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Blood is a liquid tissue. Suspended in the watery
plasma are seven types of cells and cell fragments.
-
red blood cells (RBCs) or erythrocytes
-
platelets or thrombocytes
- five kinds of white blood cells (WBCs) or leukocytes
- Three kinds of granulocytes
- Two kinds of leukocytes without granules in their cytoplasm
Blood performs two major functions:
- transport through the body of
- oxygen and carbon dioxide
- food molecules (glucose, lipids, amino acids)
- ions (e.g., Na+, Ca2+, HCO3−)
- wastes (e.g., urea)
- hormones
- heat
- 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 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 pluripotent stem cell.
These stem cells
- 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 surface protein designated CD34;
- produce, by mitosis, two kinds of progeny:
- more stem cells
- cells that begin to differentiate along the paths leading to the
various kinds of blood cells.
Which path is taken is regulated by
- the need for more of that type of blood cell which is, in turn,
controlled by appropriate
cytokines and/or hormones.
Examples:
- Interleukin-7 (IL-7) is the major cytokine in
stimulating bone marrow stem cells to start down the path leading to the
various lymphocytes (mostly
B cells and
T cells).
-
Erythropoietin (EPO), produced by the kidneys, enhances the
production of red blood cells (RBCs).
-
Thrombopoietin (TPO), assisted by Interleukin-11 (IL-11),
stimulates the production of megakaryocytes. Their fragmentation
produces platelets.
- Granulocyte-monocyte 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
eosinophils.
- 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, the precursors of macrophages.
Red Blood Cells (erythrocytes)
 The most numerous type in the
blood.
- Women average about 4.8 million of these cells per cubic millimeter
(mm3; which is the same as a microliter [µl]) of blood).
- Men average about 5.4 x 106 per µl.
- 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 µl.)
As RBC precursors mature in the bone marrow,
- they manufacture hemoglobin until it accounts for some 90% of the dry
weight of the cell.
- The nucleus is squeezed out of the cell. Nearby macrophages ingest the
extruded nuclei and break down their DNA.
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.
The hemoglobin (Hb) molecule
- consists of four polypeptides.
- Each of these is attached the
prosthetic group heme.
- There is one atom of iron at the center of each heme.
- One molecule of oxygen can bind to each heme.
 The reaction is
reversible.
- 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 Transport
Carbon dioxide (CO2) combines with water
forming carbonic acid, which dissociates into a hydrogen ion (H+)
and a
bicarbonate ions:
CO2 + H2O ↔ H2CO3 ↔ H+
+ HCO3−
95% of the CO2 generated in the tissues is carried in the red
blood cells:
- About one-half of this 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
- RBCs and/or
- the amount of hemoglobin in them.
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.
White Blood Cells (leukocytes)
White blood cells
- are much less numerous than red (the ratio between the two is around
1:700),
- 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 with granules.
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
-
B 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 where they mature. Both B cells and T cells also take up
residence in lymph nodes, the spleen and other tissues where they
- encounter antigens;
- continue to divide by mitosis;
- mature into fully functional cells.
Monocytes leave the blood and become macrophages.
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.
However,
- heavy doses of radiation
- chemotherapy
- and many other forms of stress
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 (0–450/µl).
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.
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 as:
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 from megakaryocytes.
Blood normally contains 140,000 to 440,000 per microliter (µl) or cubic
millimeter (mm3). This number is normally maintained by a
homeostatic (negative-feedback) mechanism
If this value should drop much below 50,000/µl, there is a danger of
uncontrolled bleeding because of the essential role that platelets have in
blood clotting.
Some causes:
- certain drugs and herbal remedies;
- autoimmunity.
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.
Plasma is the straw-colored liquid in which the blood cells are
suspended.
Composition of blood plasma
| Component |
Percent |
| Water |
~92 |
| Proteins |
6–8 |
| Salts |
0.8 |
| Lipids |
0.6 |
| Glucose (blood sugar) |
0.1 |
Plasma transports materials needed by cells and materials that must be
removed from cells:
- various ions (Na+, Ca2+, HCO3−,
etc.
- glucose and traces of other sugars
- amino acids
- other organic acids
- cholesterol and other lipids
- hormones
- urea and other wastes
Most of these materials are in transit from a place where they are added
to the blood (a "source")
- exchange organs like the intestine
- depots of materials like the liver
to places ("sinks") where they will be removed from the blood.
- every cell
- exchange organs like the kidney, and skin.
Proteins make up 6–8% 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
solution.
- 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
electrode.
- 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 and
retinol [vitamin A])
- beta globulins (e.g., the iron-transporting protein
transferrin)
- 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 immunizations.
If an antibody-secreting cell — called a
plasma cell — becomes cancerous, it grows into a
clone 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
IgG
myeloma protein;
- serum from a patient with Waldenström'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.
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.
| LIPID |
Typical values (mg/dl) |
Desirable (mg/dl) |
| Cholesterol (total) |
170–210 |
<200 |
| LDL cholesterol |
60–140 |
<130 |
| HDL cholesterol |
35–85 |
>40 |
| Triglycerides |
40–150 |
<135 |
- 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.
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