Hematology 1

INTRODUCTION TO
HEMATOLOGY
Copyright © 2010 Pearson Education, Inc.

TOPICS:
1. Introduction
2. Hematopoiesis
3. Erythrocyte
Formation, Structure, Physiology,
Metabolism, Destruction
4. Overview Of Hemoglobin

What is hematology?
• Hematology is the study of blood which is

composed of plasma (~55%), and the
formed elements which are:
• The erythrocytes (RBCs) (~45%)
• Contain hemoglobin
• Function in the transport of O2 and CO2
• The Leukocytes (WBCs) and platlets
(thrombocytes) (~1%)
• Leukocytes are involved in the body’s defense against
the invasion of foreign antigens.
• Platlets are involved in hemostasis which forms a
barrier to limit blood loss at an injured site.

Blood Composition
• Blood: a fluid connective tissue composed of

• Plasma
• Formed elements
• Erythrocytes (red blood cells, or RBCs)
• Leukocytes (white blood cells, or WBCs)
• Platelets

Separating Plasma From Formed
Elements of Blood
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Withdraw
blood
• hematocrit - centrifuge blood
to separate components
• erythrocytes are heaviest and
settle first
Centrifuge
• 37% to 52% total volume
• white blood cells and platelets

Plasma
(55% of whole blood) • 1% total volume
• buffy coat
Buffy coat: leukocytes
and platelets • plasma
(<1% of whole blood)
• the remainder of volume
Erythrocytes Formed
(45% of whole blood) elements • 47% - 63%
• complex mixture of water, proteins,
nutrients, electrolytes, nitrogenous
Figure 18.2 wastes, hormones, and gases
Formed
elements
Plasma
• 55% of whole blood
• Least dense component
Buffy coat
• Leukocytes and platelets
• <1% of whole blood
Erythrocytes
1 Withdraw 2 Centrifuge the • 45% of whole blood
blood and place blood sample. • Most dense
in tube. component
Copyright © 2010 Pearson Education, Inc. Figure 17.1

Physical Characteristics and Volume
• Sticky, opaque fluid

• Color scarlet to dark red
• pH 7.35–7.45
• 38C
• ~8% of body weight
• Average volume: 5–6 L for males, and 4–5
L for females

Functions of Blood
1. Distribution of
• O2 and nutrients to body cells
• Metabolic wastes to the lungs and kidneys
for elimination
• Hormones from endocrine organs to target
organs

Functions of Blood
2. Regulation of
• Body temperature by absorbing and
distributing heat
• Normal pH using buffers
• Adequate fluid volume in the circulatory
system

Functions of Blood
3. Protection against
• Blood loss
• Plasma proteins and platelets initiate clot
formation
• Infection
• Antibodies
• Complement proteins
• WBCs defend against foreign invaders

Blood Plasma
• 90% water
• Proteins are mostly produced by the liver
• 60% albumin
• 36% globulins
• 4% fibrinogen

Blood Plasma
• Nitrogenous by-products of metabolism—

lactic acid, urea, creatinine
• Nutrients—glucose, carbohydrates, amino
acids
• Electrolytes—Na+, K+, Ca2+, Cl–, HCO3–
• Respiratory gases—O2 and CO2
• Hormones

Formed Elements
• Only WBCs are complete cells

• RBCs have no nuclei or organelles
• Platelets are cell fragments
• Most formed elements survive in the
bloodstream for only a few days
• Most blood cells originate in bone marrow and
do not divide

HEMATOPOEISIS

Hematopoiesis
• Hematopoiesis (hemopoiesis): blood cell

formation
• Occurs in red bone marrow of axial skeleton,
girdles and proximal epiphyses of humerus
and femur

Hematopoiesis
• Hemocytoblasts (hematopoietic stem cells)

• Give rise to all formed elements
• Hormones and growth factors push the cell
toward a specific pathway of blood cell
development
• New blood cells enter blood sinusoids

Hematopoeisis
• Three developmental periods
• Mesoblastic
• Blood islands of yolk sac
• Primarily RBC production
• Embryonic hemoglobin produced
• Hepatic
• At 6 weeks cell production in liver
• Fetal hemoglobin produced
• Spleen, thymus, lymph nodes also active prod.
• Myeloid
• At 5th month Bone Marrow becomes site of prod.
• Liver & spleen now Extramedullary
• Hemoglobin A (22)
HEMATOPOIESIS
 MESOBLASTIC PERIOD
 Begins in the blood islands of
the yolk sac
 Earliest detected by 19-20
days AOG and remains active
at 8-12 weeks AOG
 Primarily erythropoiesis
 The immature erythroblasts
are unique in morphology as
well as the type of hemoglobin
they produce (epsilon and
zeta globins)
 GOWER I AND II
 PORTLAND

HEMATOPOIESIS
 HEPATIC PERIOD
 Begins by the 5-6 weeks up
to 6th month of pregnancy
 Cells are morphologically
identifiable
 Hematopoiesis is
INTRAVASCULAR
 Produces fetal hemoglobin
(2 a and 2 b)
 Minimal granulopoiesis
 Counterpart of adult
extramedullary
hematopoiesis
HEMATOPOIESIS
 MYELOID PERIOD
 Starts during the 5th
month of pregnancy
 Production of HgbA1
 At 3 weeks
postpartum, assumes
as the main site of
erythropoiesis but the
spleen and liver
remains available
Hematopoiesis
Copyright © 2010 Pearson Education, Inc. © The McGraw-Hill Companies, Inc, 2011
Sites of production:
• Fetus: 0-2 months (yolk sac).

2-7 months ( liver and spleen).
5-9 months (bone marrow).
• infants: bone marrow
• Adults: bone marrow, ribs, sternum, skull,
sacrum and pelvis.

• Hematopoiesis in the bone marrow is called
medullary hematopoiesis
• Hematopoiesis in areas other then the bone marrow
is called extramedullary hematopoiesis

Requirements For Hematopoiesis
• Stem Cells
• Growth Factors
• Microenviroment

Types of Human Stem Cell
1. Totipotential stem cells.
• present in the first few hours after an ovum is fertilized
• most versatile type of stem cell, can develop into any
human cell type, including development from embryo into
fetus.
2. Pluripotential stem cells.
• present several days after fertilization. can develop into
• any cell type, except they cannot develop into a fetus.
3. Multipotential stem cells.
• derived from pluripotent stem cells. They can be found in
adults, but they are limited to specifi c types of cells to
form tissues.
• For example, bone marrow stem cells can produce all
types of blood cells, bone cartilage, and adipose (fat)
cells.
Stem Cell theory
 Pluripotent stem cell originator of all cells
 Gives rise to cells committed to specific development
 Research supporting the theory
 PHSC has self-maintaining ability
 Committed cells differentiate continuously/ No
Reverse Flow

Cytokines & Growth Factors
 Cytokines stimulate or inhibit
 Prevent apoptosis
 Colony-Stimulating Factors produced by many
different cells
 Interleukins numbered according to discovery

Cellular Components
Pluripotent Stem Cell
Myeloid Multipotent Common Lymphoid

Stem Cells Stem Cells
Unipotent Lymphocytes
Progenitors
WBC’s
RBC’s
Basophils
Eosinophils
Thrombocytes Erythrocytes
Neutrophils
Monocytes Platelets Erythropoietin

Hematopoetic Growth Factor
• regulates the proliferation and differentiation of HPCs

• regulates the survival and function of mature blood cells
• capable of mobilizing HPCs
G-CSF and GM-CSF predominantly affect myeloid
cells
IL-7 stimulates T and B lymphocytes.
IL-12 targets natural killer cells.

Hematopoiesis
Copyright © 2010 Pearson Education, Inc. © The McGraw-Hill Companies, Inc, 2011
Platelets Erythrocytes Monocyte
Neutrophils Lymphocyte
PowerPoint® Lecture Slides
prepared by Vince Austin,
Bluegrass Technical
and Community College
ERYTHROPOIESIS CHAPTER
• the process of
formation of rbc

Erythropoiesis
• Erythropoiesis: red blood cell production

• A hemocytoblast is transformed into a
proerythroblast
• Proerythroblasts develop into early
erythroblasts

Erythropoiesis
• Phases in development
1. Ribosome synthesis
2. Hemoglobin accumulation
3. Ejection of the nucleus and formation of
reticulocytes
• Reticulocytes then become mature
erythrocytes

ERYTHROPOIESIS
• This takes place in the bone marrow and

therefore, the first recognizable cell which can
be identified as belonging to this series is the
pronormoblast.
• It is from this cell that the red cells develop
through a succession of maturing erythroblast
namely basophilic/ early normoblast,
polychromatic/ intermediate normoblast,
orthochromatic/late normoblast.
43
• Then from here it develops to reticulocyte and
finally ends up with erythrocyte (mature red
cell).
• The whole process takes about 7 days.
• This process of normoblastic maturation is
characterized by the following progressive
changes:-
44
1) The cell size diminishes.
2) Ripening of the cytoplasm. the staining reaction
of the cytoplasm changes, the RNA starts
diminishing) These two things take place
simultaneously.
a) So, color changes to pink from blue due to
reduction of RNA matter such that in
Romanowsky stains,
45
there is a change in colour from deep blue to
pink due to progressive formation of acidophilic
staining haemoglobin and the simultaneous
reduction of RNA which is responsible for
basophilic of cytoplasm.
b) Haemoglobin formation.
46
3) Ripening (maturing) of the nucleus having the
large reddish, purple, open-network of the
nucleus of a polychromatic normoblast
converted to small deeply staining blue black
structureless nucleus of the orthochromatic
normoblast before it is eventually lost. i.e. the
nucleus of the pronormoblast is larger than
that of the orthochromatic normoblast.
47
• The former (pronormoblast) has structures and
stains reddish purple, while the later
(orthochromatic) stains blue-black and is
structure less.
• Mitotic division of the developing cells in this
series occurs up to the stage of the
polychromatic normoblast and therefore the
orthochromatic normoblast is not considered
capable of mitotic division.
48
Regulation of Erythropoiesis
• Too few RBCs leads to tissue hypoxia

• Too many RBCs increases blood viscosity
• Balance between RBC production and
destruction depends on
• Hormonal controls
• Adequate supplies of iron, amino acids, and B
vitamins

CONTROL OF ERYTHROPOIESIS
• The major controlling factor : OXYGEN SATURATION
• HYPOXIA provides the strongest stimulus
DECREASE IN ARTERIAL
OXYGEN
DECREASE IN TISSUE
OXYGEN
RELEASE OF ERYTHROPOIETIN
BONE MARROW
ERYTHROPOIESIS
CORRECTION OF HYPOXEMIA
Hormonal Control of Erythropoiesis
• Erythropoietin (EPO)
• Direct stimulus for erythropoiesis
• Released by the kidneys in response to
hypoxia

• Causes of hypoxia
• Hemorrhage or increased RBC destruction
reduces RBC numbers
• Insufficient hemoglobin (e.g., iron deficiency)
• Reduced availability of O2 (e.g., high altitudes)

• Effects of EPO
• More rapid maturation of committed bone
marrow cells
• Increased circulating reticulocyte count in 1–
2 days
• Testosterone also enhances EPO production,
resulting in higher RBC counts in males

Characteristics of developing
normoblast
1. Pronormoblast
• Pronormoblast is a large oval cell. It comes
about as a result of activation by
erythropoeitin (hormone) which is produced
in the kidney.
55
• This hormone acts on erythroid responsive
cell.
• The cytoplasm is more and stains deep
blue.
• The nucleus is round and occupies most of
the cell and has one or two nucleoli.
• The cell measures 12-20 micrometre in
diameter.
56
Proerythroblast
(Pronormoblast/ Rubriblast)
• No hemoglobin
• Nucleus 12 um
• Contain nucleoli

2. Basophillic normoblast : (Early)
• The size varies from 10-16 micrometer.

• The nucleus is relatively large but smaller than
pronormoblast stage.
• The cytoplasm is smaller to that of
pronormoblastic but slightly stage (plentiful).
58
• The chromatic strands are more thicker and
more deeply staining living a coarser
appearance due to RNA.
• At this stage the nucleus have disappeared.
59
Basophil erythroblast (Prerubricyte)
• Early normoblast
• Nucleoli disappear
• Show mitosis
• Cytoplasm deep blue
• Increase in RNA
• Hemoglobin starts
appearing – Little Hb
3. Polychromatic normoblast
(intermediate)
• They vary from 8/14 micrometer in diameter.
• The nucleus is smaller and occupies a smaller
part of the cell.
• It is reddish purple in colour.
• The cytoplasm is large and begins to acquire
haemoglobin, thus taking acidophillic – pink or
pale pink colour.
61
Polychromatophil erythroblast (Rubricyte)
• Late normoblast
• Nucleus smaller
• Coarse Chromatin
• Hemoglobin increase
• Eosinophil Stain
• RNA – Basophil stain

4. Orthochromatic normoblast
(late)
• The size ranges from 8-10 micrometer in
diameter.
• The nucleus is small with condensed
homogenous structereless chromatin.
• It stains blue-black colour. The nucleus is
eccentric and sometimes lobulated.
63
• The cytoplasm is typically acidophillic (pink)
because haemoglobinization has started
taking place which gives it acidophillic
staining.
• The nucleus is lost at this stage.
64
Orthochromatic Erythroblast
(Metarubricyte)
• Normoblast
• Nucleus smaller
• Pyknosis
• Nuclear lysis and
• Nuclear extrusion
5. Reticulocytes
• It is a flat disc shaped and non-nucleated cell

larger than a mature red blood cell.
• When stained with romanowsky stains shows
the diffuse oale basophillia.
• The cell is called polymetachromatophillic cell,
while with supra vital stains, the basophillic
material appears in the form of reticulum and
chromatic strands, which stains dark red.
66
• The Hb content is almost the same as that of
mature RBC.
• From the stage of retic to mature RBC takes
about 1-2 days.
• The nucleus is injected out at the spleen and
the RNA and any other inclusions are removed
and then the cell is released in to the
circulation in the blood stream.
67
• As the cell matures it becomes smaller in size
and the nucleus diminishes and eventually lost
i.e. the chromatin becomes less dense and the
nucleus diminishes and eventually lost.
• Nucleoli disappear before the nucleus is lost.
• At this stage the cytoplasm losses the protein
synthesis property and acquires haemoglobin.
68
Reticulocyte
• Reticulum
• Remnant of ER & GA
• Synthesize Hb
• Few Mitochondria
• Young RBCs (34%

Hb)
• 1 % of Red Cells
ERYTHROCYTE
• Circular, anucleate, highly

flexible, biconcave disk
• 7.2 um in average
diameter
• 2.1 um in thickness
• Average volume: 87 fL
• Contains a complex
membrane of lipids and
protein

The Erythroid Series
Basophilic Orthochromic
Polychromatophilic
Pronormoblast Normoblast Normoblast Normoblast

Homeostasis: Normal blood oxygen levels
1 Stimulus:
Hypoxia (low blood
5 O2- carrying O2- carrying ability)
ability of blood due to
increases. • Decreased
RBC count
• Decreased amount
of hemoglobin
• Decreased
availability of O2
4 Enhanced
erythropoiesis
increases RBC
2 Kidney (and liver to
a smaller extent)
count.
releases
3 Erythropoietin erythropoietin.
stimulates red
bone marrow.

1 Stimulus:
Hypoxia (low blood
O2- carrying ability)
due to
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
Copyright © 2010 Pearson Education, Inc. Figure 17.6, step 1

1 Stimulus:
Hypoxia (low blood
due to
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2

a smaller extent)
releases
erythropoietin.

1 Stimulus:
Hypoxia (low blood
due to
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2

a smaller extent)
releases
stimulates red
bone marrow.

1 Stimulus:
Hypoxia (low blood
due to
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
4 Enhanced
erythropoiesis
increases RBC
a smaller extent)
count.
releases
stimulates red
bone marrow.

1 Stimulus:
Hypoxia (low blood
5 O2- carrying O2- carrying ability)
ability of blood due to
increases. • Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
4 Enhanced
erythropoiesis
increases RBC
a smaller extent)
count.
releases
stimulates red
bone marrow.

Dietary Requirements for Erythropoiesis
• Nutrients—amino acids, lipids, and carbohydrates

• Iron
• Stored in Hb (65%), the liver, spleen, and bone
marrow
• Stored in cells as ferritin and hemosiderin
• Transported loosely bound to the protein transferrin
• Vitamin B12 and folic acid—necessary for DNA
synthesis for cell division

Fate and Destruction of Erythrocytes
• Life span: 100–120 days

• Old RBCs become fragile, and Hb begins to
degenerate
• Macrophages engulf dying RBCs in the
spleen

Fate and Destruction of Erythrocytes
• Heme and globin are separated

• Iron is salvaged for reuse
• Heme is degraded to yellow the pigment
bilirubin
• Liver secretes bilirubin (in bile)) into the
intestines
• Degraded pigment leaves the body in feces as
stercobilin
• Globin is metabolized into amino acids

Degradation of Hemoglobin
Amino acid pool

120 days
GLOBIN
BILIRUBIN HEME IRON

Degradation of Hemoglobin

1 Low O levels in blood stimulate
2
kidneys to produce erythropoietin.
2 Erythropoietin levels rise
in blood.
3 Erythropoietin and necessary
raw materials in blood promote
erythropoiesis in red bone marrow.
4 New erythrocytes
enter bloodstream;
5 Aged and damaged function about 120 days.
red blood cells are
engulfed by macrophages
of liver, spleen, and bone
marrow; the hemoglobin Hemoglobin
is broken down.
Heme Globin
Bilirubin Iron stored Amino

as ferritin, acids
hemosiderin
Iron is bound to
transferrin and released
to blood from liver as
needed for erythropoiesis.
Bilirubin is picked up from blood

by liver, secreted into intestine in
bile, metabolized to stercobilin by
bacteria, and excreted in feces.
Circulation
Food nutrients,
including amino acids, 6 Raw materials are
Fe, B12, and folic acid, made available in blood
are absorbed from for erythrocyte synthesis.
intestine and enter
blood.

1 Low O2 levels in blood stimulate

in blood.

in blood.

in blood.
4 New erythrocytes
enter bloodstream;
function about 120 days.

5 Aged and damaged red Hemoglobin
blood cells are engulfed by
macrophages of liver, Heme Globin
spleen, and bone
marrow; the Bilirubin Iron stored Amino
hemoglobin is as ferritin, acids
broken down. hemosiderin

Circulation

5 Aged and damaged red Hemoglobin
blood cells are engulfed by
macrophages of liver, Heme Globin
spleen, and bone
marrow; the Bilirubin Iron stored Amino
hemoglobin is as ferritin, acids
broken down. hemosiderin
Iron is bound to

Circulation
Food nutrients,
are absorbed from
for erythrocyte synthesis.
intestine and enter
blood.

1 Low O levels in blood stimulate
2
in blood.
4 New erythrocytes
enter bloodstream;
5 Aged and damaged function about 120 days.
red blood cells are
engulfed by macrophages
of liver, spleen, and bone
marrow; the hemoglobin Hemoglobin
is broken down.
Heme Globin
Bilirubin Iron stored Amino

as ferritin, acids
hemosiderin
Iron is bound to

Circulation
Food nutrients,
are absorbed from for erythrocyte synthesis.
intestine and enter
blood.

Bone marrow cells for
Erythropoiesis
• Pluripotential hematopoietic stem cell, PHSC
• Committed stem cell that produces erythrocytes is

called
Colony-forming unit–erythrocyte, CFU-E
Factors:
• Growth inducers
• Differentiation inducers.
ERYTHROPOIESIS
PHSC
Bone marrow
CFU-E
Proerythroblast 4-5 days
Polychromatophil erythroblast
Orthochromatophil erythroblast
Reticulocyte Blood 1-2 days
Copyright © 2010 Pearson Education, Inc. Erythrocyte.

Transfer of RBC to Circulation
RBC pass from the bone marrow into the
blood capillaries
By
Diapedesis
(squeezing through the pores of the capillary
membrane).
RBCs
Form, Function, and Formation

Erythrocytes
• Biconcave discs, anucleate, essentially no

organelles
• Filled with hemoglobin (Hb) for gas transport
• Contain the plasma membrane protein
spectrin and other proteins
• Provide flexibility to change shape as
necessary
• Are the major factor contributing to blood
viscosity

2.5 µm
Side view (cut)
7.5 µm
Top view
Erythrocytes
• Structural characteristics contribute to gas

transport
• Biconcave shape—huge surface area relative
to volume
• >97% hemoglobin (not counting water)
• No mitochondria; ATP production is anaerobic;
no O2 is used in generation of ATP
• A superb example of complementarity of
structure and function!

• 7.5um in diameter
• >9um are called MACROCYTES
• <6um are called MICROCYTES
• 2.6um thick at the rim
• 0.8 um thick at the center
• Considerably shrinks when dried
• ANISOCYTOSIS – changes in size
• POIKILOCYTOSIS – changes in
shape
• Surrounded by a plasmalemma
• 40% lipids (phosphoipids,
cholesterol, glycolipids, etc)
• 50% proteins
• 10% carbohydrates
THE ERYTHROCYTE
Composition and Structure
• For normal erythrocyte production, the following are

required:
• PROTEIN AS SOURCE OF AMINO CAIDS
• IRON
• VITAMIN B12
• FOLIC ACID
• VITAMIN B6
• TRACE METALS (e.g. cobalt, nickel)

THE ERYTHROCYTE
Composition and Structure
 The erythrocyte is not an inert body but a self supporting cell capable
of existing in the intravascular circulation for up to 120 days
 Performs extremely complex and important homeostatic maneuvers
 A simple structure in that it posses only a simple
membrane, internal stroma, and 90% hemoglobin
 Biconcave shape allows maximal surface area and
greatest flexibility
 The membrane is bilayered with a lipid to protein ratio
of 1:1.6 the majority being lipoproteins
 Semipermeable to water
 Stroma is composed of lipids and proteins in the form of
fibrous proteins
THE ERYTHROCYTE
Metabolism
 Metabolism is basically:
 89% Embdden-Meyerhoff
 11% Pentose phosphate pathway
 The process of hemolysis is favored when the pathways
fail to provide sufficient reduced glutathione or sufficient
energy-providing substances (NADH, NADPH or ATP)
 About 20 chemicals are involved in the pathways

EMBDEN MEYERHOFF
PATHWAY
(Glycolysis)

PENTOSE
PHOSPHATE
PATHWAY

HEMOGLOBIN AND OXYGEN
DISSOCIATION
• Saturation of the first
heme increases the
affinity of the second
heme and so forth,
so that the affinity of
the 4th heme is many
times that of the first
• 50mmHg = 83.5%
• Conditions affecting
the curve:
• pH
• Temperature
• 2,3-DPG
2,3-Diphosphoglycerate and O2 Dissociation
• Unique to mammalian red cells
• Product of GLYCOLYSIS
• Binds to deoxyhemoglobin in the positively charged cavity between
the N-terminal of B chains
• Rule:
• THE GREATER THE DPG = THE GREATER O2
DISPLACEMENT
• Fetal hemoglobin does not have the same affinity to DPG as
adult hemoglobin
• The level of DPG falls progressively in stored blood so that 20%
remains at the end of 14 days
• DPG has an important role in anemia
• Certain intrinsic erythrocyte defects producing anemia are
associated with striking rises in DPG if the defect occurs after
DPG is formed
• Levels of DPG are low in diabetic ketoacidosis
ENERGY METABOLISM
• Less energy required
• Na + - K + pump
• Iron in Fe ++ form
• Utilize Glucose by GLUT 1
• Anaerobic respiration – Glycolysis
• Embden Meyerhof pathway
• Pentose phosphate pathway.
• Hexose monophosphate shunt

Erythrocyte Function
• RBCs are dedicated to respiratory gas

transport
• Hemoglobin binds reversibly with oxygen

• Functions:
• Rbc’s critical role is in the transport of oxygen and
carbon dioxide and is dependent on hemoglobin
• CARBONIC ANHYDRASE– enzyme in the rbcs that
catalyzes the reaction that joins carbon dioxide and
water to form carbonic acid
• CARBONIC ACID– dissociates and generates
bicarbonate ions, which diffuses out of the rbcs and
serves to transport carbon dioxide in the blood plasma

• Hemoglobin structure
• Protein globin: two alpha and two beta chains
• Heme pigment bonded to each globin chain
• Iron atom in each heme can bind to one O2
molecule
• Each Hb molecule can transport four O2

COMPONENTS OF HEMOGLOBIN
• A PROTEIN COMPONENT called globin composed of

two sets (dimers) of two different polypeptide chains
• Four molecules of NITROGENOUS SUBSTANCE
protoporphyrin IX
• Four IRON ATOMS IN THE FERROUS STATE that
combine with protoporphyrin IX for form 4 heme
molecules
• One 2,3 – DIPHOSPHOGLYCERATE molecule as a
sometimes resident molecule in the center of the Hb unit

GLOBIN CHAINS
GREEK GREEK NAME NUMBER OF COMMENTS
DESIGNATIO AMINO ACIDS
N
 Alpha 141
 Beta 146
d Delta 146 Differs from beta chains by
10 amino acids
g Gamma 146 Differs from beta chains by
39 amino acids
e Epsilon 146 Embryonic only
z Zeta 146 Embryonic only

PROTOPORPHYRIN IX and IRON
• PROTOPORPHYRIN IX is a nitrogenous
substance synthesized partly inside the
mitochondria and partly in the cytoplasm of the
nucleated erythrocyte during maturation.
• Protoporphyrin IX + Fe+2 = HEME
(ferroprotoporphyrin IX)

2,3-DIPHOSPHOGLYCERATE
• Produced by the Embden-Meyerhoff pathway

• Generates energy for the erythrocytes
• Produced specifically by the Rappaport-Luebering shunt
• When 2,3-DPG binds to Hb, OXYGEN AFFINITY
DECREASES and vice versa

Hemoglobin
• Within each rbc are ~ 200-300 million molecules of hemoglobin

• Composed of 4 globin chains ( and ) attached to a heme
molecule
 Globin chains
Heme
group
 Globin chains
(a) Hemoglobin consists of globin (two (b) Iron-containing heme pigment.
alpha and two beta polypeptide
chains) and four heme groups.

GENETIC CODING FOR GLOBIN CHAINS
• The human chromosomes 11 and 16 contain all the

necessary information necessary to direct the synthesis
of various globin chains
5’ 3’
5’ 3’

GLOBIN CHAIN STRUCTURE
PRIMARY STRUCTURE
• Specific amino acid SEQUENCE

• Alpha chain – number beginning at 1 at the N-terminal to
141 at the C-terminal of the chain
• Amino acid residues of the beta, delta, and gamma
chains are number from one through 146.

GLOBIN CHAIN STRUCTURE
SECONDARY AND TERTIARY STRUCTURES
• Secondary structure is defined by

dividing the chain into 8 separate
HELICAL segments
• 7 non-helical segments (NA, AB,
CD, EF, FG, GH, and HC) that lie
between the 8 helical segments
• Provides flexibility that allows
physical bending of the globin
chain to produce the tertiary
structure

HEME PRODUCTION AND STRUCTURE
• Requires the formation of protoporphyrin IX and iron

availability
• PORPHIN (TETRAMETHENETETRAPYRROLE) – a cyclic compound
composed of 4 pyrrole rings connected with methene
(=CH-) bridges at carbons 2 and 4 in the pyrrole rings.
Hemoglobin (Hb)
• O2 loading in the lungs

• Produces oxyhemoglobin (ruby red)
• O2 unloading in the tissues
• Produces deoxyhemoglobin or reduced
hemoglobin (dark red)
• CO2 loading in the tissues
• Produces carbaminohemoglobin (carries 20%
of CO2 in the blood)

Hemoglobin
• Hemoglobin is able to unite with 4 oxygen molecules to form

OXYHEMOGLOBIN to allow oxygen to be transported wherever it is
needed
• CARBAMINOHEMOGLOBIN - a hemoglobin molecule carrying
carbon dioxide
• CARBOXYHEMOGLOBIN – a hemoglobin molecule carrying carbon
monoxide
• Is irreversible
• A male has a greater amount of hemoglobin than females
• ANEMIA is the decrease in number or volume of functional rbc’s in a
given unit of whole blood.
• POLYCYTHEMIA is the absolute or relative increase of red cell
population or other formed elements as well.

Remember!
• The rate of porphyrin synthesis is directly
related to the rate of globin synthesis. THUS
HEME and GLOBIN SYNTHESIS IS
CLOSELY SYNCHRONIZED!

Erythrocyte Disorders
• Anemia: blood has abnormally low O2-

carrying capacity
• A sign rather than a disease itself
• Blood O2 levels cannot support normal
metabolism
• Accompanied by fatigue, paleness, shortness
of breath, and chills

Causes of Anemia
1. Insufficient erythrocytes
• Hemorrhagic anemia: acute or chronic loss
of blood
• Hemolytic anemia: RBCs rupture
prematurely
• Aplastic anemia: destruction or inhibition of
red bone marrow

Causes of Anemia
2. Low hemoglobin content

• Iron-deficiency anemia
• Secondary result of hemorrhagic anemia or
• Inadequate intake of iron-containing foods
or
• Impaired iron absorption

Causes of Anemia
• Pernicious anemia
• Deficiency of vitamin B12
• Lack of intrinsic factor needed for absorption
of B12
• Treated by intramuscular injection of B12 or
application of Nascobal

Causes of Anemia
3. Abnormal hemoglobin
• Thalassemias
• Absent or faulty globin chain
• RBCs are thin, delicate, and deficient in
hemoglobin

Causes of Anemia
• Sickle-cell anemia
• Defective gene codes for abnormal
hemoglobin (HbS)
• Causes RBCs to become sickle shaped in
low-oxygen situations

(a) Normal erythrocyte has normal
hemoglobin amino acid sequence
in the beta chain. 1 2 3 4 5 6 7 146
(b) Sickled erythrocyte results from

a single amino acid change in the
beta chain of hemoglobin. 1 2 3 4 5 6 7 146

Erythrocyte Disorders
• Polycythemia: excess of RBCs that increase

blood viscosity
• Results from:
• Polycythemia vera—bone marrow cancer
• Secondary polycythemia—when less O2 is
available (high altitude) or when EPO
production increases
• Blood doping

Hematology 1

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Hematology 1

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INTRODUCTION TO

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

• Hematology is the study of blood which is

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• Blood: a fluid connective tissue composed of

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• white blood cells and platelets

Copyright © 2010 Pearson Education, Inc. Figure 17.1

• Sticky, opaque fluid

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Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

• Nitrogenous by-products of metabolism—

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• Only WBCs are complete cells

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Copyright © 2010 Pearson Education, Inc.

• Hematopoiesis (hemopoiesis): blood cell

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• Hemocytoblasts (hematopoietic stem cells)

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Copyright © 2010 Pearson Education, Inc.

• Fetus: 0-2 months (yolk sac).

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Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Pluripotent Stem Cell

Myeloid Multipotent Common Lymphoid

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• regulates the proliferation and differentiation of HPCs

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Copyright © 2010 Pearson Education, Inc.

• Erythropoiesis: red blood cell production

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Copyright © 2010 Pearson Education, Inc.

• This takes place in the bone marrow and

• Too few RBCs leads to tissue hypoxia

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Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

• The size varies from 10-16 micrometer.

• Cytoplasm deep blue

• RNA – Basophil stain

• Nuclear lysis and

• It is a flat disc shaped and non-nucleated cell

• Young RBCs (34%

• Circular, anucleate, highly

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc. Figure 17.6

Copyright © 2010 Pearson Education, Inc. Figure 17.6, step 1

2 Kidney (and liver to

Copyright © 2010 Pearson Education, Inc. Figure 17.6, step 2

2 Kidney (and liver to

Copyright © 2010 Pearson Education, Inc. Figure 17.6, step 3

Copyright © 2010 Pearson Education, Inc. Figure 17.6, step 4

Copyright © 2010 Pearson Education, Inc. Figure 17.6, step 5