituitary Hormones.

(1) Antidiuretic hormone (also called vasopressin): causes the kidneys to retain water, thus increasing the water content of the body; also, in high concentrations, causes constriction of the blood vessels throughout the body and elevates the blood pressure.

(2) Oxytocin: contracts the uterus during the birthing process, thus perhaps helping expel the baby; also contracts myoepithelial cells in the breasts, thereby expressing milk from the breasts when the baby suckles.Adrenal Cortex.

(1) Cortisol: has multiple metabolic functions for control of the metabolism of proteins, carbohydrates, and fats.

(2) Aldosterone: reduces sodium excretion by the kidneys and increases potassium excretion, thus increasing sodium in the body while decreasing the amount of potassium.

From this overview of the endocrine system, it is clear that most of the metabolic functions of the body are controlled one way or another by the endocrine glands. For instance, without growth hormone, the person remains a dwarf. Without thyroxine and triidothyronine from the thyroid gland, almost all the chemical reactions of the body become sluggish, and the person becomessluggish as well. Without insulin from the pancreas, the body's cells can utilize very little of the food carbohydrates for energy. And, without the sex hormones, sexual development and sexual functions are absent.CHEMISTRY OF THE HORMONES

Chemically, the hormones are of three basic types:(1) Steroid hormones: These all have a chemical structure similar to that of

cholesterol and in most instances are derived from cholesterol itself. Different steroid hormones are secreted by(a) the adrenal cortex (cortisol and aldosterone),(b) the ovaries (estrogen and progesterone), (c) the testes (testosterone), and (d) the placenta (estrogen and progesterone),

(2) Derivatives of the amino acid tyrosine: Two groups of hormones are derivatives of the amino acid tyrosine. The two metabolic thyroid hormones, thyroxine and triiodothyromine, are iodinated forms of tyrosine derivatives. And the two principal hormones of the adrenal medullae, epinephrine and norepinephrine, are both catecholamines, also derived from tyrosine.(3) Proteins or peptides: All the remaining important endocrine hormones are either proteins, peptides, or immediate derivatives of these. The anterior pituitary hormones are either proteins or large polypeptides; the posterior pituitary hormones, antidiuretic hormone and oxytocin, are peptides containing only eight amino acids. And insulin, glucagon, and parathormone are all large polypeptides.HORMONE RECEPTORS AND THEIR ACTIVATIONThe endocrine hormones almost never act directly on the intracellular machinery to control the different cellular chemical reactions; instead, they almost invariably first combine with hormone receptors on the surfaces of the cells or inside the cells. The combination of hormone and receptor then usually initiates a cascade of reactions in the cell.Either all or almost all hormonal receptors are very large proteins, and each cell usually has some 2000 to 10,000 receptors.Also, each receptor is usually highly specific for a single hormone; this determines the type of hormone that will act on a particular tissue. Obviously, the target tissues that are affected by a hormone are those that contain its specific receptors.The locations of the receptors for the different types of hormones are generally the following:

(1) In the membrane. The membrane receptors are specific mostly to the protein, peptide, and catecholamine (epinephrine and norepinephrine) hormones.

(2) In the cytoplasm. The receptors for the different steroid hormones are found almost entirely in the cytoplasm.

(3) In the nucleus. The receptors for the metabolic thyroid hormones (thyroxine and triiodothyronine) are found in the nucleus, believed to be located in direct association with one or more of the chromosomes.MECHANISMS OF HORMONAL ACTION

Activation of the Receptors. The receptors in their unbound state usually are inactive, and the intracellular mechanisms that are associated with them are also inactive. However, in a few instances the unbound receptors are in the active form, and when bound with the hormone they become inhibited.

Activation of a receptor occurs in different ways for different types of receptors. In general, the transmitter substance combines with the receptor and causes a conformational change of the receptor molecule; this in turn alters the membrane permeability to one or more ions, especially sodium, chloride, potassium, and calcium ions. A few of the general endocrine hormones also function in this same way – for instance, the effect of epinephrine and norepinephrine in changing the membrane permeability in certain of their target tissues.

In addition to this occasional direct effect of hormone receptors to change cell membrane permeability, there are also two very important general mechanisms by which a large share of the hormones function: (1) by activating the cyclic AMP system of the cells, which in turn activates multiple other intracellular functions; or (2) by activating the genes of the cell, which cause the formation of intracellular proteins that in turn initiate specific cellular functions. These two general mechanisms are described as follows:

THE CYCLIC AMP MECHANISM FOR CONTROLLING CELL FUNCTION – A "SECOND MESSENGER" FOR HORMONE MEDIATION

Many hormones exert their effects on cells by first causing the substance cyclic 3' ,5'-adenosine monophosphate (cyclic AMP) to be formed in the cell. Once formed, the cyclic AMP causes the hormonal effects inside the cell. Thus, cyclic AMP is an intracellular hormonal mediator. It is also frequently called a second messenger for hormone mediation—the "first messenger" being the original stimulating hormone.

The cyclic AMP mechanism has been shown to be a way in which all the following hormones (and many more) can stimulate their target tissues:1. Adrenocorticotropin2. Thyroid-stimulating hormone3. Luteinizing hormone4. Follicle-stimulating hormone5. Vasopressin6. Parathyroid hormone7. Glucagon8. Catecholamines9. Secretin 10. The hypothalamic releasing hormones.

The stimulating hormone first binds with a specific "receptor" for that hormone on the membrane surface of the target cell. The specificity of the receptor determines which hormone will affect the target cell. After binding with the

membrane receptor, the combination of hormone and receptor activates the protein enzyme adenyl cyclase. This enzyme is also located in the membrane and is either bound directly with the receptor protein or closely associated with it. However, a large portion of the adenyl cyclase enzyme protrudes through the inner surface of the membrane into the cytoplasm and, when activated, causes immediate conversion of much of the cytoplasmic ATP into cyclic AMP.

Once cyclic AMP is formed inside the cell it activates still other enzymes. In fact, it usually activates a cascade of enzymes. That is, a first enzyme is activated and this activates another enzyme, which activates still a third, and so forth. The importance of this mechanism is that only a few molecules of activated adenyl cyclase in the cell membrane can cause many more molecules of the next enzyme to be activated, which can cause still many times that many molecules of the third enzyme to be activated, and so forth. In this way, even the slightest amount of hormone acting on the cell surface can initiate a very powerful cascading activating force for the entire cell.

The specific action that occurs in response to cyclic AMP in each type of target cell depends upon the nature of the intracellular machinery, some cells having one set of enzymes and other cells having other enzymes. Therefore, different functions are elicited in different target cells— such functions as

(1) initiating synthesis of specific intracellular chemicals,(2) causing muscle contraction or relaxation,(3) initiating secretion by the cells,(4) altering the cell permeability,(5) and many other possible effects.ACTION OF STEROID HORMONES ON THE GENES TO CAUSE

PROTEIN SYNTHESISA second major means by which hormones— specifically the steroid hormones

secreted by the adrenal cortex, the ovaries, and the testes—act is to cause synthesis of proteins in the target cells; these proteins then function as enzymes or transport proteins that in turn activate other functions of the cells.

The sequence of events in steroid function is the following:1. The steroid hormone enters the cytoplasm of the cell, where it binds with a

specific receptor protein,2. The combined receptor protein/hormone then diffuses into or is transported

into the nucleus.3. The combination now activates the transcription process of specific genes to

form messenger RNA.4. The messenger RNA diffuses into the cytoplasm where it promotes the

translation process at the ribosomes to form new proteins.To give an example, aldosterone, one of the hormones secreted by the adrenal

cortex, enters the cytoplasm of renal tubular cells, which contain its specific receptor protein. Therefore, in these cells the above sequence of events ensues. After about 45 minutes, proteins begin to appear in the renal tubular cells that promote sodium reabsorption from the tubules and potassium secretion into the tubules. Thus, there is a characteristic delay in the beginning action of the steroid

hormone of 45 minutes and up to several hours or even days for full action, which is in marked contrast to the almost instantaneous action of some of the peptide and amino acid-derived hormones, such as vasopressin and norepinephrine. CONTROL OF PITUITARY SECRETION BY THE HYPOTHALAMUS

Almost all secretion by the pituitary is controlled by either hormonal or nervous signals from the hypothalamus. Indeed, when the pituitary gland is removed from its normal position beneath the hypothalamus and transplanted to some other part of the body, its rates of secretion of the different hormones (except for prolactin) fall to low levels – in the case of some of the hormones, almost to zero.

Secretion from the posterior pituitary is controlled by nerve fibers originating in the hypothalamus and terminating in the posterior pituitary. In contrast, secretion by the anterior pituitary is controlled by hormones called hypothalamic releasing and inhibitory hormones (or factors) secreted within the hypothalamus itself and then conducted to the anterior pituitary through minute blood vessels called hypothalamic-hypophysial portal vessels. In the anterior pituitary these releasing and inhibitory hormones act on the glandular cells to control their secretion.

The hypothalamus receives signals from almost all possible sources in the nervous system. Thus, when a person is exposed to pain, a portion of the pain signal is transmitted into the hypothalamus. Likewise, when a person experiences some powerful depressing or exciting thought, a portion of the signal is transmitted into the hypothalamus. Olfactory stimuli denoting pleasant or unpleasant smells transmit strong signal components directly and through the amygdaloid nuclei into the hypothalamus. Even the concentrations of nutrients, electrolytes, water, and various hormones in the blood excite or inhibit various portions of the hypothalamus. Thus, the hypothalamus is a collecting center for information concerned with the internal well-being of the body, and in turn much of this information is used to control secretions of the many globally important pituitary hormones.

THE HYPOTHALAMIC-HYPOPHYSIAL PORTAL SYSTEMThe anterior pituitary is a highly vascular gland with extensive capillary sinuses

among the glandular cells. Almost all the blood that enters these sinuses passes first through a capillary bed in the tissue of the lower tip of the hypothalamus and then through sma:ll hypothalamic-hypophysial portal vessels into the anterior pituitary sinuses. Small blood vessels project into the substance of the median eminence and then return to its surface, coalescing to form the hypothalamic-hypophysial portal vessels. These in turn pass downward along the pituitary stalk to supply blood to the anterior pituitary sinuses.

Secretion of Hypothalamic Releasing and Inhibitory Hormones into the Median Eminence. Special neurons in the hypothalamus synthesize and secrete hormones called hypothalamic releasing and inhibitory hormones (or releasing and inhibitory factors) that control the secretion of the anterior pituitary hormones. These neurons originate in various parts of the hypothalamus and send their nerve fibers into the median eminence and the tuber cinereum, the hypothalamic tissue that extends into the pituitary stalk. The endings of these fibers are different from most endings in the central nervous system in that their function is not to transmit signals from one

neuron to another but merely to secrete the hypothalamic releasing and inhibitory hormones (factors) into the tissue fluids. These hormones are immediately absorbed into the capillaries of the hypothalamic-hypophysial portal system and carried directly to the sinuses of the anterior pituitary gland.

(To avoid confusion, the student needs to know the difference between a "factor" and a "hormone." A substance that has the actions of a hormone but that has not been purified and identified as a distinct chemical compound is called a factor. Once it has been so identified it is thereafter known as a hormone instead of simply a factor.)

Function of the Releasing and Inhibitory Hormones. The function of the releasing and inhibitory hormones is to control the secretion of the anterior pituitary hormones. For each type of anterior pituitary hormone there is usually a corresponding hypothalamic releasing hormone; for some of the anterior pituitary hormones there is also a corresponding hypothalamic inhibitory factor. For most of the anterior pituitary hormones it is the releasing hormone that is important; but, for prolactin, an inhibitory hormone probably exerts most control. The hypothalamic releasing and inhibitory hormones (or factors) that are of major importance are:

1. Thyroid-stimulating hormone releasing hormone (TRH), which causes release of thyroid-stimulating hormone

2. Corticotropin -releasing (CRF), which causes release of adrenocorticotropin3. Growth hormone releasing hormone (GHRH), which causes release of

growth hormone, and growth hormone inhibitory hormone (GHIH), which is the same as the hormone somatostatin and which inhibits the release of growth hormone

4. Luteinizing hormone releasing hormone (LRH), which causes release of both luteinizing hormone and follicle-stimulating hormone – this hormone is also called gonadotropin-releasing hormone (GnRH)

5. Prolactin inhibitory factor (PIF), which causes inhibition of prolactin secretion

In addition to these more important hypothalamic hormones, still another excites the secretion of prolactin, and several hypothalamic inhibitory hormones inhibit some of the other anterior pituitary hormones. Each of the more important hypothalamic hormones will be discussed in detail at the time that the specific hormonal system controlled by them is presented in this and subsequent chapters.

Other Hypothalamic Substances That May Have Hormonal Effects. Multiple other substances, especially many small peptides, are found in the neurons of the hypothalamus. However, functions for these as hormones are only speculative. Yet, because they are of research interest they are listed here: (1) substance P, (2) neurotensin, (3) angiotensin II, (4) enkephalins, (5) endorphins, (6) uasoactive inhibitory polypeptide, and (7) cholecystokinin-8. Many of these same substances are also found in neurons elsewhere in the brain, suggesting that they may function as neurotransmitters both in the hypothalamus and elsewhere. In addition, some of them are in the neurons of the enteric nervous system of the gastrointestinal tract,

functioning there also as neurotransmitters possibly as hormones released into the circulating blood from the nerve endings.

Key words and phrases: hypothalamus, hypophysis, epinephral glands, adrnenaline, noradrenaline, somatotropin, thyrotropin, adrenocorticotropin, lutropin, folitropin, antidiuretic hormone.Theme 2

Thyroid Gland.(1 and 2) Thyroxine and triidothyronine: increase the rates of chemical

reactions in almost all cells of the body, thus increasing the general level of body metabolism.

(3) Calcitonin: promotes the deposition of calcium in the bones and thereby decreases calcium concentration in the extracellular fluid.

Islets of Langerhans in the Pancreas.(1) Insulin: promotes glucose entry into most cells of the body, in this way

controlling the rate of metabolism of most carbohydrates.(2) Glucagon: increases the release of glucose from the liver into the

circulating body fluids. Ovaries.(1) Estrogens: stimulate the development of the female sex organs, the breasts,

and various secondary sexual characteristics.(2) Progesterone: stimulates secretion of "uterine milk" by the uterine

endometrial glands; also helps promote development of the secretory apparatus of the breasts.

Testes.(1) Testosterone: stimulates growth of the male sex organs; also promotes the

development of male secondary sex characteristics.Parathyroid Gland.(1) Parathormone: controls the calcium ion concentration in the extracellular

fluid by controlling (a) absorption of calcium from the gut, (b) excretion of calcium by the kidneys, and (c) release of calcium from the bones.

Placenta.(1) Human chorionic gonadotropin: promotes growth of the corpus luteum

and secretion of estrogens and progesterone by the corpus luteum.(2) Estrogens: promote growth of the mother's sex organs and of some of the

tissues of the fetus.(3) Progesterone: probably promotes development of some of the fetal tissues

and organs; helps promote development of the secretory apparatus of the mother's breasts.

(4) Human somatomammotropin: probably promotes growth of some fetal tissues as well as aiding in the development of the mother's breasts.

The Thyroid Metabolic HormonesThe thyroid gland, which is located immediately below the larynx on either

side of and anterior to the trachea, secretes two significant hormones, thyroxine

and triiodothyronine, that have a profound effect on the metabolic rate of the body. It also secretes calcitonin, an important hormone for calcium metabolism.

FUNCTIONS OF THE THYROID HORMONES IN THE TISSUESThe thyroid hormones have two major effects on the body: (1) an increase in

the overall metabolic rate, and (2) in children, stimulation of growth.GENERAL INCREASE IN METABOLIC RATEThe thyroid hormones increase the metabolic activities of almost all tissues of

the body (with a few notable exceptions such as the brain, retina, spleen, testes, and lungs). The basal metabolic rate can increase to as much as 60 to 100 per cent above normal when large quantities of the hormones are secreted. The rate of utilization of foods for energy is greatly accelerated. The rate of protein synthesis is at times increased, while at the same time the rate of protein catabolism is also increased. The growth rate of young persons is greatly accelerated. The mental processes are excited, and the activity of many other endocrine glands is often increased. Yet despite the fact that we know all these many changes in metabolism under the influence of the thyroid hormones, the basic mechanism (or mechanisms) by which the hormones function is much less well known.

EFFECT OF THYROID HORMONE ON GROWTHThyroid hormone has both general and specific effects on growth. For

instance, it has long been known that thyroid hormone is essential for the metamorphic change of the tadpole into the frog. In the human being, the effect of thyroid hormone on growth is manifest mainly in growing children. In those who are hypothyroid, the rate of growth is greatly retarded. In those who are hyperthyroid, excessive skeletal growth often occurs, causing the child to become considerably taller than otherwise. However, the epiphyses close at an early age so that the duration of growth, and the eventual height of the adult, may be shortened.

An important effect of thyroid hormone is to promote growth and development of the brain during fetal life and for the first few years of postnatal life. If the fetus does not secrete sufficient quantities of thyroid hormone, growth and maturation of the brain both before birth and afterward are greatly retarded. Without specific thyroid therapy within days or weeks after birth, the child will remain mentally deficient throughout life.

REGULATION OF THYROID HORMONE SECRETIONTo maintain normal levels of metabolic activity in the body, precisely the

right amount of thyroid hormone must be secreted all the time, and to provide this, specific feedback mechanisms operate through the hypothalamus and anterior pituitary gland to control the rate of thyroid secretion. These mechanisms can be explained as follows:

Effects of Thyroid-Stimulating Hormone on Thyroid Secretion. Thyroid-stimulating hormone (TSH), also known as thyrotropin, is an anterior pituitary hormone, a glycoprotein with a molecular weight of about 28,000.

Hypothalamic Regulation of TSH Secretion by the Anterior Pituitary – Thyrotropln-ReleasIng Hormone (TRH)

Electrical stimulation of multiple areas of the hypothalamus increases the anterior pituitary secretion of TSH and correspondingly increases the activity of

the thyroid gland. This control of anterior pituitary secretion is exerted by a hypothalamic hormone, thyrotropin-releasing hormone TRH), which is secreted by nerve endings in the median eminence of the hypothalamus and then transported from there to the anterior pituitary in the hypothalamic-hypophysial portal blood. The precise nuclei of the hypothalamus that are responsible for causing secreting of TRH in the median eminence are not known. However, injection of radioactive antibodies that attach specifically to TRH have shown this hormone to be present in many different hypothalamic loci, including the (1) dorsomedial nucleus, (2) suprachiasmatic nucleus, (3) ventromedial nucleus, (4) anterior hypothalamus, (5) preoptic area, and (6) paraventricular nucleus.

Insulin, Clucagon, and Diabetes MellitusThe pancreas, in addition to its digestive functions, secretes two important

hormones, insulin and glucagon. The purpose of this chapter is to discuss the functions of these hormones in regulating glucose, lipid, and protein metabolism, as well as to discuss briefly the two diseases – diabetes mellitus and hyperinsulinism—caused, respectively, by hyposecretion of insulin and excess secretion of insulin.

INSULIN AND ITS METABOLIC EFFECTSInsulin was first isolated from the pancreas in 1922 by Banting and Best, and

almost overnight the outlook for the severely diabetic patient changed from one of rapid decline and death to that of a nearly normal person.

Historically, insulin has been associated with "blood sugar," and, true enough, insulin does have profound effects on carbohydrate metabolism. Yet, it is mainly abnormalities of fat metabolism, causing such conditions as acidosis and arteriosclerosis, that are the usual causes of death of a diabetic patient. And, in patients with prolonged diabetes, the inability to synthesize proteins leads to wasting of the tissues as well as many cellular functional disorders. Therefore, it is clear that insulin affects fat and protein metabolism almost as much as it does carbohydrate metabolism.

EFFECT OF INSULIN ON CARBOHYDRATE METABOLISMImmediately after a high carbohydrate meal, the glucose that is absorbed into

the blood causes rapid secretion of insulin, which we shall discuss in detail later in the chapter. The insulin in turn causes rapid uptake, storage, and use of glucose by almost all tissues of the body, but especially by the liver, muscles, and adipose tissue. Therefore, let us discuss each of these.

Effect of Insulin on Promoting Liver Uptake, Storage, and Use of GlucoseOne of the most important of all the effects of insulin is to cause most of the

glucose absorbed after a meal to be stored almost immediately in the liver in the form of glycogen. Then, between meals, when food is not available and the blood glucose concentration begins to fall, the liver glycogen is split back into glucose, which is released back into the blood to keep the blood glucose concentration from falling too low.

The mechanism by which insulin causes glucose uptake and storage in the liver includes several almost simultaneous steps:

1. Insulin inhibits phosphorylase, the enzyme that causes liver glycogen to split into glucose. This obviously prevents breakdown of the glycogen that is already in the liver cells.

2. Insulin causes enhanced uptake of glucose from the blood by the liver cells. It does this by increasing the activity of the enzyme glucokinase, which is the enzyme that causes the initial phosphorylation of glucose after it diffuses into the liver cells. Once phosphorylated, the glucose is trapped inside the liver cells, because phosphorylated glucose cannot diffuse back through the cell membrane.

3. Insulin also increases the activities of the enzymes that promote glycogen synthesis, including phosphofructokinase that causes the second stage in the phosphorylation of the glucose molecule and glycogen synthetase that is responsible for polymerization of the monosaccharide units to form the glycogen molecules.

EFFECT Of INSULIN ON FAT METABOLISMThough not quite as dramatic as the acute effects of insulin on carbohydrate

metabolism, insulin also affects fat metabolism in ways that, in the long run, are perhaps equally as important. Especially dramatic is the long-term effect of insulin lack in causing extreme atherosclerosis, often leading to heart attacks, cerebral strokes, and other vascular accidents. But, first, let us discuss the acute effects of insulin on fat metabolism.

Effect of Insulin on Protein Synthesis and Storage. During the few hours following a meal when excess quantities of nutrients are available in the circulating blood, not only carbohydrates and fats but proteins as well are stored in the tissues; insulin is required for this to occur. The manner in which insulin causes protein storage is not as well understood as the mechanisms for both glucose and fat storage. Some of the facts known are:

1. Insulin causes active transport of many of the amino acids into the cells. Among the amino acids most strongly transported are valine, leucine, isoleucine, tyrosine, and phenylalanine. Thus, insulin shares with growth hormone the capability of increasing the uptake of amino acids into cells. However, the amino acids affected are not necessarily the same ones.

2. Insulin has a direct effect on the ribosomes to increase the translation of messenger RNA, thus forming new proteins. In some unexplained way, insulin "turns on" the ribosomal machinery. In the absence of insulin the ribosomes simply stop working, almost as if insulin operates an "on-off" mechanism.

3. Over a longer period of time insulin also increases the rate of transcription of DNA in the cell nuclei, thus forming increased quantities of RNA. Eventually, it also increases the rate of formation of new DNA and thus promotes reproduction of cells. All these effects promote still more protein synthesis.

4. Insulin also inhibits the catabolism ofproteins, thus decreasing the rate of amino acid release from the cells, especially from the muscle cells. Presumably this results from some ability of the insulin to diminish the normal degradation of proteins by the cellular lysosomes.

5. In the liver, insulin depresses the rate of gluconeogenesis. It does this by decreasing the activity of the enzymes that promote gluconeogenesis. Since the

substrates most used for synthesis of glucose by the process of gluconeogenesis are the plasma amino acids, this suppression of gluconeogenesis conserves the amino acids in the protein stores of the body.

CONTROL OF INSULIN SECRETIONFormerly, it was believed that insulin secretion is controlled almost entirely

by the blood glucose concentration. However, as more has been learned about the metabolic functions of insulin for protein and fat metabolism, it has been learned that blood amino acids and other factors also play important roles in controlling insulin secretion.

Stimulation of Insulin Secretion by Blood Glucose. At the normal fasting level of blood glucose of 80 to 90 mg/dl, the rate of insulin secretion is minimal – in the order of 25 ng/min/kg (600 (xUnits/min/kg) of body weight. If the blood glucose concentration is suddenly increased to a level two to three times normal and is kept at this high level thereafter, insulin secretion increases markedly in two stages.

1. Insulin secretion increases almost tenfold within 3 to 5 minutes after acute elevation of the blood glucose; this results from immediate dump ing of preformed insulin from the beta cells of the islets of Langerhans. However, this initial high rate of secretion is not maintained; instead, it decreases about halfway back toward normal in another 5 to 10 minutes.

2. After about 15 minutes, insulin secretion rises a second time, reaching a new plateau in 2 to 3 hours, this time usually at a rate of secretion even greater than that in the initial phase. This secretion results both from additional release of preformed insulin and from activation of some enzyme system that synthesizes and releases new insulin from the cells.

Relationship Between Blood Glucose Concentration and Insulin Secretion Rate. As the concentration of blood glucose rises above 100 mg/dl of blood, the rate of insulin secretion rises rapidly, reaching a peak some 10 to 30 times the basal level at blood glucose concentrations between 400 and 600 mg/dl. Thus, the increase in insulin secretion under a glucose stimulus is dramatic both in its rapidity and in the tremendous level of secretion achieved.

Key words and phrases: thyroid glands and hormones, pancreas (insulin,glucagons),sex glands, sex hormones (estrogen, testosteron), thymus, tissue hormones (prostaglandines).Theme 31. Neural regulation

a) Development of somatic nerves system (Spinal cord develops faster than other parts of nervous system. In the later period of embrio, columna vertebralis grows faster then spinal cord. In newborns, the length of spinal cord is 14-16 santimetres, to 10 years it double. The main tracts of spinal cord have myelin sheaths. At the moment of birth of baby medulla oblongata is rather developed, the bigger part of nuclei thalamici is developed, the striopalidal system is developed rather good. Cortex of hemisphere cerebri has the same construction as adults one. However, during the first months of life the development of cortex goes in very

fast speed. The development of the nuclei of hypothalamus is finished during the teenagers period. Frontal parts of the cortex mature the most later.)

b) Reflectory activity of fetus (After one week of fetus life begins to form reflector arc of spinal cord. When it will be the stimulation of fetus, it will be quick movement of arm, trunk, or generelazing moving reaction. That is why it presents irradiation in central nervous system, analysis of irritation. In the 9-10 weeks of fetus life present moving reaction in the case of stimulation of proprioreceptors. In 11,5 week are present seizing reactions, in 14 week beginning rythmical movement of breathing muscles. The tone of flexor muscles is increase.)

c) Development of somatic reflexes in children (In newborns tone of flexor muscles are more then tone of extensor muscles. In 1-2 months the tone of extensor muscles are more. In 3-5 months the tone of flexor and extensor muscles are balansed. These depend from the development of corpus striatum and pyramidal system. Oriental reflexes, autonomic vision, seing are inborn. The last reflex present from a middle of 3 month to 3,5 month. We can understand that child may see. In newborn present moving reflectory reaction, which are present in the case of stimulation of vestibular apparatus, present reflex of snatch to 3-6 month. To 5 years present reflex of Babinsky – straightening out the toes in the case of stimulation of outer part of sole. In newborns are present stretch reflexes (they are increase from 6 to 12 month). In newborns are present suck reflex (to the end of 1 yae). In newborns are present uncoordinating moving of arms, legs, head. In 1-1,5 month of newborn life may support the head in vertical position. From 6-7 month the infant may seat, from 10 month it may seat with different position. It may standing in the 10 month independently. Near one year baby may stand up and going.)

d) Peculiarities of electroencephalogram in children (Subcortical structures may mature earlier than cortex. Slowly activity of electroencephalogram may registrated in newborns. The alpha-rythm may registrated from 3 month, but only from 6 years it become main. From 6-8 years present teta-rythm (cortex-subcortex connection). In 10-12 years alpha-rethm is the same as in adult. From 12 to 15 years decrease the frequency of alpha-rethm.)

e) Changes of nervous system in old persons (In old person the weight of brain decrease, the gyrus become thin, the sulcus is broadened and deepened, ventricles of brain become broadened. Quantity of neurons decrease and glial cells increase. In old person increase the quantity of lipophyscin (product of oxidation of unsaturated fatty acids). Decrease the excitability, the speed of transmition of excitement, synaptic transmition, quantity of receptors, activity of Na-K-ATPase, permeability of membrane cannels, inhibitory processes. On electroencephalogram alpha-rythm is slow, increase teta and delta-rythms.)

f) Peculiarities of autonomic regulation (On early stages of postnatal period of regulation of inner organs take place sympathetic nervous system. Tone of parasympathetic nervous system is low, and include in providing of some reflex reaction from 2 to 3 month. The influence of autonomic system on different organs more strong on digestive tract (parasympathetic part), hart (sympathetic part) in

newborns. In newborns ganglion transmition act by help of adrenergic system. In old persons influence of autonomic system decrease.)

2. Hormonal regulation a) Functioning of pituitary, adrenal, sex and thyroid glands (Pituitary glands of

newborns has weight 0,1-0,15 gram and increase to 10 years to 0,3 gram, to 16 year is 0,7 gram. In old person it decrease. In 16 week of fetus life produced gonadotropins which need for differenciation of sex organs. They increase in sex micturation period. Growth hormon regulate growth from 2 to 18 years (lenth of bones). Quantity of antidiuretic hormon in newborns less. The cortex of adrenal glands is more develope than medulla in newborns. To 6-8 years sex hormones do not produced. Male sex glands begin to produce the hormons from 3 month of embrion life; it stopped to the end of embrion life. They begin to produce in the period of sex micturation in female, and second time produce in the period of sex micturation in male. Maximal production of hormones produce of male in 25-35 years, then they slowly decrease; in female sex hormones produced to the period of the end of menstruation. Thymus increase to the age 3-5 years, more intensivity grows are in 11-15 years. After 30 years it decrease in size, but increase production of glucocorticoids, sex hormones. Secretion of thiroid hormones are more in children, then in adult (maximal production in the first week of newborn life and in 12-15 years.)

b) Sex development (This is the process of forming reproductive function of organism. In female it stopped to 16-18 years, in male – to 18-20 years. There are 3 stages of sex development: prepubertate (increase the size of testis in male, increase the size of mammaliar glands in female), pubertate (to the first pollution in male and first menstruation in female), postpubertate (to the junior acne and growth of hears on face in male).)

c) Climacteric period in female (Climacteric period is the physiological period of transmition from sex development to stopped the generative function. Climacteric period in female is from 45 to 60 years and characterizated by process of slowly decrease menstruation, hormonal function of ovarium on the fone of common age change of organism. There are two period of climacteric period. First fase of climacteric period – the fase of climacteric disfanction of ovarium or premenopausa. This period is in 45 years. The menstrual cycle from 2-fases become one-fases. Second period of climacteric period – postmenopausa – characterizated by whole absent of functioning of yellow body, decrease of production of estrogens and stopping the menstrual function.)

d) Climacteric period in male (Climacteric period in male determined by age involutive processes, which are present in sex glands and are from 50 to 60 years. The quantity of testosterons and androgens decrease and honadotropic hormones are increase. These process may be with clinic picture of climacteric period, but in the biggest part of male the climacteric manifistations are absent.)

Key words and phrases: climacteric period, embrio, striopalidal system, prepubertate, pubertate, postpubertate, premenopausa, climacteric manifistations

Students must know:Theme 11. Structuro-functional characteristic of endocrine system a) Classification of endocrine glands b) Classification of hormones c) Mechanism of hormone action d) Types of hormonal effects e) Ways of regulation of endocrine glands f) Methods of studying of endocrine glands2. Physiology of hypothalamo-pituitary system a) Morpho-functional peculiarities b) Growth hormone action c) Role of gonadotropic hormones d) Influences of thyreotropic hormone e) Adrenocorticotropic hormone action f) Melanocytesstimulated hormone action g) Role of neurohypophyses hormones3. Physiology of adrenal glands a) Morpho-functional peculiarities b) Mineralocorticoids action c) Effects of glucocorticoids d) Role of sex hormones e) Adrenal medulla hormone action4. Common adaptative syndrome, its stagesTheme 21. Physiology of thyroid and parathyroid glands a) Synthesis of iodide hormones b) Action of iodide hormones c) Physiologic effect of thyreocalciotonine d) Action of parathyroid hormone2. Endocrine funcion of pancreas a) Anatomic physiology b) Action of insuline c) Influences of glucagon d) Regulation of islands secretion3. Physiology of sex glands a) Effects of male and female sex hormones b) Regulation of action of sex glands c) Female menstrual cicle d) Endocrine function of placenta4. Meaning of thymus and tissue' hormonesTheme 31. Main type of nutrients transport2. Absorption in the mouth cavity and stomach

Students should be able to:1. To analyze action of hormones2. To analyze absorptive processes3. To value the absorption processes in digestive system

Tests and Assignments for Self-assessmentMultiple Choice.Choose the correct answer/statement:Theme 11. In experiment student irritant the middle part of adrenal cortex. It was increasing and than decreasing of glucocorticoids secretion. Which hormone of pituitary gland takes part in this case?

a) Growth hormone; b) Thyroid hormone; c) Gonadotropine; d) Aldosterone; e) Adrenocorticotropin.

Real-life situation to be solved: 1. In experiment student irritant the middle part of adrenal cortex. It was increasing and than decreasing of glucocorticoids secretion. What do you think about this?

Answers for the Self-control1. e; 1. It was according to action of hypothalamus (secretion of liberins and statins) – pituipary gland (secretion of adrenocorticotropin) – adrenal gland action.

Theme 21. Student investigated action of hormones on adipose tissue. Which hormones he can take?

a) growth hormone, esrtogens; b) tissue, thyroid hormones; c) insulin, thymothin; d) insuline, glucagon; e) liberins, melatonine

Real-life situations to be solved:1. Person J., 23 years old eat cake of 150 gramms. What is about his glucose blood level?

Answers for the Self-Control1. d1 real-life situation – It normal, because of insulin action.Theme 31. Which hormones are determine the growth of organism?

a) androgens, esrtogens; b) growth hormone, thyroid hormones; c) insulin, adrenocorticotropic hormone; d) glucocorticoids, adrenalin; e) liberins, melatonine

Real-life situations to be solved:1. Child F., 3 years old has battered knees. They are battered when he was run. Why they are battered?

Answers for the Self-Control1. b1 real-life situation – To 5 years present positive reflex of Babinsky – straightening out the toes in the case of stimulation of outer part of sole. That is why the knee are battered.

References:1. Review of Medical Physiology // W.F.Ganong. – Twentieth edition, 2001. – P. 233-242, 307- 368, 383- 438.2. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Tenth edition, 2002. – P. 684, 706, 836-844, 846-856, 858-865, 869-880. 884-894, 899-910, 916-926, 929-939, 948-950. 958-959, 965-966.

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