BLOOD CHEMISTRY

Plasma

Blood Plasma

The liquid portion of the blood, the plasma, is a complex solution containing more than 90
percent water. The water of the plasma is freeiy exchangeable with that of body cells and other
extracellular fluids and is available to maintain the normal state of hydration of all tissues. Water,
the single largest constituent of the body, is essential to the existence of every living cell.
The major solute of plasma is a heterogeneous group of proteins constituting about 7 percent of
the plasma by weight. The principal difference between the plasma and the extracellular fluid of
the tissues is the high protein content of theplasma. Plasma protein exerts an osmotic effect by
which water tends to move from other extracellular fluid to the plasma. When dietary protein
is digested in the gastrointestinal tr¡ct, individual amino acids are released from
the polypeptide chains and are absorbed. The anmino acids are transported through the plasma to
all parts of the body, where they are taken up by. cells and are assembled in specific ways to form
proteins of many types. These plasma proteins are released into the blood from the cells in which
they were synthesized. Much of the protein of plasma is produced in the liver.
The major plasma protein is serum albumin, arclatively smallmolecule, the principal function of
which is to retain water in the bloodstream by its osmotic effect. The amount of serum albumin in
the blood is a determinant of the total volume of plasma. Depletion of serum albumin
permits fluid to leave the circulation and to accumulate and cause swelling of soft tissues (edema).
Serum albuminbinds certain other substances that are transported in plasma and thus serves as a
nonspecific carrier protein. Bilirubin, for example, is bound to serum albumin during its passage
through the blood. Serum albumin has physical properties that permit its separation from other
1
Gerunaloumn
nog plsna prtein
 plasma proteins, which as a group arc called gkobylins. I fact, the globulins are a
heteropencou.
array of proteins of widely varying structurend
I(inction, only alew of which will be mentioncd
here. The immunoglobulins, or antibodies, are produced in response to a specific foreign
substance, or antigen. For xample, administratior of polio vaccine, which is made from killed
or attenuated (weakencd) poliovirus, is followed by the aDpcarance in the plasma of antibodies
that react with poliovirus and efectively prevent the onset of disease. Antibodies may be induced
by many foreign substances in addition to microorgnisms; immunoglobulins are involved in some
hypersensitivity and allcrgic rcactions. Other plasma proteins are concerncd with
the coagulation of the blood.
Many proteins are involved in highly specific ways with the transport function of the blood.
Blood lipids are incorporated into protein molecules as lipoproteins, substances important in lipid
transport. Iron and coppcr arc transported in plasma by unique metal-binding proteins
(transferrin and ceruloplas1min, respectively). Vitamin B)2, an essential nutricnt, is bound to a
specific carrier protein. Although hemoglobin is not normally released into the, plasma, a
hemoglobin-binding protein (haptoglobin) is available to transport hemoglobin to
the reticuloendothelial System should
hemolysis (breakdown) of red cells OCcUr.
The serum haptoglobin level is raised during in•lammation and certain other conditions; it is
lowered in hemolytic disease and somc types of liv¢r discase.
Lipids are present in plasma in suspension and in splution. The concentration of lipids in plasma
varies, particularly in relation to mcals, but ordinarily does not exceed I gram per 100 millilitres.
The largest fraction consists of phospholipids, complex molecules containing phosphoric acid and
a nitrogen base in addition to latty acids and glyceról. Triglycerides, or simple fats, are molecules
composed only of fatty acids and glycerol. ree fatty acids, lower in concentration than
triglycerides, are responsible for amuch larger trahsport of fat. Other lipids include cholesterot. a
major fraction of the total plasma lipids. These substances exist in plasma combined with proteins
of several types as lipoproteins. The largest lipid particles in the blood are known
as chylomicrons and consist largely of triglyceridds;after absorption from the intestine, they pass
through lymphatic channels and enter the bloodstream through the thoracic lymphduct. The other
plasma lipids are derived from foodor enter the plasma from tissue sites.
Someplas1ma constituents occur in plasma in low concentration but have a high turnover rate and
great physiological importance. Among these is gludose, or blood sugar. Glucose isabsorbed from
the gastrointestinal tract or may be released into the circulation fron the liver. It provides a source
ol energy for tissue cells and is the only source tor some, including the red cells. Glucose is

2
conserved and used and is not excreted. Amino acids also are so rapidly transpotcd hat the plavma
level remains low, although they are requirdd for all protein synthesis throughout the body. Urea.
an end product of protein metabolism, is rapidly e~ereted by the kidneys.Other nilogenous waste
products uric acid and creatinine arc similarly removed.
Several inorganic materials are essential constituents of plasIa, and cach has specinl
functional atributes, The predominant cation (positively charged ion) of the plasa is sodium. n
ion that 0ccurs within cclls at a much lower concentratio. Because of the cllect ol sodium on
OSmotic pressure and luid movements, the amount of sodium in the body is an inlluentiul
determinant of the total volume of extracellular Iluid. The amount of sodum in plasma is
secreted by
controlled by the kidneys under the influcnce of he homoIc aldosteone, which is
excess is excreted by the
the adrenal gland. If dietary sodium eXCCeds requiremets, the
plasma t much lower
kidneys. Potassium, thc puncipal intracellular cation, occurs in
inluenced by aldoseronc, which
concentration han sodium. The renal cxCrction of potassium is
causes rctention of sodium and loss of potassi 'alciunin plama is in purt bond to protein
of two homones: parathyroidl homonc,
and in part ionized, Itsconcentration is under the control
to lall. Magncsium, likç potassium,
whichcauscs the level to ise, and calcitonp1, wlhich cses it
Varitions in
is a predominantly intraccllular cation
and occus in plasma nlow concentation
musecles,
have prolond eflects on the ervous ystem, the
the concentrations ofthese cations may
zine
precisc regulatory mechniss Iton,copper, nd
and the heart, cflects normally prevented by
ion is nccded in
required in trace amounts for synthes0t of evscntial enzynes, much more
are muclen.
myoglobin, the oxypen-binding pigment of
addition for production of hemoglobin and
occur in plasma in low concehtralions. The principal anion (negatively eharged io)
Thesc mctals
sodium chloride is is major salt. Bicatbonate participates in the transport
of plasma is chloride:
dioxide and in the repulation of pl. Phosphate also has a bullering etlecton the pll ot
of carbon metabolisn of ealciuun, odide is
chemical reactions of cells md lor the
the blood and is vital for
in race mounts, iN avidly taken up by the thiyoid gland, which
transported through plasma
homone
incorporules it into thyroid
bor)oncs of all the cndocine glands are Necreted into the plamu and tranpoted to their
The thee uteuy oen
opans, the orpans on which they exqt lher eflectN. The plas levelN ot
largct
thenn, nsoIe stanceN, measuCment ate
rellect the functional activity ofthe glnds hat secrete plasu
low, Amony the nany othe consituenh ot
posible though concentrations ate extrenly al have
these Ppcar Niply to luve escpcd tol ( i ecelly
are nu)erous cnzynes Soe ol
in the blood.
0 functional uyniticance
Blood cells

red blood cell

There are four major types of blood cells: red blood cells
(erythrocytes), platelets (thrombocytes), lvmphocytes, and phagocytic cells. Collectively, the
lymphocytes and phagocytic cells constitute the white blood cells (leukocvtes).Each type ofblood
cellhas a specialized function: red cells take up oxvgen from the
lungs and deliver it to the tissues:.
piatelets participate in forming blood clots; Ivnphocytes are involved with immunity:; and
phagocytic cells occur in two varietiesgranulocytes and monocytes-and ingest and break
down
microorganisms and foreign particles. The circulating blood functions as a conduit, bringing the
various kinds of cells to the regions of the body in which they are needed: red
cells to tissues
requiring Oxygen, platelets to sites of injury, Iymphocytes to areas of infection, and
phagocytic
cells to sites of microbial invasion and inflanmation. Each type of
blood cell is described in deta1l
below.
 myelocytes
bone marrow smear showing (hematopoiesis) takes place in
hematopoietic
blood cell formation
The continuous process of site' of blood formation
is the yolk sac. Later
in
embryo, the first
tissue. In the developing red blood cell-forming organ, but it is soon
becomes the most important
embryonic life, the liver only source of both red cells
and the
adult life is the
marrow, which in whereas
SuCceeded by the bone fills most of the skeleton,
hematopoietic bone marrow
granulocytes. In young children, (ribs, sternum, vertebrae, and pelvic
marrow is located mainly in the central bones cells
in adults the
developing and mature blood cells, as wellas fat
rich mixture of
bones). Bonemarrow is a architectural framework upon which the
blood
provide nutrition and an
and other cells that the marrow of a normal adult is
1,600 to
themselves. The weight of
forming elements arrange cells (18 x 10 cells per
over 1,000,000,000,000 hematopoietic
3,700 grams and contains the blood itself. Arteries pierce the
cells comes from
kilogram). Nourishment of this large mass of branches, which
' marrow, and divide into fine
bones, enter the
outer walls of the which blood flows sluggishly. In
venous sacs(sinusoids) through
ultimately coalesce into large cells enter the general circulation by
hematopoietic tissue, newly formed blood
the surrounding
sinusoids.
penetrating the walls of the 70 percent of the white cells
(i.e.,
adult the bone marrow produces all of the red cells, 60 to
In the thymus,
all of the platelets. The lymphatic tissues, particularly the
the granulocytes), and (conmprising 20 to, 30 percent of the
nodes, produce the lymphocytes
the spleen, and the lymph organs
reticuloendothelial tissues of the spleen, liver, Iymph nodes, and other
white cells). The
percent of the white cells). The platelets are formed from bits of the
produce the monocytes (4 to 8
(megakaryocytes) of the bone marrow.
cytoplasm of the giant cells
white cells arise through a series of complex transformations from primitive stem
Both the red and stem
the ability to form any of the precursors of ablood cell. Precursor cclls arc
cells, which have
 cells that have developed to the stage where they are committed to forming a particular lype of
new blood cell. By dividing and difierentiating, precursor cells give rise tothe four major blood
cell lineages; red cells. phagocytic cells, megakaryocytes, and lymphocytes. The cells of the
marrow are under complex controls that regulate their formation and adjust their production to the
changing demands of the body. When marrow stem cells are cultured outside the body, they form
tiny clusters of cells (colonies), which correspond to red cells, phagocytic cells, and
megakaryocytes. The formation of these indiyidual colonies depends on hormonal sugar
containing proteins(glycoproteins), referred tocallectively as colony-stimulatingfactors (CSFs).
These factors are produced throughout the body. Even in minute amounts, CSFs can stimulate the
division and differentiation of precursor cells into mature blood cells and thus exert powerful
regulatory influences over the production of blbod cells. A master colony-stimulating factor
(multi-CSF), also called interleukin-3, stimulates the most ancestral hematopoietic stem cell.
Further di fferentiation of this stem cell into specialized descendants requires particular kinds of
CSFs; for example, the CSF erythropoietin is needed for the maturation of red cells.
and granulocyte CSF controls the production of granulocytes. These glycoproteins, as well as other
CSFs, serve as signals from the tissues to the marrow. For instance, a decrease in the oxVgen
content of the blood stimulates the kidney to increase its production of erythropoietin, thus
ultimately raising the number of oxygen-carrying red cells. Certain bacterial components
accelerate the formation of granulocyte CSF, thereby leading to an increased production of
phagocytic granulocytes by the bone marrow during infection.
In the normal adult the rate of blood cellformation'yaries depending on the individual. but atypical
production might average 200billion red cells pe day, 10 billion white cells per day. and 400
billion platelets per day.

Red blood cells (erythrocytes)

The red blood cells are highly specialized. well adapted for their primary function ot
transporting oxygen from the lungs to all of the body tissues. Red cells are approximately 7.8 um
(| um = 0.000039 inch) in diameter and have the forn of
biconcave disks, a shape that prO\ides &
large surface-to-volume ratio. When fresh blood is examined with the microscope, red clls apper
to be yellow-green disks with pale centres containine novisible internal structures. When
blod is
centrifuged to cause the cells to settle, the volume of nacked red cells (hematocrit \alue) rangeS
between 42 and 54 percent of total volume in meo and between 37
and +7 pereent th s

6
values are somevwhat lower in children. Normal red
bhlood cells are fairly unitormn in volumne, w
that the hematocrit value is determined laredly by the
nunber of red cells per unit of blod he
normal red cell count ranges between four mlion and six
million per cubic millimere
The red blood cell is enclosed in a thin membrane that is composed of
chemically omplex ipid,
proteins,and carbohydrates in a highly organized structure. Extraordinary distortion of the red cel
occurs in its passage through minute blood vessels. manyof which have a diamneter less than that
of the red cell. When the deforming stress is remóved, the cell springs back to its original shape.
The red cellreadily tolerates bending and folding., but, if appreciable stretching of the membrane
Occurs, the cell is damaged or destroyed. The membrane is freely permeable to water,
Oxygen, carbon dioxide, glucose, urea, and certain other substances, but it is impermeable
to hemoglobin. Within the cell the major catipn is potassiun; in contrast, in plasma and
extracellular fluids the major cation is sodium. Apumping mechanism, driven by enzymes within
the red cell, maintains its sodium and potassium concentrations. Red cells are subject to osmotic
effects. When they are suspended in very dilute (hypotonic) solutions of sodiumchloride, redcells
more spheroid: in
take in water, which causes them to increase in volume and to become
concentrated salt solutions they lose water and shrink.
dissolved contents may escape from
When red cell membranes are damaged, hemoglobin and other
ghosts." This process, called hemolysis, is
the cells, leaving the membranous structures as
also by numerous other mechanisms. These
produced not only by the osmotic effects of water but
damage to red cells, as when blood is heated, is forced under great pressure
include physical
subjected to freezing and thawing: chemical damage to red cells by
through a small needle, or is
damage caused by
and cerfain snake venoms; and
agents such as bile salts, detergents,
antibodies atlach to red cells in the presence
immunologic reactions that may occur when
such destruction poceeds at a greater than normal rate,
of complement. When
hemolytic anemia results. that confer blood
molecules
has on its surt·ce a group of
The membrane of the red cel|
Most blood group substances are
differentiate blood cells into groups).
Lroup specificity (i.e., that structure of the
carbohydrate linked to protein, and it is usually the chemical
composed of
that determines th specific blood type. Blood group substances
carbohydrate portion
inducine the production of antibodies when injected into persons lacking
are antigens capable of
recognition of the blood group antigens are accomplished by the use
the antigen. Detection and makes
these antibodies. The large number of different red cell antigens
O o00d Serumcontaining
 Il eMrCmcly unlikely thut persons other than identical twins will have the
same array of bloe
Op substances.

Hemoglobin
Hemoglobin Tetramer
About 9S percent of the dry weight of the red blood ccll
consists of hemoglobin, the substance
nccessury for trnsport. lemoglobin is protein; molecule contains
four polypeptide chains(a tctramer), each chain
consisting of more than 140 amino acids. To cach
chain is attachcd a chcmical structure
known aS a heme group. Heme is
ringlike organic compound known as a composed of a
porphyrin to which an iron atom is attached. It is the
atom that reversibly binds oxvgen as the iron
blood trayels between the lungs and the
tour iron atos in cach molecule of tissues. There are
henoglobin, which, accordingly, can bind foår atoms of
Oxygen. The complex porphyrin and protein structiure provides the
atom so that it binds and releases proper environment for the iron
oNVgen appropriately under
The allinity ot hemoglobin tor physiological conditions.
oxvgen is so great that at the oxygenpressure
percent of the hemoglobin is saturated with in the lungs about 95
oxveen. As the oxvgen tension falls, as it
(issues, Oxygen dissociates from hemoglobin and is does in the
Tedcell membrane and the plasma to available to move by dittusion through the
sites where it is used. The
With oxVgen is not direcly proport proportion of hemoglobin saturated
ional to the oxvgen pressure. As the
hemoglobin gives up its oxYgen wih oxygenpressure declines,
OxVgen can be releasedwith a relativelydisproDortionate rapidity, so that the major fraction of the
smal drop in OXVgen tension. The
atinity ot
for oxygen is primarily
determined by the srueture ot hemoglobin, but it is also hemoglobin
other conditions within intluenced by
the red cell, in
particular the pH and certain organic
phosphate compounds produced during the chemical
breakdown of glucose, especially 2,3
diphosphoglycerate.
Hemoglobin has a much higher aftinity for carbon monoxide than for oxygen. Carbon monoxide
produces its lethal ctlects by
Carry ing Tuncion of binding to hemoglobin and preventing oNYgen transport. The oxvgen-
hemoglobin Can be distu urhod in other ways. The iron of
nomally the reduced or ferrous stale in both
in hemoglobin is
ilselt becomes oxidized to the nvshemoglobin deoxyhemoglobin. If the iron
and
ferric state,
Pigmentincapablc of transporting oxygen. hemoglobin is changed to methemoglobin, a brown
The red cells contain enzynnes capable of maintaining

8
the ironin its normalstate, but under abnomal enlitions large amounts of methemoglobin may
appear in the blood.

Sickle cell anemia is a serious and often fatal disease characterizcd by an inherited abnormal1ty of
hemoglobin. Persons who have sickle cell anemia are predoninantly of African descent. Thc
disease is caused by the mutation of a singe genc that deternines the structure of the hemoglobin
molecule. Sickle hemoglobin ditfers from rormal hemoglobin in that asingle amino acid(glutamic
acid) in one pair of the polypeptide chains has been replaced by another (valinc). This single
intramolecular change so alters the properties of the hcmoglobin molecule that anemia and other
eflects are produccd. May other genetically determined abnornmalities of hemoglobin have been
of altered
identified. Some of these also produce diseases of' several types. Study of the effccts
structure
structure of henmoglobin on its properties has greatly broadened knowledge of the
funetion relationships of the hemoglobin molecule.

Whitc blood cells (leukocytes)

MRSA and Neutrophil

are nucleated and independently motile.
White blood cells (leukocytes), unlike red cclls,
they do not undergo cell division (mitosis) in
Highly ifferentialed for their specialized functions, in thc
bloodstream, but some retain the capability of mitosis. As a group they are involved
the blood
activity. The number of white cells in normal
body's defense mechanisms and reparative
millimetre. Fluctuations occur during the day; lower
ranges between 4,500 and |1.000 per cubic,
during exercise. Intense physical exertion may
values are obtained during rest and higher values
are outside
cubic millimetre. Most of the white cells
cause he count to exceed 20,000 per
are in transit from one site to another. As living
the circulation, andthe few in the bloodstream
production of energy. The chemical pathways
cells, their survival depends on their continuous cells.
cells and are similar to those of other tissue
util1zed are more complex than those of the red
produce ribonucleic acid (RNA), can
White cells, containinp a nucleus and able to
cells, each unique as to structure and function,
synthesize protein. They comprise three classes of
that are designated granulocvtes, monocytes, and lymphocytes.
9
 Granulocytes
Granulocytes, the most nunerous of the white cells, are larger than red cells (approximately 1.
15 um in diameter). They have a multilobed nuclcus and contain large
numbers of cytoplasmic
granules (i.e., granules in the cell substance outside the nucleus). Granulocytes are important
mediators of the inflammatory response. There are three types of
granulocytes: neutrophils,
eosinophils, and basophils. Each type of granulocyte is identified by the colour of the granules
when the cells are stained with acompound dye. The granules of the
neutrophil are pink, those of
the eosinophil are red, and those of the basophil areblue-black. About 50 to 80
percent of the white
cells are neutrophils, while the eosinophils and basophils together
constitute no more than 3
percent.

Neutrophils
The neutrophils are fairly uniform in size with a diameter
between 12 and 15 um. The nucleus
consists of two to five lobes joined together by hairlike filaments.
Neutrophils move with
amoeboid motion. They extend long projections çalled pseudopodium into which their
granules
flow; this action is followed by contraction of filaments based in the
cytoplasm, which draws the
nucleus and rear of the cell forward. In this way 'neutrophils rapidly advance along a
surface.
The bone marrowof a normal adult produces about 100 billion neutrophils daily. It
takes about
one week to form a mature neutrophil from a precursor cell in the marrow; yet,
once in the blood,
the mature cells live only a few hours or perhaps alittle longer after migrating to the
tissues. To
guard against rapid depletion of the short-lived neutrophils (for example, during infection), the
bone marrow holds a large number of them in resetve to be mobilized in response to inflammation
or infection. Within the body, the. neutrophils miorate to areas of infection or tissue
injury. The
force of attraction that determines the directiorn in which neutrophils will
move is knoWn
as chemotaxis and is attributed to substances liberated at sites of tissue damage. Of the
l00billion
neutrophils circulating outside the bone marrow balf are in the tissues and half re in the blood
vessels. Of those in the blood vessels. half are witkin the mainstream of rapidly circulating blood.
and the other half move slowly along the inner alls of the blood vessels
(marginal pool). ready
to enter tissues onreceiving a
chemotactic signal from them.
Neutrophils are actively phagocytic: they ones.tF bacteria and other microorganisms and
microscopic particles. The granules of the neutronbil are microscopic packets or polent enyes
capable of digesting many types of cellular motorials. When a bacterium Is enguned b)
ncutrophl, Is encased in a vachale 'lined by the invag1nated membranc. Ihe
granules dsCharge their contents into the:vacuole containing the organism. As this occurs, the
granules ot the neutrophil are depleted (deuranation) A metabol ic process within the granules
produces hydrogen peroxide and a highly active forn of oxveen (superoxide), which destroy he
ingested bacteria. Final digestion of the invading organism is accomplished by enzymes.

Eosinophils
Fosinophils, like other granulocytes, are produced in the bone marrow until they are released into
the circulation. Although about the same size as neutrophils, the eosinophil contains larger
granules, and the chromatin is generally concentrated in only two nonsegmented lobes.
Tosinophils leave the circulation within hours of release from the marrow and migrate into the
lymphatic channels. Like
tiasucs (usually those of the skin, Iung, and respiratory tract)through the
site of celldestruction. They
neutrophils,cosinophils respond to chemotactic signals released at the
against parasites, and they
are actively motile and phagocytic. Eosinophils are involved in defense
primarily by dampening their
participate in hypersensitivity and inflammatory reactions,
destructive effects.

Basophils completely
granulocytes, and their large granules almost
Basophils are the leas numerous of the marrow.
underlying double-lobed nucleus. Within hours of their release from the bone
obscure the where they
barrier tissues (e.g., the skin and mucosa),
basophilsmigrate fron the circulation to the
modulator of the inflammatory response.
SVnthesize and store histamine, a natural
substances, leukotrienes,
aggravated, basophils release, along with histamine and other
When Basophils incite
anaphylaxis (a hypersensitivity reaction).
ivhich cause bronchoconstriction during neutrophils.
with platelets, macrophages, and
immediate hypersensitivity reactions in association

Monocytes make up
(averaging 15-18 um in diameter), and they
Monocytes are the largest cells of the blood folded
leukocytes. The nucleus is relatively big and tends to be indented or
about 7 percent of the
often appear
than multilobed. The cytoplasm contains large numbers of fine granules, which
rather They
the cell membrane. Monocytes are actively motile and phagocytic.
to be more numerous near particles, but they
ingesting infectious agents as well as red cells and other large
are capable of
11
 cannot replace the function of the neutrophils in the removal and
destruction of bacler.
Monocvtes usually enter areas of inflamed tissue later than the granulocytes. Often they are
folund.
at sites of chronic infections.

In the bone marrow, granulocytes and monocytes arise from a

common precursor under the
influence of the granulocyte-macrophage colony-stimulating factor. Monocytes leave the bone
marrow and circulate in the blood. After a period of hours, the monocytes enter the
tissues, where
they develop into macrophages, the tissue phagocytes that constitute the reticuloendothelial
system (or macrophage system). Macrophages occur in almost all tissues of the body. Those in
the liver are called Kupffer cells, those in the skin Langerhans cells. Apart from their role as
scavengers, macrophages play a key role in immunity by ingesting antigens and processing them
so that they can be recognized as foreign substances by lymphocytes.

Lvmphocytes
Human Lymphocvte
Lymphocytes constitute about 28-42 percent of the white cells of the blood, and they are part of
the immune response to foreign substances in the body. Most lymphocytes are small, only slightly
larger than erythrocytes, with a nucleus that occupies most of the cell. Some are larger and have
more abundant cytoplasm that contains a few granules. Lymphocytes are sluggishly motile, and
their paths of migration outside of the bloodstream are different from those of granulocytes and
monocytes. Lymphocytes are found in large numbers in the lymph nodes, spleen, thymus, tonsils,
and Iymphoid tissue of the gastrointestinal tract. They enter the circulation through lymphatic
channels that drain principally into the thoracic lymph duct, which has a connection with
the venous system. Unlike other blood cells. 'some lymphocytes may leave and reenter the

circulation, surviving for about one year or more: The principal paths of recirculating lymphocytes
are through the spleen or lymph nodes. Lvmphocytes freely leave the blood to enter lymphoid
antigen
CISsue, passing barriers that prevent the passage of other blood cells. When stimulated by
and certain other agents, some lymphocytes are activated and become capable of cell division
(mitosis).
 Human T Cell: Human TLymphocyte

immunity to foreign cells and antigens.

The lymphocytes regulate or participate in the acquired those
organisms, foreign cells such as
They are responsible for immunologic reactions to invading living
foreign proteins and other antigens not necessarily derived from
of a transplanted organ, and
lymphocytes are not distinguished by the usual microscopic examination
cells. The two classes of involved
of immune response they elieit. The B lymphocytes (or Bcells) are
butrather by the type
immunity. Upon encountering a foreign substance (or antigen), the B
in what is called humoral immunoglobulin (antibodies). The
plasma cell, which secretes
Iymphocyte differentiates into a the
lymphocytes, the T lymphocytes (or T cells), are involved in regulating
second class of T
lymphocytes as well as in directly attacking foreign antigens.
antibody-forming function ofB
what is called the cell-mediated immune response. T.lymphocytes also
lymphocytes participate in
rejection of transplanted tissues and in certain types of allergic reactions.
participate in the
their development in the bone marrow. The Blymphocytes mature partly
All lymphocytes begin Further differentiation of B
circulation.
they are released into the
in the bone marrow until by
tissues (spleen or lymph nodes), most notably on stimulation
0yimphocytes occurs in lymphoid
precursors of the T lymphocytes migrate from the marrow to the thymus,
a foreign antigen. The
under the influence ofa hormonelike substance. (The thymus is a small
where they differentiate at
breastbone in the upper portion of the chest. It is relatively large
organ lying just behind the elderly.
after puberty, and may be represented only by a fibrous cordin the
birth, begins to regress
exert its effects on the differentiation of lymphocytes before birth. The
The thymus begins to of
thymus from certain animals at birth prevents the normal development
removal of the
T lymphocytes leave the thymus and
immunologic responses.) Once they have matured, the
through the blood to the lymph nodes and the spleen. The two classes of lymphocytes
circulate that
in birds, in which it was found
originally derived their names from investigations
by the bursa of Fabricius (an
differentiation of one class of lymphocyte was influenced
lymphocytes, and the other was
outpouching of the gastrointestinal tract) and thus was called the B
influenced by the thymus and was called the T lymphocytes.
microbes. This cssential
A primary function of lymphocytes is to protcct the body from foreign
T
task is carried out by both T lymphocytes and B lymphocytes, which often act in concert. The
in
lymphocytes can recognize and respond only to antigens that appear on cell membranes
association with other molecules called major histocompatibility complex (MHC) antigens. The
latter are glycoproteins that present the antigen in a form that can be recognized by Tlymphocytes.
13
 In effect.
T
lymphocytes are responsible for continuous surveillance of cell suluce% Iu .
prescnce of foreign antigens. By contrast, the ahtibodics produccd by B lymplocytes are nd
confined to recognizing antigens on cell membran¢s; they can bind to solublc antigens in the blood
or in extravascular fluids. T lymphocytes typicallyi recognize antigens of inlectioUs organnuns that
must penetrate cells in order to multiply, such as viruses, During their intracellular Iife cycle
viruses produce antigens that appear on the cell membrane. Two classcs of T Iymphocytes can be
involved in the response to those cell-associated yiral antigens: cylotoxic T lymphocyles, which
destroy the cells by a lytic mechanism, and helper|T lymphocytes, which assist B cells to produce
antibodies against the microbial antigens. Help#r T lymphocytes exert thieir influence on B3
lymphocytes through several hormonelike peptides termed interleukins (|L). Five difercnt T
lymphocyte interleukins (IL-2, IL-3, IL-4, IL-5, and IL-6) have been discovercd, cach with
different (and sometimes overlapping) effects on Blymphocytes and other blood cells. Intcrleukin
I, produced by macrophages, is a peptide that stimulates T lymphocytes und that also acts on
the hypothalamus in the brain tó produce fever. The ability to develop an
immune response (i.c.,
the T cell-mediated and humoral immune responses) to foreign substances is called
immunologic
competence (immunocompetence). Immunologic tompctcnce, which begins to develop during
embryonic life, is incomplete at the time of birth but is fully established soon after birth. If an
antigen is introduced into a person's body before immunologic competence has been established,
animmune response willnot result upon reinfection, and that person is said to be tolerant to that
antigen.

Platelets (thrombocytes)

Platelet
The blood platelets are the smallest cells of the blood, averaging about 2to 4 un in diameter.
Although much more numerous (150,000 to 400.000 per cubic millimetre) than the white cells,
they occupy amuch smaller fraction of the voluné of the blood because of their relatively minute
SIZe. Like the red cells, they lack a nucleus and ate'incapable of cell division (mitosis), but they
have amore complex metabolism and internalstructire than have the red cells. When seen in fresh
blood they appear spheroid, but they have a tendency to extrude hairlike lilaments lrom their
membranes. They adhere to each other but not tolred cells and white cells. Tiny granules within
platelets contain substances important for the clot-promoting activity of platelets.
14
 The function of the platelets is
the endothelial
related to hemostasis, the prevention and control of bleeding. When
surface (lining) of ablood vesscl is injured, platelets inlarge numbers immediaely
attach to the injured
surface and to cach other, forming a tenaciously adherent mass of platelets,
The effect of the platelet response is to stde he
Aleeding and to form the site of the developing
blood clot, or thrombus. If platelets are
absent. this important defense reaction Cannot
protracted bleeding from small wounds (prolon ged bleeding time) results. The. normal resistance
of capillary membranes to leakage of red cells is
dependent upon platelets. Severe deficiency Ol
platelets reduces the resistance of the capillary wälls, and abnormal bleeding from
the cap1llaries
0ccurs, either spontaneously or as the result of minor iniury. Platelets also contribute substances
essential for the normal coagulation of the blood. and they cause the shrinking, or retraction, of a
clot after it has been formed.

Platelets are formed in the bone marrow by segmentation ofthe cytoplasm (the cell substance other
than the nucleus) of cells known as megakaryocytes, the largest cells of the marrow. Within the
marrow the abundant granular cytoplasm of'the megakaryocyte divides into many small segments
that break off and are released as platelets into the circulating blood. After about 10 days in
thecirculation, platelets are removed and destroyed. There are no reserve stores of plateletsexcept
in the spleen, in which platelets occur in higher concentration than in the peripheral blood. Some
platelets are consumed in exerting their hemostatic effects, and others, reaching the end of their

life span, are removed by reticuloendothelial cells (any of the tissue phagocytes). The rate of
production. A
platelet production is controlled but not so precisely as the control of red cell
chemical mediator that
hormonelike substance called thrombopoietin is believed to be the
the number and growth
reoulates the number of platelets in the blood by stimulating an increase in
rate of pltelet production.
of megakaryocytes, thus controlling the

Functions of blood
maintain the constancy of the internal
Broady conceived, the function of the blbod 1s to
environment. The circulating blood makes possible adaptability to changing conditions of life-
atmospheric pressure; the capacity to alter the
Jbe endurance of wide variations of climate and
changing diet and fluid intake; the resistance to
amount of physical activity; the tolerance of
agents. The blood has an exceedingly conmplex
nhysical injury, chemical poisons, and intectrous
components participate in its functional activities. Some of the regulatory
structure, and many
include sensors that detect alterations in
mechanisms with which the blood is involved
15
lemperature, in pll, in osygen (ension, and in concentrations of the constituents of the bloo

Tilects of these stùmuli are in sone nstances mediated via the nervous system or by the rel
ohomones (chemical mediators).

Respiration
lurnction of the blood is vital. A continuous supply
In terms of immediate urgency, the respiratory
brain,since deprivation is followed
ofoxygen isrequired by living cells -in particular,those ofthe
minutes by unconscioUSneSs and death. A normal male at rest uses about 250 millilitres of
in
during vigorous exertion. All of this oxygen
ONVgen per minute, a requirement increased many fold
transported by the blood, most of it bound to the hemoglobin of the red cells. The minute blood
is
pulmonary air spaces (alveoli),
vessels of the lungs bring the blood into close apppsition with the
difuses through the plasma and into the
where the pressure of oxygen is relatively high. Qxygen
percent saturated with oxygen on leaving
red cell, combining with hemoglobin, which is about 95
millilitres of oxygen, and about 50 times as
the lungs, One gram of hemoglobin can bind I.35
dissolved in the plasma. In tissues where the
much oNVgen is combined with henmoglobin as is
oxygen.
OxVgen tension is relatively low, henmoglobin relcases the bound
are the plH (a measure of the acidity or
The two main regulators of oxygen úptake and delivery
(2,3-DPG) in red cells. The pH of
basicity) of tissues and the content of 2,3-diphosphoglycerate
level of about 7.4 (pH less than 7 indicates
blood is kept relatively constant at the slightly alkaline
of hemoglobin to bind oxygen is
acidity, more than 7 alkalinity). The effect of pH on the ability
oxygen less strongly, and when pH is
called the Bohr etfect: when plH is low, henoglobin binds
oxygen. The Bohr effect is due to changes
high (as in the lungs), hemoglobin binds more tighily to
the shape of the henmoglobin molecule as the pH of its environment changes. The
in
2,3-DPG, a simple molecule produced by the
ONVgen aftinity of hemoglobin is also regulated by
is to reduce the oxygen affinity of
red cell when it metabolizes glucosc. The ettect of 2,3-DPG
reduced, the red cell responds by
hemoglobin. When the availability of xveen to tissues is
aperiod of hours to days. By contrast,
S\nthesIZINg more 2,3-DPG, a process that occurs over
tissue pH mediates minute-t0-minute changes in oxygen handling.
found in relatively high concentration
Carbon dioxide, a waste product of cellular metabolism, is
the lungs to be climinated with the expired
in the tissues. Itdifuses into the bloodand iscarried to
andreadily diffuses into red cells. It reacts
ar. Carbon dioxide is much more soluble than oxtoen
at the alkaline pH of the blood appears
with water to form carbonic acid. a weak aeidthat
principally as bicarbonate.

161
 with extraordinary precision
tension of carbon dioxide in the arterial blood is regulated
movements Carbon dioxide
ihrough a sensing mechanism in the brain that controls the respiratory
(i.e.
tends to lower the pH of the blood
IS QN acidic substance, and an increasein its concentration
This mav be averted by the stimulus that causes increased depth and rare
hecoming more acidic).
accelerates the loss of carbon dioxide. It is the tension of carbon
ot breathing, aresponse that
oxygen,. in the arterial blood that normally controls breathing. Inability to hold
dioxide, andnot of which
more than aminute or so is the result of the rising tension of carbon dioxide,
one s breath tor lungs
Respiratory movements that ventilate the
produces the irresistible stimulus to breathe. adequate
normal tension of carbon dioxide are. under normal conditions,
sutticiently to maintain a
genated. Control of respiration is effective. therefore. in regulating the
to keep the blood fully oxv maintaining the constancv of blood pH.
carbon dioxide and in
uptake of oxvgen and disposal of

Nutrition the blood:

nutrition of every cell in the bodv is transported by
the
Each substance required for salts: vitamins and other accessorv
and fats: minerals and
ofcarbohvdrates. proteins,
the precursors the plasma on the wav to the tissues in
which
must all pass through
food factors. These substances thev mav
enter the bloodstream trom the gastrointestinal tract, or
may
thev are used. The materials from the breakdown of
tissue.
or become available
within the body
be released from stores blood sugar (glucose) and calcium.
are
concentrations of many plasmaconstituents, including regulators
The have adverse effects. One of the
from the normal may
carefullyregulated, and deviations glandular cells in the pancreas.
the blood from
hormone released into
of glucose is insulin, a production of insulin. which tends to keep the
tollowed by increased
lngestion of carbohydrates is carbohydrates are broken down into
rising excessively as the
blood glucose level trom may severely reduce the level of glucose
molecules. But an ercess of insulin
theirconstituent sugar include coma and even death.
severe, may
reaction that. if sutticiently
in the blood, causing a proteins
simple solution. but some substances require specific binding
Glucose is transported in through the
substances form temporary unions) to convey them
which the
(with
special and necessary transport proteins. Nutrient
plasma. Iron and copper, essential minerals, have bones use large
selectively by the tissues that require them. Growing
substances may be taken up
marrow removes iron from plasma for hemoglobin synthesis.
amounts of calcium, and bone

Excretion
 I n v

The blood caiestlhe waste products ofcellular metabolism to thc cxcretory organs. The remgval
of carbon doxide via the lungs has been described above. Watcr produced by the oxidation of
loods ot available from othersources in cxcess of recds isexcrcted by the kidneys as the solvent of
the urine. Waler derivcd from the blood also is lost from the body by evaporation from the skin
nd luns and in Small amounts fromthe pastrointestinal tract. The water content of the blood and
of the body as awhole remains witbin anarrow range because of effective regulatory mechanisms,
homonal and other, that deternine the urinary volume. Thc concentrations of physiologically
important ions of thc plasa, notably sodium, potassium, and chloride, arc precisely controlled by
their retention or selective removal as blood flows through the kidneys. Of special significance is
the renal (kidney) control ofacidity of the urine, a major factor in the maintcnance of the normal
pH of te blood. UreA, creatinine, and uric acid are nitrogen-containing products of metabolism
that are transportcd by the blood and rapidly climinated by the kidneys. The kidneys clear the
blood of many other subsances, including numerous drugs and chemicals that are taken into the
body. In perfoming thcir cxurctory function, /he kidneys have a major responsibility for
maintainingthe constancy of the çomposition of the blood. (See also renal system ) The liver is in
part an cxuIctoryogan Bilirubin (bile pigment)iproduced by the destruction of hemoglobin is
conveyed by he plasma to the liver and is 'exereted through the biliary ducts into the
yastrointestinal tract. Other substances, incuding certain drugs, also are removed from the plasma
by the liver.

Immunity
Cells of the blood and constituents of theplasma interact in complex ways to confer immunity to
inleclious ayents, to resist or destroy invading organisms, to produce the inflammatory response,
and to destroy and remove forcign materials and dead cells. The white blood cells (leukocytes)
have 4primary role in these reactions. Granulocytes and monocytes phagocytize (ingest) bacteria
and other organisms, migrale to sites of infection or inflammation and to areas
containing
dead (iSUC, and participate in the enzvmatic breakdown and removal of
cellular
debiis. yInphocytes are concerned with the development of immunity. Acquired resistance to
speilie microorgarnisns is in part attributable to dntibodies, proteins that are
formed in response
ny mo he body of a foreign substance (antieen). Antibodies that have been induced by
imicroorgan1sms not only participate in eliminalinu the microbes but also prevent reintection by
ne same organisms, Cells and antibodies mav eonerale in the destruction of
invading bacteria;
he antibodies may attach to the oryanisus ther.br rondering them
susceptible to phagocytosiS.
18
Involved in some of these reactions is comnl ement a uroupof protcin cOmponent, ol plasrma that
participates in certain immunologic reacine When certain classes of antinodies hind o
microorganisms and other cells, they trigger thd atachment of components of the compleneit
System to the outer membrane of the taroet cell As they assemble on the cell membranc. the
complement components acquire enzymatic proerties.Thc activated complement system is thus
able to injure the cell by digesting (lysing) portions of the cell's protective membrane.

Temperature Regulation
Heat is produced in large amounts byphysiological oxidative reactions, and the blood is essentíal
for its distributing and disposing of this heat. The circulation assures relative uniformity of
lost
temperature throughout the body and also carries the warm blood to the surface, where heat is
brain functíons
to the external environment. A héat-regulating centre in the hypothalamus of the
through it
much like a thermostat. It is sensitive to changes in temperature of the blood flowing
that control the diameter of the blood
and, in response to the changes, gives off nerve impulses
A rise in skin temperature
vessels in the skin and thus determine bloodflow land skin temperature.
lost by evaporation of water from
increases heat loss from the body surface. Heat is continuously
increased when more water is made available from
the lungs and skin, but this loss can be greatly
Svstem under
sweat glands is controlled by the nervous
the sweat glands. The activity of the
Constancy of body temperature is achieved by
direction of the temperature-regulating centre.
mechanis.
control of the rate of heat loss by these thin and
contained under pressure in a vascular system that includes vast areas of
The blood is
membranes. Even the bumpS and knocks of everyday life are sufficient to disrupt
delicate capillary
and serious injury can be much more damaging. Loss of blood would
some of these fragile vessels, mechanisms to prevent and control
survival if it were not for protective
be a constant threat to actually
platelets contribute to the resistançe of capillaries, possibly because they
bleeding. The
the absence of platelets, capillaries become more fragile, permitting
fill chinks in vessel walls. In
Platelets
tendency to form bruises after minor injury.
Spontaneous loss of blood and increasing the
blood
at the site of injury of a blood vessel, tending to s il theaperture. A
Immediately aggregate
around the clump of adherent platelets, furth occludes the bleceding
Clot, torming in the vessel
mechanism involves a series of chemical reac ns in which spccific
Pont. Ihe coagulation
including the platelets, p part. Plasma also is
proteins and other constituents of the blood,

19
 provided with a mechanism for dissolving clots after they have been formed. Plasmin ic
proteolytic enzyme-a substance that causes breakdown of proteins-derived from an inu
plasma precursor known as plasminogen. When clots are formed within blood vessels, activation
of plasminogen to plasmin may lead to their removal. (For additional information about the
mechanics and significance of hemostasis, see bleeding and blood clotting.)

Laboratory Examination of Blood

Physicians rely upon laboratory analysis to obtain measurements of many constituents of the
blood, information useful or necessary for the detectipn and recognition of disease.
Hemoglobin contains a highly coloured pigment that interferes with the passage of a beam of light.
To measure hemoglobin concentration, blood is diluted and the red blood -cells (erythrocytes)
broken down to yield a clear red solution. A photoelectric instrument is used to measure the
absorbance of transmittedlight, from which hemoglobin concentration can be calculated. Changes
inthe hemoglobin concentration of the blood are not necessarily directly paralleled by changes in
the red cell count and the hematocrit value, because the size and hemoglobin concentration of red
cells may change in disease. Therefore, measurements of the red cell count and the hematocrit
valuemay provide useful information as well. Electronic particle counters for determining red ccll,
white cell (leukocyte), and platelet counts are widly used. Only adrop of blood is needed for the
analyses, which are completed within a minute.
Adequate examination of the blood cells requires that a thin film of blood be spread on a glass
slide, stained with a special blood stain (Wright stain), and examined under the
microscope.
Individual red cells, white cells, and platelets are examined, and the relative proportions of the
several classes of white cells are tábulated. The results may have
important diagnostic implications. In iron-deficiencv anemia, for example, the red cells look paler
than normal because they lack the normal amount off
hemoglobin; in malaria the diagnosis is
established by observing the malarial parasites within the red cells. In
pneumonia and many
intections, the proportion of neutrophilic leukocvtes is usually increased, while in others, such as
pertussis (whooping cough) and measles, there is an increase in the
proportion of lymphocytes.
Chemical analyses measure many of the constityodta ofnlasma. Often serum rather than
plasma is
used, however, since serum can be obtained 'c.s
clotted blood without the addition of
an anuc0agulant. Changes in the concentrationet ingl oonstituents of the blood can indicate
Lne presence of disease. For example.
in the blood is quantitativeidotermination
essential for the diagnosis of
of the amount o sg
diabetes, a disease in which the blood sugar tends to
20
 Nitrogenous waste products, in partiçular urea, tend to accumulate in persons with
be elevated. normal rate. An increase in the
excrete these substances at a
diseased kidneys that arc unable to an
reflects a disorder of the liver and bile ducts or
serum often
concentration of bilirubin in the
increased rate of destruction of hemoglobin. analysis: however
manually using an indiyidual procedure for each
Tests can be performed the number of chemical analyses
that
automated machine, increases
the autoanalyzer, acompletely single
laboratories. Adozen analyses may be made simultaneously by a
can be performed in a test tube
employing a small amount of serum, The serum is automatically drawn from
machine
propelled through plastic tubing of Small djameter. As the serum specimen advances, it is
and is that
divided; appropriate reagents are added;chemical reactions occur with formation of a product
the result appears as a written tracing from
can be measured with a photoelectric instrument: and
read directly. The data acquired by the
which serum concentration of various substances can be
fed automatically into a computer. and the numerical results printed on a form that
Imachine may be
analyses are not performed routinely but are
is submitted to a physician. Many of the available
poisoning, for example, detection
invaluable in special circumstances. In cases of suspected lcad
diagnostic. Some analytical procedures have
of an elevated level of lead in the blood may be
certain hormones, including measurement
specific diagnostic usefulness. These include assays for
of the thyroid hormone in the serum of patients suspected
of having. thyroid disease.

Blood Storage and Blood Transfusion

procedures are concerned with immunologic reactions of the blood.
Other important laboratory and cross matching
determinations of the blood groups of thepatient and the blood donor,
Careful
the other to ensure compatibility, are essential for the
serum of
of the cells of one with the regularly determined and is
of. a pregnant woman is
The Rh type
safe transfusion of blood. incompatibility and for proper prevention
of fetal-maternal
necessary for the early detection ofcertain
(hemolytic disease of the newborn). The diagnosis
erythroblastosis fetalis
or treatment of ofantibodies in the patient's serum.
the demonstration
infectious diseases depends upon results. Enzymes normally present in
the
useful
blood examination yield damaged by a coronary
Many other kinds of blood when the heart is
of the heart may be released into the death.
Measurement otthese
muscle
artery) with'consequent!tissue disease.
occlusion (obstruction of the coronary
of this type of heart
diagnosis nature
regularly performed to assist in cvaluation ofthe
enzymes in the serum is aidsin
measurement ofwhich recognized and
releases other enzymes, increasingly
Damage to theliver proteins are
Inherited abnormalitjes of
and severity of liver disease.
21
 hemophilia and other bleeding
identified byuse of sophisticated methods. Accurate'diagnosis of of the
possible by investisations of the coasulation mechanisn. Mcasurcments
disorders is made
the blood provide the basis for
diagnosis
concentration of folic acid and vitamin B in
deticiencies of these vitamins.

Dr. Oghagbon S.E.