The document discusses blood cells and hematopoiesis. It describes the three main blood cells - red blood cells, white blood cells, and platelets. It details their production rates, lifespans, and the process of hematopoiesis where they are formed in the bone marrow. The document also discusses erythropoiesis, the formation of red blood cells, and the factors that regulate and influence red blood cell production including erythropoietin and iron metabolism. It concludes by covering red blood cell properties and functions, as well as causes and types of anemia.

1. INTRODUCTION TO BLOOD
DR LWIINDI

2. Section 2 Blood Cells and Hematoiesis
• Red blood cell
• White blood cell
• Platelet

3. Hemopoiesis
• The process of blood generation.
Cell Lineage Lifespan Daily Production Rate
RBC 120 days 2.5  109/L
Neutrophil 7 hours 0.85  109/L
Platelet 10 days 2. 5  109/L

4. • Ontogeny of Hematopoiesis
– Prenatal stages:
• First month: yolk sac.
• Third month: liver
• Fourth month: bone marrow
– Postnatal stages:
• Bone marrow of almost any bone, predominatantly by
flat bones and long bones.

5. 0 2 3 4 5 6 7 8 9
1
100 100
birth 20 30 40 50 60 70 80 90
10
100 100
Yolk Sac Liver Bone morrow
Spleen
Lymph nodes
Prenatal age (months)
Postnatal age (years)
Tibia
Femur Ribs
Sternum
Vertebrate
Hemopoitic
activity
(%)
Proportion
of
Red
Morrow
(%)

7. Hematopoiesis: the formation of blood cells
• Hematopoiesis is the process that generates
blood cells of all lineages.
• Calculations based on the blood volume and
the level and half-life of each type of blood
cell in the circulation indicate that each day
an adult produces ~ 200 billion erythrocytes,
100 billion leukocytes, and 100 billion
platelets.
• These rates can increase by a factor of 10 or
more when the demand for blood cells
increases

11. Growth and differentiation inducers (cytokines,
hormones) for the formation of blood cells …
• Interleukin-3 (IL-3) promotes growth of most of
the different types of stem cells
• Interleukin-7 (IL-7) - major cytokine in stimulating
bone marrow stem cells to start down the path
leading to the various lymphocytes (mostly B cells
and T cells).
• Erythropoietin (EPO), produced by the kidneys,
enhances the production of red blood cells
• Thrombopoietin (TPO/ megakaryocyte growth and
development factor), assisted by Interleukin-11 (IL-
11), stimulates the production of megakaryocytes.
Their fragmentation produces platelets.

12. • Granulocyte-monocyte colony-stimulating factor
(GM-CSF), as its name suggests, sends cells down
the path leading to both those cell types. In due
course, one path or the other is taken.
• - Under the influence of granulocyte colony-
stimulating factor (GCSF), they differentiate into
neutrophils.
• - Further stimulated by interleukin-5 (IL-5) they
develop into eosinophils.
• - Stimulated by macrophage colony-stimulating
factor (M-CSF) the granulocyte/macrophage
progenitor cells differentiate into monocytes, the
precursors of macrophages.

13. ERYTHROPOIESIS
• process of the origin, development and
maturation of erythrocytes
• important changes occur:
– Decrease in RBC size (25 to 7.2um)
– Disappearance of nucleoli and nucleus
– Appearance of hemoglobin and
change in staining properties
– Formation of biconcave disc shape

14. ERYTHROPOIESIS

15. ERYTHROPOIESIS
• Factors necessary for hematopoiesis
– General stimulants
• Erythropoietin; Thyroxine; Other Hematopoietic
growth factors; Vitamins (B, C, D, E)
– Maturations Factors
• B12 and Folic Acid.
– Substrates for Hb synthesis
• Amino acids, Iron, other minerals.

16. MATURATION FACTORS - B12 Vitamin &
Folic acid
• Act on the final maturation of RBC.
• Both are essential for DNA synthesis through
the formation of an essential DNA building
block, thymidine triphosphate
• B12 Vitamin:
- the body uses 1-3 μg/day of B12 vitamin
- hepatic stores amounts 1000-3000 μg
(enough for 3-4 years…)
- intrinsic factor needed for absorption …
HOW?

17. • Vit. B12 & folic acid deficiency >> proliferation
& maturation failure:
- macrocytes (large, oval, fragile)> short life
causes:
• atrophic gastric mucosa>> intrinsic factor
deficiency> no B12 absorption (pernicious
anemia)
• Dietary deficiency (who?)
• Ileal resection

18. Erythropoietin
• Glycoprotein, MW = 34.000, T1/2 = 6 - 9 hours
• Mechanism of action:
↑ the committment of stem cells to
proerythroblasts
↑ the differentiation of erythroblastic stages
• Synthesized - 90% kidneys (renal tubular* epithelial
cells?), the rest of 10% formed mainly in the liver
• - stimulus = renal hypoxia
↑ in EPO conc. after minutes to hours, with a
maximum level after 24 h
↑ after 3 - 5 days: ↑ RBC number. 10 x
• - other non-renal hypoxia sensors act through
E, NE, PG (+) EPO production

20. • Regulation of erythropoietin control
mechanism…
• Therapeutically used: 50 – 300 U / kg, 3 times /
week
• in kidneys diseases, transplant, anemia,
pulmonary diseases, blood loss…

21. RED BLOOD CELLS

22. RED CELL COUNT
• Age It is higher in the newborn.
• Sex Cell count is relatively less in females
• Exercise During muscular exercise there is a slight
temporary elevation of cell count.
• Diural variation It is slightly reduced during sleep.
• Altitude At higher altitudes the count is increased due
to hypoxic state, which stimulates cell production.
• Emotional state There is increased secretion of
adrenaline during excitement which increases the
erythrocyte count.

23. • Normal erythrocytes have a mean diameter of 7.2
microns and an average thickness of 2.2 microns. They
contain about 65% water and the rest is made up of
solid substances, out of which the haemoglobin
constitutes 33%.
• Functions The main function of red blood cell is to
transport oxygen and carbon dioxide.
• Life period The average life of an RBC is 120days. The
old cells are destroyed in the spleen and liver.
• The physiological rise in RBC count is called
polycythaemia. This can be observed in high altitudes.

24. • Polycythaemia vera indicates the pathological
condition of raised RBC count, which is seen in
malignant condition of the red bone marrow.
• A decreased red cell count or subnormal
haemoglobin level, when present is called
anaemia.

25. HAEMOGLOBIN
• It is a chromoprotein and is red in color. Hb consists of
a protein component globin and an iron containing
pigment haem (porphyrin ring + iron)
• Iron exists in the ferrous form and each molecule of
haemoglobin contains four iron atoms. Hb combines
with the oxygen to form a loose reversible compound
oxy-haemoglobin, which rapidly dissociates in the
tissues to release oxygen.
• The formation and subsequent breakdown of
oxyhaemoglobin is influenced by various factors which
would be discussed later on in the chapter of
respiration.

26. Hemoglobin
Structure of Hemoglobin

27. Hemoglobin
Functions:
• Transports O2
• Transports CO2
• Acid-base Buffer

28. Hemoglobin
• Haemoglobin content of the blood ranges
between 14 to 18 gm% and can be
determined by haemoglobinometer.
WHY??

29. Types Of Haemoglobin
• Normal HB – HbA (α2β2); HbF (α2γ2)
• Hemoglobinopathies
– HbS
– Thalassemias
• α
• Β
• Abnormal derivates
– CarboxyHB (CO)
– MethHB (Fe3+)

30. Life Span of Red Cells and Fate of
Haemoglobin
• The average life span of erythrocytes is 120
days.
• The cells are constantly broken down,
primarily in the spleen and new cells are
formed in the bone marrow.
• This helps to maintain a constant cell count.
• The fate of haemoglobin has been
summarized below:

32. IRON METABOLISM
• The iron content of the body is about 4-5
mgm/kg of body weight.
• It is an essential constituent of haemoglobin,
myoglobin, and respiratory enzymes and its main
functions are the transport of oxygen to the
tissues and cellular oxidative mechanism.
• The important sources of iron are liver, spleen,
kidney and heart, but egg yolk, green leafy
vegetables, nuts, dates and figs also contain iron
in adequate quantities.

33. • Absorption Normally very little of dietary iron
(10%) is absorbed in the gastrointestinal tract.
• The organic ferric iron is converted into ferrous
form by gastric acidity and iron absorption
mainly occurs in the upper duodenum and
depends upon the ferritin content of the
intestinal mucosa.
• This is an iron-protein complex having 23% iron
and a protein called apoferritin.
• This theory of absorption is known as “mucosal
block theory”.

34. • Transport, Utilization and Storage Iron combines with
beta globulin and forms siderophilin or transferrin,
which is the transport form of iron.
• In the tissues iron is released from siderophilin and it is
utilized for the synthesis of haemoglobin, myoglobin
and respiratory enzymes.
• Iron is stored in liver, spleen and intestinal mucosa.
• About 0.8% of the circulating RBC undergo
disintegration daily and they liberate approximately
8gm, of haemoglobin which on degradation gives
25mgm of iron.

35. • The bulk of it is used for the resynthesis of
haemoglobin and the balance is stored.
• Excretion The efficiency of the utilization of
the endogenous iron is high and only small
quantities in the urine.

36. ANAEMIA
• It is due to the reduction of red blood cells or sub-
normal level of haemoglobin which consequently
affects the supply of oxygen to the tissues.
• Anaemia by itself is not a disease but a symptom of
some underlying cause.
• Some of the common types of anaemia are:
I. Nutritional anaemia due to a certain deficiency in
the diet
a. Pernicious anaemia due to Vit B12 deficiency .
b. Megaloblastic anaemia due to lack of folic acid.
c. Hypochromic anaemia as in iron deficiency.

37. II. Haemolytic anaemia resulting from excessive breakdown
of RBC. It may be seen in the following conditions.
a. Disease like malaria
b. Sickle cell anaemia and thalassemia due to the
presence of abnormal haemoglobin.
III. Aplastic anaemia in which there is a suppression of bone
marrow as in
a. excessive use of certain drugs like sulpha drugs or
chloramphenical.
b. exposure to X-ray radiation.
c. Malignant disease of the bone marrow.