Transcript Formation of blood cells (Haemopoiesis)

•Erythrocytes
•Leukocytes
•Platelets
Where blood is made?
Haemopoietic
cells first appear in
the yolk sac of the 2-week embryo.
By
8 weeks, blood making has
become established in the liver of
the embryo
By
12-16 weeks the liver has
become the major site of blood cell
formation.
The
spleen is also active during
this period.
The
highly cellular bone marrow
becomes an active blood making
site from about 20 weeks
Hematopoietic stem cell
At birth, active blood making red marrow occupies the entire capacity of the bones and
continues to do so for the first 2-3 years after birth.
The red marrow is then very gradually replaced by inactive, fatty, yellow, lymphoid
marrow.
They develop in the shafts of the long bones and continues until, by 20-22 years, red marrow is
present only in the upper ends of the femur and humerus and in the flat bones of the sternum, ribs,
cranium, pelvis and vertebrae
In old age, red marrow sites are slowly replaced with yellow, inactive marrow.
About two-thirds of its mass functions in leucopoiesis, and one-third in red
cell production erythropoiesis.
• The gradual appearance of hemoglobin and
disappearance of ribonucleic acid (RNA) in the cell
• The progressive degeneration of the cell's nucleus
which is eventually extruded from the cell
• The gradual loss of cytoplasmic organelles, for
example mitochondria
• A gradual reduction in cell size
The developmental pathway consists of three
phases
1 – ribosome synthesis in early erythroblasts
2 – Hb accumulation in late erythroblasts and norm
oblasts
3 – ejection of the nucleus from normoblasts and
formation of reticulocytes


Reticulocytes then become mature erythrocytes 12% of RBC in health people
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
Erythropoietin (EPO) release by the
kidneys is triggered by:

Hypoxia due to decreased RBCs or hemoglobin content

Decreased oxygen availability

Increased tissue demand for oxygen

Enhanced erythropoiesis increases the: RBC count in
circulating blood

Oxygen carrying ability of the blood
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Homeostasis: Normal blood oxygen levels
Increases O2-carrying ability of
blood
Reduces O2 levels in blood
Erythropoietin
stimulates red bone
marrow
Enhanced Erythropoiesis
increases RBC count
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Kidney (and liver to a smaller
extent) releases erythropoietin
Thyroid hormones, thyroid-stimulating hormone, adrenal cortical steroids,
adrenocorticotrophic hormone, and human growth hormone (HGH) all promote
erythropoietin formation
(erythropoiesis)
In thyroid deficiency and anterior pituitary deficiency, anaemia
may occur due to reduced erythropoiesis.
polycythaemia
Androgens stimulate and oestrogens depress the
erythropoietic response
Erythropoietin is also produced by a variety of tumours of
both renal and other tissues
very high doses of steroid hormones seem to
inhibit erythropoiesis.

Heme is degraded to a green pigment
biliverdin

Biliverdin is converted to a yellow pigment
called bilirubin
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The bilirubin is picked up by the liver and
secreted into the intestines as bile
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The intestines metabolize it into urobilinogen
and stercobilinogen

These degraded pigments leave the body
in feces and urine, in a pigment called
stercobilin and urobilin
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
Globin is metabolized into amino acids and
is released into the circulation

Hb released into the blood is captured by
haptoglobin and phagocytized
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DEGRADATION OF HEME TO BILIRUBIN
 75% is derived from RBCs
P450 cytochrome
 In normal adults this
results in a daily load of
250-300 mg of bilirubin
 Normal plasma
concentrations are less then
1 mg/dL
“unconjugated” bilirubin
 Hydrophobic – transported
by albumin to the liver for
further metabolism prior to
its excretion
Heme proteins
myoglobin, cytochromes
(20 to 25%)
Hemoglobin
(70 to 80%)
Erythroid cells
Heme
ferritin
(250 to 400 mg/day)
3 [O]
Heme oxygenase
3+
Fe + CO
apoferritin
Biliverdin
NADPH + H+
Biliverdin reductase
NADP+
Bilirubin
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albumin
indirect
unconjugated
pre-hepatic
albumin-Bilirubin
albumin
hepatocyte
ligandin
ligandin-Bilirubin
2 UDP-glucuronate
ER
UDP-Glucuronyl
transferase
2 UDP
Bilirubin diglucuronide
bile (gall bladder)
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direct
conjugated
post-hepatic
Bilirubin diglucuronide
2 glucuronate
liver
Bacterial enzyme
Intrahepatic
urobilinogen cycle
Bilirubin
8H
Bacterial enzyme
kidneys
intestines
Urobilinogen
Urobilin
urine
Stercobilin
feces
kidneys
Bacterial enzymes
Stercobilinogen
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Dietary
element
Role in red blood cell production
Protein
Required to make red blood cell proteins and also for the globin
part of haemoglobin
Vitamin B6
Not clear what the role is but deficieny has occasionally been
associated with anemia
Vitamin B12 and folic acid
Needed for DNA synthesis and are essential in the process of red
blood cell formation
Vitamin C
Required for folate metabolism and also facilitates the absorption
of iron. Extremely low levels of Vitamin C are needed before any
problems occur. Anemia caused by lack of Vitamin C (scurvy) is
now extremely rare
Iron
Required for the haem part of haemoglobin
Copper and Cobalt
There is some evidence that these two trace minerals are
essential for the production of red blood cells in other animals but
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•Monocytes are actively phagocytic (engulf other cells) and, on migration into the
tissues, they mature into larger cells called macrophages
•These cells form the mononuclear phagocytic cells of the mononuclear phagocytic
system (reticuloendothelial system) in bone marrow, liver, spleen and lymph nodes.

Lymphocytes are produced in bone
marrow from primitive precursors

The lymphoblasts and prolymphocytes.

Immature cells migrate to the thymus
and other lymphoid tissues, including
that found in bone marrow, and
undergo further division, processing
and maturation.
Granulocytes is the collective name given to three types of
white blood cell. Namely these are neutrophils, eosinophils
and basophils, respectively as figures .
They all derive from myeloblasts.
After birth and into adulthood granulopoiesis occurs in the
red marrow.
The process of producing granulocytes is characterized by
the progressive condensation and lobulation of the nucleus,
loss of RNA and other cytoplasmic organelles, for example
mitochondria, and the development of cytoplasmic granules
in the cells involved.

Mature cells pass actively through the endothelial lining of
the marrow sinusoid into the circulation.

In the circulation, about half the granulocytes adhere
closely to the internal surface of the blood vessels
(marginating cells);not normally included in white cell count.
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The other half circulate in the blood and exchange with the
marginating population.

Within 7 hours, half the granulocytes will have left the circulation in
response to specific requirements for these cells in the tissues.

Once a granulocyte has left the blood it does not return. It may
survive in the tissues for 4 or 5 days, or less, depending on the
conditions it meets.

The turnover of granulocytes is, therefore, very high. Dead cells are
eliminated from the body in faeces and respiratory secretions and
are also destroyed by tissue macrophages (monocytes).

The stem cell for platelets is the hemocytoblast

The sequential developmental pathway is as
shown
Stem cell
Developmental pathway
Hemocytoblast Megakaryoblast Promegakaryocyte Megakaryocyte Platelets
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platelet budding.
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Megakaryocytes mature in about 10 days, from the megakaryoblast.
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At any one time, about two-thirds of the body's platelets are circulating in
the blood and one-third are pooled in the spleen.
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The life span of platelets is between 8 and 12 days.
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They are destroyed by macrophages, mainly in the spleen and also in the
liver.