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Childhood hematopoiesis and hematological features
Yongmin TangDept. Hematology-oncology
Chidlren’s HospitalZhejiang University School of medicine
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?
• Hematopoietic Stem Cells (HSC), CD34 is the marker of HSCs.
5 um
• All the daughter blood cells are derived from the HSCs.
Early development of the fertilized egg.
Development of hematopoietic stem cells
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
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
Hematopoisis during fetal development
Islet of Yolk Sac In liver In BM
Migration of HSCs
liver BM
HSC
Mesoblastic Hepatic Madullary
0
2
4
6
8
10
12
yal k sac l i ver BM
(Wks )
Dynamic changes of hematopoiesis
during fetal development
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:
Comparisons of hematopoietic locations between preschool children
and adults
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
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)
Dynamic changes of RBC during infancy
Age
RB
C c
oun
ts (
x 1
012/L
)
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.
0 - 3d 4~7d 4~6wk after 5mon
4 ~ 6% 0.5~1.5% 2~8% 0.5~1.5%
Reticulocytes :
Molecular structure of hemoglobin
Types and proportions of hemoglobin during embryo, fetus and infancy stages
Different proportions of Hb during infancy and early young children
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%
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:
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
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
Important nutritional components for erythropoiesis
• Iron
• Vitamin 12
• Folic acid
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.
Anemic pale
RBCs of IDA
Blood smear(2):
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.
Pathogenesis of nutritional megaloblastic anemia
5-MythotetrahydroxylFolic acid Vit B12 + Vit C
DNA synthesis
Megaloblasts
Fragile
Invalid hematopoiesis
Uridine
dThymidine4H-FA2H-FA
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.
Hyperfragmented neutrophil
Clinical relevant cytokines or hormones associated with hematopoiesis
• EPO
• G-CSF
• GM-CSF
• IL-11
• TPO
Clinical Application of CD34+ cells
• CD34 as marker of HSC or HPC for quantitation
• 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
Thank you for attention !