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Dr. Jitendra Patel (MBBS, MD)
Medical Educator & Researcher
Associate Professor, Department of Physiology
Email: [email protected] Web: www.esphys.weebly.com
OUTLINE OF LECTURE
Learning Objectives
Introduction: Hemopoiesis
Erythropoiesis:
Site; Stages; Duration and Regulation
Applied Aspect & Facts
Summary
Key Term & Concept
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LEARNING OBJECTIVES
Describe the Term “Hemopoiesis”.
Where and How Blood Cells are Formed?
Describe the Major Changes During
Erythropoiesis
List Factors Affecting the Erythropoiesis.
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INTRODUCTION: HEMOPOIESIS
• The word Hemopoiesis refers
to the production (development,
maturation and release) of all
the blood cells.
• Monophyletic and polyphyletic
theory
• Erythrocytes: Erythropoiesis
• Leucocytes: Leucopoiesis
• Thrombocytes:
Thrombopoiesis.
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Intro…cont: Site
• In the fetus, blood cells are also formed in the yolk
sac, liver and spleen,
• In children, blood cells are actively produced in the
marrow cavities of all the bones.
• In the adult, blood cells are formed in the Red Bone
Marrow only. 7
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White marrow In very old individuals, a gelatinous transformation of fat
to a mucoid material occurs in bone marrow.
Intro…cont: Stages
• Stage I: Hemopoietic stem cells
self renewal, steady numbers,
active differentiation.
• Stage II: committed progenitors
directional differentiation (CFU-
GEMM, CFU-E, CFU-GM, CFU-MK,
CFU-TB).
• Stage III: precursors morphologic
occurrence of various original
blood cells. 11
I. PHSC
II. Progenitor cells (CFU)
III. Precursor cells (Blast cell)
III. Mature cells
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ERYTHROPOIESIS
W…h…y…?...?...?
• Because erythrocytes cannot divide to replenish their
own numbers, the old ruptured cells must be replaced by
new cells produced in an erythrocyte factory.
• The bone marrow normally generates new red blood
cells, a process known as erythropoiesis, at a rate to keep
pace with the demolition of old cells.
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Erythropoiesis…….Site
Mesoblastic stage:
• In the yolk sac
• Starts at 2 weeks of
intrauterine life
• Intravascular
Hepatic stage:
• 2-7 months
• Both liver and spleen
Myeloid stage:
• Occurs in bone marrow
• Starts at 5 months of fetal life and takes over completely at birth; Red bone marrow of all bones
• In adult life, red marrow of flat bones and proximal portion of long bone
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Erythropoiesis…….Stages I. PHSC
II. Myeloid stem cells
III. Pronormoblast (Proerythoroblasts)
IV. Basophilic erythoroblasts
(Early erythroblasts /normoblast)
V. Polychromatophil erythroblasts
(intermediate erythroblast /normoblast)
VI. Orthochromatic erythroblasts
(late erythroblast /normoblasts)
VII. Reticulocytes (young erythrocytes)
VIII.Erythrocytes (mature erythrocytes) 18
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Erythropoiesis…….Duration
• Differentiation phase:
from pronormoblast to
reticulocyte phase-
5 to 7 days
• Maturation phase:
from reticulocyte to RBC-
2 days
Average duration is 7-10
days 20
Erythropoiesis…….Changes
Major Changes during Erythropoiesis
• Decrease in cell size
• Decrease in nuclear size which later on
disappear
• Cytoplasm is initially blue but later on
becomes red
• Hemoglobin appears in the cell cytoplasm
• Mitosis is initially present but stops later on
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Erythropoiesis…….Changes
Hemocytoblast (PHSC)
• Noncommitted
• Diameter: 18-20 m
• Nucleated with thin rim of basophilic
nucleus
• They proliferate extensively and give rise
to committed stem cell
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Erythropoiesis…….Changes
Committed Stem Cell
• Developed from PHSC
• Two type: myeloid and lymphoid
• They have become committed to give rise to
a particular line of cell.
• Committed stem cell of myeloid series give
rise to all types of blood cell except
lymphocytes.
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Erythropoiesis…….Changes
Progenitor Cell
• Developed from committed stem cell
• Types: BFU-E & CFU-E
• BFU-E give rise to CFU-E cells
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Changes During Erythropoiesis
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Diameter
(m) Nucleus Cytoplasm Mitosis
Pronormoblast 15 -20 Big,
basophilic
Very Scanty; basophilic No Hb
+
Early Normoblast
12 -16 Smaller Scanty &baso.
No Hb +
Intermediate Normoblast
10 -12 Smaller
Pyknotic.
Hb appears Polychromatophilic
+
Late Normoblast
8 -10 Very small disappears
Hb abundent
Eosinophilic. _
Reticulocyte 8 Absent Remnants of RNA by cresyle blue, Hb ++
_
Mature RBC 7.5 Absent Hb +++ _
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The number of reticulocytes in the peripheral blood is an index of erythropoiesis
REGULATION OF ERYTHROPOIESIS
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Importance of Normal RBC Count
Must Not Fall:
• To supply oxygen from lungs to tissues
Must Not Rise:
• Blood viscosity may increase
• May impede blood flow
REGULATING FACTOR
A. General factor
B. Special maturation factor
C. Other Factors
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ERYTHROPOIETIN
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• It is Glycoprotein also known as a EPO
• MW 34000 Da
• Discovered by Miyake et al 1977 from urine of
anaemic patients
• Source: 85 % from kidney & 15 % from liver
• Site of action: Bone marrow
• Main Stimulator: Hypoxia (lack of oxygen at tissue
level)
Role In Erythropoiesis
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Stimulator of Erythropoietin
Role In Erythropoiesis
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Action of Erythropoietin
• Speeds up the differentiation and
proliferation of erythropoiesis.
• Formation of Pronormoblast from stem
cell.
• Promote the Hb synthesis
• Prevent apoptosis of RBC.
• Increase the release of Reticulocyte.
Factor Affecting the EPO Secretion
Factors Increasing Erythropoietin Secretion:
• Hypoxia
• Androgens
• GH; TH; ACTH
• Catecholamines
• Prostaglandins
Factors Inhibiting Erythropoietin Secretion:
• Estrogen
• Theophylline
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Clinical Significance of EPO
Synthetic/Recombinant Erythropoiten
For Rx of Anemia – CRF, AIDS, Chemotherapy
Blood Doping:
• Rigorous studies have demonstrated that injected
erythropoietin may improve an endurance athlete’s
performance by 7% to 10%.
• Synthetic erythropoietin is believed responsible for the
deaths of 20 European cyclists since 1987.
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Maturation Factor
• Vitamins
Vit B12; Folic Acid; Vit C; Vit B6
• Minerals
Iron; Cobalt; Calcium; Nickel; Mn
• Protein
• IF
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Maturation Factor
Extrinsic Factor of Castle - Vitamins B12
• Required for synthesis of DNA and maturation of
nucleus and cell
• Daily requirement: 1-2 g
• Deficiency leads to;
Megaloblastic Anaemia
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Maturation Factor
Intrinsic Factor of Castle (IF)
• Source :Parietal cells of stomach
• Function :Absorption of vitamin B12
• Deficiency causes :Pernicious anemia
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Maturation Factor
Folic Acid
• Required for synthesis of DNA along vit B12
• Daily requirement: 100 g
• Deficiency leads to;
Megaloblastic Anemia
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Maturation Factor
Iron
• Function:- synthesis of heam part of Hb
• Source:-Meat, peas, leafy vegetables, jaggery
• Daily requirement:-1-2 mg
• Intracellular iron is stored as ferritin and hemosiderin
• Deficiency of iron:-microcytic, hypochromic anemia (IDA)
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Other Factors
• Vit C; Vit B6 : synthesis of nucleic acid
• Calcium increases iron absorption
• Mn; Cu; Nickle help in haem formation
• Protein: synthesis of globin
• Bile salts for absorption of metals & fat soluble
substances
• Hormone: GH; TH; ACTH
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APPLIED ASPECT
• In adults Extramedullary Hemopoiesis may occur in
diseases in which the bone marrow becomes destroyed
or fibrosed.
• Bone marrow depression: Aplastic Anaemia
• The HSCs are few in number but are capable of
completely replacing the bone marrow when injected
into a host whose own bone marrow has been entirely
destroyed. (BM Transplantation)
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Applied….cont
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• Normally, 75% of the cells in the marrow belong to the
white blood cell and only 25% are maturing red cells, even
though there are over 500 times as many red cells in the
circulation as there are white cells. ( Life span)
• Each RBC circulates 700 miles (1126.54 km)
averagely in vessels during its life span.
• Normal reticulocyte count = 1-2% of red blood cells -
Provide an index of rate of RBC formation.
KEY TERM & CONCEPT
H e m o p o i e s i s & E r y t h r o p o i e s i s
Re d b o n e m a r r ow & Ye l l ow b o n e m a r r ow
H e m o p o i e t i c s t e m c e l l ( P H S C )
P r o g e n i t o r ( C F U ) a n d p r e c u r s o r ( B l a s t ) c e l l
Re t i c u l o c y t e
E r y t h r o p o i e t i n
M e g a l o b l a s t i c a n e m i a & Pe r n i c i o u s a n e m i a
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SUMMARY
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