# Within The Blood

Human blood is quite remarkable.  It transports oxygen, hormones and nutrients.  It tracks down and kills pathogens, carries away waste products, helps regulate body temperature, and it irrigates all our internal organs.  And the blood is packed with information.

## How much Blood do we have?

Quite how much blood you have inside you will depend on your size.

The amount of blood in the human body is generally equivalent to

##### 7 – 9 % of an adult body weight.

For example, an average 70 kg man will have about 5.6 litres circulating around his body.  But a healthy newborn baby has only about 0.25 litres – less than 5% of the adult value.

# Cells in the Blood

Blood is a living tissue.

If you spin a blood sample in a centrifuge, it will separate into four layers:

• Plasma
• Red cells (erythrocytes)
• White cells (leukocytes)
• Platelets (thrombocytes).

## Plasma

By far the most abundant component, about 55% of blood is plasma – a pale yellowish fluid that is the blood’s liquid medium.

Mostly water (90-95%), plasma maintains the normal hydration of our bodies.  It provides an aqueous medium for both intracellular and extracellular chemical reactions, as it transports electrolytes:

• Sodium Na+
• Chloride Cl
• Potassium K+
• Calcium Ca2+
• Iodide I
• Magnesium Mg2+
• Phosphate Pi
##### Plasma is very important.

Plasma circulates nutrients, such as glucose C6H12O6, amino acids, and fatty acids (dissolved in the blood or bound to plasma proteins).

And it removes waste products, such as carbon dioxide CO2, urea CO(NH2)2, and lactic acid CH3CH(OH)COOH.

Plasma also include:

• Proteins
• Albumins (about 60%) regulate the passage of water and diffusible solids through the capillary walls of blood vessels
• Fibrinogen (about 4%), essential for blood clotting
• Globulins (about 36%), such as alpha- and beta-globulins for the transport of lipids and fat-soluble vitamins, and gamma-globulins or antibodies.
• Hormones
• Steroids, i.e. sex hormones.

Serum is plasma from which the clotting proteins have been removed.  Most of the proteins that remains are albumin and immunoglobulins.

Antibodies, clotting factors, and other constituent parts of the blood can be separated out and used to treat autoimmune diseases or haemophilia.

## Red Blood Cells

5,000,000 per mm3 (cubic millimetre).

Erythrocytes are structurally homogeneous cells that do not have a nucleus.

They are disc-shaped with highly indented centres on both sides.  Seen from the side, their biconcave shape resembles a figure of eight (as in the picture).

Their diameter is approximately 8 micrometres (8 $\mu$m).

Erythrocytes were originally termed ‘red’ cells because they contain the respiratory pigment haemoglobin, which turns red when it combines with oxygen (O2).

On average, each erythrocyte circulates 1,200 kilometres ($\simeq$750 miles) around the cardio-vascular system.

### The Haematocrit Ratio

Red blood cells outnumber white blood cells by 750 : 1.

The normal haematocrit ratio is about 45%.

In order to maintain normal levels of oxygen in their blood, people living at different altitudes have different requirements.

At sea-level, about 40% of your blood volume is made up of red blood cells, but that can increase by about half as much with acclimatization to higher altitudes.

Up in the Andes of South America, a lifelong Peruvian resident would have more erythrocytes per unit volume of blood, compared to anyone habitually living at sea-level.

Their haematocrit ratio would be higher.

## White Blood Cells

7,000 per mm3.

Leukocytes lack haemoglobin, and therefore appear white.

These white blood cells can be divided into several categories according to their different structures, functions and relative numbers.

Under the microscope, leukocytes are easy to tell apart from other cells in terms of their shape and susceptibility to various histological treatments:

• ### Granulocytes

Granulocytes are larger than erythrocytes, with an approximate diameter of 16 $\mu$m.

They include:

• Neutrophils, the most numerous leukocytes in our blood, where they contribute between 40 % and 70% of the total ‘white count’.  During an infection, the number of neutrophils rises sharply.  Neutrophils only live for a few days, and they do not divide once they entered the bloodstream.  Their recognizable appearance features a multi-lobed nucleus.
• Eosinophils play an important part in allergic reactions.
• Basophils also have an important role in allergic reactions, by releasing histamin and heparin.

This terminology is based on the affinity of cellular components for a particular chemical dye.

Mast cells are a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuro-immune systems.

• ### Monocytes

Monocytes are white blood cells that can differentiate into macrophages and myeloid lineage dendritic cells.

Macrophages are highly mobile, long-lived cells that migrate through connective tissues.  Macrophages abund near blood vessels.  Less than 7% of leukocytes in the bloodstream are macrophages.  Macrophages are the largest leukocytes.  Their characteristic morphology includes a horseshoe- or kidney-shaped nucleus.

• ### Lymphocytes

• B lymphocytes produce antibodies.
• T lymphocytes are involved in cell-mediated immune responses.
• Natural Killer (NK) cells are a part of the innate immune system and play a major role in defending the host body from tumours and viruses because they can distinguish  infected cells and abnormal growths from normal and uninfected cells.  NK cells also modulate the functions of other cells, including macrophages and T cells.

## Platelets

250,000 per mm3.

Platelets, or thrombocytes, have no cell nucleus.  They are fragments of cytoplasm derived from the bone marrow, around 2-3 $\mu$m in diameter.

Thrombocytes are involved in maintaining the integrity of the wall of blood vessels.  Their role is crucial in controlling bleeding.  Platelets can clump together to stop blood loss from a damaged blood vessel and prevent a haemorrhage.

## Lifecycle of Blood Cells

Each red blood cells travels about 1,200 kilometres (750 miles) around the vasculature during its lifetime.

##### Mature blood cells are renewed continuously through a process called haematopoiesis.

Haematopoiesis stimulates the proliferation of undifferentiated precursor stem cells in bone marrow.  The origin of all erythrocytes, leukocytes and platelets is a single pool of precursor cells found in the bone marrow.

Haematopoietic stem cells (HSCs) divide to give several different lineages of differentiated cells.  As few as 30 suffice to regenerate the entire leukocyte and erythrocyte population of a mouse after the original cells have been destroyed by radiation.

Red and white blood cell production is precisely regulated in healthy humans, and the production of leukocytes is rapidly increased during infection.

The proliferation and self-renewal of these cells depend on growth factors.  One of the key players in self-renewal and development of haematopoietic cells is the stem cell factor (SCF).

##### Mature blood cells have a comparatively short lifespan.  About 120 days for erythrocytes.

Blood is a complex material, packed with information. and it can be used to establish parenthood using DNA sequencing of the human genome.

## Blood Typing and Antigens

Our modern understanding of the blood dates back to 1900.

The research of Austrian biologist Karl Landsteiner (1868 – 1943) heralded the beginning of a new era for physiology.  It categorised human blood into different groups, labelled A, B and O.

All blood cells are the same inside, but their outsides are covered with different antigens – proteins that project outwards from the cell surface.  That is what accounts for different blood types.

The discovery of blood types explained why transfusions often failed in the early days.

### ABO

The most common blood types are A, B, AB and O.

But there are others less well-known blood types, such as Kell, Giblett and Type E to name but a few.

In the main blood group system or ABO system, erythrocytes of type A blood have A surface antigens, those with type B blood have B antigens, and type AB have both A and B.

Erythrocytes from type O blood do not have any A or B antigens.

### Erythrocyte Antigen Systems and the Rh Factor

There are 12 other erythrocyte antigen systems.  The most important of them is the Rh factor (or Rh antigen).

In 1940, Landsteiner and New Yorker Alexander S. Wiener (1907-1976) injected blood from the monkey Macacus rhesus into rabbits and guinea pigs, and discovered the resulting antibody agglutinated rhesus (Rh) red cells, which appeared to have the same specificity as the neonatal antibody.  Donors whose cells were agglutinated by the antibody to Rh red cells were termed Rh positive.  Donors whose cells were not agglutinated were termed Rh negative.

People who have the Rh factor are rhesus (Rh)-positive.  And those without, are Rh-negative.

##### 15% are Rh-negative.

There are 400 kinds of antigens, but only a few have an important effect on blood transfusions.

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

##### Of all the Rh antigens, antigen D (RhD) is the most important.

The Rh factor and Rh antigen both refer to the RhD antigen only.

Unlike the ABO system, no naturally occurring antibodies develop against the Rh factors.  But Rh-negative individuals produce anti-Rh antibodies when they are first exposed to the alien Rh antigen of Rh-positive blood.

### Transfusing Blood Safely

If a patient is given a blood transfusion, it must be of a compatible blood group.

People with type A can donate to those with A or AB types, but not B.  People with type B can donate to those with B or AB types, but not A.  People with type AB can only donate to those with AB type.

People with blood type O are known as universal donors.  It means they can donate blood to all other groups of people.

Using an incompatible type of blood can result in an adverse antigen-antibody interaction leading to a fatal transfusion reaction.

Nowadays, blood transfusions can save lives.   But storing donated blood remains an expensive and risky business.

Finding a perfect substitute, the perfect artificial blood, is the next Holy Grail of biological science.