LECTURE 2

1. Erythrocytes are red blood cells in humans and warm-blooded animals that have
homogenous protoplasm but no nucleus. An erythrocyte has a stroma, the framework of the cell,
and a membrane. The membrane is composed of lipoprotein complexes. It is non-permeable for
colloids and K+ and Na+ ions but easily permeable for Cl- and HCO3- (hydrocarbonate) anions,
and also for H+ and OH- (hydroxide). The mineral composition of erythrocytes and plasma is not
identical. Human erythrocytes contain more K + than Na+, while the proportion of these ions in
plasma is reversed. Hemoglobin constitutes 90% of the dry matter of erythrocytes, while other
proteins, lipids, glucose, and mineral salts make up the remaining 10 %.
There are around 5.0 × 1012 (five times ten to the twelfth) erythrocytes per liter of the blood
of a healthy man, and about 4.5 × 1012 in that of a woman. The number of erythrocytes in the
blood of a newborn infant exceeds that in adults.
The quantity of erythrocytes in blood can vary. It increases with low barometric pressure
(at great heights) and during diseases by chronic hypoxia.
The increase in the number of erythrocytes in the blood under low barometric pressure is
caused by the diminished oxygen supply in the blood. People living at high altitudes have higher
erythrocyte content due to intensified production of red blood cells in the bone marrow. In this
state there is an increase the number of erythrocytes per unit volume of blood, and there is also
an increase the total number of red blood cells in the body. This change of erythrocytes quantity
has been named the absolute hyperglobulia.
The increase of erythrocytes quantity is not always accompanies with an increase in the
total number of erythrocytes in the body. For example, with a large water loss due to excessive
perspiration, a short-term thickening of the blood occurs and the number of erythrocytes per unit
volume increases, although their absolute number in the body does not change.
With emotional excitation or intensive physical work the number of erythrocytes in the
blood increases due to contraction of the spleen. The liberation of blood into the blood stream
from the blood depots (from the spleen, liver, lungs and skin) named the relative hyperglobulia.
Reduction of the number of erythrocytes, or anemia, is encountered after blood loss, or as
a result of their intensified disintegration, or owing to a fall in their production.
The diameter of an erythrocyte is between 7.2 and 7.5 micrometers. The size of each
erythrocyte and their total number determine the value of their total surface area, which is very
important, for the absorption and liberation of oxygen.
The sum of the total surface of all erythrocytes in the blood of a human is 3,000 square
meters on the average, i. e. 1,500 times the entire surface of the body. The peculiar shape of an
erythrocyte contributes to this large surface. Human erythrocytes have a concaved center on both
surfaces. With that shape, no point of the cell is located further than 0.85 micrometers from its
surface. The actual ratio between surface and volume facilitates better performance of their
function of transporting oxygen from the respiratory organs to the body cells.
Erythrocytes are carriage some quantity of molecular oxygen and hydrogen ions. That
function is fulfilled by means of the respiratory pigment of blood, hemoglobin. The ability of
hemoglobin to connect the hydrogen ions provides the buffer property of erythrocytes.
When red blood cells are delivered from the bone marrow into the circulatory system, they
normally circulate an average of 120 days before being destroyed. Erythrocyte metabolic
systems become progressively less active with time, and the cells cannot maintain their
membrane activity. Aging RBC have increasing osmotic fragility. That is why they rupture
during passage through some tight spot of the circulation, especially in the spleen. Their
fragments are removed in the splenetic sinusoids by tissue macrophages. When the spleen is
removed, the number of abnormal red cells and old erythrocytes circulating in the blood
increases considerably.
2. Leukocytes. The adult human being has 4 ×10 9 to 9 × 109 (four to nine times ten to the
ninth) white blood cells per liter. The leukocytes are the mobile units of the body's protective
system. They are divided into two main groups – granular (granulocytes) and agranular or non-
granular (agranulocytes) – which differ in origin and function.
Granulocytes (neutrophils, eosinophils, and basophils) develop from the myeloblasts of
bone marrow.
Neutrophils (45-76% of the total leukocyte count). Their main function is phagocytosis.
Neutrophils accumulate in vast numbers at sites of tissue injuries and bacterial penetration.
These relatively large cells are capable of active penetration of the capillary endothelium. They
active spread in the tissues to the place where bacteria have entered. Neutrophils have an
amoeboid movement due to positive chemotaxis. They engulf, digest, and destroy bacteria. This
phenomenon is named phagocytosis. One neutrophil may engulf 15 to 20 bacteria, but having
done so, it may itself die (in that case the bacteria inside it continue to multiply). The neutrophil
blood count increases markedly in acute inflammatory processes.
Normally, blood contains a definite number of mature polymorphonuclear leukocytes and
of their precursors, immature stabnuclear cells (3-5%) and juvenile forms (0-1%). In
neutrophilic leukocytosis the number of these immature forms increases, and myelocytes, from
which the juvenile cells derive, may be encountered in the blood. The vascular life-span of a
neutrophil may be as little as 10 hours.
Eosinophils form 1-5% of the leukocyte count. Eosinophils are:
a) weak phagocytes in comparison with the neutrophils. On the other hand, eosinophils are
often produced in large numbers in individuals with parasitic infections, and they migrate into
tissues diseased by parasites.
b) eosinophils attach themselves to the juvenile forms of the parasite and kill many of
them.
c) they also have a special propensity to collect in tissues in which allergic reactions have
occurred, such as in the peribronchial tissues of the lungs in people with asthma and in the skin
after allergic skin reactions. The eosinophils are believed to detoxify some of the inflammation-
including substances released by the mast cells and basophils and probably also to phagocytize
and destroy allergen-antibody complexes, thus preventing spread of the local inflammatory
process.
Basophils make up 0 to 1 % of the leukocyte count. The basophils in the circulating blood
are similar to the large mast cells located immediately outside many of the capillaries in the
body. Both mast cells and basophils liberate: 1) heparin; 2) histamine; 3) small quantities of
bradykinin and serotonin; 4) slow-reacting substance of anaphylaxis, and a number of lysosomal
enzymes.
The agranulocytes include monocytes and lymphocytes.
Monocytes make up 2 to 10% of the leukocyte count. They originate in the bone marrow,
lymph nodes, and connective tissue. Arriving at a site of inflammation from the blood, they are
transformed into macrophages (giant phagocytes).
An accumulation of incompletely oxidized products at a focus of inflammation brings
about an acid reaction which inactivates neutrophils. Macrophages differ from them in requiring
an acid medium for their phagocytic and digestive activity. When inflammation develops they
take the place of neutrophils. The macrophage activity is mach stronger than neutrophils ones (~
in 20 times). Monocytes are extremely capable to fight with disease agents and can live for
months or even years unless they are destroyed by performing phagocytic function.
Lymphocytes (18-40% of the leukocyte count) develop mainly in the lymph nodes, but
partly in the spleen, thymus, and mucous membranes. Their main function is to provide the
specific immune defence against microorganisms and antigens. The lymphocytes have life spans
of weeks, months, or even years.
They are divided into two groups – T-lymphocytes (T-cells) and B-lymphocytes (B-cells).
T-lymphocytes (T-cells) provide the «cell-mediated» immunity. After their origination in
the bone marrow, first migrate to the thymus gland. Here they divide rapidly and at the same
time develop extreme diversity for reacting against different specific antigens.
There are 3 types of T-cells: 1) helper T-cells; 2) cytotoxic T-cells; 3) suppressor T-cells.
 Helper T-cells serve as a major regulator of all immune functions by product special
substances – interleukins and granulocyte-monocyte colony stimulated factor. They stimulate
growth and proliferation of cytotoxic T-cells and suppressor T-cells; stimulate B-cell growth and
differentiation to form plasma cells and antibodies; activate the macrophage system.
Cytotoxic T-cells (killer cells) is capable of killing microorganisms and, at times, the
body’s own cells.
Suppressor T-cells are capable of suppressing the function of both cytotoxic and helper T-
cells. For this reason this type lymphocytes classified as regulatory T-cells.
B-lymphocytes. The B-cells provide the «humoral-mediated» immunity. On entry the
foreign antigen, the B-cells produce specific gamma-globulin antibodies (immunoglobulins).
These lymphocytes are called memory cells. The second contact with same antigen is
accompanied by much more rapid and much more potent antibody response. There are 5 general
classes of antibodies, respectively named IgM, IgG, IgA, IgD and IgE.
The percentage of different leukocyte types is named the leukocytic formula. In norm
these percentage is approximately the following: l) Polymorphonuclear neutrophils: 45-76%
(myelocytes: 0%; metamyelocytes: 0-1%; stabneutrophils: 1-5%; mature: 45-70%); 2)
Polymorphonuclear eosinophils: 1-5%; 3) Polymorphonuclear basophils: 0-1%; 4) Monocytes:
2-10 %; 5) Lymphocytes: 18-40%.
3. Leukopenia occurs when the bone marrow produces very few WBC. In this situation
the protect property of organism against bacteria becomes weak. The causes of leukopenia may
be irradiation of the body by gamma-rays, harmful influence of drugs and chemicals.
4. Leukocytosis is acute increase of neutrophils in the blood. There are 2 causes of
leukocytosis:
1) During emotions, exercise, after eating the quantity of neutrophils in the blood
insignificantly increases (physiological leukocytosis). However, in these conditions the
leukocytic formula not changed.
2) The products of inflammation are transported to bone marrow and mobilize neutrophils
immediately into the circulating blood. Number of leukocytes can be changed from norm up to
15,000-20,000 in microlitre (neutrophilia). In the leukocytic formula occurs «the left shift» –
the increasing of the junior neutrophil’s quantity (metamyelocytes and stabneutrophils).
5. Blood Platelets are formed by megakaryocytes, giant cells present in the red bone
marrow and in the spleen. They are plasma elements oval or spherical in shape and 2-5
micrometers in diameter. The number of platelets in human blood is 200×10 9 to 400×109 /L (two
hundred times ten to the ninth), but may vary significantly. The platelet level increases during
the daytime and decreases at night. That probably depends on the rhythm of work and rest. After
intensive muscular work the number of platelets in human blood increases 3-5 times. Platelets
survive for 2 to 5 days, so that their entire number in the blood is renewed every 2 to 5 days.
Platelets are rapidly destroyed in bleeding and factors that take part in coagulation and
retractozymes are liberated into the plasma. On disintegration, platelets liberate serotonin,
thromboxane and other substances that cause vasoconstriction. Thus, they can stop hemorrhage
not only by facilitating coagulation of the blood, but also through this vasoconstrictor effect.
6. Stimulators of Blood Cell Production. The red blood cells maturation in the bone
marrow is named erythropoiesis. Erythropoietin is the principal factor that stimulates red blood
cell production. It is a glycoprotein primarily produced by the kidney (90%) in response to
hypoxia. The remainder is formed mainly in the liver. Both norepinephrine and epinephrine and
several of prostaglandins stimulate erythropoietin production. The important effect of
erythropoietin is the stimulation of the proerythroblast production from hemopoietic stem cells in
the bone marrow.
A genesis of the white blood cells is called leukopoiesis. Leukopoietins are products of
monocytes, bone marrow and placenta. They stimulate growth and differentiation of all
leukocyte forms. The content of leukopoietins is increased during inflammation.
 Hemoglobin
Hemoglobin performs the important role of oxygen-carrier and takes part in the transport
of carbon dioxide. It is a complex chemical compound (molecular weight 68,800) consisting of a
protein globin and four molecules of heme. A heme molecule contains an atom of iron, which is
able to combine with, and give up, oxygen. The valency of iron does not change after combining
with oxygen, but remains bivalent.
A heme molecule is composed of four pyrrole rings. The atom of iron in heme binds it to
the protein part of the globin. The heme is the active, or prosthetic group, of hemoglobin, while
globin is a protein heme-carrier. On combination with oxygen, hemoglobin is converted to -
oxyhemoglobin (designated by the symbol Hb02). Oxyhemoglobin, which has given up its
oxygen, is known as reduced hemoglobin (Hb).
Oxyhemoglobin differs somewhat in colour from reduced hemoglobin, and because of that
arterial blood containing oxyhemoglobin is bright red. Venous blood, which contains a large
amount of reduced hemoglobin, is dark-cherry in colour.
On combination with carbon dioxide, hemoglobin is converted to - carbaminohemoglobin
(designated by the symbol HbC02). This combination is a reversible reaction.
Carbaminohemoglobin is provides about 30% of total quantity transported CO2 to the lungs.
The blood of adults contains 135 to 160 gram per liter in men and 125 to 145 gram per liter
in women.
Hemoglobin synthesis and decomposition associated with the formation and destruction
of erythrocytes occur continuously in the organism. Synthesis takes place in the erythroblasts of
the red bone marrow.
The destruction of erythrocytes is happened mainly in the spleen and the liver.
Hemoglobin is liberated from red blood cells. The iron splits off from the heme and, after
subsequent oxidation, the pigment bilirubin is formed from hemoglobin. Bilirubin is discharged
in the bile into the intestine where it is converted to stercobilin and urobilin and excreted in the
feces and urine.
Other hemoglobin compounds may be formed in human and animal organisms. This group
includes methemoglobin and carboxyhemoglobin. They are formed as a result of certain types of
poisoning.
Methemoglobin (MetHb) is a stable combination of hemoglobin with oxygen. But during
its formation the valency of the iron changes. The bivalent iron of the hemoglobin molecule is
transformed to the trivalent form. With accumulation of large amounts of methemoglobin in the
blood, oxygen cannot be released to the tissues and death results from asphyxia.
Methemoglobin differs from hemoglobin in its brown colour. It is formed through
exposure to the effect of strong oxidizing agents, such as ferricyanide, potassium permanganate,
amylnitrite, aniline, potassium chlorate, and phenacetin.
Carboxyhemoglobin (HbCO) is a compound formed of hemoglobin iron and carbon
monoxide (CO). It is about 150 to 300 times as stable as the compound of hemoglobin and
oxygen. Because of that even a 0.1 per cent admixture of carbon monoxide in the air inhaled
leads to a condition in which 80 per cent of the hemoglobin is bound to carbon monoxide and
cannot combine with oxygen, which is fatal.
Weak poisoning with coal gas is a reversible process. With inhalation of fresh air, carbon
monoxide splits off gradually from the carboxyhemoglobin and is eliminated. Breathing of pure
oxygen gives a twentyfold increase in the rate of carboxyhemoglobin splitting.
With severe poisoning it is necessary to apply artificial respiration with a gaseous mixture
containing 95 per cent oxygen and 5 per cent carbon dioxide, and by blood transfusion.
Myoglobin is muscular hemoglobin that occurs in skeletal muscles and in the
myocardium. Its prosthetic group, the heme, is identical with that of hemoglobin, but its protein
part, globin, has a lower molecular weight.
Human myoglobin is capable of binding 14 per cent of all the oxygen in the organism. This
property is important for the supply of oxygen to the working muscles