Blood contains many types of cells with different function, all derived from one cell of origin (stem
cells) in the bone marrow.
Red cell: the main function is to transport oxygen and delivery of 02 to tissues.
White cell: fight infection and mediate the immune response.
Platelets: responsible for the arrest of bleeding.
3 types recognised on the basis of morphology and chemistry and function.
Neutrophils: Multilobed nucleus – most common the function to phagocytose bacteria.
Basophils: Function is to secrete histamine and mediate inflammatory reaction they are the
circulating form of tissue mast cells.
Eosinophil’s : Mediate allergic inflammatory responses.
B cells – make antibodies
T cells – Kill virus infected cells and regulate the activity of other cells
NK cells – subset of lymphocytes that kill some types of tumour cells and also some virus infected
White blood cells circulate within capillaries. Damaged tissues release mediators of inflammation.
Chemotaxins towards attractants, released from damages tissues. White blood cells in connective
Bone marrow is the site of blood cell formation from hematopoietic stem cells.
Bone marrow transplantation. Bone marrow can be harvested and can be transplanted into recipient
without marrow. Expriment done, irradiated mice, halts blood cell production, the mouse will die if
no further treatment given. Treatment sia n ijection of bone marrow cells from a healthy donor. The
mouse survives, the injected stem cell colonize its hemopoietic tissues and generate a steady supply
of new blood cells.
This is the method of the production of differentiated blood cells. These include red blood cells
(erythrocytes) as well as the different white cell types i.e. NK cells, T, cells, B cells etc. The pathway
for all of the different cells begins with a single multipotent hemopoietic stem cell. This becomes a
multipotent hemopoietic progenitor cell, that is destined to become a blood cell. This differentiates
into two progenitors, a common lymphoid progenitor or a common myeloid progenitor. The
common lymphoid progenitor differentiates into cells that become NK cells, T cells, B cells and
dendritic cells. Common myeloid progenitor cells however become monocytes, neutrophils,
eosinophils, basophils, megakaryocytes and erythrocytes. Hematopoietic stem cells are regulated by
stromal cells and growth factors in the bone marrow to proliferate, differentiate or die. Granulopoiesis
This is the formation of granulocytes, which are neutrophils, basophils and eosinophils. It occurs
within the bone marrow as a part of haematopoiesis. Regulation is maintained by a number of
factors. GM-CSF stimulates maturation of these granulocytes and enhances neutrophil activity. IL-3
has multilineage mutation and proliferative effects. G-CSF is widely produced in response to
inflammatory stimuli and neutrophil maturation and mobilisation. IL-5 supports terminal
differentiation of eosinophils and synergises with GM-CSF. Stem cell factor is ligand for c-Kit receptor
tyrosine kinase. Supports mast cell differentiation and activation, It also stimulates proliferation of
hemopoietic stem cells.
CSFs and cytokine signalling. Receptors (IL3 or GMCSF) are bound to the cell membrane. A common
beta subunit is present, which binds to the receptor when ligand is bound, causing a signal.
The red cell
is a round, biconcave disc. It has no nucleus and no organelles. It does possess a complex
cytoskeleton which allows it to squeeze though the micro circulation. Its main function it to
transport oxygen around the body. It picks up oxygen from within the lungs. Haemoglobin is the
functional unit. When leaving the lungs the haemoglobin, now oxy-haemoglobin carries oxygen. It
picks up c02 from the tissus, where its travels back to the lungs as deoxy-haemoglobin to release the
co2 and pick up 02.
Erythropoietin is a glycoprotein hormone. It is synthesised in the peritubular endothelial cells of the
kidney and is triggered in response to hypoxia. It binds to receptors on primitive erythroid cells in
the bone marrow and stimulates stem cells already commited to becoming rbc. Reticulocytes are
immature red blood cells, that mature in the blood stream roughly 24 hours after release from the
bone marrow. After erythropoietin release an increase of reticulocytes is seen.
Mammalian Red Blood cells.
Mammalian red blood cells contain no nucleus, and no endoplasmic reticulum and therefore there is
no protein synthesis. No mitochondria and therefore no oxidative metabolism. It is highly specialled
cytoskeleton, therefore while this allows for ability to squeeze through microcirculation it results in
limited repair capacity. The life span of a RBC is ~120 days.
Anaemia is defined as either a reduction in blood cells, concentration of haemoglobin or volume of
red blood cells. It could also result from a combination or all of these characteristics.
Normal lifespan of a RBC is 120 days, after 100 they experience a low rate of glycolysis, low ATP and
have a loss in flexibility. These cells are removed from circulation by macrophages of the spleen and
liver. Iron is reused. Protoporphyin of hem is metabolised and excreted in the faeces or urine. Heme
is converted to biliverdin, then to bilirubin. Polycythaemia is an increase or excess of RBCs.
Anaemia’s result from iron deficiencies, haemoglobin abnormalities or abnormalities in RBC
proteins. Polycythaemias can result from chronic hypoxia, erythropoietin excess or leukaemia.
An indication of anaemia is an abnormal cell RBC size. Identification of this down a microscope may
prompt further investigation.
Iron is key nutritional requirement for erythropoiesis. It is lost though urine, feces and bleeding. Low
absorption rate requires consumption of 5-20mg/day. B12 and folic acid are required for rapid cell
divison and copper are cofactors for enzymes synthesizing RBCs. Haemoglobin
While Human haemoglobin a (adult) makes up 97.5% of total adult haemoglobin, there are 5 other
normal haemoglobins that are mainly found at other time of development. It is found in tetramers
with two alpha or alpha like chains and two beta or beta like chains. Haemoglobin production is
characterised by two significant switches in production. After the first 2 months embryonic
haemoglobin is switched to fetal. Just before birth it switches to adult. A globin and B globin are
encoded by two genetically distinct loci, chromosome 6 and 11 respectively. In both clusters, the
genes are arranged 5` to 3` in the order in which they are expressed during development.
A thalassemia is an inherited haemoglobin disorder that affects globin synthesis. Can vary from mild
to severe and arises from an imbalance between the number of a and b globin chains. Failure to
produce a is termed a thalassemia and is fatal. Failure to produce b globin is termed b thalassemia
and results in life long transfusion dependence.
Beta thalassemia (major)
this disease results in underproduction of haemoglobin and ineffective erythroid development. This
causes anaemia and and abnormal red blood cells. Anaemia develops within the first few months of
life. Haematopoiesis can outside of the bone and result in an enlarged spleen. Expansion of the bone
marrow with erythropoiesis results in thin bones and expansion of the marrow into the facial bones.
Alpha chain proceeds at normal rate, causing an imbalance and thereby excess of a chains. These for
unstable complexes which precipitate in the cell and cause haemolysis.
Severe homozygous die in utero. Milder forms survive to adult life. Beta tetramers precipitate in the
cell and inclusion bodies form with causes cell damage and destruction of the red cell occurs.
This involves the prevention and cessation of bleeding from blood vessels by formation of blood
clots. These mechanisms are usually effective at stopping bleeding from small vessels, but not
usually adequate to stop bleeding from large vessels. This mechanism is tightly regulated,
inappropriate clot formation can lead to arterial and venous thrombosis causing heart attacks or
strokes. Therefore there exists a balance between the prevention of clotting and promotion of
in the event of vessel injury. Vasoconstriction of the broken vessel occurs to reduce bleeding. A
platelet plug then forms as platelets adhere to exposed collagen fibres of the vessel wall and
temporarily seals the break. A blood clot forms as platelets and erythrocytes become enmeshed in
fibrin threads. This forms a longer lasting seal and gives the vessel a chance to repair itself.
The vascular spasm is the immediate response for protection against blood loss and in maintained
long enough for the plug to form.
The endothelial lining of blood vessels usually prevents contact between blood compartments and
subendothelium. Normally the endothelium contains and secretes anti-coagulant proteins that act
to maintain circulating blood in a fluid phase. Damage to the endothelium by trauma exposes the
subendothelium. This contains proteins such as collagen ad Von Willebrand factor and ligands for
platelet surface receptors. This causes platelet adhesion and activation. Platelets:
These are small anucleate cells that bud off from megakaryocytes and exist in circulation for 1-4
days. The accumulate at the sites of trauma by binding to the exposed subendothelium. They
adhere, clump, aggregate stopping bleeding. Pathogenic states cause stroke and heart attack. They
also secrete procoagulants and clotting factors which promote blood clotting, vasoconstrictors that
cause vascular spasm. A fall in platelet count (thrombocytopenia) is associated with significant
bleeding tendency. In the event of trauma, bleeding is continual and can occur in the skin or mouth
without any obvious trauma. Causes may include bone marrow transplant following leukemia,
chemotherapy or various autoimmune diseases.
It is important for blood clotting to occur quickly but not inappropriately, therefore it is tightly
regulated and involves over 30 specific chemical reaction and must take place on an appropriate
surface such as platelets or subendothelium. Blood coagulation proteins circulate as inactive