BLOOD

Blood - is a bodily fluid in humans and other animals that delivers different
substances (such as nutrients and oxygen to the cells and transports metabolic
waste products away from these cells). Type of connective tissue.

Composition of the blood:

I). Plasma (fluid or intercellular substance) with pH is 7,36:
– 90-93% of water;
– 7-10% of dry residue;
(7% – more than 200 types of proteins: albumins 4%, globulins 1-3%,
fibrinogen 0,2-0,4%;
3% – enzymes, vitamins, salts, waste products);

II). Formed elements

– erythrocytes (red blood cells):
a) 4,0 - 5,5×1012 /l in MALE;
b) 3,7 - 4,5×1012 /l in FEMALE;
– leucocytes (white blood cells) – 4,0 - 9,0×109/l;
– platelet (thrombocytes) – 200 - 400×109/l.

Functions of the blood:

1. Trophic: when the nutrient materials are delivered to the tissue.

2. Respiration: oxygen and carbon dioxide are transported.
3. Protective: immunity and non-specific resistance, blood coagulation.
4. Regulative: the hormones and BAS are transported.
5. Homeostatic: maintainance of water content and acid-base balance.
6. Excretive: when the metabolites are delivered from tissues to excretory organs.
7. Maintenance of body temperature: - as result of a redistribution of blood volume
between skin and the internal organs at high and low temperature of external
environment.
8. The formed elements are suspended.
9. Transportation of hormones.

Characteristic of formed elements of blood.

I. ERYTHROCYTES (red blood cells, RBC) - are the most common type of
blood cell and the vertebrate organism's principal means of delivering
oxygen (O2) to the body tissues and carbon dioxide (CO2) from the body
(table 4.1).
 Table 4.1
Types of the erythrocytes
Depending on Diameter
Microcytes Normocytes Macrocytes Megalocytes
(5-6 μm) (7-8 μm) more than 70% (9-10 μm) (more than 10 μm) pathology
Different size of red blood cells in the blood is ANISOCYTOSIS
 Anisocytosis with microcytosis – Iron deficiency, sickle cell anemia
 Anisocytosis with macrocytosis – Folate or vitamin B12 deficiency, autoimmune hemolytic anemia

Depending on Shape
Biconcave (adult) Spherical (old) / pathology Sickled cells Pathology

provides erythrocytes with large

surface-to-volume ratio, thus
facilitating gas exchange
Keratocyte Pathology Dacrocyte (tear-drop poikilocyte) Echinocyte (crenated cell) Pathology
Pathology

Different shape of red blood cells is a POIKILOCYTOSIS

(generally, poikilocytosis can refer to an increase in abnormal red blood cells of any shape where they make up 10% or more of the
total population)
 vitamin deficiency (e.g. Vitamin B12 or folic acid)
 celiac disease
 Depending on Colour of erythrocytes
Normochromia Hyperchromia Hypochromia
normal colour of RBC Dark colour of RBC (increased amount of Pale colour of RBC (decreased amount of hemoglobin)
hemoglobin) (microcytic anemia )
COLOR INDEX (CI) – the average content of hemoglobin in one erythrocyte:
Normal – CI=0.8-1 units;
Hypochromia – CI≤0.8 units,
Hyperchromia – CI≥1 units
Depending on Amount of erythrocytes
Erythrocytosis (Polychytemia) Erythropenia (anemia)
amount of RBC is more than normal amount of RBC is less than normal
- physiological
absolute
people who live at high altitude, where O2 tension is low deficiency of production
relative
exercises pregnancy (RBC dissolved in fluid)
- pathological
primary
bone marrow disorder
secondary
due to any respiratory disease due to any kidney disease
STRUCTURE of RBC:
- membrane (40% lipid, 50% protein and 10% carbohydrates);
- it lacks a nucleus and cytoplasm organelles;
- to produce small amounts of energy (ATP from glucose);
- in the center of acidophilic cytoplasm present hemoglobin (1/3 of
erythrocyte).

Hemoglobin (Hb or Hgb) – is the iron-containing oxygen-transport

metalloprotein in the red blood cells.
Normal range of Hb:
In men – 135-180 g/l.
In women – 120-140 g/l.
Types of the hemoglobin:
I). Depend on age:
Normal form:
- Embryo or primitive hemoglobin (HbP).
- Fetal (embryo or primitive) hemoglobin (HbF).
It has more affinity to oxygen and can be saturated with oxygen at a lower
oxygen tension.
- Adult hemoglobin (HbA).
In humans, only 3 forms are considered normal in postnatal life: HbA1
constitutes 97 %, HbA2 2 %, and HbF 1 % of the hemoglobin of healthy adults

Pathological form:
- HbS (insoluble at low oxygen tension) is an abnorml form of HbA that is
found in patients with sickle cell anemia (valine in HbS, glutamine in HbA).

II). Depending on substances, which are in contact with Hb:

Normal form
- Oxyhemoglobin (HbO2) – oxygen combines weakly with hemoglobin
molecule. It’s formed in the lung.
- Deoxyhemoglobin (reduced hemoglobin) – when the oxygen is released to
the tissues of the body.
- Carbhemoglobin (HbCO2) – in tissues Hb combine’s with carbon dioxide.
Pathological form
- Carboxyhemoglobin (HbCO) – is combination of hemoglobin and carbon
monoxide (it’s a gas without smell and color and has more affinity for
hemoglobin than oxygen).
- Methemoglobin – is such hemoglobin in which iron has valency 3+ (Fe3+).
Such iron creates strong chemical connection and is unable to give oxygen
to tissues.
 Erythrocyte sedimentation rate (ESR) – is the rate at which RBC sediment in
a period of one hour. RBC and plasma will be separated.

Erythrocyte sedimentation rate

Men – ESR=2-10 mm/hr
Women – ESR=2-15 mm/hr
Increased: Decreased:
- pregnancy, - polycythemia,
- inflammation, - sickle cell anemia,
- cancer - hereditary spherocytosis,
- congestive heart failure

Hematocrit (Ht, HCT) is a volume of RBC in the whole blood. This

measurement depends on the number and the size of RBC.
Hematocrit
Men – Ht=0,40-0,48
Women – Ht=0,36-0,46
Increased: Decreased:
- congenital heart disease, - anemia,
- failure of the right side of the heart - bleeding,
(cor pulmonale), - leukemia,
- dehydration, - nutritional deficiencies of iron,
- abnormal increase in RBC folate, vitamin B12 and B6,
(erythrocytosis), - malnutrition,
- low blood oxygen level (hypoxia), - destruction of RBC,
- scarring or thickening of the lung - overhydration
(pulmonary fibrosis),
- bone marrow disease that causes
abnormal increase in RBCs
(polycythemia vera)

FUNCTIONS of RBC:
- transport of the hemoglobin;
- maintains acid-base balance (Hb – acid-base buffer);
- blood group determination;
- transport gases and some nutrients.
LIFE CYCLE
Human erythrocytes are produced through a process named erythropoiesis
in the red bone marrow, developing from committed stem cells to mature
erythrocytes in about 7 days.
 When matured, in a healthy individual these cells live in blood circulation
for about 100 to 120 days.
At the end of their lifespan, they become senescent, and are removed from
circulation in the spleen.
RETICULOCYTES – are immature red blood cells, typically comprising
about 1% of the total number of circulating erythrocytes in the human body.
Reticulocytes develop and mature in the bone marrow and then circulate for
about a day in the blood stream before developing into mature red blood
cells.

STRUCTURE: do not have a cell nucleus;

cytoplasm contains granules and network of ribosomal RNA.

II. LEUKOCYTES (white blood cells) - are larger and less numerous than
erythrocytes. Leukocytes can be divided into 2 main groups, granulocytes
and agranulocytes, according to their content of.

General characteristic:
- specific granules are found only in granulocytes; their staining properties
(neutrophilic, eosinophilic, or basophilic) distinguish the 3 granulocytes types;
- azurophilic granules are found in both agranulocytes and granulocytes.
Azurophilic granules stain purple and are lysosomes;
- can leave the capillaries by passing between endothelial cells, and penetrating
the connective tissue by means of the process called diapedesis.

An increase in the number of leukocytes is called leukocytosis (systemic and

localized infectious processes, such as appendicitis or abscesses). It is a normal
response to infection. On the other hand, a decrease in the number of leukocytes is
called leukopenia (certain acute and chronic diseases, such as typhoid fever or
tuberculosis; radiation sickness).

Classification of leucocytes (depending on cytoplasm granules):

A) GRANULOCYTES (table 4.2):

- have segmented nuclei (polymorphonuclear leukocytes);
- depending on the cell type, the mature nucleus may have from 2 to 7 lobes
connected by thin strands of nucleoplasm;
- granules are all membrane-limited and bud off from the Golgi complex;
- all granulocytes have a life span of a few days, dying by apoptosis in the
connective tissue. The resulting cellular debris is removed by macrophages and
does not elicit an inflammatory response.
 Table 4.2
Characteristic’s of the granulocytes
NEUTROPHILS* (microphages)
Structural
47-72%
features/ type of EOSINOPHILS BASOPHILS
Juvenile (band) Immature Segmented
cells
(young)
Amount 0-1% 1-6% 40-68 % 0,5-5% 0-1%
Higher than Neutrophilia: Eosinophilia (allergical Basophilia (chronic
normal amount a) Physiological (exercise, pregnancy, emotional conditions, parasitic myeloid leukemia,
of cells in the stress, exposure to cold, parturition); infestations, skin disease, polycythemia)
blood b) Pathological (acute infection, noninfective collagen disease, Hodgkin’s
inflammation, noninflammatory conditions, acute disease, Addison’s disease,
hemorrhage, muscle trauma, leukemia, toxic Certain leukemias)
conditions, corticosteroid therapy)
Lower than Neutropenia: Eosinopenia (ACTH Basophilopenia
normal amount c) Physiological (after chronic exposure to severe therapy, Cushing’s disease, (septicemia, aplastic
of cells in the cold); acute pyogenic infections, anemia)
blood d) Pathological (starvation and debility, typhoid and aplastic anemia)
paratyphoid fever, aplastic anemia, parasitic
infection, viral infection, hypersplenism, drug-
induced neutropenia)
Size (diameter)
- in blood smear 10-12 µm 12-14 µm 11-12 µm
Shape of nucleus bean shape horses-shoe 3-5 lobes with 2 lobes with interlobe 2-3 irregular lobes with
shaped interlobe bridge bridge interlobe bridge
Cytoplasm a lot of glycogen; small amount the Golgi apparatus and * a weak development of
endoplasmic reticulum, mitochondria and ribosomes are organelles
sparse*
Components of the - acid phosphatase; - acid phosphatase, - as in the primary
azurophilic - mieloperoxidase cathepsin, and ribonuclease lysosomes
granules (primary,
or type A)
Components of the - alkaline phosphatase; - crystalloid with the - heparin
specific granules - bactericidal cationic proteins (lactoferrin); major basic protein; (anticoagulant);
(secondary, or type - lysozyme - peroxidase; - histamine (for
B) - histaminases vasodilation);
- cationic proteins - chemotactic factor

Migrate’s to the +; transform to the mast

- - + +
connective tissue cell
Function first line of cellular defense against the invasion of weak phagocytes; limited ameboid
bacteria; develop amoeboid motility; multifunctional antiparasitic (the killing of movement and
cells that attack and destroy viruses and bacteria; active parasitic worms); regulate phagocytosis; mediate
phagocytes mast cell (destroy the the inflammatory
histamines). response; stimulate the
formation of
immunoglobulin E
(participates in allergic
reaction along with
mast cells in tissue)

Capable of
+ - - - -
mitosis
Life cycle:
- in the blood 8-12 hours; 3-12 hours 4-8 hours
- in the tissue - - 1-7 days 8-12 hours few hours
* - In females, a small heterochromatic body often extends from one of the nuclear lobes. This represents the inactive X
chromosome, or Barr body, and is referred to as a drumstick – like appendage because of its characteristic shape.
 B) AGRANULOCYTES:
- have round unsegmented nuclei and are described as mononuclear
leukocytes;
- they lack specific granules, but they contain various number of azurophilic
granules (lysosomes).
This group includes the lymphocytes and monocytes.

LYMPHOCYTES
Amount: 19-37% of the white blood cells in healthy adults;
Lymphocytosis Lymphocytopenia
Chronic infection, infectious Immunosuppressive therapy, ACTH
mononucleosis, lymphocytic therapy, Hodgkin’s disease, bone
leukemia, lymphomas, viral marrow failure
infections

Classification:
- depend on size:
Small (85-90%) Medium (10-12%) Large (1-2%)
4,5-7 µm 7-10 µm >10 µm
nucleus is densely the nucleus is larger and less dense and stains
heterochromatic, reddish-purple; cytoplasm more abundant
staining purplish-blue to
black, and nearly fills
the cell; the cytoplasm
forms a thin rim around
the nucleus

- depending on functional classes:

1). T-cells (70-80%)
Effector cells Memory cells
Cytotoxic Helper T cells Suppressor T
(killer) cells
cells secrete enhance the inhibit the inactive state of
substances that activity of some activity of some the T cells but
kill other cells B cells and other B cells and other retain the
and in some cases T cells T cells capacity to
kill by direct respond more
contact; they play quickly to the
a major role in next encounter
graft rejection with the same
antigen
Effector cells activated to carry out an immune response to the antigen.
T Lymphocyte derivatives serve as the major cells of the cellular immune
response. They produce a variety of factors, termed lymphokines (e.g.,
 interferon) that influence the activities of macrophages and of other
leukocytes involved in an immune response.
2). B-cells (10-20%)
Effector cells Memory cells
Helper B cells Suppressor B cells
enhance the inhibit the activity inactive state but retain the
activity of some of some B cells and capacity to respond more quickly
B cells and other other T cells to the next encounter with the same
T cells antigen
B cells differentiate into plasma cells, which secrete specific antigen-binding
molecules (antibodies or immunoglobulin’s) that circulate in the blood and
lymph and serve as a major component of humoral immunity.
3). O-lymphocytes (5-10%) – natural killers among them

- according to the electron-microscopic studies:

1). Small lymphocytes (dark and light);
2). Medium lymphocytes;
3). Plasma cells (7-10 µm);
4). Lymphoplasmocytes.

- according to the receptors on the membrane:

a) CD4 (helper T cells);
b) CD8 (cytotoxic T cells);
c) CD20 (B-lymphocytes).

Structure:
- nuclei are spherical and often flattened on one side;
- cytoplasm exhibits a pale basophilia;
- a few purplish azurophilic granules but lacks specific granules;
- present many free ribosomes, few mitochondria, sparse endoplasmic
reticulum, and a small Golgi complex.

Features:
The primary (central) lymphoid organs include the thymus, where
lymphocyte precursors are programmed to become T cells and, in birds, the bursa
of Fabricius, where lymphocyte precursors are programmed to become B cells.
Humans have no bursa; our B cells appear to be programmed in the bone marrow.

Functions:
- provides immunity;
- B-lymphocytes provide humoral immunity;
- B-cells differentiate into plasma cells which further produces 5 classes of
antibodies that provides immunity;
- T-lymphocytes provides cell-mediated immunity;
- T-cytotoxic cells aim to eliminate: virus-infected cells, cancer cells and also
causes graft rejection
Life cycle: from few days to many years in the blood or the tissues.
Lymphocytes are the only type of leukocytes that return from tissue back
to the blood, after diapedesis.

MONOCYTES

Amount: 3-11% of the white blood cells in healthy adults;

Monocytosis Monocytopenia
Protozoan diseases, Hodgkin Bone marrow failure, aplastic
disease, monocytic or anemia, septicemia
myelomonocytic leukemia, ACTH
therapy

Size:
- in blood smear – 18-20 µm in diameter

Structure:
- many microvilli and pinocytotic vesicles are found at the cell surface
- nuclei may be ovoid, but are usually kidney- or horseshoe shaped and
eccentrically placed (rarely spherical) (the chromatin is less condensed; may
be 2-3 nucleoli);
- cytoplasm contains many small azurophilic granules, a small quantity of
rough endoplasmic reticulum, polyribosomes, many small mitochondria, a
well-developed Golgi apparatus.

Functions:
- they differentiate into macrophages which can phagocytose bacteria,
- antigen-presentation function

Life cycle:
- in the blood – less than a week (36-104 hours);
- in the connective tissue – transform to the macrophages

Monocytes are the direct precursors to macrophages.

THE MONONUCLEAR PHAGOCYTE SYSTEM consists of monocyte-
derived phagocytic cells distributed throughout the body.
(Examples: the Kupffer cells of the liver).
 LEUCOGRAM
a blood leucocyte profile (leucogram) provides information on total
leucocyte count, differential leucocyte count and leucocyte morphology.
Total № Neutrophils
Eosi- Baso-
of L M
Normal nophils phils band imma- seg-
range leucocytes ture mented
4,0- 0,5-5% 0-1% 0-1% 1-6% 40- 19- 3-
9,0×10 /l
9
68% 37% 11%

PHYSIOLOGICAL DECUSSATION
- normally in adults level is higher than the level of lymphocytes;
- at birth, the amount of neutrophils and lymphocytes are in the same ratio as
in adult;
- at 3-5 days, lymphocytes increase and neutrophil decrease and remains same
until 3-5 years, and then again becomes normal. This is called the
physiological cross of leucocytes in ontogenesis (fig. 4.1).

Fig. 4.1 Scheme of physiological cross of leukocytes in ontogenesis (Barakathu

Peer Fathima, 2013).

III. PLATELETS (thrombocytes) - the smallest formed elements in the

blood.

Amount: 150-300×109/l.
Shape: disk like cell fragments.
Size: 2-5 µm in diameter.

Platelets originate by budding from large cells in the bone marrow called
megakaryocytes

Structure:
- lack nuclei;
- cytoplasm is subdivided into two regions:
a) peripheral hyalomere region (contains a marginal bundle of microtubules
that helps to maintain the platelet’s discoid shape);
 b) a dense central granulomere (mitochondria; glycogen granules and other
granules)
Types of the granules:
1). Dense bodies, or delta granules (250-300 µm in diameter) contain calcium
ions, pyrophosphate, ADP, and ATP; they take up and store serotonin;
2). Alpha granules (300-500 µm in diameter) contain fibrinogen, platelet-derived
growth factor, and other platelet-specific proteins;
3). Lambda granules (platelet lysosomes) (175-200 µm in diameter) contain only
lysosomal enzymes.
4). Microperoxisomes – catalase.

Function: they promote blood clotting and help repair gaps in the walls of
blood vessels, preventing loss of blood.

Life cycle: 10 days in the blood.

A marked reduction in the number of blood platelets is called

thrombocytopenia, and a marked increase in the number of blood platelets is
called thrombocytosis.