childhood hematopoiesis and hematological...
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Childhood hematopoiesis and hematological features
Yongmin TangDept. Hematology-oncology
Chidlren’s HospitalZhejiang University School of medicine
E-mail: [email protected]
Questions: How much have you known Q yabout our hematopoietic system?
• What components does our blood system consist of ?consist of ?
• What do you think the blood components are derived from?derived from?
• What functions does our hematopoietic system undertake?undertake?
• What is the main organ that the hematopoiesis occurs in elderly children and adults? Why?occurs in elderly children and adults? Why?
• Is hematopoiesis in children different from that in adults?in adults?
H t i ti St C ll (HSC) CD34 i• Hematopoietic Stem Cells (HSC), CD34 is the marker of HSCs. • All the daughter blood cells are derived from the HSCs.from the HSCs.
5 um
TOTIPOTENT STEM CELL HEMATOPOIESIS
PLURIPOTENT STEM CELLCD34+CD38-HPP-CFU, LTC-IC,CFU-BL
SELF-RENEWAL
MYELOID STEM CELLCD34+CD38-CD33+CD13+
LYMPHOIDSTEM CELLTdT+CD34+
BFU-MKCD34+CD61+/-
CFU-GMCD34+CD33+
BFU-ECD71+CD36+/-
CD19+T PROGENITORCD7+
B PROGENITOR
CD36 /
CFU-MKCD61+
CFU-M CFU-G T4T8
CFU-ECD71+CD36+
B CELL
The features of hematopoiesis in childrenThe features of hematopoiesis in children
HEMATOPOIESIS DURING FETAL DEVELOPMENT
2 H ti h t i i : 2 d 6th th
1. Mesoblastic hematopoiesis: 3rd – 6th wks
3. Medullary hematopoiesis: 4th-5th months
2. Hepatic hematpoiesis: 2nd - 6th months
HEMATOPOIESIS AFTER BIRTHHEMATOPOIESIS AFTER BIRTH
Hematopoisis during fetal developmentHematopoisis during fetal development
Islet of Yolk Sac In liver In BMIslet of Yolk Sac In liver In BM
Mesoblastic Hepatic Madullary
liver BM
Migration of HSCsHSC
Dynamic changes of hematopoiesisDynamic changes of hematopoiesis during fetal development
yalk sac liver BM
10
12
6
8
10
2
4
6
0
1 3 5 7 9 1 1 1 3 1 5 1 7 1 9 2 1 2 3 2 5 2 7 2 9 3 1 3 3 3 5 3 7 3 9 (Wks)1 1 1 1 1 2 2 2 2 2 3 3 3 3 3 ( )
HEMAYOPOIESIS AFTER BIRTHHEMAYOPOIESIS AFTER BIRTH
1. Medullary hematopoiesis:
“red marrow”
ll“yellow marrow”
When needed: Yellow marrow red marrowWhen needed: Yellow marrow red marrow hematopoiesis compensation
2. Extramedullary hematopoiesis:
hepatosplenomegaly with circulating nucleated erythrocytes in the blood stream
Comparisons of hematopoietic locations between preschool childrenlocations between preschool children
and adults
Blood pictures in children (1)A RBCA. RBC
Afferent arteriole of glomerulus Efferent arteriole
of glomerulus
----->EPO------> RBC
Juxtaglomerular apparatus
Fetal stage: RBC 5 7 1012/LFetal stage: RBC 5 ~ 7 x 1012/LHb 150 ~ 220g/L
D namic changes of RBC d ring infancDynamic changes of RBC during infancy10
12/L
)nt
s ( x
1B
C c
oun
RB
Age
Blood pictures in children (2)
Physiological hemolysis:
circulating nucleated RBC with elevated reticulocytes
(stopping lysing within 1wk)( pp g y g )
Physiological anemia:infant 2-3 months
RBC 3 1012/LRBC 3 x1012/L
Hb 100 g/L
(self-limited, recovers within 6 months)within 6 months)
L li it f HbLow limits of Hb in different age groupsg g p
Newborns 145 g/LNewborns 145 g/L1~4m 90 g/L 4~6m 100 g/L6m~6y 110 g/L6y~14y 120 g/L
• 4% of increase per 1000 meter above sea level.
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%HbA (α2β2) 5~10% 30% 93% 95% 95%
HbA2 (α2δ2) < 1% 2~3%
Dynamic changes of WBC during childhood period
(x 109/L) at birth 6 12h day7 infant > 8yrs
B. White blood cell count and differential count:
(x 109/L) at birth 6~12h day7 infant > 8yrs
15~20 21~28 12 10 4~8
Blood pictures in children (3)Blood pictures in children (3)
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
Neutrophils
L h40
20
0
Lymphocytes
0
Age 4 ~ 6yrs4 ~ 6 d
Blood picture in children (4)
• Platelets: normal 100 ~ 300 x109/L
• Total blood volume:• Total blood volume: Newborn: 10% of body weightChildhood: 8 ~ 10% of BWAd lt 6 8% f BWAdults: 6 ~ 8% of BW
Important nutritional componentsImportant nutritional components for erythropoiesisy p
• Iron• Vitamin 12• Vitamin 12• Folic acid
Features of iron metabolism inFeatures of iron metabolism in childrenchildren
• Iron store:Iron store:
• Mechanism of iron supply in fetus: restricted
• Factors affecting fetal iron store:
Mechanism of iron supply in fetus: restricted
• Factors affecting fetal iron store:premature, severe maternal iron deficiency, i f iintra-uterus transfusion etc.
M b li f Vi B12 d F li idMetabolism of Vit B12 and Folic acid
• Folic acid:food: rich in green vegetible lack in sheep milk ;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;Absorptive site: terminus of ileum;
Absorption helping factor: internal factor.
Pathogenesis of n tritionalPathogenesis of nutritional megaloblastic anemia
5-MythotetrahydroxylFolic acid
Uridine
Folic acidVit B12 + Vit C
dThymidine
DNA synthesis
y4H-FA2H-FA
y
Megaloblasts
Fragile
Invalid hematopoiesis
Pathogenesis of Vit B12Pathogenesis of Vit B12 induced nervous system manifestation
Lipid Metabolites:Methyl Malonic acid Succinic Acid Citric 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.
Clinical relevant cytokines or hormonesClinical relevant cytokines or hormones associated with hematopoiesis
• EPO• G-CSF• GM CSF• GM-CSF• IL-11• TPO
Clinical Application of CD34+ cells
• Selection of the stem cell sources for Selection of the stem cell sources for transplantation (BM, PBSC, Cord blood)
• Positive selection of the CD34+ cells for t itumor purging
• Gene therapy