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

2. 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

3. Development of Hematopoietic System

5. in the embryo and fetus, constant changes characterize all phases of hematopoiesis.

6. Development of Hematopoietic Organs Fetal hematopoiesis –Mesoblastic Hematopoiesis –Hepatic Hematopoiesis –Myeloid Hematopoiesis Hematopoiesis after birth

7. SITESTIMEPRODUC Measoblastic hematopoisis Yolk Sac10-14 th day 3-4wk:primitive blasts 10-12wk:ceased Erythroid Hepatic hematopoiesis Liver6-8wk: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

8. Development of Hematopoietic Organs Fetal hematopoiesis Hematopoiesis after birth –Bone marrow hematopoiesis –Extrmedullary hematopoiesis

9. 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

10. 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).

11. 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

12. Table 2.The Development of Blood Cells PROGENITORCYTOKINESPRODUC CFU-GMG-CSFNUTROPHIL CFU-MegTPOPLT CFU-E BFU-E EPORBC

13. Fig 1.Hematopoisis

15. Blood Cell Counts and Hemoglobin

16. Fig2. Peripheral Blood Cells

17. RBC and Hb Level At Birth: –RBC: 5-7x10 12 /L –Hb:150 to 230g/L. Postnatal fall /physiology anemia Infancy  Preschool age: –RBC: 4 x 10 12 /L –Hb: 110 g/L 7-12yr: adult level

18. 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

19. 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

20. 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

21. Table3. HEMOGLOBINS HbChains 8周8周 6月6月出生 6-12 月 2岁2岁 EmbryGower1ζ2ε2ζ2ε2 8 周前， 3 月消 失 Gower2α2ε2α2ε2 Portlandζ2γ2ζ2γ2 FetalHbFα2γ2α2γ2 增加 90%70%<5%<2% AdultHbAα2β2α2β2 5-10%30%>95% HbA 2 α2δ2α2δ2 <1%2-3%<3.5%

22. WBC Counts At birth: 20 x 10 9 /L Infant: 12 x 10 9 /L Preschool: 8.0 x 10 9 /L

23. (%)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

24. PLT & Blood Volume PLT: 150-250 x 10 9 /L Blood Volume: –Term newborn: 85ml/kg –Premature infant: 95ml/kg –Adult: 75ml/kg –Young children: 75-80ml/kg

25. The Introduction of ANEMIA

26. Definition of Anemia a reduction of the red blood cell volume or hemoglobin concentration below the range of values occurring in healthy persons

27. Table 4. The definition of Anemia and Degree AgeAnemia ValuesAnemia Degree Newborn< 145g/L 1-4 mo< 90g/LMild: -90g/L 4-6 mo< 100g/LModerate: -60g/L 6 mo-6 yr< 110g/LSevere: -30g/L 6-14 yr< 120g/LExtremely severe:< 30g/L

28. 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.

29. Fig5:The oxygen dissociation curve

30. 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

31. 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

32. Classification- etiology Reduced capacity to produce RBC –Aplastic anemia –Bone marrow failure –Deficiency syndromes Hemolysis Blood Loss

33. 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

34. Classification- etiology Reduced capacity to produce RBC –Marrow Infiltration Leukemia Lymphoma Neuroblastom LCH

35. Classification-etiology Reduced capacity to produce RBC –Deficiency Syndrome Iron Folate Vitamin B 12 Vitamin E Vitamin B 6

36. Classification-etiology Hemolysis –Iintrinsic RBC abnormalities Hemoglobinopathies Enzymopathies Membrane disorders –extrinsic RBC abnormalities Immunologic: AIHA

37. Classification-etiology Hemolysis:intrinsic RBC abnormalities –Intrinsic membrane defects Hereditary Spherocytosis:Hereditary Spherocytosis –Hemoglobinopathy Thalassemia –RBC enzyme defects G6PD defect

38. Classification-etiology Hemolysis:extrinsic RBC abnormalities –Immunologic hemolysis Isoimmune (Rh, ABO in neonate) Autoimmune Hemolytic Anemia (AIHA)

39. Classification-etiology Blood loss –Gastrointestinal bleeding Ankylostomiasis –Menstrual –Trauma

41. 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

42. RBC Index MCV –Mean corpuscular volume MCH –Mean corpuscular hemoglobin MCHC –Mean corpuscular concertration