BLOOD

FUNCTIONS OF BLOOD

The scientific study of blood reveals characteristics as fascinating as any of these fantasies. Blood performs
many functions essential to life and can reveal much about our health. The heart pumps blood through blood vessels
that extend throughout the body. Blood helps maintain homeostasis in several ways: 

1. Transport of gases, nutrients, and waste products. Oxygen centers the blood in the lungs and is carried
to cells. Carbon dioxide, produced by cells, is carried in the blood to the lungs, from which it is expelled.
The blood transports ingested nutrients, ions, and water from the digestive tract to cells, and the blood
transports the waste products of the cells to the kidneys for elimination. 

2. Transport of processed molecules. Many substances are produced in one part of the body and
transported in the blood to another part, where they are modified. For example, the precursor to
vitamin D is produced in the skin and transported by the blood to the liver and then to the kidneys for
processing into active vitamin D. Then the blood transports active vitamin D to the small intestine, where
it promotes the uptake of calcium. Another example is lactate produced by skeletal muscles during
anaerobic respiration. The blood carries lactate to the liver, where it is converted into glucose. 

3. Transport of regulatory molecules. The blood carries many of the hormones and enzymes that regulate
body processes from one part of the body to another. 

4. Regulation of pH and osmosis. Buffers, which help keep the blood’s pH within its normal limits of 7.35–
7.45, are found in the blood. The osmotic composition of blood is also critical for maintaining normal
fluid and ion balance. 

5. Maintenance of body temperature. Warm blood is transported from the interior of the body to the
surface, where heat is released from the blood. This is one of the mechanisms that helps regulate body
temperature. 

6. Protection against foreign substances. Certain cells and chemicals in the blood constitute an important
part of the immune system, protecting against foreign substances, such as microorganisms and toxins. 

7. Clot formation. When blood vessels are damaged, blood clotting protects against excessive blood loss.
When tissues are damaged, the blood clot that forms are also the first step in tissue repair and the
restoration of normal function.

COMPOSITION OF BLOOD 

Blood is a type of connective tissue that consists of a liquid matrix containing cells and cell fragments. The
liquid matrix is the plasma, and the cells and cell fragments are the formed elements. The plasma accounts for
slightly more than half of the total blood volume, and the formed elements account for slightly less than half. The
total blood volume in the average adult is about 4–5 liters (L) in females and 5–6 L in males. Blood makes up about
8% of total body weight. 

PLASMA 

Plasma is a pale-yellow fluid that consists of about 91% water, 7% proteins, and 2% other components, such
as ions, nutrients, gases, waste products, and regulatory substances. Unlike the fibrous proteins found in other
connective tissues, such as loose connective tissue, plasma contains dissolved proteins. Plasma proteins include
albumin, globulins, and fibrinogen. Albumin makes up 58% of the plasma proteins. Although the osmotic pressure of
blood results primarily from sodium chloride, albumin also makes an important contribution. The water balance
between the blood and the tissues is determined by the movement of water into and out of the blood by osmosis.
Globulins account for 38% of the plasma proteins. Some globulins, such as antibodies and complement, are part of
the immune system. Other globulins and albumin function as transport molecules because they bind to molecules,
such as hormones, and carry them in the blood throughout the body. Some globulins are clotting factors, which are
necessary for the formation of blood clots. Fibrinogen is a clotting factor that constitutes 4% of plasma proteins.
Activation of clotting factors results in the conversion of fibrinogen to fibrin, a threadlike protein that forms blood
clots. Serum is plasma without the clotting factors. 

Plasma volume and composition remains relatively constant. Normally, water intake through the digestive
tract closely matches water loss through the kidneys, lungs, digestive tract, and skin. Oxygen enters the blood in the
lungs, and carbon dioxide enters the blood from tissues. Other suspended or dissolved substances in the blood come
from the liver, kidneys, intestines, endocrine glands, and immune tissues, such as the lymph nodes and spleen. The
concentration of these substances in the blood is also regulated and maintained within narrow limits. 

Formed Elements 

About 95% of the volume of the formed elements consists of red blood cells (RBCs), or erythrocytes. The remaining
5% of the volume of the formed elements consists of white blood cells (WBCs), or leukocytes, and cell fragments
called platelets, or thrombocytes. Red blood cells are 700 times more numerous than white blood cells and 17 times
more numerous than platelets. Table 11.2 illustrates the formed elements of the blood. 

Production of Formed Elements 

The process of blood cell production is called hematopoiesis. In the fetus, hematopoiesis occurs in several
tissues, including the liver, thymus, spleen, lymph nodes, and red bone marrow. After birth, hematopoiesis is
confined primarily to red bone marrow, but some white blood cells are produced in lymphatic tissues. 

All the formed elements of blood are derived from a single population of cells called stem cells, or
hemocytoblasts. These stem cells differentiate to give rise to different cell lines, each of which ends with the
formation of a particular type of formed element. The development of each cell line is regulated by specific growth
factors. That is, growth factors determine the types of formed elements derived from the stem cells and how many
formed elements are produced. 

Red Blood Cells 

Normal red blood cells are disk-shaped, with edges that are thicker than the center of the cell. The biconcave
shape increases the cell’s surface area compared to a flat disk of the same size. The greater surface area makes it
easier for gases to move into and out of the red blood cell. In addition, the red blood cell can bend or fold around its
thin center, decreasing its size and enabling it to pass more easily through smaller blood vessels. 

During their development, red blood cells lose their nuclei and most of their organelles. Consequently, they are
unable to divide. Red blood cells live for about 120 days in males and 110 days in females. One-third of a red blood
cell’s volume is the pigmented protein hemoglobin, which is responsible for the cell’s red color. 

Function 

The primary functions of red blood cells are to transport oxygen from the lungs to the various tissues of the
body and to help transport carbon dioxide from the tissues to the lungs. Oxygen transport is accomplished by
hemoglobin, which consists of four protein chains and four heme groups. Each protein, called a globin, is bound to
one heme, a red-pigmented molecule. 

Each heme contains one iron atom, which is necessary for the normal function of hemoglobin. Each iron in a
heme molecule can reversibly bind to an oxygen molecule. Hemoglobin picks up oxygen in the lungs and releases
oxygen in other tissues. Hemoglobin that is bound to oxygen is bright red, whereas hemoglobin without
bound oxygen is a darker red. Hemoglobin is responsible for 98.5% of the oxygen transported in blood. The
remaining 1.5% is transported dissolved in plasma. 

Because iron is necessary for oxygen transport, it is not surprising that two-thirds of the body’s iron is found
in hemoglobin. Small amounts of iron are required in the diet to replace the small amounts lost in the urine and
feces, but otherwise the existing iron is recycled, as described later in this section. Women need more dietary iron
than men do because women lose iron as a result of menstruation. 
 Although oxygen is the primary molecule that binds to hemoglobin, other molecules can also bind to
hemoglobin. Carbon monoxide, a gas produced by the incomplete combustion of hydrocarbons, such as gasoline, is
one example. It binds to the iron in hemoglobin about 210 times more readily than does oxygen and does not tend
to unbind. As a result, the hemoglobin bound to carbon monoxide no longer transports oxygen. Nausea, headache,
unconsciousness, and death are possible consequences of prolonged exposure to carbon monoxide. 

Carbon dioxide is produced in tissues and transported in the blood to the lungs, where it is removed from
the blood. Carbon dioxide transport involves bicarbonate ions, hemoglobin, and plasma. Approximately 70% of the
carbon dioxide in blood is transported in the form of bicarbonate ions. The enzyme carbonic anhydrase found
primarily inside red blood cells, catalyzes a reaction that converts carbon dioxide (CO2) and water (H2O) into a
hydrogen ion (H+) and a bicarbonate ion (HCO3−):  CO2 + H2O < -- -- > H+ + HCO3− 

Carbon dioxide can bind reversibly to the globin part of hemoglobin. About 23% of the CO2 in blood is
transported bound to hemoglobin or other blood proteins. The remaining 7% of CO2 is transported dissolved in
plasma. 

Life History of Red Blood Cells 

Under normal conditions, about 2.5 million red blood cells are destroyed every second. Fortunately, new red
blood cells are produced just as rapidly. Stem cells form proerythroblasts, which give rise to the red blood cell line.
Red blood cell production involves a series of cell divisions. After each cell division, the new cells change and become
more like mature red blood cells. In the later divisions, the newly formed cells manufacture large amounts of
hemoglobin. After the final cell division, the cells lose their nuclei and become completely mature red blood cells. 

The process of cell division requires the B vitamins folate and B12, which are necessary for the synthesis of
DNA. Iron is required for the production of hemoglobin. Consequently, a lack of folate, vitamin B12, or iron can
interfere with normal red blood cell production. 

Red blood cell production is stimulated by low blood oxygen levels. Typical causes of low blood oxygen are
decreased numbers of red blood cells, decreased or defective hemoglobin, diseases of the lungs, high altitude,
inability of the cardiovascular system to deliver blood to tissues, and increased tissue demand for oxygen, as occurs
during endurance exercises.

Low blood oxygen levels stimulate red blood cell production by increasing the formation and release of the
glycoprotein erythropoietin, primarily by the kidneys. Erythropoietin stimulates red bone marrow to produce more
red blood cells. Thus, when oxygen levels in the blood decrease, the production of erythropoietin increases, which
increases red blood cell production. The greater number of red blood cells increases the blood’s ability to transport
oxygen. This negative-feedback mechanism increases the blood’s capacity to transport oxygen and maintains
homeostasis. Conversely, if blood oxygen levels rise, less erythropoietin is released, and red blood cell production
decreases. 

When red blood cells become old, abnormal, or damaged, they are removed from the blood by macrophages
located in the spleen and liver. Within the macrophage, the globin part of the hemoglobin molecule is broken down
into amino acids that are reused to produce other proteins. The iron released from heme is transported in the blood
to the red bone marrow and used to produce new hemoglobin. Thus, the iron is recycled. The heme molecules are
converted to bilirubin, a yellow pigment molecule. Bilirubin is normally taken up by the liver and released into the
small intestine as part of the bile. If the liver is not functioning normally, or if the flow of bile from the liver to the
small intestine is hindered, bilirubin builds up in the circulation and produces jaundice, a yellowish color to the skin.
After it enters the intestine, bilirubin is converted by bacteria into other pigments. 

Some of these pigments give feces their brown color, whereas others are absorbed from the intestine into
the blood, modified by the kidneys, and excreted in the urine, contributing to the characteristic yellow color of
urine. 

White Blood Cells 

White blood cells are spherical cells that lack hemoglobin. When the components of blood are separated
from one another, white blood cells as well as platelets make up the buffy coat, a thin, white layer of cells between
plasma and red blood cells. White blood cells are larger than red blood cells, and each has a nucleus. Although white
blood cells are components of the blood, the blood serves primarily as a means of transporting these cells to other
body tissues. White blood cells can leave the blood and travel by ameboid movement through the tissues. In this
process, the cell projects a cytoplasmic extension that attaches to an object. Then the rest of the cell’s cytoplasm
flows into the extension. Two functions of white blood cells are (1) to protect the body against invading
microorganisms and other pathogens and (2) to remove dead cells and debris from the tissues by phagocytosis. 

Each white blood cell type is named according to its appearance in stained preparations. Those containing
large cytoplasmic granules are granulocytes, and those with very small granules that cannot be seen easily with the
light microscope are agranulocytes. 

There are three kinds of granulocytes: neutrophils, basophils, and eosinophils. Neutrophils, the most
common type of white blood cells, have small cytoplasmic granules that stain with both acidic and basic dyes. Their
nuclei are commonly lobed, with the number of lobes varying from two to four. Neutrophils usually remain in the
blood for a short time (10–12 hours), move into other tissues, and phagocytize microorganisms and other foreign
substances. Dead neutrophils, cell debris, and fluid can accumulate as pus at sites of infections. 

Basophils, the least common of all white blood cells, contain large cytoplasmic granules that stain blue or
purple with basic dyes. Basophils release histamine and other chemicals that promote inflammation. They also
release heparin, which prevents the formation of clots. 

Eosinophils contain cytoplasmic granules that stain bright red with eosin, an acidic stain. They often have a
two-lobed nucleus. Eosinophils are involved in inflammatory responses associated with allergies and asthma. In
addition, chemicals from eosinophils are involved in destroying certain worm parasites. 

There are two kinds of agranulocytes: lymphocytes and monocytes. Lymphocytes are the smallest of the
white blood cells. The lymphocytic cytoplasm consists of only a thin, sometimes imperceptible ring around the
nucleus. There are several types of lymphocytes, and they play an important role in the body’s immune response.
Their diverse activities involve the production of antibodies and other chemicals that destroy microorganisms,
contribute to allergic reactions, reject grafts, control tumors, and regulate the immune system. 

Monocytes are the largest of the white blood cells. After they leave the blood and enter tissues, monocytes
enlarge and become macrophages, which phagocytize bacteria, dead cells, cell fragments, and any other debris
within the tissues. In addition, macrophages can break down phagocytized foreign substances and present the
processed substances to lymphocytes, causing activation of the lymphocytes. 

Platelets 

Platelets are minute fragments of cells, each consisting of a small amount of cytoplasm surrounded by a cell
membrane. They are produced in the red bone marrow from megakaryocytes, which are large cells. Small fragments
of these cells break off and enter the blood as platelets, which play an important role in preventing blood loss. 

BLOOD LOSS 

When a blood vessel is damaged, blood can leak into other tissues and interfere with normal tissue function,
or blood can be lost from the body. The body can tolerate a small amount of blood loss and can produce new blood
to replace it. But a large amount of blood loss can lead to death. Fortunately, when a blood vessel is damaged, loss
of blood is minimized by three processes: vascular spasm, platelet plug formation, and blood clotting.

Vascular Spasm 

Vascular spasm is an immediate but temporary constriction of a blood vessel that results when smooth
muscle within the wall of the vessel contracts. This constriction can close small vessels completely and stop the flow
of blood through them. Damage to blood vessels can activate nervous system reflexes that cause vascular spasm.
Chemicals also produce vascular spasm. For example, platelets release thromboxane which are derived from certain
prostaglandins, and endothelial (epithelial) cells lining blood vessels release the peptide endothelin. 
Platelet Plug Formation 

A platelet plug is an accumulation of platelets that can seal up a small break in a blood vessel. Platelet plug
formation is very important in maintaining the integrity of the blood vessels of the cardiovascular system because
small tears occur in the smaller vessels and capillaries many times each day. People who lack the normal number of
platelets tend to develop numerous small hemorrhages in their skin and internal organs. 

The formation of a platelet plug can be described as a series of steps, but in actuality many of these steps
occur at the same time. First, platelets stick to the collagen exposed by blood vessel damage; this phenomenon is
called platelet adhesion. Most platelet adhesion is mediated through von Willebrand factor, a protein produced and
secreted by blood vessel endothelial cells. Von Willebrand factor forms a bridge between collagen and platelets by
binding to platelet surface receptors and collagen. After platelets adhere to collagen, they become activated, change
shape, and release chemicals. 

In the platelet release reaction, platelets release chemicals, such as ADP and thromboxane, which bind to
their respective receptors on the surfaces of other platelets, activating the platelets. These activated platelets also
release ADP and thromboxane, which activates more platelets. Thus, a cascade of chemical release activates many
platelets. This is an example of positive feedback. As platelets become activated, they express surface receptors
called fibrinogen receptors, which can bind to fibrinogen, a plasma protein. In platelet aggregation, fibrinogen forms
bridges between the fibrinogen receptors of numerous platelets, resulting in a platelet plug 

Blood Clotting 

Blood vessel constriction and platelet plugs alone are not sufficient to close large tears or cuts in blood
vessels. When a blood vessel is severely damaged, blood clotting, or coagulation, results in the formation of a clot. A
clot is a network of threadlike protein fibers, called fibrin, that traps blood cells, platelets, and fluid. 

The formation of a blood clot depends on a number of proteins found within plasma, called clotting factors.
Though normally present in the plasma, the clotting factors are inactive and do not cause clotting. Following injury,
however, the clotting factors are activated. Clot formation is a complex process involving many chemical reactions,
but it can be summarized in three stages.

1. The chemical reactions can be started in two ways: Inactive clotting factors come in contact with exposed
connective tissue, resulting in their activation, or chemicals, such as thromboplastin, are released from
injured tissues, causing activation of clotting factors. After the initial clotting factors are activated, they in
turn activate other clotting factors. A series of reactions results in which each clotting factor activates the
next until the clotting factor prothrombinase, or prothrombin activator, is formed. 

2. Prothrombinase converts an inactive clotting factor called prothrombin to its active form, thrombin. 

3. Thrombin converts the plasma protein fibrinogen to fibrin. 

At each step of the clotting process, each clotting factor activates many additional clotting factors, resulting in the
formation of a clot 

Most clotting factors are manufactured in the liver, and many of them require vitamin K for their synthesis.
In addition, many of the chemical reactions of clot formation require Ca2+ and the chemicals released from platelets.
The clotting process can be severely impaired by low levels of vitamin K, low levels of Ca 2+, low numbers of platelets,
or reduced synthesis of clotting factors because of liver dysfunction. 

Humans rely on two sources of vitamin K. About half comes from the diet, and the other half comes from
bacteria within the large intestine. Antibiotics taken to fight bacterial infections sometimes kill these intestinal
bacteria, reducing vitamin K levels and causing bleeding problems. Vitamin K supplements may be necessary for
patients on prolonged antibiotic therapy. Newborns lack these intestinal bacteria and thus routinely receive a vita-
min K injection at birth. Infants can also obtain vitamin K from food, such as milk. Because cow’s milk contains more
vitamin K than does human milk, breast-fed infants are more susceptible to bleeding than are bottle-fed infants.
However, maternal supple 
mentation with vitamin K, such as with oral vitamins, adequately elevates breast-fed infant vitamin K levels and
decreases the risk of bleeding. 

Control of Clot Formation 

Without control, clotting would spread from the point of its initiation throughout the blood vessels.
Fortunately, the blood contains several anticoagulants, which prevent clotting factors from forming clots under
normal conditions. For example, antithrombin and heparin inactivate thrombin. Without thrombin, fibrinogen is not
converted to fibrin, and no clot forms. At an injury site, however, the activation of clotting factors is very rapid.
Enough clotting factors are activated that the anticoagulants can no longer prevent a clot from forming. Away from
the injury site, there are enough anticoagulants to prevent clot formation from spreading.

Clot Retraction and Fibrinolysis 

After a clot has formed, it begins to condense into a more compact structure through a process known as
clot retraction. Platelets contain the contractile proteins actin and myosin, which operate in a fashion similar to that
of the actin and myosin in muscle. Platelets form small extensions that attach to fibrin through surface receptors.
Contraction of the extensions pulls on the fibrin and leads to clot retraction. During clot retraction, serum, which is
plasma without the clotting factors, is squeezed out of the clot. 

Retraction of the clot pulls the edges of the damaged blood vessel together, helping stop the flow of blood,
reducing the prob-ability of infection, and enhancing healing. The vessel is repaired as fibroblasts move into the
damaged area and new connective tissue forms. In addition, epithelial cells around the wound divide and fill in the
torn area. 

Clots are dissolved by a process called fibrinolysis. An inactive plasma protein called plasminogen is
converted to its active form, plasmin. Thrombin, other clotting factors activated during clot formation, and tissue
plasminogen activator (t PA) released from surrounding tissues can stimulate the conversion of plasminogen to
plasmin. Over a few days, plasmin slowly breaks down the fibrin. 

A heart attack can result when a clot blocks blood vessels that supply the heart. One treatment for a heart
attack is to inject certain chemicals into the blood that activate plasmin. Unlike aspirin and anticoagulant therapies,
which are used to prevent heart attacks, plasmin activators quickly dissolve the clot and restore blood flow 

BLOOD GROUPING 

If large quantities of blood are lost during surgery or due to injury, a patient can go into shock and die unless
red blood cells are replaced to restore the blood’s oxygen-carrying capacity. In this event, either a transfusion or an
infusion is called for. A transfusion is the transfer of blood or blood components from one individual to another. An
infusion is the introduction of a fluid other than blood, such as a saline or glucose solution, into the blood. In many
cases, the return of blood volume to normal levels is all that is necessary to prevent shock. Eventually, the body
produces enough red blood cells to replace those that were lost. 

Early attempts to transfuse blood were often unsuccessful because they resulted in transfusion reactions,
characterized by clumping or rupture of blood cells and clotting within blood vessels. We now know that transfusion
reactions are caused by inter-actions between antigens and antibodies. In brief, the surfaces of red blood cells have
molecules called antigens, and the plasma includes proteins called antibodies. Antibodies are very specific, meaning
that each antibody can bind only to a certain antigen. When the antibodies in the plasma bind to the antigens on the
surface of the red blood cells, they form molecular bridges that connect the red blood cells together. As a result,
agglutination or clumping of the cells, occurs. The combination of the antibodies with the antigens can also initiate
reactions that cause hemolysis, or rupture of the red blood cells. The debris formed from the ruptured red blood
cells can cause severe tissue damage, particularly in the kidneys. Hemoglobin released from lysed red blood cells can
damage kidney tissue, reducing its blood-filtering ability. If the damage is extensive, the lack of kidney function could
result in death. 

The antigens on the surface of red blood cells have been categorized into blood groups. Although many
blood groups are recognized, the ABO and Rh blood groups are the most important when discussing transfusion
reactions. 
ABO Blood Group 

• The ABO blood group system is used to categorize human blood. In this blood group system, there are two
types of antigens that may appear on the surface of the red blood cells, type A antigen and type B antigen.
Type A blood has type A antigens, type B blood has type B antigens, and type AB blood has both types of
antigens. Type O blood has neither A nor B antigens. Antibodies against the antigens are usually present in
the plasma of blood. Plasma from type A blood contains anti-B antibodies, which act against type B antigens;
plasma from type B blood contains anti-A antibodies, which act against type A antigens. Type AB blood
plasma has neither type of antibody, and type O blood plasma has both anti-A and anti-B antibodies. 

• The ABO blood types do not exist in equal numbers. In caucasians in the United States, the distribution is
type O, 47%; type A, 41%; type B, 9%; and type AB, 3%. Among African-Americans, the distribution is type O,
46%; type A, 27%; type B, 20%; and type AB, 7%. 

• Normally, antibodies do not develop against an antigen unless the body is exposed to that antigen; however,
the anti-A and/or anti-B antibodies are present in the blood even without exposure to antigens on foreign
red blood cells. One possible explanation for the production of anti-A and/or anti-B antibodies is that type A
or B antigens on bacteria or food in the digestive tract stimulate the formation of antibodies against antigens
that are different from the body’s own antigens. In support of this explanation, anti-A and anti-B antibodies
are not found in the blood until about 2 months after birth. It is possible that an infant with type A blood
would produce anti-B antibodies against the B antigens on bacteria or food. Meanwhile, an infant with A
antigens would not produce antibodies against the A antigens on bacteria or food because mechanisms exist
in the body to prevent the production of antibodies that would react with the body’s own antigens. 

• When a blood transfusion is performed, the donor is the per-son who gives blood, and the recipient is the
person who receives it. Usually, a recipient can successfully receive blood from a donor as long as they both
have the same blood type. For example, a per-son with type A blood can receive blood from a person with
type A blood. No ABO transfusion reaction occurs because the recipient has no anti-A antibodies against the
type A antigen. On the other hand, if type A blood were donated to a person with type B blood, a transfusion
reaction would occur because the person with type B blood has anti-A antibodies against the type A antigen,
causing agglutination.

• Historically, people with type O blood have been called universal donors because they can usually give blood
to the other ABO blood types without causing an ABO transfusion reaction. Their red blood cells have no
ABO surface antigens and therefore do not react with the recipient’s anti-A or anti-B antibodies. For
example, if a person with type A blood receives type O blood, the type O red blood cells do not react with
the anti-B antibodies in the recipient’s blood. 

However, the term universal donor is misleading. Transfusion of type O blood can still produce a transfusion reaction
in one of two ways: First, mismatching blood groups other than the ABO blood group can cause a transfusion
reaction. To reduce the likelihood of a transfusion reaction, all the blood groups must be correctly matched. Second,
antibodies in the donor’s blood can react with antigens on the recipient’s red blood cells. For example, type O blood
has anti-A and anti-B antibodies. If type O blood is transfused into a person with type A blood, the anti-A antibodies
(in the type O donor blood) react against the A antigens (on the red blood cells in the type A recipient blood).
Usually, such reactions are not serious because the antibodies in the donor’s blood are diluted in the large volume of
the recipient’s blood. Even though such transfusion reactions seldom occur, type O blood is given to a person with
another blood type only in life-or-death situations 

Rh Blood Group 

Another important blood group is the Rh blood group, so named because it was first studied in the rhesus
monkey. People are Rh-positive if they have certain Rh antigens on the surface of their red blood cells, and they are
Rh-negative if they do not have these Rh antigens. About 85% of caucasians and 95% of African-Americans are Rh-
positive. The ABO blood type and the Rh blood type are usually expressed together. For example, a person
designated as type A in the ABO blood group and Rh-positive is said to be A positive. The rarest combination in the
United States is AB-negative, which occurs in less than 1% of the population. 
 Antibodies against the Rh antigens do not develop unless an Rh-negative person is exposed to Rh-positive
red blood cells. This can occur through a transfusion or by the transfer of blood across the placenta to a mother from
her fetus. When an Rh-negative person receives a transfusion of Rh-positive blood, the recipient becomes sensitized
to the Rh antigens and produces anti-Rh antibodies. If the Rh-negative person is unfortunate enough to receive a
second transfusion of Rh-positive blood after becoming sensitized, a transfusion reaction results. 

Rh incompatibility can pose a major problem in a pregnancy when the mother is Rh negative and the fetus is
Rh-positive. If fetal blood leaks through the placenta and mixes with the mother’s blood, the mother becomes
sensitized to the Rh antigen. The mother pro-duces anti-Rh antibodies that cross the placenta and cause
agglutination and hemolysis of fetal red blood cells. This disorder is called hemolytic disease of the newborn (HDN),
or erythroblastosis fetalis. In the mother’s first pregnancy, there is often no problem. The leakage of fetal blood is
usually the result of a tear in the placenta that takes place either late in the pregnancy or during delivery. Thus, there
is not sufficient time for the mother to produce enough anti-Rh anti-bodies to harm the fetus. In later pregnancies,
however, a problem can arise because the mother has been sensitized to the Rh antigen. Consequently, if the fetus is
Rh-positive and if any fetal blood leaks into the mother’s blood, she rapidly produces large amounts of anti-Rh
antibodies, which can cross the placenta to the fetus, resulting in HDN. Because HDN can be fatal to the fetus, the
levels of anti-Rh antibodies in the mother’s blood should be monitored. If they increase to unacceptable levels, the
fetus should be tested to determine the severity of the HDN. In severe cases, a transfusion to replace lost red blood
cells can be performed through the umbilical cord, or the baby can be delivered if mature enough. 

Prevention of HDN is often possible if the Rh-negative mother is injected with a specific preparation called
Rho(D) immune globulin (RhoGAM), which contains antibodies against Rh antigens. The injection can be given during
the pregnancy, before delivery, or immediately after each delivery, miscarriage, or abortion. The injected antibodies
bind to the Rh antigens of any fetal red blood cells that may have entered the mother’s blood. This treatment
inactivates the fetal Rh antigens and prevents sensitization of the mother. 

DIAGNOSTIC BLOOD TESTS 

Type and Crossmatch 

To prevent transfusion reactions, the blood must be typed. Blood typing determines the ABO and Rh blood
groups of a blood sample. Typically, the cells are separated from the serum and then tested with known antibodies
to determine the type of antigen on the cell surface. For example, if a patient’s blood cells agglutinate when mixed
with anti-A antibodies but do not agglutinate when mixed with anti-B antibodies, the cells have type A antigen. In a
similar fashion, the serum is mixed with known cell types (anti-gens) to determine the type of antibodies in the
serum. 

Normally, donor blood must match the ABO and Rh type of the recipient. However, because other blood
groups can cause a transfusion reaction, a crossmatch is performed. In a crossmatch, the donor’s blood cells are
mixed with the recipient’s serum, and the donor’s serum is mixed with the recipient’s cells. 

Complete Blood Count 

A complete blood count (CBC) is an analysis of blood that provides much useful information. A CBC consists
of a red blood cell count, hemoglobin and hematocrit measurements, and a white blood cell count.

Red Blood Count 

Blood cell counts are usually performed electronically with a machine, but they can also be done manually
with a microscope. A normal red blood count (RBC) for a male is 4.6– 6.2 million red blood cells per microliter (μL) of
blood; for a female, a nor-mal RBC count is 4.2–5.4 million per μL of blood. (A microliter is equivalent to 1 cubic
millimeter [mm3] or 10−6 L, and one drop of blood is approximately 50 μL). The condition called erythrocytosis is an
overabundance of red blood cells. 

Hemoglobin Measurement 

The amount of hemoglobin in a given volume of blood is usually expressed in terms of grams of hemoglobin
per 100 mL of blood. The normal hemoglobin measurement for a male is 14–18 grams(g) per 100 mL of blood, and
for a female 12–16 g per 100 mL of blood. An abnormally low hemoglobin measurement is an indication of anemia,
which is either a reduced number of red blood cells or a reduced amount of hemoglobin in each red blood cell. 

Hematocrit Measurement 

The percentage of the total blood volume that is composed of red blood cells is the hematocrit. One way to
determine hematocrit is to place blood in a capillary tube and spin it in a centrifuge. The formed elements, which are
heavier than the plasma, are forced to one end of the tube. Of these, the white blood cells and platelets form the
buffy coat between the plasma and the red blood cells. The red blood cells account for 40–52% of the total blood
volume in males and 38–48% in females. The hematocrit measurement is affected by the number and size of red
blood cells because it is based on volume. For example, a decreased hematocrit can result from a decreased number
of normal-size red blood cells or a normal number of small red blood cells. The average size of a red blood cell is
calculated by dividing the hematocrit by the red blood cell count. A number of disorders cause red blood cells to be
smaller or larger than normal. For example, inadequate iron in the diet can impair hemoglobin production.
Consequently, red blood cells do not fill up with hemoglobin during their formation, and they remain smaller than
normal. 

White Blood Count 

A white blood count (WBC) measures the total number of white blood cells in the blood. There are normally 5000–
9000 white blood cells per microliter of blood. Leukopenia is a lower than normal WBC resulting from decreased
production or destruction of the red marrow. Radiation, drugs, tumors, viral infections, or a deficiency of the
vitamin’s folate or B12 can cause leukopenia. Leukocytosis is an abnormally high WBC. Bacterial infections often
cause leukocytosis by stimulating neutrophils to increase in number. Leukemia, a cancer of the red marrow
characterized by abnormal production of one or more of the white blood cell types, can cause leukocytosis.
However, the white blood cells do not function normally. Because these cells are usually immature or abnormal and
lack normal immunological functions, people with leukemia are very susceptible to infections. The excess production
of white blood cells in the red marrow can also interfere with the formation of red blood cells and platelets and thus
lead to anemia and bleeding. 

Differential White Blood Count 

A differential white blood count determines the percentage of each of the five kinds of white blood cells.
Normally, neutrophils account for 60–70%, lymphocytes 20–25%, monocytes 3–8%, eosinophils 2–4%, and basophils
0.5–1% of all white blood cells. Much insight into a patient’s condition can be obtained from a differential white
blood count. For example, if a bacterial infection is present, the neutrophil count is often greatly increased, whereas
in allergic reactions, the eosinophil and basophil counts are elevated. 

Clotting 

The blood’s ability to clot can be assessed by the platelet count and the prothrombin time measurement. 

Platelet Count 

A normal platelet count is 250,000–400,000 platelets per microliter of blood. In the condition called
thrombocytopenia, the platelet count is greatly reduced, resulting in chronic bleeding through small vessels and
capillaries. It can be caused by decreased platelet production as a result of hereditary disorders, lack of vitamin B12
(pernicious anemia), drug therapy, or radiation therapy. 

Prothrombin Time Measurement 

Prothrombin time measurement calculates how long it takes for the blood to start clotting, which is normally 9–12
seconds. Prothrombin time is determined by adding thromboplastin to whole plasma. Thromboplastin is a chemical
released from injured tissues that starts the process of clotting. Prothrombin time is officially reported as the
International Normalized Ratio (INR), which standardizes the time it takes to clot on the basis of the slightly different
thromboplastins used by different labs. Because many clotting factors have to be activated to form fibrin, a
deficiency of any one of them can cause the prothrombin time to be abnormal. Vitamin K deficiency, certain liver
diseases, and drug therapy can increase prothrombin time. 
Blood Chemistry 

The composition of materials dissolved or suspended in the plasma can be used to assess the functioning of many of
the body’s systems. For example, high blood glucose levels can indicate that the pancreas is not producing enough
insulin; high blood urea nitrogen (BUN) is a sign of reduced kidney function; increased bilirubin can indicate liver
dysfunction; and high cholesterol levels can signify an increased risk of cardiovascular disease. A number of blood
chemistry tests are routinely done when a blood sample is taken, and additional tests are available.