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PHYSIOLOGY-1 ON BIO-MEDICAL
ENGINEERING UNDERGRADUATE
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>[Link]/guidebio-medicaleng1 ]
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6/20/2014

MUHAMMAD-SIKANDER-KHAN-LODHI

BLOOD-PHYSIOLOGY IN PHYSIOLOGY-1 ON BIO-MEDICAL ENGINEERING

UNDERGRADUATE PROGRAM :
BLOOD-PHYSIOLOGY:
INTRODUCTION:
1. As cells differentiate and become more specialized for particular functions, they also
become less capable of an independent existence.
2. They are less able to protect themselves from extreme temperatures, toxic chemicals,
and changes in pH.
3. They cannot seek food or devour whole bits of food. And if they are firmly implanted in
a tissue they cannot move away from their own wastes.
4. The substance that bathes differentiated cells and carries out these vital functions for
them is interstitial fluid (also known as intercellular or tissue fluid).
5. When the fluid flow through lymphatic vessels its called lymph.
6. All fluids outside cells including interstitial fluid, blood-plasma (fluid in blood), lymph
and a few other such as aqueous-humor in the eyes, comprise the extracellular-fluid.
7. Homeostasis: because body cells are too specialized to adjust to more than very limited
changes in their environment , the internal environment (interstitial fluid) must be kept
within normal physiological limits. This is the condition of homeostasis . in preceding
chapters , we have discussed how the internal environment is kept in homeostasis. Now
we will look at that environment itself, beginning with the blood.
8. Cardio-vascular system: the blood,heart and blood vessels together make up the
cardiovascular system.
9. Lymphatic-system: the lymph, lymphatic-vessels that transport lymph and structures
and organs containing lymphatic tissue (large clusers of white blood cells WBCs called
lymphocytes) make up the lymphatic-system .
10. Hematology: the branch of science concerned with the study of blood , blood-forming
tissues and the disorders associated with them is called hematology(hem=blood;
logos=study of).
COMPARISON-OF-EXTRACELLULAR-FLUIDS:
1. Both interstitial fluid and lymph are similar in composition to plasma. The principal
chemical difference is that they contain less protein than plasma.
2. This is because the larger protein molecules are not easily filtered through the
endothelial cells that form capillary walls.
3. The transfer of materials between blood and interstitial fluid occurs by osmosis,
diffusion and filtration across the endothelial cells.

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4. Interstitial fluid and lymph also differ from plasma in that they contain variable
numbers of leukocytes (white-blood cells). Like plasma, interstitial fluid and lymph
lack erythrocytes (red-blood cells) and platelets.
5. Blood plasma and lymph service the interstitial fluid. Blood pick up oxygen from
lungs, nutrients from the gastrointestinal tract, and hormones from endocrine
glands.
6. Blood transports these substances to tissues, where they diffuse from capillaries
(the smallest blood vessels) into interstitial fluid . from the interstitial fluid, needed
substances enter cells and cellular wastes enter the blood.
7. The blood carries carbon dioxide and metabolic wastes to the lungs, kidneys, and
sweat glands for elimination from the body.
8. Certain wastes must be detoxified by the liver before they can be excreted .
9. Sometimes disease-causing organisms (pathogens) invade the interstitial fluid and
blood and thus can be carried throughout the body.
10. The lymphatic system helps protect the body from such spread of disease.
11. Lymph picks up materials, including wastes, from interstitial fluid , cleanses them of
bacteria and returns them to the blood.
FUNCTIONS-OF-BLOOD:
Blood is a liquid connective tissue that has three general functions: transportation, regulation
and protection.
Transportation:
a) blood transports oxygen from the lungs to the cells of the body and carbon dioxide from
the cells to the lungs .
b) it also carries nutrients from the gastrointestinal tract to the cells, heat and waste
products away from cells and hormones from endocrine glands to other body cells.
Regulation:
a) Blood regulates pH through buffers , it also adjusts body temperature through
the heat-absorbing and coolant properties of its water content and its variable
rate of flow through the skin, where excess heat can be lost to the environment.
b) Blood osmotic pressure also influences the water content of cells , principally
through dissolved ions and proteins.
Protection:
a) The clotting mechanism protects against blood loss , and certain phagocytic
white blood cells [WBCs] or specialized plasma proteins such as antibodies,
interferon , and complement protect against foreign microbes and toxins .

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--------------PHYSICAL-CHARACTERISTICS-OF-BLOOD:
i.
ii.
iii.
iv.
v.

Blood is heavier , thicker and more viscous than water , it flows more slowly than water
at least in part because of its viscosity.
The adhesive quality of blood, or its stickiness, may be observed by touching it.
The temperature of blood is about 38C , which is slightly higher than normal body
temperature, and it has a slightly alkaline pH of about 7.40(normal range 7.35 to 7.45).
Blood constitutes about 8% of the total body weight.
The blood volume is 5 to 6 liters (1.5 gal) in an average-sized male and 4 to 5 liters (1.2
gal) in an average-sized female .

-----COMPONENTS-OF-BLOOD:
a. Whole blood is composed of two portions: 55% is blood plasma, a watery liquid
containing dissolved substances, and 45% is formed elements, which are cells and cells
fragments (fig # 19.1).
Fig # 19.1

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BLOOD-PLASMA:
When the formed elements are removed from blood , a straw-colored liquid called
blood plasma or simply plasma is left.
Plasma is about 91.5% water and 8.5% solutes, most of which by weight (7%) are
proteins.
PLASMA-PROTEIN:
Some of the proteins in plasma are also found elsewhere in the body , but those
confined to blood are called Plasma-proteins.
These proteins play a role in maintaining proper blood osmotic pressure, which is
important in total body fluid balance (chapter 21).

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Most plasma-proteins are synthesized by the liver, including the Albumins (54% of
plasma-proteins), globulins (38% of plasma-proteins), and fibrinogen (7% of plasmaproteins).
OTHER-SOLUTES-IN-PLASMA:
Other solutes in plasma, include waste-products, such as urea, uric-acid, creatinine,
ammonia, and bilirubin ; nutrients; vitamins; regulatory substances such as enzymes and
hormones; gases; and electrolytes.
Exhibit 19.1 summarizes the chemical composition of plasma.

EXHIBIT 19.1
SUBSTANCES-IN-PLASMA
Constituent

Description

1. Water

Liquid portion of
blood; constitutes
about 91.5% of
plasma. Acts as
solvent and
suspending medium
for solid components
of blood and
absorbs, transports,
and releases heat.

2. Solutes

Constitute about
8.5% (by weight) of
plasma.

3. PROTEINS
Albumins(54%)

Smallest plasma
proteins , produced
by liver and exert
considerable

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osmotic pressure,
which helps
maintain water
balance between
blood and tissues
and regulate blood
volume, also
function as transport
proteins for several
steroid hormones.

Globulins (38%)

Protein group to
which antibodies
(immunoglobulins)
belong. Produced by
liver and plasma
cells that derive
from B-cell
lymphocytes.
Antibodies help to
attack measles,
hepatitis and polioviruses, and tetanusbacterium. Alpha
and beta globulins
transport iron, fats
and fat-soluble
vitamins in the
blood.

Fibrinogen (7%)

Produced by liver.
Plays essential role
in blood clotting.

4. Wastes

Most are breakdown products of

protein metabolism

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and are carried by
blood to organs of
excretion. Include
urea, uric-acid,
creatine, creatinine,
bilirubin , and
ammonium salts.
5. Nutrients

Products of digestion
passed into blood
for distribution to all
body cells . include
amino-acid (from
proteins), glucose
(from
carbohydrates), and
fatty acids and
glycerol (from
triglycerides).

6. RegulatorySubstances

Enzymes: enzymes
which produced by
body cells, to
catalyze chemical
reactions.
Hormones:
hormones which
produced by
endocrine glands, to
regulate growth and
developments in
body.

7. Gases

Oxygen , carbon
dioxide, and
nitrogen gas .
whereas there is
more oxygen gas

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associated with
hemoglobin inside
red-blood-cells,
there is more carbon
dioxide gas dissolved
in plasma . nitrogen
gas has no known
function in the
human body .
8. Electrolytes

a.
b.
c.
a.
I.
II.
b.

Inorganic salts ,
cations include
sodium, potassium
,calcium and
magnesium ; anions
include Cl-, HPO42-,
SO42-, HCO32-, help
maintain osmoticpressure, and serve
as essential
minerals.

--------- FORMED-ELEMENTS:
The formed-elements of blood are:
1) Erythocytes (Red-blood-cells [RBCs]).
2) Leukocytes(White-Blood-cells [WBCs]).
i.
Granular-Leukocytes(Granulocytes).
Neutrophils.
Eosinophils.
Basophils.
ii.
Agranular-Leukocytes (agranulocytes).
Lympho-cytes.
T-cells.
B-cells.
Mono-cytes.
3) Thrombocytes ( Platelets) .

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------------FORMATION-OF-BLOOD-CELLs:
i.
ii.

iii.

iv.
v.

vi.
vii.
viii.
ix.
x.
xi.
xii.

xiii.
xiv.

xv.
xvi.

Hemopoiesis [ or Hematopoiesis ] : The process by which blood cells are formed is

called Hemopoiesis [or Hematopoiesis].
during embryonic and fetal life, there are several centers for blood cell production. The
yolk sac, liver, spleen, thymus-gland, lymph-nodes, and bone-marrow all participate at
various times in producing the formed-elements.
After birth, however, hemopoiesis takes places in red bone marrow (myeloid-tissue).
Red-bone marrow is found in the proximal epiphyses of the humerus and femur ; flat
bones such as the sternum, ribs, and cranial-bones; and the vertebrae and pelvis .
Stem-cells, which give rise to differentiated blood cells and also replenish themselves,
reside mainly in red bone marrow, although a few circulate in the blood.
Five types of cells develop from the pluripotent hematopoietic stem-cells
(hemocytoblasts ) (fig # 19.2 ) , which are derived from mesenchyme, Recall that the
term -blast refers to a nucleated precursor cell.
a. Proerythroblasts (rubri-blasts ) form mature Erythrocytes [= RBCs] .
b. Myeloblasts form mature neutrophils, eosinophils, and basophils .
c. Monoblasts form mature monocytes.
d. Lymphoblasts form mature Lymphocytes.
e. Megakaryoblasts form mature thrombocytes (or Platelets).
Several Hematopoietic-growth-factors stimulate differentiation along particular paths
and proliferation of certain progenitor cells.
Erythropoietin (poiem = to make ) or EPO, a hormone produced mainly by the kidneys
and in small amounts by the liver, stimulates proliferation of erythrocyte precursors,
and thrombopoietin stimulates formation of thrombocytes (Platelets).
In addition, there are several different cytokines that regulate hematopoiesis of
different blood cell types.
Cytokines are small glycol-proteins produced by red-bone marrow cells , leukocytes,
macrophages and fibroblast . they act locally as autocrines or paracrines that maintain
normal cell functions and stimulate proliferation .
Two important families of cytokines that stimulate blood cell formation are called
colony-stimulating factors (CSFs) and the interleukins.
The classes of hematopoietic-growth-factors and their functions are described in Exhibit
19.2 .

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xvii.

Most growth factors are available through recombinant DNA technology. They hold
tremendous potential for medical uses in situations where a persons natural ability to
form blood cells is diminished or defective.
Recombinant Erythropoietin (EPO) is very effective in treating the diminished
erythrocyte production that accompanies end-stage kidney disease. Granulocytemacrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) or Neupogen successfully
stimulate blood cell formation in cancer patients who are receiving chemotherapy ,
which tends to kill their bone-marrow cells as well as the cancer-cells.
They also improve the outcome of bone marrow transplants . other potential uses
include treatment of AIDS (acquired immune deficiency syndrome), inborn defects of
blood cell production, blood cell cancers , and severely burned patients .

xviii.

xix.

ERYTHROCYTES [ or RED-BLOOD-CELLS (RBCs) ]:

More than 99% of the formed elements in blood are erythrocytes [ or red-blood-cells
(RBCs)] .
They contain the oxygen-carrying pigment hemoglobin which is responsible for the
red color of whole blood.
RBC-ANATOMY:
i.

ii.
iii.
iv.

v.
vi.

Under the microscope, RBCs appear as bi-concave discs averaging about 8 micro-meter
in diameter (fig # 19.3a) . the flexible , biconcave shape allows RBCs to squeeze through
narrow capillaries, which may be only 3 micro-meter wide.
Mature red blood cells are quite simple in structure, they lack a nucleus and other
organelles and can neither reproduce nor carry on extensive metabolic activities .
The plasma membrane encloses hemoglobin , which was synthesized before loss of the
nucleus and which constitutes about 33% of the cell weight.
Hemoglobin is dissolved in the cytosol , normal value for hemoglobin are 14 to 20g/100
ml of blood in infants, 12 to 15g/100ml in adult females, and 14 to 16.5g/100ml in adult
males.
As you will see later , certain proteins (antigens) on the surfaces of red-blood cells are
responsible for the various blood groups. The ABO and Rh groups are examples.
Fig # 19.11 : Antigens and antibodies involved in the ABO blood grouping system:

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RBC-PHYSIOLOGY :
i.

ii.
iii.
iv.

v.
vi.
vii.
viii.

As blood passes through the lungs , hemoglobin inside RBCs combines with oxygen
to form oxyhemoglobin. A hemoglobin molecule consists of a protein called
globin, globin [protein molecule ] composed of four polypeptide chains (two called
alpha and two called beta), plus four non-protein pigments called hemes .
Each heme contains an iron ion that can combine reversibly with one oxygen
molecule . the oxygen is transported in this state to other tissues of the body .
In the tissues, the iron-oxygen reaction reverses . hemoglobin releases oxygen ,
which diffuses into the interstitial fluid and from there into cells.
RBCs are highly specialized for their oxygen transport function . each one contains
about 280 million hemoglobin molecules . since RBCs have no nucleus , all their
internal space is available for oxygen transport.
Moreover, since they lack mitochondria and generate ATP anaerobically (without
oxygen ) .
RBCs dont consume any of the oxygen that they transport .
Even the shape of a RBC facilitates its function.
A bi-concave disk has a much greater surface area for its volume than , say, a sphere
or a cube. This shape confers two advantages . first , there is a large surface area for

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ix.
x.

xi.

xii.
xiii.

xiv.

the diffusion of gas molecules into or out of the RBC. Second , the biconcave disk is a
very flexible shape , which permits RBCs to squeeze through narrow capillaries.
A serious disorder called sickle-cell anemia (SCA) is due to a genetic defect that
results in substitution of just two out of 574 amino-acids in hemoglobin .
Replacement of the polar amino-acid glutamate by non-polar valine at one position
in each of the two beta chains greatly decreases the solubility of deoxygenated
hemoglobin in water.
When this abnormal hemoglobin is exposed to low oxygen , it forms crystals that
deform RBCs into a characteristic sickle shape (see fig 19.13). sickled RBCs are
more rigid and may lodge in small capillaries.
Sickle-cell anemia is discussed at the end of the chapter.
Hemoglobin also transports about 23% of the total carbon dioxide , a waste product
of metabolism . blood flowing through tissue capillaries picks up carbon dioxide ,
some of which combines with amino acids in the globin portion of hemoglobin to
form carbaminohemoglobin .
This complex is transported to the lungs , where the carbon dioxide is released and
then exhaled .

Fig # 19.3 : shape of RBCs and hemoglobin molecules :

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EXHIBIT 19.2
HEMATOPOLETIC-GROWTH
FACTORS
Factor

Function

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[Link] cell
growth
factor (steelfactor)

Stimulates
pluripotent
hematopoietic
stem cells
(hemocytoblasts).

2.
Stimulates
Interleukin-3 pluripotent
(multi-CSFa ) hematopoietic
stem cells and
progenitors of
eosinophils ,
neutrophils ,
basophils ,
monocytes, and
platelets .
3.
GranulocyteMacrophage
CSF (GMCSF)

Stimulates
development of
erythrocytes,
platelets,
granulocytes
(eosinophils,
neutrophils, and
basophils) and
monocytes .

4.
Macrophage
CSF (M-CSF)

Stimulates
development of
monocytes and
macrophages .

5.
Granulocyte
CSF (G-CSF)

Stimulates
development of
neutrophils.

6.
Stimulates
Interleukin-5 development of
eosinophils .

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7.
Stimulates
Interleukin-7 development of
B-lymphocytes.
{ CSF= Colony
Stimulating
Factor}

RBC-LIFE-SPAN-AND-NUMBER:i.
ii.

iii.

iv.

v.
vi.
vii.

viii.

ix.

x.

Red-blood cells live only about 120 days because of wear and tear on their plasma
membranes as they squeeze through blood capilleries.
Without a nucleus and other organelles , RBCs cannot synthesize new components
to replace damaged ones. The plasma membrane thus becomes more fragile with
age and the cell more likely to burst .
Especially as it squeezes through narrow channels in the spleen . worn-out RBCs are
removed from circulation and destroyed by fixed phagocytic macrophages in the
spleen and liver and the breakdown products are recycled .
A healthy male has about 5.4 million red blood cells per cubic millimeter (mm 3) of
blood , and a healthy female has about 4.8 million red blood cells per cubic
millimeter (mm3) of blood.
There are about 50 mm3 in a drop of blood.
The higher value in males is due to their higher levels of testosterone , which
stimulates the synthesis of erythropoietin .
To maintain normal quantities of erythrocytes [RBCs] , new mature cells must enter
the circulation at the astonishing rate of at least 2 million per second . this pace
assures a constant balance between production and destruction of RBCs .
After phagocytosis of RBCs by macrophages, hemoglobin is recycled [ fig # 19.4] .
the globin portion of hemoglobin is split from the heme and broken down into
amino-acids that may be reused for protein synthesis .
The heme portion is broken down into (1) Iron, which associates with proteins to
form ferritin or hemosiderin , and (2) bilirubin, a pigment that does not contain iron
. ferritin and hemosiderin are storage forms of iron found mostly in muscle fibers ,
liver cells and macrophages of the spleen and liver.
Upon release from a storage site or absorption from the gastro-intestinal tract , iron
attaches to a plasma beta-globulin called transferrin , in this form its delivered to

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xi.

xii.

xiii.

bone marrow , where RBC precursors take it up through receptor-mediated

endocytosis [ see fig 3.12 ] for use in production of new hemoglobin molecules.
The non-iron portion of heme is converted into biliverdin , a greenish pigment , and
then into bilirubin. Bilirubin enters the blood and is secreted by liver cells into bile .
Bile passes from the liver into the small intestine .
Bacteria in the large intestine convert bilirubin into urobilinogen . some
urobilinogen is absorbed back into the blood , converted to urobilin (yellow) , and
excreted in urine .
Most urobilinogen is eliminated in feces in the form of a brown pigment called
stercobilin , which gives feces its characteristic color.

Fig # 19.4 , Formation and destruction of red blood cells and recycling of hemoglobin
components.

PRODUCTION-OF-RBCs :i.
ii.

The process of erythrocyte formation is called erythropoiesis . it starts in red

bone marrow with a pro-erythroblast [ see fig 19.2 ] .
The proerythroblast (rubriblast) gives rise to an early erythroblast (prorubricyte), which then develops into an intermediate erythroblast (rubricyte),
the first cell in the sequence that begins to synthesize hemoglobin.

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iii.

iv.

v.
vi.

vii.
viii.

ix.

x.

xi.

xii.
xiii.
xiv.

The intermediate erythroblast next develops into a late erythroblast (metarubricyte), in which hemoglobin synthesis is at a maximum . in the next stage ,
the late-erythroblast ejects its nucleus and becomes a reticulocyte.
Loss of the nucleus allows the center of the cell to indent , giving the cell a biconcave shape . reticulocytes contain about 34% hemoglobin and retain some
mitochondria , ribosomes , and endoplasmic reticulum .
They pass from bone marrow into the blood-stream by squeezing between the
endothelial cells of blood capillaries .
Normally, they develop into erythrocytes [or mature red-blood-cells] , within one
to two days after their release from bone-marrow. (A nucleated RBC found in
red-bone-marrow, but rarely found in blood is called a normoblast).
Normally, erythropoiesis and red-blood cell destruction proceed at the same
pace.
If the oxygen-carrying capacity of the blood falls because erythropoiesis is not
keeping up with RBC destruction , a negative feedback system steps up
erythrocyte production [fig # 19.5].
The controlled condition is the rate of oxygen delivery to body tissues . oxygen
delivery may fall due to anemia , a lower than normal number of RBCs or
quantity of hemoglobin , or circulatory problems that reduce blood flow to
tissues.
Cellular oxygen deficiency , called hypoxia, may also occur if not enough
oxygen enters the blood , for example , when you dont breathe in enough
oxygen . this situation commonly occurs at high altitudes, where the air contains
less oxygen .
Whatever the cause , hypoxia stimulates the kidneys to step up release of the
hormone erythropoietin. This hormone circulates through the blood to the
red-bone marrow , where it speed the development of pro-erythro-blasts into
reticulocytes .
Anemia has many causes: lack of iron , lack of certain amino-acids , and lack of
vitamin B12 are but a few.
Iron is needed for the heme part of the hemoglobin molecule . the amino-acids
are needed for the protein, or globin, part.
Vitamin B12 helps the red-bone marrow to produce erythrocytes [RBCs].this
vitamin is obtained from meat , especially liver, but it cannot be absorbed by the
lining of the small intestine without the help of another substance ---- intrinsicfactor(IF) produced by the parietal cells of the stomach mucosa.

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xv.
xvi.

Intrinsic-factor facilitates the absorption of vitamin B12 (extrinsic-factor). Once

absorbed, its stored in the liver.
Several types of anemia are described later in the chapter .

Fig # 19.5 , Negative feedback regulation of erythropoiesis (red-blood cell formation).

..
Fig # 19.2 origin, development and structure of blood cells:-

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Fig # 19.8 : Platelet plug formation :

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Fig # 19.9 : Fibrin-threads , platelets , red blood cells and white-blood cells in a blood-clot :

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LEUKOCYTES [ WHITE-BLOOD-CELLs):
WBC-ANATOMY-AND-TYPES:
i.

ii.
iii.

Unlike red-blood cells , leukocytes or white blood cells [ WBCs ] have a nucleus and
dont contain hemoglobin molecule [see fig 19.2 ] , the two major groups of WBCs are
Granular-leukocytes and Agranular-leukocytes.
Granular-leukocytes (granulocytes) have lobed nuclei and conspicuous granules in
the cytoplasm .
The three types are neutrophils , which are 10 to 12 m in diameter; eosinophils, which
are 10 to 12 m in diameter; and basophils , which are 8 to 10 m in diameter. These
names reflect the types of granules seen when using common hematology stains, such
as wrights stain, which include both acidic cosin and a basic dye [ fig # 19.6 ].

Neutrophils:
iv.

The nuclei of neutrophils have two to six lobes , connected by very thin strands. As the
cells age, the extent of nuclear lobulation increases . because older neutrophils appear
to have many differently shaped nuclei, they are often called polymorphonuclear
leukocytes (PMNs), polymorphs, or polys.

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v.
vi.

Younger neutrophils are often called bands because their nucleus is more rodshaped.
When stained, the cytoplasm of neutrophils included fine , evenly distributed pale lilaccolored granules.

Eosinophil:
vii.

viii.

The nucleus of an eosinophil usually has two lobes connected by a thin or thick strand.
Large , uniform-sized granules pack the cytoplasm but usually do not cover or obscure
the nucleus.
These cosinophilic (= cosin loving ) granules stain red-orange .

Basophil:
ix.

A basophils nucleus is bilobed or irregular in shape, often in the form of a letter S. the
cytoplasmic basophilic granules are round , variable in size , stain blue-black , and
commonly obscure the nucleus.

Agranular-Leukocytes (Agranulocytes):
x.
xi.

In agranular-leukocytes (agranulocytes), no cytoplasmic granules can be seen under a

light microscope, owing to their small size and poor staining qualities.
The two kinds of agranular-leukocytes (agranulocytes) are lymphocytes [ T-cells and
B-cells ] which are 7 to 15 m in diameter, and monocytes which are 14 to 19 m in
diameter (fig # 19.6).

Lymphocytes:
xii.

The nuclei of lymphocytes are darkly stained , round, or slightly indented . the
cytoplasm stains sky blue and forms a rim around the nucleus.

Monocytes:
xiii.
xiv.

The nuclei of monocytes are usually indented or kidney-shaped, and the cytoplasm has
a foamy appearance .
The blood is merely a conduit for monocytes, which migrate out into the tissues ,
enlarge , and differentiate into macrophages. Some are fixed macrophages, which
means they reside in a particular tissue , for example , alveolar macrophages, spleen
macrophages, or stellate reticuloendothelial-cells in the liver. Others are wandering
(free) macrophages , which roam the tissues and gather at sites of infection or
inflammation .

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----xv.

Just as red-blood cells have surface proteins , so do white blood cells and all other
nucleated cells in the body . some of these proteins , called major histocompatibility
(MHC) antigens , are unique for each person (except for identical twins ).

WBC-PHYSIOLOGY :
[ Immune-Response = Phagocytosis ]
I.
II.

III.

The skin and mucous membranes of the body are continuously exposed to microbes
and their toxins .
Some of these microbes can invade deeper tissues to cause disease. Once pathogens
enter the body , the general function of white blood cells is to combat them by
phagocytosis [ or immune-responses ] .
Neutrophils and macrophages are active in phagocytosis: they can ingest bacteria and
dispose of dead matter (see fig 3.11).

Chemotaxis :
IV.
V.

Several different chemicals in inflamed tissue attract phagocytes toward the tissue this
phenomenon is called chemotaxis .
Among the substances that provide stimuli for chemotaxis are toxins produced by
macrobes , specialized products of damaged tissues called kinms, and some of the
colony stimulating factors, such as GM-CSF and G-CSF. The CSFs also enhance phagocytic
activity of neutrophils and macrophages.

DIAPEDESIS = EMIGRATION :
VI.

VII.
VIII.

Most leukocytes possess , to some degree, the ability to squeeze through the minute
spaces between the cells that form the walls of capillaries and through connective and
epithelial tissues.
This movement through capillary walls is called diapedesis [ or emigration ] .
First , part of the cell membrane projects outward and the cytoplasm and nucleus flow
into the projection . then , the rest of the membrane flows . another projection is made ,
and so on, until the cell has migrated to its destination (see fig # 22.11) .

NEUTROPHILS:
IX.
X.

Among the WBCs, neutrophils respond to tissue destruction by bacteria most quickly .
After engulfing a pathogen during phagocytosis , a neutrophil unleashes several
destructive chemicals . these include the enzymes lysozyme , which destroys certain

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XI.

bacteria, and strong-oxidants, such as the superoxide anion (O2- ), hydrogen peroxide
(H2O2), and hypochlorite anion (OCl- ), which is similar to household bleach .
Neutrophils also contain defensins , defensins is a proteins that exhibit a broad range
of anti-biotic activity against bacteria , fungi , and viruses. Defensins form peptide
spears that poke holes in microbe membranes . the resulting leakiness kills the invader .

Monocytes:
XII.
XIII.

Monocytes take longer to reach a site of infection than do neutrophils, but they arrives
in larger numbers and destroy more microbes .
Upon arrival they enlarge and differentiate into wandering macrophages, which clean
up cellular debris and microbes following an infection .

Eosinophils :

XIV.

XV.
XVI.

Eosinophils leave the capillaries and enter tissues fluid . they are believed to release
enzymes , such as histaminase [ enzymes are those molecules who have ase at the
end of there name ], that combat the effects of histamine and other mediators of
inflammation in allergic reactions .
Eosinophils also phagocytize antigen-antibody complexes and are effective against
certain parasitic worms .
A high eosinophil count often indicates an allergic condition or a parasitic infection.

Basophils:
XVII.

XVIII.

Basophils are also involved in inflammatory and allergic reactions . they leave capillaries
, enter tissues, and develop into mast cells, which can liberate heparin , histamine , and
serotonin .
These substances intensify the inflammatory reaction and are involved in
hypersensitivity (allergic) reactions (chapter 22 ).

Types-Of- Lymphocytes:
XIX.
XX.

The two major types of lymphocytes are B cells and T cells. These cells are the major
combatants in immune responses (detail in chapter 22).
T-cells divide into Helper T-cells and Cytotoxic(Killer) T-cells.

Antigen:

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XXI.

XXII.

Briefly , a substance that stimulates an immune response is called an antigen . most

antigens are foreign proteins , ones not synthesized by the body . they include bacterial
enzymes , toxins , and structural proteins .
In response to certain antigens , B-cells develop into plasma cells that produce
antibodies (fig # 19.7) .

(main heading ) Antigen-Antibodies Response :

(sub heading )Anti-bodies:
XXIII.

XXIV.

Anti-bodies are proteins of the immunoglobulin family . A specific antibody will

generally bind only to a certain antigen . the two together are called an antigenantibody complex.
However , unlike enzymes , which enhance the reactivity of the substrate , antibodies
cover their antigens so the antigens cannot come in contact with other chemicals in
the body . in this way , bacterial poisons are inactivated , and the bacteria themselves
are destroyed. This process is called the antigen-antibody response.

T-CELLs:
XXV.

Anti-gens also stimulate T-cells to take part in immune-responses. One group of T-cells,
the cytotoxic (killer) T-cells, react by destroying foreign invaders directly . another
group , called helper T-cells , helper T-cells assists both B-cells and cytotoxic T-cells . Tcells are especially effective against viruses, fungi, transplanted cells , cancer-cells, and
some bacteria.

IMMUNE-RESPONSES :
XXVI.

Immune-responses mediated by B and T-cells help combat infection and provide

protection against some diseases. They also are responsible for transfusion-reactions ,
allergies and the bodys rejection of organs transplanted from a person with different
MHC antigens.

-------XXVII.

An increase in the number of circulating WBCs usually indicates inflammation or

infection . because each type of WBCs plays a different role , determining the
percentage of each type in the blood assists in diagnosing the condition.

WBC-LIFE-SPAN-AND-NUMBER:
Fig # 19.7 [production of plasma cells and antigen-antibody response ]

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I. Bacteria exist everywhere in the environment and have continuous access to the body
through [via ] the mouth, nose and pores of the skin .
II. Furthermore , many cells , especially those of epithelial tissue , age and die daily , and
their remains must be disposed of by phagocytes that actively ingest bacteria and debris
.
III. However , the engulfed debris interferes with normal metabolic activities and sooner or
later causes death of the phagocyte, which then is consumed by another phagocyte.
IV. In a healthy body , some WBCs , especially lymphocytes , can live for several months or
years , but most live only a few days . during a period of infection , phagocytic WBCs
may live only a few hours .
V. WBCs are far less numerous than red-blood-cells , averaging from 5000 to 10,000 cells
per cubic millimeter (mm3) of blood .
VI. RBCs therefore outnumber white-blood-cells about 700:1 .
VII. The term leukocytosis refers to an increase in the number of WBCs.

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VIII.

An abnormally low level of WBCs (below 5000/mm3) is termed leukopenia .

THROMBOCYTES [PLATELETS]:
I. Besides the im-mature cell types that develop into erythrocytes and leukocytes,
pluripotent hematopoietic stem cells also differentiate into megakaryo-blasts (see fig
# 19.2) .
II. megakaryo-blasts ultimately transform into meta[meta = beta]-megakaryo-cytes,
large cells that shed fragments of cytoplasm .
III. Each fragment become enclosed by a piece of the cell membrane and is called a
thrombocyte [ or platelet ] .
IV. thrombocyte [ or platelet ] break off from the meta-mega-karyo-cytes in bone
marrow and then enter the blood circulation .
V. between 250,000 and 400,000 platelets are present in each cubic millimeter (mm 3) of
blood . they are disc-shaped , 2 to 4 m in diameter, and exhibit many granules but no
nucleus .
VI. platelets helps repair slightly damaged blood vessels . their granules contain chemicals
that upon release promote blood clotting .
VII. platelets have a short life span , normally just five to nine days . Aged and dead platelets
are removed by fixed macrophages in the spleen and liver .
VIII.
A summary of the formed elements in blood is presented in Exhibit 19.3.

EXHIBIT # 19.3

SUMMARY-OF-THE-FORMED-ELEMENTS-IN-BLOOD:

Formed-elements

Number

Diameter Life(in m)
span

Function

Erythrocytes (RedBlood-Cells)

4.8
million/mm3
in females;
5.4
million/mm3

Transport
oxygen and
carbon
dioxide .

120
days.

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in males.
Leukocytes (WhiteBlood-Cells )

500010,000/mm3

Granular-leukocytes

60-70% of
total.

10-12

Phagocytosis.
Destruction
of bacteria
with
lysozyme ,
defensins,
and strong
oxidants ,
such as
superoxide
anion,
hydrogen
peroxide ,
and
hypochlorite
anion .

2-4% of total

10-12

Combat the
effects of
histamine in
allergic
reactions ,
phagocytize
antigenantibody
complexes ,
and destroy
certain
parasitic
worms .

1. Neutrophils

2. Eosinophils

Fewhours to
a fewdays.

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3. Basophils

0.5-1% of
total .

8-10

Liberate
heparin ,
histamine,
and
serotonin in
allergic
reactions
that intensify
the overall
inflammatory
response .

Agranular-leukocytes

20-25% of
total .

7-15

Mediate
immuneresponses,
including
antigenantibody
reactions . Bcells develop
into plasma
cells , which
secrete
antibodies .
T-cells attack
invading
viruses ,
cancer-cells,
and
transplanted
tissue-cells.

3-8% of total
.

14-19

Phagocytosis
(after
transforming
into fixed or
wandering
macrophages

1. Lymphocytes

2. Monocytes

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).
Thrombo-cytes
(Platelets)

250,0002-4
3
400,000/mm

5-9
days .

Blood-clotting
.

--HEMOSTASIS:
Hemostasis refers to the stoppage of bleeding. When blood vessels are damaged or
ruptured , the hemostatic-response must be quick , localized to the region of damage,
and carefully controlled .
Three basic mechanisms prevent blood loss: (1) Vascular-Spasm, (2) Platelet-plugformation, and (3) Blood-coagulation (clotting ). These three mechanisms are useful for
preventing hemorrhage in smaller (micro-circulation) blood vessels, but extensive
hemorrhage from larger vessels usually requires medical intervention.
1) VASCULAR-SPASM:
I.
When blood vessels (arteries or arterioles ) are damaged , the circularly
arranged smooth muscle in its wall contracts immediately . this is called a
vascular-spasm and it reduces blood loss for several minutes to several hours
, during which time the other hemostatic mechanisms go into operation.
II.
The spasm is probably caused by damage to the smooth muscle and form
reflexes initiated by pain-receptors .
2) PLATELET-PLUG-FORMATION:
I.
In there unstimulated state , platelets are disc-shaped . considering their small
size , platelets pack an impressive array of chemicals.
II.
Two types of granules are present in the cytoplasm: (1) alpha-granules contain
clotting factors and platelet-derived growth factor [PDGF] , which can cause
proliferation of vascular endothelial cells, vascular smooth muscle fibers, and
fibroblasts to help repair damaged blood vessel walls and (2) dense granules
contain ADP,ATP,Ca2+ ions , and serotonin .
III.
Also present are enzyme systems that produce thromboxane A2, a
prostaglandin; fibrin-stabilizing factor , which helps to strengthen a blood clot;
lysosomes; some mitochondria ; membrane systems that take up and store
calcium and provide channels for release of the contents of granules ; and
glycogen .
1) PLATELET-ADHESION :

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IV.

In the first phase of platelet-plug-formation. Platelets contact and stick to

parts of a damaged blood vessel, such as collagen under the damaged
endothelial cells. This process is called Platelet-Adhesion (fig # 19.8 (a)).
2) PLATELET-RELEASE-REACTION :
V.
As a result of adhesion, the platelets become activated and their characteristics
change drastically . they extend many projections that enable them to contact
one another and begin to liberate the contents of their granules . this phase is
called the Platelet-Release-Reaction (fig # 19.8 (b)).
3) PLATELET-AGGREGATION :
VI.
Liberated ADP and thromboxane A2 play a major role by acting on nearby
platelets to activate them as well.
VII.
Serotonin and thromboxane A2 function as vasoconstrictors , causing
contraction of the vascular smooth muscle. Which decreases blood flow
through the injured vessel.
VIII. The release of ADP also makes other platelets in the area sticky . and the
stickiness of the newly recruited and activated platelets cause them to adhere
to the originally activated platelets . this gathering of platelets is called Plateletaggregation.
------IX.

3)
I.

II.
III.
IV.

Eventually , the accumulation and attachment of large numbers of platelets form

a mass called a platelet-plug (fig # 19.8 c ) . the plug is very effective in
preventing blood loss in a small vessel.
X.
Although the platelet plug is initially loose , it becomes quite tight when
reinforced by fibrin threads formed during coagulation .
XI.
A platelet plug can stop blood loss completely if the hole in a blood vessel is
small.
COAGULATION (CLOTTING):
Normally , blood remains liquid as long as it stays within its vessels. If its drawn from
the body , however , it thickens and forms a gel. Eventually , the gel separates from
the liquid .
The straw-colored liquid , called serum , serum is simply plasma minus its clotting
proteins .
The gel is called a clot and consists of a network of insoluble protein fibers called
fibrin in which the formed elements of blood are trapped (fig # 19.9 ).
The process of gel-formation is called coagulation or clotting . if blood clots too
easily , the result can be thrombosis clotting in an unbroken blood vessel.

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V.
VI.

VII.
VIII.

IX.
X.
XI.

XII.

If the blood takes too long to clot , a hemorrhage can result .

Clotting involves several enzymes and other chemicals known as Coagulation
(clotting) factors . most coagulation factors are synthesized in the liver and released
into blood plasma. Some are released by platelets , and one (tissue factor also called
thromboplastin ) is released from damaged tissue cells.
The various clotting factors and their synonyms are listed in exhibit 19.4 .
Clotting is a complex process in which coagulation factors activate each other . once
the process is initiated , there is a cascade of reactions that acts in a positive
feedback manner to form a large quantity of product. We will describe clotting in
three basic stages: (below).
Stage 1. Formation of prothrombinase(prothrombin-activator).
Stage 2. Conversion of prothrombin (a plasma protein formed by the liver) into the
enzyme thrombin by prothrombinase .
Stage 3. Conversion of soluble fibrinogen (another plasma protein formed by the
liver) into insoluble fibrin by thrombin. Fibrin forms the threads of the clot.
(cigarette smoke contains at least two substances that interfere with fibrin
formation. ).
Stage 1, the formation of prothrombinase , is initiated by the interplay of two
mechanisms : the extrinsic and intrinsic pathways of blood clotting .

Stage 1: EXTRINSIC-PATHWAY:
XIII.

XIV.

XV.

The extrinsic pathway of blood clotting has fewer steps than the intrinsic pathway
and occurs rapidly , within a matter of seconds if trauma is severe . it is so named
because a tissue protein called tissue-factor(TF), also known as thromboplastin or
coagulation factor III, leaks into the blood from cells outside (extrinsic to ) blood
vessels and initiates the formation of prothrombinase.
TF is a complex mixture of lipoproteins and phospholipids released from the surface
of damaged cells. It activates coagulation factor VII (fig # 19.10a), which next
combines with factor X, thus activating it .
Once factor X is activated , it combines with factor V in the presence of calcium ions
to form the active enzyme prothrombinase . this completes the extrinsic pathway of
stage 1.

Stage 1: INTRINSIC-PATHWAY:
XVI.

The intrinsic-pathway of blood clotting is more complex then the extrinsic pathway,
and it occurs more slowly , usually requiring several minutes .

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XVII.

The intrinsic pathway is so named because its activators are in direct contact with
blood or contained within (intrinsic to ) the blood ; outside tissue damage is not
needed .
XVIII. If endothelial cells (cells that line blood vessels) become roughened or damaged ,
blood can come in contact with collagen in the surrounding basal lamina.
XIX. In addition , trauma to endothelial cells causes damage to blood platelets , resulting
in the release of phospholipids by the platelets . contact with collagen (or with the
slippery glass sides of a blood collection tube) activates coagulation factor XII (fig #
19.10b ) .
XX.
In turn , factor XII activates XI, which activates factor IX . Activated factor VII (from
the extrinsic pathway) also can activate factor IX. Activated factor IX joins with factor
VIII and platelet phospholipids to activate factor X.
XXI. Once factor X is activated , it combines with factor V to form the active enzyme
prothrombinase , just as occurs in the extrinsic pathway. Again , Ca2+ is a cofactor in
several of the reactions. This completes the intrinsic pathway of stage 1.
Fig # 19.10 the blood clotting cascade .

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-----Stages 2 and 3: COMMON-PATHWAY:

I.

II.

III.

The steps in clotting after formation of factor X are the same in both pathways (fig #
19.10c) . prothrombinase and Ca2+ catalyze the conversion of prothrombin to
thrombin in stage 2 . in stage 3, thrombin , in the presence of Ca 2+, converts
fibrinogen , which is soluble, to loose fibrin threads, which are insoluble .
Thrombin also activates factor XIII (fibrin stabilizing factor), which strengthens and
stabilizes the fibrin threads into a sturdy clot. Factor XIII occurs in plasma, and its
also released by platelets trapped in the clot .
Thrombin has two positive feedback effects. In one, through factor V, it accelerates
the formation of prothrombinase . prothrombinase , in turn, accelerates the
production of more thrombin, and so on .

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IV.

Thrombin also activates platelets , which reinforces their aggregation and release of
phospholipids. This is a second positive feedback cycle. If unchecked , a clot would
continue to get larger and larger, as a result of the positive feedback cycles .
however, fibrin has the ability to absorb and inactivate up to 90% of the thrombin
formed from prothrombin.
This helps stop the spread of thrombin into the blood and thus limits spread of the
clot beyond the site of damage.

V.

EXHIBIT 19.4
COAGULATION-FACTORS-AND-THEIR-SYNONYMS
CoagulationFactors

Description

1.

Fibrinogen.

2.

II

Prothrombin.

3.

III

Tissue-Factor (thromboplastin).

4.

IV

Calcium-ions.

5.

Proaccelerin , labile-factor, or
accelerator globulin.

6.

VII

Serum prothrombin conversion

accelerator (SPCA), stable-factor,
or proconvertin.

7.

VIII

Antihemophilic-factor (AHF),
Antihemophilic-factor A, or
antihemophilic globulin (AHG).

8.

IX

Christmas factor, plasma

thromboplastin component (PTC),
or antihemophilic factor B.

9.

Stuart-factor, Power-factor,
thrombokinase .

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10. XI

Plasma thromboplastin
antecedent (PTA) or antihemophilic factor C.

11. XII

Hageman factor, glass-factor, or

contact factor.

12. XIII

Fibrin stabilizing factor (FSF) or

fibrinase.

There is no factor VI . Prothrombinase (prothrombin-activator) is a combination of activated

factors V and X.
NEED-FOR-VITAMIN K:
i.

ii.

iii.

iv.

Normal clotting depends on adequate vitamin K in the body . Although

vitamin K is not involved in actual clot formation, it is required for the
synthesis of four clotting factors by liver cells: factors II (prothrombin), VII, IX,
and X.
Vitamin K is normally produced by bacteria that inhabit the large intestine. It
is a fat-soluble vitamin and can be absorbed through [ via] the mucosa of the
intestine and into the blood only if fat absorption is normal .
People suffering from disorders that prevent absorption of fat (for example ,
inadequate release of bile into the small intestine) often experience
uncontrolled bleeding .
Clotting may be encouraged by applying a thrombin or fibrin spray, a rough
surface such as gauze, or heat to the wound.

CLOT-RETRACTION-AND-REPAIR :
I.

II.

III.

Once a clot is formed , it plugs the ruptured area of the blood vessel and thus
prevents hemorrhage (bleeding). Clot-retraction or syneresis is the consolidation or
tightening of the fibrin clot .
The fibrin threads attached to the damaged surfaces of the blood vessel gradually
contract owing to platelets pulling on them . as the clot retracts, it pulls the edges of
the damaged vessels closer together .
Thus the risk of hemorrhage is further decreased. During retraction , some serum
escapes between the fibrin threads, but the formed elements in blood remain
trapped in the fibrin threads.

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IV.

V.

Normal clot retraction depends on an adequate number of platelets . platelets in

the clot also release factor-XIII, which strengthens and stabilizes the clot, and other
factors, which help compress the clot.
Permanent repair of the blood vessel can then take place. In time , fibroblasts form
connective tissue in the ruptured area , and new endothelial cells repair the lining .

FIBRINOLYSIS:
I.

Many times a day little clots start to form , sometimes inappropriately, sometimes at a
site of minor roughness or at a developing atherosclerotic plaque inside a blood vessel.
Because blood clotting involves several positive feedback cycles, a clot has a tendency
to spread , which might block blood flow through undamaged vessels .
The fibrinolytic-system provides checks and balances so that clotting does not get out of
hand. It also dissolves clots at a site of damage once the damage is repaired .
Dissolution of a clot is called fibrinolysis. When a clot is formed , an inactive plasma
enzyme called plasminogen is incorporated into the clot. Both body tissues and blood
contain substances that can activate plasminogen to plasmin (fibrinolysin), an active
plasma enzyme .
Among these substances are thrombin, activated factor XII, and tissue plasminogen
activator (t-PA), which is synthesized in endothelial cells of most tissues and liberated
into the blood.
Once plasmin is formed , it can dissolve the clot by digesting fibrin threads and
inactivating substance such as fibrinogen, prothrombin , and factors V, VIII, and XII .

II.
III.
IV.

V.

VI.

HEMOSTATIC-CONTROL-MECHANISMS:
I.
II.
III.

IV.

V.

It was noted earlier that even through thrombin has a positive feedback effect on
blood clotting , clot formation normally occurs locally at the site of damage.
It does not extend beyond a wound site into the general circulation, in part because
fibrin absorbs the thrombin into the clot.
Another reason for localized clot formation is that some of the coagulation factors
are carried away by the blood so that their concentrations are not high enough to
bring about widespread clotting .
Several other mechanisms that control blood clotting also operate. For example ,
both endothelial cells and white blood cells produce a prostaglandin called
prostacyclin (PGI2) .
This substance opposes the actions of thromboxane A2. Its a powerful inhibitor of
platelet adhesion and release. Also , substances that inhibit coagulation are
present in blood . such substances are called anti-coagulants .

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UNDERGRADUATE PROGRAM :
VI.

These include antithrombin-III (AT-III), which blocks the action of factors XII,XI,IX, X
and II(thrombin); protein-C, which inactivates factors V and VIII, the two major
clotting factors not blocked by AT-III , and enhances activity of plasminogen
activators; alpha-2-macroglobulin, which inactivates thrombin and plasmin ; and
alpha-1-anti-trypsin, which inhibits factor XI.

HEPARIN:
VII.

VIII.
IX.

Heparin is another anticoagulant. Its produced by mast-cells and basophils . A

similar molecule protrudes from the plasma membrane of endothelial cells into the
blood.
Heparins anti-coagulant activity is to combine with AT-III and increase its
effectiveness in blocking thrombin.
Heparin is also a pharmacologic anti-coagulant extracted from animal lung tissue
and intestinal mucosa. Its often used in open heart surgery and during hemodialysis.

WARFARIN (COUMADIN):
X.
XI.
XII.

Another anti-coagulant is the pharmaceutical preparation warfarin (Coumadin) ,

which may be given to patients who are prone to develop clots.
It acts as an antagonist to vitamin K and thus blocks synthesis of four clotting
factors (II,VII,IX, and X ).
Warfarin is slower acting than heparin. To prevent clotting in donated blood , blood
banks and laboratories often add a substance, for example, CPD(citrate phosphate
dextrose ), that removes Ca2+.

INTRA-VASCULAR-CLOTTING:I.

II.
III.

IV.

Despite the anti-coagulating and fibrinolytic mechanisms, blood clots sometimes

form within the cardio-vascular system. Such clots may be initiated by roughened
endothelial surfaces of a blood vessel as a result of atherosclerosis, trauma, or
infection.
These conditions induce adhesion of platelets.
Intra-vascular clots may also form when blood flows too slowly (stasis), allowing
clotting factors to accumulate locally in high enough concentrations to initiate
coagulation.
Clotting in an unbroken blood vessel (usually a vein) is called thrombosis (thrombo =
clot). The clot itself is a thrombus. A thrombus may dissolve spontaneously , but if it
remains intact , there is the possibility that the thrombus will become dislodged and
be carried with the blood to the lungs .

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V.

VI.

If it occurs in an artery , the clot may block blood flow to a vital organ . a blood clot ,
bubble of air , fat from broken bones, or a piece of debris transported by the blood
stream is called an embolus (em=in; bolus=a mass).
When an embolus becomes lodged in the lungs, the condition is called pulmonaryembolism.

GROUPING(TYPING)-OF-BLOOD:
I.
II.
III.

The surfaces of erythrocytes[RBCs] contain genetically determined antigens called

agglutinogens or iso-anti-gens.
There are at least 14 blood group systems and more than 100 antigens that can be
detected on the surface of red-blood cells[RBCs].
The two major blood group classifications--- ABO and Rh---- are the ones we will
discuss in detail . among the others are the Lewis, Kell, Kidd, and Duffy-systems.

ABO :
i.

ii.
iii.

iv.

v.
vi.

vii.
viii.

The ABO blood grouping is based on two glyco-lipid agglutinogens called A and B (fig
# 19.11). people whose erythrocytes display only agglutinogen A are said to have
blood type A. those who have only agglutinogen B are have blood type B.
Individuals who have both A and B agglutinogen they are have blood type AB.
whereas those who manufacture neither are having blood type O.
Every person inherits two genes , one from each parent , that are responsible for
production of these agglutinogens. The six possible combinations are
OO,AO,AA,BO,BB,and AB.
Both A and B are inherited as dominant traits; O is inherited as a recessive trait. The
six genetic combinations determine blood type as follows:
1. OO produces type O-blood.
[Link] and AA produce type A-blood.
3. BO and BB produce type B-blood.
4. AB produces type AB-blood.
These four blood types are not equally distributed . the incidence of ABO and Rh
groups among various ethnic groups is indicated in Exhibit 19.5.
Most peoples blood plasma contains naturally occurring anti-bodies called
agglutinins , or iso-anti-bodies , that will react with the A and B agglutinogens
(antigens) if the two are mixed .
These are agglutinin -a (anti-A), which reacts with agglutinogen-A.
And agglutinin-b (anti-B), which reacts with agglutinogen-B.

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UNDERGRADUATE PROGRAM :
ix.

x.

xi.

xii.
xiii.
xiv.
xv.

xvi.

xvii.

xviii.

xix.

The agglutinins formed by each of the four blood types are shown in [fig # 19.11].
you do not have agglutinins that react with the agglutinogens of your own
erythrocytes, but most likely you do have an agglutinin for any agglutinogen your
RBCs lack.
In an incompatible blood transfusion , agglutinins in the recipients plasma bind to
the agglutinogens on the donated RBCs . this reaction is another example of an
antigen-antibody response (see fig # 19.7) .
When antigen-antibody complexes form in the body , they activate plasma proteins
of the complement family . In essence, complement molecules poke holes in the
donated RBCs , causing them to burst and release hemoglobin into the plasma.
Such a reaction is called hemolysis. The liberated hemoglobin may cause kidney
damage.
As an example of an incompatible blood transfusion, consider what happens if an
individual with type-A blood receives a transfusion of type-B blood.
The recipients blood (type-A) contains A-agglutinogens on the red-blood cells and
b-agglutinins in the plasma.
The donors blood (type-B) contains B-agglutinogens and a-agglutinins. Given this
situation , two things can happen. First , the b-agglutinins in the recipients plasma
can bind to the B-agglutinogens on the donors erythrocytes [ RBCs] , causing
hemolysis and possibly agglutination of the red-blood cells. Second, the aagglutinins in the donors plasma can bind to the A-agglutinogens on the
recipients erythrocytes [ RBCs].
However, the second reaction is usually not serious because the donors aagglutinins become so diluted in the recipients plasma that they dont cause any
significant hemolysis of the recipients RBCs .
Thus a person with type-A blood may not receive type-B or AB blood. But a person
with A-blood may receive type-A or type-O blood. The interactions of the four blood
types of the ABO-system are summarized in Exhibit 19.6.
People with type AB-blood do not have any a or b agglutinins in their plasma.
They are sometimes called universal recipients because they can theoretically
receive blood from donors of all four blood types. They have no agglutinins to attack
donated RBCs .
People with type-O blood have no A or B agglutinogens on their RBCs and are
sometimes referred to as universal donors because they can theoretically donate
blood to recipients of all four blood types . type-O persons requiring blood may
receive only type-O blood. In practice , use of the terms universal recipient and
universal-donor is misleading and dangerous .

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UNDERGRADUATE PROGRAM :
xx.
xxi.
xxii.
xxiii.
xxiv.

There are other agglutinogens and agglutinins in blood, besides those associated
with the ABO-system, that can cause transfusion problems.
Thus blood should be carefully cross-matched or screened before transfusion ,
except in extreme emergency .
Knowledge of blood types is also used in paternity law-suits, linking suspects to
crimes, and as part of anthropology studies to establish a relationship among races.
In about 80% of the population , soluble antigens of the ABO type blood group
appear in saliva and other body fluids.
In criminal investigations it has been possible to type fluids such as saliva-residues
on a cigarette or semen in cases of rape.

Rh :
i.
ii.
iii.
iv.
v.

vi.

The Rh-system of blood classification is so named because it was first worked out in
the blood of the Rhesus-monkey..
Like the ABO-grouping , the Rh-system is based on antigens on the surfaces of
erythrocytes[RBCs].
People whose RBCs have the Rh agglutinogens (D-antigens) are designated Rh+
.those who lack Rh agglutinogens are designated Rh-.
The incidence of Rh+ and Rh- individuals among various groups is shown in Exhibit
19.5.
Normally , plasma does not contain anti-Rh agglutinins. However, if an Rh- person
receives Rh+ blood, the body starts to make anti-Rh agglutinins that will remains in
the blood.
If a second transfusion of Rh+ blood is given later , the previously formed anti-Rh.

Exhibit # 19.5

INCIDENCE-OF-HUMAN-BLOOD-GROUPS-INTHE-UNITED-STATES
BLOOD GROUPS
(PERCENTAGES)

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AB

Rh+

41 10

85

48

27 21

88

Japanese

31

38 22

100

Chinese

36

28 23

13

100

76 0

100

Whites

45

Blacks

American- 23
Indians
37

61 1.5 0.5 100

Hawaiians
.
.
.
.
.
.
.
.

EXHIBIT # 19.6
SUMMARY-OF-ABO-SYSTEM-INTERACTIONS
Blood-Type

Agglutinogen(Antigen) On RBCs.

B
B

AB

A and B

Neither
A nor B

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BLOOD-PHYSIOLOGY IN PHYSIOLOGY-1 ON BIO-MEDICAL ENGINEERING

UNDERGRADUATE PROGRAM :
Agglutinin (Antibody)
in Plasma

Neither
a nor b

Compatible Donor
Blood Types

A,O

B,O

A,B,AB,O O

In-compatible Donor
Blood Types

B,AB A,AB ---

A,B,AB

Genotype (GeneticMake-Up)

AO

BO

AB

OO

AA ,
or

BB,

AB

Phenotype(Expressed- A
Blood-Types)

a and b

or
B

-----------The Blood Physiology on Bio-Medical engineering Physiology-1 finished here --------------

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