This document discusses haemopoiesis, the development of blood cells. It describes the three main sites of haemopoiesis - the yolk sac, liver, and bone marrow. It focuses on erythropoiesis, the formation of red blood cells, outlining the stages from pronormoblast to reticulocyte to erythrocyte. Key regulators of erythropoiesis discussed are erythropoietin, growth factors, hormones, and nutritional factors like iron, vitamin B12, and folic acid.

1. HAEMOPOIESIS
•Development of blood cells
•Erythropoiesis – RBCs
(Process of formation and maturation of RBCs )
•Leucopoesis – WBCs
•Megakaryopoesis- Platelets

2. Sites of haemopoiesis
1.Intrauterine life : 3 stages
A) Mesoblastic
stage :
up to 3 week of foetal life Mesoderm of the yolk
sac
B) Hepatic stage : From 3 rd week –to 6m Liver, spleen
C) Myeloid stage : From 6 mths – full term Red Bone Marrow
2) In children : Upto 6yrs marrow of all bones
3) In Adults :
Upto 20yrs long bones ,vertebrae,
skull ,Ribs, Sternum, ilia
After 20yrs: Upper ends of long
bones, vertebrae, ribs,
sternum, ilia

3. Bone Marrow
The bone marrow - one of the most active organs
Active BM: red marrow- cells at different stages of
development…
Inactive BM infiltrated with fat: yellow marrow
• BM is aspirated from iliac bone/sternum….properly
stained…examined under microscope..
• Indications: anemia..leukemia, lymphoma, pancytopenia

4. BFU-E
HEMOPOESIS

5. Bone Marrow….
• 75% of the cells in the marrow belong to the myeloid
series ( for WBC & Platelets)
• Only 25% - red cells.
• Normal myeloid- erythroid ratio is 3:1
• In circulation RBC count is 500 times more than WBC
count…because of longer life span of RBCs…

6. PPSC → COMMITTED STEM CELLS
BFU -E
↓
CFU – E
↓
PROERYTHROBLAST
↓
EARLY NORMOBLAST
↓
INTERMEDIATE NORMOBLAST
↓
LATE NORMOBLAST
↓
RETICULOCYTE
↓
ERYTHROCYTE
Stages Of Erythropoesis

7. Proerythroblast / Pronormoblast
• First identifiable cell of erythroid series
• Cell size – 15- 20 micrometer
• Nucleus occupies 3/4TH of cell volume with multiple nucleoli
• Chromatin threads present
• Cytoplasm – basophilic (high concentration of polyribosomes)
• Mitosis – present
• Hb – absent

8. Early Normoblast /Basophilic Normoblast
• 14 – 16 micrometer
• Nucleus size – decrease –nucleoli absent
• Chromatin condensation present
• Cytoplasm – basophilic
• Mitosis – present
• Hb – absent

9. Intermediate Normoblast
(Polychromatophilic normoblast )
• Cell size – decrease – 10 – 14 micrometer
• Nucleus size – decrease
• Hb – starts appearing
• Cytoplasm –Polychromatophilic
• – bluish and pinkish (basophilic RNA & acidophilic Hb)
• Mitosis – present

10. Late Normoblast/Orthochromatic Normoblast
• 8 – 10 micrometer
• Eccentric cart wheel nucleus
• Pyknotic degeneration- clumping of the chromosomes,
shrinking of the nucleus.
• Cytoplasm - reddish (Acidophilic)
• No mitosis
• Hb – present
• Nucleus is extruded out later

11. Reticulocyte
• Cell size decrease 7 – 8 micrometer
• Nucleus absent
• RNA appears as a reticulum on Supravital Staining (with
Brilliant Cresyl Blue)
• Hb increased
• Reticulocyte spends 1-2 days in bone marrow and 1-2 days in
the peripheral blood..spleen ..matures into biconcave RBC
• Mitochondria, ribosomes etc are lost when converted to
RBCs…so RBC cannot synthesize proteins..

12. Reticulocyte…..
•Normal count:
In infants: 2-6% of RBC count
Adult - 0.5 to 1% of RBC count
Reticulocytosis
• Physiological – at birth, infants ,high altitude
• Pathological – hemolytic anemia
• Reticulocytopenia – Aplastic anemia

13. Erythrocyte
• Cell size – 7.2- 7.5 micrometer
• Absence of RNA material, no organelles
• One Pronormoblast give rise to at least 8-10 RBCs
• 2 million RBCs produced each sec
• Average duration of Erythropoiesis: 7 to 9 days
Proerythroblast to reticulocyte takes 5 to 7 days
Maturation of reticulocyte to RBC takes 2 days..
• Life span = 120days

15. Factors Affecting Erythropoesis
General factors
- Hypoxia  Erythropoietin
- Growth inducers
- Hormones
Maturation factors
- Iron, Vitamin B 12,Folic acid
Factors necessary for hemoglobin production
- Vitamin C Helps in iron absorption (Fe3+  Fe2+)
- Proteins  Amino Acids for globin synthesis
- Iron, copper, cobalt & nickel Heme synthesis

16. 1.ERYTHROPOETIN ( EPO)
• Glycoprotein.
Formation
• 85% formed in endothelial cells of the
peritubular capillaries of the renal
tubules.
• 15% formed in liver
Breakdown
 In liver. Half life is 5 hours
PTC

17. Renal tissue hypoxia

tissue levels of Hypoxia-inducible Factor-1 (HIF-1),

HIF-1 binds to a hypoxia response element in the
Erythropoietin gene,

Transcription of messenger RNA and,

increased Erythropoietin synthesis

18. Stimuli increasing EPO
Hypoxia is the potent stimulus
High altitude
Anemia
Chronic lung or heart diseases
Catecholamines
Androgens
•Decreased by
Estrogen

19. Functions of EPO
Erythropoietin increases RBC production -
• Stimulates stem cells towards erythroid series
• Promotes pronormoblast production from progenitor cells
• Enhances mitosis
• Accelerates Hb synthesis
• Promotes the early release of reticulocytes.
Applied – EPO injections in treatment of anemia in renal
failure

20. 2.Growth inducers/ Differentiation inducers
• Interleukin 1, 3, 5 (IL-3 is a growth inducer for all cell lines )
Acts on stem cells to convert them to progenitor cells
• Colony stimulating factors – produced from T cells,
endothelial cells, fibroblasts stimulates production of
committed stem cells .
3. Hormones
•Androgens  & Estrogen  Erythropoesis
•. Thyroxine , GH, Cortisol –stimulates Erythropoesis

21. Maturation factors
Role of iron ,folic acid & vitamin B12.
• Iron- needed for Hb synthesis
• Folic acid & Vit B12- required for the synthesis of DNA and
maturation of nucleus and cell.
• Milk ,meat ,liver ,Green leafy vegetables
 If deficiency occurs… failure of maturation of nucleus.
 There occurs reduction in the cell division.
Cells remain large (megaloblasts) and become more
fragile.
• Intrinsic factor – needed for Vit B12 absorption

22. Other dietary factors
•Vitamin C Helps in iron absorption (Fe3+ 
Fe2+)
•Proteins  Amino Acids for globin synthesis
•Copper, cobalt & nickel.  Heme synthesis
(Copper- incorporation of Fe into Porphyrin Ring )