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Childhood hematopoiesis and hematological features

Childhood hematopoiesis and hematological features. Yongmin Tang Dept. Hematology-oncology Chidlren’s Hospital Zhejiang University School of medicine. Questions: How much have you known about our hematopoietic system?. What components does our blood system consist of ?

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Childhood hematopoiesis and hematological features

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  1. Childhood hematopoiesis and hematological features Yongmin Tang Dept. Hematology-oncology Chidlren’s Hospital Zhejiang University School of medicine

  2. Questions:How much have you known about our hematopoietic system? • What components does our blood system consist of ? • What do you think the blood components are derived from? • What functions does our hematopoietic system undertake? • What is the main organ that the hematopoiesis occurs in elderly children and adults? Why? • Is hematopoiesis in children different from that in adults?

  3. Hematopoietic Stem Cells (HSC), CD34 is the marker of HSCs. • All the daughter blood cells are derived from the HSCs. 5 um

  4. Early development of the fertilized egg.

  5. Development of hematopoietic stem cells

  6. HEMATOPOIESIS TOTIPOTENT STEM CELL PLURIPOTENT STEM CELL CD34+CD38- HPP-CFU, LTC-IC,CFU-BL SELF-RENEWAL MYELOID STEM CELL CD34+CD38- CD33+CD13+ BFU-MK CD34+ CD61+/- LYMPHOID STEM CELL TdT+CD34+ CFU-GM CD34+CD33+ B PROGENITOR BFU-E CD71+ CD36+/- CD19+ T PROGENITOR CD7+ CFU-MK CD61+ CFU-E CD71+ CD36+ B CELL T8 CFU-M CFU-G T4

  7. The features of hematopoiesis in children HEMATOPOIESIS DURING FETAL DEVELOPMENT 1. Mesoblastic hematopoiesis: 3rd – 6th wks 2. Hepatic hematpoiesis: 2nd - 6th months 3. Medullary hematopoiesis: 4th-5th months HEMATOPOIESIS AFTER BIRTH

  8. Hematopoisis during fetal development In liver Islet of Yolk Sac In BM MesoblasticHepatic Madullary liver BM HSC Migration of HSCs

  9. Dynamic changes of hematopoiesis during fetal development (Wks）

  10. HEMAYOPOIESIS AFTER BIRTH 1. Medullary hematopoiesis: “red marrow” “yellow marrow” When needed:Yellow marrow red marrow hematopoiesis compensation 2. Extramedullary hematopoiesis: hepatosplenomegaly with circulating nucleated erythrocytes in the blood stream

  11. Comparisons of hematopoietic locations between preschool children and adults

  12. Blood pictures in children (1) A. RBC Afferent arteriole of glomerulus Efferent arteriole of glomerulus ----->EPO------>RBC Juxtaglomerular apparatus Fetal stage: RBC 5 ~ 7 x 1012/L Hb 150 ~ 220g/L

  13. Blood pictures in children (2) Physiological hemolysis: circulating nucleated RBC with elevated reticulocytes (stopping lysing within 1wk) Physiological anemia: infant 2-3 months RBC 3 x1012/L Hb 100 g/L (self-limited, recovers within 6 months)

  14. Dynamic changes of RBC during infancy RBC counts ( x 1012/L) Age

  15. Low limits of Hb in different age groups Newborns 145 g/L 1～4m 90 g/L 4～6m 100 g/L 6m～6y 110 g/L 6y～14y 120 g/L • 4% of increase per 1000 meter above sea level.

  16. Reticulocytes： 0－3d 4~7d 4~6wk after 5mon 4 ~ 6% 0.5~1.5% 2~8% 0.5~1.5%

  17. Molecular structure of hemoglobin

  18. Types and proportions of hemoglobin during embryo, fetus and infancy stages

  19. Different proportions of Hb during infancy and early young children

  20. Blood pictures in children (2) fetal 6 M at birth 1yr 2 yradults HbF (22) 90% 70% < 5% < 2% < 2% HbA (22) 5~10% 30% 93% 95% 95% HbA2 (22) < 1% 2~3%

  21. Dynamic changes of WBC during childhood period B. White blood cell count and differential count: (x 109/L) at birth 6~12hday7infant > 8yrs 15~20 21~28 12 10 4~8

  22. Blood pictures in children (3) DC (%) at birth 4~6dd7~ 4yrs 4 ~ 6 yrs 7 yrs N L N L N L N L N L 65 35 50 50 35 65 50 50 as adult (%) 80 60 50 40 20 0 Neutrophils Lymphocytes Age 4 ~ 6 d 4 ~ 6yrs

  23. Blood picture in children (4) • Platelets: normal 100 ~ 300 x109/L • Total blood volume: Newborn: 10% of body weight Childhood: 8 ~ 10% of BW Adults: 6 ~ 8% of BW

  24. Important nutritional components for erythropoiesis • Iron • Vitamin 12 • Folic acid

  25. Features of iron metabolism in children • Iron store: • Mechanism of iron supply in fetus: restricted • Factors affecting fetal iron store: premature, severe maternal iron deficiency, intra-uterus transfusion etc.

  26. Anemic pale

  27. Blood smear(2): RBCs of IDA

  28. Metabolism of Vit B12 and Folic acid • Folic acid: food: rich in green vegetible, lack in sheep milk ; Absorptive site: at upper portion of jejunum; • Vitamin B12: • Food: rich in animal derived food; • Absorptive site:terminus of ileum; • Absorption helping factor: internal factor.

  29. Pathogenesis of nutritional megaloblastic anemia Uridine dThymidine 5-Mythotetrahydroxyl Folic acid Vit B12 + Vit C 2H-FA 4H-FA DNA synthesis Megaloblasts Fragile Invalid hematopoiesis

  30. Pathogenesis of Vit B12 induced nervous system manifestation Lipid Metabolites: Methyl Malonic acid Succinic AcidCitric Cycle Vit B12 Vit B12: associated with the formation of nerve sheath lipoprotein to maintain the integrated function of CNS and peripheral nerve fibers. Vit B12 deficiency：degeneration of peripheral nerve,combined subacute degeneration of spinal cord and damage to the brain.

  31. Hyperfragmented neutrophil

  32. Clinical relevant cytokines or hormones associated with hematopoiesis • EPO • G-CSF • GM-CSF • IL-11 • TPO

  33. Clinical Application of CD34+ cells • CD34 as marker of HSC or HPC for quantitation

  34. Clinical Application of CD34+ cells • Selection of the stem cell sources for transplantation (BM, PBSC, Cord blood) • Positive selection of the CD34+ cells for tumor purging • Gene therapy

  35. Thank you for attention !

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