A. V. Evseev, V. A. Pravdivtsev, L. P. Narezkina, L.Y. Putenkova, O. E. Shalaeva
PHYSIOLOGY OF VISCERAL AND SOMATIC
SYSTEMS IN SCHEMAS AND CHARTS
Textbook for foreign students
2019-2020
1
Name –
Gr –
1920-2019
Smolensk 2019
УДК 612(076.5)
Физиология висцеральных и соматических систем в рисунках и схемах. Учебное пособие. - Смоленск:
СГМУ 2019. – 69 с.
В учебное пособие включены рисунки и схемы, иллюстрирующие основные закономерности
функционирования ЦНС. При подготовке пособия использовались материалы «Руководства к практическим
занятиям по нормальной физиологии» (Издательство «Медицина», Москва, 2002 г. Коллектив авторов –
Судаков К. В., Котов А. В., …Правдивцев В. А. и др.,) учебника «Физиология человека» (Издательство
«Медицина», Москва, 2012 г. Коллектив авторов – Смирнов В. М., Агаджанян Н.А. и др.), «Альбома
основных физиологических показателей в графиках, схемах, цифрах» (Издательство РУДН, Москва, 1998,
авторы – И. Г. Власова, В. И. Торшин), «Тестов по нормальной физиологии» (Издательство РГМУ, Москва,
2000, авторы – Т. Е. Кузнецова, Д. С. Свешникова, Л. В. Трубецкая). Предназначено для студентов
иностранного лечебного факультета, обучающихся в СГМУ.
Составители – А. В. Евсеев, В. А. Правдивцев, Л. П. Нарезкина, Л. Ю. Путенкова, О.Е. Шалаева
Рецензенты:
Заведующая кафедрой иностранных языков Т. В. Николаева
Доктор медицинских наук, профессор А.В. Авчинников
Печатается по решению ЦМС Смоленского государственного медицинского университета
Протокол №6 от 29 мая 2017
© Смоленский государственный медицинский университет, 2019
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PHYSIOLOGY OF BLOOD SYSTEM
THEME 1: BLOOD FUNCTIONS, COMPOSITION OF BLOOD
Internal environment of organism.
Homeostasis.
Basic functions of a blood.
Composition of the blood.
Hematocrit.
Plasma osmotic pressure.
Plasma oncotic pressure.
Hemolysis.
Osmotic resistance of erythrocytes.
Blood sedimentation rate.
PROCEDURE 1: Determination of hematocrit. Software "PhysioEx 9.0". Exercise 11
"Blood analysis". Activity 1.
Open the program. Drag a heparinized capillary tube to the first test tube (make sure the capillary
tube touches the blood) to fill the capillary tube with the first patient's sample (the sample from
the healthy male living in Boston).
Drag the capillary tube containing Sample 1 to the container of capillary tube sealer to seal one
end of the tube.
Drag the capillary tube to the microhematocrit centrifuge. The remaining samples will
automatically be prepared for centrifugation. Recall that the remaining samples were drawn from
the following individuals:
Sample 2: a healthy female living in Boston
Sample 3: a healthy male living in Denver Sample 4: a healthy female living in Denver
Sample 5: a male with aplastic anemia
Sample 6: a female with iron-deficiency anemia
Note that the timer is set to 5 minutes. Click Start to centrifuge the samples for 5 minutes at
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14,500 revolutions per minute. The simulation compresses the 5-minute time period into 5
seconds of real time.
Drag capillary tube 1 from the centrifuge to the metric ruler to measure the height of the column
of blood and the height of each layer. Click Record Data to display your results in the grid. Drag
capillary tube 1 to the biohazardous waste disposal.
Predict Question. Predict how the hematocrits of the patients living in Denver, Colorado
(approximately one mile above sea level), will compare with the hematocrit levels of the patients
living in Boston, Massachusetts (at sea level).
a) The hematocrits of the Denver residents will be lower than those of the Boston residents.
b) The hematocrits of the Denver residents will the same as those of the Boston residents.
c) The hematocrits of the Denver residents will be higher than those of the Boston
You will now measure the column and layer heights of the remaining samples. Drag the next
capillary tube from the centrifuge to the metric ruler. Click Record Data to display your results
in the grid. The tube will automatically be placed in the biohazardous waste disposal. Repeat this
step for each of the remaining samples.
Stop &Think Question. Why would the hemoglobin levels of an anemic patient be lower than
the hemoglobin levels of a normal, health individual?
a) Anemic patients have an elevated hematocrit, which causes their hemoglobin levels to
decrease below normal levels.
b) The anemic patient is more susceptible to infection, so you would anticipate a lower
hematocrit.
c) Because hemoglobin resides in RBCs, you would anticipate a low hematocrit level to
coincide with a low hemoglobin level
d) This observation cannot be explained.
Experiment is completed.
PROCEDURE 2: Osmotic and chemical hemolysis.
1) Osmotic hemolysis: Prepare solutions
of a Sodium
chloride in such concentration:
0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, and 0.9%.
Add to each test tube a drop of erythrocyte suspension. Mix them cautiously (not shake up!).
Leave them by one hour.
Laboratory report:
In which test tube there is an initial hemolysis?
Which attributes do confirm it?
In which test tubes there is complete hemolysis?
Which attributes do confirm it?
2) Chemical hemolysis: Add 2 drops of a blood into a test tube with a solution of Hydrochloric
Acid and same portion of blood into a test tube with a solution of Sodium chloride (0.9 %). Leave
the test tubes by 15 min.
Laboratory report:
1) Explain the chemical hemolysis mechanism.
PROCEDURE 3: Erythrocyte sedimentation rate. Software "PhysioEx 9.0". Exercise 11
"Blood analysis". Activity 2.
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Drag a test tube to the first holder (1) in the orbital shaking unit. Five more test tubes will
automatically be placed into the unit.
Drag the dropper cap of the sample 1 bottle (the sample from the healthy individual) to the first
test tube (1) in the orbital shaking unit to dispense one milliliter of blood into the tube. The
remaining five samples will be automatically dispensed. Recall that the samples were drawn from
the following individuals:
Sample 2: menstruating female
Sample 3: individual with sickle cell anemia
Sample 4: individual with iron-deficiency anemia
Sample 5: individual suffering a myocardial infarction
Sample 6: individual with angina pectoris
Drag the dropper cap of the 3.8% sodium citrate bottle to the first test tube to dispense 0.5 mL of
sodium citrate into each of the tubes. Click Mix to mix the samples.
Drag the first test tube to the first sedimentation tube in the incubator to pour the contents of the
test tube into the sedimentation tube.
Drag the now empty test tube to the biohazardous waste disposal. The contents of the remaining
test tubes will automatically be poured into the sedimentation tubes, and the empty tubes will
automatically be placed in the biohazardous waste disposal.
Note that the timer is set to 60 minutes. Click Start to incubate the sedimentation tubes for 60
minutes. The simulation compresses the 60-minute time period into 6 seconds of real time.
Drag the first sedimentation tube to the magnifying chamber to examine the tube. The tube is
marked in millimeters (the distance between two marks is 5 mm).
Click Record Data to display your results in the grid. Drag the sedimentation tube to the
biohazardous waste disposal.
Stop & Think Question
What is in the beige-colored portion of the sedimentation tube?
a. hemoglobin.
b. white blood cells.
c. plasma
d. heme.
Predict Question
How will the sedimentation rate for sample 6 (individual with angina pectoris) compare with the
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sedimentation rate for sample 1 (healthy individual)?
a. It will be greater.
b. It will be lower.
c. It will be the same
d. It is not possible to answer this question.
You will now measure the sedimentation rate for the remaining samples. Drag the next
sedimentation tube to the magnifying chamber to examine the tube. Click Record Data to display
your results in the grid. The tube will automatically be placed in the biohazardous waste disposal.
Repeat this step for each of the remaining samples.
Experiment is completed.
COMPLETION:
The internal environment of the organism includes _________________________________
__________________________________________________________________________
The total amount of blood in the human organism is ________________________________
__________________________________________________________________________
The blood depots include such organs as _________________________________________
__________________________________________________________________________
In men, the measured hematocrit is normally about ____________, and in women, it is about
___________________________________________________________________________
Another names for red blood cells and white blood cells are __________________________
The specific gravity of whole blood is ___________________________________________
NaCl is responsible for about ______________ per cent of osmotic pressure of blood plasma.
Erythrocytes placed in a salt solution of a lower osmotic pressure ______________________
___________________________________________________________________________
Blood plasma consists of ____________ per cent water and ___________ per cent dry matter.
Blood plasma contains several proteins differing in their properties and functional
importance: __________ (about 4.5 per cent), ____________ (1.7 to 3.5 per cent), and
______________________ (about 0.4 per cent).
Solutions with an osmotic pressure greater than that of the blood are called
___________________, and those with a lesser pressure, ______________________________
The part of osmotic pressure produced by the plasma proteins is known as
____________________________________________________________________________
Oncotic pressure of plasma is _______________________________________mm of mercury.
Gamma-globulins have great importance in protecting the organism against
___________________________________________________________________________
The main part of the oncotic pressure (80%) is provided by quantity of
________________
___________________________________________________________________________
The destruction of the erythrocyte membrane and the release of hemoglobin into the blood
plasma is named_________________________________________________________
Osmotic hemolysis begins in human blood in a __________per cent solution of NaCl, and all its
erythrocytes are destroyed in a ___________ per cent solution.
Chemical hemolysis can be caused by the effect of certain chemicals, for example, by
___________________________________________________________________________
Hemolysis within the organism under the influence of certain types of snake poisons or through
the action of hemolysins, special substances that form in the plasma as a result of repeated
introduction of erythrocytes derived from other animals is called _________________________
_____________________________________________________________________________
_____________________________________________________________________________
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The normal sedimentation rate value in adults age is ________________ (men) and
____________________________ (women).
An increase in the ________________________________ content of the blood plasma is
presumed to be the cause of the accelerated rate of sedimentation during pregnancy.
MULTIPLE CHOICE:
Fluid part of the blood is: 1) plasma;
2) lymph;
3) tissue fluid.
White blood cells are: 1) erythrocytes; 2) leukocytes; 3) platelets.
In men measured hematocrit is normally about: 1) 0.30; 2) 0.35; 3) 0.40; 4) 0.45; 5) 0.50.
Viscosity of whole blood is: 1) 3.0;
2) 4.0;
3) 5.0;
4) 6.0;
5) 7.0
Basically blood viscosity is conditioned by the presence of:
1) erythrocytes;
2) leukocytes ;
3) platelets;
4) electrolytes.
In basic the osmotic pressure of plasma depends on the content of:
1) K+;
2) Cl-;
3) Na+;
4) Ca2+;
5) proteins.
The osmotic pressure of human blood is:
1) 7.6 atmospheres;
2) 6.6 atmospheres;
3) 9.6 atmospheres; 4) 8.6 atmospheres; 5) 10.6 atmospheres.
NaCl is responsible for about: 1) 20 % of osmotic pressure; 2) 40 % of osmotic pressure; 3)
50 % of osmotic pressure; 4) 60 % of osmotic pressure; 5) 80 % of osmotic pressure.
What main organ provides a normal osmotic pressure level?
1) brain; 2) kidney;
3) lien;
4) heart;
5) liver.
What proteins compound 80 % of all blood proteins?
1) albumins; 2) globulins; 3) fibrinogen.
Normal level of a glucose in blood is: 1) 1.3-3.5 mmol per liter;
2) 3.3-5.5 mmol per liter;
3) 5.3-7.5 mmol per liter; 4) 6.3-8.5 mmol per liter.
Solutions with an osmotic pressure greater than that of blood are called:
1) isotonic;
2) hypotonic;
3) hypertonic.
The isotonic concentration of NaCl solution is:
1) 0.6%;
2) 0.7%;
3) 0.8%;
4) 0.9%;
5) 1.0%.
The oncotic pressure of human blood is: 1) 10-15 mm of mercury; 2) 20-25 mm of mercury; 3)2530 mm of mercury; 4) 35-40 mm of mercury; 5) 45-50 mm of mercury.
The main part of oncotic pressure of blood plasma is provided by quantity of:
1) erythrocytes;
2) Na+;
3) albumins;
4) globulins;
5) platelets.
Gamma-globulins have great importance in:
1) coagulation;
2) immunity; 3) acid-base
equilibrium; 4) sedimentation of erythrocytes; 5) maintaining blood pressure.
Initial osmotic hemolysis is begun in human blood in:
1) 0.26% NaCl;
2) 0.46 % NaCl;
3) 0.66% NaCl;
4) 0.86% NaCl.
Complete osmotic hemolysis is begun in human blood in:
1) 0.12% NaCl; 2) 0.22% NaCl; 3) 0.32% NaCl; 4) 0.42% NaCl; 5) 0.52% NaCl.
The normal rate of erythrocyte sedimentation in men is:
1) 1-5 mm/h;
2) 1-10 mm/h;
3) 1-15 mm/h;
4) 1-20 mm/h;
5) 1-45 mm/h.
The normal rate of erythrocyte sedimentation in women (non pregnant) is:
1) 2-5 mm/h;
2) 2-10 mm/h;
3) 2-15 mm/h;
4) 2-20 mm/h;
5) 2-45 mm/h.
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THEME 2: FORMED ELEMENTS OF BLOOD
Functions and properties of erythrocytes.
Hyperglobulia (absolute and relative) and anemia.
Leukocyte groups.
Leukocytic formula.
Functions and properties of single form leukocytes.
Leukopenia.
Physiological leukocytosis and neutrophilia.
Platelets.
Erythropoesis and erythropoietins.
Leukopoiesis and leukopoietins.
PROCEDURE 1: Red blood cell counting.
It is necessary before the erythrocyte counting to dilute the blood by mixing pipette for creation
of standard suspension. The mixing pipette is the capillary that has dilation and three marks: 0.5,
1, and 101. The cytometer is a thick glass with four excavations.
There are three narrow platforms on them. The average platform is 0.1 mm below than lateral
ones. It is graduated by the special scale grid. If you place a clean cover glass on the cytometer
surface there is the free space between the glass and the grid. Its depth is 0.1 mm. There are 225
large squares in the scale grid. Some of them include 16 small squares. You can find 5 divided
squares. The volume above each small square is 1/4000 cubic mm.
Pour the Sodium chloride solution (3 %) into a ceramic cup. Take the blood by the mixing pipette
up to the mark «0.5». Place the pipette tip into the solution. Collect the solution with the portion
of blood up to the mark «101» (the result is the 200 times dilution of blood). Shake up the mixing
pipette and let out three drops of a fluid from the tip (there are no erythrocytes within this portion).
Put the cover glass on the cytometer surface. Place a drop of the diluted blood into the space
between the cytometer and the cover glass. Remove all moisture with cotton cautiously. Place
the cytometer under a microscope.
Count all erythrocytes in the small squares of five large squares in a diagonal direction. Use
Yegorov's rule for the account accuracy: erythrocytes posed at the top and at the left square
borders belong to that square. Erythrocytes at the inferior and at the dextral borders belong to
other squares (do not count). After erythrocyte calculation inside of five large squares (i.e. in 80
small squares) apply the result (A) to the formula:
X =
A × 4000 × 200
------------------------------------80
X – quantity of erythrocytes in 1 microlitre; A – quantity of erythrocytes in 80 small squares;
1/4000 – volume of a small square; 200 – degree of dilution.
Laboratory report:
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Count up the amount of erythrocytes. Compare the result with norm.
COMPLETION:
The life span of a red blood cell is approximately _____________________________________
There are about ___________________ erythrocytes per liter of the blood of a healthy man, and
about ____________________ in that of a woman.
The increasing of the erythrocyte number in an organism is named _______________________
______________________________________________________________________
The increasing of the erythrocyte number in bloodstream without their increasing in organism is
named _______________________________________________________________________
The reduction of the erythrocyte number is called ____________________________________
Leukocytes
are
divided
into
two
main
groups
1)______________
and
2)___________________________________________________________________________
The granular leukocytes are formed in ________________________________________ tissue.
Neutrophils engulf, digest, and destroy bacteria. This phenomenon is named _______________
_____________________________________________________________________________
Eosinophyls normally constitute about ________________________ % of all blood leukocytes.
Basophils liberate:
1) ______________________,
2) _______________,
3)_________________, 4)_________________, 5) __________________________________
The monocytes having arrived from a blood to a site of inflammation transform itself in
_____________________________________________________________________________
The activity of monocytes stronger in ____________________ times than the neutrophils ones.
Lymphocytes
are
divided
into two groups
1)_____________________ and
2)___________________________________________________________________________
The «cell-mediated» immunity is provided by ________________________________________
Helper T-cells serve as a major regulator of all immune functions by product special substances
1) ____________________________________ and 2) _________________________________
T-lymphocytes killing microorganisms and, at times, the body’s own cells are named
_____________________________________________________________________________
On entry of a foreign antigen, the B-cells produce ____________________________________
_____________________________________________________________________________
The percentage of different types leukocytes is named _________________________________
_____________________________________________________________________________
When the bone marrow produces few white blood cells occurs the pathological condition called
_____________________________________________________________________________
Leukocyte number increasing during an inflammation is named __________________________
_____________________________________________________________________________
The number of platelets per liter found normally in blood is _____________________________
The red blood cells maturation in the bone marrow is named ____________________________
_____________________________________________________________________________
Leukopoietins stimulate 1)_____________ and 2)________________ of all leukocyte forms.
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MULTIPLE CHOICE:
The erythrocyte membrane is non-permeable for: 1) HCO3-;
2) Cl-;
3) Na+;
4) H+.
Quantity of erythrocytes per liter of a blood of men is:
1) 2.0×1012;
2) 3.0×1012;
3) 4.0×1012;
4) 5.0×1012;
5) 6.0×1012.
The increasing of the total number of erythrocytes in the body is called:
1) relative hyperglobulia;
2) absolute hyperglobulia;
3) anaemia;
4) erythremia.
Erythrocytes in a hypertonic salt solution: 1) decreased in the dimension; 2) enlarged in the
dimension;
3) not change the form;
4) exposed to a hemolysis.
Reduction of erythrocyte number is named:
1) relative hyperglobulia;
2) absolute hyperglobulia;
3) anaemia;
4) erythremia.
The life span of a red blood cell is approximately:
1) 10 days;
2) 30 days;
3) 60 days;
4) 100 days;
5) 120 days.
Quantity of leukocytes per liter of a blood is:
1) 1-3×109;
2) 2-4×109;
3) 4-9×109;
4) 8-14×109;
5) 10-16×109.
Which leukocytes are named mast cells?
1) monocytes; 2) neutrophils;
3) basophils; 4) B-lymphocytes;
5) eosinophyls.
The neutrophils normally constitute about: 1) 20 % of all leukocytes; 2) 33% of all leukocytes;
3) 46% of all leukocytes;
4) 62 % of all leukocytes; 5) 80 % of all leukocytes.
Histamine is secreted by:
1) basophils;
2) neutrophils;
3) monocytes;
4) B-lymphocytes;
5) eosinophyls.
The «cell-mediated» immunity is provided by:
1) B-lymphocytes; 2) neutrophils; 3) monocytes;
4) T-lymphocytes;
5) eosinophyls.
T-lymphocytes killing microorganisms are named:
1) suppressor T-cells;
2) helper T-cells;
3) T-lymphocytes;
4) cytotoxic T-cells.
What leukocyte is an agranulocyte?
1) basophil;
2) monocyte;
3) eosinophil;
4) neutrophil.
What leukocytes the first appear in the center of an inflammation?
1) basophil;
2) macrophage;
3) eosinophil;
4) neutrophil; 5) T-lymphocytes.
B-cell produces: 1) immunoglobulins;
2) interleukins;
3) slow reacting substance of
anaphylaxis;
4) heparin;
5) serotonin.
The platelet number in human blood is: 1) 200-400×109 per liter;
2) 400-600×109 per liter;
3) 600-800×109 per liter;
4) 80-100×1010 per liter;
5) 200-400×1010 per liter
Platelets survive for:
1) 10-12 hours;
2) 2-5 days;
3) 25-30 days;
4) 2-3 months;
5) 2-3 years.
Primarily erythropoietins are made in:
1) heart;
2) lungs;
3) spinal cord;
4) kidneys;
5) bone marrow.
Leukopoietins are products of:
1) basophil;
2) monocyte;
3) eosinophil;
4) neutrophil;
5) lymphocyte.
The content of leukopoietins is increased during:
1) hypoxia;
2) inflammation;
3) allergic reactions;
4) radioactive irradiating.
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THEME 3: HEMOGLOBIN AND BLOOD GROUPS
Hemoglobin structure and functions.
Physiological bonds of a hemoglobin.
Pathological bonds of a hemoglobin.
Agglutinins and agglutinogens. Agglutination of erythrocytes.
ABO system. Features characterizing each blood group.
Rh-factor.
Post-transfusion shock.
Modern rules of a hemotransfusion.
PROCEDURE 1: Hemoglobin determination. Software "PhysioEx 9.0". Exercise 11 "Blood
analysis". Activity 3.
Drag a clean blood chamber slide from the blood chamber dispenser to the workbench. Drag the
dropper cap from the sample 1 bottle (the sample from the healthy male) to the depression in the
blood chamber slide to dispense a drop of blood into the depression.
Drag a hemolysis stick to the drop of blood in the chamber to stir the blood sample for 45 seconds,
lysing the red blood cells and releasing their hemoglobin. Drag the hemolysis stick to the
biohazardous waste disposal.
Drag the blood chamber slide to the dark rectangular slot on the hemoglobinometer to analyze the
sample. After you insert the blood chamber slide into the hemoglobinometer, you will see a
blowup of the inside of the hemoglobinometer.
The left half of the circular field shows the intensity of green light transmitted by blood sample
The right half of the circular field shows the intensity of green light for known levels of
hemoglobin present in blood.
Drag the lever on the right side of the hemoglobinometer down until the shade of green in the
right half of the field matches the shade of green in the left half of the field and then click
Record Data to display your results in the grid. Click Eject to remove the blood chamber slide
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from the hemoglobinometer. Drag the blood chamber slide from the hemoglobinometer to the
biohazardous waste disposal.
Predict Question
How will the hemoglobin levels for the female Olympic athlete (sample 5) compare with the
hemoglobin levels for the healthy female (sample 2)?
a. The hemoglobin levels for the female Olympic athlete will be lower than those for the
healthy female.
b. The hemoglobin levels for these two individuals will be the same.
c. The hemoglobin levels for the female Olympic athlete will be greater than those for the
healthy female
You will now measure the hemoglobin levels for each of the remaining samples. Drag a blood
chamber slide to the workbench. Drag the dropper cap from the next sample bottle to the
depression in the slide. Drag a hemolysis stick to the drop of blood in the chamber (after stirring
the sample, the hemolysis stick will automatically be placed in the biohazardous waste disposal).
Drag the blood chamber slide to the dark rectangular slot on the hemoglobinometer. Drag the
lever on the right side of the hemoglobinometer down until the shade of green in the right half of
the field matches the shade of green in the left half of the field and then click Record Data to
display your results in the grid.
Click Eject to remove the blood chamber slide from the hemoglobinometer (the slide will
automatically be placed in the biohazardous waste disposal). Repeat this step until you analyze
all five samples. Stop &Think Question
Why is the average hematocrit higher in males than in females?
a. Males tend to eat more red meat.
b. Higher estrogen levels in females inhibit RBC production.
c. Higher testosterone levels in males promotes more RBC production
Experiment is completed.
PROCEDURE 2: Blood typing with antitoxins. Software "PhysioEx 9.0". Exercise 11
"Blood analysis". Activity 4.
12
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Drag a blood-typing slide from the slide dispenser to the workbench. Note that the three wells
on the slide are labeled "A," "B," and "Rh."
Drag the dropper cap of the sample 1 bottle to well A on the blood-typing slide to dispense a
drop of blood into each well.
Drag the dropper cap of the anti-A serum bottle well A on the blood-typing slide to dispense
a drop of anti-A serum into the well.
Drag the dropper cap of the anti-B serum bottle to well В on the blood-typing slide to dispense
a drop of anti-B serum into the well.
Drag the dropper cap of the anti-Rh serum bottle to well Rh on the blood- typing slide to
dispense a drop of anti-Rh serum into the well.
Drag a blue-tipped stirring stick to well A to mix the blood and anti-A serum.
Drag the stirring-stick to the biohazardous waste disposal.
Drag a yellow-tipped stirring stick to well В to mix the blood and anti-B serum.
Drag the stirring-stick to the biohazardous waste disposal.
Drag a white-tipped stirring stick to well Rh to mix the blood and anti-Rh serum.
Drag the stirring-stick to the biohazardous waste disposal.
Drag the blood-typing slide to the light box and then click Light to analyze the slide.
Under each of the wells, click Positive if agglutination occurred (the sample shows clumping)
or click Negative if agglutination did not occur (the sample looks smooth).
Click Record Data to display your results in the grid.
Drag the blood-typing slide to the biohazardous waste disposal.
Predict Question
If the patient's blood type is AB-, what would be the appearance of the A, B, and Rh samples?
a. A, clumped; B, unclumped; Rh, clumped.
b. A, clumped; B, clumped; Rh, unclumped
c. A, unclumped; B, unclumped; C, clumped.
16. You will now analyze the remaining samples. Drag a blood-typing slide from the slide
dispenser to the workbench. The next sample will be added to each well on the slide, the
appropriate antiserum will be added to each well, the sample and antisera will be mixed, and
the slide will be placed in the light box. Under each of the wells, click Positive if agglutination
occurred (the sample shows clumping) or click Negative if agglutination did not occur (the
sample looks smooth). Click Record Data to display your results in the grid. Repeat this step
until you analyze all six samples.
17.
18. You will now indicate the blood type for each sample and indicate whether the sample is Rh
positive or Rh negative. Click the row for the sample in the grid. Click А, В, AB, or О above
the blood type column to indicate the blood type. Click the - button or the + button above the
blood type column to indicate whether the sample is Rh negative or Rh positive. Repeat this
step for all six samples.
Stop & Think Question
Why are individuals with the AB- blood type known as universal recipients for blood transfusions?
a. They have neither A nor В antigens on the surface of their RBCs, and their blood
serum contains antibodies against the A, B, and Rh antigens.
b. Although their blood serum contains antibodies against Rh, it does not contain
antibodies to A or В antigens.
c. They have both A and В antigens on the surface of their RBCs, and their blood serum
does not contain antibodies against A, B, or Rh antigens
Experiment is completed.
13
COMPLETION:
On combination with oxygen, hemoglobin is converted to ______________________________
Oxyhemoglobin which has given up its oxygen is known as _____________________________
_____________________________________________________________________________
On combination with carbon dioxide, hemoglobin is converted to ________________________
_____________________________________________________________________________
The blood of adults contains __________ to __________ per cent of hemoglobin in men and
_________ to __________ per cent in women.
The greatest possible absolute quantity of a hemoglobin in a blood is named ________________
_____________________________________________________________________________
The relation of absolute quantity of a hemoglobin to ideal quantity is named ________________
_____________________________________________________________________________
The pigment termed as _______________________ is formed from hemoglobin after its
oxidation in a liver.
The valency change of a hemoglobin molecule iron (divalent in trivalent) is accompanied by
formation of __________________________________________________________________
The interaction of a hemoglobin with carbon monoxide results in formation
_____________________________________________________________________________
Skeletal muscles contain ____________________________________ (a bond similar to a
hemoglobin).
Transfused blood contains an agglutinable substance ( _____________________) and the plasma
of
the
recipient
contains
a
corresponding
agglutinant
substance
(____________________________________________________________________________)
The erythrocyte agglutination followed by haemolysis causes a severe body condition termed as
_____________________________________________________________________________
Membranes of human erythrocytes may include ______________________________________
___________________________ (A,B and Rh).
In the human plasma may be found two agglutinant agents 1)________ (anti-A) and
2)_______________ (anti-B).
Individuals with I(0) blood Group have __________________________ in the red blood cells,
but their plasma contains ________________________________________________________
Individuals with II(A) blood Group have _______________________________ in their
erythrocytes and ___________________________________________________ in the plasma.
Individuals with III(B) blood Group have ______________________ in the erythrocytes and
_________________________________________________________________ in the plasma.
Individuals with IV(AB) blood Group have ____________________________ in the
erythrocytes and ___________________________________________________ in the plasma.
People with 0(I) blood Group are known as _________________________________________
There is the Rhesus factor in the erythrocyte membranes of _______________ per cent people.
A repeated transfusion of Rhesus-positive blood can cause ____________________________
____________________________________________________________________________
Is necessary before a transfusion to execute ______________________________________ test.
14
MULTIPLE CHOICE:
Hemoglobin molecular weight is: 1) 68,800;
2) 46,400; 3) 32,200;
4) 78,600.
Hemoglobin which has released an oxygen is known as:
1) oxyhemoglobin;
2) carbaminohemoglobin;
3) reduced hemoglobin; 4) carbohemoglobin;
5)
methemoglobin.
On combination with carbon dioxide, hemoglobin is converted to: 1) oxyhemoglobin;
2)
carbaminohemoglobin; 3) reduced hemoglobin; 4) carbohemoglobin; 5) methemoglobin.
Quantity of a hemoglobin in men blood is:
1) 9-12%;
2) 12.5-14.5%;
3) 13.5-16.0%;
4)15-17.5%.
What volume of transported CO2 provides by carbaminohemoglobin?
1) 100%;
2) 50%;
3) 30%;
4) 10%.
Synthesis of hemoglobin takes place in:
1) megakaryocytes;
2) erythroblasts;
3) proerythroblasts;
4) erythrocytes;
5) myeloblasts.
On combination with carbon monoxide, hemoglobin is converted to:
1) oxyhemoglobin;
2) carbaminohemoglobin;
3) reduced hemoglobin;
4) carbohemoglobin;
5) methemoglobin.
Human myoglobin is capable of binding:
1) 5% of all oxygen;
2) 14% of all oxygen;
3) 27% of all oxygen;
4) 43% of all oxygen;
5) 65% of all oxygen.
How many blood groups AB0 system includes?
1) 2;
2) 3; 3) 4;
4) 5;
5) 6
+
Specify a symbol of agglutinin.
1) A;
2) Rh ;
3) 0;
4) ;
5) B
Individuals with IV blood Group:
1) have agglutinogens A in the erythrocytes;
2) have agglutinogens B in the erythrocytes;
3) have agglutinogens A and B in the erythrocytes;
4) no agglutinogens in the erythrocytes.
Specify a designation of the third blood Group:
1) B;
2) A;
3) AB;
4) 0
What group of a blood contains both agglutinins?
1) I;
2) II;
3) III;
4) IV
What component is absent in standard Serum of a blood?
1) globulins
2) albumins;
3) fibrinogen;
4) agglutinins.
Rhesus factor is in:
1) basophils;
2) thrombocytes;
3) erythrocyte membranes;
4) a wall of a vessel;
5) a blood plasma.
Universal donor is person: 1) having I(0) blood Group; 2) having II(A) blood Group; 3) having
III(B) blood Group; 4) having IV(AB) blood Group; 5) not having the Rhesus factor in a blood.
Erythrocytes of a researched blood had reaction of agglutination only in Anti-A serum. Define the
Group of a blood.
1) I;
2) 2;
3) 3;
4) 4.
Erythrocytes of a researched blood had reaction of agglutination in both Anti-A and Anti-B
serum. Define the Group of a blood.
1) I;
2) 2;
3) 3;
4) 4.
Is it possible to execute for the resus-negative patient the transfusion of rhesus-positive blood?
1) sometimes; 2) at once; 3) in no event; 4) once a year; 5) it is possible, if the transfusion
is carried out to according to ABO system.
It is necessary to execute a compatibility test before blood transfusion. They use for this test:
1) 1-2 ml of a blood;
2) 3-5 ml of a blood;
3) 10-20 ml of a blood;
4) 30-40 ml of a blood;
5) 50-60 ml of a blood.
15
THEME 4: HEMOSTASIS AND COAGULATION OF BLOOD. BLOOD pH
Types of hemostasis.
Stages of platelet plug formation.
Coagulative hemostasis.
Phase of the prothrombin activator formation (intrinsic and extrinsic pathways).
Phase of the active thrombin formation.
Fibrin formation phase.
The thrombus retraction.
Prevention of blood clotting in the normal vascular system.
Fibrinolis.
Anticoagulants.
Acid-base equilibrium of blood.
Buffer systems of blood.
Acidosis and alkalosis.
HEMOSTASIS.
THE COAGULATION CASCADE
Fig. 1. Steps in the coagulation cascade. The extrinsic pathway is initiated by tissue factor (factor
III) released from damaged cells. In the presence of Ca2+, factor III converts factor VII to factor
VIIa, which then forms a complex with factor III and Ca2+. This complex converts factor X to
factor Xa. In the intrinsic system, factor XII is first converted to factor XIIa following its exposure
to foreign surfaces, such as subendothelial matrix. Factor XIIa initiates a cascade of events,
including activation of factor X, subsequent conversion of prothrombin to thrombin, and, finally,
fibrin formation.
16
Factors of coagulation cascade:
Factor I
Fibrinogen
Factor II Prothrombin
Factor III Tissue thromboplastin (Tissue factor)
Factor IV Calcium
Factor V
Proaccelerin Labile factor
Factor VII Proconvertin Serum prothrombin conversion accelerator (SPCA)
Factor VIII Antihemophilic factor (Platelet cofactor 1)
Factor IX Christmas factor (Platelet thromboplastin component)
Factor X Stuart factor
Factor XI Plasma thromboplastin antecedent
Factor XII Hageman factor (Contact factor)
Factor XIII Fibrin stabilizing factor
PROCEDURE 1:
1) Prothrombin determination.
Put a special concave glass on the surface of a warm water bath (temperature: 37-380С). Add 30
mm of the prothrombin activator, 30 mm of the researched blood and 30 mm of Calcium
Chloridum solution (0.1 M) on the glass with single Panchenkov's capillaries. The Calcium
Chloridum addition is necessary for restoration of calcium ion concentration in the blood (since
the used in this procedure donor blood does not contain free calcium ions). Mix this admixture
with a glass rod (activate a stop watch at moment of the mixing beginning). Stop a stop watch at
moment of appearance of fibrin fibers clinging to the rod tip. It is the prothrombin time.
As definition was carried out with an excess of prothrombin activator than a coagulation depends
upon the prothrombin content only. A standard prothrombin time determined by this method is
35 seconds. Use the result for a definition of a prothrombin index (PI) that characterizes the
process of blood coagulation.
PI
=
standard prothrombin time
------------------------------------
×
100%
found prothrombin time
A norm of prothrombin index changes from 80 to 100%.
Laboratory report:
Define the prothrombin time and the prothrombin index. Compare the results to normal
parameters.
The task: The prothrombin time is 50 seconds. What does it mean? Explain the answer.
2) Buffer properties of blood
Take two glasses. Add into the first glass 5 ml of Serum of horse (serum is diluted in 50 times).
Add into the second glass 5 ml of water. Add into both glasses by one drop of Methylorange.
Titrate them with 0.1 N HCl. You should to stop the titration at the moment of an occurrence of
an inconvertible red colour. First of all it is necessary to execute titration of water. Water has no
buffer properties. It is used as a control.
17
Then titrate the Serum and water (a control) with 0.1N NaOH at presence of Phenolphthaleinum
(by one drop into both glasses). You should to stop the titration at the moment of occurrence of
inconvertible violet colour. Multiply the results of Serum titration by 50 (quotient of the dilution).
Laboratory report:
Write down the results. Compare the buffer properties of the horse Serum to its ability to an acid
and an alkali neutralization.
COMPLETION:
There are two main mechanisms of a hemostasis: 1) _________________________and
2)___________________________________________________________________________
The place of a trauma has ______________________charge. The surface of thrombocytes is
charged ______________________________________________________________________
A prothrombin activator is generally considered to be formed in two ways:
1)______________________________________, 2) __________________________________
During a prothrombin activator formation by the intrinsic pathway take part the factors such as
_____________________________________________________________________________
The main part of a prothrombin activator is __________________________________________
Formation of a prothrombin activator lasts __________________________________________
Factor VIII is the factor that is missing in a person who has _____________________________
_____________________________________________________________________________
Hemophilia characterized by greatly reduced capacity of the blood to
_____________________________________________________________________________
Formation of an active thrombin lasts ______________________________________________
An active thrombin formation needs the factors ______________________
_____________________________________________________________________________
Platelets release ________________________________________ which form a fibrin polymer.
Traumatized tissue releases a complex several factors called ____________________________
_____________________________________________________________________________
During a prothrombin activator formation by the extrinsic pathway take part the factors such as
_____________________________________________________________________________
A prothrombin activator formation by the extrinsic pathway lasts ________________________
_____________________________________________________________________________
Substances preventing a coagulation of blood are named _______________________________
The serum proteins include substance, namely _________________________, an enzyme that
dissolves fibrin being formed.
The pH index of arterial blood is ______________; of venous blood is ____________________
The buffer properties of blood form four buffer systems: 1) ______________________;
2)______________________________; 3) ________________; 4) _____________________
Hemoglobin accounts for about ____________________________% of a blood buffer activity.
Alkaline salts of the weak acids contained in the blood are known as its ___________________
_____________________________________________________________________________
Constant ratio between the acid and alkaline equivalents in the blood is named
_____________________________________________________________________________
A shift of reaction to acidity is known as ________________________, and a shift to alkalinity
as ___________________________________________________________________________
18
MULTIPLE CHOICE:
Platelet plug stops a bleeding from:
1) large vessels;
2) fine vessels;
3) both large and fine vessels.
Platelet surface is charged:
1) negatively;
2) positively;
3) has not a charge.
Inspissation and fastening of a thrombus in a vessel is provided with:
1) plasmin;
2) prothrombin;
3) thrombosthenin;
4) thromboxane A2
Collagen activates the factor:
1) VII;
2) V;
3) XII;
4) calcium ions; 5) X
A prothrombin activator contains:
1) IX, VIII, Ca2+;
2) XII, XI, Ca2+;
3) X, V, Ca2+;
4) VII, X, Ca2+.
Following factors are necessary for an active thrombin formation:
1) V, X, Ca2+;
2) VII, X, Ca2+;
3) XII, XI, Ca2+;
4) IX, VIII, Ca2+.
What is termed an insoluble fibrin?
1) fibrin I;
2) fibrin S; 3) fibrin D; 4) fibrinogen.
What substance is not anticoagulant? 1) antithrombin III;
2) heparin;
3) fibrin fibers;
4) tissue thromboplastin;
5) Sodium citratum.
Precursor of a plasmin is:
1) fibrinolysin;
2) profibrinolysin;
3) prothrombin;
4)
thrombosthenin;
5) antithrombin III.
It is used for conservation of a donor blood:
1) heparin;
2) antithrombin III; 3)
Sodium citratum;
4) plasmin;
5) Calcium chloride.
Blood coagulation lasts:
1) 5-10 seconds;
2) 2-3 minutes; 3) 5-7 minutes; 4) 1-2 hours.
Formation of a platelet plug lasts:
1) 5-10 seconds;
2) 2-3 minutes;
3) 5-7 minutes;
4) 1-2 hours.
An acid substance that dissociated into:
1) OH-;
2) H+;
3) HCO3-;
4) Na+
Which of the following pH is more acidic?
1) 6.89;
2) 6.91;
3) 7.00;
4) 6.83
The most abundant buffer system in plasma is: 1) carbonate buffer system; 2) phosphate buffer
system;
3) plasma protein buffer system; 4) haemoglobin buffer system.
What part of the hemoglobin buffer capacity a common capacity of all blood buffer systems
includes?
1) 10%;
2) 25%;
3) 50%;
4) 75%;
5) 90%.
The pH index of arterial blood is:
1) 7.0;
2) 7.1;
3) 7.2;
4) 7.3;
5) 7.4
The pH index of venous blood is:
1) 7.05;
2) 7.15;
3) 7.25;
4) 7.35;
5) 7.45
What organ provides a normal рН level?
1) pancreas;
2) kidney;
3) lien;
4) heart;
5) thymus.
What kind of situation can provide an alkalosis development?
1) strong cooling; 2) prolonged run; 3) hyperthermia; 4) high frequency and depth of respiration;
5) hard respiration; 6) hypodynamia.
THEME 5:
CREDIT-TEST – PHYSIOLOGY OF BLOOD
19
PHYSIOLOGY OF EXCITABLE TISSUES
THEME 6: RESTING MEMBRANE POTENTIAL.
Types of the cell reactions on action of effective agents.
Measuring of resting membrane potential.
Formation of resting membrane potential.
Recording and measuring of the resting membrane potential (RMP)
Fig. 1. The difference of the potentials between the outside surface and inside surface of muscle
cell membrane in rest is called by the resting membrane potential (RMP)
Fig. 2. Measuring of RMP with the help of the microelectrode and the electronic device.
20
Polarization, hyperpolarization, depolarization, repolarization
Fig. 3. Initial polarization (1), hyperpolarization (2), depolarization (3), repolarization (4) of the
cell membrane.
Recording of resting membrane potential (RMP) of the muscle cell
Ion theory of RMP and AP
Fig. 1. Asymmetrical distribution of K+ and Na+ concerning the cell membrane. The main
cause is the work of the Na+-K+-pump in the structure of the cell membrane.
Ion theory of the RMP forming
Fig. 2. Forming of the RMP as a result of very big membrane permeability for K+ ions.
21
Position 1. Electroneutral cell. The number of K+ cations are equal the number of protein anions.
Position 2. The cell is placed in intercellular fluid. The membrane K+-channels is opened. As
a result, some K ions moves to outside according diffusion gradient.
For example, one or two K+ ion pass through the membrane to outside. The moving of cations
give the moving of anions. Anion migrates to cation on electrical gradient. But anion can not
pass through membrane channel. It has very big dimensions and it remains inside surface of
membrane. However, outside surface becomes positive, inside negative.
PROCEDURE 1: The resting membrane potential. Software "PhysioEx 9.0". Exercise 3
"Neurophysiology of nerve impulses". Activity 1.
1. Note that the neuron in this experiment is magnified relative to the Petri dish. In a typical
neuron, the cell body, which is the thickest part, is 5-100 mkm wide, and the axon might be
only 0.5 mkm wide. Click the Control extracellular fluid (ECF) container to fill the Petri dish
with 5 mM K+ and 150 mM Na+ (this solution mimics the normal extracellular concentrations
of potassium and sodium).
2. Note that a reference electrode is already positioned in the Petri dish. This reference electrode
is connected to ground through the amplifier. Click position 1 on the microelectrode
manipulator controller to position the microelectrode tip in the solution, just outside the cell
body, and observe the tracing that results on the oscilloscope.
3. Note the oscilloscope tracing of the voltage outside the cell body and click Record Data to
display your results in the grid.
4. Click position 2 on the microelectrode manipulator controller to position the microelectrode
tip just inside the cell body and observe the tracing that results.
5. Note the oscilloscope tracing of the voltage inside the cell body and click Record Data to
display your results in the grid. This is the resting membrane potential. That is, the potential
difference between intracellular and extracellular membrane voltages. By convention, the
extracellular resting membrane voltage is taken to be 0 mV.
Stop & Think Question
What is the polarity of the resting membrane potential (voltage)?
a. positive.
b. negative
c. uncharged.
22
6. Click position 3 on the microelectrode manipulator controller to position the microelectrode
tip in the solution, just outside the axon, and observe the tracing that results.
7. Note the oscilloscope tracing of the voltage outside the axon and click Record Data to display
your results in the grid.
8. Click position 4 on the microelectrode manipulator controller to position the microelectrode
tip just inside the axon and observe the tracing that results.
9. Note the oscilloscope tracing of the voltage inside the axon and click Record Data to display
your results in the grid.
Stop & Think Question
What does it mean that the voltage just inside the membrane is negative?
a. There are exactly the same number of positive charges and negative charges just inside
the membrane.
b. There are more negative charges than positive charges just inside the membrane
c. There are more positive charges than negative charges just inside the membrane.
Stop & Think Question
The membrane of most cells, including neurons, contains passive, open, К+ leak channels. Given
the normal K+ concentrations and the resultant concentration gradient, which direction would K+
be expected to move (diffuse) through these leak channels?
a. into the cell.
b. out of the cell
Predict Question
Predict what will happen to the resting membrane potential if the extracellular 1С concentration
is increased.
a. The resting membrane potential will become more negative.
b. The resting membrane potential will become less negative
c. The resting membrane potential will not change.
10.You will now change the concentrations of the ions in the extracellular fluid to determine
which ions contribute most to the separation of charge across the membrane. The extracellular
potassium concentration is normally low, so you will first increase the extracellular potassium
concentration. In the high K+ ECF the solution the K+ concentration has been increased 5 fold,
from 5 to 25 mM. To keep the number of positive charges in the extracellular solution constant,
the Na+ concentration has been reduced by 20 mM, from 150 to 130 mM. As you will see, this
relatively small decrease in Na+ will not by itself change the membrane potential. Note that, in
this activity, the generation of the action potential (which is covered in Activities 3-9) is
blocked with a toxin. Click the High K+ ECF container to change the solution in the Petri dish
to 25 mM K+ and 130 mM Na+.
11.Note the voltage inside the axon and click Record Data to display your results in the grid.
12.Click position 3 on the microelectrode manipulator controller to position the microelectrode
tip in the solution, just outside the axon, and observe the tracing that results.
13. Note the voltage outside the axon and click Record Data to display your results in the grid.
14.Click position 1 on the microelectrode manipulator controller to position the microelectrode
tip in the solution, just outside the cell body, and observe the tracing that results.
15.Note the voltage outside the cell body and click Record Data to display your results in the
grid.
16.Click position 2 on the microelectrode manipulator controller to position the microelectrode
tip just inside the cell body and observe the tracing that results on the oscilloscope.
17.Note the voltage inside the cell body and click Record Data to display your results in the grid.
18.Click the Control ECF container to change back to the normal K+ concentration and note the
change in voltage inside the cell body.
23
Stop & Think Question
What effect does increasing extracellular К have on the net diffusion of K+ out of the cell?
a. It increases the net diffusion of K+.
b. It decreases the net diffusion of K+
19.You will now decrease the extracellular Na+ concentration (the extracellular Na+concentration
is normally high.) The extracellular sodium concentration in the low Na+ solution has been
decreased 5 fold, from 150 mM to 30 mM. To keep the number of positive charges constant in
the extracellular solution, the Na+ has been replaced by the same amount of a large monovalent
cation. Note that the extracelllular Na+concentration, even in the low Na+ ECF, is higher than
the intracellular Na+concentration. Click the Low Na+ ECF container to change the solution in
the petri dish to 5 mM K+ and 30 mM Na+.
17.Note the voltage inside the cell body and click Record Data to display your results in the grid.
Stop & Think Question
Which way would Na+ move across the membrane if there were open Na+ channels?
a. Na+ would diffuse into the cell
b. Na+ would diffuse out of the cell.
18.Click position 1 on the microelectrode manipulator controller to position the microelectrode
tip in the solution, just outside the cell body, and observe the tracing that results.
19.Note the voltage outside the cell body and click Record Data to display your results in the
grid.
20.Click position 3 on the microelectrode manipulator controller to position the microelectrode
tip in the solution, just outside the axon, and observe the tracing that results.
21.Note the voltage outside the axon and click Record Data to display your results in the grid.
22.Click position 4 on the microelectrode manipulator controller to position the microelectrode
tip just inside the axon and observe the tracing that results on the oscilloscope.
23.Note the voltage inside the axon and click Record Data to display your results in the grid.
Stop & Think Question
The membrane has open K+ channels, and changing extracellular 1С concentration results in a
change in membrane potential. Changing the extracellular Na+ concentration does not
significantly change the membrane potential. What do your results suggest about the number
or state (open or closed) of Na+channels in the resting membrane of a neuron?
a. Na+ channels are mostly open.
b. Na+ channels are mostly closed
Experiment is completed.
COMPLETION:
There are three types of the cell reactions on action of effective agents:
1) ______________________ 2) _______________________ 3) ________________________
Human ontogenesis, the growth and development of the cell are the result of
_________________________________________________________ type of the cell reaction.
The metabolic reaction of the cell is characterized by ______________________________ of
cell metabolism.
The specific functional response of the muscular tissue is _______________________, of the
glandular cells is ___________________________________, and of the nervous cell is
_____________________________________________________________________________
Excitation is the ________________ reaction of cells as a result of _______________________
Excitation forms ________________________________________________ of excitable cells.
24
Excitable tissues have ability to be __________________________ under influence of some
stimulus.
The kinds of excitable tissues are: 1) ________________, 2) ____________, 3)_____________
The resting membrane potential can measure by means of _____________________
_____________________________________________________________________________
The resting membrane potential is ______________________________________________
_____________________________________________________________________________
The size of muscle normal cell resting potential is equal to ____________________________
Term “polarization of the cell membrane” means ____________________________________
Term “repolarization of the cell membrane means ____________________________________
The K+-Na+-pump continuously moves a potassium ________________________ of a cell, and
sodium _______________________________________________________________________
The main ion mechanism of the RMP is ____________________________________________
The cell membrane consists of a double layer of ______________________________________
In the membrane there are ____________________ for moving of _______________________
All ion channels are very ________________________________________________________
The cytoplasm of muscle cells contains _____________ potassium ions than ______________
The extracellular fluid contains __________________ sodium ions than the ______________
The main cause of big concentration difference for potassium and sodium is the working of __
_____________________________________________________________________________
SUPPLEMENTARY TESTS FOR CREDIT TEST AND EXAM:
What does the term "excitable tissues" mean?
– "Excitable tissues" are the tissues which cells are able to excite during the stimulation.
What is the resting membrane potential?
– Resting membrane potential is a difference of the potentials across the cell membrane in
millivolts (mV).
By which means can the resting membrane potential be measured accurately?
– The resting membrane potential can be measured by means of microelectrode for intracellular
recording.
What is a microelectrode for intracellular recording?
– A microelectrode is a micropipette with diameter at its tip around 0.5-1.0 micrometers.
What does the term " polarization of cell membrane" mean?
– "Polarization" means a presence of some negative potential inside the cell relatively outside
the cell membrane at the rest .
What does the term "depolarization" of cell membrane mean?
– "Depolarization" of the cell membrane means a reduction of the resting membrane potential.
What does the term " hyperpolarization" of cell membrane mean?
– "Hyperpolarization" of cell membrane means an increase of resting membrane potential.
Draw the scheme of the depolarization process.
Draw the scheme of the hyperpolarization process.
Draw the scheme of the recording RMP using the microelectrode and electronic device.
Draw the scheme of the variation of the oscillograph beam before and after the microelectrode
moving through the cell membrane.
25
THEME 7: EXCITATION. ACTION POTENTIAL. REFRACTORY PERIOD.
PROPAGATION OF EXCITATION IN NERVES
Excitation and excitability of tissue.
Action potential recording.
Threshold (critical level) of depolarization.
Properties of excitation.
Refractory period.
Laws of action potential (AP) propagation.
Mechanisms of AP propagation along unmyelinated and myelinated nerve fibers.
Chemical synapses transmission and neurotransmitter release (neuromuscular synapse).
Mechanism of impulse transfer from nerve to skeletal muscle
Contraction of skeletal muscle
Mechanism of muscular contraction
EXCITATION. ACTION POTENTIAL
Recording of RMP during irritation of the muscle cell by electrical stimulus
Fig. 1. Left position – the cell in rest. Right position – Electrogramme of the RMP measuring.
Zero line (up) and line of the intracellular potential (down). Distance AB between zero line
and intracellular potential line is the RMP, 80 mV [ 0 - (-80 mV) = 80 mV ].
Fig. 2. The same cell as Fig. 1, but there are stimulating electrodes and stimulator for the
irritation of the muscle cell.
Week electric current (A)
26
Fig. 3. The first experiment of the irritation of the muscle cell by very weak electric current.
You can see absence of the muscle contraction (myogram, down) but presence of the small
convertible decreasing of the RMP (electrogramme, up).
Strong electric current (B)
Fig. 4. A-position – 1-st experiment, B-position – 2-nd experiment. The moment of the irritation
is indicated by the pointer. The top – the RMP registration. The bottom – the myogram. You can
see that deflection of the RMP in b-situation is more strong, but we have absence of the contraction
activity of the muscle cell.
Very strong electric current (C)
Fig. 5. The irritation of the cell with very strong current. On the myogram you can see the
contraction reaction of the muscle cell.
Action potential
27
Fig. 6. Specific changes of the RMP under influence of threshold irritation of the muscle cell –
action potential.
Polarization of the cell membrane for rest position and for excitation position
Fig. 7. Position A – the electrical status of the cell in rest. Inside is negative. Position B –
inside is positive when the cell demonstrates specific reaction to the irritation by the threshold
stimulus.
Local potential and action potential
Fig. 8. The phases of the action potential of the muscle fiber.
The critical level of depolarization
28
Fig. 9. Action potential under influence of the threshold (1) and suprathreshold irritation (2, 3).
PROPERTIES OF EXCITATION
Summation of the local potential
Fig. 1. The summation of the local potentials results the AP or excitation of the cell. Left
position – the cell is in the rest in spite the irritation. Right – the summation of the local potentials
under influence of the increased the frequency stimulation. All stimuli in this situation are
subthreshold, but we get AP ( excitation of the cell).
Action potentials are not able to sum
Fig. 2. The first threshold stimulus. We get local potential, next phase of the depolarization AP
(left position).
Does we get second AP if second suprathreshold stimulus irritates the cell at the top moment
of the AP overshoot?
It has been shown new AP under influence of the second stimulus during of evolution the first
AP does not arise (right position). The second stimulus can be very big, but new action potential
never arise in this experiment. Summery - Excitability of the cell during AP is equal to zero.
Ion theory of AP
29
Fig. 3. Forming of the AP as a result of very big membrane permeability for Na + ions during
phase of the depolarization and for K ions during phase of the repolarization.
The ion mechanism of AP is double current of ions. First – all rising phase of the action potential
is provided with a current of ions of sodium inside of the cell. Second – all declining phase of
action potential is provided with the reinforced current of a potassium outside of the cell.
The scheme of tissue excitability during action potential. Refractory period.
Fig. 4. A – action potential (AP), B – the scheme of the excitability during the evolution of the
AP. Note – 1 position – normal level of excitability. The shift upward – excitability is more.
The shift downward – excitability is less.
During the local potential (2 position) excitability becomes more. During the AP (3 position)
excitability disappears – the absolute refractory period. 4 – relative refractory period during
positive afterpotential.
PROPAGATION OF EXITATION
Laws of AP propagation in nerves
1. The law of anatomical and functional intactness of a nerve.
2. The law of two-way propagation.
Fig. 1. Demonstration of two-way propagation of nerve impulse (AP) in a nerve fiber.
3. The law of isolated propagation along a nerve fiber.
30
Mechanisms of AP propagation in nerves
The propagation of nerve impulses along fiber involves two related processes –
(1) Local ion current.
(2) Generation of action potential.
Propagation of excitation by unmyelinated nerve fibers.
Fig. 2. Propagation of excitation (action potential) in a unmyelinated nerve fiber.
In unmyelinated nerve fibers excitation (action potential) is propagated continuously along the
membrane from one excited site (A) to next unexcited site (B).
Propagation of excitation by myelinated nerve fibers.
Fig. 3. Saltatory propagation of excitation (action potential) in a myelinated nerve fiber.
In myelinated fibers the action potentials jump over the myelin sheath from one node of Ranvier
to another. This mechanism of the propagation is called by saltatory propagation. The «jump
propagation» of the action potential has several advantages over the continuous conduction of
unmyelinated fibers: (1) Saltatory propagation of excitation is more faster type of propagation
than continuous propagation; (2) Saltatory propagation saves metabolic energy. The membrane
is not activated as a whole, but only small portions in the region of the Ranvier nodes.
PROCEDURE 1: Determination of conduction velocity and the way it depends on axon
diameter and on the presence or absence of myelin. Software "LuPraFi-Sim". "Neuros
system". Activity 3.
31
Nervous influx is the manifestation of the action potential in neurons. The nervous influx is the
result of the following properties of the neuron: (1) excitability; (2) conduction.
Excitability is the ability of the neuron to respond to the action of certain stimuli (electrical,
mechanical or chemical etc.) by generating an action potential. Conduction is the ability of the
neuron to propagate the action potential the full length of its axon.
During resting periods the neuronal membrane is polarized, having the so-called resting
membrane potential. The resting membrane potential represents the distribution of the positive
charges outside the neuron and of the negative ones inside the neuron. The process of polarization
of the neuronal membrane is active (it is made with energy consumption) and it is made by the
ionic pumps of Na+-K+. These are responsible for the simultaneous active transport of 3 Na+ ions
from the interior of the cell into the intercellular space and of 2 K+ ions from the intercellular
space inside the neuron.
The result of this process is the prevalent accumulation of positive charges outside the neuron and
of negative charges inside the neuron (polarization). Measurement of the resting membrane
potential can be made by means of a voltmeter whose electrodes are placed in the following way:
one outside the neuronal membrane and the other one inside the neuron. The difference of
potential recorded by the device will be of -70mV on an average (-40mV -90mV).
If the neuron receives a stimulus of a certain intensity which is higher than the excitability
threshold, the resting potential is replaced by the action potential. This way the neuronal
membrane becomes hyperpermeable for Na+ and the action of Na+-K+ pumps is useless. A high
number of Na+ ions enter the neuron and they suddenly reverse the distribution of electrical
charges which is characteristic of the resting membrane potential (the great majority7 of charges
inside the neuron are positive). During this process, at the very moment when the membrane
potential tends to 0, Na+ channels close (Na+ stops entering the cell) and K+ channels open (K+
begins to come out of the cell). This stops the depolarization of the membrane (at about +30+35mV) and initiates its repolarization. Repolarization is intense and it determines a membrane
potential of -75mV (hyperpolarization). This makes K+ channels close and the normal level of
membrane polarization is reached due to Na+-K+ pumps.
During the massive influx of Na+ the neuron is refractory to further stimulation, no matter how
strong a stimulus is applied, and this stage is called absolute refractory period. Throughout a
period of repolarization the neuron can be stimulated only by a strong stimulus and this is called
relative refractory period. The action potential which appears in a certain area of the neuron moves
towards the extremities of the neuron, obeying the all-or-none principle: it either propagates
throughout the full length of the neuron or it does not propagate at all.
32
Objective: Measurement of conduction velocity using the following types of nerves:
- thin myelinated frog nerve;
- unmyelinated rat nerve;
- thick myelinated rat nerve.
Principle: Electrical stimuli are applied on different types of nerves and conduction velocity is
measured by using two electrodes placed at a known distance from each other. Knowing the
distance and measuring the time we can determine the conduction velocity. The experimental
device is made up of:
- stimulator – electrical stimulation machine, which includes:
- a device which adjusts the intensity of electrical stimuli;
- a button which turns the stimulator on or off;
- a device which measures time;
- signal amplifier;
- a support to fix to nerve.
Technique
1. Apply an electrical stimulus on the sciatic nerve of the frog and measure the necessary time for
the action potential to propagate through the predifined distance and determine the value of
conduction velocity tin case of this type of nerve.
2. Apply an electrical stimulus on the unmyelinated rat nerve and measure the necessary time for
the action potential to propagate through the predifined distance and determine the value of
conduction velocity tin case of this type of nerve.
3. Apply an electrical stimulus on the myelinated rat nerve and measure the necessary time for the
action potential to propagate through the predifined distance and determine the value of
conduction velocity tin case of this type of nerve.
4. Conclusions: how does the presence or absence of myelin influence conduction velocity?
Experiment is completed.
PROCEDURE 2: The effect of anesthetic substances and low temperature on the excitability
of the nerve. Software "LuPraFi-Sim". "Neuros system". Activity 2.
The experimental device is made up of:
33
Stimulator – electrical stimulation machine, which includes: a device which adjusts the intensity
of electrical stimuli; a button which turns the stimulator on or off; signal amplifier (it amplifies
the resting potential in order to visualize it on the screen of the oscilloscope); board for fixing
the nerve.
Technique:
1. Apply an electrical stimulus on the frog's sciatic nerve and measure the necessary time for
the influx to arrive at the destination and determine the conduction velocity.
2. Moisten the sciatic nerve of the frog with lidocain and apply an electrical stimulus and
evaluate its effect 011 the excitability of the nerve.
3. Moisten the sciatic nerve of the frog with ether and apply an electrical stimulus and
evaluate the effect of this substance on the excitability of the nerve.
4. Place a few ice crystals on the sciatic nerve and apply an electrical stimulus on it, then
evaluate the excitability of the nerve and determine the conduction velocity in these
conditions.
Experiment is completed.
COMPLETION:
If we’ll irritate the muscle cell by subthreshold electric current RMP _____________________
The skeletal muscle during irritation by subthreshold electric current _____________________
If we’ll irritate the muscle cell by threshold electric current RMP ________________________
The skeletal muscle during irritation by threshold electric current _______________________
Characterize conception "subthreshold strength of the irritation” _________________________
Characterize conception "threshold strength of the irritation” ____________________________
Threshold stimulus reflects _______________________________________________________
The ________________ threshold strength the ____________________ the tissue excitability.
The threshold current for A cell is 45 mV, the threshold current for B cell is 35 mV. What cell
is more excitable? ______________________________________________________________
During small depolarization the cell excitability is ______________________ than during initial
polarization.
During small hyperpolarization the cell excitability is ________________________ than during
initial polarization.
An action potential can spread ___________ distance along a membrane of nervous or muscle
fibers.
A local potential is ______________________________________________________potential.
Local potential has no distinct ____________________________________________________
The more stimulus the ______________________________ amplitude of the local potential.
Action potential has distinct _______________________________. Action potential amplitude
does not depend from the ______________________________________ of the current applied.
Local potentials can give ________________________________________________________
As a result of _______________________________________ the cell gives excitation under of
influence of the series of _______________________________________________ stimuli.
Action potentials are not able to __________________________________________________
The cell excitability during excitation, during evolution of any AP is ___________________
During local potential tissue excitability is ___________________________________________
The ion mechanism of AP is ______________________________________________________
SUPPLEMENTARY TESTS FOR CREDIT TEST AND EXAM:
34
What is the term "excitation"?
– "Excitation" is the complex processes which is characterized by electrical changes in the
excitable cells. The most important of these phenomena is bioelectrical event called action
potential. The action potential next transforms functional status of the cell. For example, muscle
cell at first exited, next it contracted – the excitation activates the mechanism of the contraction.
What is the stimulus classification relative to capacity of stimuli to excite an action potential?
– There are three kinds of stimuli relative to their capacity to excite tissue: threshold stimuli (the
lowest strength of stimulation required to excite an action potential), suprathreshold stimuli (more
stronger than threshold stimuli and subthreshold stimuli (stimuli below threshold strength which
are not able to produce an action potential).
What does the term "local response (local depolarization)" mean?
– Local response means an active reaction of excitable tissue if the acting stimulus strength is
subthreshold.
What is an action potential termed?
– Action potential is a property of excitable cells (nerve, muscle) consisting of a rapid
depolarization followed by repolarization of the membrane as a reaction of excitable tissue on
threshold and suprathreshold stimuli.
What does the term "the critical level of depolarization" mean?
– The critical level of depolarization is the membrane potential at which local potential transforms
at the action potential.
What does the term "threshold potential" ("threshold depolarization") mean? Represent the
corresponding formula.
– Threshold potential (TP, threshold depolarization) is the difference between the resting
membrane potential (RMP ) and the critical level of depolarization (CLD), therefore the formula
is as follows:
TD = RMP - CLD = 80mV - 60mV = 20 mV.
-What is the term "excitation"?
-"Excitation" is the complex processes which is characterized by electrical changes in the
excitable cells. The most important of these phenomena is bioelectrical event called action
potential.
The action potential next transforms functional status of the cell. For example, muscle cell at first
exited, next it contracted – the excitation activates the mechanism of the contraction.
What is the relationship between threshold potential and excitability of excitable cell?
– The relationship is inversely proportional: than greater threshold potential than less cell
excitability and on the contrary than less threshold depolarization than greater tissue excitability.
Cell B – RMP = 90 mV, CLD = 60 mV, Cell C – RMP=85 mV, CLD=60 mV.
What cell is more excitable?
Cell D – RMP = 80 mV, CLD = 60 mV, Cell F – RMP=90 mV, CLD=60 mV.
What cell is more excitable?
Draw the AP, indicate the phases.
Draw the AP, indicate the RMP and CLD
Enumerate the general properties of a local response as important kind of reaction excitable
35
tissue on the subthreshold stimulation.
– The local potential differs substantially in its properties from the action potential: 1) it has no
distinct threshold strength stimulus; 2) the amplitude of the local response, unlike the action
potential, depends on the strength of the stimulus applied, i.e. the stronger the stimulus the greater
is the local response; 3) during local response tissue excitability is increased; 4) it is nonpropagated response of the membrane; 5) local responds are able to sum their effects on the excite
tissue.
What does the expression "the local response is non-propagated response of the excitable
membrane" mean?
– That means that the local response doesn't propagate far from the point of stimulation, that is it
propagates only with decrement.
What does the notion "summation of local responses" mean?
– The application of a subthreshold stimulus has some local potential on excitable tissue, an
action potential is not elicit. If the second some subthreshold stimulus is applied during previous
local potential two local potentials must be give summation and resting potential does for critical
level. As a result summation the action potential is elicited.
What is an action potential termed?
– Action potential is a property of excitable cells (nerve, muscle) consisting of a rapid
depolarization followed by repolarization of the membrane as a reaction of excitable tissue on
threshold and suprathreshold stimuli.
Enumerate the general properties of an action potential as important kind of reaction excitable
tissue on the threshold and suprathreshold stimuli.
– An action potential differs substantially in its properties from a local potential: 1) it has the
distinct threshold strength stimulus; 2) action potential has stereotypical size and shape, its
amplitude, unlike the local response, doesn't depend on the strength of the stimulus applied ("allor-none" principle); 3) during action potential the tissue excitability diminishes to zero (the
absolute refractory period) ; 4) it is propagating response of the membrane; 5)action potentials
can't sum.
What does the expession "all-or none principle" in relation to the action potential mean?
– That is either the action potential is elicited with maximum amplitude if the applied stimulus
has threshold or suprathreshold strength, or the action potential isn't elicited if the strength
stimulus is less threshold level.
What kind of excitability change is an action potential phase of rapid depolarization and
repolarization accompanied with?
– An action potential phase of rapid depolarization and repolarization is accompanied with the
complete lack of excitability known as the absolute refractory period.
What does the expression "absolutely refractory period" mean?
– The expression "absolute refractory period" means the period during which another action
potential can't be elicited no matter how large the stimulus.
What kinds of materials are cell membranes composed of?
– Cell membranes are composed of phospholipids and proteins
Ву which ways can water-soluble substances cross cell membranes?
– Water-soluble substances cannot dissolve in the lipid of the membrane, but must cross through
36
water-filled channels or may be transported by carriers.
What factors does membrane conductance depend on?
– If the solute is an ion, then its flux through membrane (membrane conductance) depends on
both the concentration difference and the potential difference across membrane.
What does the term Na+-K+-pump mean?
– Na+-K+-pump is the active transport mechanism in cell membrane, which transports Na+ from
intracellular to extracellular fluid and K+ from extracellular to intracellular fluid; it maintains low
intracellular Na+ and high intracellular K+.
Why is Na+-K+-pump mechanism called "active mechanism"?
– Because this mechanism occurs against an electrochemical gradient ("uphill") and requires
direct input of metabolic energy in the form of ATP.
What kinds of the transport across cell membrane can be distinguished?
– There are two general kinds: active transport (with utilization of metabolic energy ATP and
solutes moving "uphill") and passive mechanism (without utilization of the ATP metabolic energy
and with solutes moving "downhill").
What kinds of passive transport mechanism of the solute transport across cell membrane can be
distinguished?
– There are diffusion, osmose and filtration.
What is the term "ion channel"?
– Ion channel is the specific membrane protein. It permit, when open, the passage of certain ions.
Are the ion channels selective and what it means?
– Yes, ion channels are selective, they permit the passage of some ions but not others.
What does ion channel selectivity depend on?
– Ion channel selectivity depends on the diameter of the channel and the distribution of charges
on the its wall.
When can the ion for which channel is selective flow through?
– The ion for which channel is selective can flow through when the channel is open. When it is
closed, ions cannot flow through.
By which means are opening and closing of channels controlled?
– Opening and closing of ion channels are controlled by the gate mechanism.
What three factors are essential for development of bioelectrical events in excitable tissues?
– There are: 1) ion asymmetry, 2) active transport (Na+-K+-pump), 3) selective permeability of
cell membrane for different ions in different conditions.
What does the term “ion asymmetry" mean?
– Ion asymmetry is the presence of the ion concentration differences across cell membrane. For
example, Na+ are much larger cell outside than inside and K+ is vice versa.
What ions make the greatest contribution to the establishment of the resting membrane potential?
– The resting membrane potential of nerve is 80 mV, close to the calculated K+ equilibrium
37
potential of about 90 mV. Therefore, namely K+ ion make the greatest contribution in the resting
membrane potential.
What indirect contribution does the Na+-K+-pump contribute to the resting membrane potential?
– The Na+-K+-pump contributes indirectly to the resting membrane potential by maintaining,
across the cell membrane, the Na+ and K+ concentration gradients that then produce diffusion
potentials.
Why does local response transform at the action potential if the critical level of the membrane
depolarization is achieved?
– If the critical level of the membrane depolarization is achieved, a lot of Na+ ions entering the
cell becomes greater than the number of K+ ions leaving the cell because of a lot of Na+ channels
are opened. As a result the local response transforms at the potential action.
Express in sequence the chain of events developing, in an excitable tissue during electrical
stimulation.
– Start depolarization of membrane from stimuli —> increase in sodium permeability —>
increase in flow of sodium ions across the membrane into the cell —> local response —> action
potential.
What ions make the greatest contribution to the development of the rapid repolarization phase of
action potential?
– The repolarization of action potential is caused by an outward K+ current related with combined
effect of closing the Na+ channels and r opening of the voltage-gated K+ channels that makes the
K+ membrane conductance higher than the Na+ membrane conductance. The membrane is
repolarized.
What two processes does the propagation of nerve impulse involve?
– The propagation of nerve impulse along nerve fiber involves two independent but related
processes: 1) local ion current and 2) generation of action potential.
Describe shortly process of action potential propagation along a nerve fiber.
– Assume that a nerve has been exited in its midportion and an action potential is generated. This
results in an appearance of local currents to adjacent resting areas of membrane, which are then
depolarized to critical level and generate new action potentials. These newly depolarized areas
(AP) produce local currents still further along the membrane, causing progressively more and
more depolarization. Thus, the depolarization process (generation of AP) is self-propagated along
the entire extent of the axon.
What factors does the nerve fiber conduction velocity depend on?
– The nerve fiber conduction velocity depends on four general factors as follows:
1) amplitude of action potential; 2) threshold potential; 3) fiber diameter; 4) myelination.
How is the nerve conduction velocity affected by the nerve myelination?
– Myelin sheath promotes to increase of conduction velocity.
What does the term “node of Ranvier" mean?
– A node of Ranvier is a small area only 2 to 3 micrometers in length at the junction between
each two successive Schwann cells along the myelinated nerve axon.
What peculiarities of membrane electrical properties do myelinated sites and Ranvier's node sites
38
of myelinated axon have?
– Ions can't flow through the thick myelin sheath, but they can flow with ease through the nodes
of Ranvier because there are a lot of rapid Na+-channels there.
What peculiarities of action potential conduction do the myelinated nerve fibers have?
– Myelinated nerves exhibit saltatory conduction because action potentials can be generated only
at the nodes of Ranvier, where there are gaps in the myelin sheath. Nerve impulse "jumps" down
the fiber, which is origin of term "saltatory".
Why is saltatory conduction of value?
-Saltatory conduction is of value for two reasons: 1) increases the velocity of nerve transmission
in myelinated fibers up to 120 m/s; 2)conserves energy for the axon because only the nodes
depolarize.
What is the most known classification of nerve fibers? What properties of nerve fibers is this
classification based on?
– According to the most known classification of nerve fibers there are three main types axons
which are A, B and C. This classification of nerve fibers is based on nerve fiber diameters and
their sheath state (myelinated and unmyelinated).
What are general properties of A, B, C group nerve fibers (diameter, sheath state and conduction
velocity) and their functions?
– A group consists of myelinated fibers about 1-20 mkm with conduction velocity about 5 to 120
m/s, they are sensory and motor in function.
– B group consists of myelinated fibers about l-3 mkm with conduction velocity about 3 to 14
m/s, they are solely in preganglionic autonomic nerves.
– C group consists of unmyelinated fibers, less than 1 mkm with conduction velocity about 2 m/s
or less, they are in postganglionic autonomic nerves.
Enumerate general laws (principles) of conduction along the nerve fiber.
– 1) Anatomical and physiological intact nerve needs for continuous action potential propagation;
2) impulses propagation along the axon is isolated from other fibers within nerve trunk consisting
of lots of nerve fibers; 3) action potential travels in both directions away from the stimulus.
Draw the scheme of propagation excitation (action potential) in a unmyelinated nerve fiber.
Draw the scheme of propagation excitation (action potential) in a myelinated nerve fiber.
39
THEME 8: NEUROMUSCULAR SYNAPSES.
MUSCLE
CONTRACTION OF SKELETAL
Structure of neuromuscular synapses.
Mechanism of synaptic transmission of impulses.
Postsynaptic cholinoreceptor and postsynaptic potential.
Single and tetanic contraction of skeletal muscle.
Mechanism of muscular contraction
Molecular mechanism of the muscle sarcomer contraction
NEUROMUSCULAR SYNAPSES
The structural formation for the transmission of impulses from a nerve fiber to the muscle cell it
is known as a synapse. All synapses, both in the central nervous system and on the periphery,
consist of three principal elements: presynaptic membrane, postsynaptic membrane, and
synaptic cleft (fig. 1).
The cleft is filled with intercellular fluid. The presynaplic membrane is the membrane covering
the nerve ending. This is a neurosecretory device, in which nerve ending secretes the mediator
that made stimulating effect on the muscle cell. At rest the mediator is contained in synaptic
vesicles of the nerve ending. During depolarization of the nerve ending and presynaptic
membrane these vesicles burst, releasing the mediator which goes through the presynaptic
membrane into the synaptic cleft.
The mediator goes through the cleft acting on the muscle cell postsynaptic membrane. The
postsynaptic membrane differs in its properties from the membrane covering the remainder of the
cell. The chief difference being that it has very high chemical sensitivity to the mediator and
unsensitive to an electric current.
The mechanism of synaptic transmission of impulses is based on the interaction of the mediator
and specific receptor protein of the postsynaptic membrane. The presence of a chemical link in
the mechanism helps us to understand two properties of synapses: (1) the one way transmission
of impulses across the synapse from the presynaptic membrane to postsynaptic one. In contrast
we have two-way transmission in nerve fibers; (2) – synaptic delay. One-way transmission is
related the mediator secreted by the nerve ending stimulates the postsynaptic membrane, but the
action potential that arises in the muscle fibre cannot stimulate the nerve endings because of the
synaptic cleft. Synaptic delay is the delay in the going of impulses across a synapse. It is
determined mainly by the time it takes the mediator to diffuse from the presynaptic membrane to
postsynaptic membrane. Synaptic delay of the myoneural junction continues between one and
three milliseconds.
Fig. 1. Diagram of the relation between the nerve fiber, nerve ending and skeletal muscle fiber.
Mechanism of impulse transfer from nerve to skeletal muscle
The mediator for the transfer of impulses from a motor nerve to a skeletal muscle is acetylcholine.
The high sensitivity of the postsynaptic membrane to acetylcholine is result high affinity to the
mediator molecule from special protein named cholinoreceptor (fig 2).
40
The acetylcholine secreted from a nerve ending as reaction to a nerve impulse. Next,
acetylcholine interacts with the cholinoreceptor of certain type postsynaptic membrane channel
(fig. 2 – acetylcholine channel). This gets a conformation of the cholinoreceptor gate protein of
the postsynaptic membrane channels. The channel gate for muscle fiber in rest is closed (1
position), but they become opened when acetylcholine interacts with the cholinoreceptor (2
position). The permeability of the postsynaptic membrane to sodium in this situation considerably
increases. This leads to postsynaptic membrane depolarization which takes the form of an
electronegative postsynaptic potential or end-plate potential (fig.3). This potential is as local
potential for nerve fiber.
Fig. 2. Аcetylholine channel. 1 – closed state. 2 – after acetylcholine (Ach) has attached.
Conformational changes make the channel opened that allow sodium ions to enter the muscle fiber
and generate the action potential. Note negative charges at the channel mouth prevent passage of
negative ions such as chloride ions.
The postsynaptic potential (end-plate potential) stimulates neighbor extrasynaptic membrane.
Here take place membrane potential decreasing. As soon as it reaches the critical level, an action
potential is generated. So, action potential spreads along the muscle fiber.
The postsynaptic potential (end plate potential) differs considerably in its properties from the
action potential. It is not subject to the all-or-none law. Its value depends on how much of the
mediator has been secreted in the nerve ending, and on how sensitive the postsynaptic membrane
is to acetylcholine. The larger the amount of the mediator, the greater is the amplitude of the
postsynaptic potential.
Fig. 3. A – Normal postsynaptic potential eliciting muscle action potential when it goes to
critical level of depolarization of the elecrtoexcitable (extrasynaptic) muscle membrane.
The process of transfer of excitation from a nerve fibre to a muscle fibre can be presented as
follows: nerve impulse → release of the acetylcholine by the nerve ending → interaction of
acetylcholine with the cholinoreceptor of the postsynaptic membrane → increase of the Na+ ion
permeability of the postsynaptic membrane → appearance of the postsynaptic potential →
generation of an action potential spreading along the muscle fibre.
41
PROCEDURE 1: Chemical synapses transmission and neurotransmitter release. Software
"PhysioEx 9.0". Exercise 3 "Neurophysiology of nerve impulses". Activity 8.
1. Click the control Ca2+ extracellular solution to fill the Petri dish with the control extracellular
solution.
2. Click Low Intensity on the stimulator and then click Stimulate to stimulate the neuron (axon)
with a threshold stimulus that generates a low frequency of action potentials and observe the
release of neurotransmitter.
3. Click High Intensity on the stimulator and then click Stimulate to stimulate the neuron with a
longer, more intense stimulus to generate a burst of action potentials and observe the release
of neurotransmitter.
Stop & Think Question
Why does the stimulus intensity affect the amount of neurotransmitter release at the axon
terminal?
a. The stimulus intensity directly affects the amount of calcium entering the axon
terminal.
b. The stimulus intensity directly affects the number of synaptic vesicles that discharge
their contents into the synaptic cleft
c. The stimulus intensity directly affects the amount of neurotransmitter released per
synaptic vesicle.
d. Both a and bare correct
Predict Question 1.
You have just observed that each action potential in a burst can trigger additional neurotransmitter
release. If calcium ions are removed from the extracellular solution, what will happen to
neurotransmitter release at the axon terminal?
a. There will be no change in neurotransmitter release.
b. There will be more neurotransmitter release.
c. There will be less neurotransmitter release.
d. There will be no neurotransmitter release
4. Click the no Ca2+ extracellular solution to fill the Petri dish with an extracellular solution that
does not contain calcium.
5. Click Low Intensity on the stimulator and then click Stimulate to stimulate the neuron (axon)
with a threshold stimulus that generates a low frequency of action potentials and observe the
release of neurotransmitter.
6. Click High Intensity on the stimulator and then click Stimulate to stimulate the neuron with a
42
longer, more intense stimulus to generate a burst of action potentials and observe the release
of neurotransmitter
Stop & Think Question
Why is there no neurotransmitter release from the axon terminal when there are no calcium ions
in the extracellular solution?
a. Action potential propagation in the axon is calcium dependent.
b. Neurotransmitter channels in the nerve terminal are calcium dependent.
c. Exocytosis of the synaptic vesicles is calcium dependent
d. Our visualization of neurotransmitter release is calcium dependent.
Predict Question 2
What will happen to neurotransmitter release when low amounts of calcium are added back to the
extracellular solution?
a. There will still be no neurotransmitter release.
b. Neurotransmitter release will increase a small amount
c. Neurotransmitter release will increase to control levels.
d. Neurotransmitter release will increase above control levels.
7. Click the lowCa2+ extracellular solution to fill the Petri dish with an extracellular solution in
which the calcium concentration has been reduced from that in the control solution.
8. Click Low Intensity on the stimulator and then click Stimulate to stimulate the neuron (axon)
with a threshold stimulus that generates a low frequency of action potentials and observe the
release of neurotransmitter.
9. Click High Intensity on the stimulator and then click Stimulate to stimulate the neuron with a
longer, more intense stimulus to generate a burst of action potentials and observe the release
of neurotransmitter.
10.The magnesium ion (Mg2+) is another divalent ion, and it can compete with calcium and block
its role in neurotransmitter release. Click the Mg2+ extracellular solution to fill the Petri dish
with an extracellular solution that contains Mg2+. Note that this solution also contains the same
amount of Ca2+ as the control solution.
Predict Question 3
What will happen to neurotransmitter release when magnesium is added to the extracellular
solution?
a. There will be no neurotransmitter release.
b. There will be less neurotransmitter release than in the control solution
c. Neurotransmitter release will the same as that in the control solution.
d. Neurotransmitter release will be greater than in the control solution.
11.Click Low Intensity on the stimulator and then click Stimulate to stimulate the neuron (axon)
with a threshold stimulus that generates a low frequency of action potentials and observe the
release of neurotransmitter.
12.Click High Intensity on the stimulator and then click Stimulate to stimulate the neuron with
a longer, more intense stimulus to generate a burst of action potentials and observe the release
of neurotransmitter.
Stop & Think Question
Why did the high intensity stimulation fail to trigger the same amount of neurotransmitter release
in the presence of extracellular Mg?+ as in the control extracellular solution?
a. Mg2+ blocks the calcium channels in the axon terminal
b. Mg2+ blocks action potential propagation in the axon.
с. Mg2+ blocks the voltage-gated sodium channels in the axon.
d. Mg2+ blocks the exocytosis channels in the axon.
Experiment is completed.
43
CONTRACTION OF SKELETAL MUSCLE
Single contraction
Fig. 4. The curves of action potential and single muscle contraction. Stimulus – moment of
stimulation; latent period; period of contraction; period of relaxation.
PROCEDURE 2: The muscle twitch and the latent period. Software "PhysioEx 9.0".
Exercise 3 "Skeletal muscle physiology". Activity 1.
1. Note that the voltage on the stimulator is set to 0.0 volts. Click Stimulate to deliver an
electrical stimulus to the muscle and observe the tracing that results.
44
2. The tracing on the oscilloscope indicates active muscle force. Note that no muscle force
developed because the voltage was set to zero. Click Record Data to display your results in
the grid.
3. Increase the voltage to 3.0 volts by clicking the + button beside the voltage display.
4. Click Stimulate and observe the tracing that results.
5. Note the muscle force that developed. Click Record Data to display your results in the grid.
6. Click Clear Tracings to remove the tracings from the oscilloscope.
7. Increase the voltage to 4.0 volts by clicking the + button beside the voltage display.
8. Click Stimulate and observe the tracing that results. Note that the trace starts at the left side of
the screen and stays flat for a short period of time. Remember that the X-axis displays elapsed
time in milliseconds. Also note how the force during the contraction also changes.
Stop & Think Question
What is the period of time that elapses between the generation of an action potential and the start
of muscle tension development in a muscle fiber?
a. the relaxed period.
b. the contractile period.
c. the latent period
d. the recess period.
9. Click Measure on the stimulator. A thin, vertical yellow line appears at the far left side of the
oscilloscope screen. To measure the length of the latent period, you measure the time between
the application of the stimulus and the beginning of the first observable response (here, an
increase in force). Click the + button beside the time display. You will see the vertical yellow
line start to move across the screen. Watch what happens in the time (ms) display as the line
moves across the screen. Keep clicking the + button until the yellow line reaches the point in
the tracing where the graph stops being a flat line and begins to rise (this is the point at which
muscle tension starts to develop). If the yellow line moves past the desired point, click the
button to move it backward. When the yellow line is positioned correctly, click Record Data
to display the latent period in the grid.
10. Click Clear Tracings to remove the tracings from the oscilloscope.
Predict Question
Will changes to the stimulus voltage alter the duration of the latent period?
a.Yes, changing the stimulus voltage will change the latent period duration proportionately.
b.No, changing the stimulus voltage will not change the latent period duration.
1 1 . You will now gradually increase the voltage to observe how changes to the stimulus voltage
alter the duration of the latent period. Increase the voltage by 2.0 volts. Click Stimulate and
observe the tracing that results. Click Measure on the stimulator and then click the + button
until the yellow line reaches the point in the tracing where the graph stops being a flat line and
begins to rise. Click Record Data. Repeat this step until you reach 10.0 volts.
Stop & Think Question
What occurs during the latent period of these isometric contractions?
a. The length of the muscle fiber is sliding into an optimal length.
b. All the steps of excitation-contraction coupling occur.
c. Muscle fiber cross bridges are cycling at sub-maximal rates.
d. The required amounts of ATP are being generated.
Experiment is completed.
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Summation of contractions.
Incomplete tetanus
Fig. 5. Summarized contraction of the muscle ( incomplete summation – incomplete tetanus –
summarized contraction with waves). St1 – moment of first stimulus – contraction (1) under
influence of stimulus 1. St2 – moment of second stimulus. We use second stimulus during
relaxation phases from previous muscle reaction. New contraction (2) under influence of stimulus
2. The 2 contraction are summarized. As a result of the summation we get summarized contraction
– incomplete tetanus.
Complete tetanus
Fig. 6. Summarized contraction of the muscle (complete summation – complete tetanus –
summarized contraction without waves). St1 – moment of first stimulus – contraction (1) under
influence of stimulus 1. St2 – moment of second stimulus. We use second stimulus during
contraction phases from previous muscle reaction. The 2 contraction are summarized. As a result
of the summation we get new summarized contraction – complete tetanus without the waves.
PROCEDURE 3: The composed contraction of skeletal muscle. Software "LuPraFi-Sim".
"Muscles". Activity 2.
46
Summation of contractions represents the contractile response of the skeletal muscle following
the application of at least two stimuli before the contraction period elicited by the first stimulus
ended (15-20 ms).
Considering the possibility that we can apply two stimuli according to the announced theory, the
second stimulus can find the muscle in one of the three phases of the twitch (latent period,
contraction period or relaxation period). Indeed, there are three possibilities that we can observe,
leading to three different myograms:
1. The second stimulus finds the muscle in the latent period: there is no result, the muscle is
unexcitable in this period.
2. The second stimulus finds the muscle in the contraction period: we observe a greater response,
but the two twitches are incompletely fused.
3. The second stimulus finds the muscle in the relaxation period: we observe a specific aspect of
the myogram, the two twitches are partially fused (the relaxation period of the first twitch is
interrupted by the intervention of the second stimulus).
In conclusion, regarding the moment of appearance of the second stimulus, the composed
contraction can follow one of the next two patterns:
1. Incomplete tetanus occurs when every second stimulus finds the muscle in the relaxation period.
Observe the specific aspect of the upper part of the myogram.
2. Complete tetanus occurs when every second stimulus finds the muscle in the contraction period.
Observe the specific aspect of the upper part of the myogram.
Objective: study the summation of contractions of the skeletal muscle and analyze the resulted
myograms.
Principle: apply a complex of stimuli with different frequencies on the skeletal muscle, recording
the resulting myograms on a graphical surface.
Technique:
The session has two different moments: Recording of the myogram of the complete tetanus.
1. Set the frequency of the stimuli at 20 stimuli/s with the right buttons and then apply a complex
of stimuli for 5-6 s. Analyze the resulting myogram.
2. Recording of the myogram of the incomplete tetanus.
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Set the frequency of the stimuli at 10 then at 6.5 and finally at 5 stimuli/s, applying each time a
complex of stimuli for 5-6 s. Analyze the resulting myogram.
Experiment is completed.
The types of the muscle contraction
Fig. 7. Muscular contractions with stimuli of different frequency. Single stimuli cause single
contractions (1, 2); more frequent stimuli – incomplete tetanus (3 - 10 Hz, 4 - 15 Hz ), more
frequent still – complete tetanus – 20 Hz (5). Time – 1 s. 1, 2 – Single contraction. 3, 4 –
Incomplete tetanus. 5 - Complete tetanus.
Mechanism of muscular contraction
The myofibril at rest
The myofibril during contraction
Fig. 8. Schematic presentation of the electron microscopy picture of a myofibril at rest (up) and
at contraction (down).
The molecular mechanism of the muscle sarcomer contraction
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Fig. 9. Schematic presentation of the molecular characteristics of the sarcomer contraction.
COMPLETION:
If membrane mechanisms of the nerve fibers are broken excitation (AP) is _________________
If we stimulate some site of a nerve excitation is conducted in __________________________
The propagation of nerve impulses along unmyelinated fiber involves 2 related processes:
1) _____________________________________ 2) __________________________________
The main properties of the muscles are _____________________________________________
The muscle gives single contraction to ______________________________________________
The single contraction is divided into phases ________________________________________
Under influence of the frequency stimulation skeletal muscle gives _______________________
Tetanic contraction is result of the summation of _____________________________________
Tetanic contraction is divided into _________________________________________________
Incomplete tetanus is a result ______________________ summation of muscular contractions.
Complete tetanus is a result _______________________ summation of muscular contractions.
SUPPLEMENTARY TESTS FOR CREDIT TEST AND EXAM:
Draw the electron microscopy scheme of the myofibril for muscle at rest.
Draw the electron microscopy scheme of the myofibril for muscle during contraction.
Draw the scheme of single muscle contraction with action potential correlation
Draw the scheme of incomplete tetanus with action potential correlation.
Draw the scheme of complete tetanus with action potential correlation.
What kind of contractions are distinguished depending on the frequency stimulation?
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– A single action potential will generate response termed a twitch or single contraction. At
increasing stimulation frequencies twitches occur progressively closer together until they
summarized – tetanic response. A tetanic response is achieved when the summarized contractions
shows no evidence of the individual component twitch responses – tetanus (incomplete tetanus
and complete tetanus).
What does each myofibril contain?
– Each myofibril contains interdigitating thick (myosin) and thin (actin) filaments that are
arranged longitudinally in sarcomeres. Interaction between these filaments causes contraction.
Repeating units of sarcomeres account for the unique pattern in striated muscle.
What does the term "sarcomere" mean?
– Sarcomer is the smallest contractile unit of skeletal muscle fiber. It is the portion of a myofibril
that lies between two successive Z-lines.
What does the thick filament contain?
– Thick filament contains myosin. Each myosin molecule has heads attached to a tail. The myosin
heads bind actin and ATP are involved in cross-bridge formation.
What does the thin filament contain? Where are thin filaments located in the sarcomeres?
– Thin filament contain actin, tropomyosin, and troponin. Troponin is the protein that permits
cross-bridge formation when it binds Ca2+. Thin filaments are anchored at the Z-lines.
What is the main function of the muscle membrane in muscle contraction?
– The main function is to conduct the wave of depolarization over the entire cell surface to initiate
contraction.
What are the T tubules and what is their meaning for excitation-contraction coupling?
– The T (transverse)- tubules are an extensive tubular network of the invaginations of cell
membrane, open to the extracellular space and extend deep into the fiber, which carry the
depolarization to the cell interior. T-tubules are located at the level of the Z-lines.
What do the terms "sarcoplasmic reticulum" (SPR), "terminal cisternae", mean?
– Sarcoplasmic reticulum (SPR) is the internal anastomosing tubular network which surrounds
the myofibrils and runs parallel to the myofilaments. Terminal cisternae are dilated ends of the
SPR tubules, which lie on opposite sides of the T-tubules.
What is the functional meaning of SPR?
– SPR is the site of Ca2+ storage and release for excitation-contraction coupling?
What main event immediately leads to the beginning of interaction between actin and myosin?
Enumerate steps in excitation-contraction coupling in skeletal muscle promoting to this event.
– The main event is increasing of intracellular Ca2+. The steps promoting to this event are:
l) The action potential in the muscle fiber surface membrane passes down T-tubules.
2) Depolarization of the T-tubules is passed to the SPR membrane, opens Ca2+-channels in SPR
(terminal cisternae), releasing of Ca2+ from the SPR into the intracellular fluid.
3) Intracellular Ca2+ increases.
What does Ca2+ released from SPR following the muscle fiber excitation do for muscle
contraction?
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– Ca2+ released from SPR diffuses to the contractile proteins where it removes the inhibition of
the interaction of the two main contractile proteins, myosin (thick filaments) and actin (thin
filament), by binding to specific sites on the regulatory protein troponin.
What does it occur after binding of Ca2+ ions to specific sites on the regulatory protein troponin?
– Binding of Ca2+ ions to specific sites on the regulatory protein troponin causes a conformational
change in troponin, as a result tropomyosin is moved out of the way so that the cross-bridge cycle
can begin.
What is the sliding filament theory of contraction based on?
– The sliding filament theory of contraction is based on the idea about that during contraction
thick and thin filaments do not change length but instead, slide past each other resulting in a
change in length of the each sarcomer and of the whole fiber.
What is the main condition for realization of relaxation? What is the mechanism of creating of
this condition?
– The main condition for realization of muscle relaxation is the decreasing of intracellular Ca2+.
Upon cessation of excitation (i. e. end of action potentials) Ca2+ is resequestered into the
sarcoplasmic reticulum and cross-bridge cycling ceases. ATP is consumed by special Ca2+ pump
in the process of Ca2++ uptake as well as during the cross-bridge cycle.
What is the neuromuscular junction?
– The neuromuscular junction is the specialized junction between an axon terminal and a muscle
fiber.
How many neuromuscular junctions does each skeletal muscle fibers have?
– With the exception of about 2% of the muscle fibers, there is only one neuromuscular junction
per each muscle fiber near its midpoint.
Is there direct contact between nerve and muscle membrane? By which means are signals passed
between the nerve terminal and muscle fiber?
– There is no direct contact between nerve and muscle membrane. A gap or cleft exists between
membranes which is too large to permit electrical transmission of the excitatory nervous impulse.
Signals are passed between the nerve terminal and muscle fiber by means of the chemical
neurotransmitter, acetylcholine.
Describe the successive events occurring during neuromuscular junction transmission.
– An action potential arriving at the axon terminal causes depolarization of the presynaptic
membrane. 2) As a result of the depolarization the Ca2+ channels are opened and Ca2+ rushes into
the presynaptic terminal down its electrochemical gradient. 3) The influx of Ca2+ into terminal
causes release of acetylcholine from its storage vesicles in the terminal into the synaptic cleft. 4)
Released acetylcholine diffuses across the synaptic cleft and combines with receptors on the
postsynaptic cell membrane (motor end-plate), and opens cation channels in this area of
membrane.
What is the transmitter released from presynaptic terminal of neuromuscular junction?
– The neurotransmitter released from presynaptic terminal is acetylcholine (ACh).
Where is acetylcholine synthesized and stored?
– Acetylcholine is synthesized from acetyl coenzyme A (CoA) and choline in the cytoplasm of
the presynaptic terminal. Synthesized ACh is rapidly absorbed into many small synaptic vesicles,
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about 300,000 of which are normally in the terminals of a single neuromuscular junction.
What is the acetylcholine receptors in the postsynaptic muscle membrane?
– There are many acetylcholine receptors in the muscle membrane; these are actually
acetylcholine-gated ion channels.
What does it occur after the binding ACh to the specific postsynaptic (nicotinic) membrane
receptors?
– It's known that the ACh receptor is also an ion channel and it remains constricted if the ACh is
absent. Binding of ACh to the channel protein causes a conformational change that opens the
channel and increases its conductance to predominantly for Na+. As a result the postsynaptic
membrane potential is depolarized.
What is postsynaptic potential called? What properties does the end plate potential has?
– As a result the binding ACh to ACh receptors the internal membrane potential in the local area
of the end plate is decreased, creating a local potential called the end plate potential or excitatory
postsynaptic potential (EPSP). Therefore the EPSP has the properties which are similar local
response ones. The EPSP is not an action potential, but a depolarization of the postsynaptic
membrane. The muscle postsynaptic membrane is not able to generate an action potential.
By which means is the muscle fiber membrane excited after the appearance of the EPSP?
– The appearance of the EPSP causes the ion currents between the muscle postsynaptic membrane
and adjacent areas of muscle fiber membrane (extrasynaptic membrane) which are able to
generate an action potential. As result of these currents the adjacent membrane is depolarized to
the critical level and an action potential is generated. So, the excitation eventually reaches the
entire fiber membrane.
How long does ACh continue to activate the ACh-receptors of postsynaptic membrane? What
processes stop the action of ACh?
– The ACh, once released into the synaptic space, continues to activate the ACh-receptors a few
milliseconds at most, after that ACh is removed.
By which means the released ACh is removed from the synaptic cleft?
– Most of the ACh is destroyed by the enzyme acetylcholinesterase, that is attached mainly to the
basal lamina of the synaptic cleft.
THEME 9:
CREDIT-TEST – PHYSIOLOGY OF EXCITABLE TISSUES
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PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM (CNS)
PHYSIOLOGY OF NEURONS. THE STRUCTURE AND FUNCTION OF NEURONS
Fig. 1. Structure of a neuron.
Underline on the figure – cell body, dendrites, axon hillock, axon.
SYNAPSES IN THE CENTRAL NERVOUS SYSTEM
The neurons of the CNS are connected with one another through synapses (see – Fig. 2).
Fig. 2. Synapse between A and B neurons.
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Fig. 3. Axosomatic synapse, axodendritic synapse, axoaxonal synapse of the A neuron – mark all these
structural elements.
Fig. 4. Synapse of a neuron. Find and mark – presynaptic membrane, synaptic cleft, postsynaptic
memnrane.
Home work -
The basic unit of the nervous system is __________________________________
The body and processes of a neuron are coated with ________________________
The function of the dendrites is ________________________________________
The function of the axon is ____________________________________________
The place where axon begins from the neuron body is called _________________
The functional role of the axon hillock is ________________________________
Synapses, located on the body of a neuron, are called _______________________
Synapses, located on the dendrites, are called _____________________________
Synapses, located on the axon of a neuron, are called _______________________
THE MECHANISM OF TRANSMITTING IMPULSES IN EXCITATORY SYNAPSES.
EXCITATION OF NEURON
The mediator, produced in an axon endings, is liberated from its bound state under influence of the
incoming nerve impulses. Next the mediator is secreted into the synaptic cleft. The mediator quickly
diffuses to the postsynaptic membrane. In consist the postsynaptic membrane mediator interacts with the
receptor proteins.
Fig. 5. Excitation of neuron. A – resting neuron with normal RMP ( 65 mV). B – neuron in an excited
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state with a less negative membrane potential caused by sodium influx – the moving of the sodium ions is
followed by depolarization of the postsynaptic membrane and the appearance of the local potential. For
synapse local potential under influence of the mediator and sodium influx is called the excitatory
postsynaptic potential (EPSP). Find and mark - EPSP.
INHIBITION OF NEURONS
Inhibition of a neuron is the specific neuron state, when the neuron dose not react under excitatory
influences of other neurons. There are several types of inhibition in the CNS.
Fig. 6. Neuron in an inhibited state with more membrane potential during interaction of the inhibitory
transmitter and proteins of the postsynaptic membrane caused by potassium ion efflux and chloride ion
influx. Find and mark – inhibitory neuron, inhibitory mediator, IPSP.
Fig. 7. Postsynaptic inhibition.
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Fig. 8. Axo-axonal synapse, responsible for presynaptic inhibition. C neuron releases GABA, which
open Cl-channels of the axon B neuron. In a result we have got block of passing of excitation from B to
A. Find and mark - inhibitory neuron, inhibitory transmitter, the place of the presynaptic block.
Home work –
A synapse consists of ________________________________________________
The main excitatory mediator in the CNS is ______________________________
The main excitatory mediator in the peripheral NS is ______________________
EPSP as the local potential can ____________ migrate from the place of its generation on small
distance – about _______________
The result of the EPSP moving is ______________ of the electrically excitable membrane of
__________________________
Postsynaptic inhibition is provided by ___________________________________
Inhibitory mediators are ______________________________________________
Hyperpolarization under influence of GABA is called _______________________
During IPSP the excitability of the axon hillock is __________________________
Presynaptic inhibition is localized in _____________________________________
THE REFLEX ACTIVITY OF THE NERVOUS SYSTEM
A reflex, or reflex act is a reaction of the organism, provided through the CNS in response to the stimulation
of sensory receptors. Reflexes manifest themselves in the appearance of some activity of the organism – f/
ex/ - contraction of muscles, glandular secretion, constriction of blood vessels, variation of the heart
activity, kidney activity, etc.
THE REFLEX ARC
The pathway for the nerve impulses from a sensory receptor to an effector organ during the performance
of any reflex is known as a reflex arc.
Fig. 9. A – Reflex arc of the somatic spinal reflex; B – Reflex arc of the autonomic spinal reflex. Find
and mark – sensory receptors, receptor neuron, motor neuron, effector.
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Fig. 10. The schema of the monosynaptic reflex arc.
PHYSIOILOGY OF NERVE CENTRES
A nerve centre is a group of neurons, acting together providing reflex regulation of the particular function.
THE PROPERTIES OF NERVE CENTERS
- ONE-WAY CONDUCTION
In a nerve fiber APs can be conducted in both directions, but in the NC APs can be conducted only in one
direction – from input neuron to output neuron.
Fig. 11. One-way conduction of the nerve centre because impulses pass across the synapses of the nerve centre
in one direction only.
- DELAYED CONDUCTION
Fig. 12. Conduction of the excitation across synapse. Find and mark – synaptic delay and EPSP.
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- SUMMATION (ADDITION) OF EXCITATION
Fig. 13. Temporal (serial) summation. Summation of postsynaptic excitatory potentials in a spinal
motoneuron produced by two weak afferent stimuli applied one after the other at varying intervals. Each
stimulus generates a subthreshold postsynaptic potential only. After reduction of the intervals between
stimuli the total postsynaptic potential reaches critical level (indicated by arrow) and evokes an action
potential.
Fig. 14. The spatial summation of impulses into the nerve centre, when two or more stimuli are acting
simultaneously on different sensory receptors.
- TRANSFORMATION OF THE RHYTHM OF INPUT EXCITATION
Fig. 15. The interrelation between stimulating impulses and the action potentials of the nerve fiber.
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For nerve center you may obtain another interrelation.
rFig. 16. Instances of the transformation of the rhythm excitation by the nerve centre.
Fig 17. The schema of the neuronal increasing of an input signal (2) and the schema of the neuronal
decreasing of an input signal (3).
- IRRADIATION OF EXCITATION
Impulses, arriving in the CNS during strong stimulation, can induce excitation not only in a one nerve
center but also in other nerve centers. This travel of excitation through the CNS is known as irradiation.
Fig 18. The schema of irradiation of excitation into CNS.
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- FATIGUE OF NERVE CENTRES
In contrast to nerve fibbers, nerve centers have property to be easily fatigued. The fatigue can be detected
in a gradual reduction and a complete cessation (elimination) of the responses output central neuron during
stimulation of the input nerve fibbers. The fatigue of nerve centers is result of disorder conduction the
synapses between neurons.
- DEPENDENCE OF NERVE-CENTRE FUNCTIONS ON OXYGEN SUPPLY
Nerve cells take oxygen very intensive. A decrease in oxygen supply to the CNS quickly leads to functional
disturbances in the nerve centers.
- THE SPECIFIC ACTION OF CERTAIN POISONS ON THE CNS
Nerve cells and synapses in consist CNS possess a very big sensitivity to many poisons. These are
strychnine, morphine, narcotic drugs, alcohol, and many others.
- AFTER-ACTION
Fig. 19. The schema of the circulation nerve impulses in consist nerve reflex centre. Find and mark – the
circulation of excitation.
PRINCIPLES OF COORDINATION WORK OF THE NERVE CENTERS
The coordination work of CNS is such the work of neurons which provides adaptive nature of the
organism reactions.
- PRINCIPLE OF CONVERGENCE
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Fig 20. Convergence of various excitations on the motor neuron of spinal cord.
- PRINCIPLE OF RECIPROCAL INNERVATION OF THE EFFECTOR ORGANS BY NEURONS OF AN
NERVE CENTRE
Fig. 21. The schema of the reciprocal innervation of the antagonist muscles. Find and mark on the figure
activated neurons and contracted flexor muscle. Find and mark inhibited motor neuron and relaxed
extensor muscle.
- PRINCIPLE OF "FEEDBACK"
The all nerve centres work in consist of the complex organizations. These organizations are called as
the functional systems.
Fig. 22. The schema of the functional system with feed-back. Mark the channel of the feed-back.
- PRINCIPLE OF THE DOMINANT
The dominant centre is overactive nerve centre. Nerve centre can be in state of inhibition, it can be in state
of normal activity, but sometimes nerve centre can be in state of overactivity. If nerve centre is overactive
we say – the nerve centre is dominant.
- PLASTICITY OF NERVE CENTRES
The plasticity is the property of any nerve centre to vary quality their functional activity.
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Fig. 23. Plasticity of nerve centre.
Fig. 24. The dog after section and cross ligation of the nerve trunks back legs. But gradually under influence
of the regular exercises situation is transformed. The locomotion of our dog is restored. This result is the
consequence of the plasticity rearrangement of the neuronal activity in consist the spinal centres of the
dog.
Fig. 25. The cerebral cortex plays a main role in the compensatory reactions in CNS after damage.
METHOD OF RECORDING OF EEG (ELECTROENCEPHALOGRAM)
Fig. 26. The schema of recording of an electroencephalogram at the person - electrodes (1) on a scalp,
amplifier (2), recorder (3).
Fig. 27. Transformation of alpha rhythm for beta of person (reaction of the activation EEG, or reaction of
the arousal (desynchronization) EEG) under influence of the loud bell. Mark the arousal reaction of
EEG.
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Origin of EEG. In the opinion of most investigators, the origin of EEG waves is connected with an
algebraic summation of excitation and inhibibition postsynaptic potentials cortical neurons. The various
combination of these postsynaptic potentials forms various EEG-rhythms.
Home work
Conduction across one synapse requires ____________________________________________
The more the number______________ into nerve centre, the more ___________________ for
conduction of the excitation through this centre.
The travel of excitation in the CNS is known _____________________
Nerve cells and synapses in the CNS have a very big sensitivity to many __________________
The feedback includes: a) special ______________ for detecting of any deviations controlled
physiological process and b) ___________________ for transmission certain information to
nerve centre.
The dominant nerve center is ___________________ nerve center in the CNS.
Alpha rhythm is a rhythmic wave of an almost sinusoidal form, with a frequency of
____________ per second and amplitude up to ___________________
Beta rhythm is characterized by wave frequencies of _____________per second and amplitude
up to ________________
EEG waves is algebraic summation of _________________________________
Control questions and tasks to credit tests and to examination
Physiology of neurons
What is the basic functional unit of the nervous system and what are its specific functions?
Draw the figure of a neuron. Identify structural elements of neuron (Fig. 1).
Characterize the functions of the neuron dendrites.
Characterize the function of the neuron axon. Where is the place of initial originating of the neuron
action potentials?
Characterize the function of the neuron body and axon hillock.
By which means are the CNS neurons connected with one another?
Draw the schema of the neuron synapse. Sign the main structure elements of synapse (Fig. 2, 4, 5)
Draw the schema of the neuron with the synaptic contact of the various types. Identify the morphological
types of the synaptic contacts (Fig. 3).
What is the reason of the secretion of the mediator in the synaptic cleft?
What are the postsynaptic membrane and receptor proteins?
What happens after the excitatory mediator has bound with a receptor proteins of postsynaptic
membrane?
What change of the resting membrane potential makes the neuron membrane more excitable? What is such influence
called?
Decreasing the voltage of resting membrane potential of a motor neuron soma to a less negative value makes the
neuron membrane more excitable. Such influence is called an excitatory effect and such change of membrane
potential is called a depolarisation.
Explain the mechanism of the forming EPSP.
Can the action potential be produced at site of membrane receptor (postsynaptic membrane)?
The action potential can't be produced at site of membrane receptor (postsynaptic membrane). There can be only a
63
local (graded) changes in membrane potentials called the excitatory (EPSP) postsynaptic potentials.
Draw the schema illustrating the process of the synaptic excitation of a neuron (Fig. 5).
What mediator is the main excitatory mediator in the CNS?
What mediator is the main excitatory mediator in the peripheral NS?
What change of the resting membrane potential makes the neuron membrane less excitable? What are both such
influence and such change of membrane potential called?
Increasing the voltage of resting membrane potential of a motor neuron soma to a more negative value makes the
neuron membrane less excitable. Such influence is called inhibitory effect such change of membrane potential is
called a hyperpolarization.
What are three special characteristics of the synaptic transmission in contrast to the nerve fiber transmission?
Special of synaptic transmission: 1) one-way conduction; 2) delayed conduction; 3) fatiguability. (For nerve fiber
transmission: two-way transmission, no delay of impulse conduction along individual fiber, relative infatigability).
Give the classification of the inhibition types in the CNS.
Draw the schema of the IPSP ( Fig. 6). Explain the ion mechanism of the IPSP.
Draw the schema of the postsynaptic inhibition (Fig. 7). Explain the mechanism of the postsynaptic
inhibition.
Draw the schema of the presynaptic inhibition (Fig. 8). Explain the mechanism of the presynaptic
inhibition.
Explain the ion mechanism of the presynaptic inhibition.
Characterize the more important small molecule inhibitor transmitters of the amino acid class.
- There are two important small-molecule inhibitor transmitters of the amino acid class, namely: 1)Glycine,
which is secreted mainly at synapses in the spinal cord and brainstem. It always acts as an inhibitory
transmitter, increase Cl- conductance; 2) GABA (-aminobutyric acid), which is secreted by nerve
terminals in the spinal cord, cerebellum, basal ganglia, and many areas of the cortex. GABA increases
Cl-conductance and increases K+ conductance.
What is the fatiguability of synaptic transmission called?
The fatigue of synaptic transmission is progressively decrease of the number of discharges by the
postsynaptic neuron when excitatory synapses are repetitively stimulated at a rapid rate. Synaptic fatigue
means simply that synaptic transmission becomes progressively weaker the more prolonged and more
intense the period of excitation.
The mechanism of fatigue is mainly decrease of transmitter substance in the presynaptic terminals.
The reflex activity of the CNS
What is a reflex called?
What is reflex arc called?
What parts is a reflex arc composed of?
A reflex arc is composed of following parts: 1) sensory receptor; 2) afferent neurons and its processes carrying waves
of excitation to the central nervous system; 3) interneurons and synapses conveying impulses to the effector neurons;
4)efferent neurons and its fibers transmitting impulses from the central nervous system to the periphery;
5) the
effector organ whose activity is changed by the reflex.
What is receptor and what is its function?
Receptors are the special structures which transform environmental signals (external or internal) into neural impulses.
The environmental signals that can be detected include mechanical force, light, sound, chemicals, and temperature.
What are reflex time, latent reflex time and central reflex time called?
The reflex time is the period of time from the beginning of stimulation to the end of reflex reaction; the latent reflex
time is the period of time from the beginning of stimulation to the beginning of reflex reaction; the central reflex time
is interval of time, which is necessary to pass nerve impulses through the central part of the reflex arc. The more
numbers of interneuronal synapses in the reflex nerve center the more central time of reflex.
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What is the reflexogenous zone or receptive field of the reflex called?
The reflexogenous zone or receptive field of the reflex is called the area of the body (for example, a portion of the
skin) stimulation of which causes a definite reflex. The receptive field of various reflexes may overlap, and in
consequence a stimulus applied to a certain part of the skin can elicit one reflex or another depending on its strength
and the state of the central nervous system.
What is the classification of reflexes as regards their biological importance for organism?
The reflexes are divided as regards their biological importance for organism into nutritional, defensive, sexual,
orientation, postural-tonic, and locomotor ( i.e. reflexes of attitude and movement of the body in space).
What is the classification of reflexes according to the location of receptors whose stimulation induces a given reflex?
According to the location of receptors whose stimulation induces a given reflex act, reflexes are divided into
exteroceptive (i.e. those caused by stimulation of receptors on the outer surface of the body), viscero- or interoceptive
(arising from stimulation of the receptors of the internal organs and blood vessels), and proprireceptive (i.e. those
caused by stimulation of the receptors of the skeletal muscles, joints, and tendons).
What is the classification of reflexes according to the parts of the central nervous system involved in their occurrence?
According to the parts of the central nervous system involved in their occurrence reflexes are divided into spinal, in
which the neurons of the spinal, in which the neurons of the spinal cord take part; bulbar, which require the neurons
of the medulla oblongata; mesencephalic, which involve the neurons of the midbrain; diencephalic, involving
neurons of the inter-brain, cortical involving neurons of the cerebral cortex take part.
What is the classification of reflexes according to the organs involved?
According to the organs involved reflexes are divided into motor reflexes, in which effector organ is a muscle;
secretory reflexes, which terminate in glandular secretion; and vasomotor reflexes, which are manifested by
constriction or dilation of blood vessels. This classification is acceptable for more or less simple reflexes, but with
complex ones, in which various neurons of the higher parts of the central nervous system take part, different effector
organs are involved, as a rule, in the reflex reaction.
Draw the schema of the somatic spinal reflex ( Fig. 9 a).
Draw the schema of the autonomic spinal reflex ( Fig. 9 b).
Draw the schema of the monosynaptic reflex arc (Fig. 10).
The properties of nerve centres
What is a nerve center called?
A reflex arc nerve center is called the central part of reflex arc.
A nerve center is a totality ("ensemble") of neurons located in different parts of CNS and acting together in the
performance of a definite reflex or in the regulation of a particular function.
Enumerate the main properties of nerve centers.
The main properties of nerve centers are as follows: one-way conduction, delayed conduction, summation of
excitation, transformation of the rhythm of excitation, irradiation of excitation, after-action, fatiguability,
dependence on oxygen supplies, dependence on different metabolites and drugs.
Characterize one-way conduction of the nerve centres. Draw the schema (Fig. 11).
Characterize delayed conduction of excitation through the nerve centres.
What time components form the time of conduction excitation through one synapse. Draw the schema
(Fig. 12).
What is the temporal summation of excitation in consist nerve centres? Draw the schema illustrating the
mechanism of the temporal summation (Fig. 13).
What is the spatial summation of excitation in consist nerve centres? Draw the schema illustrating the
mechanism of the spatial summation (Fig. 14).
What is transformation of the input excitation in consist nerve centres?
Draw the schema of the neuronal increasing of an input signal of nerve centre (Fig. 17, 2).
What is irradiation of excitation into CNS?
Draw the schema of irradiation of excitation into CNS? (Fig. 18)
What is after-action called?
Characterize the mechanism of the after-action into nerve centres.
Draw the schema of the circulation nerve impulses in consist nerve centre ( Fig.19).
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What is the cause of sudden cessation of circulation (reverberation) within a typical reverberatory circuit?
The usual cause of sudden cessation of reverberation within a typical reverberatory circuit is fatigue of synaptic
junctions in the circuit, because fatigue lowers the excitability of the next neuron in the circuit so that the circuit
feedback is suddenly broken.
Principles of coordination work of the nerve centers
What is the coordination of nervous system activity called?
- The coordination of nervous system activity is called the interaction of neurons and of nervous processes in the
central nervous system which provides adaptive nature of the organism reactions.
Enumerate the general factors of coordination of nervous system activity?
- The general factors of coordination activity are: l) convergence; 2) principle of reciprocal innervation; 3) the
principle of structure-functional connections (feedforwards, feedback) 4) principle of the dominant; 5) plasticity of
nerve centers and compensatory mechanisms.
What does "convergence" mean?
“Convergence” means the coming together of the input axon terminals on the same neuron.
Draw the schema of convergence various excitation to motor neuron of spinal cord (Fig. 20).
Draw the schema of reciprocal innervation of the antagonist muscles (Fig. 21).
Draw the schema of the functional system with feedforward and feedback (Fig. 22).
What is the principle of the "feedback", or secondary afferent impulses called?
The “feedback” is channel of the communication between the regulated physiological constant (as a result of special
activity of effector organs) and the nerve centre for correction nerve centre and effector organs activity.
What is the dominant center? Give some examples of dominant center
What are the causes of dominant state of nerve centers?
What basic features are the dominant foci of excitation characterized?
What is the plasticity of nerve centers called?
The plasticity of nerve centers is called the compensating properties of nerve centers, and the variability of their
functional significance.
Illustrate by means of an example of the variability of functional significance (the plasticity) of nerve
centers in experiments in cross-suturing nerve trunks.
What part of CNS plays a very great role in the compensatory phenomena in nerve centers after damage, and in
their functional reconstruction in man and the higher animals?
The cerebral cortex plays a very great role in the compensatory phenomena in nerve centers after damage, and in
their functional reconstruction in man and the higher animals. It has been shown that, if the cerebral cortex is
removed from an animal following an operation to suture nerves of a different order, to amputate the paws, or to
extirpate the cerebellum, then, after adaptation to the damage has occurred and movement has been restored, there
is a new disorganization of the movements characteristic of the operations earlier performed.
EEG- method of researching CNS
Draw the schema of EEG recording (Fig. 26).
What does the term " desynchronization, or activation" of EEG? What are its components?
- A transition from alpha rhythm to beta rhythm is observed with stimulation of the sensory receptors.
What are the parameters of alpha rhythm?
- A rhythmic wave of an almost sinusoidal form, with a frequency of 8 to 13 per second and amplitude up to 50
microvolts. Alpha rhythm is distinctly expressed in a subject at rest physically and mentally, lying in a comfortable
chair, with his muscles relaxed and his eyes closed, and no external stimuli
What are the parameters of beta rhythm?
- A rhythm is characterized by wave frequencies above 13 per second and amplitude up to 20 or 25 microvolts. The
greater the strain of attention during mental work, or the greater the stimulus acting on the receptors, the more rapidly
is alpha rhythm replaced by beta.
CARDIAC CYCLE. HEART SOUNDS. AUSCULTATION OF HEART
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Laboratory works
1. Cardiac cycle
The mechanocardiogram (MCG) recording from the frog heart (fig. 1, fig. 2).
Pay attention: MCG is mechanical but not electrical heart performance.
Fig. 1. Procedure of the mechanocardiogram (MCG) recording in experiment on a frog
Fig. 2. The frog mechanocardiogram (MCG)
Laboratory report:
Count the frequency of frog heart beats in your experiment __________ beats/min
The simple analysis of the frog MCG
a-a1 – Cardiac cycle
a-b – Atrial systole
b-a1 – Atrial diastole
b-c – Ventricular systole
c-b1 – Ventricular diastole
2. Calculation of cardiac cycle duration by pulse palpation in rest condition and after standard physical
exercise in a person
Laboratory report:
1. Count up the pulse in rest condition during 1 min ________________________________________________
2. Calculate duration of the cardiac cycle in rest condition ____________________________________________
3. Make 20 knee-bends per 30 seconds
 Calculate the cardiac cycle duration after the exercise –
 Calculate the cardiac cycle duration for maximal cardiac frequency (180/min) –
3. Phonocardiography (homework)
Detailed analysis of heart sounds has become possible with the use of electronic apparatus. If a sensitive microphone
is connected to an amplifier and an oscilloscope, and pressed against the chest, heart sounds can be registered as
tracings on moving film or paper. The technique is called phonocardiography (PCG). The curve shows 1-st and 2-d
sounds that can be heard with an ear too, but method gives possibility to register two additional enough weak heart
sounds – the 3-d and 4-th. These two sounds can’t be heard by ear or by stethoscope.
The 1-st sound appears on curve in a moment of atria-ventricular valves closing. The 2-d sound occurs in a moment
of semilunar valves closing. The 3-d sound occurs 0.11 to 0.18 seconds after the 2-d sound as the result of the cardiac
wall vibrations in phase of maximal filling of the ventricles. The 4-th sound precedes the 1-st one. It is a result of
ventricular walls vibrations during entry of the additional blood portion in the atrial systole end.
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Fig. 3. Cardiac cycle and phonocardiogram
Procedure
1. Point (draw arrows) on the fig. 3 moments of atria-ventricular valves closing and opening, and same for semilunar
valves. Mark on the phonocardiogram all cardiac sounds.
2. Demonstration of phonocardiogram recording.
Laboratory report:
1. Which heart sound is the loudest? _______________________________________________________
2. What causes make a 1-st sound? ________________________________________________________
3. What causes make a 2-st sound? ________________________________________________________
4. Can we hear 3-d and 4-th sounds by ear? _________________________________________________
5. What changes of heart sounds can be occur after strenuous physical activity? _____________________
__________________________________________________________________________________
6. Which sound (1-st or 2-d) does rise more significantly after strenuous physical activity? ______________
__________________________________________________________________________________
Heart sounds (home work)
The beating of a human heart usually produces four sounds, but only two may be detected with a stethoscope. The
remaining two sounds may be heard if adequately amplified electronically.
The first sound is created by blood turbulence associated with the closure of the atria-ventricular valves soon after
ventricular systole begins. This sound is the loudest and longest of the two sounds, and may be best heard over the
apex of the heart. The sound produced by the tricuspid valve is best heard in the fifth intercostal space just lateral to
the left border of the sternum, while the mitral valve sound is best heard in the fifth intercostal space at the apex of
the heart (fig. 4).
The second heart sound is created by blood turbulence associated with closure of the semilunar valves at the beginning
of ventricular diastole. This sound is of shorter duration and lower intensity, and has a more snapping sound as
compared to the quality of the first heart sound. The second heart sound produced by the aortic semilunar valve
closing is best heard in the second intercostal space to the right of the sternum. The second sound produced by the
pulmonary semilunar valve is best heard in the second intercostal space just to the left of the sternum (fig. 4).
Heart sounds provide valuable information about the valves. Abnormal sounds made by the valves are termed
murmurs. Murmurs do not always indicate that the valves are not functioning properly. Many individuals possess a
functional murmur that has no clinical significance at all. Listening to sounds of the body is called auscultation.
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Fig. 4. Surfaces of areas where heart valve sounds are best heard
Procedure:
1. The stethoscope should be used in a quiet room.
2. The earpieces of the stethoscope should be cleaned with alcohol just before using.
3. Listen to the heart sounds of your laboratory partner by placing the diaphragm of the stethoscope to the skin at
several positions on the chest wall illustrated in fig. 4.
4. The first sound is best heard at the apex of the heart.
5. The second sound is best heard in the second intercostal space.
6. Ask your partner to run in place about 25 steps. Listen to the heart sounds again.
Supplementary information (answers to questions of credit test and exam)
1. What is the primary function of heart?
The function of the heart is rhythmic pumping of blood that it receives from the veins into the arteries. It is
performed by alternate rhythmic contraction and relaxation of the muscular fibers that form the walls of the atria
and ventricles. Contraction of the myocardium of these chambers is known as their systole, and relaxation as their
diastole. In normal physiological conditions systole and diastole occur in a definite coordination and constitute
the cardiac cycle.
2. What valves does the heart have and what is their main function?
There are two types of valves in the heart – the atria-ventricular valves (AV-valves), and the semilunar valves.
The atria-ventricular valves separate the atria from the ventricles, and the semilunar valves which separate the
right ventricle from the pulmonary trunk and the left ventricle from the aorta. Blood flow in the right direction is
provided by the coordinated work of the cardiac valves. The opening or closing of the valves is determined by the
pressure of either side of the valve. Due to valves in normal physiological conditions blood flows in only one
direction in the heart cavities – from the atria into the ventricles, and from the ventricles into the arterial system.
3. Describe the phase of asynchronous contraction of the ventricular and what is the state of valves during of this
phase?
The phase of the ventricular systole during which the wave of excitation and contraction spreads along the
myocardium is known as the phase of asynchronous contraction; it lasts 0.05 of a second. During this phase the
contraction wave which gradually spreads along the myocardium does not involve the entire ventricle
simultaneously; some of the fibers are contracting, which stretches those that have not yet contracted.
4. Describe the phase of isometric (isovolumic) contraction of the ventricular and what is the state of valves during
of this phase?
All the ventricular muscle fibers become involved in contraction, the pressure of the blood in the ventricular
cavities begins to rise, and the atria-ventricular valves close as a result. The semilunar valves are still closed at
this time as the pressure in the ventricles is still below in the aorta and pulmonary trunk.
5. What is the phase of rapid ejection of the ventricular ejection period? How the intraventricular pressure does
change and what is the state of valves during development of this phase?
The phase of rapid ejection of the ventricular ejection period is the beginning or the first third of the ejection
period. During this phase the blood pressure within the ventricles continues to rise up to 120 to 130 mm of mercury
in the left ventricle and 25 to 30 mm of mercury in the right ventricle. Atria-ventricular valves are close, semilunar
valves are open.
6. What is the phase of slow ejection of the ventricular ejection period? How the intraventricular pressure does
change and what is the state of valves during development of this phase?
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The phase of slow ejection of the ventricular ejection period begins when the inflow of blood into the aorta and
pulmonary trunk becomes less than their outflow. At this time of the myocardium of the ventricles begins to relax.
Blood pressure does not increase, and at the end of systole begins to fall, but still higher than the aorta and
pulmonary trunk pressure. Atrioventricular valves are close, semilunar valves are open.
7. What are the periods of ventricular diastole and their durations?
The ejection phase of ventricular systole is followed by the ventricular diastole. There are two periods of
ventricular diastole which are as follows: period of ventricular relaxation lasting about 0.12 second and period of
ventricular filling which lasts about 0.35 second.
8. What is the protodiastolic phase of the relaxation period of ventricular diastole? How the intraventricular
pressure does change and what is the state of valves during development of this phase?
At the end of the systole, ventricular relaxation begins suddenly, allowing the intraventricular pressures to fall
rapidly. The pressure in the aorta becomes higher than that in the ventricle, and the semilunar valves close. The
interval between beginning relaxation of the ventricles and closure of the valves is known as the protodiastolic
interval. It lasts 0.04 of a second.
9. How the intraventricular pressure does change and what is the state of valves during development of the phase
of isometric (isovolumic) relaxation of ventricular diastole?
After closing of semilunar valves at the end of protodiastolic interval the ventricles continue to relax about 0.08
s. During this period the atria-ventricular and semilunar valves remain closed and intraventricular pressures fall
rapidly. When the pressure in the ventricles falls below than in the atria, the AV-valves open and blood from the
atria flows into the ventricles and to begin a period of ventricular filling.
10. What are the phases of period of ventricular diastole filling? How the intraventricular pressure does change and
what is the state of valves during development of this period?
Just after opening of AV-valves at the end of isovolumic relaxation phase of ventricular diastole, the blood from
the atria enters the ventricles rapidly at first because the pressure in them drops to zero after their relaxation (the
phase of rapid filling of the ventricles). This phase lasts for about the first third of diastole. As the ventricles fill
with blood, pressure rises slightly, and the flow of blood into them becomes slower, therefore, during the middle
third of diastole, only a small amount of blood normally flows into the ventricles; this is blood that continues to
empty into the atria from the veins and passes on through the atria directly into the ventricles. At the end of the
diastole, the atria systole occurs, lasting 0.1 second, and give an additional thrust to the inflow of blood into the
ventricles; this accounts for about 25% of the filling of the ventricles during each heart cycle (presystole). During
all ventricular diastole AV-valves are open, semilunar valves remain closed.
11. What are the sound manifestations of cardiac activity? What is the auscultation?
The auscultation is the method which is usually used to explore heart sounds by listening to them with the aid of
an ear or, more usual, a stethoscope pressed to the chest on a level of the heart.
12. How many heart sounds can be usually distinguished with the auscultation? Describe their main peculiarities?
Under auscultation two sounds are heard – the first at the beginning of the ventricular systole, and the second at
the beginning of the ventricular diastole. The first sound is dull, prolonged, and low, while the second is short and
high.
Completion
1. Cardiac cycle is _________________________________________________________. Its average duration is
_____________seconds.
2. Atria systole lasts __________________seconds.
3. Atria diastole lasts _________________seconds.
4. Ventricular systole lasts _____________seconds.
5. Ventricular diastole lasts _____________seconds.
6. Presystole is ________________________________________________________________________________
7. The ventricular systole include following periods
__________________________________________________.
Their durations are________and _________
seconds.
8. There are two phases of the ventricular tension period _______________________________________________
Their durations are _______________and ______ seconds.
9. There are two phases of the period of ejection
_____________________________________________________________________________________
Their durations are ___________and ____________ seconds.
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10. There are two phases of the ventricular relaxation period
________________________________________. Their duration _________________and______________
second.
11.Name 2 phases of the period of ventricular filling.
1) _____________________________________________________________________________________
2) __________________________________________. Their durations are _______________and _________
seconds.
12.Heart sounds provide valuable information about the
______________________________________________________________________________________
Multiple choice
1. At the cardiocycle beginning heart valves are in the position:
1) AV-valves are opened, semilunar are opened, 2) AV-valves are closed, semilunar are closed, 3) AV-valves
are closed, semilunar are opened, 4* ) AV-valves are opened, semilunar are closed
2. Duration of systole ventricle takes: 1) 0.4 s, 2) 0.2 s, 3*) 0.З3 s
3. What are the phases of the ventricular tension period and their duration?
1*)Two phases of the ventricular tension period: the phase of asynchronous contraction (0.05 s) and the phase of
isometric or isovolumic contraction (0.03 s), 2) Two phases of the ventricular tension period: the phase of
asynchronous relaxation (0.05 s) and the phase of isometric or isovolumic relaxation (0.03 s)
4. What are the phases of the ventricular ejection systolic period and their duration?
1) Two phases of the period of ejection are as follows: the phase of rapid relaxation, lasting about 0.10-0.12
second, and the phase of slow relaxation, which lasts 0.10 to 0.15 of a second), 2*) Two phases of the period of
ejection are as follows: the phase of rapid ejection, lasting about 0.12 second, and the phase of slow ejection,
which lasts 0.13 of a second).
5. The maximum value of the blood pressure in left ventricle in the systole reaches
1) 70-80 mmHg, 2) 25-30 mmHg, 3*) 120-130 mmHg
6. The maximum value of the blood pressure in right ventricle in the systole reaches
1) right ventricle 80 mmHg, 2) right ventricle 100 mmHg, 3*) right ventricle 30 mmHg, 4) right ventricle 120
mmHg
7. Closure of aortic (semilunar) valve occurs at the end of which phase of cardiac cycle?
1) Isovolumetric contraction, 2) Rapid injection, 3) Rapid filling (rapid inflow), 4) Isovolumetric relaxation,
5*) Protodiastole
8. Closure of AV-valves occurs at the onset of which phase of cardiac cycle?
1*) Isovolumetric
contraction, 2) Rapid injection, 3) Rapid filling (rapid inflow), 4) Isovolumetric
relaxation, 5) Protodiastole
9. Opening of aortic (semilunar) valve occurs at the onset of which phase of cardiac cycle?
1) Isovolumetric contraction, 2*)Rapid injection,
3) Rapid filling (rapid
inflow),
4) Isovolumetric
relaxation, 5) Protodiastole
10. Opening of AV-valves occurs at the onset of which phase of cardiac cycle?
1) Isovolumetric contraction, 2) Rapid injection, 3*)Rapid filling (rapid inflow), 4) Isovolumetric relaxation,
5) Protodiastole
11. The protodiastole period is
1) Time of exile of blood from ventricle, 2) Time of reduction of atria, 3*) Time from the relaxation beginning
ventricle to closed semilunar valves
12. What part of cardiac cycle is the first sound generated?
1*) The first sound is associated with closure of the atria-ventricular (AV) valves at the beginning of systole;
2) The first sound is associated with closure of the semilunar valves at the beginning of systole
13. What part of cardiac cycle is the second sound generated?
1) The second sound is associated with closure of the atria-ventricular (AV) valves at the beginning of systole.
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2*) The second sound is associated with closure of the semilunar valves at the beginning of diastole.
14. What is the origin of the first sound?
1*) The first sound is mainly caused by vibrations of the stretched cusps of the atria-ventricular valves and their
tendinous cords. 2) The first sound is mainly caused by vibrations of the stretched cusps of the semilunar valves.
15. What is the origin of the second sound?
1) The second sound results from the closing of the atria-ventricular valves.
2*) The second sound results from the closing of the semilunar valves
PHYSIOLOGICAL PROPERTIES OF CARDIAC MUSCLE
Laboratory works
1. Analysis of the heart conductivity (Stannius experiment)
Pacemaker activity or automatism is one of the characteristic properties of the heart. The term designates the capacity
of an organ, tissue, or cell to be excited by impulses originating intrinsically without an external stimulus. Automatism
can most easily be studied and proved in experiments on an isolated frog heart which will continue to contract for
hours, and even days, after being removed from the body when placed in Ringer solution.
In mature animals and man pacemaker activity is an inherent property of the fibers of the atypical muscles
concentrated in the conducting system of the heart. Rhythmic generation of impulses without the influence of any is
demonstrated in vivo in cardiac cell cultures. The experiments with the cell cultures show that the anatomical
substratum of automatism is formed by certain myocardial cells, as would be expected from the myogenic theory of
cardiac automatism.
In the experiment it is necessary to study a frog heart performance in conditions of isolation of the SA node (isolation
of the heart pacemaker).
Place first Stannius ligature. For this purpose, manipulating an ophthalmic forceps, lead the ligature (10-15 cm) under
the aorta. Make a closed loop on the border between viens sinus and rightl atrium. The SA node (pacemaker) will be
isolated. Heart will stop in a diastole (fig. 5), though the pulsing viens sinus will be prolonged.
Fig. 5. First ligature of Stannius
Wait 1-2 minutes. If for this time the heart will not begin contraction, use the second Stannius ligature on border
between atria and ventricle. The purpose of applying second ligature is mechanical stimulation АV node. Usually
mechanical stimulation gives self-excitation AV node and the heart restores a performance (fig. 6). Pay attention to
some feature of a heart performance after applying the second ligature. AV node has smaller ability to automatism
and the frequency of heart beats is less. The heart working in a new rhythm has no a normal sequence of contraction
atrium and ventricle. After the second ligature they are usually contracting simultaneously. During recording
mechanocardiogram has one deflection. It is explained by that the action potential from the AV node after isolation
of the SA node is simultaneously spread to ventricle and to atrium.
Fig. 6 Second ligature of Stannius
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Laboratory report: draw the frog mechanocardiogram after preforming of the first and the second ligatures of
Stannius.
2. Refractory period of cardiac muscle
The refractoriness is the inability of the excitable tissue to initiate new action potential in response to an inward,
depolarizing current during the course of its excitation (an action potential) because of the certain time period is
required for the cell to recover partial and full excitability during the repolarization process. These periods are called
the refractory periods and have been divided into several segments: (1) the absolute refractory period during which
the membrane cannot be reexcited by an outside stimulus, regardless of the level of external voltage applied; (2) the
relative refractory period during which a propagated action potential can be generated but with a depolarizing stimulus
that is larger than normal; (3) the supernormal period is a short interval during which the cell is more excitable than
normal; that is, a weaker than usual depolarizing stimulus can initiate a propagated action potential (fig. 7).
Cardiac muscle, like all excitable tissue, is refractory to restimulation during the action potential. Therefore, the
absolute refractory period of the heart is the interval of time during which a normal cardiac impulse cannot re-excite
an already excited area of cardiac muscle. It begins with the upstroke of the action potential and ends after the plateau
and reflects the time during which no action potential can be initiated. The normal absolute refractory period of the
ventricle is 0.25 to 0.30 second (250 to 300 ms), which is about the duration of the action potential. It is contrasts
with the brief action potential and accordingly the brief absolute refractory period of skeletal muscle which lasts about
of 0.003 to 0.005 second (3-5 ms).
With termination of the absolute refractory period, excitability returns to its initial level. There is an additional relative
refractory period just following the absolute refractory period when repolarization is almost complete. It lasts of about
0.05 second during which the muscle is more difficult than normal to excite but nevertheless it can be excited by very
strong stimuli exceeding the initial threshold of stimulation and the early premature contraction (extrasystole) can be
occurred as a result.
Fig. 7. The correlation between myocardial excitability and action potential dynamics.
1 – absolute refractory period; 2 – relative refractory period; 3 – supernormality period
An extrasystole is called one of the types of a disturbance in cardiac rhythm which is encountered in pathology,
marked by episodic or regular appearance of a premature systole.
3. Modeling of premature contraction (an extrasystole)
Objective: To examine the mechanism of premature contraction (an extrasystole).
1. Draw MCG and indicate a moment of the suprathreshold electrical stimulus action (arrow) on the ventricles
myocardium during systole.
Explain the observed phenomenon.
2. Draw MCG and indicate a moment of the suprathreshold electrical stimulus action (arrow) on the ventricles
myocardium during diastole.
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Explain the observed phenomenon.
Supplementary information (answers to questions of credit test and exam)
1. What three major types of cardiac muscle is the heart composed and what are their main functions?
The heart is composed of three major types of cardiac muscle: contractile atrial muscle, contractile ventricle
muscle, and specialized excitatory and conductive muscle fibers. The atrial and ventricular types of muscle
contract in much the same way as skeletal muscle except that the duration of contraction is much longer. On the
other hand, the specialized excitatory and conductive fibers contract only feebly because they contain few
contractile fibrils; instead, they exhibit rhythmicity and varying rates of conduction, providing an excitatory
system for the heart.
2. What is the conducting system of the heart called and what is its main significance for cardiac activity?
The conducting system of the heart is called a specialized system of atypical muscle fibers which are the poorlydifferentiated muscle fibers close in structure to the embryonic muscles. The heart is endowed with this system
for (1) generating rhythmical impulses to cause rhythmical contraction of the heart muscle (heart automatism)
and (2) conducting these impulses rapidly throughout the heart. Due to the conducting system the atria contract
about one sixth of a second ahead of ventricular contraction (the coordination of cardiac cycle occurs), which
allows extra filling of the ventricles before they pump the blood through the lungs and peripheral circulation.
Another special importance of this system is that it allows all portions of the ventricles to contract almost
simultaneously, which is essential for effective pressure generation in the ventricular chambers.
3. List all of the parts of the conducting system of the heart in proper order (in sequence).
The cardiac conducting system consists of the following parts: (1) the sinus node (also called sino-atrial or S-A
node), in which the normal rhythmical impulse is generated; (2) the internodal pathways that conduct the impulse
from the sinus node to the atrioventricular (A-V) node; (3) the A-V node, in which the impulse from the atria is
delayed before passing into the ventricles; (4) the bundle of His, which conducts the impulse from the atria into
the ventricles; and (5) the left and right branches of the bundle of His, one of which passes into the right ventricle
and the other into the left; (6) the terminal branches of the conducting system, which are represented by a network
of Purkinje's fibers widely distributed in the subendocardial tissue and form anastomoses with the muscle fibers
of the myocardium.
4. Where is the sinus node located, what are its peculiarities?
The sinus node (S-A node) is located in the superior-lateral wall of the right atrium immediately below and slightly
lateral to the opening of the superior vena cava. The sinus nodal fibers connect directly with the atrial muscle
fibers, so that any action potential that begins in the sinus node spreads immediately into the atrial muscle wall.
5. What is pacemaker activity of the heart called? How can the heart automatism be proved?
Pacemaker activity or automatism is one of the characteristic properties of the heart. The term designates the
capacity of an organ, tissue, or cell to be excited by impulses originating intrinsically without an external stimulus.
Automatism can most easily be studied and proved in experiments on an isolated frog's heart which will continue
to contract for hours, and even days, after being removed from the body when placed in Ringer's solution.
6. Describe the principle properties of the automatism of the various parts of the heart.
Excitation of the heart normally proceeds from the sino-atrial node which is the natural (physiological) pacemaker
of the heart. But certain other parts of heart also possess the property of automatism. They are known as the latent
pacemakers since they do not display this property under normal conditions but act only when the function of the
principal pacemaker is impaired. Pacemaker activity is the A-V node, the fibers of which, when not stimulated
from some outside source, discharge at an intrinsic rhythmical rate of 40 to 50 times per minute, the left and right
branches of the bundle of His discharge at rhythmical rate of 30 to 40 times per minute, and the Purkinje fibers,
which discharge at a rate somewhere between 15 and 20 times per minute. These rates are in contrast to the normal
rate of the sinus node of 60 to 80 times per minute.
7. What are gap junctions or "nexuses" called and what is their functional significance for myocardium?
The gap junctions are present at the intercalated discs of myocardial cells. These junctions are the parts of
intercalated disks where the cell membranes fuse with one another in such a way that they form permeable
"communicating" junctions (so-called "nexuses") that allow relatively free diffusion of ions. Therefore, from a
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functional point of view, ions move with ease along the longitudinal axes of the cardiac muscle fibers, so that
action potentials travel from one cardiac muscle cell to another, past the intercalated discs, with only
slight hindrance.
8. Why myocardium is called an electrical syncytium?
This is accounted for the observation that the heart behaves as an electrical syncytium due to the presence of
"nexuses" which are low-resistance paths between cells, allowing for rapid electrical spread of action potentials.
Thus, cardiac muscle conductivity is different from the skeletal muscle one because of cardiac muscle cells are
so interconnected that when one of these cells becomes excited, the action potential spreads to all of them,
spreading from cell to cell as well as throughout the latticework interconnections (so-called, diffused conduction
of excitation).
9. Describe the contractile reactions of cardiac muscle to the single stimuli of the gradual increasing in the strength.
How is this type of the contractile response called? What is the explanation for such responses of cardiac muscle?
Compare with the skeletal muscle.
Under stimulation of cardiac muscle with a gradual increase in the strength of single stimuli the following
phenomena may be observed: the heart responds to a threshold stimulus by a contraction of maximum force.
Further intensification of the stimulus brings no changes in contraction, which shows that the strength of
contraction does not depend upon the strength of the stimulus, in other words, the heart either does not respond
to a stimulus that is too weak, or responds by maximal contraction to one that is stronger than the threshold. This
type of the contractile reaction is called "the law of all-or-nothing". The explanation for these responses lies in
the fact that the cardiac muscle is an electrical syncytium and it always behaves itself as an indivisible whole. In
contrast, the skeletal muscle that is not an electrical syncytium reacts under similar conditions in accordance with
"the law of strength", that is the more strength of stimulation the more strength of contractions.
10. What is the primary peculiarity of the action potentials in cardiac non-pacemaker tissues in comparison with the
action potentials in skeletal muscle fibers?
The primary peculiarity of the action potentials is the far greater duration of the former. Normal ventricular and
atria muscle cells have relatively high (more negative) and stable resting membrane potentials of about -85 to 90
mV. Action potentials are characterized by a very rapid onset and long duration, especially in the ventricle, with
a duration of about 300 msec.
11. Describe four (0-4) phases of a typical ventricle action potential.
There are four (0-4) phases of the fast action potentials which are characterized of ventricle muscle. The rapid
upstroke is termed phase 0, the initial rapid repolarization phase 1, the plateau period phase 2, the final rapid
repolarization phase 3, and the resting membrane potential phase 4.These phases of the action potential are related
to marked and rapid changes of ion permeability through separate ionic channels in the cell membrane.
12. What the refractoriness and the refractory periods are called? Enumerate the typical refractory periods and
define each of them.
The refractoriness is the inability of the excitable tissue to initiate new action potential in response to an inward,
depolarizing current during the course of its excitation (an action potential) because of the certain time period is
required for the cell to recover partial and full excitability during the repolarization process. These periods are
called the refractory periods and have been divided into several segments: (1) the absolute refractory period during
which the membrane cannot be reexcited by an outside stimulus, regardless of the level of external voltage
applied; (2) the relative refractory period during which a propagated action potential can be generated but with a
depolarizing stimulus that is larger than normal; (3) the supernormal period is a short interval during which the
cell is more excitable than normal; that is, a weaker than usual depolarizing stimulus can initiate a propagated
action potential.
13. Describe the absolute refractory period of cardiac muscle and compared with the skeletal muscle.
Cardiac muscle, like all excitable tissue, is refractory to restimulation during the action potential. Therefore, the
absolute refractory period of the heart is the interval of time during which a normal cardiac impulse cannot reexcite an already excited area of cardiac muscle. It begins with the upstroke of the action potential and ends after
the plateau and reflects the time during which no action potential can be initiated. The normal absolute refractory
period of the ventricle is 0.25 to 0.30 second (250 to 300 ms), which is about the duration of the action potential.
It is contrasts with the brief action potential and accordingly the brief absolute refractory period of skeletal muscle
which lasts about of 0.003 to 0.005 second (3-5 ms).
14. What are the relatively long refractory periods of cardiac muscle responsible for?
The relatively long refractory periods of cardiac conducting system and of heart muscle (which are due to the long
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plateau of these action potentials) are responsible for inability to produce a sustained (tetanic) contraction of the
heart by a series of rapid impulses (which sometimes can occur during abnormal cardiac rhythms) and also prevent
single extra depolarizations (so-called premature depolarizations), which occur spontaneously, from occurring so
early that one contraction superimposes on another.
15. Define the relative refractory period of cardiac muscle. What is an extrasystole called?
With termination of the absolute refractory period, excitability returns to its initial level. There is an additional
relative refractory period just following the absolute refractory period when repolarization is almost complete. It
lasts of about 0.05 second during which the muscle is more difficult than normal to excite but nevertheless it can
be excited by very strong stimuli exceeding the initial threshold of stimulation and the early premature contraction
(extrasystole) can be occurred as a result. An extrasystole is called one of the types of a disturbance in cardiac
rhythm which is encountered in pathology, marked by episodic or regular appearance of a premature systole.
Completion
1. The conducting system of the heart is
____________________________________________________________________________________________
2. Conduction system of the heart consists of the following elements:
_______________________________________
__________________________________________________________________________________________
3. The pacemaker of the first order of the heart is named the
_______________________________________________________________________________________node.
4. The gradient of automaticity is
____________________________________________________________________________________________
____________________________________________________________________________________________
__
5. Pacemaker activity of the atrioventricular node is____________________ times per minute. The activity of the
His’s
bundle branches is _______________ times per minute. The Purkinje fibers activity is ___________ times per
minute
6. Latent pacemakers are
__________________________________________________________________________________________
7. The heart is an electrical syncytium because of
____________________________________________________________________________________________
8. Nexuses are called ___________________________________________________________________________
9. Action potential of typical cardiomyocytes comprises the following phases:
_________________________________
__________________________________________________________________________________________
10. Resting membrane potentials in cardiac non-pacemaker tissues of about
_______________________________mV.
Its duration is about _______________________________________________________________________
msec.
11. Rapid upstroke (Phase 0) of a cardiomyocyte action potential is provided by following ions entering
__________________________________________________________________________________________
12. Plateau phase is provided by entering of _________________ ions and by exit of ______________________
ions.
13. The duration of absolute refractory period is about of
____________________________________________msec.
14. Extrasystole is ____________________________________________________________________________
_________________________________________________________________________________________
Multiple choice
1. What three major types of cardiac muscle is the heart composed?
1) The heart is composed of two major types of cardiac muscle: contractile ventricle muscle, and specialized
excitatory and conductive muscle fibers. 2) *The heart is composed of three major types of cardiac muscle:
contractile atrial muscle, contractile ventricle muscle, and specialized excitatory and conductive muscle fibers. 3)
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The heart is composed of four major types of cardiac muscle: contractile skeletal muscle, contractile atrial muscle,
contractile ventricle muscle, and specialized excitatory and conductive muscle fibers.
2. What is the conducting system of the heart called?
1) The conducting system of the heart is called a specialized system of typical muscle fibers which are the
differentiated muscle fibers close in structure to the skeletal muscles. 2)* The conducting system of the heart is
called a specialized system of atypical muscle fibers which are the poorly-differentiated muscle fibers close in
structure to the embryonic muscles.
3. What is main conducting system significance for cardiac activity?
1) *The heart is endowed with system significance for (a) generating rhythmical impulses to cause rhythmical
contraction of the heart muscle (heart automatism) and (b) conducting these impulses rapidly throughout the heart.
2) The heart is endowed with system significance for (a) conducting rhythmical impulses rapidly throughout the
heart. 3) The heart is endowed with system significance for (a) generating rhythmical impulses to cause rhythmical
contraction of the heart muscle (heart automatism).
4. The pacemaker of the first order in heart is?
1) The His's bundle branches. 2) The A-V node. 3) The Purkinje system. 4) *The sinus node.
5. Where is the sinus node located? What are its peculiarities?
1) The sinus node is located in the superior lateral wall of the left atrium immediately below and slightly lateral
to the opening of the aorta. 2)* The sinus node is located in the superior lateral wall of the right atrium immediately
below and slightly lateral to the opening of the superior vena cava.
6. Where is the A-V node positioned?
1) *The AV node is positioned at the lower part of the septum dividing the two atria. 1) The A-V node is positioned
at the lower part of the septum dividing the ventricles.
7. What is the delay in impulse conduction from the atria to the ventricles called?
1) It is in the A-V junction that impulses traversing the atria are collected and delayed for a period of time
(normally up to 600 ms), so that contraction of the ventricles precedes activation of the atria. 2)*It is in the A-V
junction that impulses
traversing the atria are collected and delayed for a period of time (normally up to 200
ms), so that contraction of the atria precedes activation of the ventricles.
8. What does the term «nexus» mean?
1)* Low-resistance path between cells cardiac muscle. 2) High-resistance path between cells cardiac muscle.
9. Point the values of the action potential duration which are characteristic of the atrial and ventricular muscles.
1) *Action potentials are characterized by a very rapid onset and long duration, especially in the ventricle, with
duration of about 300 msec (0.3 s). 2) Action potentials are characterized by a very rapid onset and long duration,
especially in the ventricle, with duration of about 600 msec (0.6 s).
10. What does the absolute refractory period mean?
1)* The absolute refractory period during which the membrane cannot be reexcited by an outside stimulus,
regardless of the level of external voltage applied; 2) The absolute refractory period during which the membrane
can be reexcited by an outside stimulus, regardless of the level of external voltage applied.
11. What does the relative refractory period mean?
1) The relative refractory period during which a propagated action potential cannot be generated but with a
depolarizing stimulus that is larger than normal; 2)* The relative refractory period during which a propagated
action potential can be generated but with a depolarizing stimulus that is larger than normal.
12. What does the term “extrasystole“ mean?
1)* premature contraction,
2) more rapid rate of contraction
13. What the duration of the absolute refractory period is?
1) *0.25-0.30 s,
14. What the duration of the relative refractory period is?
1) 0.1 s,
2) 0.40-0.50 s,
2) 0.5 s,
3) *0.05 s
15. What the rhythmical heart rate if pacemaker activity is A-V node is?
1) 70-80 times per minute,
2) *40-60 times per minute,
3) 90-100 times per minute
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3) 0.1-0.15 s
16. What the rhythmical heart rate if pacemaker activity of Purkinje fibers is?
1) 50-60 times per minute, 2) 70-80 times per minute,
3) *15-20 times per minute
17. What the rhythmical heart rate of pacemaker activity of sinus node is (in quiet rate)?
1) 50-60 times per minute, 2) *60-80 times per minute,
3) 90-100 times per minute
ELECTROCARDIOGRAM (ECG)
The electrocardiogram (ECG) provides a record of the electrical events happening within the heart. The ECG is
obtained by placing recording electrodes on the surface of the body. These recording electrodes detect the changing
potential differences of the heart on the body's surfaces, and a time-dependence plot of these differences is called an
electrocardiogram (ECG). An electrocardiograph is an instrument used to record these changes. As the electrical
impulses are transmitted throughout the cardiac conduction system and myocardial cells, a different electrical impulse
is generated. These impulses are transmitted from the electrodes to a recording needle that graphs the impulses as a
series of up-and-down (vertical) waves called deflection waves (fig. 8).
Electrocardiogram recordings
Electrocardiograms are usually recorded by indirect leads (recording electrodes placed some distance from the heart
on the skin of the subject rather than directly on the heart). The electrocardiogram represents a two-dimensional
tracing of electrical changes that occur within the heart during the electrical processes (but not mechanical processes)
of the cardiac cycle. Because of the differences in the size and shape of any one individual's heart and body
dimensions, the electrocardiogram varies from individual to individual. In addition, within any one individual the
ECG pattern varies with the placement of the leads.
The ECG recordings that will be obtained in the laboratory utilize the three standard limb leads. A lead is defined as
two electrodes working as a pair. Electrodes are sensing devices of sensitive metal plates that can detect
electrophysiological phenomena. The three standard limb leads (Fig.16) are typically attached to the right and left
wrists and the left leg. Lead I records the potential difference between the left and right arms (LA and RA,
respectively). Lead II records the potential difference between the right arm (RA) and left leg (LL). Lead III, therefore,
would record the potential difference between the left arm (LA) and the left leg (LL).
A typical lead II ECG record is composed of an orderly series of deflections and intervals. The first deflection, or
wave, is termed the P wave, and represents atrial depolarization. After the P wave the ECG returns to baseline level
because the electrodes are no longer recording any potential differences. This time period is termed the P-Q segment.
During this time period, however, the electrical activity of the heart is not quiescent, as the action potential is being
propagated through the AV node, the AV bundle branches, the conduction myofibers, and ventricular myocardium.
In response, ventricular muscle cells depolarize.
The QRS complex of the ECG represents ventricular depolarization. The QRS complex also represents atrial
repolarization, since the atria repolarize at the same time the ventricles depolarize. No separate deflection for atrial
repolarization is found because of the significantly smaller amount of atrial muscle mass as compared to the
ventricular muscle mass.
In the time period between the QRS complex and the repolarization of the ventricles (during the T wave described
below) the ECG again returns to, or very closely to its baseline level. This time period is termed the S-T segment.
During the S-T segment of the ECG all of the ventricular muscle is depolarized. This segment of the ECG represents
the plateau phase of the ventricular action potential.
The final wave is termed the T wave, and represents ventricular repolarization. The T wave is smaller (but with a
longer duration) than the QRS complex because the rate of repolarization is slower than the rate of depolarization
within the ventricles.
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Fig. 8. Recording of a normal ECG, lead II, interval R-R1 is 0. 8 s.
Duration and amplitude of waves: P – 0.08 s, 0.15 mV;
QRS – 0.06-0.09 s, 1.5 mV;
T – 0.16 s, 0.5
mV.
Intervals and segments: PQ-interval – 0.16 s; PQ-segment – 0.08 s; ST-segment – 0.08 s; QRST (QT) interval – 0.32
s
In reading and interpreting an electrocardiogram, you must note – the lead type of configuration from which the ECG
was recorded, the lengths of the P-Q interval, S-T segment, Q-T interval – “electrical systole of the heart”, the size
of the deflection waves.
Fig. 9. The standard limb leads
An attempt will not be made to interpret an electrocardiogram, but only to become familiar with a normal ECG. The
ECG is valuable in diagnosing abnormal cardiac rhythms and conducting patterns, detecting the presence of fetal life,
determining the presence of more than one fetus, and following the course of recovery from a heart attack.
Procedure of an electrocardiograph using
In recording the ECG we will use only three standard limb leads. Usually only two electrodes will be in actual use at
any one time. The third electrode will be automatically switched off by the lead-selector switch of the
electrocardiograph or most general purposes three leads are usually used. However, cardiologists use additional leads.
Procedure of electrocardiogram recording
1. Either you or your laboratory partner should lie on a cot, roll down long stockings or socks to the ankles, and
remove all metal jewelry.
2. Swab the skin with alcohol where electrodes will be applied. Electrode cream, jelly, or saline paste is applied to
the skin only where the electrode will make contact.
3. The cream is then applied on the concave surface of the electrode plates, which are then fastened securely to the
limb area surfaces with rubber straps.
4. Firmly connect the proper end of the electrode cables to the electrode plates, using the standard limb leads
previously described.
5. After you apply the electrodes and connect the instrument to the subject, ascertain the following before actually
recording: (a) Recording power switch is on. (b) Paper is sufficient for the entire recording. (c) Preamplifier
sensitivity has been set at 10 mm per millivolt. (d) Subject is lying quietly and is relaxed. Note: Usually five or
six ECG complex recordings from each lead are sufficient. All electrocardiographers have chosen a standard
paper speed of 25 mm per second.
6. Turn the instrument on and record for 30 seconds from each lead.
7. When the recording is finished, turn off the reading instrument and disconnect the leads from the subject and
remove the electrodes.
8. Identify and letter the P, QRS, and T waves, and compare the waves with those shown in Fig. 8.
Laboratory work:
1. The ECG analysis
1. Frequency of cardiac activity - the number of ECG cycles for 1 min calculated by the formula:
60 s
N = ---------------R-R1 s
A) Indicate waves of ECG (fig. 10).
B) Determine the duration of the interval RR1
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C) Calculate the frequency of cardiac activity by the formula
Fig. 10. ECG in humans
2. Cardiac rhythm. The activity of a heart must be rhythmic. Arrhythmia is a condition when the difference between
adjacent intervals R-R more than 10% of the mean cardiac cycle duration.
– Abnormal rhythmicity of the pacemaker (R-R1 ≠ R1-R2 ≠ R2-R3…, if the R-R1, R1-R2, R2-R3 intervals increase
or decrease more than 10%)
– Tachycardia – means fast heart rate – faster than 90 beat /minute instead of normal rate 60-90 /minute)
– Bradycardia – means a slow heart rate usually defined as fewer than 60 beat per minute.
Fig. 11. Registration of breezing curve and ECG in experiment on a rabbit. During ammonia solution inhalation the
inhibitory effect is observed. a) Breezing rate significantly decreases during ammonia solution inhalation (arrow
dawn) and restores after finishing of action (arrow up). b) Arrhythmia and bradycardia on ECG during ammonia
solution inhalation
3. The location of the pacemaker of the heart can be determined by ECG. A pacemaker in norm is a sinus node. In
this case the heart rate is defined as sino-atrial one (fig. 11-1). If a pacemaker is atrioventricular node the rhythm is
defined as the atrioventricular.
Fig. 11. ECG of a frog in norm (1) and after ligation between the atria and ventricles (2) which caused a total blockade
of the excitation in the atrioventricular node.
1) Initial ECG shows that the P wave is always preceded interval QRST that shows sino-atrial (or sinus) rhythm.
2) ECG after putting a ligature in a point separates the atria from the ventricles. The ligature prevents the excitation
spreading from atria to ventricles because of blockade forming at the atrioventricular node. The result: the atria still
contract in sinus rhythm (rhythmical appearance of P wave on ECG) (fig. 11-2). However, ventricular complex QRST
not follows P wave. In is formed under the own activity of the atrioventricular node, i.e. the ventricles operate in
atrioventricular rhythm.
Answer the question: Which signs define the differences between sinus rhythm and atrioventricular rhythm of a
heart?
Answer the question: What shows a PQ interval on the electrocardiogram? Which parameter of this interval
characterizes the propagation of excitation along atrioventricular node?
4. Determining of waves, segments, and intervals durations in ECG (fig. 10).
80
a) Waves –
P ___________ s,
QRS _________ s,
b) Intervals –
PQ _________ s,
QRST or QT (electrical systole) _________ s
c) Segments –
PQ __________ s,
T__________ s
ST _________ s
5. Calculation of systolic parameter (SP). SP = QRST/ RR1 × 100%.
In norm systolic index usually is 37-41% in men, and 41-47% in women.
Calculate the systolic index (SP) –
Answer the question: What shows the systolic index?
6. Analysis amplitude of ECG waves in three standard bipolar leads (fig. 12).
Fig. 12. Amplitude analysis of ECG (3 variants)
a)
P ___ mV
Q ___mV
R ___mV
S _____mV
T _____ mV
b) P ___ mV
Q ___mV
R ___mV
S _____mV
T _____ mV
c)
Q ___mV
R ___mV
S _____mV
T _____ mV
P ___ mV
7. In fig. 13 estimate a relationship between ECG waves and duration of myocardial action potential and phases of
heart mechanical activity (MCG) after their simultaneous recording in experiment in the frog.
Identify intervals on MCG (note the letters) for the atrial systole, the atrial diastole, the ventricular systole, the diastole
of ventricles.
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Fig. 13. Simultaneous record of electrocardiogram (ECG, 1),
mechanocardiogram (MCG, 3) in experiment in the frog
Atrial systole (interval)
–
Ventricular systole (interval) –
Atrial diastole (interval)
myocardial action potential (2), and
–
Ventricular diastole (interval) –
Supplementary information (answers to questions of credit test and exam)
1. What is the ECG?
The electrocardiogram (ECG) is a graphic recording of the changes occurring in the electrical potentials between
different sites on the skin (leads) as a result of cardiac activity. Electrocardiograms are made by means of special
apparatus, electrocardiograms, the graphs are traced on moving bands of paper.
2. What manifestation of cardiac activity does the ECG show?
The ECG thus reflects the electrical events connected with cardiac excitation and provides information about the
anatomical orientation of the heart, heart rate, rhythm and origin of excitation, spread of the impulse, decay of
excitation and disturbances in the above events, irrespective of whether they are due to anatomical, mechanical,
metabolic or circulatory defects. The ECG shows only cardiac electrical events. The ECG gives no information
about the contraction and pumping efficiency of the heart.
3. What are main elements include of normal ECG? What is an ECG wave (positive, negative) called?
There are distinguished three main types of the ECG elements: waves, segments and intervals. The wave means
a deflection from the baseline (isoline), if the downward deflection is called a positive wave, upwards deflection
is called a negative wave. The normal ECG is composed of a P wave, a QRS complex, and a T wave. The QRS
complex is often three separate waves, the Q wave, the R wave, and the S wave.
4. What are an ECG segment and ECG interval called? What ECG segments and ECG intervals are distinguished?
The segment of ECG is called the piece of isoline (an isoline means that it is no difference potentials between the
electrodes of ECG lead), without the waves. There are distinguished several ECG segments: PQ, ST, TP. The
ECG interval is called the part of ECG curve of segment and close-fitting wave (or waves). There are several
ECG intervals: P-Q (P wave plus PQ segment), Q-T (complex QRS, S-T segment and T-wave ), S-T interval ( ST
segment plus T wave), R-R interval.
5. What are the P wave and QRS complex of ECG caused by?
The P wave is caused by electrical potentials generated when the atria depolarize before atrial contraction begins.
The P wave represents depolarization of atrial muscle. The normal ECG curve does not include atrial
repolarization, which is "buried" in the QRS complex. The amplitude of the P wave is within 0.15-0.25 mV,
duration - 0.1 seconds. The QRS complex is caused by potentials generated when the ventricles depolarize before
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their contraction, that is, as the depolarization wave spreads through the ventricles. When the initial wave of the
QRS complex is negative, it is called a Q wave. The Q wave is usually followed by a positive deflection, the R
wave, and then by a small negative deflection, the S wave, the form the QRS complex, although not all of these
waves need be present in any single lead to apply this term. The duration of the QRS complex normally measures
about 0.08s (normal is up to 0.09 s).
6. What are the P-Q (PR) interval and P-Q (PR) segment of ECG caused by?
PQ interval is the interval from first atrial depolarization to the beginning of the Q wave (initial depolarization of
the ventricle). The P-R interval normally is about 0.14 s but may range between 0.12 and 0.2 s in normal
individuals. PQ segment is often called AV delay and represents the passage of the electrical wave front into the
atrioventricular (AV) node and subsequent entry into the his bundle which are electrically silent events in the
standard ECG.
7. What does the T wave of ECG represent?
T wave of ECG represents ventricular repolarization and is caused by potentials generated as ventricles recover
from the state of depolarization. This process normally occurs in ventricular muscle 0.25 to 0.35 second after
depolarization, and this wave is known as a repolarization wave.
8. What the dipole concept of ECG is?
The chambers of the entire heart contain millions of cells that are depolarized nearly simultaneously. At any
instant in time, the entire electromotive force generated by the heart can be thought of as a dipole centered in the
middle of a large volume conductor (the body), and it is the sequence of these instantaneous dipoles recorded
from the body surface throughout the cardiac cycle that makes up the electrocardiogram.
9. What is the electrical axis of the heart called? What its direction for the normal heart is?
The electrical axis of the heart is called the predominant direction of the vectors during depolarization of the
ventricles (negative to positive), that is, the "resultant" vector of QRS (mean QRS vector). The direction of the
electrical axis of normal heart usually coincides with the direction of its anatomic axis (from the base of the
ventricles toward the apex) and is about 59 degrees. But there are also vertical and horizontal positions of anatomic
and electric axises of heart as the variants of norm. In certain pathological conditions of the heart, this direction
is changed markedly – sometimes even to opposite poles of the heart.
10. What the standard ECG leads are?
An ECG lead is called a combination of two wires and their electrodes to make a complete circuit with the
electrocardiograph. One electrode is connected to the positive pole of the electrocardiograph and the other to the
negative one. Recording are made from electrodes situated of the skin of both arms and of the left leg, and the
changes in the potential difference between the right arm and left arm (I); to the right arm and left leg (II); to the
left arm and left leg (III) are measured.
Completion
1. The electrocardiogram (ECG) is ______________________________________________________________
2. ECG in the clinical investigation shows ___________________________________ manifestation of cardiac
activity.
3. The main types of ECG elements are called
__________________________________________________________________________________________
4. There are following standard leads of ECG
__________________________________________________________________________________________
5. The direction of the electrical axis heart in norm is _______________________________________________
degree
6. The normal rate of the cardiac rhythm is ___________________________________________________ per
minute.
7. The typical ECG produces three clearly recognizable waves.
The first wave, which indicates depolarization of
atria, is called ______________________________________________________________________________
8. The QRS complex represents _____________________ of the ventricles. The duration of the QRS complex
normally is about
__________________________________________________________________________sec.
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9. The wave indicates the repolarization of the ventricles is called
__________________________________________
10. The PQ interval characterizes carrying out of action potential from
_______________________________________
11. QT interval called
______________________________________________________________________________
12. The "cardiac dipole" called
_____________________________________________________________________________
Multiple choice
1. Which of the following events is represented on an ECG?
1) SA node depolarization 2) AV node depolarization; 3) Bundle of his depolarization; 4) Atrial muscle
depolarization. 5) *Realization of excitation on all areas of the heart.
2. The ECG that reveals no P wave in any leads indicates a block of impulses coming from the
1)* S-A node; 2) Bundle of his; 2) A-V node;
3) Ventricular muscle
3. The ECG is least effective in detecting abnormalities in
1) Cardiac rhythm; 2) Frequency of heart activity; 3) Cardiac contractility; 4)* Propagation of the action potential
through the heart.
4. Impulses are conducted from the SA node of the heart to the AV node at an approximate time of
1) 0.1 ms;
2) 1.0 ms;
3)* 0.1 s;
4) 1.0 s.
5. The repolarization phase of the cardiac cycle is represented by which portion of the ECG?
1) P;
2) Q;
3) R;
4) S;
5)* T
6. The PQ interval in an RCG is measured by finding the interval between the
1) Beginning of P wave and the beginning of the R wave; 2)* Beginning of P wave and the beginning of the QRS
complex; 3) Beginning of P wave and the end of the QRS complex; 4) End of P wave and the beginning of the
QRS complex.
7. Lead I it records the potential difference between
1)*left and right arms (LA and RA); 2) right arm (RA) and left leg (LL); 3) left arm (LA) and left leg (LL)
8. Lead II it records the potential difference between
1) left and right arms (LA and RA); 2)*right arm (RA) and left leg (LL); 3) left arm (LA) and left leg (LL)
9. Lead III it records the potential difference between
1) left and right arms (LA and RA); 2) right arm (RA) and left leg (LL); 3)*left arm (LA) and left leg (LL)
10. What is the P wave of ECG caused by?
1) *The P wave represents depolarization of atrial muscle and is caused by electrical potentials generated as the
atria depolarize before their contraction; 2) The P wave represents depolarization of ventricular muscle and is
caused by electrical potentials generated as the atria depolarize before their contraction.
11. What is the QRS complex of ECG caused by?
1)* The QRS complex represents depolarization of the ventricular muscle; 2) The QRS complex represents
depolarization of atrial muscle; 3) The QRS complex represents depolarization of the right ventricular muscle.
12. What is the duration of GRS complex?
1) *The duration of the QRS complex normally measures about 0.08 s (normal is up to 0.09 s); 2) The duration
of the QRS complex normally measures about 0.18s (normal is up to 0.2 s); 3) The duration of the QRS complex
normally measures about 0.3 s (normal is up to 0.4 s)
13. What is the duration of T wave?
1)* The duration of the T wave normally measures about 0.25 to 0.35 s; 2) The duration of the T wave normally
measures about 0.45 to 0.55 s; 3) The duration of the T wave normally measures about 0.15 to 0.20 s.
14. What does the T wave of ECG represent?
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1) T wave of ECG represents atrial repolarization and is caused by potentials generated as atria recover from the
state of depolarization; 2)* T wave of ECG represents ventricular repolarization and is caused by potentials
generated as ventricles recover from the state of depolarization.
15. What is Q-T interval of ECG called?
1)* Q-T interval is the interval from the beginning of the Q wave to the end of the T wave; it represents the entire
period of depolarization and repolarization of the ventricle; 2) Q-T interval is the interval from the beginning of
the Q wave to the beginning of the T wave; it represents the entire period of depolarization and repolarization of
the ventricle; 3) Q-T interval is the interval from the beginning of the Q wave to the end of the T wave; it
represents the entire period of depolarization atria and repolarization of the atria.
16. What is the duration of the Q-T interval?
1) The duration of the Q-T interval normally measures about 0.55 s. 2) The duration of the Q-T interval normally
measures about 0.65 s. 3)* The duration of the Q-T interval normally measures about 0.35 s.
17. What is ST segment of ECG called?
1) ST segment is the segment from the beginning of the S wave to the beginning of the T wave; it is isoelectric
and represents the period when the entire ventricle is depolarized; 2)* ST segment is the segment from the end
of the S wave to the beginning of the T wave; it is isoelectric and represents the period when the entire ventricle
is depolarized; 3) ST segment is the segment from the end of the S wave to the end of the T wave; it is isoelectric
and represents the period when the entire ventricle is depolarized.
18. What does the term «tachycardia» mean?
1) tachycardia means fast heart rate – faster than 70 beat/minute instead of normal 90-100 /minute); 2) tachycardia
means fast heart rate – faster than 50 beat/minute instead of normal 60-80/minute); 3)* tachycardia means fast
heart rate – faster than 80 beat/minute.
19. What does the term «bradycardia» mean?
1) bradycardia means a slow heart rate usually defined as fewer than 80 beat/minute; 2)* bradycardia means a
slow heart rate usually defined as fewer than 60 beat/ minute; 3) bradycardia means a slow heart rate usually
defined as fewer than 100 beat/minute.
20. The PQ interval characterizes carrying out of action potential from
1) Realization of excitation from A-V node to S-A node; 2)* Realization of excitation from S-A node to A-V
node.
85