BLOOD- HEMATOPOEISIS 3.

Transport of hormones from the

endocrine organs to their target organs
-A highly complex suspension of cells in a
4. Maintenance of body temperature
viscous medium.
through the absorption and distribution
Physical Characteristics of body heat.

1. Accounts for approximately 8% of the B. Protection Function

body wt.
Volume in a healthy males- 5-6L
Volume in a healthy females- 4-5L
2. pH- slightly alkaline- between
(7.35-7.45)
3. Viscosity- 5x more viscous than water
because of its formed elements
4. Color
- scarlet (oxygen-rich) arterial blood
-dark red (oxygen-poo) venous blood
5. Sticky, opaque fluid with characteristic
salty taste
1. Maintenance of normal pH of body
tissues.
2. Maintenance of an adequate fluid
volume in circulatory system.
3. Prevention of blood loss.
4. Prevention of infection.
Composition of Bloods
1. Formed Elements- cellular elements=
constitute 45% by volume
A. RBC- normal RBC are none
nucleated biconcave disc

-Mean diameter- 7.8 micrometer

-Thickness- 2.5 micrometer at thickest

point and 1 micron or less at the center

- Volume- 90-95 cubic micrometers

-Concentration of Blood

Normal Males- 5.2M /cu.mm+300,000

Normal Females- 4.7M/cu.mm+300,000

B. WBC- mobile units of body’s

protective system

Functions:

A. Distribution Functions
1. Delivery of oxygen from lungs and of
nutrients from digestive tract to all
body cells.
2. Transport metabolic waste products
from cells to elimination sites (to the
lungs for elimination of CO2 and to the
kidneys for elimination of nitrogenous
waste in urine)
 C. Platelets
- Small granulated bodies, 2-4 micra
in diameter
- Fragments of the megakaryocyte
- About 300,000/cu. m of circulating
blood
- Function: to activate the blood
clotting mechanism
- Thrombopoiesis is controlled by the
hormone thrombopoietin
- Platelets are minute fragments of
cells, each consisting of a small
amount of cytoplasm surrounded
by a cell membrane.
- They are produced in the red bone
marrow from large cells called
megakaryocytes.
- Small fragments break off from the
megakaryocytes and enter the
blood as platelets.
- Platelets play an important role in
preventing blood loss.
Differentiation of Plasma and Serum
Plasma- with anti-coagulant (anti-
coagulated)
Serum-without anti-coagulant; after
coagulation (clotted)
Quantity of Hemoglobin (Hgb)
o RBC’s can concentrate Hgb up to
about 34g in each 100 ml of cells.
o In normal people, almost about
always near the maximum.
o If hematocrit and Hgb in each cell
are normal, then
Men: Hgb of 15g/100ml
Women: Hgb of 14g/100ml
o Each gram of hemoglobin can
combine with 1.34ml of oxygen
Fate of Old Erythrocytes and Hemoglobin
- Old red blood cells are removed from blood by
macrophages in spleen and liver
- Hemoglobin is broken down
- Globin is broken down into amino acids
- Hemoglobin’s iron is recycled
- Heme is converted to bilirubin
- Bilirubin is taken up by liver and released into
small intestine as part of bile
Hematopoiesis
Hematopoiesis is the process that produces
formed elements.
In the fetus, hematopoiesis occurs in several
tissues, including the liver, thymus, spleen,
lymph nodes, and red bone marrow.
After birth, hematopoiesis is confined primarily
to red bone marrow, but some white blood cells
are produced in lymphatic tissues.
All the formed elements of blood are derived
from a single population of cells called stem
cells, or hemocytoblasts.
These stem cells differentiate to give rise to
different cell lines, each of which ends with the
formation of a particular type of formed
element.
Production of RBCs
o Embryonic life- yolk sac
o Middle trimester-liver (main
organ), spleen, lymph nodes
o Third trimester and after birth-
bone marrow
Postnatal hematopoiesis
- Bone marrow of essentially all bones
produce RBCs until about5 years old-
bone marrow becomes fatty (except
 proximal portions of humerus and tibia, o CFU-GM-produces granulocytes and
which produces RBC until age 20) monocyte
- After age 20- marrow of membranous
o Growth Inducers- proteins which
bones
control growth and reproduction of
different stem cells.

Ex. Interleukin-3- promotes growth and

reproduction of virtually all the types of
committed stem cells

o Differentiation Inducers- promote

differentiation

Genesis of blood cells

PHSC- pluripotential hematopoietic stem cells

o Cells in the BM which all the cells in

the circulating blood are derived
o Cells continually reproduce
throughout the life of the
person, but a portion remain
exactly like the original
pluripotential cells & are
retained in the BM to maintain
a supply, though their members
decrease with age.
Growth inducers and Differentiation inducers
The larger portion of the
reproduced stem cells differentiate o Are by factors outside the bone
to form other cells. The early marrow
offspring still can’t be recognized as o RBC- exposure of the body to low
different from the pluripotential oxygen for a long period
stem cells, even though they have o WBC- infectious diseases cause
already committed to a particular growth differentiation & eventual
line of cells & are called Committed formation of specific types of WBC
Stem cells. that are needed to combat
o CFU-E -produces erythrocytes infection.
o CFU-M - produces platelets
RBC Differentiation

1. Proerythroblast/
PRnormoblast/Rubriblast= 1st cells that
can be identified
2. Basophilic erythroblast/ Basophilic
normoblast/ Prorubricyte= stain with
basic dyes- very little hgb
3. Polychromatophilic erythroblast/
Polychromatophilic normoblast/
Rubricyte
4. Orthochromatic erythroblast or
normoblast/polychromatophilic
5. Diffusely basophilic erythroblast or
normoblast/ polychromatic
erythrocyte/ reticulocyte- remnants of Regulation of RBC Production
RNA (golgi apparatus, mitochondria and - Tissue oxygenation= basic regulator
a few other cytoplasmic organelles). of RBC production
Diapedesis 1-2 days - Any condition that
6. Erythrocyte-most mature stage causes a decrease in the amount of
RBC oxygen that is transported in the
blood produces an increase in red
-life span of 120 days cell production
-contain cytoplasmic enzymes that are
capable of metabolizing glucose and  Erythropoietin
forming small amounts of ATP o Principal factor that stimulates RBC
Enzymes also: production
1. Maintain pliability of cell o Tissue oxygenation is the most
membrane. essential regulator of RBC
2. Maintain membrane transport iron. production.
3. Keep iron in ferrous form. o At very high altitudes- oxygen in the
4. Prevent oxidation of the proteins in air is decreased- RBC production
the RBCs increased
o 90% formed in kidneys, 10% in liver.
o Renal tissue hypoxia leads to
increased levels of hypoxia-
inducible factor-1 (HIF-1)
o HIF -1 binds to a hypoxia response
element in the erythropoietin gene-
increased erythropoietin synthesis.
o Hypoxia in other parts of the body
send signals to the kidney to
produce erythropoietin.
o If both kidneys removed- Anemia
 o Stimulates production
proerythroblasts from stem cells.
o Causes proerythroblasts to pass
more rapidly through the different
erythroblast stages.
o In the absence of erythropoietin,
few RBCs are formed by bone
marrow.
Maturation of RBC
o Requires Vit. B12 (Cyanocobalamin)
and Folic Acid
o B12 and FA are required for
formation of thymidine
triphosphate, one of the essential
building blocks of DNA
o Lack of B12 or FA causes abnormal
and diminished DNA, and
consequently, failure of nuclear
maturation and cell division-
Macrocytes
o Macrocytes-mainly larger than
normal RBCs, flimsy membrane,
fragile
of Hemoglobin
-Synthesis of Hgb begins in the proerythroblast
and continues even into the reticulocyte stage
-Each heme molecule combines with a long
polypeptide chain, a goblin synthesized by
ribosomes, forming a subunit of HGB called
hemoglobin chain
-4 hemoglobin chains = Hemoglobin molecule
-Each hgb chain has a heme prosthetic group
containing an atom of iron
-Each hgb molecule has 4 chains= 4 atoms of
iron
-Each iron molecule can bind with one molecule
of oxygen
- Hgb= 4 molecules of oxygen or 8 atoms of
oxygen
-Hgb chains are alpha, beta, gamma & delta
-Most common form of HGB is HGB A – two
alpha chains and two beta chains
-Type of HGB chains determine the binding
affinity of the HGB for oxygen
-Abnormalities of chains can alter physical
characteristics of HGB molecule
Ex. Sickle Cell Anemia- Valine is substituted for
Glutamic Acid at one point in each of the two
beta chains
Hemoglobin
  Primary function is to combine
reversely with oxygen
 Releases oxygen readily in the
peripheral tissue capillaries, where
the gaseous tension of oxygen is
much lower than in the lungs
IRON
o Total body quantity- 4 to 5 grams
o 69% in HGB
o 4% in myoglobin
o 1% in various heme
compounds
o 0.1% combines with the
protein Transferrin
o 15-30% stored for later use
Transport and Storage of Iron
1. Iron absorbed in the intestines
2. Iron combines with
3. Transferrin is transported in the plasma.
Excess iron is stored mainly in liver hepatocytes
and less in the reticuloendothelial cells of the
bone marrow
ANEMIA
o Means deficiency of hemoglobin in
the blood, which can be caused by
either too rapid loss or too slow
production of RBCs or too little HGB
A. Blood Loss Anemia (Hemorrhagic
Anemia) – due to rapid hemorrhage.
Fluid portion of plasma replaced in 1-3
days. RBC normal within 3-6 weeks.
o When chronic blood loss occurs,
inadequate iron absorption to
replace RBC loss - microcytic,
hypochromic anemia
o Acute Hemorrhagic Anemia-
following a severe wound
o Chronic Hemorrhagic Anemia-
slight persistent blood loss, as
might result from hemorrhoids
or undiagnosed bleeding ulcer
o Once the primary problem is
resolved normal erythropoietic
mechanism replace the
deficient cells
B. Aplastic Anemia- BM is not functioning
o due to bone marrow dysfunction
person exposed to gamma ray
radiation, excessive x-ray treatment
(chemotherapy or radiation),
certain industrial chemicals and
drugs which the person might be
sensitive.
o Leads to stem cell damage. Can also
be due to autoimmune diseases
-in half of aplastic anemias, cause is
unknown- Idiopathic Aplstic Anemia
C. Megaloblastic Anemia- Vit. B12, Folic
acid deficiency and intrinsic factor
deficiency
o Cells grow large with odd shapes,
called megaloblasts
D. Hemolytic Anemia- normal production
of RBC life span is short
o due to different abnormalities of
the RBC which maybe hereditary,
acquired and make cells very fragile
so they rapture easily
Examples:
Sickle cell anemia= abnormal Hb= HbS
Thalassemia’s- thin and delicate RBCs
(RBC count less than 2 M/cu.mm)
o Erythroblastosis Fetalis- RH
positive RBCs in the fetus are
attacked by antibodies from an
RH negative mother
Effects of Anemia on Circulatory System
 In severe anemia- blood viscosity may
fall to as low as 1.5x that of water
(normally, 3x that of water). The
decreased viscosity decreases the
 resistance to blood flow in the  Lack hemoglobin
peripheral vessels blood return to the  Larger than erythrocytes
heart.  Contain a nucleus
 Hypoxia causes peripheral tissue blood  Mobile units of the body’s protective
vessels to dilate, allowing a further system
return of blood to the heart and  Acting together, theses cells provide the
increasing the cardiac output body with powerful defenses against
tumors, viral infections, bacterial
Anemia leads to greatly increased cardiac
infections and parasitic infections
output and increased pumping workload on
 4000-11000/cu.mm.
the heart.
Functions:
POLYCYTHEMIA
 fight infections
- Increased amount of RBC in  remove dead cells and debris by
circulation phagocytosis
o Secondary Polycythemia- secondary
to tissue hypoxia. RBC count
commonly rises to 30% above Types of WBC
normal
a. Granulocytes- contain specific granules
- Physiological Polycythemia- natives
and include neutrophils, eosinophils,
who live at altitudes of 14000 to
and basophils
17000 feet
a1. Neutrophil
o Polycythemia Vera- RBC count may
a2. Eosinophil
be up to 7.8 million/cubic milliliter.
a3. Basophil
HCT may be 60-70% instead of
b. Agranulocytes- no specific granules
normal 40-45%
b1. Lymphocytes
- Due to genetic aberration in the
b2. Monocyte
hemocytoblastic cells that produce
the RBC. The blast cells no longer
stop producing RBCs when too
many cells are already present
- Total blood volume also increases.
As a result, the entire vascular
system becomes intensely
engorged.

Effects of Polycythemia

- Blood flow is sluggish

- Increasing blood viscosity decreases
venous return to the heart
- Increased blood volume increases
venous return to the heart
- Arterial pressure may be elevated
WBC
Lifespan of granulocytes once releases from the
BM is 4-8 hours circulating in the blood and
another 4-5 days in the tissues. It will be
shortened though in infection. They ingest the
invading organisms and in the process are they
destroy themselves.
Production and Life Span Leukocytes
- Like erythropoiesis, leukopoiesis is
hormonally stimulated.
hematopoiesis hormones
CSFs, or COLONY STIMULATING
FACTORS, not only prompt the WBC
precursors to divide and mature but
also enhance the protective
potency of mature leukocytes.
- WBC are able to slip into and out of
the vessels by DIAPEDESIS.
Types of WBC
These
1. Neutrophil- for phagocytosis
• most numerous of the WBC
• remain in blood for 10 to 12 hours
then move to tissues
• phagocytes
• exhibits phenomenon of
chemotaxis (attraction to the
injures sites)
• Neutrophilia and neutrophil
invasion of the inflamed area--- 2nd
line of defense against infection
2. Eosinophil- slightly phagocytic
• reduce inflammation
• destroy parasites
• plays a part in detoxication and also
in the disintegration and removal of
proteins
• increase in number in parasitic
infection and allergy attacks
3. Basophil
• least numerous
• release histamine and heparin
• exhibit local anticoagulation in
cases of inflammation and this
ability is due to its elaboration of a
heparin like subs,
4. Lymphocytes
• immune response
• several different types (T cells and B
cells)
• lead to production of antibodies
• concerned with the formation of
gamma- globulin which now serves
as AB’s
• Remain in the blood for a few hours
—pass by diapedesis into the
tissues, then reenter the lymph and
return to the blood again.
 • Life span varies from 100 to 300
days or in some even years
depending on the body’s need
5. Monocytes- Phagocytes
• largest sized white blood cells
• produce macrophages
• they are mobilized along with
neutrophils as part of the
inflammatory response and
constitute a first line of defense
against bacterial infection
• has a short transit tissue in the
blood before wandering through
the capillary membrane into the
tissues.
• Once in the tissue they swell to
much larger size to become tissue
macrophage and can live for
months or even years unless
destroyed by performing phagocytic
functions
 Tissue macrophage system- provides a
first line of defense in the tissues
against infection.
Ex.
- Histiocytes- tissue macrophage in
the skin and subcutaneous tissues
- Tissue macrophages of the lymph
nodes
- Alveolar macrophages-lungs
- Kuffler cells- liver
- Microglia- brain
Inflammation
- The “WALLING OFF” effect of
inflammation.
- One of the first results of
inflammation is to “wall off” the
area of injury from the remaining
tissues. This delays the spread of
bacteria or other toxic products
- Pus- mixture of necrotic tissue
condition where in the BM stops
producing WBC, leaving the body
unprotected against bacteria and
other agents that might invade
tissues.
The process of inflammation:
When tissue injury occurs, whether it is caused
by bacteria, trauma, chemicals, heat, or any
other phenomenon, multiple substances that
causes dramatic secondary changes in the
tissues are released by the injured tissues.
These secondary changes are called
INFLAMMATION. Inflammation is characterized
by:
1. Vasodilation of the local blood vessels.
2. Increases permeability of the capillaries
with leakage of large quantities of fluid
into the interstitial spaces.
3. Often clotting of the fluid in these
spaces because of excessive amounts of
fibrinogen and other proteins.
4. Swelling of the cells.
LEUKEMIAS
- The uncontrolled production of
WBC caused by cancerous mutation
 of myelogenous or lymphogenous Rodak, Bernadette, Clinical Lab
cells. Principles in Hematology.
- Characterized by greatly increased
Guyton and Hall, Textbook of
numbers of abnormal white blood
Medical Physiology, 13th edition.
cells in the circulating blood.
Lospeich Steininger, Clinical
Types of Leukemias
Hematology, Principles,
1. Lymphogenous Leukemia- Procedures, Correlation.
caused by cancerous
production of lymphoid cells,
beginning first in the lymph
node or other lymohogenous
tissue then spreading to other
areas of the body.
2. Myelogenous Leukemia- begins
by cancerous production of
young myelogenous cells in the
BM and then spread
throughout the body so that
WBCs are produced in many
extramedullary organs.

LEUKEMIC CELLS- especially the

very undifferentiated cells are
usually nonfunctional, so that they
cannot provide the usual protection
associated with WBCs.

1st effect: metabolic growth of

leukemic cells in abnormal areas of
the body. The leukemic cells in the
BM may reproduce so greatly that
they invade the surrounding bone
causing pain and eventually a
tendency to easy fracture. They
utilize the metabolic elements of
the tissues & cause tissues
destruction.

REFERENCES:

Marieb, Elaine Essentials of Human

Anatomy & Physiology, 11th
edition.