Development of the Hematopoietic System & the Introduction of Anemia

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. 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

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

13. Fig1.Hematopoisis

15. Blood Cell Counts and Hemoglobin

16. Fig2. Peripheral Blood Cells

17. 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

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. 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% Table3. HEMOGLOBINS

22. WBC Counts • At birth: 20 x 109/L • Infant: 12 x 109/L • Preschool: 8.0 x 109/L

23. Fig4. WBC Ratio (%)70 淋巴细胞 60 50 40 30 20 10 4-6天 4-6岁 中性粒细胞 1 3 5 7 9 日数 1 3 5 7 9 11 岁数

24. 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

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. 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 Table 4. The definition of Anemia and Degree

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. 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 B12 • Vitamin E • Vitamin B6

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

37. Classification-etiology • Hemolysis:intrinsic RBC abnormalities • Intrinsic membrane defects • 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

40. Mount Raniner, Seattle

41. 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 Hematopoiesis Regulation Related terms

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