Group F-PBL Problem 2

GROUP F
PBL PROBLEM 2
THE SECONDARY FUNCTION OF THE
SPLEEN UNDER HEMATOPOIETIC STRESS
GROUP LEADER: Kimberly George

SCRIBE: Krystle Choo-Ying- Samson
Table 5: Timeline of Group F Activities.

Monday 1st
Tuesday 2nd
Wednesday 3rd
Thursday 4th Friday 5th
Saturday
Individual
Group
Group
Individual
Individual
6th
Individual
summary,
brainstorming
brainstorming
research
research
research &
identification
hypothesis &
hypothesis &
Group
Group
of unknown
SGLOs
SGLOs
brainstorming
discussion
words &
generation
generation
SGLOs &
phrases.
Individual
Group
Definitions
research Group
discussion
with
discussion
regarding
appropriate
deadline for
citations.
individual
reports
submission,
Saturday or
Sunday
Sunday 7th
Monday 8th
Wednesday
Tuesday 9th
10th
2
Group
discussion,
Group
discussion
Submissions
of individual
reports
Submission of
individual
Group report
Compilation
of group
report
Compilation
of group
report
Compilation of
group report
Submission of
individual
report
Compilation
of group
report
PROBLEM ANALYSIS:
Krystle Choo-Ying Samson
Research have determined how the body responds to hematopoietic stress and its physiological
importance. In times of emergency and abnormal circumstances such as tissue damage, excessive
bleeding, chemotherapy and pregnancy the body experiences hematopoietic stress in which case,
quick recovery of blood cells count is required to maintain normal blood cells count.
Haematopoiesis occurs in the bone marrow where hematopoietic stem cells are predominantly
found. However, under hematopoietic stress, activation of the bodys secondary, emergency,
hematopoietic system in the spleen responds to the bodys need for more blood cells.
Haematopoiesis expands to the spleen by the migration of hematopoietic stem cells from the
bone marrow to the spleen making it a hematopoietic organ.
The spleen possess only a few hematopoietic stem cells however, it also possess cells that
provides the supporting microenvironment/ niche for the existing hematopoietic stem cells of the
spleen and influx of hematopoietic stem cells from the bone marrow.
Two recognized niche cell factors, stem cell factor (SCF) and CxCL12, expression patterns were
examined in the characterization of the supporting niche for haematopoiesis in the spleen.
Research found that it is located proximal to sinusoidal blood vessels and is formed by
endothelial cells and perivascular stromal cells, same as the supporting microenvironment for
hematopoietic in the bone marrow. Under hematopoietic stress the residing endothelial cells and
perivascular stromal cells of the spleen proliferate in order to sustain the newly migrated
hematopoietic stem cells.
In the future, therapeutic interventions to enhance hematopoietic after chemotherapy or bone
marrow transplantation for accelerated regeneration of blood cell counts could be developed
based on research findings about the spleens contingent role for hematopoietic.
4
Kimberly George
The article generally states that a secondary blood formation system is activated in the spleen
during times of excessive bleeding or pregnancy. At times of hematopoietic stress, it is seen that
the hematopoietic stem cells move from the bone marrow to the spleen, in which it becomes a
hematopoietic organ for blood formation. It was also found that the environment suitable for the
formation of blood is located near the sinusoidal blood vessels and is formed by the endothelial
cells and perivascular stromal cells, which is similar to the one in the bone marrow. Therefore by
learning this new information on the spleen, new therapeutic treatments could be created to
quickly regenerate blood cell counts after chemotherapy or a bone marrow transplant.
Giselle Jack
Under normal conditions new blood cell formation occurs within the bone marrow where
hematopoietic cells are mainly found. In times of hematopoietic stress however blood formation
expands to the spleen. Hematopoietic cells from the bone marrow migrate to the spleen and as
such it becomes a hematopoietic organ and blood formation can occur there.
The blood forming microenvironment in the spleen is similar to that in the bone marrow. It is
found near the sinusoidal blood vessels and is created by endothelial cells and perivascular
stromal cells. Under times of hematopoietic stress these cells are induced to proliferate so that
they can sustain the blood forming cells that migrate to the spleen. The discovery of the spleens
backup role in blood cell formation allows for the development of therapeutic interventions to
enhance blood formation in times of tissue damage or excessive blood loss.
Darien Karim
Scientists have discovered that during hematopoietic stress or times of emergency when the body
requires more blood cells, the spleen acts as an emergency backup organ. The spleen has a
specific micro environment that facilitates an influx of new blood forming stem cells from bone
marrow. Based on this research new advancements in the medical field could be made to enhance
blood cell formation and accelerate the recovery of blood cell counts following chemotherapy or
bone marrow transplantation
Alex Pardasie
The article touches on aspects relating to blood counts and the secondary function of the spleen.
It was mentioned that in times of emergency, when the body is under haematopoietic stress, and
the bone marrow is unable to provide the necessary amount of blood cells required, the process
of blood formation goes beyond the bone marrow and associates the function with the spleen.
The spleen is said to have a specific microenvironment suitable for the accommodation of the
influx for blood forming or haematopoietic stem cells, as it is somewhat similar to the niche of
the bone marrow. Upon analysis of these newly founded information it is believed that further
interventions can be formulated in the near future, to alleviate problems associated with blood
formation, such as after chemotherapy for instance.
Nicholas Persad
This article states that when the body goes through trauma for instance like excessive bleeding,
tissue damage or in case of pregnancy, a secondary emergency blood formation system in the
spleen is activated. Normal blood formation takes place in the bone marrow with hematopoietic
cells but doctors from this article suggest the under stress blood forming stem cells move to the
spleen making it a hematopoietic organ where blood is formed.
Usually some blood-forming stem cells are found in the spleen but through research of mice it
has shown that the micro environment of the spleen is just like that of the bone marrow which in
turn means that it can support and is ready to respond in times of hematopoietic stress. Based of
these findings of a secondary blood formation system further advancements can be made in the
recovery of blood formation in chemotherapy and bone marrow transplant patients.
Aruna Ramnarine
Blood cell formation occurs in the bone marrow which consists of hematopoietic cells. However,
according to a study published by Nature, when the body requires the formation of new blood
cells, due to excessive bleeding, pregnancy or tissue damage, or times of emergency, the spleen
becomes the hematopoietic organ. Hematopoietic cells from the bone marrow migrate to the
spleen, during hematopoietic stress, thereby expanding the formation of blood.
From experiments conducted, CRI researchers found that, like the niche in bone marrow,
the microenvironment for the formation of blood, in the spleen, is found near sinusoidal blood
vessels and is created by endothelial cells and perivascular stromal cells. When hematopoietic
stress occurs, these cells are induced to proliferate, thereby being able to sustain the new blood
forming stem cells which are migrated into the spleen. This new information about the spleens
backup role in the formation of blood cells, allows for future development of therapeutic
interventions to enhance blood formation in cases of excessive blood loss, and pregnancy.
TERMS&DEFINITION:
Krystle Choo-Ying Samson
Haematopoiesis - formation of elements (erythrocytes, leukocytes and thrombocytes) of
the blood.
Hematopoietic stem cells (HSCs) stem cells that produce all the cells contained in
blood.
Hematocrit (HCT) also known as packed cells volume (PCV) which describes the
volume of red blood cells present in a blood sample.

Hematopoietic stress stress experienced by hematopoietic system due to increased
demand in blood supply.
Kimberly George
Hematopoietic: The production of all types of blood cells including formation,
development, and differentiation of blood cells.(MedicineNet, 2016)

Microenvironment:a small or relatively small usually distinctly specialized and
effectively isolated habitat or environment (as of a nerve cell).(Merriam-webster.com,
2016)
Stem cell- an unspecialized cell that gives rise to differentiated cells such as the
hematopoietic stem cells in bone marrow.(Merriam-webster.com, 2016)
8
Giselle Jack
Spleen an organ in the lymphatic system located near the stomach that destroys worn-
out red blood cells and produces white blood cells (Merriam-webstercom, c2015).
Hematopoietic the formation and development of blood cells (Thefreedictionarycom,
c2016)
Stem cells an undifferentiated cell that divides and gives rise to specialized cells
(Dictionarycom, c2016)
Bone marrow the soft blood forming tissue that fills the cavities of bones and contains
fat, both mature and immature blood cells and platelets (Medicinenetcom, c2016)
Niche a job or position that is especially suitable for someone (Cambridgeorg, c2016)
Sinusoidal blood vessels a blood vessel having lining of reticuloendothelium but little
or no adventitia found in organs such as the liver heart and spleen (Thefreedictionarycom,
c2016)
Perivascular stromal cells connective tissue cells occurring around blood vessels which
providing support.
Darien Karim
Proliferate- to reproduce rapidly

Stem cell factor- or SCF can exist as a transmembrane protein or a soluble protein, it is a
cytokine which binds to the c-KIT receptor (CD117).

CXCL12- stromal cell-derived factor 1 is a chemokine protein that is encoded by the
CXCL12 gene.
Alex Pardasie
Chemotherapy: this relates to therapy (treatment) of ailments with the help of chemicals.
Haematopoietic: associated with some aspect of blood formation
Proliferate: elevate or multiply, in relation to numbers
Nicholas Persad
Aruna Ramnarine
Hematopoietic the formation of blood cells. (thefreedictionary.com, 2012)
Spleen- A highly vascular organ, which resides in the lymphatic system, on the left side
of the stomach. Its role is the storage and filtration of blood, the disintegration of old
blood and the production of lymphocytes. (thefreedictionary.com, 2011)
Stem Cells Cells which are not specialized, which develops into differentiated cells.
Niche/ Microenvironment- A specialized position which is suitable for the role of

something or someone.
Stem Cell Factor (SCF)- A cytokine which promotes the growth and differentiation of
hematopoietic stem cells into a variety of cell types. (thefreedictionary.com, 2007)
CXCL12- This is a a gene, located in chromosome 10q11.1 which encodes a stromal cell
derived alpha chemokine that is chemotactic for T-Lymphocytes and Monocytes, once
bound to its CXCR4 receptor. This interaction has been implicated in the metastasis of
cancers, especially breast cancer. (Segen's, 2011)
10
o .
Bone Marrow Transplantation This is the process by which damaged bone marrow,
after procedures such as chemotherapy, is replaced by healthy bone marrow stem cells to
re-establish its function of blood cell formation. (Segen's, 2011)
IDENTIFICATION OF MAIN ISSUES:

Mitigation of hematopoietic stress. Emergency and abnormal circumstances such as tissue
damage, excessive bleeding, chemotherapy and pregnancy the body experiences hematopoietic
stress in which case, quick recovery of blood cells count is required to maintain normal blood
cells count.
Therapeutic interventions are required for the formation of blood following processes such as
chemotherapy and bone marrow transplantation.
The body's hematopoietic secondary response to emergencies such as excessive bleeding or
tissue damage is blood formation system in the spleen.
HYPOTHESES:
1. The blood-forming microenvironment in the spleen is similar to the niche in the bone
marrow.
2. The spleen is the bodys secondary hematopoietic system.
3. The microenvironment of the spleen allows for the increased proliferation of
hematopoietic stem cells which results in increased blood cell formation?
LEARNING OBJECTIVES:
11
1. Describe the anatomy and physiology of the spleen and the characteristics of blood.
2. Indicate the steps in hematopoiesis.
3. Discuss factors which stimulate haematopoiesis.
4. Describe how hematopoietic stress is mitigated in the body.
5. Explain why blood formation is required following procedures such as
OBJECTIVES 1: Describe the anatomy and physiology of the spleen and the characteristics
of blood
Krystle Choo-Ying-Samson
Located in the left hypochondriac region of the abdominal cavity, between the ninth and twelfth
rib, inferior to the diaphragm, posterior to the stomach, approximately the size of a clenched fist,
the oval shaped, flat, brown colored, lymphatic organ known as the spleen, refer to
figure1:Anterior view of the spleen.
12
Figure 1: Anterior view of the spleen.

The spleens superficial, protective layer is made up of tough connective tissue which
encapsulates the spongy, soft, deeper tissues of abundant blood vessels and hollow sinuses
serving as a blood store. The red pulp, the white pulp and the marginal zone between both pulps,
surrounds these vessels and sinuses. The red pulp consists of reticular fibers that filter damaged
erythrocytes from the blood that passes through the spleen. These captured erythrocytes are
catabolized to recycle the iron and protein of hemoglobin. The marginal zone filters pathogens in
the blood passing through the spleen and direct them into the white pulp. The white pulp of
lymphatic tissue filled with macrophages, T- lymphocytes and B- lymphocytes destroy these
captured pathogens and produce antibodies. The spleen performs many functions, filters blood,
recycles erythrocytes, stores leukocytes and thrombocytes that assists the body to fight
13
pneumonia and meningitis bacteria, hence the spleen is vulnerable to many disorders. The spleen
is a support organ instead of a vital organ because the lymph nodes, the liver, red bone marrow
can carry out filtration and recycling functions in its absence.
Blood is the circulatory fluid of the body. Typically, 8% of body weight accounts for blood
volume, approximately 5 liters in an average adult. The blood is composed of two potions,
plasma, the liquid portion (complex solution / extra cellular matrix) and the formed element
portion which contains erythrocytes, leukocytes and platelets. Generally blood volume is
dependent on body size, adipose tissue quantity, changes in the plasma and electrolyte
concentrations.
A typical blood sample has an average 45% hematocrit value which erythrocytes accounts for
45% and leukocytes together with thrombocytes account for <1%. The remaining 55% accounts
for the straw colored plasma in which is made up of 92% water, organic and inorganic
components as electrolytes, vitamins, hormones, amino acids, protein, carbohydrates, lipids and
cellular waste, refer to figure 2: Blood Composition in the Human Body, page #
14
Figure 2: Blood Composition in the Human Body.

Kimberly George
The largest lymphatic organ is essentially the spleen. It is located in the upper left portion of the
abdominal cavity, inferior to the diaphragm, posterior and lateral to the stomach. It contains an
organ called the hilum from which the splenic arteries and veins enter and exit.(Shier, Butler &
Lewis, 2006) The organ is surrounded by a fibrous capsule of connective tissue in which
trabeculae emerge in order to support the larger vasculature. (Uniroma2.it, 2016) It contains
lymphocytes, macrophages and a large number of erythrocytes.
The spleen is divided into two main compartments which the:
15
Red pulp this fills the venous sinuses and the space around them which make up the remaining
spaces of the lobules. It contains macrophages, lymphocytes and red blood cells. The captured
red blood cells are assimilated in order to recycle haemoglobin.
(Humanbiologylab.pbworks.com, 2016) It is made up of the remaining splenic sinuses that are
involved in the disposal of the ruptured red blood cells and blood borne pathogens, hence
filtering the blood. Macrophages are responsible for phagocytizing and removing the cellular
debris and bacteria that may be carried in the blood. (Shier, Butler & Lewis, 2006)
White pulp this is made up of splenic nodules and periarteriolar lymphoid sheaths (PALS)
which contains mostly lymphocytes which are involved in immune functions. Central arteries
within the spleen are surrounded by the sheaths which contain T lymphocytes that play a role in
the immune response by attacking foreign bodies, as the filtration of blood into the spleen
occurs. In the splenic nodules, B-lymphocytes mostly reside thereby producing antibodies to coat
pathogens and prepare them for removal by scavenger cells.(Cashin-Garbutt, 2009)
16
Figure 3 showing the histology of the spleen clearly labelling the various components.
(Faculty.southwest.tn.edu, 2016)
Functions of the spleen include:
-
Site of lymphocyte proliferation

Involved in the immune response and supervision
Filters the blood by removing old and ruptured red blood cells
Stores breakdown products of red blood cells to be utilised later
Spleen macrophages save and store iron for later use by the bone marrow.
Site of foetal erythrocyte production.(Borow, 2016)
Blood is considered the only liquid connective tissue in the body. It is composed of formed
elements such as cells and cell fragments in a matrix or plasma. The average blood volume in an
adult is around 5 litres which makes up about 8% of body weight. The cells in blood include:
17
Red blood cells (Erythrocytes) 95.1%

White blood cells (Leukocytes) 0.1%
Platelets (Thrombocytes) cellular fragments- 4.8%
Plasma a solution which comprises water, amino acids, proteins, carbohydrates, lipids,
vitamins, hormones, electrolytes and cellular wastes- 55%
The characteristics of blood include:

-
More viscous than water

Temperature of 100.4o F
Makes up about 8% of body weight (around 5 litres)
Operates using hormonal negative feedback systems maintain constant blood volume and
osmotic pressure.
There are many functions of blood which are:
Transportation- blood circulates oxygen and nutrients to cells, carbon dioxide and waste
away from cells and hormones to their target tissues.

Regulation- assists to sustain stable body temperature, pH, water and electrolyte levels.
Protection blood clotting prevents loss of fluid from the body and white blood cells
play a role in immune function.(Homepage.smc.edu, 2016)
18
Cell Type
Erythrocyte
Leukocytes
Neutrophil
Eosinophil
Main Products or
Main Functions
Components
Haemoglobin
CO2 and O2 transport
Specific granules
Specific granules
Phagocytosis of bacteria
Defence against parasites,
regulates the inflammatory
Basophil
Specific granules containing
response
Release of histamine
Monocyte
histamine and heparin

Granules with enzymes
Phagocytosis and digestion of

bacteria and virus infected
B lymphocyte (Plasma cell)

T lymphocyte
Immunoglobulins
Substances that kill cells,
cells
Generation of plasma cells
Killing of virus-infected cells
substances that control the

Natural killer cell
activity of other leukocytes

Attacks virus-infected cells
Killing of some tumour and
Platelet
and cancer cells

Blood- clotting substances
virus-infected cells
Clotting of blood.
Table 1 showing the products and functions of the blood cells(Uth.tmc.edu, 2016)
19
Figure
4 showing the constituents

of blood and their
associated
functions(Slideshare.net, 2016)
Giselle Jack
The spleen is a purplish brown, flat, oval shaped, highly vascular organ located in the left
hypochondriac region of the abdominal cavity (Innerbodycom, c2016). It is inferior to the
diaphragm, posterior lateral to the stomach and is protected by the rib cage. The spleen is the
largest lymphatic organ in the body, like the lymph nodes it has a hilum on one surface through
which nerves and blood vessels enter however the spaces in the spleen are filled with blood
instead of lymph (Shier, Butler & Lewis, 2015).
Tough connective tissue encloses the soft inner tissue of the spleen. The connective tissue
extends inwards to subdivide the organ into lobules. The tissues in the lobules of the spleen are
of two types, red pulp and white pulp with a marginal zone in the middle.
20
The red pulp- contains numerous netlike reticular fibres that filter worn out red blood
cells from blood flowing through the spleen. This pulp contains several erythrocytes,
lymphocytes and macrophages. The macrophages engulf the worn out erythrocytes and
recycle the iron and protein components of the haemoglobin.
White pulp made up of lymphatic tissue, this region contains macrophages, T and B
lymphocytes.
They destroy pathogens in the blood and produce antibodies
(Innerbodycom, c2016).
The marginal zone in between of the red and white pulp, acts as a filter to capture pathogens
in the blood and pass them unto the white pulp (Innerbodycom, c2016).
Figure 5: Showing the Anatomy of the spleen (Pinterestcom, c2016)
21
Characteristics of Blood:
Blood is a type of connective tissue, with its cells suspended in a liquid extracellular matrix
(Shier, Butler & Lewis, 2015). The cells and proteins contained in the liquid portion of blood
make it more viscous than water. It is red in colour and has a pH ranging from 7.35 7.45. It
constitutes about 8% the total body weight with the average adult having approximately five
liters of blood (Shier, Butler & Lewis, 2015).
Blood consists of about 55% plasma, which is the yellow liquid containing mainly water along
with along with dissolved proteins, salts and nutrients, and about 45% formed elements which
are the cells and cellular fragments (Slidesharenet, c2016).
22
Figure 6: Showing the Characteristics of Blood (Tdmueduua, c2016)
The formed elements of blood consist of three cell types, the red blood cells (erythrocytes), white
blood cells (leukocytes) and platelets (thrombocytes). All three cell types are formed in the bone
marrow via haematopoiesis. The red blood cells and platelets function entirely within the blood
vessels while the white blood cells function mainly in tissues outside the blood vessels. The table
below lists the characteristics of the cellular component of blood (Tdmueduua, c2016).
23
Table 2: Showing the Characteristics of blood cells (Candelalearningcom, c2016)
The major functions of blood include
24
1. Transportation blood transports oxygen and nutrients to cells and transports carbon
dioxide and waste away from the cells (Slidesharenet, c2016). Hormones are also
transported to target tissues via the blood.
2. Protection white blood cells protect the body against pathogens and platelets aid in
blood clotting preventing excess fluid loss
3. Regulation blood aid in the maintenance of stable body temperature, pH, water and
electrolyte levels (Slidesharenet, c2016).
Darien Karim
The spleen is a flat, brown oval shaped lymphatic organ that stores and removes erythrocytes
from the blood and also functions to protect from infections by performing antigen surveillance
and antibody protection .
The spleen lies vertically on the left side of the cranial abdomen where it is attached to the
stomach by a gastrospleenic ligament. Surrounding the inner spongy tissue of the spleen is a
capsule of tough fibrous and elastic connective tissue. In the spleen there are regions of red pulp
and white pulp which surrounds tiny blood vessels and hollow sinuses that store blood and
platelets which aid in blood clotting or hemostasis.
25
Figure 7 showing the structure of the spleen(Britannicacom, 2016)

The majority of the spleen is made up of the red pulp which is comprised of a network of cell
chords with vascular sinuses net like reticular fibres in this region aid to filter out worn out red
blood cells. Red blood cells are captured and digested to recycle the iron and protein components
of haemoglobin. Between the red and white pulp is a marginal zone that acts as a filter capturing
pathogens in the blood which is passed onto the white pulp. Composed of the white pulp is
lymphatic tissue which contains T-lymphocytes, B- lymphocytes and macrophages that produce
antibodies and destroy pathogens.
Characteristics of blood:
Blood is the only liquid tissue in the body, it is connective tissue

Blood consists of formed elements in a liquid intercellular matrix ( i.e. plasma)
Blood is more viscous and heavier than water
Blood acts as a buffer system
Blood acts as a heat generator
Blood aids in protection by conducting hemostasis and protecting against disease
Blood helps to regulate stable body pH, temperature, water and electrolyte levels
Blood transports oxygen and nutrients to cells and carbon dioxide and waste away from
cells
26
Alex Pardasie
The spleen can be classified as an lymphatic organ that possesses some beneficial qualities, but is
not necessarily an essential one, as its functions can easily be adopted by already existing organs
in the body. It is primarily responsible for the storage and filtering of blood and in most cases,
fighting against pathogens and diseases. This organ can be found in the upper abdominal region,
between the stomach and the diaphragm, and is predominantly composed of red pulp and white
pulp. Blood generally flows through the spleen where the filtration process takes place. More
specifically, the red pulp region, aids in the removal of the deteriorated blood cells with the help
of its encompassing fibres. The marginal zone is another area located between the red and white
pulp that somewhat assists the white pulp by passing on pathogens it encountered. The reason it
is passed along to the white pulp region is because its composing materials and pathogendestroying cells like macrophages, for instance, can demolish them and thus eventually produce
antibodies.(Cesta, 2006)
27
Figure 8 showing the general location of the spleen in relation to other parts of the body.
(78stepshealth.us, 2016)
In addition to the spleen, blood is associated with all other organs in the body, some way or the
other. In relation to body weight, it encompasses around 8% and in terms of an average human
being, their volume of blood would be about 5 litres. Blood is composed of red and white blood
cells, platelets and plasma (constitutes approximately 55% of the blood). The red blood cells are
termed erythrocytes whilst the white blood cells (leukocytes) are further categorised as
neutrophils, basophils, eosinophils, monocytes and lymphocytes.(Sigma-Aldrich, 2016)
Nicholas Persad
Spleen
28
Located to the left of the stomach lays the spleen. This organ varies in size for different people
but are usually purple, fist shaped and about 4 inches long. One of the major functions of the
spleen is to filter the blood. It removed old and damaged blood cells. The spleen is basically like
a filtration system for blood where red blood cells pass through narrow passages in the spleen.
The healthy blood cells pass through as normal and continue out to circulate the body. The cells
that do not pass through are unhealthy cells and are broken down by macrophages (white blood
cells) in the spleen.
Also useful is that the spleen saves all the iron from all the old and damaged blood cells it
destroys and stores it as ferritin. This iron is usually returned to the bone marrow where
hemoglobin is made.
The spleen can stored a good deal of blood. Its vessels can expand allowing it to hold up to one
cup of blood. This reserve blood can be released back into the blood stream if trauma causes the
person to lose a lot of blood.
29
Figure 9 Spleen (WebMD.com, 2016)
Characteristics of blood
Transport
The blood is transports dissolves gases like oxygen and carbon. All the waste products of
metabolism like urea for instance are also transported by the blood. Hormone and enzymes are
transported. Nutrients like glucose, vitamins, minerals etc. as well as plasma proteins associated
with defenses such as anti bodies are transported by the blood.
pH and Temperature control
The blood maintains the body temperature and also controls the pH to about 6.8 to 7.4.
30
Removal of toxins
The kidneys filter all the blood in the body about 36 times per day. The waste of this filtration
process is removed from the body through urine.
Figure 10 Constituents of blood (Slideshare.net)

Aruna Ramnarine
The spleen is a lymphatic organ , located on the left hypochondriac region of the abdominal
cavity, between the diaphragm and the stomach, which functions in the storage and filtration of
blood, production of lymphocytes and it recycles red blood cells (hematopoiesis).
31
Figure 11 showing the anatomy of the Spleen. (UAB.edu, 2014)

The spleen is an oval-shaped organ, made up of an outer tough connective tissue capsule
which surrounds and protects the spongy inner tissue. This spongy inner tissue consists of
numerous tiny blood vessels and hollow sinuses which plays the role of storage of blood in the
spleen. The blood supply of the spleen consists of the splenic artery and the splenic vein.
Oxygenated blood is carried to the spleen via the splenic artery, which is a branch from the aorta
and the celiac trunk. Deoxygenated blood, however, is carried away from the spleen, to the
hepatic portal vein, via the splenic vein. (Taylor, c2016)
There are areas located around the blood vessels and hollow sinuses known as red and
white pulp, divided by a marginal zone. The region of red pulp plays a role in the filtration and
recycling of red blood cells. Numerous net-like reticular fibers filter old and damaged red blood
32
cells before the blood passes through the spleen. These red blood cells which are filtered out, are
digested so that the iron and protein components of hemoglobin is recycled. The white pulp
region, however, plays a role in the immune response. This white pulp region, made up of
lymphatic tissue, contains macrophages, B lymphocytes and T lymphocytes. These white blood
cells destroys pathogens in the blood and produces antibodies for these pathogens. The marginal
zone, dividing the red pulp region from the white blood region, filters pathogens out of the
blood, after it has passed through the red pulp region and passes them to the white pulp region,
where they are destroyed. (Taylor, c2016)
CHARACTERISTICS OF BLOOD
Blood is the only tissue in the body which is liquid. The physical characteristics of blood
are as follows;
-
It is a connective tissue.
Blood volume is approximately 8% of body weight.
It consists of formed elements in a liquid intercellular matrix known as plasma. It is made
up of 55% plasma and 45% formed elements. The formed elements in blood are made up
of 99% erythrocytes (red blood cells), less than 1% leukocytes (white blood cells) and
less than 1% thrombocytes (platelets). The plasma content of blood consists of 90% water
and the remaining 10% are hormones, serum proteins, electrolytes, nutrients and wastes
such as urea.
The leukocytes (WBCs) are arranged in two categories, Granulocytes and Agranulocytes.
The granulocytes are neutrophil, eosinophil and basophil whereas the agranulocytes are
monocytes and lymphocytes.

It has a pH of around 7.4-7.45, therefore it is slightly alkaline
It has a high viscosity which is more than water. Its viscosity depends on the amount of
red blood cells present.
33
Blood plays a vital role in the functioning of the body. The process by which blood cells
are formed is known as hematopoiesis. Blood has three main functions, transport, regulation
and protection.
Blood transports respiratory gases such as oxygen to cells and carbon dioxide away from
cells in the body.Red blood cells consists of hemoglobin which carries oxygen to cells
throughout the body via blood. It also transports nutrients to cells, wastes away from cells
and hormones to target tissues in the body.
Blood also functions in regulating body temperature, pH, water and levels of electrolyte.
It functions as a buffer system which ensures that an acid-base balance is maintained to allow
important processes in the body to occur. Therefore, the pH for blood is maintained at around
7.4 which is slightly alkaline.
Blood is a protective tissue in the body. The platelet component of blood allows for
clotting to occur, to prevent fluid loss. The white blood cells in blood is the bodys defense
system against disease, thus protecting the body.
OBJECTIVES 2:Indicate the steps in hematopoiesis

THE STEPS INVOLVED IN HAEMATOPOIESIS
34
Hematopoiesis is the formation of elements (erythrocytes, leukocytes and thrombocytes) of the
blood, occurs during embryonic development and throughout adulthood for the production and
continuous replenishment of cellular components. All the distinctive cells of blood and those of
the immune system originates from hematopoietic stem cells (hemocytoblasts) of the red bone
marrow. Hemocytoblasts divide producing myeloid and lymphoid stem cells that respond to
various hematopoietic growth factors affecting which genes are switched on or off resulting in
formation of the many differentiated cells, refer to figure #: Hematopoietic, page .
35
Figure 12 showing Hematopoiesis

Kimberly George
Hematopoiesis is the process of creating and developing new blood cells in the body. Initially all
blood cells begin as hematopoietic stem cells or hemocytoblast and then they differentiate into
myeloid cells or lymphoid cells. Myeloid cells consist of erythrocytes, megakaryocytes,
monocytes, neutrophils, basophils and eosinophils whereas lymphoid cells consist of T-
36
lymphocytes and B-lymphocytes.All the immature forms of these cells are called -blasts and
when they mature they are referred to as -cytes.
Erythropoiesis formation of erythrocytes. It begins with the stem cell in which it becomes
specialized forming a colony-forming unit erythrocyte, which then forms the erythroblast
undergoes cell division to form a reticulocyte and then it finally matures to form the erythrocyte.
Leukopoiesis formation of leukocytes. All myeloblasts form neutrophils, eosinophils,
basophils, monoblasts form monocytes and lymphoblasts give rise to all forms of lymphocytes
Thrombopoiesis- formation of platelets. It begins with a megakaryoblast which undergoes
division into a promegakaryocyte and then a megakaryocyte. The cell bulges and is separated
into fragments called thrombocytes or platelets.
The stages of hematopoiesis include:
1. Mesoblastic stage this occurs in the foetus which is the first 3 months of life where
stem cells are formed outside of the yolk sac.
2. Hepatic stage- in the 4th month blood cell formation begins in the liver and spleen until
the 7th month of being in the uterine.
3. Medullary stage- in the bone marrow and spleen
Bone marrow: By the 5th month, it becomes the only hematopoietic organ in which blood
cell formation occurs here.
Spleen and lymph nodes it becomes the secondary hematopoietic organ in times of
excessive blood loss and also for further specialization and formation of lymphocytes.
(Sugiritama, 2011)
37
Figure 13 showing the process of hematopoiesis starting with a hemocytoblast in humans

(Homepage.smc.edu, 2016)
Giselle Jack
Haematopoiesis can be defined as the formation of blood cells. It adults it normally occurs in the
bone marrow of flat bones such as the pelvis, sternum and the ribs. Haematopoietic stem cells
(haemocytoblasts) are the cells from which blood cells are created. Haemocytoblasts can be
described as pluripotent stem cells, they have the ability to replicate themselves (self-renewal) as
well as to differentiate into other blood cells thereby providing a constant supply of blood and
38
ensuring that the pool of haemocytoblasts is not depleted (Almostadoctorcouk, 2015). This is
called asymmetric division.
Haematopoiesis starts when haemocytoblasts divide giving rise to one stem cell and another cell
committed to differentiation (progenitor cell) (Blackwellpublishingcom, 2006). The progenitor
call can be either of two types myeloid or lymphoid. Progenitors express low levels of
transcription factors which commit them to discrete cell linages (Blackwellpublishingcom,
2006). The diagram below shows the possible differentiation pathways that can be taken by
haematopoietic progenitor cells leading to the production of one or more specific type of blood
cells
Figure 14: Diagram showing the stages of haematopoiesis (Cnxorg, c2016)
39
Haematopoiesis depends on favourable micro-environment conditions and the presence of

growth factors (Tdmueduua, c2016). The red bone marrow is composed of stromal cells,
haematopoietic chords and sinusoidal capillaries. The stromal cells include endothelial cells,
adipocytes, macrophages and fibroblasts which secrete extracellular molecules such as collagen,
glycoproteins and glycosaminoglycans to form an extracellular matrix (Blackwellpublishingcom,
2006). Stromal cells also secrete the growth factors required for stem cell survival.
40
Figure
15:
Diagram
showing
the
micro-environment
stroma(Blackwellpublishingcom,
of
the
bone
marrow
2006
41
IL2, 3 an 4 regulators involved in T cell and B cell maturation
M-CSF a key regulator in the development of monocytes.
Darien Karim
Indicate the steps in hematopoiesis.
New blood cells are formed by the process of hematopoiesis. Blood cells originate in the red
bone marrow from hematopoietic stem cells. Stem cells can divide into more stem cells or they
can be specialized. When hematopoietic stem cells divide they form new cells called myeloid or
lymphoid stem cells that respond to different hematopoietic growth factors that usually work by
turning genes on or off. It is the exposure to these growth factors which determines the
distinctive formed elements of blood which include the cellular components of the immune
system.
The formation of red blood cells is known as erythropoiesis which initially begins in the yolk
sac, liver and spleen. This is then done in the tissue lining spaces in bones with red bone marrow.
Erythroblasts are formed when hematopoietic stem cells divide. These can then divide to give
rise to other new cells. By a process called nuclear extrusion the nuclei of the new cells can
shrink and become pinched off with a cytoplasmic covering this is followed by macrophages
engulfing and degrading the extruded materials. For a few days the young cells may contain a net
like structure they are called reticulocytes this is when cells leave the bone marrow and enter the
blood stream. The sign of full maturity is indicated when all the remaining organelles are
degraded forming and erythrocyte.
42
Leukocytes or white blood cells are developed from hematopoietic stem cells in response to
hormones which are classed into two groups: interleukins and colony stimulating factors.
43
Fig 16 showing the process of hematopoiesis (Wikimediaorg, 2016)
Alex Pardasie
Haematopoiesis is generally the process involving the formation of blood constituents such as
erythrocytes (red blood cells), thrombocytes (platelets), granulocytes (eosinophils, basophils, and
neutrophils) and agranulocytes (monocytes, T lymphocytes and B lymphocytes). This process
predominantly takes place in certain parts of the body but varies with time such as in the yolk sac
(for the first few weeks after birth), liver and spleen (second to seventh month in relation to
development) and later on in the bone marrow. The common denominator to all the products of
haematopoiesis is the haematopoietic stem cells.
44
Haematopoietic stems cells divide into: myeloid and lymphoid stem cells
Myeloid stem cells are then used to form erythrocytes, thrombocytes and granulocytes
(eosinophils, basophils, and neutrophils) whilst lymphoid stem cells lead to the formation of
agranulocytes (monocytes, T lymphocytes and B lymphocytes). Two of these agranulocytes
further develop into macrophages (monocytes) and plasma cells (B lymphocytes).
A) Formation of an erythrocyte:
The haematopoietic stem cell develops into a myeloid stem cell, which forms a proerythroblast,
which then develops into an early, intermediate and late erythroblast respectively. The late
erythroblast then advances into a reticulocyte that finally leads to the formation of an
erythrocyte.
B) Formation of a platelet (thrombocyte):
In this case, the haematopoietic stem cell develops into a myeloid stem cell, which forms a
megakaryoblast, which goes on to form a megakaryocyte, which forms the resulting platelets.
C) Formation of the granulocytes(eosinophils, basophils, and neutrophils):
Common pathway: For all granulocytes the haematopoietic stem cell develops into a myeloid
stem cell and then into myeloblasts, followed by a promyelocyte.
45
Different pathways:
- For eosinophils, the promyelocyte is developed into an eosinophilic myelocyte, followed by an
eosinophilic band cell, which finally leads to the formation of the eosinophil.
- For basophils, the promyelocyte is developed into a basophilic myelocyte, followed by a
basophilic band cell, which finally forms a basophil.
- For neutrophils, the promyelocyte is developed into a neutrophilic myelocyte, followed by a
neutrophilic band cell, which leads to the end result: a neutrophil.
D) Formation of agranulocytes (monocytes, T lymphocytes and B lymphocytes):
- A monocyte, which later develops into a macrophage, is the only agranulocyte than develops
from a myeloid stem cell. First the hematopoietic stem cell develops into the myeloid stem cell,
followed by a monoblast, which forms a promonocyte, which goes on to a monocyte.
- For a T lymphocyte, the starting haematopoietic stem cell develops into a lymphoid stem cell,
then to a lymphoblast T cell precursor, followed by a prolymphocyte which lastly develops into a
T lymphocyte.
- For a B lymphocyte, which later develops into a plasma cell, the starting haematopoietic stem
cell develops into a lymphoid stem cell, followed by lymphoblast B cell precursor, followed by a
prolymphocyte, which finally develops into a B lymphocyte.(Mhlearnsmart.com, 2016)
Nicholas Persad
Hematopoiesis is the development of all blood cells. These blood cells come from
haemocytoblasts also known as pluripotential stem cells which have the ability to replicate
46
themselves as well as differentiate into other cells thereby providing the constant supply of
blood.
The life cycle of the cells are short.
Red blood cells lifecycle 120 days
Platelets lifecycles 7 days
Granulocytes lifecycle about 7 hours
Stages of Hematopoiesis
1. Mesoblastic stage - First month of the embryonic life where cells are formed outside the
embryo in the mesenchyme of the yolk sac.
2. Hepatic stage - by the 6th weeks to 6th months
3. Medullary stage - By the 6th month blood cell formation occurs in the bone marrow.
Marrow - stem cells and progenitor cells
Spleen - lymphocyte differentiation and development
47
Figure 17 Showing the process of Hematopoiesis
Aruna Ramnarine
Hematopoiesis is the process by which blood cells are formed, in red bone marrow, and is
controlled by several hematopoietic growth factors. (Blogspot.com, 2010)There are
multipotential hematopoietic stem cells called hemocytoblasts, located in the bone marrow. The
first step of hematopoiesis is the differentiation of the stem cells into two common progenitors,
known as myeloid and lymphoid progenitors. These progenitors mature in several distinct
pathways which are precursors to adolescent cells which mature and results in the formation of
the different types of blood cells. The myeloid progenitor leads to the formation of red blood
cells, white blood cells and platelets whereas the lymphoid progenitor leads to the formation of
plasma cells. (Blogspot.com, 2010) The figure below shows the different pathways of the
progenitors and the types of cells produced.
48
Figure 18 showing the stages involved in Hematopoiesis.(MicrobiologySpring2011, c2016)
49
OBJECTIVES 3: Discuss factors which stimulate hematopoiesis.

FACTORS WHICH STIMULATE HAEMATOPOIESIS
Hematopoiesis is regulated by positive and negative feedback mechanisms of humoral activities,
HSCs self-renewal and differentiation, local interactions between stromal elements of the
hematopoietic niche with HSCs and progenitor cells. Therefore favorable micro niche conditions
and the availability of growth factors.
Erythropoiesis occurs in the yolk sac, liver and spleen before birth, after birth it is occurs in the
red bone marrow and is regulated by a negative feedback mechanism. HSCs responds to the
hormone, erythropoietin (EPO) forming erythrocytes. Extended oxygen deficiencies stimulate
hematopoiesis and during these periods the kidneys secrete EPO, to a greater extent than the liver
in adults. In the fetus the liver is the principal production site of EPO, refer to figure # Low
oxygen level and RBCC stimulates kidneys to secrete EPO intern initiates erythropoietin, page
50
Figure 19 Low oxygen level or low RBCC stimulates kidneys to secrete EPO intern initiates
erythropoiesis.
The tiny, flexible, biconcave disc shaped erythrocytes are 7.5m in diameter, medially thin
relative to their thicker outer rim allow them to squeeze through capillaries. Its distinct shape
increases surface area, brings the cell membrane in close proximity to the oxygen rich, carrying
hemoglobin molecules within the cells. Erythrocytes lack of mitochondria increases available
space coupled with the mature erythrocytes extruding their nuclei increasing their oxygen
carrying capacity. Together all these characteristics make erythrocytes adaptive for gaseous
transportation.
Each erythrocyte is one third hemoglobin by volume, this protein gives blood its distinctive red
color and each molecule contains four heme groups surrounding an iron (Fe) atom. The intensity
of color is dependent on whether is proportional to the amount of oxygen it combines with in the
formation of oxyhemoglobin or the amount that remains when it releases oxygen becoming
deoxyhemoglobin. Red blood cell count (RBCC) varies according to sex, whether its an adult or
51
child. For example a typical adult male RBCC ranges from 4,700,000 6,100,000, average adult
female RBCC 4,200,000 5,400,000 and a childs 4,500,000 5,100,000.
Dietary deficiencies like low vitamin B12 and folic acid absorption in the small intestines affects
DNA synthesis, therefore, erythropoiesis is affected. Iron deficiency from low absorption in the
small intestines and decreased recycling of RBCs affects hemoglobin production, refer to figure
# page .Thus, hematopoiesis is affected.
A typical white blood cell count, WBCC in a microliter of blood is 3,500- 10,500 cells.
Leukocytes develop from HSCs in the red bone marrow responding to two groups of hormones,
the interleukins such as interleukin-3 (IL-3) and colony stimulating factors, CSFs like
granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating
factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Leukocytes are the
cornerstone of the immune system, they travel via the blood to sites of infection. Lifespan of
WBCs, lymphocytes live -1 day, neutrophils and monotypes live 2-5 days, eosinophils live 712days and basophils live 12-15days.
When HSCs respond to the hormone, thrombopoietin, megakaryocytes are formed.
Thrombocytes are formed when the long extensions of megakaryocytes break into small sections
in the red bone marrow. These tiny cellular fragments are half the size of RBCs, non-nucleated,
membrane bound with a typical life span of ten days and is responsible for blood clotting.
Thrombocytes blood count averages 150,000-350,000 per microliter.
Kimberly George
There are many factors that stimulate or cause haematopoiesis to occur; they include:
52
1. Low blood oxygen levels due to anaemia, disease or high altitudes this triggers the
release of the hormone erythropoietin
2. Excessive blood loss or hypoxia due to haemorrhaging, donating blood, and injury etc.
results in the loss of blood at a faster rate than erythrocytes can be replaced.
3. Hemolysis is the lysis or breaking of erythrocytes which results in reduction of red
blood cells.
4. Bone marrow failure decrease in the production of erythrocytes due to cancer or toxic
drugs.
5. Kidney disease can result in a decline in the synthesis of the hormone erythropoietin
which stimulates erythrocyte formation.
6. Cytokines and interleukins (growth factors) these stimulate hematopoiesis by binding to
membrane receptors and thus activating signal transduction pathways. (Santos, 2015)
7. Leukopenia- is a decrease in the total number of leucocytes due to malnutrition, typhoid
fever, some drugs, vitamin B12 and a deficiency in folic acid.
8. Lack of or defective haemoglobin- this lowers the oxygen in the blood which causes a
decrease in the amount of red blood cells in the blood. Sickle cell anaemia results from
defective haemoglobin in which times of low oxygen, the haemoglobin within red blood
cells crystallizes. As a result of this the red blood cells assume a sickled shape, which
makes them weak and easily broken.
9. Dietary deficiencies of
A. Iron- Haemoglobin production tends to gradually slow down in the absence of iron
which lowers the amount of erythrocytes in the blood.
B. Vitamin B12 and folic acid- these are needed for the synthesis of DNA before cell
division. A deficiency in these vitamins cause a reduction in the production of
erythrocytes. B12 deficiency is caused by the lack of an intrinsic factor which
maximises the absorption of B12 out of the small intestine of the stomach and into the
blood.(Biosbcc.net, 2016)
10. Erythropoiesis
53
This is the process of regulating and producing red blood cells. This negative feedback
mechanism starts off in the kidney where the oxygen levels in the blood are screened. When
oxygen levels are low, the hormone erythropoietin is released into the blood stream and is
distributed throughout the body. Only the red bone marrow cells have the receptors which bind to
the erythropoietin in order to stimulate the formation of erythrocytes in the bone marrow. Then
the erythrocytes move from the bone marrow and back into the bloodstream where red blood cell
count is restored and as a result the oxygen in the blood increases. Therefore the secretion of
erythropoietin by the kidney slows down until next time when the red blood cell count decreases
again. (Biosbcc.net, 2016)
Figure 20 showing the negative feedback mechanism of erythropoiesis(Shier, Butler & Lewis,
2006)
54
There are certain ways in which the blood cell count could be restored through these various
methods:
Dietary requirements to increase red blood cell count:
Consuming the correct foods can increase the red blood cells in the body. Below lists a certain
ways in which you can increase the blood count in the body.
1. Iron Builds back blood in the body. E.g. lentils and legumes
2. Copper found in shellfish, poultry, liver, whole grains, beans, cherries, chocolate and
nuts.
3. Folic Acid- it helps in restoring blood count for pregnant and nursing mothers e.g. lentils,
dark green leafy vegetables, black eyed peas and cereals fortified with folic acid.
4. Vitamin A found in fruits, including grapefruit, mango, watermelon, plums, cantaloupe
and apricots.
5. Vitamin B12 - found in meat, eggs and fortified cereals
6. Vitamin B6- found in meats, whole grains and bran, nuts and seeds, fish, vegetables and
legumes.(Md-health.com, 2016)
Certain supplements can be used to increase the production of red blood cells in the body, which
include:
55
1. Iron Blood cells require iron needed to form haemoglobin and the protein ferritin found
in the bone marrow, liver and spleen. Women require 18 mg however men require 8 mg
of iron per day.
2. Vitamin B12. Mostly come from animals however persons need 2.4 mcg per day so a
supplement could supply that.
3. Vitamin B6 - Requirement of women is 1.5 mg of this vitamin while men require 1.7mg
or more per day.
4. Vitamin E - provides good health, including red blood cells. Persons require about 15mg
per day in which supplements provide more than the daily recommended dose. (Mdhealth.com, 2016)
There could be certain lifestyle changes that could increase the production of red blood cells in
the body which are:
1. Exercise uses the oxygen in the body and blood which stimulates the production of
more red blood cells.
2. Changes in diet (avoid alcohol) - Consumption of too much alcohol can lower red
blood cell count for instance if you are given a diagnosis of thrombocytopenia, which is
low amounts of platelets in the blood, then you might want to avoid aspirin and alcohol.
(Md-health.com, 2016)
Various medical procedures could be used to increase red blood cell count if none of the other
methods work, these include:
56
1. Medications- Use of antibiotics for infections, drugs that help fight auto-immune
disorders and hormones that regulate menstrual bleeding.
2. Surgery- Spleen and tumour removal or the treatment of bleeding ulcers can all increase
the red blood cell count.
3. Blood Transfusions - transfusion of packed red blood cells can assist in the oxygen
carrying properties of the body and also regulate bleeding and blood pressure
4. Erythropoietin. this stimulates red blood cell production in the bone marrow. This is
used for patients suffering from failure to the kidney or undergoing chemotherapy. (Mdhealth.com, 2016)
Giselle Jack
The production of blood cells is usually under the control of growth factors sometimes called
haematopoietins, however there are other factors which can stimulate the production of blood
cells. Some of these factors are listed below
1. Oxygen concentration erythropoietin is secreted in response to low blood oxygen
concentrations, for example, at high altitudes. It is released from the kidney peritubular
interstitial cells. Erythropoietin expression increases logarithmically once levels fall
below 120g/L (Sharinginhealthca, c2016).
2. Infection When the body is infected by pathogens, white blood cell production is
increased. A microliter of blood normally contains 3,500-10,500 white blood cells. A total
number above this value is indicative of an infection. The table below shows the effect of
some infectious diseases on white blood cell count
57
Table 3: Showing the effect of some Infectious diseases on white blood cell count
Effect on white blood cell population
High number of neutrophils
High number of eosinophils
High number of monocytes
High number of lymphocytes
Infectious Disease
Bacterial infection
Tapeworm or hookworm infestation
Typhoid fever, malaria, tubercolosis
Whooping cough, infectious mononucleosis
3. Other disease Cancers such as leukemia cause a drastic increase in white blood cell
population. The type of white blood cell which proliferates excessively depends on the
type of leukemia and how fast they are produced depends on whether the condition is
acute or chronic.
4. Diet There are some food which help to increase red blood cell count. Foods rich in
iron, copper, folic acid, vitamins A, B6 and B12 have been proven to increase red blood
cell production as they are involved in DNA and haemoglobin synthesis.
5. Medication Dietary supplements containing vitamin B6, vitamin B12 or iron can be
taken to increase blood cell count. Medication containing erythropoietin is also frequently
used by individuals who are experiencing kidney failure or going through
chemotherapy (Md-healthcom, c2016).
Darien Karim
Cytokines are involved in regulating haematopoiesis within a complex network of positive and
negative regulators. They exert effects on the formation and maturation of hematopoietic cells
some of these factors are stem cell factor (SCF), macrophage colony stimulating factor( M-CSF)
and leukaemia inhibitory factor.
58
The hormone erythropoietin controls the rate of red blood cell formation. EPO is released from
the kidney in response to prolonged oxygen deficiency and to a smaller extent from the liver
which travels via the blood to the red bone marrow and increases erythrocyte production. Loss of
blood together with chronic lung disease can also stimulate EPO release.
Red blood cell production is also significantly influenced by the availability of the B- complex
vitamins B12 and folic acid in addition iron is also required for haemoglobin synthesis. Both
vitamin B12 and folic acid play a role in DNA synthesis.
Alex Pardasie
The overall process of haematopoiesis is associated with the formation of red blood cells
(erythrocytes), thrombocytes (platelets) and white blood cells. In relation to their formation and
the corresponding, influential factors, various aspects are involved, one major factor being the
needs of the body.
White blood cells, platelets and red blood cells survive on average for a few days, ten days and
120 days respectively, so therefore reproduction of new blood components would need to occur,
which is where the process of haematopoiesis comes into play. In spite of the amount of the
blood components, other factors such as oxygen concentration in the body may lead to the
release of erythropoietin (from kidneys) to produce the required amount of red blood cells whilst
infections and bleeding can act as stimulants for other cells (white blood cells and platelets
respectively).(Lichtin, 2016)
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In addition to this, various diseases and illnesses present in the body of a human being can cause
a general increase in haematopoiesis of specified cells such as erythrocytes, granulocytes and
agranulocytes.
Table 4 showing diseases and illnesses that result in increased production of corresponding
cells(Unomaha.edu, 2016)
Blood Cells
Diseases/Illnesses responsible for increased

haematopoiesis of these cells
GRANULOCYTES:
-Neutrophils
-Acute infections (appendicitis or smallpox)
-Eosinophils
-Parasitic diseases, hay fever or bronchial

asthma
-Basophils
-Hemolytic anemia, chicken pox
AGRANULOCYTES:
-Lymphocytes
-Infectious mononucleosis or chronic infection
-Monocytes
-Malaria, typhoid fever
ERYTHROCYTES
-Polycythemia
Nicholas Persad
Hematopoeisis Growth Factors
Haematopoietic growth factors (HGFs) regulate the production of all the cellular elements of
blood by stimulating the proliferation, survival and differentiation of haematopoietic cells in
various stages of maturation and also enhancing mature cell functions. Certain factors are critical
for haematopoiesis in normal health (erythropoietin, thrombopoietin, granulocyte colony
60
stimulating factor, macrophage colonystimulating factor, interleukin7 and stem cell factor)
while other growth factors (interleukin3, interleukin5, interleukin6, interleukin11 and
granulocytemacrophage colonystimulating factor) exert their effects principally in
inflammatory states as a response to infection or trauma. Similar to immune cytokines, many
HGFs exhibit overlapping roles (redundancy) and dramatic synergy when acting in combination.
HGFs transduce their potent biological effects through growth factor receptors which bind HGFs
with high affinity and signal through JAK family tyrosine kinases. Recombinant HGFs are used
in a wide variety of clinical settings including the treatment for anaemia in kidney disease
(erythropoietin), chemotherapyinduced neutropenia (granulocyte colonystimulating factor) and
immunemediated thrombocytopenia (thrombopoietin) and to aid in the collection of bone
marrow stem cells (GCSF). (els.net, 2016)
Aruna Ramnarine
Growth factors also known as hematopoietins, control hematopoiesis. However, the production
of blood cells may be stimulated by other factors such as hematopoietic stress, diseases,
infections, low levels of oxygen, as well as diet.
Under conditions such as excessive blood loss, tissue damage or pregnancy,
hematopoietic stress occurs. The decrease in blood stimulates the formation of new blood cells in
the red bone marrow. Diseases such as cancers and infectious diseases causes the increased
production of white blood cells. When pathogens enter the body, the production of white blood
cells is increased, therefore haematopoiesis is stimulated. When low levels of oxygen is detected,
the kidneys release the hormone erythropoietin which stimulates the production of erythrocytes
61
(red blood cells). The production of red blood cells is also dependant on the levels and
availability of dietary substances such as iron, B12, B-complex and folic acid. Iron is required
for the synthesis of hemoglobin while folic acid and B12 is required for synthesis of DNA.
Foods rich in these vitamins, assists in increasing the amount of red blood cells.
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OBJECTIVES 4: Describe how hematopoietic stress is mitigated in the body

HOW HAEMATOPOIETIC STRESS IS MITIGATED IN THE BODY
In healthy homeostasis, under normal physiological conditions, hematopoiesis occurs in the red
bone marrow and its rate is adjusted according to the bodys requirement. Sometimes a several
fold increase in short periods due to hematopoietic stress like tissue damage, excessive bleeding
and chemotherapy where large quantity of mature blood cells are lost. This signals activation of
the dormant HSCs via feedback mechanisms to produce new blood elements.
Additionally hematopoiesis expands to the spleen by the migration of hematopoietic stem cells
from the bone marrow to the spleen making it a hematopoietic organ. The spleen possess only a
few hematopoietic stem cells however, it also possess cells that provides the supporting
microenvironment/ niche for the existing hematopoietic stem cells of the spleen and influx of
hematopoietic stem cells from the bone marrow.
Two recognized niche cell factors, stem cell factor (SCF) and CxCL12, expression patterns were
examined in the characterization of the supporting niche for hemostasis in the spleen. Research
found that it is located proximal to sinusoidal blood vessels and is formed by endothelial cells
and perivascular stromal cells, same as the supporting microenvironment for hematopoietic in
the bone marrow. Under hematopoietic stress the residing endothelial cells and perivascular
63
stromal cells of the spleen proliferate in order to sustain the newly migrated hematopoietic stem
cells.
Kimberly George
Haematopoietic stress causes the migration of hematopoietic stem cells from the bone marrow to
the spleen which triggers extra medullary haematopoiesis.(Inra et al., 2015) Hematopoietic stress
is considered any condition that causes excessive blood loss from the body for example during
pregnancy, chemotherapy or after blood transfusions. The reason in which the stem cells migrate
to the spleen is to create the peri-sinusoidal microenvironment of that of bone marrow. The
microenvironment of bone marrow is described as a niche consisting of circulating
hematopoietic cells together with stromal cells, including fat cells, blood vessel cells, bone cells,
and fibroblasts, which release signals to induce the proliferation of blood cells thus changing the
microenvironment when needed.(Iwata, Sandstrom, Delrow, Stamatoyannopoulos & TorokStorb, 2014)
Therefore under emergency conditions or hematopoietic stress, the endothelial and stromal cells
that are located within the red pulp of the spleen are forced to proliferate so they could maintain
the microenvironment similar in bone marrow. The proliferation of these cells are stimulated by
two main signalling factors called stem cell factor (SCF) and CXCL12 which trigger signal
transduction pathways. (News-Medical.net, 2015) Due to the proliferation of these cells it creates
a niche which causes erythropoiesis, leucopoiesis and thrombopoiesis from the hematopoietic
stem cells.
Giselle Jack
64
In adults haematopoiesis takes place mainly in the red bone marrow of certain bones. However in
certain situations, example, in cases of excessive blood loss, diseases such as chronic
myelogenous leukemia and myelofibrosis, during pregnancy or as a result of tissue damage
extramedullary haematopoiesis occurs (EMH). EMH refers to haematopoiesis occurring outside
of the medullary cavity of the bone. It occurs most often in organs such as the liver, spleen and
lymph nodes (Radswiki, c2016) and may cause these organs to increase in size.
EMH occurs as long as there are appropriate supporting cells, accommodation of haematopoietic
progenitors and local production of soluble and cell bound haematopoietic factors which
maintain and induce differentiation of stem cells and progenitor cells (Chang, 2010). As such the
spleen and the liver having micro-environments somewhat similar to that of the bone marrow are
the first observed sites of haematopoiesis. Research has shown that stem cells which migrate to
the spleen during haematopoietic stress are sustained by stromal cells in the red pulp of the
spleen allowing EMH to occur.
Darien Karim
Chronic variable stress activates hematopoietic stem cells such as during viral infections or in
times of blood loss where large amount of mature blood cells are lost. Feedback signals are sent
to the dormant hematopoietic stem cells which activates them and leads to the production of new
mature blood cells.
Studies have shown that the spleen plays an emergency backup role and aids in blood cell
formation in times of hematopoietic stress. Blood forming stem cells migrate to the spleen which
plays the role as a hematopoietic organ as the cells in the spleen create a supporting environment
65
for the hematopoietic stem cells which multiply rapidly and help to revitalize blood cell counts in
the body.
Alex Pardasie
In the human body, stress in relation to haematopoiesis can be lessened to a great extent, by
specific ways based on the overall situation. In the case of tissue damage, or the loss of blood,
red blood cells would be lost thus resulting in a reduction of the oxygen concentration of the
blood in that specified area of the body, as proper circulation is disrupted. New red blood cells
are therefore required to be produced, to replace the lost blood cells which is somewhat causing
stress within the body. To alleviate this stress, chemoreceptors found in the kidneys detect the
low levels of oxygen and as a result, released a specific hormone that goes by the name of
erythropoietin which travels to the red bone marrow, where red blood cells (erythrocytes) are
predominantly produced, and initiates erythropoiesis (red blood cell production).
In the bone marrow are the haematopoietic stem cells that are somewhat unique, but can form
multiple blood cells such as thrombocytes (platelets), granulocytes, agranulocytes and in this
case, erythrocytes. In relation to the red blood cell production, an overall increase in the level of
erythrocytes would aid in the recovery of oxygen levels to a specified set point, as more oxygen
is being permitted to be taken to the damage area. The mechanism involved is one associated
with negative feedback, since a restoration is brought about producing changes in the opposite
direction, for instance in this case, where to mitigate the haematopoietic stress as a result of a
loss of blood, more erythrocytes are made. Furthermore, when the oxygen levels and red blood
cell numbers return to normal, erythropoietin secretion would lessen.
66
Extramedullary haematopoiesis, can also occur to alleviate the stress associated with
haematopoiesis as it provides an alternative to the original site of red blood cell production (bone
marrow) which can be the spleen. As a result of the similar microenvironments, the spleen is
enabled to perform this task and aids in reducing the overall stress level, when the bone marrow
is unable to do so. In the spleen via the red pulp region, haematopoiesis occur with the help of
the proliferation of specified cells in the region, like the stromal cells for instance.(Johns &
Christopher, 2012)
Nicholas Persad
Hematopoietic stem cells can self renew and also give rise to the entire repertoire of
heamtopoietic cells. During acute infection and inflammatory stresses, the hematopoietic system
can quickly adapt to demand by increasing output of innate immune cells many-fold, often at the
expense of lymphopoiesis and erthropoiesis. (Wolters Kluwer Health, 2015)
Dormant HSCs can be activated to produce new blood by feedback from excessive blood loss,
pregnancy and tissue damage. With the detection of this loss of blood and oxygen by the
chemoreceptors found on the kidney, the hormone erythropoietin is release which travels to the
bone marrow stimulating the production of my red blood cells. When the levels of oxygen and
blood return to normal the release of the hormone erythropoietin decreases.
Aruna Ramnarine
67
Hematopoietic stress is the occasion where enough blood isnt being formed by
hematopoietic stem cells in the bone marrow, which may be due to instances of excessive blood
loss, and tissue damage. Under normal physiological conditions, hematopoiesis occurs in the
bone marrow, however, during hematopoietic stress, there are several hematopoietic backup
systems in the body which assist to lessen the extent of hematopoietic stress.
The excessive blood loss leads to the decrease in oxygen levels due to the lack of red
blood cells which transports oxygen around the body. Chemoreceptors in the kidneys detects this
fall in oxygen level and releases the hormone erythropoietin which stimulates the production of
red blood cells, thereby replacing the red blood cells lost which results in oxygen levels returning
back to normal. Thus hematopoietic stress is reduced to some extent.
Hematopoietic back up systems such as extramedullary hematopoiesis, which occurs in
the spleen also helps to mitigate hematopoietic stress in the body. When the body is under
hematopoietic stress, hematoblasts or hematopoietic stem cells from the bone marrow migrates
to the spleen where hematopoiesis occurs. The microenvironment in the spleen is similar to that
of the red bone marrow so the formation of blood cells can occur. When the bone marrow is not
able to produce the amount of blood cells required, the spleen assists in the production of these
blood cells thereby lessening the extent of hematopoietic stress.
68
OBJECTIVES 5: Explain why blood formation is required following procedures such as

THE NEED FOR BLOOD TRANSFUSIONS FOLLOWING CHEMOTHERAPY AND
BONE MARROW TRANSPLANTS
RBCC, WBCC and Thrombocytes numbers are constantly, periodically checked as part of
chemotherapy protocol because of their dwindling numbers as a side effect of the potent
medicinal drugs used in this therapy.Consequently, the healthy, normal homeostasis of the body
is jeopardized by the reduction in RBCC, WBCC and thrombocytes. For example
thrombocytesdecrease after chemotherapy inciting thrombocytopenia which leaves the body
susceptible to bleeding as blood clotting function of thrombocytes is impaired. Additionally, life
threatening diseases exert their effects on bloodformedelements of the blood such as Leukemia,
in which case bone marrow transplantation is necessary to replace the bodys ability to produce
these cells. The blood, vital connective tissue, is important physiological functions as in
transportation of gases and nutrients, assist in excretion of waste, maintain circulation, immunity
and blood clotting. Hence, hematopoiesis is vital for the restoration of cells to their normal levels
conducive to healthy homeostasis.
Kimberly George
69
Chemotherapy is a type of cancer treatment that uses drugs to destroy cancer cells. Blood
formation is required after receiving forms of chemotherapy. This is because certain
chemotherapeutic drugs damage the spongy material in the bone called bone marrow. The blood
cells produced in the bone marrow become sensitive to the effects of chemotherapy thereby
causing the death of these cells. The drugs and therapies used in chemotherapy decreases the red
blood cell, white blood cell and platelet counts. As a result of having a low white blood cell or
more specifically low neutrophil count, there is a risk of contracting neutropenia and thus having
a high risk of infection. Also by having a low red blood cell count there is risk of getting anaemia
which is why you tend to feel symptoms of tiredness and breathlessness.(Cancerresearchuk.org,
2016)
A bone marrow transplant involves taking stem cells found in the bone marrow, filtering them
and then reinserting them into the donor or to another person. The general aim of a bone marrow
transplant is to transfuse healthy stem cells into a person after his or her own harmful bone
marrow has been treated to kill the abnormal cells. Blood formation is definitely needed after a
bone marrow transplant since the depletion of platelets and red blood cells occur. This can occur
due to a non-operational bone marrow which can lead to thrombocytopenia (low platelets) and
anaemia (low red blood cells). The low platelet count can lead to excessive bleeding in the lungs,
gastrointestinal (GI) tract and brain.(Cumc.columbia.edu, 2016)
Giselle Jack
Persons who are diagnosed with cancer may develop anaemia due to the caner itself or because
of the side effects of treatment for the disease. Cancers such as leukemia which start in the bone
marrow crowd out normal blood making cells leading to low blood count, while others can cause
70
internal bleeding giving rise to anaemia (Cancerorg, c2016). Some chemotherapy drugs can lead
to a need for blood transfusions as they affect cells in the bone marrow leading to low blood
counts, radiation treatment also leads to low blood count as it can affect the bone marrow
(Cancerorg, c2016).
Bone marrow transplant or peripheral blood cell transplant patients get large doses of
chemotherapy and/or radiation therapy which destroys the blood making cells in the bone
marrow (Cancerorg, c2016). As such patients have very low blood count after these types of
medical procedures and are in blood transfusions are therefore required.
Darien Karim
Chemotherapy is a type of cancer treatment which utilizes chemical substances.
Chemotherapeutic agents are found to be cytotoxic where it kills cells that divide rapidly. This
cytotoxicity also harms cells that divide rapidly under normal circumstances including bone
marrow cells. Blood formation occurs in the red Bone marrow and if the bone marrow cells are
destroyed or ablated then blood formation would be disrupted. Hence following chemotherapy,
blood formation is required.
A bone marrow transplant is a procedure which replaces damaged or destroyed bone marrow
with healthy bone marrow stem cells. Stems cells are immature bone marrow cells that give rise
to various blood cells. Hence after a bone marrow transplantation, blood formation would be
required since new, healthy bone marrow cells would have been introduced into the body and the
damaged or destroyed bone marrow would not have been able to effectively carry out
hematopoiesis.
71
Alex Pardasie
Chemotherapy is predominantly the use of chemical-based substances to treat cases of cancer.
Their drugs, along with the cancer itself, can diminish the overall blood cell counts in the body,
leading to the utilisation of blood transfusions for instance to return blood component levels to
normal amounts. Some cancer itself may even cause bleeding internally resulting in anaemia and
in some situation, even affect associated organs like the spleen for instance. Additionally, the
bone marrow (spongy filler in bones) can also be altered by the developing cancers in that area
leading the reduced blood counts and thus develops a need for blood formation. (Cancer.org,
2016)
Drugs associated with chemotherapy and even radiation also affects the bone marrow, leading to
the requirement associated the overall need for blood and its components. Generally, blood
formation is required following the process of chemotherapy as the drugs themselves, reduce the
blood cell levels thus leading to necessary blood formation or blood from another source.
Furthermore, blood formation is needed via this procedure (transfusions) for white blood cells
since the life span is relatively small and must be replaced as soon as possible to prevent possible
infections due to weakened state of the body. In relation to red blood cells and platelets however,
blood would be required to replenish the diminished amounts caused by the drugs, and to
alleviate cases of anaemia and increased bleeding respectively.(Cancerresearchuk.org, 2016)
Bone marrow transplantation is also another procedure requiring blood formation after it has
taken place, as it associated with tremendous levels of chemotherapy to elevate the overall
chances of curing the cancer, like lymphoma for instance. These levels of chemotherapy, more or
less, kills off the bone marrow, which is the primary blood producing centre of the body, so
72
measures are taken to introduce bone marrow cells back into the body to initiate blood formation
and thus return the blood components' levels within a specified range or number.
(Cancerresearchuk.org, 2016)
Nicholas Persad
When chemotherapy is given it not only affects the rapidly dividing cancer cells but it also
affects some of the normal cells of the body These effects particularly occur on normal cells that
divide rapidly such as, the hair, the lining of the mouth, the cells lining the intestinal tract and the
blood cells (white and red blood cells as well as platelets).
In the bone marrow, the spongy inner core of the larger bones in the body is where blood cells
are made. There are very immature cells called stem cells, from which the various types of blood
cells develop These stem cells do not reproduce quickly and are less likely to be affected by
chemotherapy. As cells are maturing there are certain phases in which they divide faster. It is
during these times that the cells are most sensitive to chemotherapy. The more mature cells can
continue to become fully mature cells for several days after chemotherapy is given. When these
cells live out their life span, the circulating supply is depleted and the blood counts fall to a low
point, the nadir. (chemocare.com, 2016)
For bone marrow transplant a great deal of chemotherapy is needed for the procedure this tries to
ensure that the disease is cured. This also kills the bone marrow which is needed by the body to
produce blood. Whether marrow from the person themselves or from a donor is returned to the
person, their bodies will still be very weak following the procedure. However the bone marrow
introduces should return blood levels back to normal over time.
73
Aruna Ramnarine
Chemotherapy is a process whereby powerful chemicals or drugs are used to destroy fastgrowing cells in the body and is used in the treatments of cancers.(MayoClinic.org, 2014) Since
cancer cells grows faster than normal body cells, they are killed first, however, chemotherapeutic
drugs are toxic to normal, healthy blood forming cells, thereby resulting in a decreased blood
count. Also, some chemotherapy drugs can damage bone marrow, since blood cells which grows
rapidly, are formed in the bone marrow. (MayoClinic.org, 2014) Due to the destruction of blood
cells, the bodys blood cell count decreases and blood formation is required to replace these
blood cells.
Bone marrow transplantation is a process whereby damaged bone marrow, due to
chemotherapy, disease or infection, is replaced by healthy bone marrow. (Healthline.com, c2016)
Blood stem cells are transplanted and they travel to bone marrow, thereby producing new blood
cells , thus promoting the growth of a new, healthy bone marrow. During the procedure of bone
marrow transplantation, there may be complications such as anemia, whereby the body lacks the
production of red blood cells, and infections. The formation of blood is required to elevate the
amount of red blood cells to prevent anemia and also the production of white blood cells to fight
off infections. (Healthline.com, c2016)Hence, blood formation is required to prevent these
complications.
74
Were the hypotheses relevant? Please explain?

1. The blood-forming microenvironment in the spleen is similar to the niche in the bone
marrow.
Yes this hypotheses was relevant. According to research result thus far suggests that spleen
possess only a few hematopoietic stem cells however, it also possess cells that provides the
supporting microenvironment/ niche for the existing hematopoietic stem cells of the spleen and
influx of hematopoietic stem cells from the bone marrow. Thus, the spleen provides similar
favorable microenvironment drugs of the bone marrow for hematopoiesis.
2. The spleen is the bodys secondary hematopoietic system.
Yes this hypothesis was relevant. The favorable micro niche conditions and the availability of
growth factors are determinant factors for hematopoiesis to occur.
Based on research it is suggested that spleen HSCs are activated under hematopoietic stress,
CGFs are present in the spleen and migration of HSCs from the bone marrow to the spleen is
supported for the differentiation of HSCs into distinctive blood cellular elements.
3. The microenvironment of the spleen allows for the increased proliferation of
hematopoietic stem cells which results in increased blood cell formation?
Yes this hypothesis was relevant. According to the research the spleens micro niche is favorable
in supporting the influx of HSCs migration from the bone marrow to the spleen, adding to the
spleens HSCs that are already present, resulting increased hematopoiesis.
Did the generated SGLOs prove/disprove the hypotheses?

75
Yes the generated SGLOs proved the hypotheses.
How has the problem helped you in understanding the course concepts?
Firstly, there are always new developments and discoveries in science and this problem helped
me understand the course concept, the blood, by relating it to the problem.
76
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GROUP F

GROUP LEADER: Kimberly George

Table 5: Timeline of Group F Activities.

Thursday 4th Friday 5th

Haematopoiesis - formation of elements (erythrocytes, leukocytes and thrombocytes) of

volume of red blood cells present in a blood sample.

Hematopoietic: The production of all types of blood cells including formation,

development, and differentiation of blood cells.(MedicineNet, 2016)

Proliferate- to reproduce rapidly

cytokine which binds to the c-KIT receptor (CD117).

Hematopoietic the formation of blood cells. (thefreedictionary.com, 2012)

Niche/ Microenvironment- A specialized position which is suitable for the role of

IDENTIFICATION OF MAIN ISSUES:

Figure 1: Anterior view of the spleen.

Figure 2: Blood Composition in the Human Body.

Site of lymphocyte proliferation

Red blood cells (Erythrocytes) 95.1%

The characteristics of blood include:

More viscous than water

There are many functions of blood which are:

away from cells and hormones to their target tissues.

CO2 and O2 transport

Specific granules containing

histamine and heparin

Phagocytosis and digestion of

B lymphocyte (Plasma cell)

substances that control the

activity of other leukocytes

Killing of some tumour and

and cancer cells

4 showing the constituents

They destroy pathogens in the blood and produce antibodies

Figure 5: Showing the Anatomy of the spleen (Pinterestcom, c2016)

Figure 6: Showing the Characteristics of Blood (Tdmueduua, c2016)

Table 2: Showing the Characteristics of blood cells (Candelalearningcom, c2016)

The major functions of blood include

Figure 7 showing the structure of the spleen(Britannicacom, 2016)

Blood is the only liquid tissue in the body, it is connective tissue

Figure 9 Spleen (WebMD.com, 2016)

Figure 10 Constituents of blood (Slideshare.net)

Figure 11 showing the anatomy of the Spleen. (UAB.edu, 2014)

monocytes and lymphocytes.

OBJECTIVES 2:Indicate the steps in hematopoiesis

Figure 12 showing Hematopoiesis

Figure 13 showing the process of hematopoiesis starting with a hemocytoblast in humans

Haematopoiesis depends on favourable micro-environment conditions and the presence of

IL2, 3 an 4 regulators involved in T cell and B cell maturation

M-CSF a key regulator in the development of monocytes.

Fig 16 showing the process of hematopoiesis (Wikimediaorg, 2016)

Figure 17 Showing the process of Hematopoiesis

Figure 18 showing the stages involved in Hematopoiesis.(MicrobiologySpring2011, c2016)

OBJECTIVES 3: Discuss factors which stimulate hematopoiesis.

Diseases/Illnesses responsible for increased

-Acute infections (appendicitis or smallpox)

-Parasitic diseases, hay fever or bronchial

-Hemolytic anemia, chicken pox

-Infectious mononucleosis or chronic infection

-Malaria, typhoid fever

OBJECTIVES 4: Describe how hematopoietic stress is mitigated in the body

OBJECTIVES 5: Explain why blood formation is required following procedures such as

Were the hypotheses relevant? Please explain?

Did the generated SGLOs prove/disprove the hypotheses?

Yes the generated SGLOs proved the hypotheses.