dr. jitendra patel (mbbs, md)...•in adults extramedullary hemopoiesis may occur in diseases in...

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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

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

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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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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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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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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dr. jitendra patel (mbbs, md)...•in adults extramedullary hemopoiesis may occur in diseases in...

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