series lecture in clinical hematology for medical student Prof. Waseem Al Tameemi Al Nahrain University college of medicine

1. HEMATOLOGY COURSE
Introduction
1st
19th feb.2017

2. Learning objectives
 ✓ To understand the process of formation of
blood cells
 ✓ To understand the concept of a stem cell
 ✓ To understand the normal role of each
mature cell type in the blood
 ✓ Describe the Oxygen -Hb dissociation curve

3. Hematopoiesis
(hemopoiesis)
 continuous, regulated process of blood cell
formation, production, differentiation, and
development.
 To replenish dying cells with new blood
cells and
 be able to respond to increased demands
(Ex.bleeding or infection.)
 (erythropoiesis,myelopoiesis &
thrombopoiesis)

4. Hematopoiesis
 HSC and endothelial cells are derived
 AGM (aorta‐gonads‐mesonephron)
system
 definitive haemopoiesis
 (haemangioblasts)
 Yolk sac
 the liver, spleen and bone marrow.

5. Hematopoiesis

6. Hematopoiesis

7. Hematopoiesis
 starts with a
pluripotential stem cell
 This haemopoietic stem
cell (HSC)
 The self‐renewal will
maintain marrow
cellularity in a normal
healthy steady state.

8. Hematopoiesis
CD34+ CD38− and negative
for lineage markers (Lin−)
one stem cell is capable of
producing about 106 mature
blood cells after 20 cell
divisions

9. Hematopoiesis
Under normal conditions
most HSC are dormant.
With aging:
 the number of stem cells falls
 accumulate genetic mutations

10. a)Bone marrow cells are increasingly differentiated and lose the
capacity for self‐renewal as they mature.
b) A single stem cell gives rise, after multiple cell divisions to >
106 mature cells.

11. Regulation of Hematopoiesis
 Non lineage specific :
 stem cell factor (SCF) ,
 granulocyte macrophage-colony stimulating
factor (GM-CSF)
 interleukin-3 (IL-3)
 Lineage specific:
 erythropoietin (Epo),
 granulocyte-colony stimulating factor (G-
CSF) and
 thrombopoietin (Tpo).

12. Growth factors : to stimulate

13. Regulation of Hematopoiesis
 HSCs are mostly concentrated in the
bone marrow
 HSC can be induced to circulate by
administration of granulocyte colony -
stimulating factor (G - CSF)

14. Functionally, human stem cells
may be:
1. Totipotent SC:
2. Pluripotential
SC:
3. Multipotential
SC:
4. Unipotent SC:

15. Hematopoiesis
 stem-cell plasticity :
Recent evidence suggests that the
bone marrow pluripotent SC can be
differentiated into tissue cells other
than the blood, such as nerve,
skeletal muscle, cardiac muscle,
liver and blood vessel endothelium.

16. Hematopoiesis
 Hematopoietic (hemopoietic)
System
 consists of all tissues involved in
hematopoiesis (bone marrow, liver,
spleen, lymph nodes, and thymus),
 myeloid tissue
 lymphoid tissue.

17. Hematopoietic
(hemopoietic) System
1.The myeloid tissue consists of bone
marrow (medullary cavity) which
include
 Red blood cells (RBCs/ erythrocytes)
 White blood cells (WBCs/leukocytes)
 Granulocytes: Neutrophils,
 eosinophils
 basophils
 Monocytes
 Platelets (thrombocytes)

18. Hematopoietic
(hemopoietic) System
2.The lymphoid tissue consists of
thymus, lymph nodes and spleen.
 The common lymphoid progenitor cell
gives rise to B cell, T cell and natural
killer (NK) cell precursors.

20. Extramedullary hematopoiesis:
 With reactivation of hematopoietic
islands in liver and spleen ,etc…
,whenever the BM is
1. unable to meet the demands (hemolytic
anemias).
2. becomes infiltrated by malignant cells
( leukemia).
3. replaced by fibrous tissue
(myelofibrosis).

21. Erythrocytic
Maturation Series
1. CFUGEMM
2. BFUE
3. CFUE
4. Pronormoblast
 One pronormoblast
usually gives rise to
16 mature red cells
5. Normoblasts
6. Reticulocyte
7. Erythrocyte.

22. Erythrocytic
Maturation Series
 normoblasts
=erythroblasts
=nucleated RBC
 are not present in
normal human
peripheral blood
 Reticulocyte
non-nucleated red cell
which still contains
ribosomal material in
the cytoplasm.

23. Reticulocytes
 BM
 peripheral blood:
 The normal range is
0.5% - 2.0% in adults.
 In newborn infants, the
range is 2.5% - 6.0%.
 In blood smear:
polychromatophilia
 reticular appearance caused
by remaining RNA if stained
with a supravital stain

24. ERYTHROPOIESIS

25. ERYTHROPOIESIS
 ERYTHROPOIETIN
• produced by renal tubular cells
(peritubular interstitial).
• under control of the oxygen (O2)
tension in the kidney
• CFU-E & pronormoblast
• no preformed stores
• normal concentration up to 20
mU/mL.

26. ERYTHROPOIESIS
 Tissue hypoxia :
 hypoxia inducible factors (HIF‐1α and β),
 stimulate Epo production :
1. new vessel formation
2. Transferrin receptor synthesis,
3. reduces hepcidin synthesis
4. Increasing iron absorption
 Epo increases in anaemia, hypoxia.
 Epo reduces in high red cell mass,
increased O2 supply, RF

27. ERYTHROPOIESIS
 Recombinant human erythropoietin is produced :
 Erythropoietin alpha or beta
 Darbepoetin alpha
 Micera
 Indications for erythropoietin therapy:
1) Anaemia of chronic renal disease
2) Myelodysplastic syndrome
3) Anaemia associated with malignancy and chemotherapy
4) Anaemia of chronic diseases, e.g. rheumatoid arthritis
5) Anaemia of prematurity
 need oral or intravenous iron
 rise in blood pressure,
 thrombosis

28. Red Blood Cells
 Hemoglobin molecule:
Protein adapted for gas
transport to & from the
lungs &then to rest of
tissues.
 4 globin chains( 2α &2 non α
chains),
 porphyrin pigment (haem)
 ferrous iron atom( Fe2+) in order
to bind O2 molecule (reversible,O2
–Hb curve)

29. Oxygen Hb. Dissociation curve
 the relationship between
oxygen content (percentage
of saturation) and partial
pressure of oxygen (PO2).
 The P50 value :
 the partial pressure of oxygen
required to produce 50%
saturation of hemoglobin,
 deoxyhemoglobin (reduced
hemoglobin) concentration
= oxyhemoglobin
(oxygenated hemoglobin)
concentration at a
constant pH and temperature

30. Oxygen- Hb Dissociation curve