Blood is a liquid tissue. Suspended
in the watery plasma
are seven types of cells and cell fragments.
blood cells (RBCs) or erythrocytes
- five kinds of white blood cells (WBCs) or leukocytes
- Three kinds of granulocytes
- Two kinds of leukocytes without granules in their cytoplasm
two major functions:
|If one takes a sample of blood, treats it with an agent to prevent
clotting, and spins it in a centrifuge,
The fraction occupied by the red cells is called the
hematocrit. Normally it is approximately 45%. Values much lower
than this are a sign of anemia.
- the red cells settle to the bottom
- the white cells settle on top of them forming the "buffy
- transport through the body of
- oxygen and carbon dioxide
- food molecules (glucose, lipids, amino acids)
- ions (e.g., Na+, Ca2+,
- wastes (e.g., urea)
- defense of the body against infections and other foreign materials. All
the WBCs participate in these defenses.
The formation of blood cells (cell types and
acronyms are defined below)
All the various types of blood cells
These stem cells
- are produced in the bone marrow (some 1011 of them each
day in an adult human!).
- arise from a single type of cell called a hematopoietic stem cell
an "adult" multipotent
Which path is taken is regulated by
- are very rare (only about one in 10,000 bone marrow cells);
- are attached (probably by adherens
junctions) to osteoblasts
lining the inner surface of bone cavities;
- express a cell-surface protein designated CD34;
- produce, by mitosis, two kinds of progeny:
- more stem cells (A mouse that has had all its blood stem cells killed by
a lethal dose of radiation can be saved by the injection of a single living
- cells that begin to differentiate along the paths leading to the various
kinds of blood cells.
- the need for more of that type of blood cell which is, in turn, controlled
by appropriate cytokines
For example, Interleukin-7 (IL-7) is the major cytokine in
stimulating bone marrow stem cells to start down the "lymphoid"
path leading to the various lymphocytes
cells and T
cells). Some of the cytokines that drive the differentiation of the "myeloid"
(EPO), produced by the kidneys, enhances the production of red blood
(TPO), assisted by Interleukin-11 (IL-11), stimulates the
production of megakaryocytes. Their fragmentation produces platelets.
- Granulocyte-macrophage colony-stimulating factor (GM-CSF),
as its name suggests, sends cells down the path leading to both those cell
types. In due course, one path or the other is taken.
- Under the influence of granulocyte colony-stimulating factor
(G-CSF), they differentiate into neutrophils.
- Further stimulated by interleukin-5 (IL-5) they develop into
- Interleukin-3 (IL-3) participates in the differentiation of most
of the white blood cells but plays a particularly prominent role in the
formation of basophils
(responsible for some allergies).
- Stimulated by macrophage colony-stimulating factor (M-CSF)
the granulocyte/macrophage progenitor cells differentiate into monocytes,
macrophages, and dendritic
Red Blood Cells (erythrocytes) The most numerous type in
RBC precursors mature in the bone marrow
closely attached to a macrophage.
- Women average about 4.8 million of these cells per cubic millimeter
(mm3; which is the same as a microliter [΅l]) of blood.
- Men average about 5.4 x 106 per ΅l.
- These values can vary over quite a range depending on such factors as
health and altitude. (Peruvians living at 18,000 feet may have as many as 8.3
x 106 RBCs per ΅l.)
- They manufacture hemoglobin until it accounts for some 90% of the dry
weight of the cell.
- The nucleus is squeezed out of the cell and is ingested by the macrophage.
- No-longer-needed proteins are expelled from the cell in vesicles called exosomes.
This scanning electron micrograph (courtesy of Dr. Marion J. Barnhart) shows
the characteristic biconcave shape of red blood cells.
Thus RBCs are terminally differentiated; that is, they can never divide. They
live about 120 days and then are ingested by phagocytic cells in the liver and
spleen. Most of the iron in their hemoglobin is reclaimed for reuse. The
remainder of the heme portion of the molecule is degraded into bile
pigments and excreted by the liver. Some 3 million RBCs die and are
scavenged by the liver each second. Red blood cells are responsible for the
transport of oxygen and carbon dioxide.
In adult humans the hemoglobin (Hb)
- consists of four polypeptides:
- two alpha (α) chains of 141 amino acids and
- two beta (β) chains of 146 amino acids
- Each of these is attached the prosthetic
- There is one atom of iron at the center of each heme.
- One molecule of oxygen can bind to each heme.
- Under the conditions of lower temperature, higher pH, and increased oxygen
pressure in the capillaries of the lungs, the reaction proceeds to the right.
The purple-red deoxygenated hemoglobin of the venous blood becomes the
bright-red oxyhemoglobin of the arterial blood.
- Under the conditions of higher temperature, lower pH, and lower oxygen
pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin
gives up its oxygen.
Carbon Dioxide TransportCarbon dioxide (CO2)
combines with water forming carbonic acid, which dissociates into a hydrogen ion
(H+) and a bicarbonate
CO2 + H2O ↔ H2CO3 ↔
H+ + HCO3−
95% of the CO2 generated in the tissues is carried in the red
- It probably enters (and leaves) the cell by diffusion through the plasma
membrane assisted by facilitated
diffusion through transmembrane channels in the plasma membrane. (One of
the proteins that forms the channel is the D antigen that is the most
important factor in the Rh
system of blood groups.)
- Once inside, about one-half of the CO2 is directly bound to
hemoglobin (at a site different from the one that binds oxygen).
- The rest is converted following the equation above by the enzyme
carbonic anhydrase into
- bicarbonate ions that diffuse back out into the plasma and
- hydrogen ions (H+) that bind to the protein portion of the
hemoglobin (thus having no effect on pH).
Only about 5% of the CO2 generated in the tissues dissolves
directly in the plasma. (A good thing, too: if all the CO2 we make
were carried this way, the pH of the blood would drop from its normal 7.4 to an
instantly-fatal 4.5!) When the red cells reach the lungs, these reactions
are reversed and CO2 is released to the air of the alveoli.
Anemia is a shortage of
Anemia has many causes. One of
the most common is an inadequate intake of iron
in the diet.
Red blood cells have surface
antigens that differ between people and that create the so-called blood groups
such as the ABO system and the Rh system.
- RBCs and/or
- the amount of hemoglobin in them.
White Blood Cells (leukocytes)White blood cells
There are several kinds of
lymphocytes (although they all look alike under the microscope), each with
different functions to perform . The most common types of lymphocytes are
- are much less numerous than red (the ratio between the two is around
- have nuclei;
- participate in protecting the body from infection;
- consist of lymphocytes and monocytes with relatively clear
cytoplasm, and three types of granulocytes, whose cytoplasm is filled
lymphocytes ("B cells"). These are responsible for making antibodies.
- T lymphocytes ("T cells"). There are several subsets of these:
Although bone marrow is the ultimate source of lymphocytes, the lymphocytes
that will become T cells migrate from the bone marrow to the thymus [View]
where they mature. Both B cells and T cells also take up residence in lymph
nodes, the spleen and other tissues where they
Monocytes leave the blood and become
macrophages and dendritic
- encounter antigens;
- continue to divide by mitosis;
- mature into fully functional cells.
This scanning electron micrograph (courtesy of Drs. Jan M. Orenstein and Emma
Shelton) shows a single macrophage surrounded by several
lymphocytes.Macrophages are large, phagocytic cells that engulf
- foreign material (antigens) that enter the body
- dead and dying cells of the body.
The most abundant of the WBCs. This photomicrograph shows a single neutrophil
surrounded by red blood cells.
Neutrophils squeeze through the capillary walls and into infected tissue
where they kill the invaders (e.g., bacteria) and then engulf the remnants by phagocytosis.
This is a never-ending task, even in healthy people: Our throat, nasal
passages, and colon harbor vast numbers of bacteria. Most of these are commensals,
and do us no harm. But that is because neutrophils keep them in check.
can reduce the numbers of
neutrophils so that formerly harmless bacteria begin to proliferate. The
resulting opportunistic infection can be life-threatening.
The number of eosinophils in the
blood is normally quite low (0450/΅l). However, their numbers increase sharply
in certain diseases, especially infections by parasitic worms. Eosinophils are
cytotoxic, releasing the contents of their granules on the invader.
- heavy doses of radiation
- and many other forms of stress
The number of basophils also increases during infection. Basophils leave the
blood and accumulate at the site of infection or other inflammation. There they
discharge the contents of their granules, releasing a variety of mediators such
which increase the blood flow to the area and in
other ways add to the inflammatory process. The mediators released by basophils
also play an important part in some allergic responses such as
Platelets are cell fragments produced
Blood normally contains 150,000450,000 per microliter (΅l) or cubic
millimeter (mm3). This number is normally maintained by a homeostatic
(negative-feedback) mechanism [Link].
If this value should drop much below 50,000/΅l, there is a danger of
uncontrolled bleeding because of the essential role that platelets have in blood
- certain drugs and herbal remedies;
- autoimmunity. [Link]
When blood vessels are cut or damaged, the loss of blood from the system must
be stopped before shock
and possible death occur. This is accomplished by solidification of the blood, a
process called coagulation or clotting.A blood clot consists of
- a plug of platelets enmeshed in a
- network of insoluble fibrin molecules.
|Details of the clotting process are in a separate page. Link
Plasma is the straw-colored liquid in which the blood cells are
Composition of blood plasma
|Glucose (blood sugar)
Plasma transports materials needed by cells and materials that must be
removed from cells:
Most of these materials are in transit from
a place where they are added to the blood (a "source")
- various ions (Na+, Ca2+,
- glucose and traces of other sugars
- amino acids
- other organic acids
- cholesterol and other lipids
- urea and other wastes
to places ("sinks") where they
will be removed from the blood.
- exchange organs like the intestine
- depots of materials like the liver
- every cell
- exchange organs like the kidney, and skin.
Proteins make up 68% of the blood. They are about equally divided between
serum albumin and a great variety of serum globulins.
After blood is withdrawn from a vein and allowed to clot, the clot slowly
shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:
Serum is blood plasma without fibrinogen and other clotting factors.
The serum proteins can be separated by electrophoresis.
- A drop of serum is applied in a band to a thin sheet of supporting
material, like paper, that has been soaked in a slightly-alkaline salt
- At pH 8.6, which is commonly used, all the proteins are negatively
charged, but some more strongly than others.
- A direct current can flow through the paper because of the conductivity of
the buffer with which it is moistened.
- As the current flows, the serum proteins move toward the positive
- The stronger the negative charge on a protein, the faster it migrates.
- After a time (typically 20 min), the current is turned off and the
proteins stained to make them visible (most are otherwise colorless).
- The separated proteins appear as distinct bands.
- The most prominent of these and the one that moves closest to the positive
electrode is serum albumin.
- Serum albumin
- is made in the liver
- binds many small molecules for transport through the blood
- helps maintain the osmotic
pressure of the blood
- The other proteins are the various serum globulins.
- They migrate in the order
- alpha globulins (e.g., the proteins that transport thyroxine
- beta globulins (e.g., the iron-transporting protein
- gamma globulins.
- Gamma globulins are the least negatively-charged serum proteins. (They
are so weakly charged, in fact, that some are swept in the flow of buffer
back toward the negative electrode.)
- Most antibodies are gamma globulins.
- Therefore gamma globulins become more abundant following infections or
If a precursor of an antibody-secreting cell becomes cancerous, it
divides uncontrollably to generate a clone
cells secreting a single kind of antibody molecule. The image
(courtesy of Beckman Instruments, Inc.) shows from left to right the
electrophoretic separation of:
- normal human serum with its diffuse band of gamma globulins;
- serum from a patient with multiple myeloma producing an
- serum from a patient with Waldenstrφm's macroglobulinemia where the
cancerous clone secretes an IgM antibody;
- serum with an IgA myeloma protein.
- Gamma globulins can be harvested from donated blood (usually pooled
from several thousand donors) and injected into persons exposed to certain
diseases such as chicken pox and hepatitis. Because such preparations of
immune globulin contain antibodies against most common infectious
diseases, the patient gains temporary protection against the disease. [More]
Because of their relationship to cardiovascular disease, the analysis of
serum lipids has become an important health measure. The table shows the
range of typical values as well as the values above (or below) which the subject
may be at increased risk of developing atherosclerosis.
||Typical values (mg/dl)
In the United States,
in 2001, some 15 million "units" (~475 ml) of blood were collected from blood
- Total cholesterol is the sum of
- HDL cholesterol
- LDL cholesterol and
- 20% of the triglyceride value
- Note that
- high LDL values are bad, but
- high HDL values are good.
- Using the various values, one can calculate a
cardiac risk ratio
= total cholesterol divided by HDL cholesterol
- A cardiac risk ratio greater than 7 is considered a warning.
- Some of these units ("whole blood") were transfused directly into patients
(e.g., to replace blood lost by trauma or during surgery).
- Most were further fractionated into components, including:
- RBCs. When refrigerated these can be used for up to 42 days.
- platelets. These must be stored at room temperature and thus can be
saved for only 5 days.
- plasma. This can be frozen and stored for up to a year.
Ensuring the safety of donated bloodA variety of infectious agents can
be present in blood.
and could be transmitted to
recipients. To minimize these risks,
Most of these tests are performed with enzyme immunoassays (EIA) Link
and detect antibodies against the agents. However, it takes a period of
time for the immune system to produce antibodies following infection, and during
this period ("window"), infectious virus is present in the blood. For this
reason, blood is now also checked for the presence of the RNA of these RNA
- donors are questioned about their possible exposure to these agents;
- each unit of blood is tested for a variety of infectious agents.
by the so-called nucleic acid-amplification
- hepatitis C
- West Nile virus
Thanks to all these precautions, the risk of acquiring an infection from any
of these agents is vanishingly small. Despite this, some people in
anticipation of need donate their own blood ("autologous blood donation")
prior to surgery.
Donated blood must also be tested for certain cell-surface antigens that
might cause a dangerous transfusion reaction in an improperly-matched recipient.
This is discussed in a separate page link
Years of research have
gone into trying to avoid the problems of blood perishability and safety by
developing blood substitutes. Most of these have focused on materials that will
transport adequate amounts of oxygen to the tissues.
- Some are totally synthetic substances.
- Others are derivatives of hemoglobin.
Although some have reached clinical
testing, none has as yet proved acceptable for routine use.
16 July 2008