lectures series in basic hematology

3.  Hemo: Referring to blood cells
 Poiesis: “The development or production of”
 The word Hematopoiesis refers to the production &
development of all the blood cells:
◦ Erythrocytes: Erythropoiesis
◦ Leucocytes: Leucopoiesis
◦ Thrombocytes: Thrombopoiesis.
 Begins in the 20th week of life in the fetal liver &
spleen, continues in the bone marrow till young
adulthood & beyond!

4.  Medullary
◦ Origin of blood cells and sequential sites of normal
blood production within the bone marrow
 Extramedullary
◦ Blood cell production in hematopoietic tissue
other than bone marrow
 Liver
 Spleen
◦ Compensatory mechanism to provide blood cells
in times of need

5. AGE SITE
Fetus: 0-2 months Yolk sac
2-7 months Liver, spleen
5-9 months Bone marrow
Infants Bone marrow, practically all bones
Adults Vertebrae, ribs, sternum, sacrum and
pelvis, proximal ends of femur

8.  Suitable environment for
SC growth & development.
 Composed of stromal cells
+ microvascular network.
Stromal cells:
• Adipocytes
• Fibroblast
• Reticular cells
• Endothelial cells
• Macrophages
Extracellular molecules:
• Collagen
• Glycoprotein (fibronectin,
thrombospondin)
• Glycosaminoglycans
(hyaluronic acid &
chondroitin derivates)
• Growth factors  for cell
survival

9.  Glycoprotein hormones  regulate proliferation
& differentiation of HPC & function of mature
blood cells.
 Biological effects of HGF mediated through
specific receptors on target cells.
 Act:
◦ Locally  at the site where they are produce  by
cell-cell contact.
◦ Circulate in plasma

10.  Major sources (except erythropoietin):
◦ T-lymphocytes
◦ Monocytes (& macrophages)
◦ Stromal cells
 Erythropoietin  90% synthesized in kidney
 Thrombopoietin  largely made in liver
 Leukopoiesis also stimulates by endotoxin

11.  Synthesized by peritubular cells of kidney in
response to hypoxemia
 Present in minute amounts in urine
 Liver secretes 10% of endogenous
erythropoietin.
 Responsible for low level erythroid activity.
 Half life of 6-9 hrs. in anemic patient

12. 1. Impaired O2 delivery to the kidney resulting
to decreased red cell mass
2. Impaired O2 loading of the hemoglobin
molecule
3. Impaired blood flow to the kidney

13.  It is a glycoprotein hormone produced
mainly by liver and kidney that regulates
the production of platelets in bone
marrow.
 It stimulates the production and
differentiation of Megakaryocytes

14. 3. GM-CSF:
 Produced by fibroblasts, stromal
cells,T.lymphocytes and endothelial cells.
 Stimulate progenitors for granulocytes,
monocytes and erythrocytes

15. 4. G-CSF:
 LMW glycoprotein
 Stimulates proliferation and maturation of
granulocyte precursors.
 Produced by stromal cells, monocytes,
macrophages, and endothelial cells.

16. 5.M-CSF:
 Secreted by stromal cells, macrophages and
fibroblasts.
 Heavily glycosylated glycoprotein
 Potent stimulator of macrophage function
and activation as it increases the expression
of MHC.II antigen on macrophages.

17. Site of action HGF
Stromal cell IL-1, TNF
Pluripotential stem cell Stem cell factor (SCF), Flt ligand
(Flt-L)
Multipotential progenitor
cell
IL-3, GM-CSF, IL-6, G-CSF,
thrombopoietin
Committed progenitor
cell
G-CSF, M-CSF, IL-5 (eosinophil-
CSF), erythropoietin,
thrombopoietin

18. Binding of GF to its receptor activates JAKs 
then phosphorylate STATs which translocate to the
nucleus and activate transcription of specific genes

20.  Homeostasis:
- cell production ↔ cell destruction
 Regulated process of physiological cell death 
triggered to activate intracellular proteins 
lead to cell death.
 Important proses for maintaining tissue
homeostasis in hematopoiesis & lymphocytes
development

21.  Apoptosis results from the action of
intracellular cysteine proteases called
CASPASES which are activated following
cleavage and lead to endonuclease digestion of
DNA and disintegration of the cell skeleton.

22.  There are two major pathways by which
CASPASES can be activated:
1. By signaling through membrane proteins such as
Fas or TNF receptor via their intracellular death
domain.
2. Via the release of cytochrome c from
mitochondria. Cytochrome c
binds to APAF‐1 which then activates caspases.

24.  Apoptosis have the Following steps:
1) Cell shrinkage
2) Organelle reduction
3) Mitochondrial leakage
4) Chromatin condensation
5) Nuclear fragmentation
6) Membrane blebbing & changes

26.  Differentiate into multiple cell lines.
 Proliferation is under influence of hematopoietic
growth factors present in reticuloendothelial
system.
 Morphologically they resemble large immature
lymphocytes
 Exact phenotype unkown  immunological testing:
CD34+, CD38-
 1 SC capable of producing + 106 mature blood cells
after 20 cell divisions.

27.  Pluripotent Stem cells undergo several divisions and
become committed unipotent cells(CFU) to either
myeloid or lymphoid lineage
 Committed stem cells lose self-renewal capability but
retain the potential to differentiate
 They acquire distinguishing cell surface receptors
and respond to specific signals and growth factors

28.  Myeloid lineage stem cells mature in bone
marrow to become :
 Erythrocytes/red blood cells
 Granulocytes including segmented neutrophils,
eosinophils, and basophils
 Monocytes/macrophages
 Platelets/thrombocytes

29.  Lymphoid lineage stem cells will become either a pre-
Bcell or a prothymocyte(pre-Tcell) and will travel to
the Thymus and lymph nodes for further maturation
into lymphocytes

30.  Myeloid and lymphoid cells are progenitor cells.
 Both cell types originate from hematopoietic
stem cells.
 Both cell types are produced in bone marrows.
 Both cell types produce different types of
daughter cells.

31. LymphoidMyeloid
Lymphoid cells are
daughter cells of
hematopoietic stem cells
which produce
lymphocytes.
Myeloid cells are daughter cells
of hematopoietic stem cells which
give rise to several other types of
blood cells.
Definition
T cells, B cells, and
natural killer cells (NK).
Monocytes, macrophages,
neutrophils, basophils, eosinophils,
erythrocytes, dendritic cells,
megakaryocyte, and platelets.
Daughter
cells

32.  Changes in cytoplasm
 Changes in nucleus
 Reduction in cell size
 Gradual transformation
 Changes are simultaneous and parallel

33.  Loss of basophilia:
◦ Romanowsky staining (Giemsa)
◦ The more basophilic cytoplasma, the more immature cell
 Cytoplasmic granules in granulocytes
◦ Azurophil (primary granules)
◦ Specific (secondary granules):
 Eosinophilic
 Basophilic
 Neutrophilic

34.  Elaboration of hemoglobin: blue cytoplasm in
pronormoblast and red cytoplasm in
erythrocyte in pronormoblast

35. Nuclear Maturation:
1. Shape
◦ Round or oval in blasts
◦ Striking changes in granulocytes
2. Structure delicate netlike or sponge like
◦ chromatin in blasts
◦ Chromatin strands become more coarse and clumped as the
cells matures
◦ Reduction in the number of nucleoli

36.  A feature of all cells, except in the
megakaryocytic series.
 N/C ratio is high in young cells and low in
mature cells.

37.  Asynchronous maturation of cytoplasma and
nucleus  atypical cells.
 Granulocytes:
- A granular
- Persistent primary granules
- Abnormal inclusions
- Large nucleus
- Hypersegmentation/hyposegmentation
 Erythrocytes:
- persistent basophilia