A specialized bodily fluid that delivers necessary substances to the body’s cells such as nutrients, oxygen and transports waste products away from those same cells

Blood accounts for 7% of the human body weight

By volume the red blood cells constitute about 45% of whole blood, the plasma constitutes about 55%

Plasma

Formed elements

Erythrocytes (red blood cells)

Adult humans have roughly 2–3 × 1013 red blood cells

Leukocytes (white blood cells) and 4,000–11,000 white blood cells

Thrombocytes (platelets). 150,000–400,000 platelets in each microliter

Men about 5 to 6 million;

People living at high altitudes with low oxygen tension will have more

Supply of oxygen to tissues (bound to haemoglobin which is carried in red cells)

Supply of nutrients such as glucose, amino acids and fatty acids (dissolved in the blood or bound to plasma proteins (e.g. blood lipids)

Removal of waste such as carbon dioxide, urea and lactic acid

Immunological functions, including circulation of white cells, and detection of foreign material by antibodies

Messenger functions, including the transport of hormones and the signalling of tissue damage

Regulation of body pH (the normal pH of blood is in the range of 7.35 – 7.45)

Regulation of core body temperature

Blood type (group)

A classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs).

These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system, and some of these antigens are also present on the surface of other types of cells of various tissues

The ABO system is the most important blood group system in human blood transfusion.

It is associated with anti- A antibodies and anti-B antibodies, which are usually “Immunoglobulin M”, antibodies to the RBC surface antigens abbreviated IgM, antibodies.

ABO IgM antibodies are produced in the first years of life by sensitization to environmental substances such as food, bacteria and viruses in the same way as other antibodies.

Individuals have both A and B antigen on the surface of their RBCs, and their blood serum does not contain any antibodies against either A or B antigen.

Therefore, an individual with type AB blood can receive blood from any group (with AB being preferable), but can donate blood only to another group AB individual.

Individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen.

Therefore, a group A individual can receive blood only from individuals of groups A or O (with A being preferable), and can donate blood to individuals with type A or AB.

Individuals have the B antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the A antigen.

Therefore, a group B individual can receive blood only from individuals of groups B or O (with B being preferable), and can donate blood to individuals with type B or AB.

Individuals do not have either A or B antigens on the surface of their RBCs, but their blood serum contain IgM anti-A antibodies and anti-B antibodies against the A and B blood group antigens.

Therefore, a group O individual can receive blood only from a group O individual, but can donate blood to individuals of any ABO blood group (i.e. A, B, O or AB) if anyone needs a blood.

The Rhesus system is the second most significant blood group system in human blood transfusion.

The term Rhesus (Rh) blood group system refers to the 5 main Rhesus antigens (C, c, D, E and e) as well as the many other less frequent Rhesus antigens.

The most significant Rhesus antigen is the RhD antigen because it is the most immunogenic of the five main rhesus antigens.

The terms “positive” or “negative” refer to either the presence or absence of the RhD antigen irrespective of the presence or absence of the other antigens of the Rhesus system.

The fluid portion of the blood, the plasma, is a remarkable solution containing an immense number of ions, inorganic molecules, and organic molecules that are in transit to various parts of the body or aid in the transport of other substances.

Plasma clots on standing, remain fluid only if an anticoagulant is added.

If whole blood is allowed to clot and the clot is removed, the remaining fluid is called serum.

Serum has essentially the same composition as plasma except that its fibrinogen and clotting factors II, V, and VIII have been removed and it has higher serotonin content because of the breakdown of platelets during clotting.

The plasma consist of protein; albumin, globulin, and fibrinogen fractions.

The capillary walls are relatively impermeable to the proteins plasma, and the proteins are therefore exerting an osmotic force of about 25 mm Hg across the capillary wall (oncotic pressure) that pulls water into the blood.

Red Blood Cells Formation

Red blood cells (Erythrocytes) are the most common type of blood cell.

The cells are filled with hemoglobin, a biomolecule that can bind to oxygen.

They take up oxygen in the lungs and release it while squeezing through the body’s capillaries.

In humans, red blood cells develop in the bone marrow, take the form of flexible biconcave disks, lack a cell nucleus, subcellular organelles and the ability to synthesize protein, it takes about 7 days for erythrocytes to mature and live a total of about 120 days.

Erythropoiesis is the process by which red blood cells (erythrocytes) are produced.

In human adults, this usually occurs within the bone marrow.

By the third or fourth month, erythropoiesis moves to the spleen and liver.

In humans with certain diseases, erythropoiesis also occurs outside the bone marrow, within the spleen or liver.

This is termed extramedullary erythropoiesis.

The tibia and femur cease to be important sites of hematopoiesis by about age 25; the vertebrae, sternum, pelvis and ribs, and cranium bones continue to produce red blood cells throughout life.

Erythrocytes and granulocytes belong to the myeloid lineage.

The earliest identifiable erythroid stem cells are capable of rapid bursts of cell division to form numerous daughter cells.

In the process of red blood cell maturation, a cell undergoes a series of differentiations.

Pluripotent haematopoietic stem cell is cells which are capable of giving rise to all blood cell types.

The first readily identifiable cell of the erythroid series is the proerythroblast, a large cell with a large euchromatic nucleus and moderately basophilic cytoplasm.

The proerythroblast contains small amounts of ferritin and bears some of the protein spectrin on its plasma membrane.

Proerythroblasts proliferate to produce smaller basophilic erythroblasts, rich in ribosomes, in which haemoglobin-RNA synthesis begins.

The nucleus becomes intensely pyknotic and is finally extruded from the cell, leaving an anucleate reticulocyte, which enters a sinusoid.

Its reticular staining pattern, visible using special stains, results from residual cytoplasmic RNA which is lost within 24 hours of entering the peripheral blood circulation.

The whole process of erythropoiesis takes 5-9 days.

After these stages, the cell is released from the bone marrow, and ultimately becomes an ‘erythrocyte’ or matures red blood cell circulating in the peripheral blood.

Erythropoietin (EPO) is a glycoprotein (protein-sugar conjugate) that serves as the primary regulator of red blood cells (erythrocytes).

It stimulates bone marrow stem cells to differentiate into red blood cells and controls haemoglobin synthesis and red blood cell concentration.

EPO production is stimulated by reduced oxygen content in arterial blood in the kidneys.

Circulating EPO binds to receptors on the surface of erythroid progenitor cells that in turn mature into red blood cells.

In infants, EPO is produced mostly in the liver, but the kidneys become the primary site of EPO synthesis shortly after birth.

White blood cells, or leukocytes, are cells of the immune system defending the body against both infectious disease and foreign materials.

Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell.

Leukocytes are found throughout the body, including the blood and lymphatic system.

There are normally between 4×109 and 11×109 white blood cells in a litre of blood, making up approximately 1% of blood in a healthy adult.

In conditions such as leukemia, the number of leukocytes is higher than normal, and in leukopenia, this number is much lower.

There are several different types of white blood cells.

They all have many things in common, but are all different.

One primary technique to classify them is to look for the presence of granules, which allows the differentiation of cells into the categories granulocytes and agranulocytes

Leukocytes characterised by the presence of differently staining granules in their cytoplasm when viewed under light microscopy.

These granules are membrane-bound enzymes which primarily act in the digestion of endocytosed particles.

There are three types of granulocytes: neutrophils, basophils, and eosinophils, which are named according to their staining properties.

Granulocyte formation involves major changes in nuclear morphology and cytoplasmic contents which are best known for the neutrophil.

Initially, myeloid stem cells transform into large myeloblasts which are similar in general size and appearance to proerythroblasts.

These proliferative cells have large euchromatic nuclei and lack cytoplasmic granules.

They differentiate into slightly larger promyelocytes, in which the first group of specific proteins is synthesized in the rough endoplasmic reticulum and Golgi apparatus.

The proteins are stored in large primary (non-specific) granules, which are large lysosomes containing acid phosphatase.

Smaller secondary (specific) granules are formed in the smaller myelocyte, which is the last proliferative stage.

In metamyelocyte, stage, the cell size decreases, the nucleus becomes heterochromatic and horse-shoe shaped, and protein synthesis almost stops.

As the neutrophil is released, the nucleus becomes first heavily indented and subsequently segmented into up to six lobes, characteristic of the mature neutrophil.

Neutrophils may then be stored in the marrow for a further 4 days, depending on demand, before their final release into the circulation.

Eosinophils and basophils pass through a similar sequence but their nuclei do not become as irregular as that of the neutrophil.

Basophils nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules which hide it.

They are characterised by their large blue granules.

Eosinophils nucleus is bi-lobed.

The cytoplasm is full of granules which assume a characteristic pink-orange color with eosin stain.

They have a multilobed nucleus which may appear like multiple nuclei, hence the name polymorphonuclear leukocyte.

The cytoplasm may look transparent because of fine granules that are faintly pink in color

Leukocytes characterized by the apparent absence of granules in their cytoplasm.

Although the name implies a lack of granules these cells do contain non-specific azurophilic granules, which are lysosomes.

The cells include monocytes, macrophages and lymphocytes.

Monocyte progenitors pass through a proliferative monoblast stage.

A typical monoblast is about 12 to 20 μm in diameter, has a round to oval nucleus with fine chromatin structure.

The nucleus can be central or eccentric and it can show evidence of indentation or folding.

The cytoplasm is agranular, stains moderately to lightly basophilic, and often has an intensely stained periphery and a prominent perinuclear zone.

They mature into monocytes which in turn develop into macrophages.

The monoblast is the first stage of monocyte-macrophage maturation.

Pluripotential Hemopoietic Stem Cell or hemocytoblast

Monoblast

Promonocyte

Monocyte

Macrophage

Lymphoblasts are normally found in the bone marrow, but in acute lymphoblastic leukaemia (ALL), lymphoblasts proliferate uncontrollably and are found in large numbers in the peripheral blood.

Neutrophils defend against bacterial or fungal infection and other very small inflammatory processes that are usually first responders to microbial infection; their activity and death in large numbers forms pus.

Neutrophils are very active in phagocytosing bacteria and are present in large amount in the pus of wounds.

These cells are not able to renew their lysosomes used in digesting microbes and die after having phagocytosed a few pathogens

Eosinophils primarily deal with parasitic infections and an increase in them may indicate such.

They are also the predominant inflammatory cells in allergic reactions.

The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and also parasitic infections.

Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing inflammation.

They have the kidney shaped nucleus and are typically agranulated.

They also possess abundant cytoplasm.

Monocytes share the ‘vacuum cleaner’ (phagocytosis) function of neutrophils, but are much longer lived as they have an additional role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted.

Monocytes eventually leave the bloodstream to become tissue macrophages which remove dead cell debris as well as attacking microorganisms.

Neither of these can be dealt with effectively by the neutrophils.

Unlike neutrophils, monocytes are able to replace their lysosomal contents and are thought to have a much longer active life.

Once monocytes move from the bloodstream out into the body tissues, they undergo changes (differentiate) allowing phagocytosis and are then known as macrophages.

Lymphocytes are much more common in the lymphatic system.

Lymphocytes are distinguished by having a deeply staining nucleus which may be eccentric in location, and a relatively small amount of cytoplasm.

B cells; which make antibodies that bind to pathogens to enable their destruction.

T cells; these include CD4+ (helper) T cells co-ordinate the immune response (they are what become defective in an HIV infection).

CD8+ (cytotoxic) are able to kill virus-infected and tumor cells.

T cells are crucial to the immune response because they possess a unique ‘memory‘ system which allows them to remember past invaders and prevent disease when a similar invader is encountered again.

Natural Killer Cells (NK cells). are able to kill cells of the body that are infected by a virus or have become cancerous.

Platelets or thrombocytes are minute fragment of cells consisting of a small amount of cytoplasm surrounded by a plasma membrane.

Platelets are roughly disk-shaped and an average about 3μm in diameter.

They play an important role in controlling blood loss by forming platelets plugs which seal holes in small vessels.

The life expectancy of platelets is about 5 – 9 days.

Platelets arise in a unique manner by the shedding of thousands of cytoplasmic fragments from the tips of processes of megakaryocytes in the bone marrow.

The first detectable cell of this line is the highly basophilic megakaryoblast, followed by a promegakaryocyte stage, in which synthesis of granules begins.

Finally, the fully differentiated megakaryocyte, a giant cell with a large, dense, polyploid, multilobed nucleus, appears.

Almost always, an individual has the same blood group for life; but very rarely an individual’s blood type changes through addition or suppression of an antigen in infection, malignancy or autoimmune disease.

An example of this rare phenomenon is the case of an Australian citizen, whose blood group changed after a liver transplant.

Another more common cause in blood type change is a bone marrow transplant.

If a person receives a bone marrow from someone who is a different ABO type (ex. A type a patient receives a type O bone marrow), the patient’s blood type will eventually convert to the donor’s type.

Some blood types are associated with inheritance of other diseases.

Certain blood types may affect susceptibility to infections, an example being the resistance to specific malaria species seen in individuals lacking the Duffy antigen.

The Duffy antigen is a protein located on the surface of red blood cells and is named after the patient in which it was discovered.

On erythrocytes the Duffy antigen acts as a receptor for invasion by the human malarial parasites Plasmodium vivax.

Duffy negative individuals whose erythrocytes do not express the receptor are believed to be resistant to merozoite invasion.

The presence of the Duffy antigen receptor appears to increase the susceptibility to infection by HIV.

After birth an infant gut becomes colonized with normal floras which express these A-like and B-like antigens, causing the immune system to make antibodies to those antigens that the red cells do not possess.

So, people who are blood type A will have Anti-B, blood type B will have Anti-A, blood type O will have both Anti-A and Anti-B, and blood type AB will have neither.

Because of these so called “naturally occurring” and expected antibodies, it is important to correctly determine a patient’s blood type prior to transfusion of any blood component.

Cross-matching for the RhD antigen is extremely important, because the RhD antigen is immunogenic, meaning that a person who is RhD negative is very likely to make Anti- RhD when exposed to the RhD antigen (perhaps through either transfusion or pregnancy).

Once an individual is sensitised to RhD antigens their blood will contain RhD IgG antibodies which can bind to RhD positive RBCs and may cross the placenta.

A RhD negative patient who does not have any anti-RhD antibodies (never being previously sensitized to RhD positive RBCs) can receive a transfusion of RhD positive blood once, but this would cause sensitization to the RhD antigen, and a female patient would become at risk for hemolytic disease of the newborn

RhD positive blood should never be given to RhD negative women of childbearing age or to patients with RhD antibodies.

In extreme circumstances, such as for a major bleed when stocks of RhD negative blood units are very low at the blood bank, RhD positive blood might be given to RhD negative

females above child-bearing age or to Rh negative males, providing that they did not have anti-RhD antibodies, RhD positive patients do not react to RhD negative blood.