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Development of the
Hematopoietic System
& the Introduction of
AnemiaThe department of Pediatric, Hematology
/Oncology, Dr.Jie Yu, MD. Associate Professor
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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
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Development of Hematopoietic
System
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in the embryo and fetus,
constant changes characterize
all phases of hematopoiesis.
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Development of Hematopoietic Organs
• Fetal hematopoiesis– Mesoblastic Hematopoiesis
– Hepatic Hematopoiesis
– Myeloid Hematopoiesis
• Hematopoiesis after birth
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SITES TIME PRODUC
Measoblastic hematopoisis
Yolk Sac
10-14th day3-4wk:primitive blasts10-12wk:ceased
Erythroid
Hepatichematopoiesis
Liver 6-8wk:appear12-16wk:active6mo:diminish/ stop at birth
Erythroid
Myeloid hematopoiesis
Bonemarrow
4mo:start6mo:increase/steadyafter birth: the only
ErythroidNeutrophilsMacrophages
Table 1. Fetal Hematopoiesis
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Development of Hematopoietic Organs
• Fetal hematopoiesis
• Hematopoiesis after birth– Bone marrow hematopoiesis– Extrmedullary hematopoiesis
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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
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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 sit
es ( liver and spleen).
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Development of the Hematopoietic Blood Cells• Pluripotent Stem Cells:
– which are capable of both self-renewal and of cl
onal maturation into all blood cell lineages.
– Progenitor cells differentiate under the influenc
e of hematopoietic growth factors
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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
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Fig1
.Hem
ato
poisis
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Blood Cell Counts and Hemoglobin
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Fig2. Peripheral Blood Cells
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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
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RBC and Hb level
• Postnatal Fall & Physiological Anemia. – Hemoglobin values in term infants drop to thei
r lowest mean of 100g/L at 2-3 mo – Causes
• Erythropoietin production
• Red cell life span (90/120)• Blood volume
– Preterm infant
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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
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HEMOGLOBIN. • Function
– transport oxygen.
• Construction– iron-containing heme plus globins which is a tetramer m
ade up of two pairs of polypeptide chains,
Fig3. Hb structure
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Table3. HEMOGLOBINS
Hb Chains 8 周 6 月 出生 6-12 月 2 岁
Embry Gower1 ζ2ε2
8 周前,
3 月消失
Gower2 α2ε2
Portland ζ2γ2
Fetal HbF α2γ2 增加 90% 70% <5% <2%
Adult HbA α2β2 5-10% 30% >95%
HbA2 α2δ2 <1% 2-3% <3.5%
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WBC Counts
• At birth: 20 x 109/L• Infant: 12 x 109/L• Preschool: 8.0 x 109/L
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(%)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
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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
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The Introduction of ANEMIA
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Definition of Anemia
• a reduction of the red blood cell
volume or hemoglobin
concentration below the range of
values occurring in healthy
persons
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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
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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.
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Fig5:The oxygen dissociation curve
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Manifestation of Anemia
• Acute onset– elevated pulse, hemic flow murmur, poor exerc
ise 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
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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-morphologyTable 5
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Classification- etiology
• Reduced capacity to produce RBC– Aplastic anemia– Bone marrow failure – Deficiency syndromes
• Hemolysis
• Blood Loss
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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
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Classification- etiology
• Reduced capacity to produce RBC– Marrow Infiltration
• Leukemia• Lymphoma• Neuroblastom• LCH
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Classification-etiology • Reduced capacity to produce RBC
– Deficiency Syndrome• Iron • Folate• Vitamin B12
• Vitamin E• Vitamin B6
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Classification-etiology
• Hemolysis– Iintrinsic RBC abnormalities
• Hemoglobinopathies• Enzymopathies• Membrane disorders
– extrinsic RBC abnormalities• Immunologic: AIHA
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Classification-etiology
• Hemolysis:intrinsic RBC abnormalities
– Intrinsic membrane defects• Hereditary Spherocytosis:
– Hemoglobinopathy• Thalassemia
– RBC enzyme defects• G6PD defect
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Classification-etiology
• Hemolysis:extrinsic RBC abnormalities
– Immunologic hemolysis • Isoimmune (Rh, ABO in neonate)
• Autoimmune Hemolytic Anemia (AIHA)
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Classification-etiology
• Blood loss– Gastrointestinal bleeding
• Ankylostomiasis– Menstrual– Trauma
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Hematopoiesis Regulation Related terms
• CFU-GM– colony –forming units gra
nulocyte-macrophages• CFU-Meg
– colony-forming unite-megakaryocyte
• CFU-E– colony-forming units-
erythroid• BFU-E
– burst-forming units-erythroid
• G-CSF– colony-stimulating fact
or• TPO
– thrombopoietin• EPO
– erythropoietin
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RBC Index
• MCV– Mean corpuscular volume
• MCH– Mean corpuscular hemoglobin
• MCHC– Mean corpuscular concertration
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