Development of the
Hematopoietic System &
the Introduction of Anemia
The department of Pediatric,
Hematology/Oncology,
Dr.Jie Yu,MD,Associate Professor
Contents
? Development of hematopoietic system
– Hematopoietic organs
– Hematopoietic blood cells
? Characteristic of cell counts and hemoglobin
– RBC and Hb level
– Hemoglobin
– WBC/Platelet/Blood volume
? Anemia
Development of
Hematopoietic System
in t h e e m b r y o a n d f e t u s,
c o n s t a n t c h a n g e s c h a r a c t e r i z e
a l l p h a s e s of h e m a t o p o i e s i s,
Development of
Hematopoietic Organs
? Fetal hematopoiesis
– Mesoblastic Hematopoiesis
– Hepatic Hematopoiesis
– Myeloid Hematopoiesis
? Hematopoiesis after birth
SITES TIME PRODUC
Measoblastic
hematopoisis
Yolk Sac 10-14th day
3-4wk:primitive blasts
10-12wk:ceased
Erythroid
Hepatic
hematopoiesis
Liver 6-8wk:appear
12-16wk:active
6mo:diminish/ stop at birth
Erythroid
Myeloid
hematopoiesis
Bone
marrow
4mo:start
6mo:increase/steady
after birth,the only
Erythroid
Neutrophils
Macrophages
Table 1,Fetal Hematopoiesis
Development of
Hematopoietic Organs
? Fetal hematopoiesis
? Hematopoiesis after birth
– Bone marrow hematopoiesis
– Extrmedullary hematopoiesis
Development of
Hematopoietic Organs
? Hematopoiesis after birth
– Bone marrow hematopoiesis
? All blood cells are produced in the marrow
after 2nd trimester
? Newborn and early infancy,red marrow
? 5-7yr, yellow marrow
– Extrmedullary hematopoiesis
Development of
Hematopoietic Organs
? Hematopoiesis after birth
– Bone marrow hematopoiesis
– Extramedullary hematopoiesis
? In diseases status,red cell production?
hematopoietic tissue?,
? blood production expands to replace fatty marrow,
? blood cells production extends to extramedullary
sites ( liver and spleen).
Development of the
Hematopoietic Blood Cells
? Pluripotent Stem Cells:
– which are capable of both self-renewal and of
clonal maturation into all blood cell lineages.
– Progenitor cells differentiate under the
influence of hematopoietic growth factors
Table 2.The Development of Blood Cells
PROGENITOR CYTOKINES PRODUC
CFU-GM G-CSF NUTROPHIL
CFU-Meg TPO PLT
CFU-E
BFU-E
EPO RBC
Fi
g
1.H
em
at
op
ois
is
Blood Cell Counts
and Hemoglobin
Fig2,Peripheral Blood Cells
RBC and Hb Level
? At Birth:
– RBC,5-7x1012/L
– Hb:150 to 230g/L.
? Postnatal fall /physiology anemia
? Infancy ? Preschool age:
– RBC,4 x 1012/L
– Hb,110 g/L
? 7-12yr,adult level
RBC and Hb level
? Postnatal Fall & Physiological Anemia.
– Hemoglobin values in term infants drop to
their lowest mean of 100g/L at 2-3 mo
– Causes
? Erythropoietin production?
? Red cell life span (90/120)
? Blood volume?
– Preterm infant
RBC and Hb level
? Reticulocytes
– At Birth,5% / 10%
– 1-2mo,fall down to 0.3%
– Later adult level,0.5-1.5%
? Nucleated Red Blood Cells
– At birth,3-10/100 WBC; 10-20/100WBC
– 1wk,disappear
HEMOGLOBIN.
? Function
– transport oxygen.
? Construction
– iron-containing heme plus globins which is a tetramer
made up of two pairs of polypeptide chains,
Fig3,Hb structure
Table3,HEMOGLOBINS
Hb Chains 8周 6月 出生 6-12月 2岁
Embry Gower1 δ2ε2
8周前，
3月消
失
Gower2 α2ε2
Portland δ2γ2
Fetal HbF α2γ2 增加 90% 70% <5% <2%
Adult HbA α2β2 5-10% 30% >95%
HbA2 α2δ2 <1% 2-3% <3.5%
WBC Counts
? At birth,20 x 109/L
? Infant,12 x 109/L
? Preschool,8.0 x 109/L
(% )70
淋巴细胞
中性粒细胞
4-6岁4-6天
60
50
40
30
20
10
1 3 5 7 9
日数
1 3 5 7 9 11
岁数
Fig4,WBC Ratio
PLT & Blood Volume
? PLT,150-250 x 109/L
? Blood Volume,
– Term newborn,85ml/kg
– Premature infant,95ml/kg
– Adult,75ml/kg
– Young children,75-80ml/kg
The Introduction of
ANEMIA
Definition of Anemia
? a reduction of the red blood cell volume
or hemoglobin concentration below the
range of values occurring in healthy
persons
Table 4,The definition of Anemia and Degree
Age Anemia Values Anemia Degree
Newborn < 145g/L
1-4 mo < 90g/L Mild,-90g/L
4-6 mo < 100g/L Moderate,-60g/L
6 mo-6 yr < 110g/L Severe,-30g/L
6-14 yr < 120g/L Extremely severe:< 30g/L
Pathophysiology of Anemia
? Pathophysiology
– increased cardiac output
– increased oxygen extraction
– blood flow toward vital organs and
tissues,
– In addition,the concentration of 2,3-
DPG increases within the RBC,
Fig5:The oxygen dissociation curve
Manifestation of Anemia
? Acute onset
– elevated pulse,hemic flow murmur,poor
exercise tolerance,headache,excessive
sleeping,poor feeding,and syncope may occur,
? Slow onset
– weakness,tachypnea,shortness of breath on
exertion,tachycardia,cardiac dilatation,and
congestive heart failure
MCV（ fl） MCH（ pg） MCHC（ %）
Normal ranges 80-94 28-32 32-38
Macrocytic >94 >32 32-38
Normocromic
/Normocytic
80-94 28-32 32-38
Microcytic <80 <28 32-28
Hypochromic
/Microcytic
<80 <28 < 32
Classification-morphology
Table 5
Classification- etiology
? Reduced capacity to produce RBC
– Aplastic anemia
– Bone marrow failure
– Deficiency syndromes
? Hemolysis
? Blood Loss
Classification- etiology
? Reduced capacity to produce RBC
– Aplastic anemia
? Fanconi’s anemia
? Acquired aplastic anemia
– Pure red cell aplasia
? congenital hypoplastic anemia
(Diamond-Blackfan)
? Acquired hypoplastic anemia
Classification- etiology
? Reduced capacity to produce RBC
– Marrow Infiltration
? Leukemia
? Lymphoma
? Neuroblastom
? LCH
Classification-etiology
? Reduced capacity to produce RBC
– Deficiency Syndrome
? Iron
? Folate
? Vitamin B12
? Vitamin E
? Vitamin B6
Classification-etiology
? Hemolysis
– Iintrinsic RBC abnormalities
? Hemoglobinopathies
? Enzymopathies
? Membrane disorders
– extrinsic RBC abnormalities
? Immunologic,AIHA
Classification-etiology
? Hemolysis:intrinsic RBC abnormalities
– Intrinsic membrane defects
? Hereditary Spherocytosis:
– Hemoglobinopathy
? Thalassemia
– RBC enzyme defects
? G6PD defect
Classification-etiology
? Hemolysis:extrinsic RBC abnormalities
– Immunologic hemolysis
? Isoimmune (Rh,ABO in neonate)
? Autoimmune Hemolytic Anemia (AIHA)
Classification-etiology
? Blood loss
– Gastrointestinal bleeding
? Ankylostomiasis
– Menstrual
– Trauma
Hematopoiesis Regulation Related terms
? CFU-GM
– colony –forming units
granulocyte-macrophages
? CFU-Meg
– colony-forming
unite-megakaryocyte
? CFU-E
– colony-forming
units-erythroid
? BFU-E
– burst-forming
units-erythroid
? G-CSF
– colony-stimulating
factor
? TPO
– thrombopoietin
? EPO
– erythropoietin
RBC Index
? MCV
– Mean corpuscular volume
? MCH
– Mean corpuscular hemoglobin
? MCHC
– Mean corpuscular concertration
Hematopoietic System &
the Introduction of Anemia
The department of Pediatric,
Hematology/Oncology,
Dr.Jie Yu,MD,Associate Professor
Contents
? Development of hematopoietic system
– Hematopoietic organs
– Hematopoietic blood cells
? Characteristic of cell counts and hemoglobin
– RBC and Hb level
– Hemoglobin
– WBC/Platelet/Blood volume
? Anemia
Development of
Hematopoietic System
in t h e e m b r y o a n d f e t u s,
c o n s t a n t c h a n g e s c h a r a c t e r i z e
a l l p h a s e s of h e m a t o p o i e s i s,
Development of
Hematopoietic Organs
? Fetal hematopoiesis
– Mesoblastic Hematopoiesis
– Hepatic Hematopoiesis
– Myeloid Hematopoiesis
? Hematopoiesis after birth
SITES TIME PRODUC
Measoblastic
hematopoisis
Yolk Sac 10-14th day
3-4wk:primitive blasts
10-12wk:ceased
Erythroid
Hepatic
hematopoiesis
Liver 6-8wk:appear
12-16wk:active
6mo:diminish/ stop at birth
Erythroid
Myeloid
hematopoiesis
Bone
marrow
4mo:start
6mo:increase/steady
after birth,the only
Erythroid
Neutrophils
Macrophages
Table 1,Fetal Hematopoiesis
Development of
Hematopoietic Organs
? Fetal hematopoiesis
? Hematopoiesis after birth
– Bone marrow hematopoiesis
– Extrmedullary hematopoiesis
Development of
Hematopoietic Organs
? Hematopoiesis after birth
– Bone marrow hematopoiesis
? All blood cells are produced in the marrow
after 2nd trimester
? Newborn and early infancy,red marrow
? 5-7yr, yellow marrow
– Extrmedullary hematopoiesis
Development of
Hematopoietic Organs
? Hematopoiesis after birth
– Bone marrow hematopoiesis
– Extramedullary hematopoiesis
? In diseases status,red cell production?
hematopoietic tissue?,
? blood production expands to replace fatty marrow,
? blood cells production extends to extramedullary
sites ( liver and spleen).
Development of the
Hematopoietic Blood Cells
? Pluripotent Stem Cells:
– which are capable of both self-renewal and of
clonal maturation into all blood cell lineages.
– Progenitor cells differentiate under the
influence of hematopoietic growth factors
Table 2.The Development of Blood Cells
PROGENITOR CYTOKINES PRODUC
CFU-GM G-CSF NUTROPHIL
CFU-Meg TPO PLT
CFU-E
BFU-E
EPO RBC
Fi
g
1.H
em
at
op
ois
is
Blood Cell Counts
and Hemoglobin
Fig2,Peripheral Blood Cells
RBC and Hb Level
? At Birth:
– RBC,5-7x1012/L
– Hb:150 to 230g/L.
? Postnatal fall /physiology anemia
? Infancy ? Preschool age:
– RBC,4 x 1012/L
– Hb,110 g/L
? 7-12yr,adult level
RBC and Hb level
? Postnatal Fall & Physiological Anemia.
– Hemoglobin values in term infants drop to
their lowest mean of 100g/L at 2-3 mo
– Causes
? Erythropoietin production?
? Red cell life span (90/120)
? Blood volume?
– Preterm infant
RBC and Hb level
? Reticulocytes
– At Birth,5% / 10%
– 1-2mo,fall down to 0.3%
– Later adult level,0.5-1.5%
? Nucleated Red Blood Cells
– At birth,3-10/100 WBC; 10-20/100WBC
– 1wk,disappear
HEMOGLOBIN.
? Function
– transport oxygen.
? Construction
– iron-containing heme plus globins which is a tetramer
made up of two pairs of polypeptide chains,
Fig3,Hb structure
Table3,HEMOGLOBINS
Hb Chains 8周 6月 出生 6-12月 2岁
Embry Gower1 δ2ε2
8周前，
3月消
失
Gower2 α2ε2
Portland δ2γ2
Fetal HbF α2γ2 增加 90% 70% <5% <2%
Adult HbA α2β2 5-10% 30% >95%
HbA2 α2δ2 <1% 2-3% <3.5%
WBC Counts
? At birth,20 x 109/L
? Infant,12 x 109/L
? Preschool,8.0 x 109/L
(% )70
淋巴细胞
中性粒细胞
4-6岁4-6天
60
50
40
30
20
10
1 3 5 7 9
日数
1 3 5 7 9 11
岁数
Fig4,WBC Ratio
PLT & Blood Volume
? PLT,150-250 x 109/L
? Blood Volume,
– Term newborn,85ml/kg
– Premature infant,95ml/kg
– Adult,75ml/kg
– Young children,75-80ml/kg
The Introduction of
ANEMIA
Definition of Anemia
? a reduction of the red blood cell volume
or hemoglobin concentration below the
range of values occurring in healthy
persons
Table 4,The definition of Anemia and Degree
Age Anemia Values Anemia Degree
Newborn < 145g/L
1-4 mo < 90g/L Mild,-90g/L
4-6 mo < 100g/L Moderate,-60g/L
6 mo-6 yr < 110g/L Severe,-30g/L
6-14 yr < 120g/L Extremely severe:< 30g/L
Pathophysiology of Anemia
? Pathophysiology
– increased cardiac output
– increased oxygen extraction
– blood flow toward vital organs and
tissues,
– In addition,the concentration of 2,3-
DPG increases within the RBC,
Fig5:The oxygen dissociation curve
Manifestation of Anemia
? Acute onset
– elevated pulse,hemic flow murmur,poor
exercise tolerance,headache,excessive
sleeping,poor feeding,and syncope may occur,
? Slow onset
– weakness,tachypnea,shortness of breath on
exertion,tachycardia,cardiac dilatation,and
congestive heart failure
MCV（ fl） MCH（ pg） MCHC（ %）
Normal ranges 80-94 28-32 32-38
Macrocytic >94 >32 32-38
Normocromic
/Normocytic
80-94 28-32 32-38
Microcytic <80 <28 32-28
Hypochromic
/Microcytic
<80 <28 < 32
Classification-morphology
Table 5
Classification- etiology
? Reduced capacity to produce RBC
– Aplastic anemia
– Bone marrow failure
– Deficiency syndromes
? Hemolysis
? Blood Loss
Classification- etiology
? Reduced capacity to produce RBC
– Aplastic anemia
? Fanconi’s anemia
? Acquired aplastic anemia
– Pure red cell aplasia
? congenital hypoplastic anemia
(Diamond-Blackfan)
? Acquired hypoplastic anemia
Classification- etiology
? Reduced capacity to produce RBC
– Marrow Infiltration
? Leukemia
? Lymphoma
? Neuroblastom
? LCH
Classification-etiology
? Reduced capacity to produce RBC
– Deficiency Syndrome
? Iron
? Folate
? Vitamin B12
? Vitamin E
? Vitamin B6
Classification-etiology
? Hemolysis
– Iintrinsic RBC abnormalities
? Hemoglobinopathies
? Enzymopathies
? Membrane disorders
– extrinsic RBC abnormalities
? Immunologic,AIHA
Classification-etiology
? Hemolysis:intrinsic RBC abnormalities
– Intrinsic membrane defects
? Hereditary Spherocytosis:
– Hemoglobinopathy
? Thalassemia
– RBC enzyme defects
? G6PD defect
Classification-etiology
? Hemolysis:extrinsic RBC abnormalities
– Immunologic hemolysis
? Isoimmune (Rh,ABO in neonate)
? Autoimmune Hemolytic Anemia (AIHA)
Classification-etiology
? Blood loss
– Gastrointestinal bleeding
? Ankylostomiasis
– Menstrual
– Trauma
Hematopoiesis Regulation Related terms
? CFU-GM
– colony –forming units
granulocyte-macrophages
? CFU-Meg
– colony-forming
unite-megakaryocyte
? CFU-E
– colony-forming
units-erythroid
? BFU-E
– burst-forming
units-erythroid
? G-CSF
– colony-stimulating
factor
? TPO
– thrombopoietin
? EPO
– erythropoietin
RBC Index
? MCV
– Mean corpuscular volume
? MCH
– Mean corpuscular hemoglobin
? MCHC
– Mean corpuscular concertration
