Hematopoeitic Hematopoeitic SystemSystem

dr. Alya Amila Fitrie, M.Kes dr. Zulham, M.BiomedDepartment of HistologyMedical FacultyN th S t U i itNorth Sumatera University

Blood Cells

M t bl d ll l ti l h t Mature blood cells : relatively short life span → continuously replaced with the progeny of stem cells with the progeny of stem cells produced in the hematopoeitic organsorgans.

STEM CELLS, GROWTH FACTORS & DIFFERENTIATIONFACTORS & DIFFERENTIATION

Stem CellsStem Cells

Stem cells

Pluripotential cells capable of self renewal

Remain stem

Specific, irreversiblystem

cellsirreversibly

differentiated cell types

Pluripotential Hematopoietic Stem Cells

L h id ll

Migrate from the bone marrow to the lymphoid organ, where they proliferate : lymphocytes

Lymphoid cells

All blood cells arise from a single type of stem cell in the bone marrow →

pluripotential stem cells

Myeloid cellsy

Develop in bone marrow : granulocytes, monocytes, erythrocytes & megakaryocytes

Progenitor & Precursor Cells

Stem cells, pluripotential cells

Progenitor cells, unipotential or bipotential cell

Precursor cells The morphologic characteristics differentiate for the first time

Mature cells

Differentiation of pluripotential cells during hematopoeisis

Hematopoeitic Growth Factors

Have different chemical composition Have different chemical composition & complexHave overlapping functionsHave overlapping functionsAct mainly by :1 Stimulating proliferation of immature 1. Stimulating proliferation of immature

cells2. Supporting the differentiation of

llmaturing cells3. Enhancing the functions of mature cells.

Hematopoeitic Growth Factors (Colony-forming substances)(Colony forming substances)

Name Human Gene Location & Producing Cells

Main Biologic Activity

Granulocyte-CSF Chromosome 17 Stimulates formation of granulocytes.Enhance metabolism of granulocytesEnhance metabolism of granulocytes.Stimulates malignant (leukemic) cells.Macrophages, Endothelium, Fibroblast

Granulocyte +Macrophage (GM-

Chromosome 5 Stimulates in vitro and in vivo production of granulocytes and macrophages.p g (

CSF)g y p g

T lymphocytes, Endothelium, Fibroblast

Macrophage (M-CSF) Chromosome 5 Stimulates formation of macrophages in vitro.Increases antitumor activity ofMacrophages, Endothelium, Fibroblast Increases antitumor activity of macrophages.

p g , ,

Interleukin 3 (IL-3) Chromosome 5 Stimulates in vivo and in vitro production of all myeloid cells.

T lymphocytes

Erythropoeitin (EPO) Chromosome 7 Stimulates red blood cells formation in vivo and in vitro.

Renal interstisial cells (outer cortex)

BONE MARROW

Found in the medullary canals of long bones & in the cavities of cancellous the cavities of cancellous bone.Two types of bone marrow yp:1. Red or hematogenous bone

marrow → blood & blood-a o → b ood & b oodforming cells

2. Yellow bone marrow →adipose cellsp

All newborn → red b.m.Growth : red → yellow b.m.

Red Bone Marrow

Composed of : stroma, hematopoietic cords & sinusoidal capilarries.pRelease of mature blood cells →releasing factors , e.q. C3,hormone, g , q , ,some bacterial toxins.Function : production blood Function : production blood cells,destruction of worn-out RBC & storage of iron derived from the gbreakdown of Hb.

The passage of blood cells across a p gsinusoid capillary in red bone marrow

MATURATION OF ERYTHROCYTESERYTHROCYTES

Summary of erythrocyte maturation

Hemoglobine concentration ↑↑concentration ↑↑Nuclear volume↓graduallyg adua yChromatin condensation ↑↑Extrussion of pyknotic nucleus

Differentiation of Erythrocytes

Proerythroblast

Basophilic

Large cell, lacy chromatin, visible nucleoli, basophilic cytoplasm

St l b hili t l d dBasophilic erythroblast

Polychromatophilic

Strongly basophilic cytoplasm, condensed nucleus, no visible nucleolus

Appear several colors in the cellPolychromatophilic erytroblast

Orthochromatophilic

Appear several colors in the cell

Condensed nucleus, no basophilic t l if l id hili t lOrthochromatophilic

erythroblast

Reticulocyte

cytoplasm, a uniformly acidophilic cytoplas

Small number of polyribosomes, nucleus (-)Reticulocyte

Erythrocyte Biconcave form, nucleus (-)

GRANULOPOEISISGRANULOPOEISIS

Maturation Process of Granulocytes

1. Cytoplasmic changes : synthesis of 1. Cytoplasmic changes : synthesis of a number of proteins that are packed in 2 organelles : p gazurophilic & specific granules

2. Change in synthetic activity →2. Change in synthetic activity →production of several proteins that are packed in specific granulesp p g

Differentiation of Granulocytes

Myeloblast

Promyelocyte φ larger, spherical or ovoid nucleus, basophilic cytoplasm but, locally acidophilic (+) as azurophilic granules.

Myelocyte Specific granules <<, Azurophilic >>, band nucleus

Metamyelocyte Abundant specific granules, Azurophilic’s <<, Lobulated nucleus except basophilia

Granulopoeisis

Stages in the development of erytrocytes and granulocytes

Section of stimulated red bone marrow

Section of red bone marrow with a group of erythropoeitic cells & a group of erythropoeitic cells & a group of neutrophilopoeitic cells

KINETICS OF NEUTROPHIL PRODUCTIONPRODUCTION

Kinetics of Neutrophil Production

MATURATION OF LYMPHOCYTES & MONOCYTESLYMPHOCYTES & MONOCYTES

Lymphocytes

Lymphocytes progenitor cells

in the bonemigrate in the bone marrow

Thymus → full attributes of T

In the bone marrow, lymphocytes differentiate

migrate

attributes of T lymphocytes

lymphocytes differentiate → B lymphocytes

migrate

T lymphocytes populate spesific regions of

peripheral lymphoid

Peripheral lymphoid organs, B lymphocytes

inhabit & multiply in their

Peripheral lymphoid organs, B lymphocytes

inh bit & m ltipl in theiorgans inhabit & multiply in their own special compartmentsinhabit & multiply in their own special compartments

Monocytes

MonoblastIdentical to the myeloblast in its morphologic characteristic

Promonocyteφ up to 18 μm, basophilic cytoplasm, large & slightly indented nucleus, nucleoli are evident

differentiation

Monocyte Macrophagesbloodstream --- connective tissue

ORIGIN OF PLATELETSORIGIN OF PLATELETS

Origin of Platelets

φ 15-50 μm, large ovoid nucleus, numerous nucleoli, cytoplasm homogenous and basophilic

Differentiation

φ 35-150 μm, irregularly lobulated nucleus, coarse chromatine, no visible nucleoli

Fragmentation of the cytoplasm of mature megakaryocyte

Megakaryocyte

A megakaryocyte in a section of red bone marrow.One nucleusGranular cytoplasmGranular cytoplasm

Referensi

Basic Histology, Text and Atlas, tenth edition, Luis Carlos Junqueira & Jose , qCarneiro, 2003.Histology & Cell Biology,Kierszenbaum.E ti l f H Hi t l S d Essentials of Human Histology, Second Edition, William J.Krause, 1996.Color Atlas of Basic Histology, Second Color Atlas of Basic Histology, Second Edition, Lange, Irwin Berman, 1998.Wheather’s Functional Histology, A Text and Colour Atlas Fifth Edition Barbara and Colour Atlas, Fifth Edition, Barbara Young, et al., 2006

Thank youTerima kasih

Thank you…Terima kasih…