Tabuk UniversityTabuk UniversityFaculty of Applied Medical SciencesFaculty of Applied Medical SciencesDepartment Of Medical Lab. Department Of Medical Lab.

TechnologyTechnology

22ndnd Year – Level 4 – Year – Level 4 – AY 1433-1434 AY 1433-1434

Normal Haemopoiesis

الدم خاليــا إنتاج

Mr. Waggas Elaas, M.Sc, MLT

ReferencesReferences For theory : For theory : 1.1. Essential Haematology, John Wiley & Sons Ltd ,6th Edition,Victor Hoffbrand.Essential Haematology, John Wiley & Sons Ltd ,6th Edition,Victor Hoffbrand.2.2. Harmening, Denise. (2009) . Harmening, Denise. (2009) . Clinical Hematology and Fundamentals of HemostasisClinical Hematology and Fundamentals of Hemostasis . 5th . 5th

Edition, F. A. Davis Company Edition, F. A. Davis Company For practical : For practical : 1.1. Practical Haematology, Churchill Livingstone, Eighth edition, John V. Dacie, S. M. Lewis, Practical Haematology, Churchill Livingstone, Eighth edition, John V. Dacie, S. M. Lewis, 2.2. Fischbach and Dunning. (2009). Fischbach and Dunning. (2009). A Manual on Laboratory Diagnostic TestsA Manual on Laboratory Diagnostic Tests. 8. 8thth Edition. Wolters Edition. Wolters

Kluwer Health Lippincott Williams and Wilkins, PAKluwer Health Lippincott Williams and Wilkins, PA ATLAS:ATLAS:1.1. Carr and Rodak. (2008). Carr and Rodak. (2008). Clinical HematologyClinical Hematology. 3rd Edition, Saunders/Elsevier . 3rd Edition, Saunders/Elsevier Internet site(s):Internet site(s):1.1. http://www.essentialhaematology6.com/default.asp = MCQshttp://www.essentialhaematology6.com/default.asp = MCQs2.2. http://www.hematologyatlas.com/http://www.hematologyatlas.com/3.3. http://pathy.med.nagoya-u.ac.jp/atlas/doc/atlas.htmlhttp://pathy.med.nagoya-u.ac.jp/atlas/doc/atlas.html4.4. http://themedicalbiochemistrypage.org/http://themedicalbiochemistrypage.org/5.5. http://www.bloodline.net/http://www.bloodline.net/

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MarksMarks

Final Theoretical exam : 40Final Theoretical exam : 40 Final Practical exam : 20 (including written questions)Final Practical exam : 20 (including written questions) 11stst Periodic exam : 10 theory, 5 Practical Periodic exam : 10 theory, 5 Practical 22ndnd Periodic exam : 10 theory, 5 Practical Periodic exam : 10 theory, 5 Practical Homework and class activities : 5 Theory, 5 PracticalHomework and class activities : 5 Theory, 5 Practical Total : 100Total : 100

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ObjectivesObjectives1. To introduce Hematology to the students as a new science.2. To identify blood components and the function of each.3. To know the sites of Hemopoiesis (blood production).4. To know the different stages of cell production of each cell

linage.5. To be able to differentiate between blood cells especially

white cells.

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What is hematologyWhat is hematology??

Hematology is the study of Hematology is the study of bloodblood which is composed of which is composed of plasma (55%), and the formed elements which are:plasma (55%), and the formed elements which are:– The The erythrocyteserythrocytes (RBCs) (44%) (RBCs) (44%)

Contain hemoglobin Contain hemoglobin Function in the transport of OFunction in the transport of O22 and CO and CO22

– The The LeukocytesLeukocytes (WBCs) and (WBCs) and plateletsplatelets (thrombocytes) (1%) (thrombocytes) (1%) Leukocytes are involved in the body’s defense against Leukocytes are involved in the body’s defense against

the invasion of foreign antigens.the invasion of foreign antigens. Platelets are involved in hemeostasis which forms a Platelets are involved in hemeostasis which forms a

barrier to limit blood loss at an injured site.barrier to limit blood loss at an injured site.

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Functions of blood :Functions of blood :

1.Transports O2 and Co2 between tissues.

2. Transports nutrients (Glucose, vitamins ..etc).3. Take waste products such as lactic acid away from

the muscles ; and urea from the liver to the kidneys.4. Maintain body temperature.5. Defense – White blood cells.6. Coagulation.

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Hematopoiesis =Hematopoiesis = Hemopoiesis Hemopoiesis

Hematopoiesis is a term describing the formation Hematopoiesis is a term describing the formation and development of blood cells.and development of blood cells.

Hematopoiesis in the bone marrow is called Hematopoiesis in the bone marrow is called Medullary hematopoiesisMedullary hematopoiesis..

Hematopoiesis in areas other than the bone marrow Hematopoiesis in areas other than the bone marrow is called is called Extramedullary hematopoiesisExtramedullary hematopoiesis

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Sites of HaemopoiesisSites of Haemopoiesis Fetus : Fetus : 0 – 2 months Yolk sac0 – 2 months Yolk sac 2 – 7 months Liver2 – 7 months Liver 5 – 9 months Bone marrow5 – 9 months Bone marrow Liver and spleen continue to produce cells until 2 weeks Liver and spleen continue to produce cells until 2 weeks

after birth.after birth.

In infancy, all the B.M is hemopoietic with progression In infancy, all the B.M is hemopoietic with progression to fatty tissues.to fatty tissues.– Gradual replacement of active (red) marrow by inactive (fatty) tissue (50% of Gradual replacement of active (red) marrow by inactive (fatty) tissue (50% of

hemopoietic B.M in adults is fatty tissues)hemopoietic B.M in adults is fatty tissues)– Expansion can occur during increased need for cell productionExpansion can occur during increased need for cell production

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In adult life, hemopoietic B.M is restricted to In adult life, hemopoietic B.M is restricted to central skeleton – proximal ends of femurs central skeleton – proximal ends of femurs (( الفخذ الفخذ عظم ).and humeri.() and humeri (عظم العضد العضد عظم ((عظم

Hemopoiesis can extend to long bones.Hemopoiesis can extend to long bones. Liver & spleen can resume hemopoiesis = Liver & spleen can resume hemopoiesis =

Extramedullary Hemopoiesis.Extramedullary Hemopoiesis.

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First cell : First cell : Pluripotential Stem Cell (Pluripotential Stem Cell (PCSPCS))

Appear like small Lymphocyte.Appear like small Lymphocyte. Rare in B.M : 1 in every 20 million nucleated Rare in B.M : 1 in every 20 million nucleated

cell.cell. Self – renewal capacity B.M cellularity Self – renewal capacity B.M cellularity

remain constant.remain constant.Hemopoietic progenitors : Hemopoietic progenitors : When stem cells When stem cells

differentiatedifferentiate

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11stst progenitor cell : progenitor cell : CFU-GEMMCFU-GEMM CColony olony FForming orming UUnit – nit – GGranulocyte, ranulocyte,

EErythrocyte, rythrocyte, MMonocyte, onocyte, MMegakaryocyteegakaryocyte stem cell (self – renewal)stem cell (self – renewal)

Stem cell divide Stem cell divide

Committed stem cellCommitted stem cell (progenitor)(progenitor)

differentiation & division differentiation & division

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Stem cells are linked with Stromal cell Stem cells are linked with Stromal cell (adipocyte, fibroblast, endothelial cells, (adipocyte, fibroblast, endothelial cells, macrophagesmacrophages).).

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Stromal cells secrete substances needed by Stromal cells secrete substances needed by stem cell to survive . ( collagen, fibronoectin, stem cell to survive . ( collagen, fibronoectin, growth factors).growth factors).

Growth factors are hormones that regulate Growth factors are hormones that regulate proliferation & differentiation of cells.proliferation & differentiation of cells.

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Erythropoiesis and erythrocytesErythropoiesis and erythrocytes Lifespan of Red cells – 120 daysLifespan of Red cells – 120 days Non nucleatedNon nucleated Biconcave discBiconcave disc Production regulated by ErythropoietinProduction regulated by Erythropoietin Needs Fe, BNeeds Fe, B1212, folate & other elements , folate & other elements

for development.for development.

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CFUe the first recognizable cell in this lineage. Large CFUe the first recognizable cell in this lineage. Large cell with dark blue cytoplasm, central nucleus and cell with dark blue cytoplasm, central nucleus and nuclei and slightly clumped chromatin. The nuclei and slightly clumped chromatin. The cytoplasm stains paler blue as it loses its RNA and cytoplasm stains paler blue as it loses its RNA and protein synthesis apparatus and nuclear chromatin protein synthesis apparatus and nuclear chromatin becomes more condense. The nucleus is finally becomes more condense. The nucleus is finally extruded from the late normoblast with in the extruded from the late normoblast with in the marrow and reticulocyte are formed which still marrow and reticulocyte are formed which still contains RNA and still can synthesize hemoglobin.contains RNA and still can synthesize hemoglobin.

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WBCs = LeucocytesWBCs = Leucocytes

PhagocytesPhagocytes ImmunocytesImmunocytes (granulocytes +monocytes) (lymphocytes)(granulocytes +monocytes) (lymphocytes)

- Neutrophils (polymorphs)Neutrophils (polymorphs)- EosinophilsEosinophils- BasophilsBasophils- MonocytesMonocytes

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Leucopoiesis Leucopoiesis MyeloblastMyeloblast Promyelocyte Promyelocyte myelocytemyelocyte

MetamyelocyteMetamyelocyte

Band/stab/juvenileBand/stab/juvenileNeutrophilNeutrophil

NeutrophilNeutrophil

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MonocyteMonocyte::

Monoblast promonocyte Monocyte Monoblast promonocyte Monocyte (myelomonblast)(myelomonblast)

MacrophageMacrophage(in tissues)(in tissues)

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LymphopoiesisLymphopoiesis Primary lymphoid organs (Primary lymphoid organs (lymphocytes developlymphocytes develop))

Bone marrowBone marrow ThymusThymus

Secondary lymphoid organs (Secondary lymphoid organs (specific immune responses are generatedspecific immune responses are generated)) Lymph nodesLymph nodes SpleenSpleen Lymphoid tissuesLymphoid tissues

LymphocytesLymphocytes according to according to sizesize : small & large lymphocytes : small & large lymphocytes

according to according to immunityimmunity : T & B lymphocytes : T & B lymphocytes

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B cells mature in the bone marrow and circulate in the peripheral blood until they B cells mature in the bone marrow and circulate in the peripheral blood until they undergo recognition of antigen. The B-cell receptor is membrane-bound undergo recognition of antigen. The B-cell receptor is membrane-bound immunoglobulin and after activation this is secreted as free soluble immunoglobulin and after activation this is secreted as free soluble immunoglobulin. At this point they mature into memory B cells or plasma cellsimmunoglobulin. At this point they mature into memory B cells or plasma cells

T cells develop from cells that have migrated to the thymus where they T cells develop from cells that have migrated to the thymus where they differentiate into mature T cells during passage from the cortex to the medulla. differentiate into mature T cells during passage from the cortex to the medulla.

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ThrombopoiesisThrombopoiesis Platelets play a major role in primary hemostasis,Platelets play a major role in primary hemostasis, Life span 7-10 days.Life span 7-10 days. Small discoid non nucleated.Small discoid non nucleated. Produced in B.M by fragmentation of cytoplasm of Produced in B.M by fragmentation of cytoplasm of

megakaryocytes.megakaryocytes. Megakaryocytes undergoes endomitotic division = DNA Megakaryocytes undergoes endomitotic division = DNA

replication without nuclear or cytoplasmic division.replication without nuclear or cytoplasmic division. One megakaryocyte gives 1000 – 5000 pltsOne megakaryocyte gives 1000 – 5000 plts Thrombopoietin hormone (produced by liver & kidney) is the Thrombopoietin hormone (produced by liver & kidney) is the

main regulator.main regulator.

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Stem cellStem cell

megakaryoblastmegakaryoblast

promegakaryocytepromegakaryocyte

megakaryocytemegakaryocyte

plateletsplatelets

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HomeworHomework-1k-11. List the organs or systems involved in adult hematopoiesis. 1. List the organs or systems involved in adult hematopoiesis. 2. Describe a "pluripotent cell". 2. Describe a "pluripotent cell". 3. Define the following terms: 3. Define the following terms: a. erythropoiesis a. erythropoiesis b. granulopoiesis b. granulopoiesis c. lymphopoiesis c. lymphopoiesis

d. megakaryopoiesis d. megakaryopoiesis 4. Differentiate between a monocyte and a macrophage. 4. Differentiate between a monocyte and a macrophage. 5. The hematopoietic stem cell is capable of :5. The hematopoietic stem cell is capable of :a-Replicationa-Replicationb-Differentiationb-Differentiationc-Replication and differentiationc-Replication and differentiation6. The process of hematpoiesis under the control of:6. The process of hematpoiesis under the control of:a- Growth hormonea- Growth hormoneb- Hematopoietic growth factorscb- Hematopoietic growth factorscc- Thyroid hormonec- Thyroid hormone 2929