HEMATOPOIESIS B.

Progenitor cells – “unipotential” stem

cells
 Cellular formation, proliferation,
Can differentiate into ONE cell line.
differentiation and maturation of blood C. Precursor cells – “immature” or blast
cells. cells
Stages: Can differentiate into ONE SPECIFIC cell.

1. Mesoblastic ERYTHROPOIESIS
 19th day in yolk sac of embryo.  Production of RBC
 Forms embryonic hemoglobin:  Erythropoietin – hormone produced by
o Gower I the kidneys.
o Portland  Hypoxia – primary stimulus for
o Gower II erythropoietin production.
2. Hepatic Decreased blood oxygen levels
 3rd month in fetal liver  120 days – average life span
 Produces granulocytes and erythrocytes  8 – 10 um – average size
with hemoglobin:  Smokers have flushed cheeks due to
o HbF
high RBC.
o HbA1 Stages:
o HbA2 1) Pronormoblast: “rubriblast” – first
3. Myeloid recognizable stage.
 5th to 6th month from bone marrow 2) Basophilic normoblast:
 Primary site = bone marrow until “prorubricyte”
adulthood. (sternum and flat bones) 3) Polychromatophilic normoblast:
Hemoglobin structure: “rubricyte” – start of hemoglobin
Depends on 4 globin chain it contains synthesis, last stage capable of
mitosis, checkerboard pattern.
 Gower I (onZE) 4) Ortochromic normoblast:
2 Zeta + 2 Epsilon “metarubricyte” – youngest
 Portland (Ziga ang Portland) incapable of mitosis, last nucleated
2 Zeta + 2 Gamma stage, sunny side up egg
 Gower II (T-A-E) appearance.
2 Alpha + 2 Epsilon 5) Polychromatophilic erythrocyte:
 HbF (fetus) “reticulocyte” – end of hemoglobin
2 Alpha + 2 Gamma synthesis, stained by SUPRAVITAL
 HbA1 (adults) stain.
2 Alpha + 2 Beta 6) Erythrocyte: “mature
 HbA2 RBC/discocyte” – non-nucleated,
2 Alpha + 2 Delta biconcave.
Cells of Hematopoiesis: ERYTHROCYTE MEMBRANE:
A. Stem cells – “pluripotential” or 50% Protein:
“multipotential” cells
Can differentiate into ANY cell line.  Integral protein – Glycophorin A and
Leukemia – disease that manifests lots Component A (for communication).
of stem cells.  Peripheral protein – Spectrin and Actin
(maintains the biconcave shape of
RBCs).

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40% Lipid:  Last step of heme synthesis:
o Protoporphyrin + Fe2 = heme
 External surface –
▪ Ferrochelatase
o Phosphatidylcholine
o Glycolipid Hemoglobin-Oxygen Dissociation Curve
o Sphingomyelin
 Internal surface –  Left shift – shows blood with increased
o Phosphatidylethanolamine affinity to oxygen.
o Phosphatidylinositol  Right shift – Decreased affinity.
o Phosphatidylserine LIRD
Lecithin - Cholesterol Acyl Transferase LEFT SHIFT RIGHT SHIFT
(LCAT) maintains the cholesterol of RBC. Increased affinity Decreased affinity
10% Carbohydrate: Increased pH in blood Decreased pH
All other factors are All other factors are
Determine the blood type
decreased: increased:
 N-acetyl-D-galactosamine – A antigen ▪ H+ ▪ H+
 D-galactose – B antigen ▪ pCO2 ▪ pCO2
▪ Temperature ▪ Temperature
BIOCHEMISTRY ▪ Altitude ▪ Altitude
Embden Meyerhoff Pathway: ▪ 2,3-DPG ▪ 2,3-DPG
Causes shift to the left: Causes shift to the right:
 Anaerobic glycolysis in RBC due to ▪ Carboxyhemoglobin ▪ High altitude
absence of nucleus. ▪ Methemoglobin ▪ Anemia
 Provides 90% of energy (ferric)
▪ Fetal hemoglobin
Hexose Monophosphate Shunt or Pentose
Phosphate Pathway:
 Aerobic glycolysis in RBC. HALDANE VS BOHR EFFECT
 Provides 10% HALDANE EFFECT BOHR EFFECT
 Provides GLUTATHIONE (antioxidant) Increased O2 release Increased CO2 and H+
 Glucose-6-Phosphate Dehydrogenase – CO2 from hemoglobin. release O2 from
important enzyme to produce Shift to the LEFT hemoglobin.
glutathione. Shift to the RIGHT
 G-6-P D deficiency causes hemolysis.
H – hemoglobin bO – oxygen
Hemoglobin Structure and Synthesis: A – affinity H – hemoglobin
L – shift to LEFT R – shift to RIGHT
 Hemoglobin: 4 subunits of heme and DANE – carbon DIOXIDE
globin.
 Each unit carries oxygen molecule = 4
oxygen molecule.
 First step of heme synthesis:
o Glycine + Succinyl CoA = d-ALA
▪ ALA synthetase
▪ ALA: Amino Luvenelic
Acid

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LEUKOPOIESIS  Pink to rose violet specific
granules:
I. Granulopoiesis
o Myeloperoxidase
 6 stages, 3 lineages (MPO)
o Myeloblast o Lactoferrin
o Promyelocyte o Lysozyme
o Myelocyte  For bacterial infections –
o Metamyelocyte gram-positive.
o Band/Stab cell b. Eosinophil:
o Mature granulocytes  Usually 2 lobes (bilobed)
 Neutrophil, eosinophil and basophil  Reddish orange granules
 Younger cell = bigger nucleus; o MBP
mature = small nucleus
o EDN
o 1:1 young o ECP
o 1:4 old o histaminase
Stages:  For parasitic infection and
allergic (hypersensitivity)
1. Myeloblast : reactions
 1st recognizable stage.  Parasites:
 No granules o Major Basic Protein
 N:C ratio is almost 1:1 o Eosinophil Derived
o Promyelocyte: Neurotoxin
 Has PRIMARY or NONSPECIFIC o Eosinophil Cationic
granules. Protein
 Azurophilic – half nucleus with big  Allergy: Histaminases
blue granules. c. Basophil:
 N:C ratio is 1:2  Dark purple to blue black
2. Myelocyte: granules
 Last stage CAPABLE of mitosis.  Usually 2 lobes (bilobed),
 Youngest cell where it can be but often obscured by the
differentiated. granules
 Has SECONDARY or SPECIFIC  Granules contain:
granules. o Histamine
3. Metamyelocyte: o Heparin
 Youngest stage NOT capable of 1. For allergic (hypersensitivity
mitosis. reactions)
 With indented or kidney shaped
nucleus. II. Lymphopoiesis
4. Band/Stab/Staff cell: 2. 3 Stages
 Youngest cell to normally appear on o Lymphoblast – N:C – 1:1
peripheral blood stream. o Prolymphocyte – N:C –
 With sausage or elongated or band 1:2
shaped nucleus (C or S) – no o Mature lymphocyte –
lobulation. “robin’s egg” blue color
5. Mature:
a. Neutrophil:
 Nucleus = segmented 2 – 5
lobes.

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 Classified according to size in relation 5. IgD – incomplete immunoglobulin
with the size of RBC: (partners with IgM and Eosinophil).
• Small lymphocyte: 8 – 10 µm Name Properties Structure
• Medium lymphocyte: 10 – 12 IgA Found in
µm mucous, saliva,
• Large lymphocyte: 12 – 16 µm tears, and breast
milk. Protects
Classified according on the surface
against
markers:
pathogens.
T cell B cell NK cell
IgD Part of B cell
receptor,
Production Bone Bone Bone activates
marrow marrow marrow basophils and
Maturation Thymus Bone Bone mast cells.
marrow marrow
Population 60 – 80 10 – 20 < 10 %
% % IgE Protect against
parasitic worms.
Responsible for
Maturation of T cells: allergic
reactions.
1. T-helper - activation of B cells and
macrophages.
2. T-cytotoxic – kill virally infected cells. IgG Secreted by
3. T-memory – T cell that remember plasma cells in
antigens previously encountered. the blood. Able
4. T-suppressor cells – moderate immune to cross the
response of other leukocytes; also placenta into
called T-regulatory cells (Tregs). the fetus.
Maturation of B cells: IgM May be attached
to the surface of
• Plasmacyte/Plasma cells: a B cell or
o Eccentric nucleus with secreted into
CARTWHEEL appearance or the blood.
SPOKES OF A WHEEL. Responsible for
o Produced antibodies or early stages of
immunoglobulins. immunity.
• Immunoglobulins:
1. IgG – most numerous, slowest (later
infections). III. Monocytopoiesis
2. IgM – earliest to act, largest 1. Monoblast
(pentameric immunoglobulin). 2. Promonocyte
3. IgE – parasitic and hypersensitivity 3. Monocyte:
reaction. o Largest cell in peripheral
4. IgA – secretions. bloodstream.

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 o Blue-gray cytoplasm with o 2/3 of the population is found
ground glass appearance. in the blood stream.
o Large, kidney-shaped nucleus or
appear as brain convolutions Stages:
(horse shoe). 1. Megakaryoblast
o Action: 2. Promegakaryocyte
i. APC – Antigen 3. Granular megakaryocyte (only 1
Presenting Cells with granules)
ii. Phagocytosis 4. Mature megakaryocyte (largest cell
in bone marrow, stars endomitosis)
Tissue Macrophages:
5. Metamegakaryocyte (Steininger) –
1. Kupffer cells – liver separation of platelets with hair-like
2. Sinus histiocytes – lymph nodes projections
3. Alveolar macrophages (dust cells – 6. Platelet/thrombocyte
carbon materials, heart failure cells
– RBC) – lungs Platelet structure:
4. Microglia – brain  Parts according to microscopic
5. Mesangial cells – kidneys picture:
6. Osteoclasts – bones 1. Chromomere – granular and
7. Hofbauer cells – placenta located centrally.
2. Hyalomere – nongranular
which surrounds the
Differential count: (Reference ranges) chromomere.
 Parts according to functional zones:
 Neutrophils = 55 – 65 % 1. Peripheral zone
 Lymphocyte = 20 – 30 % o Consist of glycocalyx,
 Monocyte = 2 – 6 % plasma membrane and
 Eosinophil = 1 – 3 % glycoproteins.
 Basophil = 0 – 1% a) Gp Ib/IX/V –
“Never Let Monkey Eat Bananas” receptor for von
Willebrand factor
IV. Thrombopoiesis/Megakaryopoiesis (CF 8).
 Biggest in bone marrow. b) Gp IIb/IIIa –
 Maturation time: 5 days receptor for
 Life span: fibrinogen (CF 1).
o 7 – 10 (Rodak’s) c) Gp Va – receptor
o 8 – 11 (Henry’s) for thrombin (CF 2).
o 9 – 12 (Brown’s) 2. Sol-Gel zone
 Platelets are produced directly from the o Microfilaments:
megakaryocyte cytoplasm. a) ACTINOMYOSIN or
 Endomitosis – nuclear division without THROMBOSTHENIN
cytoplasmic division (2 nucleus, 1 (responsible for clot
cytoplasm). retraction) –
 Each megakaryocyte produces 2000 to separation of clot.
4000 platelets. o Microtubules:
o 1/3 of population is found in a) TUBULIN
the spleen. (responsible for

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 shape Primary Hemostasis:
maintenance).
3. Membranous system PROCESS RESPONSIBLE CHEMICALS
o Dense tubular system –
serves as the site of Vasoconstriction Serotonin and
ARACHIDONIC ACID Thromboxane A2
(mother of thromboxane A2 Platelet adhesion Von Willebrand factor
Prostacyclin, Prostaglandin, using Glycoprotein Ib/IX/V
Phospholipid) metabolism. Platelet will adhere to
o Open canalicular system – Collagen (in vivo) and
for the release of granules. Glass (in vitro).
4. Organelle zone Platelet activation Thromboxane A2, PAF
o Alpha granules: (Platelet Activating Factor)
1) Platelet factor Platelet secretion Alpha granules – growth
2) Thrombospondin factors, clotting factors
3) Fibronectin Dense granules – CAPAS
4) Fibrinogen Platelet aggregation Fibrinogen through the use
5) PLT-derived growth factor of Glycoprotein IIb-IIIa.
(PDGF) Platelet aggregates using
6) Endothelial DGF collagen, ADP and
o Dense granules: epinephrine and
1) Calcium ristocetin.
2) ADP
3) Phospholipid
4) ATP Preferred Synonyms
5) Serotonin Name
“CAPAS” I Fibrinogen

Hemostatic Mechanism II Prothrombin Pre-thrombin

• Hemostasis – hemo (blood) + stasis III Tissue factor Tissue thromboplastin
(stop) IV Calcium
V Proaccelerin Labile factor,
Primary Secondary Accelerator globulin
hemostasis hemostasis (aCg)
Processes Vasoconstriction Coagulation VII Proconvertin Stable factor, SCPA
Platelet adhesion factors (Serum Prothrombin
Platelet activation Conversion
Platelet secretion Accelerator)
Platelet VIII Antihemophilic Antihemophilic
aggregation factor globulin (AHG)
Antihemophilic factor
Final Platelet plug Fibrin clot A
product Platelet Cofactor 1
IX Plasma Christmas factor
Thromboplastin Antihemophilic factor
Component B

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 X Stuart-Prower Stuart factor
Factor Autoprothrombin III
XI Plasma Antihemophilic factor
Thromboplastin C
Antecedent
XII Hageman Glass factor
factor Contact factor
XIII Fibrin Laki-Lorand factor
stabilizing Fibrinase
factor
Prekallikrein Fletcher factor
HMWK (High Fitzgerald factor
Molecular Contact Activation
Weight cofactor Fibrinolysis:
Kininogen) Williams factor
 Final stage of coagulation after
Flaujeac factor
fibrin polymerization and cross-
Coagulation factor groups
linking.
Fibrinogen Prothrombin Contact Group  THROMBOSIS - inability or deficient
Group Group process of fibrinolysis will form.
I, V, VIII, XIII II, VII, IX, X XII, XI,  Over-reactive fibrinolysis is also
Prekallikrein, fatal as it may destroy the fibrin clot
HMWK without stabilizing the bleeding.
Calcium Calcium Calcium  There should be a BALANCE
dependent dependent independent between Pro and Anti-fibrinolytic
Vitamin K Vitamin K Vitamin K proteins.
independent dependent independent PRO-Fibrinolysis Proteins:
Present in Present in Present in
plasma but plasma and both plasma  Plasminogen – inactive form of Plasmin.
absent in serum (except and serum  Plasmin – digests fibrinogen and fibrin.
serum FII, only  Urokinase Plasminogen Activator
present in (UPA) – Activates plasminogen secreted
<20% in by kidneys.
serum).  Streptokinase – Activates plasminogen
Secondary Hemostasis: present in patients with previous
streptococcal infection.
Stages:
ANTI-Fibrinolysis Proteins:
1) Generation of thromboplastin (III)
2) Conversion of Prothrombin to Thrombin  Plasminogen activator inhibitor-1 –
(II) Inhibits tissue plasminogen activator.
3) Conversion of Fibrinogen to Fibrin (I)  α2-antiplasmin – inhibits plasmin.

Pathways: Fibrin Degradation Products (FDP):

1) Intrinsic pathway  After plasmin degrades fibrinogen and

2) Extrinsic pathway fibrin, it will produce a series of fibrin
3) Common pathway fragments or also known as Fibrin

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 Degradation Products (cause of death
of dengue patients).
 Actions of fragments or FDPs:
o Inhibit hemostasis
o Prevents platelet activation
o Hinders fibrin polymerization

Fibrin Degradation Products (FDPs)

FIBRINOGEN
Fragment X D-E-D
Fragment Y D-E
Fragment D & E E/D/D

FIBRIN
Fragment YY D-E/D-E
Fragment DXD D=D/E/D=D
Fragment DED D=D/E
Fragment E E
Fragment DD D=D

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