HemopoiesisAbbas A. Abbas Shawka

What did the word ( hemopoiesis ) mean ?

• (Gr. haima , blood + poiesis , a making)

Blood formation

Stem cells • pluripotent cells capable of asymmetric

division and self-renewal.

When a stem cells divide, they give at the same time1.specifi c, irreversibly differentiated cell types.2. Pools for slowly dividing stem cells ( self renewal ).

Hemopoietic stem cells

• It is simply stem cells that found in bone marrow.

• This type of cells are rare

Blood formation during life

Hemopoietic bonemarrow occurs in many locations through puberty, but then becomes increasingly restricted to components of the axial skeleton.

Stages of developement

Mature cells

Precursor cells

Progenitor cells

Stem cells

Progenitor cells• The progenitor cells for blood cells are commonly

called colony-forming units (CFUs), because they give rise to colonies of only one cell type

there are four major types of progenitor cells/CFUs:

1- Erythroid lineage 2- Thrombocytic lineage3- Granulocyte-monocyte lineage 4- Lymphoid lineage

Precursor cells• Each progenitor cell/CFU lineage produces

precursor cells (or blasts) that gradually assume the morphologic characteristics of the mature, functional cell types they will become In contrast, stem and progenitor cells cannot be morphologically distinguished and simply resemble large lymphocytes.

Colony stimulating factors

Factors that stimulate production of one cell line ( type ) in the bone marrow .

They also called “ cytokines “

They are glycoproteins that stimulate proliferation of progenitor and precursor cells and promote cell differentiation and maturation within specific lineages

Bone marrow Found in medullary canals of

long bones and small cavities of cancellous bone

Tow types1- red bine marrow2- yellow bone marrow due to accumulation of fat ( adibocyte ) Bone marrow contain 1- reticular connective tissue stroma 2- hemopoietic cords or islands ( c ) 3- sinusoidal capillaries The hematopoietic niche in

marrow includes the stroma, osteoblasts, and megakeryocytes

Between the hematopoieticcords run the sinusoids, which have discontinuous endothelium, through which newly blood cells and platelets enter the circulation

Maturation of erythrocyte

1- Micrographs showing a very large and scarce proerythroblast (P)

2- a slightly smaller basophilic erythroblast (B) with very basophilic cytoplasm

3-typical and late polychromatophilic erythroblasts (Pea nd LPe) with both basophilic and acidophilic cytoplasmic regions

4- small orthochromatophilicerythroblast (Oe) with cytoplasm nearly like that of the mature erythrocytes in the field

5- reticulocytes (arrows) that have not yet completely lost the polyribosomes used to synthesize globin, as demonstrated by a stain for RNA

So in the maturation of erythrocyte,

size of cell ( decrease ) size of nucleus ( decrease ) Basophilia ( decrease ) eosinophilia ( increase ) organelles ( disappeared ) nucleus ( extrusion ) polysome ( disappeared in Pe ) ribosome ( disappeared in R to

Er )

The source of basophilia ( decreased ) in stages of maturation erythrocyte is from

1- polysomes 2- RER

The source of eosinophilia ( increased ) in stages of maturation erythrocyte is from hemoglobin

• Reticulocyte constitute 1% of the red blood cells quickly lose the polyribosomes, and mature as erythrocytes.

Mature ErythrocyteThe only cell in the blood that its function is do not required to leave the circulation

BBCs

Ertrhrocyte cell membrane

• The cell membrane of RBCs is well developed and organized because of its function ( to exchange )

• cell membrane consist of 40% lipid, 50% protein, and 10% carbohydrate

• Most of the latter are integral membrane proteins1- glycophorin A. ( basis of ABO blood typing system )2- band 3 protein ( ion transport )• Several peripheral proteins are associated with the

inner surface of the membrane include ( spectrin , ankyrin )

• This submembranous meshwork stabilizes the membrane, maintains the cell shape, and provides the cell elasticity required for passage through capillaries.

Clinical correlates • Low number of erythrocyte in the

circulation or low amount of hemoglobin in the RBCs will lead to anemia

• High number of erythrocyte in the circulation is called polycythemia

Maturation of

granulocyte

Granulopoiesis: Formation of granules.

Neutroplils• neutrophilic granulocyte passes through an

intermediate stage, the band cell (or stab cell), in which the nucleus is elongated but not yet polymorphic.

• The appearance of large numbers of immature neutrophilsn(band cells) in the blood, sometimes called a “shift to the left,” is clinically significant, usually indicating a bacterial infection.

- Larger than erythrocyte - Mutilobulated ( 3-5 ) - Also called polymorphonuclear leukocytes- Micrograph showing a neutrophil from a female in which the condensed X chromosome

appears as a drumstick appendage to a nuclear lobe (arrow)

Eosinophils

-Eosinophils are about the same size as neutrophils but have bilobed nuclei and more abundant coarse cytoplasmic granules. The cytoplasm is often filled with brightly eosinophilic specific granules, but it also includes some azurophilic granules. -Micrograph shows an eosinophil (E) next to a neutrophil (N) and a small lymphocyte (L).- Even with granules filling the cytoplasm, the two nuclear lobes of eosinophils are usually clear.

Clinical correlate • An increase in the number of eosinophils in blood

(eosinophilia) is associated with 1- allergic reactions and,2- helminth parasitic infections.• In patients with such conditions,• eosinophils are found in the connective

tissues underlying epithelia of the bronchi, gastrointestinal tract, uterus, and vagina, and surrounding any parasitic worms present.

Basophils

• Basophils are also approximately the same size as neutrophils and eosinophils,

• they have large, strongly basophilic specific granules that usually obstruct the appearance of the nucleus which usually has two large irregular lobes.

Clinical correlate • In some individuals a second exposure to a

strong allergen, such as that delivered in a bee sting, may produce an intense, adverse systemic response.

• Basophils and mast cells may rapidly degranulate, producing vasodilation in many organs, a sudden drop in blood pressure, and other effects comprising a potentially lethal condition called anaphylaxis or anaphylactic shock.

Maturation of monocyte

Monopoiesis• The monoblast is a committed

progenitor cell that is virtually identical to the myeloblast morphologically

• Further differentiation leads to the promonocyte, a large cell with basophilic cytoplasm and a large, slightly indented nucleus

• chromatin is lacy and nucleoli are evident.

• Promonocytes divide twice as they develop into monocytes.

Monocyte• Monocytes are large agranulocytes with diameters

from 12 to 20 μm that circulate as precursors to macrophages andother cells of the mononuclear phagocyte system.

• Micrographs of monocytes showing their distinctive nuclei which are indented, kidney-shaped, or C-shaped.

• Differentiating monocytes contain extensive RER and large Golgi complexes forming lysosomes, which are observed as fine azurophilic granules at maturity.

• Monocytes circulate in blood for several hours and enter tissues where they mature as macrophages (or other phagocytic cells) and function for up to several months.

Clinical correlate • Extravasation or the accumulation of immigrating

monocytes occurs in the early phase of inflammation following tissue injury.

• Acute inflammation is usually short-lived as macrophages undergo apoptosis or leave the site

• chronic inflammation usually involves the continued recruitment of monocytes. The resulting continuous presence of macrophages can lead to excessive tissue damage that is typical of chronic inflammation.

Maturation of lymphocyte

Lymphocytopoiesis• all lymphocyte progenitor cells originate in the

bone marrow• Some of these lymphocytes migrate to the

thymus, where they acquire the properties of T lymphocytes.

• Subsequently, T lymphocytes populate specific regions of peripheral lymphoid organs

• Other bone marrow lymphocytes differentiate into B lymphocytes in the bone marrow and then

• migrate to peripheral lymphoid organs, where they inhabit and multiply within their own niches.

• The first identifiable progenitor of lymphoid cells is the lymphoblast.

• Lymphoblast is a large cell capable of dividing two or three

• times to form lymphocytes • As lymphocytes develop, their nuclei become smaller,

nucleoli become less visible, and the cells decrease in size overall.

• In the bone marrow and in the thymus, these cells synthesize the specific cell surface proteins that characterize B or T lymphocytes,

• respectively. Mature and functionally active B and T cells are generally larger than newly formed lymphocytes.

Lymphocyte

Lymphocytes are agranulocytes and lack the specific granules characteristic of granulocytes. Lymphocytes circulating in blood generally range in size from 6 to 15 μm in diameter and are sometimes classified arbitrarily as small, medium, and large. (a) The most numerous small lymphocytes shown here are slightly larger than the neighboring erythrocytes and have only a thin rim of cytoplasm surrounding the spherical nucleus.(b) Medium lymphocytes are distinctly larger than erythrocytes.(c) Large lymphocytes, much larger than erythrocytes, may represent activated cells that have returnedto the circulation.

Maturation the platelets

• The membrane-enclosed cell fragments called platelets or thrombocytes originate in the red bone marrow by dissociating from mature megakaryocytes (Gr. megas, big + karyon, nucleus, + kytos),

• (a) Megakaryoblasts (Mb) are very large, fairly rare cells in bone marrow, with very basophilic cytoplasm.

• (b) Megakaryoblasts undergo endomitosis (DNA replication without intervening cell divisions), becoming polyploid as they differentiate into megakaryocytes (M). These cells are even larger but with cytoplasm that is less intensely basophilic.

• (c) Micrograph of sectioned bone marrow in which a megakaryocyte (M) is shown near sinusoids (S).

• Megakaryocytes produce all the characteristic components of platelets (membrane vesicles, specific granules, marginal microtubule bundles, etc) and in a complex

• process extend many long, branching pseudopodia-like projections called proplatelets, from the ends of which platelets are pinched off almost fully formed.

Platelets

• In a blood smear, platelets (arrows) are often found as aggregates. Individually they show a lightly stained hyalomere region surrounding a more darkly stained central granulomere containing membrane-enclosed granules.

• The role of platelets is preventing blood loss (hemorrhage)

Clinical correlate • Aspirin and other nonsteroidal anti-

inflammatory agents have an inhibitory effect on platelet function and blood coagulation because they block the local prostaglandin synthesis that is needed for platelet aggregation, contraction, and exocytosis at sites of injury.