HAEMATOLOGY

RED BLOOD CELLS

DISORDERS

‫ميسم مؤيد علوش‬.‫د‬.‫م‬.‫أ‬

LEC.1
Assistant Professor Dr.Maysem Alwash /Hematopathologist
HAEMOPOIESIS:

OBJECTIVES:
1-Define haemopoiesis and main site of haemopoiesis
2-Define medullary and exteamedulary haemopoiesis
4-Define the surface markers of haemopoietic stem cell
5-Define haemopoietic growth factors
6-Know the function of erythropoietin and stimulants for its production
7-Know haemoglobin types in adults and the red cell indicies
8-Define anemia ,clinical features and laboratory investigations
9-Classify anemia
Assistant Professor Dr.Maysem Alwash
 HAEMOPOIESIS:
It is the continuous, regulated process of
renewal, proliferation, differentiation, and
maturation of all blood cell
lines(RBCs,WBCs and platelets).

Assistant Professor Dr.Maysem Alwash

 BLOOD FILM FROM
A HEALTHY SUBJECT

Assistant Professor Dr.Maysem Alwash

Stages and Sites of Hematopoiesis:

-- Hematopoiesis starts during embryonic life and

continues through FETAL, NEONATAL, AND ADULT
LIFE.

-Sites of Hematopoiesis Change during

Development,as seen in the followings:

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 1-Embryonic hemopoeisis:

A-Yolk sac:
in the first few weeks of gestation, the extra
embryonic yolk sac is a transient site of
haemopoiesis called ‘primitive haemopoiesis’.

B-Aorta– gonad–mesonephros or AGM

region:
definitive haemopoiesis’ derives from a
population of stem cells first observed on the
aorta-gonads-mesonephros (AGM) region of
the Alwash
Assistant Professor Dr.Maysem developing embryo.
2-FETUS HEMOPOEISIS :

(LIVER, PLACENTA ,SPLEEN ,BONE MARROW)

• From 6 weeks until 6–7 months of fetal life, the liver and
spleen are the major haemopoietic organs and continue
to produce blood cells until about 2 weeks after birth
• The placenta also contributes to fetal haemopoiesis.
• At 4 to 5 months of gestation, hematopoiesis begins to
occur in the bone marrow, a process termed medullary
hematopoiesis, which continues after birth and
throughout postnatal
Assistant Professor Dr.Maysem Alwash life.
 3- AFTER BIRTH:

• Hemopoeisis is confined to the bone

marrow(termed medullary hemopoiesis because
it occurs in the medulla or inner part of the
bone cavity) begins between the fourth and
fifth month of fetal development and
continues after birth and throughout postnatal
life

Assistant Professor Dr.Maysem Alwash

 HAEMOPOEISIS
‫ااااااااااااااااااااااا‬HAEMOPOE
AGM
ISIS

and
Haemopoiesis Spleen

Assistant Professor Dr.Maysem Alwash

Bone marrow, one of the largest organs in the body, is
located within the cavities of the cortical bones.
Normal bone marrow contains two major components:

1-Red marrow:
hematopoietically active marrow that is
composed of developing blood cells and their
progenitors

2-Yellow marrow:
hematopoietically inactive marrow composed
primarily of adipocytes (fat cells), with
Assistant Professor Dr.Maysem Alwash undifferentiated mesenchymal cells and

macrophages.
  During infancy and early childhood, all
the bones in the body contain primarily
red (active) marrow.

 Between 5 and 7 years of age,

adipocytes become more abundant and
begin to occupy the spaces in the long
bones previously dominated by active
marrow.
Assistant Professor Dr.Maysem Alwash
The process of replacing the active marrow by
adipocytes (yellow marrow) during development
eventually results in restriction of the active marrow in
the adult to the sternum, vertebrae, scapulae, pelvis,
ribs, skull, and proximal portion of the long bones .
.

In adults, there is
approximately equal
amounts of red and yellow
marrow in these areas

Assistant Professor Dr.Maysem Alwash

 The ratio of the red marrow to the
yellow marrow (i.e., the
hematopoietic cells to the
adipocytes), often termed marrow
cellularity, typically decreases
.with age

Assistant Professor Dr.Maysem Alwash

HYPOCELLULAR NORMOCELLULAR

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 HYPERCELLULAR BONE MARROW

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Yellow marrow is capable of reverting
back to active marrow in cases of
increased demand on the bone marrow,
such as in excessive blood loss or
hemolysis.

Assistant Professor Dr.Maysem Alwash

-

In adults, hematopoietic tissue is located in the

bone marrow, lymph nodes, spleen, liver, and
thymus, but the marrow is the only source of
new blood cells during normal childhood and
adult life

Assistant Professor Dr.Maysem Alwash

• MEDULLARY HEMATOPOIESIS :
Hematopoiesis in the bone marrow because it
occurs in the medulla or inner part of the bone
cavity)

In states of medullary insufficiency, as in

patients with thalassemia and
myelofibrosis, hematopoiesis can revert to
its original sites, including the liver and
spleen . This is termed
EXTRAMEDULLARY HEMOPOIESIS
Assistant Professor Dr.Maysem Alwash
• All the blood cells are derived ,in the
bone marrow ,from a pluripotent
haemopoietic stem cell ..

• This haemopoietic stem cell is rare,

perhaps 1 in every 20 million
nucleated cells in bone marrow.
Assistant Professor Dr.Maysem Alwash
• It is CD34+ CD38-
 Morphologically, HSCs have the appearance of
a small or medium-sized lymphocyte . the
cells reside adjacent to osteoblasts or to
endothelial cells of sinusoidal vessels in
endosteal or vascular ‘niches’, where they are
surrounded by stromal cells, with which they
interact in numerous ways.

• Self-renewal and differentiation are

•
the key characteristics of hscs, which
are essential for hematopoiesis.
Assistant Professor Dr.Maysem Alwash
• Haemopoietic stem cells give rise to mixed and then
single lineage progenitor and precursor cells which,
after multiple cell divisions and differentiation, form
red cells, granulocytes (neutrophils, eosinophils and
basophils), monocytes, platelets, b and t lymphocytes
and natural killer cells.

• AS HSCS differentiate into different lineages,

their CD expression changes. CDs are thus used
to identify the different cells in the hierarchy
and have numerous clinical and research
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applications
 HAEMOPOIESIS

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Assistant Professor Dr.Maysem Alwash
 Erythroblasts (normoblasts) at varying
stages of development..
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 MEGAKARYOCYTE

Assistant Professor Dr.Maysem Alwash

Assistant Professor Dr.Maysem Alwash
 THE HAEMOPOIETIC
GROWTH FACTORS:
A group of specific glycoproteins called hematopoietic
growth factors or cytokines regulate the
proliferation, differentiation, and maturation of
hematopoietic precursor cells.e.g.: erythropoietin
ep, thrombopoietin , Granulocyte colony-
stimulating factors G-CSF , IL-2,IL-3, IL-6 ,,
chemokines, interferons, and others.
Assistant Professor Dr.Maysem Alwash
 Erythropoiesis.
We each make approximately 1012 new
erythrocytes (red cells) each day by the complex and

finely regulated process of Erythropoiesis.

The first recognizable erythrocyte

precursor in the bone marrow, is the
Assistant Professor Dr.Maysem Alwash Pronormoblast.
Assistant Professor Dr.Maysem Alwash
Erythropoiesis
• - is regulated by the
hormone erythropoietin.. normally, 90%
of the hormone is produced in the
peritubular interstitial cells of the
kidney and 10% in the liver and
elsewhere.

There are no preformed stores

and the stimulus to
erythropoietin production is
the oxygen (02) tension in the
tissues of the kidney.
Assistant Professor Dr.Maysem Alwash
Erythropoietin production

Erythropoietin production
therefore increases in:

-Anaemia
- Haemoglobin for some
metabolic or structural reason is
unable to give up 02 normally,
-Atmospheric 02 is low
-Defective cardiac or pulmonary
function
-Damage to the renal circulation
affects 02 delivery to the kidney
Assistant Professor Dr.Maysem Alwash
  The marrow requires many other precursors for
effective erythropoiesis.
these include metals such as iron or cobalt,
vitamins (especially vitamin B12, folate, vitamin
c, vitamin e, vitamin b6, thiamine and riboflavin)
and hormones such as androgens and thyroxine.

 Deficiency in any of these may be associated

with anaemia
Assistant Professor Dr.Maysem Alwash
 Haemoglobin synthesis

Normal adult blood contains three types of

haemoglobin:
1. Adult haemoglobin (Hb A ) 96-98 % : Hb A
:α2β2'

2. Fetal Hb (Hb F ) 0.5-0.8 % : α 2 γ2

3. Hb A2 1.5-3.2 % : α2δ2

At birth Hb F is the dominant haemoglobin

in the blood.

The major switch from fetal to adult

Assistant Professor Dr.Maysem Alwash
haemoglobin occurs 3-6 months after
birth
 Haemoglobin

2α +2 non α
4 haem
Globin chain
4 globin

Protoporphyrin
ring+ferrous iron in
centre=hem

Assistant Professor Dr.Maysem Alwash

 RED BLOOD CELL INDICIES

1.RED BLOOD CELL COUNT (RBC).

• : HB CONCENTRATION
2. THE (HB).
13.5 – 17.5 G/DL ♂
11.5 – 15.5 G/DL ♀
3.The haematocrit (Hct) or packed cell volume PCV.
PCV 0.39-0.50 male, 0.36-0.46 female

4.The mean cell volume (MCV): PCV/RBC.

MCV 80-95 fimtoliter( fl)
Assistant Professor Dr.Maysem Alwash
5.The mean cell haemoglobin (MCH): the average
amount of haemoglobin in an individual red cell.
MCH 27-32(pigogram) pg

6.The maen cell haemoglobin concentration(MCHC)

is the average concentration of haemoglobin ,rather
than the absolute amount,in an individual red cell.
MCHC 32-36 gm/dl

Assistant Professor Dr.Maysem Alwash

• Definition of anemia : is defined a reduction
in the haemoglobin concentration of the blood
below the reference interval for healthy
individuals of similar age, sex, and race, under
similar environmental conditions

• A functional definition of anemia is a decrease in

the oxygen carrying capacity of the blood. It can
arise if there is insufficient hemoglobin or the
hemoglobin has impaired function. The former is
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the more frequent cause.

 CLINICAL FEATURES OF ANAEMIA

:
SYMPTOMS:

• -Shortness of breath, particularly on exertion,

weakness, lethargy, palpitation ,headaches.
• -In older subjects, symptoms of cardiac failure,
angina pectoris or intermittent claudication or
confusion may be present.
Assistant Professor Dr.Maysem Alwash
 SIGNS:

• GENERAL SIGNS :
•
pallor of mucous membranes or nail beds,
conversely, skin colour is not a reliable sign.
tachycardia, a bounding pulse,
cardiomegaly and a systolic flow murmur,
especially at the apex, particularly in the
elderly, features of congestive heart failure
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 Pallar

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 PALLAR

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 • SPECIFIC SIGNS
are associated with particular types of
anaemia, e.g. koilonychia (spoon nails) with
iron deficiency, jaundice with haemolytic or
megaloblastic anaemias .
• LEG Ucers with sickle cell and other
haemolytic anaemias, or bone deformities
with thalassaemia major.
Assistant Professor Dr.Maysem Alwash
 KOILONYCHIA

Assistant Professor Dr.Maysem Alwash

 Classification of anemias according to the RBC indices

Microcytic, hypochromic Macrocytic Normocytic,

normochromic
-Iron deficiency - Megaloblastic: vitamin - haemolytic anaemias
- Thalassaemia B12 or folate deficiency - Anaemia of chronic
- Anaemia of chronic disease
disease (some cases) -Non-megaloblastic: - After acute blood loss
- Sideroblastic anaemia alcohol, liver disease, -Renal disease
(some cases) myelodysplasia, aplastic -Mixed deficiencies
anaemia -Bone marrow failure
(e.g.
post-chemotherapy,
infiltration by carcinoma,
etc.)
Assistant Professor Dr.Maysem Alwash
Laboratory Diagnosis:

• Laboratory procedures helpful in the initial

diagnosis of anemia include:
1-The complete blood count (CBC)
2-Examination of the peripheral blood film.
3-Bone marrow examination : .
4-Other tests , such as serum iron, total iron-binding
capacity, and serum ferritin (for microcytic anemias) and
serum folate and vitamin b12 (for macrocytic anemias)
Assistant Professor Dr.Maysem Alwash
• REFERENCES:
1-Rodak s hematology:
Clinical principles and Applications , 6 th edition
2-Hoffbrand s essential haematology 8th edition

Assistant Professor Dr.Maysem Alwash

Assistant Professor Dr.Maysem Alwash