Childhood hematopoiesis and hematological features. Yongmin Tang Dept. Hematology-oncology Chidlren s Hospital Zhejiang University School of medicine
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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 TOTIPOTENT STEM CELL HEMATOPOIESIS SELF-RENEWAL PLURIPOTENT STEM CELL CD34+CD38- HPP-CFU, LTC-IC,CFU-BL BFU-MK CD34+ CD61+/- MYELOID STEM CELL CD34+CD38- CD33+CD13+ CFU-GM CD34+CD33+ LYMPHOID STEM CELL TdT+CD34+ BFU-E CD71+ CD36+/- T PROGENITOR CD7+ B PROGENITOR CD19+ CFU-MK CD61+ CFU-E CD71+ CD36+ CFU-M CFU-G T4 T8 B CELL
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 Islet of Yolk Sac In liver In BM Mesoblastic Hepatic Madullary liver BM HSC Migration of HSCs
9 Dynamic changes of hematopoiesis during fetal development yalk sac liver BM (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 A. RBC Afferent arteriole of glomerulus Blood pictures in children (1) Efferent arteriole of glomerulus -----> EPO------> RBC Juxtaglomerular apparatus Fetal stage: RBC 5 ~ 7 x /L Hb 150 ~ 220g/L
13 Dynamic changes of RBC during infancy RBC counts ( x /L) Age
14 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 x10 12 /L Hb 100 g/l (self-limited, recovers within 6 months)
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
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19 Types and proportions of hemoglobin during embryo, fetus and infancy stages
20 Blood pictures in children (2) fetal 6 M at birth 1yr 2 yr adults HbF (α2γ2) 90% 70% < 5% < 2% < 2% HbA (α2β2) 5~10% 30% 93% 95% 95% HbA2 (α2δ2) < 1% 2~3%
21 Dynamic changes of WBC during childhood period B. White blood cell count and differential count: (x 10 9 /L) at birth 6~12h day7 infant > 8yrs 15~20 21~ ~8
22 Blood pictures in children (3) DC (%) at birth 4~6d d7~ 4yrs 4 ~ 6 yrs 7 yrs N L N L N L N L N L as adult (%) Neutrophils Lymphocytes 0 Age 4 ~ 6 d 4 ~ 6yrs
23 Blood picture in children (4) Platelets: normal 100 ~ 300 x10 9 /L Total blood volume: Newborn: 10% of body weight Childhood: 8 ~ 10% of BW Adults: 6 ~ 8% of BW
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35 Important nutritional components for erythropoiesis Iron Vitamin 12 Folic acid
36 Features of iron metabolism in Iron store: children Mechanism of iron supply in fetus: restricted Factors affecting fetal iron store: premature, severe maternal iron deficiency, intra-uterus transfusion etc.
37 Anemic pale
38 Blood smear(2): RBCs of IDA
39 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.
40 Pathogenesis of nutritional megaloblastic anemia 5-Mythotetrahydroxyl Folic acid Vit B 12 + Vit C 2H-FA 4H-FA Uridine dthymidine DNA synthesis Megaloblasts Fragile Invalid hematopoiesis
41 Pathogenesis of Vit B12 induced nervous system manifestation Lipid Metabolites: Methyl Malonic acid Succinic Acid Citric Cycle Vit B 12 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.
42 Hyperfragmented neutrophil
43 Clinical relevant cytokines or hormones associated with hematopoiesis EPO G-CSF GM-CSF IL-11 TPO
44 Clinical Application of CD34 + cells CD34 as marker of HSC or HPC for quantitation
45 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
46 Thank you for attention!
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