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2 blood hemopoiesis
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Transcript of 2 blood hemopoiesis
HEMOPOIESIS1
Haemopoiesis Process of formation of blood cells is
called haemopoiesis
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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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
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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”
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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
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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
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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
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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
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Thank you!!
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