HEMATOPOIESIS

By Professors
Dr. Ahmed ElGendy – Dr. Ahmed Agamy
 Objectives
General composition of the blood
Stages of hematopoiesis in bone marrow
Plasma proteins
Types and sites of formation
Functions
Red blood corpuscles
Normal count and normal Sites of formation of RBCs
Factors affecting erythropoiesis
Function of RBCs & variation in RBCs count
White blood cells
Normal count and normal Sites of formation of WBCs
Types, functions of WBCs & variation in WBCs count
Platelets
Normal count and Site of formation
Prof. Ahmed ElGendy - Prof
Function & variation in platelet count Ahmed Agamy
*Def : It is a tissue ( cellular element )
fluid ( plasma ) .
Blood circulation was first explained by
William Harvey
*General functions of blood :
1- Transport functions
2- Haemostatic function
3- Homeostatic function
4- Defensive function
Prof. Ahmed ElGendy - Prof Ahmed Agamy
1- Yellowish fluid =
plasma=55%

2- Cellular element = blood

cells=45%
Prof. Ahmed ElGendy - Prof Ahmed Agamy
 Blood composition
Blood is a modified connective tissue composed of:-
A-Cellular component (45%):-
1- Red blood corpuscles (RBCs) or erythrocyte.
2- White blood cells (WBCs) or leukocytes.
3- Platelets or thrombocytes.
F. luid component (plasma) 55%:- Composed of :-
a) water 90%.
b) dissolved substances 10%.
1 plasma proteins.
2 Other organic substances as nutrients and
waste products.
3 Inorganic substances e.g. Na+ , K+ , Ca2+ , Cl- etc.

Prof. Ahmed ElGendy - Prof Ahmed Agamy

 Hematopoiesis in bone marrow
Multipotential hematopoietic stem cell
(Hemocytoblast)

Myeloid stem cell Lymphoid stem cell

Lymphoblast

Erythroblast
Lymphocyte
T and B
Reticulocyte

Erythrocyte

Prof. Ahmed ElGendy - Prof Ahmed Agamy

Prof. Ahmed ElGendy - Prof Ahmed Agamy
-Functions:-
A.Specific functions:- i.e. related to a specific type of plasma
proteins.
(1)Osmotic pressure of plasma :-
• Albumin is responsible for most (80%) of this osmotic pressure,
because it has the highest concentration and smallest molecular
size i.e. great number of molecules.
• The total osmotic pressure of plasma = 5000 mm Hg (nearly 300
m.osmol/L) it is due to crystalloids (Na+, Cl- , K+ etc.) and colloids
(plasma proteins).
• The crystalloid are responsible for most of plasma osmotic pressure
but less important regarding movement of fluid across the capillary
wall because it is equally distributed inside and outside capillaries.
• The colloids (plasma proteins) responsible only for 25 – 30 mm Hg of
the plasma osmotic pressure but more important, because plasma
proteins are present only in plasma (tissue fluid is almost free of
proteins). Prof. Ahmed ElGendy - Prof Ahmed Agamy
(2)Defensive functions:- gamma globulins are the antibodies that
protect the body against the micro-organisms and their toxins.
(3)Viscosity of the plasma:- Fibrinogen is the main plasma proteins
responsible for it. Viscosity is important for maintaining the blood
pressure.
(4)Clotting of blood:- Is the function of fibrinogen and prothrombin
Prof. Ahmed ElGendy - Prof Ahmed Agamy
A.Non specific functions:-
(1)Buffering function:-
• Buffer system is composed of weak acid and its salt with a strong
base.
• At normal pH of blood(7.4, slightly alkaline) plasma proteins are
present in the form of proteinic acid (weak acid) and Na proteinate
(its salt with a strong base). Thus it acts as a buffer system
preventing excessive changes in pH.
(2)Carrier function :-
Plasma proteins acts as carriers for many substances e.g.
-Vitamins e.g. vitamin A -Hormones e.g. thyroxine and insulin
-Metals e.g. iron -Ions e.g. calcium
Significance of this carrier function:-
1 The combined form acts as a reservoir from which the free
substance is slowly released to tissues.
2 Prevent filtration of substances in the kidney and loss in urine.
Prof. Ahmed ElGendy - Prof Ahmed Agamy
Red (active) Yellow (inactive) Red (active) Bone Red (active) Bone
Bone Marrow Bone Marrow Marrow In children Marrow In adults

Shape:- Circular, biconcave, non-nucleated discs.

This characteristic shape:- (biconcavity)
1-Increases the surface area in relation to volume.
2-Enables it to pass through narrow capillaries
without rupturing during deformation. Prof. Ahmed ElGendy - Prof Ahmed Agamy
Life span:-
120 days + 7 days.
Factors affecting erythropoiesis :-
1-Oxygen supply to tissues (hypoxia):-
The primary stimulus for erythropoiesis is the decreased oxygen
supply to tissues i.e. hypoxia.
Mechanism:- Hypoxia stimulate secretion of erythropoietin
hormone mainly from the kidney (90%) and also from liver (10%).
Erythropoietin stimulate erythropoiesis in the bone marrow.
Hypoxia

liver Kidney

Erythropoietin
10% 90%

Bone marrow RBCs production.

Prof. Ahmed ElGendy - Prof Ahmed Agamy
2-Hormones:-
The following hormones stimulates erythropoiesis:-
1Androgens e.g. testosterone.
2Thyroid hormones (T3 and T4).
3- Glucocorticoids e.g. Cortisone.
3 Diet:-
1 Proteins:- Needed for formation of globin part of
hemoglobin.
2 Vitamins:- Especially vitamin B12 (cyanocobalamin)
and folic acid (a member of vitamin B complex).
They are needed for RBCs maturation (maturation
factors) because both of them are essential for
synthesis of DNA. Prof. Ahmed ElGendy - Prof
3 Metals:- Ahmed Agamy
a.Iron:- In the ferrous state is needed for the
formation of haem part of hemoglobin.
b.Copper:- Acts as a catalyst in hemoglobin formation.
c- Cobalt:- Stimulates erythropoietin release.
4-Organs:-
a. Liver:- Essential for normal erythropoiesis, it:-
1 Helps in formation of globin part of hemoglobin.
2 Stores iron, copper and vitamin B12
3 Synthesizes erythropoietin.
b. Bone marrow:-
It is the only site in adults for normal erythropoiesis.
c. Kidney:-
Synthesizes erythropoietin.
Function of RBCs:-
The main function of RBCs is to enclose hemoglobin inside
it. If hemoglobin is free in the plasma it will lead to many
disorders (discussed with blood transfusion).
Hemoglobin
1CarryO2 from lung to tissues and CO2 from tissues to
lung. Prof. Ahmed ElGendy - Prof
2 Acts as a buffer for regulation of pH Ahmed Agamy
Variation in RBCs count:
1Anemia: Decreased RBCs count
2Polycythemia: Increased RBCs count
Type and causes:-
(1)Primary polycythemia (polycythemia vera):- due to
tumour like condition of blood forming cells.
(2)Secondary polycythemia:- Develops as a response to
chronic hypoxia, which triggers increased production of
erythropoietin by the kidneys. May be:-
A- Physiological e.g. in high altitudes.
B- Pathological:- as in heart failure and chronic lung
diseases.
Effect on CVS:-
a- blood viscosity  in peripheral resistance  blood
pressure  work of the heart lastly may lead to heart failure.
b- viscosity also  the blood flow to tissues  stagnant
hypoxia. Prof. Ahmed ElGendy - Prof
 White blood cells (WBCs) (leukocytes)
Total count 4000-11000/mm3
Non Granular Granular

30%
Acquired 3%
(specific) -Weak Phagocytes
60%
immunity 6% -Anti Parasites
Phagocytosis
-Phagocytosis -Slow and modulate
(Microphages)
(Macrophages) allergic reaction
-Help T&B Lymph 1%
Prof. Ahmed ElGendy - Prof
Role in allergy
Ahmed Agamy Synthesize heparin
 White blood cells (WBCs) (leukocytes)
Total count:- 4000 -11000/mm3.
Site of formation:-
1 Granulocytes (Neutrophils, eosinophils, basophiles) +
monocytes are formed in the bone marrow from
myeloblast.
2 Lymphocytes are formed early in life from lymphoblast in
bone marrow but after that it is formed in lymphatic
tissue in lymph nodes, spleen, liver etc.
Types and functions:-
A-Granular leukocytes: Contain granules in their cytoplasm.
1-Neutrophils (microphages):- 60% of the total WBCs.
Function: they are potent phagocytes i.e. they attack and
destroy the invading bacteria and foreign substances.

Prof. Ahmed ElGendy - Prof

Ahmed Agamy
1- Margination
2- Diapedesis
3- Amoeboid movement
4- Chemotaxis by chemotaxins :
- Bacterial or viral toxins
- Tissue products
- Complement
- Leukotrienes
5- Phagocytosis
Prof. Ahmed ElGendy - Prof Ahmed Agamy
*It is a granular leukocytes
*Acidic in histological stains
*1-5% of total leukocytic count
*Functions :
1- Weak phagocytic & show chemotaxis
2- Antiparasitic : kill Bilharziasis by ;
- Hydrolytic enzymes
- Free radicals ( O2 )
- Major basic protein ( larvicidal )
3- Anti-allergic : by ;
- Detoxication of antigen ( Ag )
- Phagocytosis of Ag-Ab complex
- Destruction of histamine by histaminase
4- Produce fibrinolysin which when activated will
digest blood clot
Prof. Ahmed ElGendy - Prof Ahmed Agamy
*It is a granular leukocytes
*Basic in histological stains
*0.0 – 1% of total leukocytic count
*Functions :
1- Secretion of heparin
2- Allergic manifestations
3- Inflammatory reactions

Prof. Ahmed ElGendy - Prof Ahmed Agamy

 B-Non granular leukocytes: No granules in their cytoplasm.
1-Lymphocytes:- 30% of total WBCs count.
They are 2 types B and T lymphocyte, both are responsible
for acquired immunity.
2-Monocytes (Macrophages):- 6% of total WBCs count.
Functions:
1- Phagocytosis:
▪ They are immature in the blood (have no phagocytic
activity) on entering the tissues they enlarge and become
highly phagocytic cells called macrophages.
▪ Macrophages show all the characters of neutrophils
(Diapedesis chemotaxis etc.) but it is much more powerful
phagocytic cell than neutrophils because:
a. It can engulf large particles e.g. whole RBC (neutrophils
engulf small particles only).
b. It can engulf as many as 100 bacteria (neutrophil engulf
only 5-20).
2- Macrophages help the function of T and B lymphocytes
 Variation of leukocytic count:
1. Leukocytosis: Increase number of WBCs (more than
11.000). it may be:
I) Physiological: all types increase in the same proportion
as in: 1-Exercise 2-Emotions 3-
Pregnancy
II) Pathological: one type increase at the expense of
others A)Neutrophilia: occur in:
1) Pyogenic infections e.g. abscess, pneumonia etc.
2) Tissue damage e.g. surgery, myocardial infarction etc.
B)Eosinophilia: occur in:
1)Parasitic infections e.g. bilharziasis.
2)Allergic conditions e.g. bronchial asthma.
C)Basophilia: occur in allergic conditions
D)Lymphocytosis and Monocytosis : occur in:
1) Viral infections e.g. mumps.
2) Chronic bacterial infections e.g. tuberculosis.
Prof. Ahmed ElGendy - Prof Ahmed Agamy
2. Leucopenia: decrease number of WBCs (less than
4000/mm3). Occur in:
a) Some bacterial infections e.g. typhoid fever.
b) Some viral infections e.g. hepatitis.
3. Leukemia: marked increase in WBCs due to
malignant disease of bone marrow.
4. Agranulocytosis: marked decrease in WBCs (less than
500/mm3) due to failure of bone marrow to produce WBCs.
It may result from irradiation or drug intoxication.

Prof. Ahmed ElGendy - Prof Ahmed Agamy

Shape : Oval or rounded or convex
non nucleated with granular
cytoplasm

Size : small = 2-4 um

Number = 150000 – 450000 /cmm

Life span = 8-12 days

Prof. Ahmed ElGendy - Prof Ahmed Agamy
High number reserve

Bleeding not occur except platelets

number is less than 50000 / cmm
Normal = 300000 / cmm in average)

N.B : duration of formation of both

platelets & RBCs last for 7 days
Prof. Ahmed ElGendy - Prof Ahmed Agamy
Prof. Ahmed ElGendy - Prof Ahmed Agamy
Resources
▪ Guyton AC, and Hall JE (2010); Text book
of
medical physiology, 12th ed., W.B.
Saunders Company
▪ Ganong WF. (2012) ; Review of Medical
Physiology, 24th ed., Lange Basic Science
▪ Lauralee Sherwood (2012); Human
physiology, from cell to system, 8th ed.,
Blackwell Press
▪ www.advan.physiology.org
Prof. Ahmed ElGendy - Prof Ahmed Agamy