Childhood hematopoiesis and hematological features

Yongmin TangDept. Hematology-oncology

Chidlren’s HospitalZhejiang University School of medicine

E-mail: y_m_tang@zju.edu.cn

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

Early development of the fertilized egg.

Development of hematopoietic stem cellsp p

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.

R ti l tReticulocytes：

0－3d 4~7d 4~6wk after 5mon

4 ~ 6% 0.5~1.5% 2~8% 0.5~1.5%

Molecular structure of hemoglobinMolecular structure of hemoglobin

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

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.

Anemic paleAnemic pale

Blood smear(2):Blood smear(2):

RBCs of IDA

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.

Hyperfragmented neutrophil

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

• CD34 as marker of HSC or HPC for quantitation

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

Thank you for attention !y