بسم الله الرحمن الرحيم. oi myeloid tissue myeloid tissue bone marrow is found in...

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بسم الله الرحمن بسم الله الرحمن الرحيمالرحيم

بسم الله الرحمن بسم الله الرحمن الرحيمالرحيم

MYELOIOID

TISSUE

MYELOIOID

TISSUE

Myeloid TissueMyeloid TissueMyeloid TissueMyeloid Tissue Bone marrow is found in the medullary canals Bone marrow is found in the medullary canals

of long bones and in the cavities of cancellous of long bones and in the cavities of cancellous bones.bones.

Two types of bone marrow have been described Two types of bone marrow have been described based on their appearance on gross based on their appearance on gross examination:examination:

1.1. Red,Red, or or hematogenous, bone marrowhematogenous, bone marrow,, whose color is produced by the presence of whose color is produced by the presence of blood and blood-forming cells;blood and blood-forming cells;

2.2. Yellow bone marrowYellow bone marrow,, whose color is whose color is produced by the presence of a great number of produced by the presence of a great number of adipose cells.adipose cells.

Bone marrow is found in the medullary canals Bone marrow is found in the medullary canals of long bones and in the cavities of cancellous of long bones and in the cavities of cancellous bones.bones.

Two types of bone marrow have been described Two types of bone marrow have been described based on their appearance on gross based on their appearance on gross examination:examination:

1.1. Red,Red, or or hematogenous, bone marrowhematogenous, bone marrow,, whose color is produced by the presence of whose color is produced by the presence of blood and blood-forming cells;blood and blood-forming cells;

2.2. Yellow bone marrowYellow bone marrow,, whose color is whose color is produced by the presence of a great number of produced by the presence of a great number of adipose cells.adipose cells.

Myeloid TissueMyeloid TissueMyeloid TissueMyeloid Tissue In newbornsIn newborns, all bone marrow is red and , all bone marrow is red and

is therefore active in the production of is therefore active in the production of blood cells.blood cells.

As the child growsAs the child grows, most of the bone , most of the bone marrow changes gradually into the marrow changes gradually into the yellow variety.yellow variety.

Under certain conditionsUnder certain conditions, such as severe , such as severe bleeding or hypoxia, yellow bone marrow bleeding or hypoxia, yellow bone marrow is replaced by red bone marrow.is replaced by red bone marrow.

In newbornsIn newborns, all bone marrow is red and , all bone marrow is red and is therefore active in the production of is therefore active in the production of blood cells.blood cells.

As the child growsAs the child grows, most of the bone , most of the bone marrow changes gradually into the marrow changes gradually into the yellow variety.yellow variety.

Under certain conditionsUnder certain conditions, such as severe , such as severe bleeding or hypoxia, yellow bone marrow bleeding or hypoxia, yellow bone marrow is replaced by red bone marrow.is replaced by red bone marrow.

Red Bone MarrowRed Bone MarrowRed Bone MarrowRed Bone Marrow Red bone marrow is composed of a Red bone marrow is composed of a stromastroma , ,

hematopoietic cords (or islands),hematopoietic cords (or islands), and and sinusoidal capillariessinusoidal capillaries..

The stroma is a three-dimensional meshwork The stroma is a three-dimensional meshwork of reticular cells and a delicate web of of reticular cells and a delicate web of reticular fibers containing hematopoietic cells reticular fibers containing hematopoietic cells and macrophages.and macrophages.

The stroma of bone marrow contains collagen The stroma of bone marrow contains collagen types I and III, fibronectin, laminin, and types I and III, fibronectin, laminin, and proteoglycans.proteoglycans.

The sinusoids are formed by a discontinuous The sinusoids are formed by a discontinuous layer of endothelial cells.layer of endothelial cells.

Red bone marrow is composed of a Red bone marrow is composed of a stromastroma , , hematopoietic cords (or islands),hematopoietic cords (or islands), and and sinusoidal capillariessinusoidal capillaries..

The stroma is a three-dimensional meshwork The stroma is a three-dimensional meshwork of reticular cells and a delicate web of of reticular cells and a delicate web of reticular fibers containing hematopoietic cells reticular fibers containing hematopoietic cells and macrophages.and macrophages.

The stroma of bone marrow contains collagen The stroma of bone marrow contains collagen types I and III, fibronectin, laminin, and types I and III, fibronectin, laminin, and proteoglycans.proteoglycans.

The sinusoids are formed by a discontinuous The sinusoids are formed by a discontinuous layer of endothelial cells.layer of endothelial cells.

Red Bone MarrowRed Bone MarrowRed Bone MarrowRed Bone Marrow The islands of hemopoietic cells are composed The islands of hemopoietic cells are composed

of of blood cells in various stages of maturation as blood cells in various stages of maturation as well as well as macrophagesmacrophages..

The macrophages The macrophages destroy the extruded nuclei destroy the extruded nuclei of erythrocyte precursors, malformed cells, and of erythrocyte precursors, malformed cells, and excess cytoplasm.excess cytoplasm.

Macrophages also Macrophages also regulate hemopoietic cell regulate hemopoietic cell differentiation and maturation, transmit iron to differentiation and maturation, transmit iron to developing erythroblasts to be utilized in the developing erythroblasts to be utilized in the synthesis of the heme portion of hemoglobin.synthesis of the heme portion of hemoglobin.

Frequently, processes of macrophages Frequently, processes of macrophages penetrate the spaces between endothelial cells penetrate the spaces between endothelial cells to enter the sinusoidal lumina. to enter the sinusoidal lumina.

The islands of hemopoietic cells are composed The islands of hemopoietic cells are composed of of blood cells in various stages of maturation as blood cells in various stages of maturation as well as well as macrophagesmacrophages..

The macrophages The macrophages destroy the extruded nuclei destroy the extruded nuclei of erythrocyte precursors, malformed cells, and of erythrocyte precursors, malformed cells, and excess cytoplasm.excess cytoplasm.

Macrophages also Macrophages also regulate hemopoietic cell regulate hemopoietic cell differentiation and maturation, transmit iron to differentiation and maturation, transmit iron to developing erythroblasts to be utilized in the developing erythroblasts to be utilized in the synthesis of the heme portion of hemoglobin.synthesis of the heme portion of hemoglobin.

Frequently, processes of macrophages Frequently, processes of macrophages penetrate the spaces between endothelial cells penetrate the spaces between endothelial cells to enter the sinusoidal lumina. to enter the sinusoidal lumina.

HEMATOPOIESHEMATOPOIESISIS

HEMATOPOIESHEMATOPOIESISIS

Mature blood cells have a relatively Mature blood cells have a relatively short life spanshort life span, and the population , and the population must be replaced with the progeny of must be replaced with the progeny of stem cells produced in the stem cells produced in the hematopoietichematopoietic organs organs..

In the earliest stages of In the earliest stages of embryogenesis, blood cells arise from embryogenesis, blood cells arise from the the yolk sac mesodermyolk sac mesoderm..

Later, the Later, the liver and spleen liver and spleen serve as serve as temporary hematopoietic tissues.temporary hematopoietic tissues.

After Birth, the After Birth, the bone marrow bone marrow becomes becomes an increasingly important an increasingly important hematopoietic tissue.hematopoietic tissue.

Mature blood cells have a relatively Mature blood cells have a relatively short life spanshort life span, and the population , and the population must be replaced with the progeny of must be replaced with the progeny of stem cells produced in the stem cells produced in the hematopoietichematopoietic organs organs..

In the earliest stages of In the earliest stages of embryogenesis, blood cells arise from embryogenesis, blood cells arise from the the yolk sac mesodermyolk sac mesoderm..

Later, the Later, the liver and spleen liver and spleen serve as serve as temporary hematopoietic tissues.temporary hematopoietic tissues.

After Birth, the After Birth, the bone marrow bone marrow becomes becomes an increasingly important an increasingly important hematopoietic tissue.hematopoietic tissue.

Erythrocytes, granular leukocytes, Erythrocytes, granular leukocytes, monocytes, and plateletsmonocytes, and platelets are derived are derived from from stem cells located in bone stem cells located in bone marrowmarrow. The origin and maturation of . The origin and maturation of these cells are termed, respectively, these cells are termed, respectively, erythropoiesis, granulopoiesis, erythropoiesis, granulopoiesis, monocytopoiesis, and monocytopoiesis, and megakaryocytopoiesismegakaryocytopoiesis..

The bone marrow also produces cells The bone marrow also produces cells that that migrate to the lymphoid organsmigrate to the lymphoid organs, , producing the producing the various types of various types of lymphocyteslymphocytes..

Erythrocytes, granular leukocytes, Erythrocytes, granular leukocytes, monocytes, and plateletsmonocytes, and platelets are derived are derived from from stem cells located in bone stem cells located in bone marrowmarrow. The origin and maturation of . The origin and maturation of these cells are termed, respectively, these cells are termed, respectively, erythropoiesis, granulopoiesis, erythropoiesis, granulopoiesis, monocytopoiesis, and monocytopoiesis, and megakaryocytopoiesismegakaryocytopoiesis..

The bone marrow also produces cells The bone marrow also produces cells that that migrate to the lymphoid organsmigrate to the lymphoid organs, , producing the producing the various types of various types of lymphocyteslymphocytes..

Stem CellsStem CellsStem CellsStem Cells Stem cells are Stem cells are pluripotentialpluripotential cells cells

capable of self-renewal.capable of self-renewal.

Some of their daughter cells form Some of their daughter cells form specific, irreversibly specific, irreversibly differentiated cell differentiated cell typestypes..

Other daughter cells Other daughter cells remain stem cellsremain stem cells..

A constant number of pluripotential stem A constant number of pluripotential stem cells is maintained in a pool, and cells cells is maintained in a pool, and cells recruited for differentiation are replaced recruited for differentiation are replaced with daughter cells from the pool.with daughter cells from the pool.

Stem cells are Stem cells are pluripotentialpluripotential cells cells capable of self-renewal.capable of self-renewal.

Some of their daughter cells form Some of their daughter cells form specific, irreversibly specific, irreversibly differentiated cell differentiated cell typestypes..

Other daughter cells Other daughter cells remain stem cellsremain stem cells..

A constant number of pluripotential stem A constant number of pluripotential stem cells is maintained in a pool, and cells cells is maintained in a pool, and cells recruited for differentiation are replaced recruited for differentiation are replaced with daughter cells from the pool.with daughter cells from the pool.

Progenitor CellsProgenitor CellsProgenitor CellsProgenitor Cells They have They have reduced potentiality reduced potentiality and are and are

committed to a single cell linage.committed to a single cell linage.

They proliferate and differentiate into They proliferate and differentiate into precursor cells precursor cells in the presence of in the presence of appropriate growth factors.appropriate growth factors.

They are morphologically They are morphologically indistinguishable (similar) to the stem indistinguishable (similar) to the stem cells, and both appear similar to small cells, and both appear similar to small lymphocytes.lymphocytes.

They have They have reduced potentiality reduced potentiality and are and are committed to a single cell linage.committed to a single cell linage.

They proliferate and differentiate into They proliferate and differentiate into precursor cells precursor cells in the presence of in the presence of appropriate growth factors.appropriate growth factors.

They are morphologically They are morphologically indistinguishable (similar) to the stem indistinguishable (similar) to the stem cells, and both appear similar to small cells, and both appear similar to small lymphocytes.lymphocytes.

Precursor CellsPrecursor CellsPrecursor CellsPrecursor Cells precursor cellsprecursor cells ( (blastsblasts) ) have their own have their own

morphological characteristics, and when morphological characteristics, and when they differentiate for the first time, they they differentiate for the first time, they indicate the mature cell types which they indicate the mature cell types which they will become.will become.

Whereas progenitor cells can divide and Whereas progenitor cells can divide and produce both progenitor and precursor produce both progenitor and precursor cells, cells, precursor cells produce only mature precursor cells produce only mature blood cellsblood cells..

precursor cellsprecursor cells ( (blastsblasts) ) have their own have their own morphological characteristics, and when morphological characteristics, and when they differentiate for the first time, they they differentiate for the first time, they indicate the mature cell types which they indicate the mature cell types which they will become.will become.

Whereas progenitor cells can divide and Whereas progenitor cells can divide and produce both progenitor and precursor produce both progenitor and precursor cells, cells, precursor cells produce only mature precursor cells produce only mature blood cellsblood cells..

Hemopoietic Growth Hemopoietic Growth FactorsFactors

Hemopoiesis is regulated by a number of Hemopoiesis is regulated by a number of cytokines and growth factorscytokines and growth factors, such as , such as interleukins, colony-stimulating factors (CSF, interleukins, colony-stimulating factors (CSF, macrophage inhibiting protein-a, and steel macrophage inhibiting protein-a, and steel factor.factor.

Hemopoiesis is regulated by Hemopoiesis is regulated by numerous growth numerous growth factors factors produced by various cell types. Each produced by various cell types. Each factor acts on specific factor acts on specific stem cells, progenitor stem cells, progenitor cells, and precursor cellscells, and precursor cells, generally inducing , generally inducing rapid mitosis, differentiation, or both.rapid mitosis, differentiation, or both.

Some of these growth factors also Some of these growth factors also promote the promote the functioning of mature blood cellsfunctioning of mature blood cells. Most . Most hemopoietic growth factors are hemopoietic growth factors are glycoproteinsglycoproteins..

Hemopoiesis is regulated by a number of Hemopoiesis is regulated by a number of cytokines and growth factorscytokines and growth factors, such as , such as interleukins, colony-stimulating factors (CSF, interleukins, colony-stimulating factors (CSF, macrophage inhibiting protein-a, and steel macrophage inhibiting protein-a, and steel factor.factor.

Hemopoiesis is regulated by Hemopoiesis is regulated by numerous growth numerous growth factors factors produced by various cell types. Each produced by various cell types. Each factor acts on specific factor acts on specific stem cells, progenitor stem cells, progenitor cells, and precursor cellscells, and precursor cells, generally inducing , generally inducing rapid mitosis, differentiation, or both.rapid mitosis, differentiation, or both.

Some of these growth factors also Some of these growth factors also promote the promote the functioning of mature blood cellsfunctioning of mature blood cells. Most . Most hemopoietic growth factors are hemopoietic growth factors are glycoproteinsglycoproteins..

Hemopoietic Growth Hemopoietic Growth FactorsFactors

Certain growth factors Certain growth factors such as steel factor (also such as steel factor (also known as stem cell factor), granulocyte-known as stem cell factor), granulocyte-macrophage colony-stimulating factor (GM-CSF) macrophage colony-stimulating factor (GM-CSF) and two interleukins (IL-3 and IL-7) and two interleukins (IL-3 and IL-7) stimulate stimulate proliferationproliferation of pluripotential stem cells, thus of pluripotential stem cells, thus maintaining their populations.maintaining their populations.

Additional cytokinesAdditional cytokines, such as granulocyte colony-, such as granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), IL-2, IL-5, IL-6, IL-11, stimulating factor (M-CSF), IL-2, IL-5, IL-6, IL-11, IL-12, macrophage inhibitory protein-α (MIP-α), IL-12, macrophage inhibitory protein-α (MIP-α), and erythropoietin, are believed to be and erythropoietin, are believed to be responsible responsible for the mobilization and differentiation of these for the mobilization and differentiation of these cells into unipotential progenitor cellscells into unipotential progenitor cells..

Certain growth factors Certain growth factors such as steel factor (also such as steel factor (also known as stem cell factor), granulocyte-known as stem cell factor), granulocyte-macrophage colony-stimulating factor (GM-CSF) macrophage colony-stimulating factor (GM-CSF) and two interleukins (IL-3 and IL-7) and two interleukins (IL-3 and IL-7) stimulate stimulate proliferationproliferation of pluripotential stem cells, thus of pluripotential stem cells, thus maintaining their populations.maintaining their populations.

Additional cytokinesAdditional cytokines, such as granulocyte colony-, such as granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), IL-2, IL-5, IL-6, IL-11, stimulating factor (M-CSF), IL-2, IL-5, IL-6, IL-11, IL-12, macrophage inhibitory protein-α (MIP-α), IL-12, macrophage inhibitory protein-α (MIP-α), and erythropoietin, are believed to be and erythropoietin, are believed to be responsible responsible for the mobilization and differentiation of these for the mobilization and differentiation of these cells into unipotential progenitor cellscells into unipotential progenitor cells..

Hemopoietic Growth Hemopoietic Growth FactorsFactors

It has been suggested that there are It has been suggested that there are

factors responsible for the factors responsible for the release of release of

maturemature (and almost mature) blood cells (and almost mature) blood cells

from the marrow.from the marrow.

These proposed factors have not yet been These proposed factors have not yet been

characterized completely, but they characterized completely, but they

include interleukins, CSF, and steel factor. include interleukins, CSF, and steel factor.

It has been suggested that there are It has been suggested that there are

factors responsible for the factors responsible for the release of release of

maturemature (and almost mature) blood cells (and almost mature) blood cells

from the marrow.from the marrow.

These proposed factors have not yet been These proposed factors have not yet been

characterized completely, but they characterized completely, but they

include interleukins, CSF, and steel factor. include interleukins, CSF, and steel factor.

ErythropoiesisErythropoiesis ErythropoiesisErythropoiesis, the formation of red blood cells, is , the formation of red blood cells, is

under the control of several cytokines, namely under the control of several cytokines, namely steel factor, IL-3, IL-9, GM-CSF, and steel factor, IL-3, IL-9, GM-CSF, and erythropoietin.erythropoietin.

The process of erythropoiesis, red blood cell The process of erythropoiesis, red blood cell formation, formation, generates 2.5 × 10generates 2.5 × 101111 erythrocytes erythrocytes every dayevery day..

In order to produce such a huge number of cells, In order to produce such a huge number of cells, two types of unipotential progenitor cellstwo types of unipotential progenitor cells arise arise from the from the CFU-GEMMCFU-GEMM (colony-forming units- (colony-forming units- granulocyte, erythrocyte, monocyte, granulocyte, erythrocyte, monocyte, megakaryocyte): the burst-forming units-megakaryocyte): the burst-forming units-erythrocyte (erythrocyte (BFU-EBFU-E) and colony-forming units-) and colony-forming units-erythrocyte (erythrocyte (CFU-ECFU-E))

ErythropoiesisErythropoiesis, the formation of red blood cells, is , the formation of red blood cells, is under the control of several cytokines, namely under the control of several cytokines, namely steel factor, IL-3, IL-9, GM-CSF, and steel factor, IL-3, IL-9, GM-CSF, and erythropoietin.erythropoietin.

The process of erythropoiesis, red blood cell The process of erythropoiesis, red blood cell formation, formation, generates 2.5 × 10generates 2.5 × 101111 erythrocytes erythrocytes every dayevery day..

In order to produce such a huge number of cells, In order to produce such a huge number of cells, two types of unipotential progenitor cellstwo types of unipotential progenitor cells arise arise from the from the CFU-GEMMCFU-GEMM (colony-forming units- (colony-forming units- granulocyte, erythrocyte, monocyte, granulocyte, erythrocyte, monocyte, megakaryocyte): the burst-forming units-megakaryocyte): the burst-forming units-erythrocyte (erythrocyte (BFU-EBFU-E) and colony-forming units-) and colony-forming units-erythrocyte (erythrocyte (CFU-ECFU-E))

ErythropoiesisErythropoiesisErythropoiesisErythropoiesis If the circulating red blood cell level is If the circulating red blood cell level is

low, the kidney produces a high low, the kidney produces a high concentration of concentration of erythropoietinerythropoietin,, which, in the presence of IL-3, IL-9, which, in the presence of IL-3, IL-9, steel factor, and GM-CSF (granulocyte-steel factor, and GM-CSF (granulocyte-monocyte colony stimulating factor), monocyte colony stimulating factor), induces induces CFU-GEMM to differentiate CFU-GEMM to differentiate into BFU-Einto BFU-E. These cells undergo a . These cells undergo a "burst" of "burst" of mitoticmitotic activity, forming a activity, forming a large number of CFU-Elarge number of CFU-E

If the circulating red blood cell level is If the circulating red blood cell level is low, the kidney produces a high low, the kidney produces a high concentration of concentration of erythropoietinerythropoietin,, which, in the presence of IL-3, IL-9, which, in the presence of IL-3, IL-9, steel factor, and GM-CSF (granulocyte-steel factor, and GM-CSF (granulocyte-monocyte colony stimulating factor), monocyte colony stimulating factor), induces induces CFU-GEMM to differentiate CFU-GEMM to differentiate into BFU-Einto BFU-E. These cells undergo a . These cells undergo a "burst" of "burst" of mitoticmitotic activity, forming a activity, forming a large number of CFU-Elarge number of CFU-E

ErythropoiesisErythropoiesisErythropoiesisErythropoiesis CFU-E require a low concentration of CFU-E require a low concentration of

erythropoietin not only to survive but also erythropoietin not only to survive but also to form the first recognizable erythrocyte to form the first recognizable erythrocyte precursor, the precursor, the proerythroblastproerythroblast..

The proerythroblasts and their progeny The proerythroblasts and their progeny form spherical clusters around form spherical clusters around macrophages macrophages (nurse cells)(nurse cells) which which phagocytose extruded nuclei and excess phagocytose extruded nuclei and excess or deformed erythrocytes.or deformed erythrocytes.

Nurse cells may also provide growth Nurse cells may also provide growth factors to assist erythropoiesis.factors to assist erythropoiesis.

CFU-E require a low concentration of CFU-E require a low concentration of erythropoietin not only to survive but also erythropoietin not only to survive but also to form the first recognizable erythrocyte to form the first recognizable erythrocyte precursor, the precursor, the proerythroblastproerythroblast..

The proerythroblasts and their progeny The proerythroblasts and their progeny form spherical clusters around form spherical clusters around macrophages macrophages (nurse cells)(nurse cells) which which phagocytose extruded nuclei and excess phagocytose extruded nuclei and excess or deformed erythrocytes.or deformed erythrocytes.

Nurse cells may also provide growth Nurse cells may also provide growth factors to assist erythropoiesis.factors to assist erythropoiesis.

MonocytopoiesisMonocytopoiesisMonocytopoiesisMonocytopoiesis Monocytes share their bipotential cells with Monocytes share their bipotential cells with

neutrophils.neutrophils.

CFU-GM undergoes mitosis and gives rise to CFU-G CFU-GM undergoes mitosis and gives rise to CFU-G

and and CFU-M (monoblasts).CFU-M (monoblasts).

The progeny of CFU-M are The progeny of CFU-M are promonocytes,promonocytes, large cells large cells

(16 to 18 μm in diameter) that have a kidney-shaped, (16 to 18 μm in diameter) that have a kidney-shaped,

acentrically located nucleus.acentrically located nucleus.

The cytoplasm of promonocytes is bluish and houses The cytoplasm of promonocytes is bluish and houses

numerous azurophilic granules.numerous azurophilic granules.

Monocytes share their bipotential cells with Monocytes share their bipotential cells with

neutrophils.neutrophils.

CFU-GM undergoes mitosis and gives rise to CFU-G CFU-GM undergoes mitosis and gives rise to CFU-G

and and CFU-M (monoblasts).CFU-M (monoblasts).

The progeny of CFU-M are The progeny of CFU-M are promonocytes,promonocytes, large cells large cells

(16 to 18 μm in diameter) that have a kidney-shaped, (16 to 18 μm in diameter) that have a kidney-shaped,

acentrically located nucleus.acentrically located nucleus.

The cytoplasm of promonocytes is bluish and houses The cytoplasm of promonocytes is bluish and houses

numerous azurophilic granules.numerous azurophilic granules.

MonocytopoiesisMonocytopoiesisMonocytopoiesisMonocytopoiesis Electron micrographs of promonocytes disclose a well-Electron micrographs of promonocytes disclose a well-

developed Golgi apparatus, abundant RER, and numerous developed Golgi apparatus, abundant RER, and numerous

mitochondria.mitochondria.

The azurophilic granules are lysosomes, about 0.5 μm in The azurophilic granules are lysosomes, about 0.5 μm in

diameter.diameter.

Every day, the average adult forms more than 10Every day, the average adult forms more than 101010

monocytes, most of which enter the circulation. monocytes, most of which enter the circulation.

Within a day or two, the newly formed monocytes enter the Within a day or two, the newly formed monocytes enter the

connective tissue spaces of the body and differentiate into connective tissue spaces of the body and differentiate into

macrophages. macrophages.

Electron micrographs of promonocytes disclose a well-Electron micrographs of promonocytes disclose a well-

developed Golgi apparatus, abundant RER, and numerous developed Golgi apparatus, abundant RER, and numerous

mitochondria.mitochondria.

The azurophilic granules are lysosomes, about 0.5 μm in The azurophilic granules are lysosomes, about 0.5 μm in

diameter.diameter.

Every day, the average adult forms more than 10Every day, the average adult forms more than 101010

monocytes, most of which enter the circulation. monocytes, most of which enter the circulation.

Within a day or two, the newly formed monocytes enter the Within a day or two, the newly formed monocytes enter the

connective tissue spaces of the body and differentiate into connective tissue spaces of the body and differentiate into

macrophages. macrophages.

Platelet FormationPlatelet FormationPlatelet FormationPlatelet Formation The formation of platelets is under the control of The formation of platelets is under the control of

thrombopoietin, which induces the development thrombopoietin, which induces the development and proliferation of giant cells known as and proliferation of giant cells known as megakaryoblasts. megakaryoblasts.

The unipotential platelet progenitor, The unipotential platelet progenitor, CFU-Meg,CFU-Meg, gives rise to a very large cell, the gives rise to a very large cell, the megakaryoblastmegakaryoblast (25 to 40 μm in diameter), (25 to 40 μm in diameter), whose single nucleus has several lobes.whose single nucleus has several lobes.

These cells undergo These cells undergo endomitosis,endomitosis, whereby the whereby the cell does not divide; instead, it becomes larger and cell does not divide; instead, it becomes larger and the nucleus becomes polyploid, as much as 64 N.the nucleus becomes polyploid, as much as 64 N.

The formation of platelets is under the control of The formation of platelets is under the control of thrombopoietin, which induces the development thrombopoietin, which induces the development and proliferation of giant cells known as and proliferation of giant cells known as megakaryoblasts. megakaryoblasts.

The unipotential platelet progenitor, The unipotential platelet progenitor, CFU-Meg,CFU-Meg, gives rise to a very large cell, the gives rise to a very large cell, the megakaryoblastmegakaryoblast (25 to 40 μm in diameter), (25 to 40 μm in diameter), whose single nucleus has several lobes.whose single nucleus has several lobes.

These cells undergo These cells undergo endomitosis,endomitosis, whereby the whereby the cell does not divide; instead, it becomes larger and cell does not divide; instead, it becomes larger and the nucleus becomes polyploid, as much as 64 N.the nucleus becomes polyploid, as much as 64 N.

Platelet FormationPlatelet FormationPlatelet FormationPlatelet Formation The bluish cytoplasm accumulates azurophilic The bluish cytoplasm accumulates azurophilic

granules. These cells are stimulated to granules. These cells are stimulated to differentiate and proliferate by thrombopoietin. differentiate and proliferate by thrombopoietin.

Megakaryoblasts differentiate into Megakaryoblasts differentiate into megakaryocytesmegakaryocytes , which are large cells (40 to , which are large cells (40 to 100 μm in diameter), each with a single 100 μm in diameter), each with a single lobulated nucleus.lobulated nucleus.

Electron micrographs of megakaryocytes Electron micrographs of megakaryocytes display a well-developed Golgi apparatus, display a well-developed Golgi apparatus, numerous mitochondria, abundant RER, and numerous mitochondria, abundant RER, and many lysosomes .many lysosomes .

The bluish cytoplasm accumulates azurophilic The bluish cytoplasm accumulates azurophilic granules. These cells are stimulated to granules. These cells are stimulated to differentiate and proliferate by thrombopoietin. differentiate and proliferate by thrombopoietin.

Megakaryoblasts differentiate into Megakaryoblasts differentiate into megakaryocytesmegakaryocytes , which are large cells (40 to , which are large cells (40 to 100 μm in diameter), each with a single 100 μm in diameter), each with a single lobulated nucleus.lobulated nucleus.

Electron micrographs of megakaryocytes Electron micrographs of megakaryocytes display a well-developed Golgi apparatus, display a well-developed Golgi apparatus, numerous mitochondria, abundant RER, and numerous mitochondria, abundant RER, and many lysosomes .many lysosomes .

Platelet FormationPlatelet FormationPlatelet FormationPlatelet Formation Megakaryocytes are located next to sinusoids, Megakaryocytes are located next to sinusoids,

into which they protrude their cytoplasmic into which they protrude their cytoplasmic processes. These cytoplasmic processes fragment processes. These cytoplasmic processes fragment along complex, narrow invaginations of the along complex, narrow invaginations of the plasmalemma, known as plasmalemma, known as demarcation demarcation channels,channels, into clusters of into clusters of proplatelets.proplatelets.

Shortly after the proplatelets are released, they Shortly after the proplatelets are released, they disperse into individual platelets. Each disperse into individual platelets. Each megakaryocyte can form several thousand megakaryocyte can form several thousand platelets. platelets.

The remaining cytoplasm and nucleus of the The remaining cytoplasm and nucleus of the megakaryocyte degenerate and are megakaryocyte degenerate and are phagocytosed by macrophages. phagocytosed by macrophages.

Megakaryocytes are located next to sinusoids, Megakaryocytes are located next to sinusoids, into which they protrude their cytoplasmic into which they protrude their cytoplasmic processes. These cytoplasmic processes fragment processes. These cytoplasmic processes fragment along complex, narrow invaginations of the along complex, narrow invaginations of the plasmalemma, known as plasmalemma, known as demarcation demarcation channels,channels, into clusters of into clusters of proplatelets.proplatelets.

Shortly after the proplatelets are released, they Shortly after the proplatelets are released, they disperse into individual platelets. Each disperse into individual platelets. Each megakaryocyte can form several thousand megakaryocyte can form several thousand platelets. platelets.

The remaining cytoplasm and nucleus of the The remaining cytoplasm and nucleus of the megakaryocyte degenerate and are megakaryocyte degenerate and are phagocytosed by macrophages. phagocytosed by macrophages.

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