HEMOPOIESIS & ERYTHROPOIESIS

By Dr. M.Anthony David MD Professor of Physiology

HEMOPOIESIS: INTRO
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Hemo: Referring to blood cells Poiesis: “The development or production of” The word Hemopoiesis refers to the production & development of all the blood cells:
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Begins in the 20th week of life in the fetal liver & spleen, continues in the bone marrow till young adulthood & beyond!

Erythrocytes: Erythropoiesis Leucocytes: Leucopoiesis Thrombocytes: Thrombopoiesis.

SITES OF HEMOPOIESIS

Active Hemopoietic marrow is found, in children throughout the:

Appendicular skeleton:

Bones of the Upper & Lower limbs

Axial skeleton:
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Cranium Ribs. Sternum Vertebrae Pelvis

In Adults active hemopoietic marrow is found only in:
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The axial skeleton The proximal ends of the appendicular skeleton.

STEM CELL THEORY

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The dazzling array of all the blood cells are produced by the bone marrow. They all come from a single class of primitive mother cells called as: PLURIPOTENT STEM CELLS. These cells give rise to blood cells of:

Myeloid series: Cells arising mainly from the bone marrow. Lymphoid series: cells arising from lymphoid tissues.

CLONAL HEMOPOIESIS
PLURIPOTENT STEM CELL MULTIPLICATION COMMITTMENT COMMITTED STEM CELL

STEM CELL COMMITTED STEM CELL

MULTIPLICATION

PROGENITOR CELL CFU: COLONY FORMING UNIT

CLONAL HEMOPOIESIS: (Contd)
COLONY FORMING UNIT (CFU)

MORPHOLOGICALLY RECOGNIZABLE

INTERMEDIATE BLAST CELLS

MATURE BLOOD CELLS END CELLS: FINITE LIFE SPAN

STEM CELLS

These cells have extensive proliferative capacity and also the:

Ability to give rise to new stem cells (Self Renewal) Ability to differentiate into any blood cells lines (Pluripotency)

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They grow and develop in the bone marrow. The bone marrow & spleen form a supporting system, called the “hemopoietic microenvironment”

STEM CELLS: Types

Pluripotent Stem cells:
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Myeloid Stem cells: Generate myeloid cells:
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Has a diameter of 18 – 23 μ. Giving rise to: both Myeloid and Lymphoid series of cells Capable of extensive self-renewal. Erythrocytes Granulocytes: PMNs, Eosinophils & Basophils. Thrombocytes. Lymphocytes: T type mainly.

Lymphoid Stem cells: Giving rise only to:

PROGENITOR CELLS

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Committed stem cells lose their capacity for self-renewal. They become irreversibly committed. These cells are termed as “Progenitor cells” They are regulated by certain hormones or substances so that they can:
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Proliferate Undergo Maturation.

CELL LINE REGULATORS
CELL LINE
ERYTHROID: BFU-E: CFU : E GRANULOCYTE-MONOCYTE: CFU-GM MEGAKARYOCYTES: CFU-M MEGAKARYOCYTES

REGULATOR
BURST PROMOTING ACTIVITY ERYTHROPOIETIN COLONY STIMULATING FACTOR(CSF) MEGAKARYOCYTIC STIMULATING ACTIVITY THROMBOPOIETIN

BLOOD CELLS: DEVELOPMENT
PROG ENI TOR CE LL S

LY MPHO ID PRO MEGA MYELO BLA ST MONOBL AST CE LLS NORMOBL AST KA RYO BL AST

LYMP HO CY TESERYTHROCYTESTH ROMB OCY TES GRANUL OCYTE S MONOCYTE S

ERYTHROPOIESIS: SITES/PHASES

INTRA UT ER INE LIF E:

INTRAVASC UL AR PH ASE : Up to 3 rd mo nth of Intr a U te ri ne Life.

End ot helial cell s = = = RBCs

HEPATI C P HAS E : 3 rd t o 5 th mo nth IU L
Li ver & Sp lee n  nR BCs from M ese nchymal cell s.

MYEL OI D PH ASE : Fr om 5 th m onth of IUL onwar ds.

ERYTHROPOIESIS: SITES/PHASES contd.

POST NATAL LIFE:

CHILDREN:

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Predominantly Red Bone Marrow of skeleton:
Axial & Appendicular.

ADULTS:

Red Bone Marrow of Axial Skeleton.

ERYTHROPOIESIS
PROERYTHROBLAST BASOPHILIC ERYTHROBLAST POLYCHROMAT OPHILIC ERYTHROBL AST ORTHOCHROMATIC ERYTHROBLAST

RETICULOCYTE

MATURE ERYTHROCYTES

FACTORS REGULATING ERYTHROPOIESIS
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SINGLE MOST IMPORTANT REGULATOR: “TISSUE OXYGENATION” BURST PROMOTING ACTIVITY ERYTHROPOIETIN IRON VITAMINS:
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Vitamin B12 Folic Acid

MISCELLANEOUS

ERYTHROPOIETIN
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A hormone p ro duced by the Ki dn ey. A c irc ula ti ng Gl yc oprot ei n Now adays a vailabl e a s Syn thet ic Epo ie ti n Act s ma inly on C FU – E . Incre as es the n umbe r of :
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Nucl eate d p recur so rs i n t he m ar ro w. Ret icul ocyte s & Matur e Er yth rocyte s i n the blood .

VITAMINS

B 12 : Cya noco ba la mi ne & Fol ic Ac id:
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Is also cal led Ex tr insi c Facto r of Ca stle . Needs th e Intr insi c Facto r from th e Gastri c j ui ce for ab so rpti on f rom S mal l Inte sti ne. De ficiency cause s Per nicious (Wh en I F is mi ssi ng) o r Me gal ob lasti c An emi a. Sti mulat es Er yt hrop oiesis Is foun d in meat & diar y prod ucts.

IRON

Esse ntia l f or the synthe si s o f Hem og lo bin . Def icie ncy ca use s Microc yti c, Hypoc hro mic A nemi a. The MCV , C olo r Ind ex & MC H a re low .

ERYTHROPOIESIS: SEQUENTIAL CHANGES
I V P R O N O R M O B L A S T II VI E A R L Y N B L A S T III I N T E R N B L A S T L A T E N B L A S T IV R E T I C U L O C Y T E M A T U R E R B C

MITOCHONDRIA BASOPHILIA HEMOGLOBIN

ERYTHROID PROGENITOR CELLS

BF U- E : Bu rst Fo rmi ng Unit – Eryt hroc yt e:

Give rise e ac h to t housan ds of nucl eat ed e ryt hro id p re curs or cells, in vi tro . Underg o som e ch an ge s to become t he Col ony Fo rmi ng Un its-Er yth rocyte ( CFU E) Regul ato r: Bur st Pr om ot ing Activi ty ( BPA )

ERYTHROID PROGENITOR CELLS

CFU- E : Col ony Formi ng Un itEryt hroc yt e:
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We ll d iff eren tiate d e ryth roi d proge nito r cel l. Pre se nt on ly i n th e R ed Bo ne Mar ro w. Can for m up to 64 nuc leate d ery th roid precur so r ce ll s. Regul ato r: Ery th ropoi eti n .

Bo th t hese P rogenit or c ell s ca nn ot be dis ti nguished e xc ept b y in vit ro cultu re me thods .

Normoblastic Precursors

PROE RY THR OBL AST :
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Lar ge cell : 15 – 20 Micr on s in diam ete r. Cyto plasm is deep vio let -b lue stai ning Has no Hemo gl ob in . Lar ge nuc leus 12 Mi crons o ccup ies 3/4 th of th e cell volume . Nucl eus has fi ne sti pple d reti cul um & man y n ucle oli.

Normoblastic Precursors

EARLY NORMOBLAST:
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Smaller in size. Shows active Mitosis. No nucleoli in the nucleus. Fine chromatin network with few condensation nodes found. Hemoglobin begins to form. Cytoplasm still Basophilic.

Normoblastic Precursors

INTERMEDIATE NORMOBLAST:
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Has a diameter of 10 – 14 Microns. Shows active Mitosis. Increased Hemoglobin content in the cytoplasm Cytoplasm is Polychromatophilic.

Normoblastic Precursors

LATE NORMOBLAST:
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Diameter is 7 – 10 Microns. Nucleus shrinks with condensed chromatin. Appears like a “Cartwheel” Cytoplasm has a Eosinophilic appearance.

Normoblastic Precursors

RETICULOCYTE:
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The penultimate stage cell. Has a fine network of reticulum like a heavy wreath or as clumps of dots This is the remnant of the basophilic cytoplasm, comprising RNA. In the Neonates, Count is 2 – 6/Cu.mm. Falls to <1 in the first week of life. Reticulocytosis is the first change seen in patients treated with Vit B12

Normoblastic Precursors

MATURE ERYTHROCYTE:
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Biconcave disc. No nucleus. About One-third filled with Hemoglobin.

Regulation of Erythropoiesis
Sti mulat es

CFU – E
An example of a Negative feed back mechanis m

Proerythroblasts ERY THROPOIET IN Mature Erythrocytes
De cr ease s

Tissue Oxygenation Factors decreasing:

Hypovolemia
Anemia

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Poor blood flow Pulmonary Disease

HEMOPOIESIS: REVIEW I
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Hemopoiesis: Production of blood cells. Site: Predominantly in the Bone Marrow. Both axial & appendicular skeletons. Erythropoiesis: Production of Erythrocytes. Leucopoiesis: Production of Leucocytes. Thrombopoiesis: Production of Thrombocytes.

HEMOPOIESIS: REVIEW II

Cell lines:
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Pluripotent Stem Cell Progenitor Stem Cells: Committed
Proerythroblasts  Myeloblasts  Monoblasts  Lymphoid cells  Megakaryoblasts

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