OBJECTIVES

TO GET BETTER UNDERSTANDING OF :

Definition of erythropoiesis
Stages of erythropoiesis
Description of various cell stages
Duration of erythropoiesis
Factors affecting erythropoiesis
Description of erythropoietin
 FORMATION OF RBC
DEFINITION
Erythropoiesis is the process of the origin, development and
maturation of erythrocytes. Hemopoiesis or hematopoiesisis the
process of origin, development and maturation of all the blood cells.
STAGES IN FETAL LIFE
1. Mesoblastic Stage
2. Hepatic Stage
3. Myeloid Stage
 STAGES IN ERYTHROPOISIS FETAL LIFE
1.MESOBLASTIC STAGE
During the first two months of intrauterine life, the RBCs
are produced from mesenchyme of yolk sac.

2.HEPATIC STAGE
From third month of intrauterine life, liver is the main
organ that produces RBCs. Spleen and lymphoid
organs are also involved in erythropoiesis.

3.MYELOID STAGE
During the last three months of intrauterine life, the RBCs
PHASES IN FORMATION OF
BLOOD CELLS
IN NEWBORN BABIES, CHILDREN AND ADULTS

In newborn babies, growing childrens and adults, RBCs are produced only from the
red bone marrow.
1. UPTO THE AGE OF 20 YEARS:- RBCs are produced from red bone marrow of all
bones (long bones and all the flat bones).
2. AFTER THE AGE OF 20 YEARS:- RBCs are produced from membranous bones like
vertebra, sternum, ribs, scapula, iliac bones and skull bones and from the ends of
long bones. After 20 years of age, the shaft of the long bones becomes yellow bone
marrow because of fat deposition and looses the erythropoietic function.
• In adults, liver and spleen may produce the blood cells if the bone marrow is
destroyed or fibrosed.
• Collectively bone marrow is almost equal to liver in size and weight.
• It is also as active as liver.
• Though bone marrow is the site of production of all blood cells, comparatively
75% of the bone marrow is involved in the production of leukocytes and only
25% is involved in the production of erythrocytes.

• But still, the leukocytes are less in number than the erythrocytes, the ratio being
1:500.
• This is mainly because of the lifespan of these cells.
• Lifespan of erythrocytes is 120 days whereas the lifespan of leukocytes is very
short ranging from one to ten days.
• So the leukocytes need larger production than erythrocytes to maintain the
required number.
RED BONE MARROW YELLOW BONE MARROW
Red color Yellow color
Consists mainly of hematopoietic Yellow marrow is found in
tissue blood making. medullary cavity
Found in flat bones (pelvis, Mainly fat cells
sternum, cranium, ribs, scapula), During aging red marrow is
epiphyses of long bones. replaced by yellow
Produces red blood cells, white In case of severe blood loss the
blood cells and platelets. body can convert the yellow
marrow back to red
 PROCESS OF ERYTHROPOIESIS
There are four major cell stages
• Stem cells Lymphoid stem cells
• Committed PHSCs
• CFU-E Colony forming blastocytes
1. Proerythroblast
2. Early normoblast CFU-E CFU-M
3. Intermediate normoblast CFU-GM
4. Late normoblast
5. Reticulocyte
6. Matured erythrocyte
 STEM CELLS
Pluripotent stem cells are the mother stem cells that form stem cells
for different cell lines.
It possess two fundamental properties:
Self replication – they are capable of giving rise to more stem cells.
Differentiation – they have the ability to differentiate into specialized
cells are called progenitor cells.
• Hemopoietic stem cells in the bone marrow are called uncommitted pluripotent
hemopoietic stem cells (PHSC).
• PHSC is defined as a cell that can give rise to all types of blood cells.
• In early stages, the PHSC are not designed to form a particular type of blood cell.
• It is also not possible to determine the blood cell to be developed from these
cells. hence they are known as uncommitted PHSCs
• In adults, only a few number of these cells are present. But the best source of
these cells is the umbilical cord blood.
 Committed PHSCs are of two
types:
1. Lymphoid stem cells (LSC) which give rise to lymphocytes and
natural killer (NK) cells
2. Colony forming blastocytes, which give rise to myeloid cells.
Myeloid cells are the blood cells other than lymphocytes. When grown
in cultures, these cells form colonies hence the name colony forming
blastocytes.
Different units of colony
forming cells are:
i. Colony forming unit-erythrocytes (CFU-E) Cells of this unit develop
into erythrocytes
ii. Colony forming unit-granulocytes/monocytes (CFU-GM) – These
cells give rise to granulocytes (neutrophils, basophils and eosinophils)
and monocytes
iii. Colony forming unit-megakaryocytes (CFU-M) Platelets are
developed from these cells.
 CHANGES DURING
ERYTHROPOIESIS
• Cells of CFU-E pass through different stages and finally become the matured
RBCs.
• During these stages four important changes are noticed.
1. Reduction in size of the cell (from the diameter of 25
to 7.2 µ)
2. Disappearance of nucleoli and nucleus.
3. Appearance of hemoglobin.
4. Change in the staining properties of the cytoplasm.
 STAGES OF ERYTHROPOIESIS
. 1. Proerythroblast

2. Early normoblast

3. Intermediate normoblast.

4. Late normoblast

5. Reticulocyte

6. Matured erythrocyte.
 Proerythroblast (Megaloblast)
 Have the ability to give rise to clones.
 First blast cells to appear in the bone marrow and the first identifiable cells of
erythroid series.
 MORPHOLOGICAL FEATURES
1. Size: 15 – 20 µm.
2. Shape: irregularly rounded or slightly oval
3. Cytoplasm: Less, basophilic due to the presence of polyribosomes,
high content of RNA.
4. Nucleolus: Large, multiple nucleoli.
5. Hb: not yet formed.
PROERYTHROBLAST
 EARLY NORMOBLAST
 Proerythroblast progresses into early normoblast.

MORPHOLOGICAL FEATURES :

1. SIZE: 12- 16 µm
2. SHAPE: irregularly rounded or slightly oval
3. CYTOPLASM: Scanty, Blue, basophilic
4. NUCLEUS: Large, chromatin strands are thicker.
5. HB: Not present.
IT IS ALSO KNOWN AS BASOPHILIC NORMOBLAST.
 INTERMEDIATE NORMOBLAST
Intermediate normoblast appears after following the process of mitotic division
of every early normoblast.
It is also called as polychromophilic or polychromatic erythroblast.

MORPHOLOGICAL FEATURES
1. SIZE: 10 – 14 µm
2. CYTOPLASM: Polychromatophilic (contains admixture of basophilic
RNA and acidophilic Hb )
3. NUCLEUS: coarse, condense, deeply basophilic with no nucleoli.
4. HB: Appears
It stains with both acidic as well as basic due to the presence of
 LATE NORMOBLAST
Last nucleated cell of erythrocyte series.
Also called as Orthochromatophilic normoblast.

MORPHOLOGICAL FEATURES
1. SIZE: 8 -10 µm.
2. CYTOPLASM: Deeply acidophilic with diffuse basophilic hue. It gives
an appearance of an orthochromatic cell.
3. NUCLEUS: small, pyknotic with dark chromatin.
4. HB: Present
cytoplasm becomes almost acidophilic.
The process by which nucleus disappears is called pyknosis.
 RETICULOCYTES
Immediate precursors of red cells.
Also called as juvenile red cells/ immature RBC.

MORPHOLOGICAL FEATURES
1. SIZE: 7 – 7.5 µm.
2. CYTOPLASM: Contains small amount of RNA. With supravital stains
like brilliant cresyl blue, the RNA appears in the form of reticulum
and hence the cell is called reticulocyte.
3. NUCLEUS: Absent
4. HB: Increases.
It is basophilic due to the presence of different cell organelles.
In newborn babies, the reticulocyte count is 2% to 6% of RBCs, i.e. 2 to 6
reticulocytes are present for every 100 RBCs.

 The number of reticulocytes decreases during the first week after birth. Later,
the reticulocyte count remains constant at or below 1% of RBCs.
 Matured Erythrocyte
 Final cells in erythropoiesis.
Reticulocytes spends 1 – 2 days in the marrow and circulate for 1 – 2 days in
the peripheral blood before maturing to from erythrocytes.

MORPHOLOGICAL FEATURES
1. SIZE: 7.5 µm.
2. SHAPE: Biconcave disc
3. NUCLEUS: Absent
4. HB: Present.
The matured RBC is with hemoglobin but without nucleus.
 TIME PERIOD
It requires 7 days for the development and maturation of RBC from
proerythroblast.

It requires 5 days up to the stage of reticulocyte.

 Reticulocyte takes 2 more days to become the matured RBC.

 STAGES OF ERYTHROPOIESIS IMPORTANT EVENT
Proerythroblast Synthesis of hemoglobin starts

Early normoblast Nucleoli disappear

Intermediate normoblast Hemoglobin starts appearing

Late normoblast Nucleus disappears

Reticulocyte Reticulum is formed.

Cell enters capillary from site of
production

Matured RBC Reticulum disappears

Cell attains biconcavity
FACTORS NECESSARY FOR
ERYTHROPOIESIS
 Development and maturation of erythrocytes require varies
types of factors, which are classified into three categories:

1. General factors

2. Maturation factors

3. Factors necessary for hemoglobin formation.

 GENERAL FACTORS
• General factors necessary for erythropoiesis are:
I. Erythropoietin
II. Thyroxine
III. Hemopoietic growth factors
IV. Vitamins
 ERYTHROPOIETIN
 Most important general factor for erythropoiesis is the hormone called
erythropoietin.
It is also called hemopoietin or erythrocyte stimulating factor.
SOURCE
• Produced mainly by the interstitial cells in peritubular capillary bed of
kidneys.
• Also produced by juxtaglomerular cells and extraglomerular cells.
• Kidney – 85% of EPO secretion; Kupffer cells and prevenous
hepatocytes in Liver – 15% of EPO production.
STRUCTURE
• Erythropoietin is a glycoprotein with 165 amino acids.
• Molecular weight – 34,000 Dalton.

STIMULUS FOR PRODUCTION

• Hypoxia is the stimulant for the secretion of erythropoietin.
 ACTIONS OF ERYTHROPOIETIN
• Erythropoietin causes formation and release of new RBCs into
circulation.
• After secretion, it takes 4 to 5 days to show the action.
Erythropoietin promotes the following processes:
• Production of proerythroblasts from CFU-E of the bone marrow
• Development of proerythroblasts into matured RBCs through the
several stages – early normoblast, intermediate normoblast, late
normoblast and reticulocyte
• Release of matured erythrocytes into blood. Even some reticulocytes
(immature erythrocytes) are released along with matured RBCs.
• Blood level of erythropoietin increases in anemia.
 THYROXINE
Being a general metabolic hormone, thyroxine accelerates
the process of erythropoiesis at many levels. So,
hyperthyroidism and polycythemia are common.
 HEMOPOIETIC GROWTH
FACTORS

 Definition
• An immature cell that can develop into all types of blood cells,
including white blood cells, red blood cells, and platelets.
• Hemopoietic growth factors or growth inducers are the
interleukins and stem cell factor (steel factor).
• Generally these factors induce the proliferation of PHSCs.
Interleukins (IL) are glycoproteins, which belong to the
cytokines family.
IL( interleukins ) – 1,3 and 5 produced from T-cells act on stem cells
and convert them to progenitor cells.

IL( interleukins ) -6 secreted by T-cells, endothelial cells and

macrophages

IL (interleukins ) -11 secreted by osteoblast.

 VITAMINS
• Some vitamins are also necessary for the process of erythropoiesis.
• Deficiency of these vitamins cause anemia associated with other
disorders.
Vitamins necessary for erythropoiesis:

Vitamin C Vitamin D

Vitamin B Vitamin E
Vitamin B: Its deficiency causes anemia and pellagra (disease characterized by
skin lesions, diarrhea, weakness, nervousness and dementia).

Vitamin C: Its deficiency causes anemia and scurvy (ancient disease

characterized by impaired collagen synthesis resulting in rough skin, bleeding gum,
loosening of teeth, poor wound healing, bone pain, lethargy and emotional
changes).

Vitamin D: Its deficiency causes anemia and rickets (bone disease).

Vitamin E: Its deficiency leads to anemia and malnutrition.

 MATURATION FACTORS
Vitamin B12, intrinsic factor and folic acid are necessary for the maturation of
RBCs.

Vitamin B12
• It is also called as cyanocobalamin.
• Vitamin B12 is the maturation factor necessary for erythropoiesis.
SOURCE
• Vitamin B12 is called extrinsic factor since it is obtained mostly from diet.
• Its absorption from intestine requires the presence of intrinsic factor of Castle.
• Vitamin B12 is stored mostly in liver and in small quantity in muscle.
• It is also produced in the large intestine by the intestinal flora.
• It is transported to the bone marrow to promote maturation of RBCs.
  ACTION
• Vitamin B12 is essential for synthesis of DNA in RBCs.
• Its deficiency leads to failure in maturation of the cell and reduction in the cell
division.
• Also, the cells are larger with fragile and weak cell membrane resulting in
macrocytic anemia.
• Deficiency of vitamin B12 causes pernicious anemia. So, vitamin B12 is called
antipernicious factor.
 INTRINSIC FACTOR OF CASTLE
• Produced in gastric mucosa by the parietal cells of the gastric glands.
• It is essential for the absorption of vitamin B12 from intestine.
Deficiency of intrinsic factor occurs in:
1. Severe gastritis
2. Ulcer
3. Gastrectomy.
Hematinic principle
Hematinic principle is the principle thought to be
produced by the action of intrinsic factor on extrinsic
factor. It is also called or antianemia principle. It is a
maturation factor.
 FOLIC ACID
• Folic acid is also essential for maturation.
• It is required for the synthesis of DNA.
IN THE ABSENCE OF FOLIC ACID
the synthesis of DNA decreases causing failure of maturation.
MEGALOBLASTIC ANEMIA.
anemia in which the cells are larger and appear in megaloblastic
(proerythroblastic)stage.
 FACTORS NECESSARY FOR
HEMOGLOBIN FORMATION
• Various materials are essential for the formation of hemoglobin in the RBCs.
• Deficiency of these substances decreases the production of hemoglobin leading
to anemia.
• Factors are First class proteins and amino acids, Iron, Copper, Cobalt and nickel
and Vitamins.
 FIRST CLASS PROTEINS AND
AMINO ACIDS
• Proteins of high biological value are essential for the formation of hemoglobin.
• Amino acids derived from these proteins are required for the synthesis of protein
part of hemoglobin, i.e. the globin
IRON
• Necessary for the formation of heme part of the hemoglobin.
COPPER
• Necessary for the absorption of iron from the gastrointestinal tract.
Cobalt and nickel
• These metals are essential for the utilization of iron during hemoglobin formation.
Vitamins
• Vitamin C, riboflavin, nicotinic acid and pyridoxine are also essential for the
formation of hemoglobin.
 EYRTHROPOIESIS

BIBLIOGRAPHY
 BOOK:- Essentials of
Medical Physiology
 AUTHOR:- K Sembulingam PhD
and
Prema Sembulingam PhD
THE END PEEPS!
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QUESTIONS???