Development of the Hematopoietic System & the Introduction of Anemia The department of Pediatric, Hematology/Oncology, Dr.Jie Yu, MD. Associate Professor.

Development of the

Hematopoietic System

& the Introduction of

AnemiaThe 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 the embryo and fetus,

constant changes characterize

all phases of hematopoiesis.

Development of Hematopoietic Organs

• Fetal hematopoiesis– Mesoblastic Hematopoiesis

– Hepatic Hematopoiesis

– Myeloid Hematopoiesis

• Hematopoiesis after birth

  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

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 sit

es ( liver and spleen).

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

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

Fig1

.Hem

ato

poisis

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 thei

r 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 m

ade 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 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%

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 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

  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

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 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

RBC Index

• MCV– Mean corpuscular volume

• MCH– Mean corpuscular hemoglobin

• MCHC– Mean corpuscular concertration