childhood hematopoiesis and hematological features
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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 ? - PowerPoint PPT PresentationTRANSCRIPT
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Childhood hematopoiesis and hematological features
Yongmin TangDept. Hematology-oncology
Chidlren’s HospitalZhejiang University School of medicine
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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?
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• Hematopoietic Stem Cells (HSC), CD34 is the marker of HSCs.
5 um
• All the daughter blood cells are derived from the HSCs.
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Early development of the fertilized egg.
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Development of hematopoietic stem cells
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PLURIPOTENT STEM CELL CD34+CD38- HPP-CFU, LTC-IC,CFU-BL
MYELOID STEM CELLCD34+CD38-CD33+CD13+
LYMPHOIDSTEM CELLTdT+CD34+
BFU-MKCD34+CD61+/-
BFU-ECD71+CD36+/-
CFU-GMCD34+CD33+
CFU-M CFU-G
CD19+T PROGENITOR CD7+
TOTIPOTENT STEM CELL
T4T8
CFU-ECD71+CD36+
CFU-MKCD61+
SELF-RENEWAL
B CELL
B PROGENITOR
HEMATOPOIESIS
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The features of hematopoiesis in children
HEMATOPOIESIS DURING FETAL DEVELOPMENT
HEMATOPOIESIS AFTER BIRTH
3. Medullary hematopoiesis: 4th-5th months
2. Hepatic hematpoiesis: 2nd - 6th months
1. Mesoblastic hematopoiesis: 3rd – 6th wks
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Hematopoisis during fetal development
Islet of Yolk Sac In liver In BM
Migration of HSCs
liver BM
HSC
Mesoblastic Hepatic Madullary
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0
2
4
6
8
10
12
yal k sac l i ver BM
(Wks )
Dynamic changes of hematopoiesis
during fetal development
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hepatosplenomegaly with circulating nucleated erythrocytes in the blood stream
HEMAYOPOIESIS AFTER BIRTH
1. Medullary hematopoiesis:
“ red marrow”
“yellow marrow”
When needed: Yellow marrow red marrow hematopoiesis compensation
2. Extramedullary hematopoiesis:
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Comparisons of hematopoietic locations between preschool children
and adults
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Blood pictures in children (1)
Juxtaglomerular apparatus
A. RBC
----->EPO------> RBC
Fetal stage: RBC 5 ~ 7 x 1012/L
Hb 150 ~ 220g/L
Afferent arteriole of glomerulus Efferent arteriole
of glomerulus
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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)
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Dynamic changes of RBC during infancy
Age
RB
C c
oun
ts (
x 1
012/L
)
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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.
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0 - 3d 4~7d 4~6wk after 5mon
4 ~ 6% 0.5~1.5% 2~8% 0.5~1.5%
Reticulocytes :
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Molecular structure of hemoglobin
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Types and proportions of hemoglobin during embryo, fetus and infancy stages
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Different proportions of Hb during infancy and early young children
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Blood pictures in children (2)
fetal 6 M at birth 1yr 2 yr adults
HbF (22) 90% 70% < 5% < 2% < 2%
HbA (22) 5~10% 30% 93% 95% 95%
HbA2 (22) < 1% 2~3%
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Dynamic changes of WBC during childhood period
(x 109/L) at birth 6~12h day7 infant > 8yrs
15~20 21~28 12 10 4~8
B. White blood cell count and differential count:
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DC (%) at birth 4~6d d7~ 4yrs 4 ~ 6 yrs 7 yrsN L N L N L N L N L65 35 50 50 35 65 50 50 as adult
(%)80
605040
20
0
Neutrophils
Lymphocytes
Age
Blood pictures in children (3)
4 ~ 6yrs4 ~ 6 d
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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
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Important nutritional components for erythropoiesis
• Iron
• Vitamin 12
• Folic acid
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Features of iron metabolism in children
• Iron store:
• Factors affecting fetal iron store:
• Mechanism of iron supply in fetus: restricted
premature, severe maternal iron deficiency, intra-uterus transfusion etc.
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Anemic pale
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RBCs of IDA
Blood smear(2):
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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.
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Pathogenesis of nutritional megaloblastic anemia
5-MythotetrahydroxylFolic acid Vit B12 + Vit C
DNA synthesis
Megaloblasts
Fragile
Invalid hematopoiesis
Uridine
dThymidine4H-FA2H-FA
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Lipid Metabolites: Methyl Malonic acid Succinic Acid Citric Cycle Vit B12
Pathogenesis of Vit B12 induced nervous system manifestation
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.
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Hyperfragmented neutrophil
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Clinical relevant cytokines or hormones associated with hematopoiesis
• EPO
• G-CSF
• GM-CSF
• IL-11
• TPO
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Clinical Application of CD34+ cells
• CD34 as marker of HSC or HPC for quantitation
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• Selection of the stem cell sources for transplantation (BM, PBSC, Cord blood)
• Positive selection of the CD34+ cells for tumor purging
• Gene therapy
Clinical Application of CD34+ cells
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Thank you for attention !