DEFINITION AND SCOPE OF HEMATOLOGY HEMATOPOIESIS

FUNCTIONS OF THE BLOOD SYSTEM DEVELOPMENT

1. Transport 1. Erythropoiesis
2. Temperature regulation 2. Leukopoiesis
3. Immunity 3. Thrombopoiesis
4. Communication
5. Defense MORPHOGENESIS
a. ONTOGENY: embryonic development
BLOOD COMPONENTS 1. Primitive (mesenchymal cells)
1. LIQUID: Plasma 55% i. Yolk sac: 3rd-4th week
a. Water 2. Definitive
b. Electrolytes i. Liver: 3rd month, main
c. Plasma proteins ii. Spleen: 3rd month
i. Acc. to function: enzymes, antibodies, iii. Bone marrow: starts at 4th, main
coag, fibrinolytic by 6th month
ii. Acc. to structure: simple & complex iv. Lymph nodes & thymus: 4th,
proteins secondary source of lymphocytes MICROANATOMY OF THE BONE MARROW
iii. Acc. to water solubility: albumins, throughout life  Mesenchymal cells  stem cell for connective
globulins tissues and blood cells
 Major Functions 3. Notes:  Hemocytoblasts  pluripotent (give rise to all
o Transport: carrier proteins  Liver and spleen: has residual blood cell lines), contained only in the bone
o Regulation of water movement: albumin hematopoietic capacity, revert to marrow after birth
o Coagulation: fibrinogen, fibrinolytic factors embryonic role if needed  Foramina  ducts where arteries enter the bone
o Immunoglobulins (antibodies): γ  Medullary hematopoiesis: in bone  Sinusoids  substitute for capillary beds
o Inflammation marrow, all bones til 25  26  Wheel with spokes (sinusoids) and a central hub
2. SOLID onwards, happen in flat bones (vein)  bone marrow cross-section
a. Red Blood Cells (erythrocytes) 45%  Extramedullary hematopoiesis:  Marrow stroma  where blood cell formation take
b. White Blood Cells (leukocytes) <1% outside bone marrow  lymph place (extravascular)
i. Granulocytes (acc to cytoplasmic nodes, liver, spleen  Sinusoidal wall layers
granules) b. PHYLOGENY: evolution o Endothelial cells (internal)
1. Neutrophils c. HISTOLOGY: maturation o Basement membrane (middle)
2. Eosinophils  Undifferentiated mesenchymal reticular cell  o Adventitial reticular cells (outer)
3. Basophils pluripotent stem cell (hemocytoblast)  myeloid, o Where the reticulocyte squeeze out and
ii. Lymphocytes (acc to fxn) lymphoid nucleus is removed  circulation
1. B cells  plasma cells  Bone marrow
2. T cells o Red marrow  hematopoietic tissue, ribs
a. Cytotoxic T-cells and sternum of young adults
b. Helper T cells o Yellow marrow  fatty tissue, increased
c. Natural Killer Cells as a person ages, long bones of adults
3. Monocytes
c. Platelets (thrombocytes) <1%
TWO METHODS OF BONE MARROW STUDY BLOOD CELL LINES HB, BLOOD TRANSPORT
1. Aspiration  Lymphoid-myeloid CFU
 Needle inserted posterior iliac crest (adult)/ tibia o Lymphoid-CFU
(infant)  small quantity of tissue  smeared,  Pre-B cell  B cell  plasma cell
fixed, stained and examined  Pre-T cell
 Disturbs bone marrow architecture  for types  NK cell
and number of cells  Helper T cell
2. Biopsy  Cytotoxic T cell
 Biopsy needle into iliac crest  Piece of bone o GEMM-CFU (Granulocyte-Erythrocyte-
marrow  fixed, embedded in paraffin, examined magakaryocyte-monocyte)
 Traumatic and dangerous  better picture of the  Erythroid-CFU  RBC
real structure  Granulocyte-monocyte-CFU 
 G-CFU  neutrophil
STUDYING STEM CELLS & HEMATOPOEISIS  M-CFU  monocyte
 Colony-Forming Units: identify and count stem cells then macrophage
o Hematologically empty mice  bone  Eosinophilic-CFU  Eosinophil
marrow cells  undifferentiated   Basophil-CFU  Basophil
myeloid or lymphoid SC  Megakaryocyte-CFU  platelets
 Stem Cell Kinetics
Characteristics
o Self-maintaining  divide into daughter
cells with parent capabilities
o Can differentiate
Renewal Theories
o Asymmetric cell division
o Replacement by progeny of other
pluripotent stem cells
 Cytokinetics
o Study of the method by which blood cells
proliferate (constantly dividing and proliferate on demand)
 Mass or size (total #)
 Maturation
 Life span
 Turnover rate  Growth Factors
o Colony Stimulating Factors (CSF)
 GM-CSF: G-CSF, M-CSF
o Interleukins: IL-3, IL-4, IL-5, IL-6, IL-7, IL-9
o Erythropoeitin (EPO)
 Cytokine, secreted by the kidney in response
to cellular hypoxia (non-steady state)
 stimulates red blood cell production in the
bone marrow
METABOLISM AND FATE OF RBC
RBCs get energy only from GLUCOSE  Anaerobic Glycolysis
(ATP) and Pentose Phosphate Pathway (NADPH)
ENERGY REQUIREMENTS OF RBC
Energy required for:
1. Keeping cation (Na, Ca) pumps going
2. Generation of NAD+ needed to produce NADH
- NADH: (a) provides NADH the energy for
conversion of pyruvate to lactate; (b) helps in
regulation of the methemoglobin reduction
system
3. Generation of NADP+ needed to produce NADPH
- NADPH: (a) generated via PPP (or Pentose
Monophosphate shunt/ Hexose
monophosphate shunt) (b) major energy source
in keeping Hb in reduced state (Fe2+, if Fe3+,
cannot transport oxygen)
4. Generation of 2,3 BPG
- 2,3 BPG: essential ingredient for proper
functioning of Hb as oxygen carrier
5. Maintenance of RBC shape (biconcave discs)
GLUCOSE METABOLISM IN RBCS
Energy molecules:
1. ATP
a. Run the cationic pumps (Na+ & Ca+) to maintain
the osmotic balance of erythrocytes
b. Keep the cell membrane in good shape
 by ensuring proper lipid turnover
 by phosphorylation of membrane proteins
c. providing phosphates needed to prime the
Embden-Meyerhof pathway (anaerobic
pathway)
d. contributing the active phosphates (NADH
NADPH)
2. NADH: antioxidant function  reduces hydrogen
peroxide
3. NADPH: antioxidant function  reduces
glutathione
RBC GLUCOSE-CONVERSION PATHWAYS:
1. Embden-Meyerhof (EM) Pathway (Anaerobic
Pathway)
 Utilizes 90-95% of all the glucose
 Supplies 75% of the cell’s energy
 Produce:
o All the ATP (2ATPs/ glucose mol)
o NADH
o 2,3 BPG
 Why anaerobic  RBC lack mitochondria,
prevent aerobic oxidation glucose &
pyruvate
 Phosphorylation: before glucose is broken
down, ATP  ADP
 Glucose  pyruvate
 Net gain: 2 ATP, 2 NADH (reduced, energy-
carrying)
2. Hexose monophosphate shunt (HMS)/ Pentose
Phosphate Pathway (PPP)
 Utilizes 5-10% of the glucose
 Supplies 25% of the potential energy of
the cell
 Produce: All NADPH
 NADP  NADPH (involves enzyme G6PD)
 NADPH
o Keep glutathione in reduced-state
o Reduced-gluta  major role in
prolonging life of RBCs (~120days)
o Any defect in PPP  early RBC
hemolysis
SURVIVAL
Classification of Anemia
1. MORPHOLOGY
I. Size (MCV): normo/macro/microcytic
II. Hb concentration (MCHC):
normo/hypo/hyperchromic
A. Normocytic-normochromic
1. Bleeding
2. Bone marrow failure
- Hypo-proliferation of hematopoietic stem
cells in the bone marrow (aplastic anemias,
anemia of chronic renal failure,
myelophthisic anemia)
3. Toxic depression of the bone marrow
(hemolytic anemias)
B. Microcytic-hypochromic
1. Iron deficiency anemia
2. Sideroblastic anemia II.
C. Macrocytic- normochromic
1. Megaloblastic anemia
2. Certain hemolytic anemias
2. ETIOLOGY
I. Decreased RBC production
A. Decreased proliferation
1. Decreased EPO
a. Impaired production by the kidney
(anemia of renal failure)
b. low oxygen requirement (anemia of
endocrine disease)
c. impaired stem cell response to EPO
2. Bone marrow damage/defect
a. replacement of normal marrow by
tumor (Myelophthisic anemia)
b. replacement of normal marrow by
cancerous cell line (anemia
associated with myeloproliferative
disease)
c. damage to bone marrow by physical,
chemical or infectious agents (aplastic
anemia)
d. inherited bone marrow defect
(Fanconi’s anemia)
B. Impairment in the maturation of new RBCs
1. Macrocytic-normochromic
a. Folic acid deficiency (Megaloblastic
anemia)
b. Vitamin B12 deficiency (Megaloblastic
anemia)
2. Microcytic-hypochromic
a. Iron deficiency (Iron deficiency
anemia)
b. unavailability of iron to blast cells
(anemia of chronic disease)
c. impaired heme synthesis
(sideroblastic anemia)
d. impaired globin synthesis
(thalassemia syndromes)
II. Increased RBC loss
A. Hemorrhage: acute or chronic
B. Intravascular hemolysis
1. Hereditary factors
a. Defects in RBC membrane (hereditary
spherocytosis/elliptocytosis)
b. Defect in RBC metabolism (G-6-PD
deficiency anemia)
c. Abnormal Hgb production (sickle cell
anemia, HbC disease, HbD disease,
HbE disease)
2. Acquired accelerated hemolysis
a. Activation of the immune system
(hemolytic anemia)
b. Physical factors (red cell
fragmentation syndromes)
c. Chemical agents (various forms of
hemolytic anemia)
d. Microorganisms (various forms of
anemia e.g. anemia of malaria)
e. Secondary to other diseases (various
forms of anemia e.g. anemia of
hepatic failure)
f. Sensitivity to complement
(paroxysmal nocturnal
hemoglobinuria)