Hematology

MLT Department

2nd |Stage

Theoretical Part/ Lecture No. 1

By; Dilgeer Ahmed Kalari

An Introduction to blood

• Your body is constantly exchanging chemicals with its external

environment. The lining of the digestive tract absorbs nutrients, gases move
across the thin epithelium of the lungs, and wastes are excreted in the feces
and urine.
Blood is a body fluid in the circulatory system of humans  and other vertebrates that
delivers necessary substances such as nutrients and oxygen to the cells, and
transports metabolic waste products away from those same cells.
 Blood in the circulatory system is also known as peripheral blood, and the blood cells
it carries, peripheral blood cells.
Blood is composed of blood cells suspended in blood plasma. Plasma, which constitutes
55% of blood fluid, is mostly water (92% by volume), and contains proteins, glucose,
mineral ions, hormones, carbon dioxide (plasma being the main medium for excretory
product transportation), and blood cells themselves. Albumin is the main protein in
plasma, and it functions to regulate the colloidal osmotic pressure of blood.
The blood cells are mainly red blood cells (also
called RBCs or erythrocytes), white blood cells (also
called WBCs or leukocytes) and platelets (also called
thrombocytes). The most abundant cells in vertebrate
blood are red blood cells. These contain hemoglobin,
an iron-containing protein, which facilitates oxygen
transport by reversibly binding to this respiratory gas
thereby increasing its solubility in blood.

 In contrast, carbon dioxide is mostly

transported extracellularly as bicarbonate ion
transported in plasma.
Blood has six major functions:
The circulating fluid of the body is blood, a specialized connective tissue that
contains cells suspended in a fluid matrix.
1.Transporting dissolved gases, nutrients, hormones, and metabolic wastes. Blood
carries oxygen from the lungs to the body’s tissues, and carbon dioxide from
these tissues to the lungs.
2.Blood distributes nutrients absorbed by the digestive tract or released from
storage in adipose tissue or in the liver. It also absorbs and carries the wastes
produced by active cells to the kidneys for excretion.
3. Regulating the pH and ion composition of interstitial fluids.
4.Restricting fluid losses at injury sites. Blood contains enzymes and factors that
respond to breaks in vessel walls by initiating the process of blood clotting.
5.Defending against toxins and pathogens. Blood transports white blood cells,
specialized cells that migrate into body tissues to fight infections or remove
debris.
6.Stabilizing body temperature. Blood absorbs the heat generated by active skeletal
muscles and redistributes it to other tissues.
 Basic physical characteristics of blood

Whole blood from any source—veins, capillaries, or

arteries—has the same basic physical characteristics:

⦁ Temperature; The temperature of blood is roughly

38. 8C (100.48F), slightly above normal
body temperature.

⦁ Viscosity; Blood is five times as viscous (“thick”)

as water. It is five times stickier, more cohesive, and
resistant to flow than water. The high viscosity
results from interactions among the dissolved
proteins, formed elements, and water molecules in
plasma.

⦁ pH; Blood is slightly alkaline, with a pH between

7.35 and 7.45 (average: 7.4).
Hematology

Hematology is the science or study of

blood, blood-forming organs and blood
diseases.
Blood is composed of a cellular portion,
called formed elements (RBCs, WBCs, &
Platelets) , and a fluid portion, called
plasma.
When a blood sample is centrifuged, the
heavier formed elements are packed into
the bottom of the tube, leaving plasma at
the top. The formed elements constitute
approximately 45% of the total blood
volume, and the plasma accounts for the
remaining 55%.
the percentage of red blood cell volume
to total blood volume in a centrifuged
blood sample (a measurement called the
hematocrit ).
 Plasma
Plasma is a straw-colored liquid consisting of water and dissolved solutes. The
major solute of the plasma in terms of its concentration is Na + . In addition to Na
+ , plasma contains many other ions, as well as organic molecules such as
metabolites, hormones, enzymes, antibodies, and other proteins.

Plasma proteins constitute 7% to 9% of the plasma. The three types of proteins

are ;

1. Albumins account for most (60% to 80%) of the plasma proteins and are the
smallest in size. They are produced by the liver and provide the osmotic pressure
needed to draw water from the surrounding tissue fluid into the capillaries. This
action is needed to maintain blood volume and pressure. Transport proteins bind
small ions, hormones, or compounds that might otherwise be lost at the kidneys
or that have very low solubility in water. One example is thyroid-binding
globulin, which binds and transports thyroid hormones.
Plasma

2. Globulins are grouped into three subtypes: alpha globulins, beta globulins,
and gamma globulins. The alpha and beta globulins are produced by the
liver and function in transporting lipids and fat-soluble vitamins.

Gamma globulins are antibodies produced by lymphocytes (one of the formed

elements found in blood and lymphoid tissues) and function in immunity.

3. Fibrinogen, which accounts for only about 4% of the total plasma proteins,
is an important clotting factor produced by the liver. During the process of clot
formation (described later in this section), fibrinogen is converted into
insoluble threads of fibrin. Thus, the fluid from clotted blood, called serum,
does not contain fibrinogen but is otherwise identical to plasma.
Red blood cells

formed by erythropoiesis, contain hemoglobin that can be recycled

 Red Blood Cells (RBCs):
1. Also called ‘erythrocytes’.
2. Contain the red pigment called ‘Hb’ which binds and transports O2 and CO2.
3. RBCs are the most abundant blood cells accounting for 99.9% of the formed elements.
This unusual shape has three important effects on RBC’s function:
4. It gives each RBC large surface area to carry large amounts of O2.
5. It enables to form stacks, like dinner plates that smooth the flow through narrow blood vessels these
stacks called rouleaux.
6. It enables them to bend and flex when entering small capillaries and branches, so they are very flexible.
 The erythrocytes lose most of their organelles during differentiation including:
1. Nuclei and ribosome; so they cannot divide and synthesize structural proteins or enzymes.
2. They cannot perform repairs, and their life span is relatively short (<120 days).
3. Mitochondria; they obtain the energy through the anaerobic metabolism of glucose absorbed from the
surrounding plasma. However, it ensures that absorbed oxygen will be carried to peripheral tissues, not
“stolen” by mitochondria in the cytoplasm.
The Anatomy of RBC
RBC Life Span and Circulation

RBCs are exposed to severe

mechanical stresses, a single round- trip from
the heart through the peripheral tissues, and
back to the heart usually takes less than a
minute and no repair mechanisms, a typical
RBC has a relatively short life span.
After travelling about 700 miles in 120 day,
either the cell membrane ruptures or the damage
is detected by phagocytic cells, and the cell is
engulfed. About 1% of the circulating RBCs are
replaced each day, and in the process
approximately 3 million new erythrocytes enter
the circulation each second.
Hemoglobin Structure and Function

A mature RBC consists of a cell membrane enclosing a

mass of transport proteins. Molecules of hemoglobin
In adult humans the Hb (Hb) molecule:
(HĒ-mō-glō-bin) (Hb; Hgb) account for over 95% of an
RBC’s intracellular proteins. Hemoglobin is responsible consists of four polypeptides:

for transporting oxygen and carbon dioxide. 1. Two α (α) chains of 141 amino acids and

A hemoglobin molecule consists of four globular protein 2. Two beta (β) chains of 146 amino acids.

subunits, arranged in two pairs. The members of each pair There is one atom of iron at the center of each heme.
are composed of slightly different polypeptide chains.
Each of the four globular subunits includes a single
molecule of an organic pigment called heme.

A heme molecule holds an iron ion in such a way that it

can interact with an oxygen molecule. The iron–oxygen
interaction is very weak, and the two can easily separate.
RBCs containing hemoglobin with bound oxygen give
blood a bright red color. When oxygen is not bound to
hemoglobin, the RBCs give blood a dark red.
Hb characteristics

1. Hb is responsible for transporting of O 2 and CO2. (Hb + Iron + O2) This interaction called oxyHb

(HbO2) which is bright red color.

2. There are nearly 280 million Hb in each RBC, 33% of an RBC is Hb..
3. Each RBC can potentially carry more than a billion molecules of O 2. 98% of O2 carried by Hb;
the other 2% is dissolved in the plasma.
4. When plasma CO2 elevates, the Hb binds to CO2, forming carboaminoHb.
5. RBCs contain an enzyme called carbonic anhydrase which helps the reaction of carbon dioxide
(CO2) and water (H2O) to occur 5,000 times faster. Carbonic acid is formed, which then
separates into hydrogen ions and bicarbonate ions:
 

Carbonic Anhydrase
CO2 + H2O H2CO3 H+ + HCO3-

Carbon dioxide + water carbonic acid hydrogen ion + bicarbonate  

Heme Synthesis

 Heme is synthesized in a complex

series of steps involving enzymes in
the mitochondrion and in the cytosol
of the cell (Figure 1). The first step in
heme synthesis takes place in the
mitochondrion, with the
condensation of succinyl CoA and
glycine by ALA synthase to form 5-
aminolevulicacid (ALA). This
molecule is transported to the cytosol
where a series of reactions produce a
ring structure called
coproporphyrinogen III. This
molecule returns to the
mitochondrion where an addition
reaction produces protoporhyrin IX.
Globin Synthesis

Two distinct globin chains (each with its individual

heme molecule) combine to form Hb.

1. Alpha (α.) chain.

2. "non-α". Chain.
• With the exception of the very first weeks of

embryogenesis, one of the globin chains is always α.

• The fetus has a distinct non-α chain called gamma.
After birth, a different non-α globin chain, called
beta, pairs with the α chain.
• The combination of two α chains and two non-α
chains produces a complete Hb molecule (a total of
four chains per molecule).
The combination of two α chains and two gamma chains form
"fetal" Hb, termed "Hb F".
• With the exception of the first 10 to 12 weeks after conception, (Figure 2).
fetal Hb is the primary Hb in the developing fetus.

• The combination of two α chains and two beta chains

form "adult" Hb, also called "Hb A". it becomes the
predominate Hb within about 18 to 24 weeks of birth. The

pairing of one α chain and one non-α chain

produces a Hb dimer (two chains).

• The genes that encode the α globin chains are on chromosome

16 (Figure 2).
• Those that encode the non-α globin chains are on chromosome
11. Multiple individual genes are expressed at each site.
• The α complex is called the "α globin locus", while the non-α
complex is called the "beta globin locus".
Types of Hemoglobin

 There are 5 globin genes α, β, γ, δ, and ε. There are 2 pairs of α gene on (chromosome
16), two different pairs of γ, and one pair of genes for β (chromosome 11) and δ.
The genes are coordinately regulated and expressed at restricted periods in
development. The α cluster produces 2 types of globin, (α and ζ), ζ- globin is produced
during the 1st 8 weeks in the human embryo.
a. From 2 months until birth, Hb F is the major Hb species responsible for O2 delivery.
b. At the end of gestation, under normal conditions, the β-subunit is synthesized and the
Hb F concentration begins to fall.

c. After birth, Hb A continues to rise, and 30 weeks after delivery, Hb F levels fall below
10% of the Hb concentration.
Types of Hb during embryogenesis
Human Hbs
Embryonic Hb  Fetal Hb  Adult Hb
1-2 months 2-10 months
 gower 1- (ζ 2 ε 2)     Hb A- (α 2 β 2) increases
 gower 2- (α 2 ε 2)   Hb F- (α 2 γ 2)  Hb F (α 2 γ 2) diminishes
 Portland- (ζ 2 γ 2)  Hb A (α 2 β2) being to  Hb A2- (α 2 δ 2) appear in very
appear low ratio
Note\\ α- α, β- beta, ζ- zeta, γ- gamma, δ- delta, ε- epsilon
White Blood Cells (also called leukocytes) and Platelets
• White blood cells protect the body from infection. They are much fewer in
number than red blood cells, accounting for about 1% of your blood.

• The most common type of white blood cell is the neutrophil, which accounts for 55
to 70% of the total white blood cell count. Each neutrophil lives less than a day, so
your bone marrow must constantly make new neutrophils to maintain protection
against infection.

• The other major type of white blood cell is a lymphocyte. There are two main
populations of these cells. T lymphocytes help regulate the function of other immune
cells and directly attack various infected cells and tumors.

• B lymphocytes make antibodies, which are proteins that specifically target bacteria,
viruses, and other foreign materials.

• Unlike red and white blood cells, platelets are not actually cells but rather small
fragments of cells. Platelets help the blood clotting process (or coagulation) by
gathering at the site of an injury.
HEMATOPOIESIS (Hemopoiesis)

• Hematopoisis; Is the dynamic processes of blood cell production and development of

the various cells of the blood.
• All blood cells arise from a single major type of pluripotent stem cell also called
Multipotential HSC in the bone marrow that can give rise to all the blood cell types
( Figure 13–2 ).

• Pluripotent stem cells are rare, but they have the capacity for self-renewal proliferate
and form two major lineages of progenitor cells: one for lymphoid cells
(lymphocytes) and another for myeloid cells (Gr. myelos , marrow) that develop in
bone marrow.

• Myeloid cells include granulocytes, monocytes, erythrocytes, and megakaryocytes.

The hematopoietic system consists of the bone marrow, liver, spleen, lymphnodes, and
thymus.
 Progenitor & Precursor Cells

The progenitor cells for blood cells are commonly called colony-forming units
(CFUs), because they give rise to colonies of only one cell type when cultured or
injected into a spleen. As shown in Figure 13–2, there are four major types of
progenitor cells/CFUs:

■■ Erythroid lineage of CFU-erythrocytes (CFU-E),

■■ Thrombocytic lineage of CFU-megakaryocytes (CFU-Meg),

■■ Granulocyte-monocyte lineage of CFU-granulocytes monocytes (CFU-GM),

and

■■ Lymphoid lineage of CFU-lymphocytes of all types (CFU-L).

 Origin of Hematopoiesis (Ontogeny)
1. During the first few weeks of embryonic life, hematopoiesis begins in the mesoderm of the yolk sac;
yolk sac produces nucleated erythroid cells in first 6 weeks and ends in about 2 months.
2. During the second month, the fetal liver assumes responsibility for hematopoiesis, with the yolk sac
nucleated RBCs migrating to the liver and remaining in the liver until the seventh month.
3. From the third to six month, splenic hematopoiesis also occurs. At approximately 7 months of the
liver to the bone marrow, this then becomes the major site of blood cell development in the fetus.
4. Fetal marrow becomes filled with RBCs during hematopoiesis, bones of the toes, fingers, vertebrae,
ribs, pelvis, long bones, and cranium are filled with erythroid cells; early hemocytic cells also
maybe formed during fetal life.
5. A few megakaryocytes (precursors to platelets) first appear at three months of fetal life, and
granulocytes are observed at about 5 months.
6. At birth, the liver and spleen have ceased hematopoietic cell development, and the active sites of
hematopoiesis are in bone cavities (red marrow).
 Bone marrow hematopoietic activity can be divided into two
separate pools –
1. the stem cell pool
2. the bone marrow pool
The bone marrow pool also can be divided into two distinct
pools: cells that are proliferating and maturing, and cells that
are stored for later release into the peripheral blood.
There are also two separate granulocytic pools in the
peripheral blood: those that are functional within the circulation
and those that exist in a storage form.
• In the granulocytic cell line in the bone marrow pool, there is a
component for proliferation and maturation, as well as a
storage component.
• The granulocytic cells in the peripheral blood also contain
50% of circulating cells and 50% of storage cells.
• For platelets, the peripheral blood contains 70% of platelets
that circulate, with 30% being stored in the spleen.
• 100% of RBCs, known as erythrocytes, circulate in the
peripheral blood in a functional state;
• Erythrocytes in various stages of development are a large
component of proliferating and maturing red cell precursors
found in the bone marrow.