HEMOPOIESIS1

Haemopoiesis Process of formation of blood cells is

called haemopoiesis

2

Types of haemopoiesis

A.Medullary haemopoiesis Production of blood cells in Haemopoietic tissue of bone

marrow

B.Extra-medullary haemopoiesis Production of blood cells in other sites other than bone

marrow e.g. blood cells are produced in liver, spleen and lymph nodes  These extra-medullary organs produce blood cells especially

in very large quantity in following condition Increase demand of body Following hemorrhage Severe pernicious anaemia and hemolytic anaemia Myelosclerosis: this is condition when bone marrow is

replaced by fibrous tissue

3

Sites of blood cells formation

Blood cells are produced in different sites during intrauterine and extra uterine life

In intrauterine life Age Site

 

Developing fetus 1st – 2nd month of fetal life

Mesoderm of yolk sac(only primitive RBC)

3rd –7th month of fetal life Liver, spleen and thymus

5th month till birth Bone marrow, liver, spleen and lymph node 4

Extra uterine life

Red cells, granulocytes and platelets: bone marrow

Lymphocytes: lymph node and other lymphoid tissue

Bone marrow(main site)

Monocyte: Bone marrow (main site) Spleen and other lymphoid tissue

5

Development of blood cells (genesis of blood cells)

Blood cells are derived from primitive undifferentiated marrow cells known as “stem cells” (Pluripotential Haemopoietic stem cells)

Stem cell can develop along various pathways; hence they are also called “Multipotent uncommitted stem cell”

Stem cell increase in number by mitosis From multipotent stem cells committed

or Unipotent stem cell develop Unipotent stem cell give rise to

erythrocytes, granulocytes, lymphocytes, monocytes or platelets through a series of stages

E.g. a committed stem cell that produces erythrocyte is called a colony-forming unit erythrocytes (CFU-E)

So committed stem cell will produce colonies of specific type of blood cells

6

7

8

9

10

11

GROWTH INDUCERS

Multiple different proteins which controls growth and reproduction of different stem cells are called growth inducer

Four major growth inducers have been found One of them is interleukin-3; this promotes

growth and reproduction of virtually all the different type of stem cell

Remaining other induce growth of only specific types of committed stem cells

 12

DIFFERENTIATION INDUCER

These are the proteins, which function for differentiation of cells

Each of differentiation inducer cause one type of stem cell to differentiate one or more steps toward a final type of adult blood cell

 

• Growth inducer promote growth but not differentiation of cells

Formation of growth inducer and differentiation inducers is itself controlled by factors outside the bone marrow

E.g. when any person is exposed to low oxygen for a long period. Then growth inducer and differentiation inducer for RBC increase, which increase RBC number

13

RED BLOOD CELLS (RBC)

Mature RBC is circular, biconcave disc

Mature RBC contains hemoglobin

Mature RBC has no nucleus

Morphology Shape: circular of flat biconcave Size: diameter: 7.8 micrometer Thickness: 2.5 micrometer

at thickest point 1 micrometer or less at center

Average volume: 90-95 cubic

micrometers Life span: 120 days

14

Normal count of RBC In normal adult male: Range: 4.5 –5.5 million/ cu. mm of blood Average: 5,200,000(300,000) In normal adult female Range: 4.0-5.0 million/ cu mm of blood Average: 4.7(0.3) million/ cubic mm of

blood

In new born: 6-7 million / cu mm of blood 15

16

Structure of RBC 1.Outer: cell membrane Composed of two layer (i.e. bimolecular layer of phospholipid covered on both side protein layer ) 2. Inner: stroma and hemoglobin

Composition of RBC 1. Water: 60% 2. Solid: 40% Solid are 1. Hemoglobin 2.Stroma: stroma consists of Protein (stomatin)

Lipid (phospholipid, cholesterol)Neutral fat Glucose, lactic acid 2,3 DPGElectrolytesEnzymes

17

ERYTHROPOIESIS

This process of formation of RBC under normal physiological condition is called erythropoiesis

Types of erythropoiesis 1. Mesoblastic erythropoiesis 2. Hepatic erythropoiesis 3. Myeloid erythropoiesis

18

Mesoblastic erythropoiesis In the early few weeks of embryonic life, primitive nucleated RBC are produced in yolk sac which is called Mesoblastic erythropoiesis

Hepatic erythropoiesis During middle trimester of gestation, liver is the main site for production of RBC, although reasonable numbers of RBC are also produced by spleen and lymph nodes

Myeloid erythropoiesis During last month or so of gestation and after birth, red cells are produced exclusively by bone marrow, this is called myeloid erythropoiesis  Until age of 5, bone marrow of all bone produce RBC. After age of 20, red bone marrow of all long bones changes and become fatty except for proximal portion of humerous and tibia. So beyond this age (20 yrs) most red cells are produced in marrow of membranous bone such as vertebrae, sternum, ribs and iliac bone

Even in these bone the marrow becomes less productive as age increases 19

STAGE OF DEVELOPMENT (DIFFERENTIATION) OF RBC

The first cell that can be identified as belonging to red blood cell series is Pro-erythroblast.

CFU-E stem cells (colony forming unit erythrocytes) forms large numbers of these proerythroblast under appropriate stimulation

Precurssor cell: “Bone marrow stem cells”

Stage –1: Pronormoblast (pro-erythroblast)

Cell size: 15- 20 micron in diameter

Nucleus: 12 micron in diameter

Hb: synthesis of Hb starts

Cytoplasm: deep violet blue colored

Mitosis: occurs only in state of stress

20

STAGE OF DEVELOPMENT (DIFFERENTIATION) OF RBC

Stage –2: Early normoblast (early erythroblast)

Cell size: 11-17 micron in diameter

Nucleus : 10 micron (

Hb: begins to appear

Cytoplasm : basophilic

Mitosis: occurs

21

Stage-3: intermediate normoblast (late erythroblast)

Cell size: 10-14 micron on diameter

Nucleus : shows further condensation

Hb: increase gradually

Cytoplasm : polychromatic appearance

Mitosis : occurs

22

Stage-4: late normoblastCell size : 7-10 micron on diameter

Nucleus : become dense and take deep stain looking like a drop of ink. Later on when nucleus further maturates nucleus undergoes “ pyknosis”

Pyknosis:

Fragmentation: breakdown of nucleus

Extraction: disappearance of nucleus

23

Stage-5: reticulocyte Next stage is reticulocyte. Reticulocyte cell

pass from bone marrow into blood capillaries by diapedesis (squeezing through pores of capillaries membrane)

Nucleus: disappears during this stage

Reticulocytes convert into mature RBC within 1-2 days. So because of short life of reticulocytes their concentration among all red cells of blood is normally 1% or less

24

25

Stage-6: normal erythrocyte (mature RBC)These are last stage in development of RBC so called mature RBC  Time requirement From Pronormoblast upto reticulocyte: 7 dayFrom reticulocyte upto mature RBC: 2 days

26

BASIC CHANGES DURING PROCESS OF ERYTHROPOIESIS

Two distinct changes occurs during process of erythropoiesis

1.Multiplication 2.Maturation

Multiplication This is the process by which number of cell

increase

Maturation This is process by which immature Red cell

become mature RBC, this include a. A gradual reduction of cell size and

alteration of shape b. Acquirement of hemoglobin c. Disappearance of nucleus d. Cessation of cell division

27

28

FACTOR REGULATING / CONTROLLING ERYTHROPOIESIS

A.) Diet: Protein of high biological value supplies essential aminoacid

for synthesis of globinportion of hemoglobin

B) Hypoxia: Hypoxia is decrease oxygen conc at tissue level

Hypoxia stimulates liberation of hormone erythropoietin, which in turn stimulate bone marrow for erythropoiesis

 C) Erythropoietin( hemopoietin): It is hormone, which acts on bone marrow and stimulates

erythropoiesis

D)Endocrine (hormones) ACTH and thyroxin stimulates bone marrow for production

of RBC Testosterone also have positive effect on RBC production

29

ERYTHROPOIETIN:~ is a glycoprotein

Molecular wt: 34,000

Site of formation: 90% in kidney

10% in liver

 

Cause of release of erythropoietinHypoxia: decrease O2 conc at tissue

level

Cause of hypoxia

High altitude

Heart disease (cardiac failure)

Lung diseases

Hemorrhage (blood loss)

Some anaemia

Function of erythropoietin

Erythropoietin stimulate production of erythroblast from haemopoietic stem cell in bone marrow

They also help in speeding the different stage of RBC development i.e. they cause proerythroblast that are newly formed to pass more rapidly through different stages than normally

 

30

31

32

Maturing factors of RBC

1.Vit B122.Folic acid3.Intrinsic factor of Castle

 Vitamin B12 & folic acid are required for final maturation of RBC.

Vitamin B12 & folic acid are required for formation of thymidine triphosphate, which is one of the building blocks of DNA. So, deficiency of Vit B12 & folic acid decrease formation of thymidine triphosphate, which in turn diminishes DNA.

DNA is required for nuclear maturation & cell division. So, inability of cells to synthesize adequate quantities of DNA lead to slow division of cells. But RNA is being continuously formed from DNA in those cells that are produced by bone marrow. So, quantity of RNA in each cell becomes greater than normal, as cell is not dividing. So, increased RNA means increased production of cytoplasmic protein like hemoglobin and other constituent, which causes cell to enlarge than normal called macrocytes. 

33

These macrocytes have flimsy membrane and are often irregular, large and oval instead of usual biconcave disc. After these cells enter in circulation from bone marrow they are capable of carrying O2

normally, but their fragility cause them to have a short life, one half to one third of normal.

This condition in which RBC increase in size due to deficiency of Vit B12 and or folic acid is called megaloblastic anaemia

34

Intrinsic factor

IF of Castle help to absorb the Vit B12 from the GIT. So, when due to any condition there is deficiency of IF e.g. atrophy of gastric mucosa, then there occurs deficiency of Vit B12. So, when megaloblastic anaemia develops due to deficiency of IF it is called “Pernicious anaemia”

35

TERMINOLOGY

Normocyte: When RBC is normal in size

Microcyte: When RBC is smaller than normal

Macrocyte: When RBC is larger than normal

Anisocytosis: Variation from normal size of RBC

Poikilocytosis: Deviation from normal shape of RBC

Hypochromic: When conc of Hb in RBC is less than normal

Hemolysis: process of breakdown of RBC

36

FUNCTION OF RBC

1.Hb in RBC carries oxygen from lungs and CO2 vice versa

2.Buffering action of Hb presents in RBC maintains 50% of buffering action of whole blood (acid-base balance)

3.RBC maintains viscosity of blood: more RBC ---- more viscosity of blood

4.RBC contains certain antigen or group specific substance which determine blood group

37

THOUGH RBC HAVE NO NUCLEUS IT IS CALLED CELL

Though RBC has no nucleus it is called cell because

1.Recent studies has shown that nucleus is not essential for survival of cell

2.It has definitive life span

3.It is highly adapted cell in our body

4.Though it doesn’t contain mitochondria, Golgi apparatus but it contains all the enzymes necessary for providing energy from glucose metabolism via hexosemonophosphate shunt pathway

5.It also carries all the metabolic function as other cell of body by help of different enzyme present in them

38

FRAGILITY OF RBC

It means the tendency of RBC to breakdown or disintegrate ,discharging its content (Hb) into surrounding fluid.

Osmotic fragility of RBC

Osmotic fragility of RBC means breakdown of RBC mem( hemolysis) in solution due to osmotic effect  1. RBC when suspended in normal saline (0.9% NaCl): no hemolysis

2. RBC when suspended in hypotonic solution Water enters into the Red cells and cell gradually increase in size and ultimately it burst

3.RBC when suspended in hypertonic solution Water comes out of RBC and RBC shrinks

4.RBC when suspended in water Water enters into RBC and so RBC ultimately burst

39

Thank you!!

40