BLOOD
Blood is a connective tissue. It
provides one of the means of communication between the cells of different parts
of the body and the external environment, e.g. it carries:
• Oxygen from the lungs to the
tissues and carbon dioxide from the tissues to the lungs for excretion
• Nutrients from the alimentary
tract to the tissues and cell wastes to the excretory organs, principally the
kidneys
• Hormones secreted by endocrine
glands to their target glands and tissues
• Heat produced in active tissues to
other less active tissues
• Protective substances, e.g.
antibodies, to areas of infection
• clotting factors that coagulate
blood, minimising its loss from ruptured blood vessels.
Blood makes up about 7% of body
weight (about 5.6 litres in a 70 kg man). This proportion is less in women and
considerably greater in children, gradually decreasing until the adult level is
reached.
Blood in the blood vessels is always
in motion. The continual flow maintains a fairly constant environment
For the body cells. Blood volume and
the concentration of its many constituents are kept within narrow limits by
homeostatic mechanisms.
CHARACTERISTICS OF BLOOD
Blood
has distinctive physical characteristics:
Amount—a
person has 4 to 6 litters of blood, depending on his or her size. Of the total
blood volume in the human body, 38% to 48% is composed of the various blood
cells, also called formed elements. The remaining 52% to 62% of the blood
volume is plasma, the liquid portion of blood.
Colour—you’re
probably saying to yourself, “Of course, it’s red!” Mention is made of this
obvious fact, however, because the color does vary. Arterial blood is bright
red because it contains high levels of oxygen. Venous blood has given up much
of its oxygen in tissues, and has a darker, dull red color. This may be
important in the assessment of the source of bleeding. If blood is bright red,
it is probably from a severed artery, and dark red blood is probably venous
blood.
pH—the
normal pH range of blood is 7.35 to 7.45, which is slightly alkaline. Venous
blood normally has a lower pH than does arterial blood because of the presence
of more carbon dioxide.
Viscosity—this
means thickness or resistance to flow. Blood is about three to five times
thicker than water. Viscosity is increased by the presence of blood cells and
the plasma proteins, and this thickness contributes to normal blood pressure.
COMPOSITION OF BLOOD
Blood is composed of a straw-coloured
transparent fluid, plasma, in which different types of cells are suspended. Plasma
constitutes about 55% and cells about 45% of blood volume.
A.
The proportions of blood cells and plasma in
whole blood separated by gravity. B. A blood clot in serum.
Plasma
The constituents of plasma are water (90
to 92%) and dissolved substances, including:
• Plasma proteins: albumins, globulins
(including antibodies), fibrinogen, clotting factors
• Inorganic salts (mineral salts):
sodium chloride, sodium bicarbonate, potassium, magnesium, phosphate, iron,
calcium, copper, iodine, cobalt
• Nutrients, principally from digested
foods, e.g. monosaccharides (mainly glucose), amino acids, fatty acids,
glycerol and vitamins
• Organic waste materials, e.g. urea,
uric acid, creatinine
• Hormones
• Enzymes, e.g. certain clotting factors
• Gases, e.g. oxygen, carbon dioxide, nitrogen.
Plasma proteins
Plasma proteins, which make up about 7%
of plasma, are normally retained within the blood, because they are too big to
escape through the capillary pores into the tissues. They are largely responsible
for creating the osmotic pressure of blood (normally 25 mmHg or 3.3 kPa*),
which keeps plasma fluid within the circulation. If plasma protein levels fall,
because of either reduced production or loss from the blood vessels, osmotic
pressure is also reduced, and fluid moves into the tissues (oedema) and body
cavities.
Albumins. These are
formed in the liver. They are the most abundant plasma proteins and their main
function is to maintain a normal plasma osmotic pressure. Albumins also act as
carrier molecules for lipids and steroid hormones.
Globulins. Most are
formed in the liver and the remainder in lymphoid tissue. Their main functions
are:
• As antibodies (immunoglobulins), which
are complex proteins produced by lymphocytes that play an important part in
immunity. They bind to, and neutralise, foreign materials (antigens) such as micro-organisms.
• Transportation of some hormones and
mineral salts; e.g. thyroglobulin carries the hormone thyroxine and transferrin
carries the mineral iron
• Inhibition of some proteolytic enzymes,
e.g. macroglobulin inhibits trypsin activity.
Clotting factors. These are substances essential for
coagulation of blood. Serum is plasma from which clotting factors have been
removed. Fibrinogen. This is synthesised in the liver and is essential for
blood coagulation. Plasma viscosity (thickness) is due to plasma proteins, mainly
albumin and fibrinogen. Viscosity is used as a measure of the body's response
to some diseases.
Inorganic salts (mineral salts)
These are involved in a wide variety of
activities, including cell formation, contraction of muscles, transmission of
nerve impulses, formation of secretions and maintenance of the balance between
acids and alkalis. In health the blood is slightly alkaline. Alkalinity and
acidity are expressed in terms of pH, which is a measure of hydrogen ion
concentration, or [H+] (p. 21 and Fig. 2.6).
The pH of blood is maintained between
7.35 and 7.45 by an ongoing complicated series of chemical activities, involving
buffering systems.
Nutrients
Food is digested in the alimentary tract
and the resultant nutrients are absorbed, e.g. monosaccharides, amino acids,
fatty acids, glycerol and vitamins. Together with mineral salts they are required
by all body cells to provide energy, heat, materials for repair and replacement,
and for the synthesis of other blood components and body secretions.
Organic waste products
Urea, creatinine and uric acid are the
waste products of protein metabolism. They are formed in the liver and conveyed
in blood to the kidneys for excretion. Carbon dioxide, released by all cells,
is conveyed to the lungs for excretion.
Hormones
These are chemical compounds synthesised
by endocrine glands. Hormones pass directly from the cells of the glands into
the blood which transports them to their target tissues and organs elsewhere in
the body, where they influence cellular activity.
Gases
Oxygen, carbon dioxide and nitrogen are
transported round the body in solution in plasma. Oxygen and carbon dioxide are
also transported in combination with haemoglobin in red blood cells. Most
oxygen is carried in combination with haemoglobin and most carbon dioxide as
bicarbonate ions dissolved in plasma. Atmospheric nitrogen enters the body in
the same way as other gases and is present in plasma but it has no
physiological function.
BLOOD CELLS
There are three kinds of blood cells: red blood
cells, white blood cells, and platelets. Blood cells are produced from stem
cells in hemopoietic tissue. After birth this is primarily the red bone marrow,
found in flat and irregular bones such as the sternum, hip bone, and vertebrae.
Lymphocytes mature and divide in lymphatic tissue, found in the spleen, lymph
nodes, and thymus gland. The thymus contains stem cells that produce T
lymphocytes, and the stem cells in other lymphatic tissue also produce
lymphocytes.
RED BLOOD CELLS
Also called erythrocytes, red blood cells
(RBCs) are biconcave discs, which means their centers are thinner than their
edges. You may recall from Chapter 3 that red blood cells are the only human
cells without nuclei. Their nuclei disintegrate as the red blood cells mature
and are not needed for normal functioning. A normal RBC count ranges from 4.5
to 6.0 million cells per microliter (L) of blood (1 microliter 1 mm3 one millionth
of a litter, a very small volume). RBC counts for men are often toward the high
end of this range; those for women are often toward the low end. Another way to
measure the amount of RBCs is the hematocrit. This test involves drawing blood
into a thin glass tube called a capillary tube, and centrifuging the tube to
force all the cells to one end. The percentages of cells and plasma can then be
determined. Because RBCs are by far the most abundant of the blood cells, a
normal hematocrit range is just like that of the total blood cells: 38% to 48%.
Both RBC count and hematocrit (Hct) are part of a complete blood count (CBC).
Function
Red blood cells contain the protein haemoglobin
(Hb), which gives them the ability to carry oxygen. Each red blood cell contains
approximately 300 million haemoglobin molecules, each of which can bond to four
oxygen molecules (see Box Fig. 3–B). In the pulmonary capillaries, RBCs pick up
oxygen and oxyhaemoglobin is formed. In the systemic capillaries, haemoglobin
gives up much of its oxygen and becomes reduced haemoglobin. A determination of
haemoglobin level is also part of a CBC; the normal range is 12 to 18 grams per
100 mL of blood. Essential to the formation of haemoglobin is the mineral iron;
there are four atoms of iron in each molecule of haemoglobin. It is the iron
that actually bonds to the oxygen and also makes RBCs red. Haemoglobin is also
able to bond to carbon dioxide (CO2), and does transport some CO2 from the
tissues to the lungs. But haemoglobin accounts for only about 10% of total CO2
transport (most is carried in the plasma as bicarbonate ions).
Production and Maturation
Red blood cells are formed in red bone marrow
(RBM) in flat and irregular bones. Within red bone marrow are precursor cells
called stem cells. That stem cells are unspecialized cells that may develop, or
differentiate, in several ways. The stem cells of the red bone marrow may also
be called hemocytoblasts, and they constantly undergo mitosis to produce all
the kinds of blood cells, many of which are RBCs. The rate of production is
very rapid (estimated at several million new RBCs per second), and a major
regulating factor is oxygen. If the body is in a state of hypoxia, or lack of
oxygen, the kidneys produce a hormone called erythropoietin, which stimulates
the red bone marrow to increase the rate of RBC production (that is, the rate
of stem cell mitosis). This will occur following haemorrhage or if a person
stays for a time at a higher altitude. As a result of the action of
erythropoietin, more RBCs will be available to carry oxygen and correct the
hypoxic state. The stem cells that will become RBCs go through a number of
developmental stages, only the last two of which we will mention (see Fig.
11–2). The normoblast is the last stage with a nucleus, which then
disintegrates. The reticulocyte has fragments of the endoplasmic reticulum,
which are visible when blood smears are stained for microscopic evaluation.
These immature cells are usually found in the red bone marrow, although a small
number of reticulocytes in the peripheral circulation is considered normal (up
to 1.5% of the total RBCs). Large numbers of reticulocytes or normoblasts in
the circulating blood mean that the number of mature RBCs is not sufficient to
carry the oxygen needed by the body. Such situations include hemorrhage, or
when mature RBCs have been destroyed, as in Rh disease of the new-born, and
malaria. The maturation of red blood cells requires many nutrients. Protein and
iron are necessary for the synthesis of haemoglobin and become part of haemoglobin
molecules. Copper is part of some enzymes involved in haemoglobin synthesis.
The vitamins folic acid and B12 are required for DNA synthesis in the stem
cells of the red bone marrow. As these cells undergo mitosis, they must continually
produce new sets of chromosomes. Vitamin B12 is also called the extrinsic
factor because its source is external, our food. Parietal cells of the stomach
lining produce the intrinsic factor, a chemical that combines with the vitamin
B12 in food to prevent its digestion and promote its absorption in the small
intestine. A deficiency of either vitamin B12 or the intrinsic factor results
in pernicious anaemia
Blood Types
Our blood types are genetic; that is, we
inherit genes from our parents that determine our own types. There are many red
blood cell factors or types; we will discuss the two most important ones: the
ABO group and the Rh factor. The ABO group contains four blood types: A, B, AB,
and O. The letters A and B represent antigens (protein-oligosaccharides) on the
red blood cell membrane. A person with type A blood has the A antigen on the
RBCs, and someone with type B blood has the B antigen. Type AB means that both
A and B antigens are present, and type O means that neither the A nor the B antigen
is present. Circulating in the plasma of each person are natural antibodies for
those antigens not present on the RBCs. Therefore, a type A person has anti-B
antibodies in the plasma; a type B person has anti-A antibodies; a type AB
person has neither anti-A nor anti-B antibodies; and a type O person has both
anti-A and anti-B antibodies. These natural antibodies are of great importance
for transfusions. If possible, a person should receive blood of his or her own
type; only if this type is not available should another type be given. For
example, let us say that a type A person needs a transfusion to replace blood
lost in hemorrhage. If this person were to receive type B blood, what would
happen? The type A recipient has anti-B antibodies that would bind to the type
B antigens of the RBCs of the donated blood. The type B RBCs would first clump
(agglutination) then rupture (hemolysis), thus defeating the purpose of the
transfusion. An even more serious consequence is that the haemoglobin of the
ruptured RBCs, now called free haemoglobin, may clog the capillaries of the
kidneys and lead to renal damage or renal failureThis procedure helps ensure
that donated blood will not bring about a hemolytic transfusion reaction in the
recipient. You may have heard of the concept that a person with type O blood is
a “universal donor.” Usually, a unit of type O negative blood may be given to
people with any other blood type. This is so because type O RBCs have neither
the A nor the B antigens and will not react with whatever antibodies the
recipient may have. If only one unit (1 pint) of blood is given, the anti-A and
anti-B antibodies in the type O blood plasma will be diluted in the recipient’s
blood plasma and will not have a harmful effect on the recipient’s RBCs. The
term negative, in O negative, the universal donor, refers to the Rh factor,
which we will now consider. The Rh factor is another antigen (often called D)
that may be present on RBCs. People whose RBCs have the Rh antigen are Rh
positive; those without the antigen are Rh negative. Rh-negative people do not
have natural antibodies to the Rh antigen, and for them this antigen is
foreign. If an Rh-negative person receives Rh-positive blood by mistake,
antibodies will be formed just as they would be to bacteria or viruses. A first
mistaken transfusion often does not cause problems, because antibody production
is slow upon the first exposure to Rh-positive RBCs. A second transfusion,
however, when anti-Rh antibodies are already present, will bring about a transfusion
reaction, with hemolysis and possible kidney damage.
White blood cells (WBCs) are also called leukocytes. There
are five kinds of WBCs; all are larger than RBCs and have nuclei when mature.
The nucleus may be in one piece or appear as several lobes or segments. Special
staining for microscopic examination gives each kind of WBC a distinctive
appearance.
A normal WBC count (part of a CBC) is 5,000 to 10,000 per
_L. Notice that this number is quite small compared to a normal RBC count. Many
of our WBCs are not circulating within blood vessels but are carrying out their
functions in tissue fluid or in lymphatic tissue.
Classification
A differential WBC count (part of a CBC) is the
percentage of each kind of leukocyte, along with other normal values of a CBC.
Functions
White
blood cells all contribute to the same general function, which is to protect
the body from infectious disease and to provide immunity to certain diseases.
Each kind of leukocyte makes a contribution to this very important aspect of
homeostasis. Neutrophils and monocytes are capable of the phagocytosis of
pathogens. Neutrophils are the more abundant phagocytes, but the monocytes are
the more efficient phagocytes, because they differentiate into macrophages,
which also phagocytize dead or damaged tissue at the site of any injury,
helping to make tissue repair possible. During an infection, neutrophils are
produced more rapidly, and the immature forms, called band cells may appear in
greater numbers in peripheral circulation (band cells are usually less than 10%
of the total neutrophils). The term “band” refers to the nucleus that has not
yet become segmented, and may look somewhat like a dumbbell. Eosinophils are
believed to detoxify foreign proteins and will phagocytize anything labelled
with antibodies. This is especially important in allergic reactions and
parasitic infections such as trichinosis (a worm parasite). Basophils contain
granules of heparin and histamine. Heparin is an anticoagulant that helps
prevent abnormal clotting within blood vessels. Histamine, you may recall, is
released as part of the inflammation process, and it makes capillaries more
permeable, allowing tissue fluid, proteins, and white blood cells to accumulate
in the damaged area. There are two major kinds of lymphocytes, T cells and B
cells, and a less numerous third kind called natural killer cells. For now we
will say that T cells (or T lymphocytes) help recognize foreign antigens and
may directly destroy some foreign antigens. B cells (or B lymphocytes) become
plasma cells that produce antibodies to foreign antigens. Both T cells and B
cells provide memory for immunity. Natural killer cells (NK cells) destroy
foreign cells by chemically rupturing their membranes. As mentioned earlier,
leukocytes function in tissue fluid as well as in the blood. Many WBCs are
capable of self-locomotion (ameboid movement) and are able to squeeze between
the cells of capillary walls and out into tissue spaces. Macrophages provide a
good example of the dual locations of leukocytes. Some macrophages are “fixed,”
that is, stationary in organs such as the liver, spleen, and red bone marrow
(part of the tissue macrophage or RE system—the same macrophages that
phagocytize old RBCs) and in the lymph nodes. They phagocytize pathogens that
circulate in blood or lymph through these organs. Other “wandering” macrophages
move about in tissue fluid, especially in the areolar connective tissue of
mucous membranes and below the skin. Pathogens that gain entry into the body
through natural openings or through breaks in the skin are usually destroyed by
the
Macrophages
and other leukocytes in connective tissue before they can cause serious
disease. The alveoli of the lungs, for example, have macrophages that very
efficiently destroy pathogens that enter with inhaled air. A high WBC count,
called leucocytosis, is often an indication of infection. Leukopenia is a low
WBC count, which may be present in the early stages of diseases such as
tuberculosis. Exposure to radiation or to chemicals such as benzene may destroy
WBCs and lower the total count. Such a person is then very susceptible to
infection. Leukaemia, or malignancy of leukocyte-forming tissues,
PLATELETS
The more formal name for platelets is
thrombocytes, which are not whole cells but rather fragments or pieces of
cells. Some of the stem cells in the red bone marrow differentiate into large
cells called megakaryocytes, which break up into small pieces that enter
circulation. These small, oval, circulating pieces are platelets, which may
last for 5 to 9 days, if not utilized before that. Thrombopoietin is a hormone
produced by the liver that increases the rate of platelet production. A normal
platelet count (part of a CBC) is 150,000 to 300,000 (the high end of the range
may be extended to 500,000). Thrombocytopenia is the term for a low platelet
count.
Function
Platelets
are necessary for haemostasis, which means prevention of blood loss. There are
three mechanisms, and platelets are involved in each. Two of these mechanisms
1.
Vascular spasm— when a large vessel such as an artery or vein is severed, the
smooth muscle in its wall contracts in response to the damage (called the myogenic
response). Platelets in the area of the rupture release serotonin, which also
brings about vasoconstriction. The diameter of the vessel is thereby made
smaller, and the smaller opening may then be blocked by a blood clot. If the
vessel did not constrict first, the clot that forms would quickly be washed out
by the force of the blood pressure.
2.
Platelet plugs—when capillaries rupture, the damage is too slight to initiate
the formation of a blood clot. The rough surface, however, causes platelets to
change shape (become spiky) and become sticky. These activated platelets stick
to the edges of the break and to each other. The platelets form a mechanical
barrier or wall to close off the break in the capillary. Capillary ruptures are
quite frequent, and platelet plugs, although small, are all that is needed to
seal them. Would platelet plugs be effective for breaks in larger vessels? No,
they are too small, and though they do form, they are washed away (until a clot
begins to form that can contain them). Would vascular spasm be effective for
capillaries? Again, the answer is no, because capillaries have no smooth muscle
and cannot constrict at all.
3.
Chemical clotting—The stimulus for clotting is a rough surface within a vessel,
or a break in the vessel, which also creates a rough surface. The more damage
there is, the faster clotting begins, usually within 15 to 120 seconds. The
clotting mechanism is a series of reactions involving chemicals that normally
circulate in the blood and others that are released when a vessel is damaged.
The chemicals involved in clotting include platelet factors, chemicals released
by damaged tissues, calcium ions, and the plasma proteins prothrombin,
fibrinogen, Factor 8, and others synthesized by the liver. (These clotting factors
are also designated by Roman numerals; Factor 8 would be Factor VIII.) Vitamin
K is necessary for the liver to synthesize prothrombin and several other
clotting factors (Factors 7, 9, and 10). Most of our vitamin K is produced by
the bacteria that live in the colon; the vitamin is absorbed as the colon
absorbs water and may be stored in the liver. Chemical clotting is usually
described in three stages, which are listed in. Stage 1 begins when a vessel is
cut or damaged internally, and includes all of the factors shown. As you follow
the pathway, notice that the product of stage 1 is prothrombin activator, which
may also be called prothrombinase. Each name tells us something. The first name
suggests that this chemical activates prothrombin, and that is true. The second
name ends in “as,” which indicates that this is an enzyme. The traditional
names for enzymes use the substrate of the enzyme as the first part of the
name, and add “ase.” So this chemical must be an enzyme whose substrate is
prothrombin, and that is also true. The stages of clotting may be called a
cascade, where one leads to the next, as inevitable as water flowing downhill.
Prothrombin activator, the product of stage 1, brings about the stage 2
reaction: converting prothrombin to thrombin. The product of stage 2, thrombin,
brings about the stage 3 reaction: converting fibrinogen to fibrin. The clot
itself is made of fibrin, the product of stage 3. Fibrin is a thread-like
protein. Many strands of fibrin form a mesh that traps RBCs and platelets, and
creates a wall across the break in the vessel. Once the clot has formed and
bleeding has stopped, clot retraction and fibrinolysis occur. Clot retraction
requires platelets, ATP, and Factor 13 and involves folding of the fibrin
threads to pull the edges of the rupture in the vessel wall closer together.
This will make the area to be repaired smaller. The platelets contribute in yet
another way, because as they disintegrate they release platelet-derived growth
factor (PDGF), which stimulates the repair of blood vessels (growth of their
tissues). As repair begins, the clot is dissolved, a process called
fibrinolysis. It is important that the clot be dissolved, because it is a rough
surface, and if it were inside a vessel it would stimulate more and unnecessary
clotting, which might eventually obstruct blood flow.
Prevention of Abnormal Clotting
Clotting should take place to stop bleeding, but too much
clotting would obstruct vessels and interfere with normal circulation
of blood. Clots do not usually form in intact vessels because the endothelium
(simple squamous epithelial lining) is very smooth and repels the platelets and
clotting factors. If the lining becomes roughened, as happens with the lipid
deposits of atherosclerosis, a clot will form. Heparin, produced by basophils,
is a natural anticoagulant that inhibits the clotting process (although heparin
is called a “blood thinner,” it does not “thin” or dilute the blood in any way;
rather it prevents a chemical reaction from taking place). The liver produces a
globulin called antithrombin, which combines with and inactivates excess
thrombin. Excess thrombin would exert a positive feedback effect on the
clotting cascade, and result in the splitting of more prothrombin to thrombin,
more clotting, more thrombin formed, and so on. Antithrombin helps to prevent
this, as does the fibrin of the clot, which adsorbs excess thrombin and renders
it inactive. All of these factors are the external brake for this positive
feedback mechanism. Together they usually limit the fibrin formed to what is
needed to create a useful clot but not an obstructive one. Thrombosis refers to
clotting in an intact vessel; the clot itself is called a thrombus. Coronary
thrombosis, for example, is abnormal clotting in a coronary artery, which will
decrease the blood (oxygen) supply to part of the heart muscle. An embolism is
a clot or other tissue transported from elsewhere that lodges in and obstructs
a vessel.
