Hematopoiesis

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Hematopoiesis
-Cell renewal
-Must never stop but must be regulated
-The ones that regulates (controls ng bilis or bagal) hematopoiesis are hormones
-Bone marrow- major blood forming organ (particularly happens in red bone marrow)
-When hematopoiesis has stopped, RBC, WBC and platelets count will decrease
-Pag bagsak ang 3 cellular elements ng blood will lead to pancytopenia- pan (all) cyto (cells)
penia (decreased)
-Pag sobrang dami ang RBC, WBC and platelets will lead to pancytosis
-Cells elevated (pancytosis)
-Cells decreased (pancytopenia)

-Life Span
-RBC: 120 days (4 months), after this, they will die (sometimes hindi umaabot ng 120 days kasi may mga
factors na nagpapaaga ng pagkamatay ng RBC)
*RBC must be renewed because when it is not renewed or lowered RBC count will lead to anemia

-WBC: 5-7 days

*After 5-7 days, WBC must also be replenished or renewed
*Decreased wbc count will lead to leukopenia or leukocytopenia
*Increased wbc count or uncontrolled wbc count will lead to leukemia

-Plateletes: 7-10 days

*After 7-10 days, they will die
*Must also be replenished or renewed
*Decreased platelet count will lead to thrombocytopenia

Proliferation
-Pagdami
-Among the 3 cells of the blood, the most abundant (pinakamarami) is RBC, followed by WBC and least
abundant is platelets

Differentiation
-RBC, WBC and platelets ay nanggaling lang sa iisang cell
Maturation
-After differentiation, maturation
-Blast- young or immature
*Usually still stored in bone marrow
-Cyte- mature cell or counter part of young cell
*Can leave the bone marrow

-Functions
RBC: gas exchange (O2 and CO2)
WBC: defense and protection
Platelets: for coagulation or clotting of blood
*Hemostasis- proper term for coagulation or clotting of blood

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Hematopoiesis ppt
Theories
1. Monophyletic theory
-Currently accepted theory
-Single type of stem cell gives rise to all the mature blood cells in the body
-Yung isang cell daw, sa kanya nanggaling lahat ng cells (RBC, WBC, platelets)
-Theory states that all cells derived from a single type of stem cell called pluripotential stem cell or
multipotent progenitor hematopoietic stem cell

2. Polyphyletic theory
-Theory states that iba-iba pinanggalingan ng RBC, WBC, platelets

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Origin of Blood Cells ppt
Types of human Stem Cells
1. Totipotential Stem Cells
-First type of stem cell that is being produced
-First few hours after ovum is fertilized the first stem cell that is being formed
-Most versatile (pwede maging kahit anong cell, pwedeng cell sa ganitong organ or ganung organ)
-Can develop into any cell type ppt

2. Pluripontential Stem Cell or Multipotent Progenitor Hematopoietic Stem Cell

-From totipotential to pluripotential
-2nd type of stem cell
-Several days after fertilization
-Can develop into ppt
-Versatile also but except developing into fetus
-Pag hindi nag develop, magkakaroon ng abnormalities kaya dapat maging multipotential stem cell
3. Multipotential Stem Cell
-Derived from pluripotent stem cells
-Totipotential (few hours after ovum is fertilized) -> pluripotential (several days) -> multipotential
-Can now be found in adults
-They are limited to specific types of cell ppt (hindi sila versatile)
-Multipotential could be RBC, WBC and platelets (blood cells), bone cartilage, and adipose or fat cells

Note:
Monophyletic theory
-All cells in the blood are only derived in pluripotent or pluripotential stem cell

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3 Phases/ Stages of Hematopoiesis
1. Mesoblastic Phase/ Yolk Sac Phase
-Target destination: yolk sac
-Begins around ppt
-Cells from the ppt
*3 Germ Layers
1. Endoderm (inside)
2. Mesoderm (center or middle)
3. Ectoderm (outside)
-After they entered the yolk sac, some if these cells form primitive erythroblast (immature rbc)
-This process occurs intravascularly (loob ng blood vessels)
-Thus, mesoblastic phase only happens inside the blood vessel
-This process (mesoblastic phase) remains active for 8-12 weeks

Note:
Progenitor cells of mesenchymal region ppt
Also, hindi lahat makakarating sa yolk sac

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-Aorta-gonad-mesonephron (AGM) gives rise to Hematopoietic stem cells (HSCs) but not Primitive
erythroblast (PE)
-PE arise from ppt
-Yolk sac was ppt
-Hemoglobins (seen inside the RBC) produced during mesoblastic phase
*Gower-1, Gower-2 and Portland for rapid delivery of oxygen to developing blood vessels
-Remaining cells become angioblast (angio- blood vessel, blast- young)
*Angioblast will form new blood vessels
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2. Hepatic phase
-2nd phase
-Occurs primarily in liver
-Begins at 5-7 gestational weeks but the peak level is on the 3 rd month and declines after 6th month
-Characterized by recognizable clusters of developing erythroblast, granulocytes (in the WBC) and
monocytes colonizing (inside of) fetal liver, thymus, ppt
*Nagkakaroon na ng WBC ang fetus kasi at this phase, pwede na dapuan ng microbes or pwede na
magkaroon ng infection yung fetus or baby sa loob ng womb ng mother
-Pag nag simula na ang hepatic phase, unti-unti nang nadedecline ang yolk sac phase
-Lymphoid cells (lymphocytes for viral infection) begin to appear because common infection of fetus is
viral in nature
-Haptic phase is extravascular (kasi nagnyayari sa liver or labas ng blood vessels)

Additional note:
Yolk sac started at the 19th day that remains active up until 8-12 weeks (12 th week, mag stop na ang
mesoblastic phase)
But, 5th week palang (5-7 gestational weeks), umaangat na ang hepatic phase
It is because hematopoiesis is continuous (tuloy tuloy hindi napuputol)
Bago matapos yung isa, nagsisimula na yung isa

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-Hematopoiesis in the ppt
-Hematopoiesis in the fetal liver reaches ppt
* Begins at 5-7 gestational weeks but the peak level is on the 3 rd month and declines after 6th month
-Thymus ppt
*Site of production for T cells- dun ginagawa ang T cells sa thymus
*Site of production for B cells- kidneys and spleen
*However, site of maturation of T cells- also thymus
*For site of maturation of B cells- bone marrow
-Hepatic phase has predominant (pinakamarami) hemoglobin: fetal hemoglobin (Hb F)
*Small amounts of: Adult Hemoglobin or Hemoglobin A (Hb A) or (Hb A1)

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3. Medullary Phase/ Myeloid Phase
-Myelo (from the bone marrow particulary in red bone marrow)
-3rd and last phase of hematopoiesis
-Prior to 5th month hematopoiesis in medullary or bone marrow starts
-During this phase, the hematopoietic stem cells and mesenchymal cells migrate into the core of the
bone (medulla)
-RBCs and WBCs begin to rise kaya minemeasure na ang M:E ratio (M- Myeloid- WBCs & E- Erythroid-
RBCs) or dami ng WBCs and RBCs
-Average M:E ratio is 3:1 (3x na mas marami ang WBCs compared to RBCs) and
the normal range is 2:1 – 4:1 (thus, 2:1, 4:1, normal)
-Inside the bone marrow, mas maraming WBCs (3x na mas marami compared to RBCs)

Summary of the Phases:

1st phase (mesoblastic or yolk sac during 19th day of fetal development and will remain active up until 8-
12 weeks) -> (before 8-12 weeks stops, during 5 th gestational week, hepatic phase will start and it will
reach its peak during the 3rd month and will decline after 6th month ) -> (before hepatic phase stops,
during the 5th month, medullary /myeloid phase starts)

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-By the end of 24 weeks/6 months ppt
-In medullary/ myeloid phase
-Bone marrow becomes the primary site wherein hematopoiesis occurs

-In medullary/myeloid phase, makakita or measurable levels of erythropoietin (EPO) (hormone that
controls RBC production), G-CSF (Granulocyte Colony Stimulating Factor, hormones that stimulates
granulocyte production), GM-CSF (Granulocyte Monocyte Colony Stimulating Factor, hormones that
controls or stimulates monocyte and granulocytes), Hgb F and A or A1 and also Hbg A2 but small
amounts only
*WBCs with granules (BEN- Basophil, Eosinophil, Neutrophil)

-In adults, medullary/ myeloid phase happens in sternum and other flat bones

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Adult Hematopoietic Tissue
-In adults, dito nalang pwedeng icheck ang hematopoiesis. Thus, other parts of the body, hindi na
involved
-Meron nalang 5 locations:
Bone marrow (particularly red bone marrow)
-Major hematopoietic tissue
Lymph Nodes
Thymus
Spleen
Liver
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Primary Lymphoid Tissue
Bone Marrow
-Maturation site of B lymphocytes (short lived)

Thymus
-Maturation of T lymphocytes (long lived)

Secondary Lymphoid Tissue

-Where the lymphoid cells respond to foreign antigens
-Area where accumulated or trapped foreign materials are found
-Where:
Spleen
Lymph Nodes
Mucosa-associated Tissue (malt)
*Can be found in intestine or GI tract

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Bone Marrow
-Tissue located ppt
-Major site of cell production
-Contains developing:
Erythroid (rbc)
Myeloid (wbc)
Megakaryocytic (platelets)
Lymphoid cells (lymphocytes)

Functions:
Major
-Hematopoiesis
Minor
-Involvement in the immune system or immunity

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Major Components of Bone Marrow
Red Marrow/ Active Marrow
-As we grow old, active marrow decreases and yellow marrow/inactive marrow (consists adipose tissue
or adipocytes and it doesn’t have involvement in hematopoiesis) increases

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Yellow Marrows/ Adipocytes
-Between 5-7 years of age, yellow marrow increases and red marrow decreases
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-Retrogression- the process of replacing active marrow by adipocytes
-Adults, mga butong pwedengmag perform ng hematopoiesis:
*Sternum
*Vertebrae
*ppt

Pwede bang dumami ulit yung red bone marrow at kumonti ulit yung yellow bone marrow?
-Yes in cases of increased demand on the bone marrow such as in:
Excess blood loss
Hemolysis

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Myeloid: Erythroid (M:E) Ratio
-We compare numbers of WBCs and RBCs
-Comparing relative number of granulocytic (BEN- Baso, Eo, Neutro, Hinid kasama si Lymph and Mono)
precursors with relative erythroid precursors in the bone marrow ppt
-Normal ppt
-Bakit sa bone marrow mas maraming WBCs compared sa RBCs?
*Kasi mas maikli ang buhay ng WBCs, dapat mas mabilis silang palitan
-Granulocytes are more numerous ppt
-Granulocytes or WBCs (usual life span: 5-7 days) pero pag sila ay nautilized, may infection or microbes,
within 1-2 days, pwede na silang mamatay

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Pagkapanganak mas marami yung red marrow compared to yellow marrow
Bone Marrow Cellularity
%Red
-At birth up to less than 2 years old (100%) some other books (80%-90%)
-Young adults or 20 y/o and above (60%)
-Older adults or 55 y/o and above (40%)

%Yellow
-At birth up to less than 2 years old (10%-20%)
-Young adults or 20 y/o (40%)
-Older adults or 55 y/o and above (60%)

Note:
Between 5-7 y/o (age when red marrow decreases and yellow marrow increases or AKA retrogression)
%Hematopoietic cells in the bone marrow
-If 30%-70% (Normocellular)
-If > 70% (Hypercellular or Hyperplastic)
-If < 30% (Hypocellular or Hypoplastic)
-If few or no hematopoietic cells (aplastic)

Abnormal M:E Ratio

M:E (Myeloid: Erythroid)
Myeloid or WBCs (Only BEN- Baso, Eo, Neutro)
Normal: 2:1-4:1
Ave: 3:1

Infection (6:1)
Leukemia or Blood Cancer (25:1)
Myeloid hyperplasia (20:1)
Myeloid hypoplasia (3:20)
Erythroid hyperplasia (1:20)
Erythroid hypoplasia (5:1)

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Collection of the Bone Marrow
-Doctors collect bone marrow sample not medical technologists
Through:
A- aspirate
B- Biopsy

Bone Marrow Biopsy ppt

-Using needle (there are needles for bone marrow biopsy)
-Trephine
-ppt
-Purpopse of bone marrow biopsy: provides adequate red marrow

Note: ppt
-Site of bone marrow biopsy collection
-Also ang unang ginagawa ay biopsy before aspiration
-B before A
-Thus, parehas ginagawa (B 1st followed by A)
-Inuuna ang biopsy because aspiration may destroy bone marrow architecture
Note:
Biopsy
-Purpose
*Demonstrates bone marrow architecture
*Estimate cellularity
*Evaluate diseases that characteristically produce focal lesions (Hodgkin’s lymphoma, non-Hodgkin’s
*lymphoma, multiple myeloma, and metastatic tumors)

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Bone Marrow Aspiration
-Volume being aspirated (1.0-1.5ml)
-Only for adults
-Needle used: University of Illinois sternal needle
-Site of puncture: posterior iliac crest (bandang pwetan)
-Pag children (not baby), the site of puncture: tibia
-Dry tap- unsuccessful procedure of bone marrow aspiration
*Usually happened if
1. The bone marrow of the patient is fibrotic
2. No cells in the bone marrow (aplastic or acellular)
3. Packed with leukemia cells or leukemic cells

Note:
Aspiration
-Purpose
*Identifies the types and proportions of hematologic cells
*Look for morphological variance

Additional Notes:
PATIENT PREPARATION FOR ASPIRATION OR BIOPSY
-LESS THAN 24 HOURS BEFORE THE PROCEDURE
-Blood must be collected for CBC and PBS (peripheral blood smear) before performing procedures

MATERIALS USED FOR ASPIRATION OR BIOPSY

1. Anesthesia - 1-2% Lidocaine or Procaine (alternative)
-Anesthesia is not more than 20ml and administered through 25 gauge needle
2. Scalpel- no. 11 scalpel and 3mm incision
3. Biopsy needle (Trephine Biopsy Needle, Jamshidi Needle (gauge:11), Westerman-Jensen, Islam)
4. Aspiration needle: gauge 14-18
5. Fixative (for specimen preservation)- Zenker’s fluid or B5 Fixative
6. Slides (for bone marrow aspirate smear) washed with ethanol
Note:
AFTER THE COLLECTION:
-The patient is advised to remain in the same position for 60 minutes to prevent bleeding
-Aspirate is immediately transferred onto 6-8 ethanol washed slides and smears are made (length: ½ to
¾ of the slide)

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Marrow Differential
-After smear, i-stain para makita kung anong klaseng cells ang nakuha ni doctor sa bone marrow
Note ppt
-Count atleast 500 (kung hindi ganun karami yung cells) but preferably is 1000 (kung madami) cells

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Other Normal Marrow Cells (normal findings)
-Macrophage
-Mast Cells
-Osteoblast (bone forming cell)
-Osteoclast (bone destroying cell)

Review of macrophages ppt

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Extramedullary Hematopoiesis
-Hindi lang sa bone marrow yung organ na capable of hematopoiesis
-Bone marrow
*Major blood forming organ but not all the time

Sites (other sites): liver ppt

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Regulation of hematopoiesis
-Hormones
*Erythropoietin (EPO) (manufactured in kidneys)- regulates ppt
*Thrombopoietin (TPO) (manufactured in liver or kidneys)- regulates ppt
*G-CSF
*GM-CSF
*Interlukins- regulates hematopoiesis
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2 METHODS OF REMOVING SENESCENT OR ABNORMAL RBC’S FROM THE CIRCULATION
Note:
-Senescence- refers to the process whereby RBC’s aged or grow old. With this, the RBC’s loses its
deformability. Thus, it will be considered as useless
-Spleen- kills useless rbcs
-Perfect RBC: size must be 6-8um and shape must be biconcave discoid shape
-After 120 days, rbcs will die, and their death is called (apoptosis but apoptosis is only used when cell
that died has nucleus or nucleated thus instead, eryptosis is the proper term to denote death of RBC
because it has no nucleus)

1. Culling
-Panget na rbc ay papatayin agad

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2. Pitting
-Pagbibigyan pa ang cell lalo na pag young rbc kahit panget na young rbc (may abnormalities)
-Tatanggalin lang yung area na panget
-Bite cell- cell na tinanggalan ng imperfection
-Pero pag bumalik sa spleen yug rbc na bite cell and pangit pa rin, papatayin na ni spleen (culling)

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Spleen
-Indiscriminate filter of circulating blood
-Graveyard of RBC
-Storage site for platelets (1/3) or 30% of platelets
-Receives blood supply 350ml per min (has rich blood supply)

Add summary notes:

-RBC- controlled by erythropoietin
-WBC- G-CSF & GM-CSF
*sometimes can also be controlled by interlukins
-Platelets- EPO or Thrombopoietin