Transcript Blood

Blood
1
Blood
Blood is not an epithelial tissue, and it’s
not loose or dense connective tissue; it’s
classified as a “special connective tissue”.
 You have about 5 liters of blood (30 pints),
but that is only half of the body fluid.
 The other half includes fluid around each
cell, and joint fluids, etc.

2
Blood plasma circulates outside
of the blood vessels too!
PLASMA
EXTRACELLULAR FLUID
↑↓
↓↑
↓↑
SYNOVIAL FLUIDS
JOINTS
CSF
3
Blood consists of the following:
Plasma
 Red blood cells
 White blood cells
 Platelets

4
FUN FACTS
In one day, your blood travels nearly
12,000 miles.
 Your heart beats around 35 million times
per year. Your heart pumps a million
barrels of blood during the average
lifetime -- enough to fill three
supertankers. If an artery is cut, blood will
shoot out 30 feet.

5
Plasma
Plasma is what the blood cells float around in. If
you spin a blood sample in a test tube, the red
blood cells sink to the bottom, and you’ll see the
yellow plasma on top.
 Some people who need blood just need the
packed RBCs, some need the platelets, others
need the plasma, and some need whole blood,
which is both plasma and RBCs.

6
Overview: Composition of Blood
Figure 17.1
7
8
PLASMA CONTENTS
Water (90%)
Dissolved substances (10%)


–
Proteins




–
Nutrients


–
–
–
Albumin (egg white). Most common protein in blood
(homeostasis)
Antibodies
Clotting factors called fibrinogen and fibrin.
Lipoproteins (move fats through blood: HDL, LDL)
Glucose (main energy source)
Amino Acids (builds proteins)
Wastes (urea)
Gases (O2, CO2, Nitrogen)
Electrolytes = ions (Na+, K+, Cl-, Ca++)
9
10
Blood Cells
11
ERYTHROCYTES
(Red blood cells)


5 million
Like a doughnut with the hole not fully
cut out.
– These are among the smallest cells in the
body
– They have no nucleus
– Biconcave to increase surface area
– Filled with hemoglobin (Hgb), which carries
O2 throughout the body. Oxygenated Hgb is
bright red, deoxy Hgb is deeper red, almost
12
a bluish-purple.
Erythrocytes
13
Hemoglobin Molecule
14
Hemoglobin Molecule
15
ERYTHROCYTES:
– Average life span is 120 days. Old ones are
destroyed in the spleen and liver, and Hgb
and iron are recycled.
– There are 30 trillion RBCs in the body.
– About 25% of the body’s cells are RBCs.
– 2.4 million RBCs are destroyed per second
so that’s how many are made per second.
– 8.6 billion RBCs are made each hour.
– 200 billion are made each day.
– They are made in the red bone marrow
(spongy bone).
16
17
Disorders of RBCs


Polycythemia
Anemia
– Too few RBC’s
– Iron deficiency
– Hemorrhagic anemia (person lost blood)
– Hemolytic anemia (immune disorder, infection, blood transfusion)
 G6PD deficiency
– Hemoglobin abnormalities
 Pernicious (Megaloblastic) anemia (lack of vitamin B12 or intrinsic
factor)
 Thalassemia
 Sickle cell disease
 Hereditary spherocytosis
18
Polycythemia
Too many RBC’s; can cause clots. Need to donate
blood frequently
19
20
ANEMIA
Any condition of RED BLOOD CELLS in
which the blood’s capacity for carrying
oxygen is diminished.
 HYPOXIA is lack of oxygen to tissues.

– It can be caused from:
 Ischemia (reduced blood flow to a tissue)
 Malfunctioning hemoglobin
 Increasing altitude
21
Anemia


Characteristic sign of anemia: see
reticulocytes in the blood (immature red
blood cells).
Remnants of the nucleus are still in the
cell.
22
Reticulocytes
23
Anemia can be caused by many things. One
type of anemia is from too few RBC’s.
24
Anemia can also be caused from
Iron Deficiency
25
IRON DEFICIENCY ANEMIA
that was treated with blood transfusion
These are the healthy RBCs from
blood transfusion
26
Hemolytic Anemia

Hemolysis means rupture of RBC’s.
– Hereditary (born with the genes that cause
the disease)
 Immune disorders and G6PD deficiency.
– Acquired
 Infections (malaria), and receiving the wrong
blood type in a transfusion.
27
G6PD Deficiency




Hereditary, X-linked; almost all are males
G6PDH is an enzyme which is important for RBC
metabolism.
G6PD is the most common human enzyme defect.
A person with this would have a hard time maintaining
iron in a reduced state, and they develop hereditary
(NOT acquired) hemolytic anemia in response to a
number of causes, most commonly infection or exposure
to certain medications, chemicals, or ingestion of fava
beans.
28
HEMOGLOBINOPATHIES
Pernicious anemia (megaloblastic anemia)
 Thalassemia
 Sickle Cell Disease
 Hereditary Spherocytosis

29
Pernicious anemia
(megaloblastic anemia)




Caused by lack of vitamin B12 or intrinsic factor
When a person has gastric bypass surgery, the stomach
is no longer able to produce intrinsic factor, which is
needed to absorb vitamin B12, which is needed to make
hemoglobin in RBC’s.
Without this vitamin, the blood cells are fewer and much
larger than normal (megaloblastic).
The surgery patient must take vitamin B12 shots or
sublingual supplements for the rest of their life.
30
Megaloblastic Anemia
(Large RBCs: Note that the lymphocyte is the
same size as the huge RBCs)
31
Thalassemia A hereditary form of anemia where
the RBCs have abnormal hemoglobin that deforms the cells
TEAR DROP
TARGET CELLS
SPHEROCYTE
32
Sickle Cell Disease
A hereditary mutation resulting in one
valine amino acid substituted for glutamic
acid.
 Present in African Americans more than
in other groups, and is always
characterized by sickled erythrocytes.
 The sickle shape helps prevent malaria
infections, but it also causes blood clots.

33
Sickle Cell Anemia
SICKLE CELL
34
35
Hereditary spherocytosis

The red blood cells shrink over time due
to problems with the red blood cell
membrane.
Many of the RBC’s
look small and round.
36
RBC, Hgb, Hct

Red blood cell (RBC) count is a count of the actual
number of red blood cells per volume of blood. Both
increases and decreases can point to abnormal
conditions.

Hemoglobin (Hgb) measures the amount of oxygencarrying protein in the blood.

Hematocrit (Hct) measures the percentage of red
blood cells in a given volume of whole blood.
37
Hematocrit





A quick screening test for anemia is the
hematocrit.
A drop of blood is drawn up a small glass
capillary tube and the tube is centrifuged to
pack the red blood cells at the bottom with the
plasma on top.
Hematocrit measures the percentage of blood
volume that consists of erythrocytes.
The hematocrit is the ratio of packed red blood
cells to total blood volume.
Normal is about 45% (46% for men and 38%
for women.)
38
Hematocrit
39
Mean Corpuscular Volume



Mean corpuscular volume (MCV) is a measurement of
the average size of your RBCs.
The MCV is elevated when your RBCs are larger than
normal (macrocytic), for example in anemia caused by
vitamin B12 deficiency.
When the MCV is decreased, your RBCs are smaller than
normal (microcytic) as is seen in iron deficiency anemia
or thalassemias.
40
Mean Corpuscular Hemoglobin


Mean corpuscular hemoglobin (MCH) is a calculation of
the average amount of oxygen-carrying hemoglobin
inside a red blood cell.
Macrocytic RBCs are large so tend to have a higher MCH,
while microcytic red cells would have a lower value.
41
Mean Corpuscular Hemoglobin
Concentration



Mean corpuscular hemoglobin concentration (MCHC) is a
calculation of the average concentration of hemoglobin
inside a red cell.
Decreased MCHC values (hypochromia) are seen in
conditions where the hemoglobin is abnormally diluted
inside the red cells, such as in iron deficiency anemia
and in thalassemia.
Increased MCHC values (hyperchromia) are seen in
conditions where the hemoglobin is abnormally
concentrated inside the red cells, such as in burn
patients and hereditary spherocytosis, a relatively rare
congenital disorder.
42
Red Cell Distribution Width




Red cell distribution width (RDW) is a calculation of the
variation in the size of your RBCs.
Having a few RBC’s with various shapes is called
aniscocytosis.
Having many RBC’s with various shapes is called
poikilocytosis.
In some anemias, such as pernicious anemia,
anisocytosis and poikilocytosis causes an increase in the
RDW.
43
BLOOD TYPING: The ABO SYSTEM
Blood typing is the technique for
determining which specific protein type is
present on the RBC membranes.
 Only certain types of blood transfusions
are safe because the cell membranes of
the red blood cells carry certain types of
proteins that another person’s body will
think is a foreign body and reject it.

44
BLOOD TYPING





These proteins are called antigens (something
that causes an allergic reaction). There are two
types of blood antigens: Type A and Type B.
A person with Type A antigens on their blood
cells have Type A blood.
A person with Type B antigens have Type B
blood.
A person with both types has type AB blood.
A person with neither antigen has type O blood.
45
46
BLOOD TYPING





If a person with type A blood gets a transfusion
of type B antigens (from Type B or Type AB, the
donated blood will clump in masses
(coagulation), and the person will die.
The same is true for a type B person getting
type A or AB blood.
Type O- blood is called the universal donor,
because there are no antigens, so that blood
can be donated to anyone.
Type AB+ blood is considered the universal
acceptor, because they can use any other type
of blood. This blood type is fairly rare.
The rarest blood type is AB negative.
47
RH FACTOR
There is another term that follows the
blood type. The term is “positive” or
“negative”. This refers to the presence of
another type of protein, called the Rh
factor. A person with type B blood and
has the Rh factor is called B positive.
 A person with type B blood and no Rh
factor is called B negative.

48
RH FACTOR

The reason this is so important is that if
an Rh- mother has an Rh+ fetus in her
womb (from an Rh+ father), her
antibodies will attack the red blood cells of
the fetus because her body detects the Rh
protein on the baby’s red blood cells and
thinks they are foreign objects. This is
called Hemolytic Disease of the Newborn
(HDN).
49
50
HDN
This can be prevented if the doctor knows
the mother is Rh- and the father is Rh+,
because that means the baby has a 50%
chance of being Rh+ like the father.
 Therefore, anytime a mother is Rh-, even
if the mother says the father is Rh-, you
can’t be sure who the father is, so they
will proceed as though the baby may be
Rh +.
 They will give her an injection of a
medicine (Rhogam) that will prevent her
immune system from attacking the baby.

51
Rhogam





Rhogam is given at 18 weeks into the pregnancy and
again within 72 hours after giving birth.
It is usually given within 2 hours after giving birth since
you can’t trust the patient to return after they leave the
hospital.
The first baby is not at risk; during the first birth (or
miscarriage), the placenta tears away and that’s when
the baby’s blood cells get into the mother’s bloodstream.
She then forms antibodies against the Rh factor, which
are ready to attack the second fetus.
The baby does not make the Rh factor until about 18
weeks into the pregnancy.
52
ReynoldsUnwrapped.com offers FANTASTIC,
inexpensive daily email subscriptions, where
you can receive a HILARIOUS new cartoon
every day, and it is a MARVELOUS idea for a
UNIQUE gift for your family and friends as
well. That is how I learned about this...one of
my fellow teachers gave me a subscription as
a birthday present.
He also has FUNNY greeting cards and
BEAUTIFUL paintings for sale as well.
You can also get reprints suitable for framing,
or originals. Here is more info about his work
and a YOUTUBE video.
https://nccnews.expressions.syr.edu/?p=11515
53
Microbiology

To understand the function of white blood
cells, you will need to learn some general
concepts and terminology from
Microbiology:
– Pathogen
– General size of bacteria and viruses
– Antigen
54
Pathogen
“Path” = disease “ogen” = generating
A pathogen is something that causes
disease.
 A biological pathogen is a bacterium,
virus, fungi, yeast, protozoa, worms, etc.
 A non-biological pathogen can be a toxic
chemical, asbestos, etc.
 Usually, the term “pathogen” refers to a
biological pathogen.

55
Sizes of Pathogens

Bacteria are so small that hundreds of them can
fit inside one white blood cell.


However, bacteria usually do not invade body cells.
They live between the cells of the body, using up
nutrients in the area, and they cause harm by
secreting toxins.
Viruses are so small that thousands of them can
fit inside the NUCLEUS of one white blood cell.


They always try to invade body cells because they
need a piece of our DNA or RNA in order to replicate.
When a body cell has been invaded by a virus, the
entire cell must be killed by a white blood cell.
56
Antigen
An antigen is anything that causes an
immune response, which isn't necessarily
a biological pathogen (disease-causing
organism).
 A non-biological antigen can be pollen,
dust, grass, or anything that a person is
allergic to.
 Pollen can be an antigen to a person with
allergies, but it is not an antigen to a
person without allergies, because no
immune response was launched.

57
LEUKOCYTES (White blood cells)
all fight infection

BASOPHILS
– MAST CELL
EOSINOPHILS
 NEUTROPHILS
 MONOCYTES

– MACROPHAGES

LYMPHOCYTES
– B CELLS
– T CELLS
too many is ___philia
too few is ___penia
58
BASOPHILS

Basophils – only about
0.5% of all leukocytes
– Granules secrete
histamines (vasodilation;
more WBCs can get to the
infection site)
– Antihistamines interfere
with the function of
basophils.
– Mast Cell: a basophil that
leaves the blood vessel
and enters the tissues.
59
Eosinophils

Eosinophils –
compose 1-4% of all
WBCs
– Play roles in:
 Ending allergic
reactions, parasitic
infections
 During these conditions
they increase in
numbers: eosinophilia
60
61
62
Neutrophils
Neutrophils – most
numerous WBC
 First to respond to
infection

– Phagocytize and destroy
bacteria
– Also destroy bacterial
toxins in body fluids
– Nucleus – has two to six
lobes
63
Neutrophils
Neutrophils are the white blood cells that
contribute to immunity mainly by
engulfing BACTERIA and foreign bodies
(thorns, dirt, etc) in a process called
phagocytosis.
 They release the contents of their
lysosomes onto the invader, dissolving it.
 When a bacterium has a capsule, it makes
it hard to phagocytize, so the neutrophil
requires opsonization by antibodies.

64
Opsonization
Some bacteria have evolved a slippery
capsule around them as a defense against
phagocytosis. The neutrophil cannot
engulf this type of bacteria. Neither can a
macrophage.
 When an antibody attaches to this type of
bacteria, the neutrophil can now grab onto
the antibody like a handle, enabling it to
phagocytize the bacteria.
 This process of facilitation of phagocytosis
is called opsonization.

65
When an invading bacteria has the antibody
attached to its cell membrane, the entire
structure is now called an antigen-antibody
complex.
 If a bacterium does not have a capsule, the
neutrophil can destroy it without opsonization.
The antibody can also destroy the bacterium by
itself by popping the cell membrane.
 But when a capsule is present, the neutrophil
and antibody work best together.
 Neutrophils are also the ones that
primarily destroy the dissolved toxins that
bacteria secrete into body fluids.
66

Monocytes




Comprise about 5% of all WBC’s.
Like neutrophils, they phagocytize
(eat) bacteria, old cells, and
foreign bodies. They have more
types of lysosome enzymes than
neutrophils so they are better at
killing difficult pathogens.
They also use antibodies for
opsonization.
When they leave the
bloodstream and enter the
tissues, they are called
MACROPHAGES.
67
WBC’s leave the blood vessel
to enter the tissues
68
What’s the Difference between Neutrophils and
Monocytes/Macrophages?





There are 10x more neutrophils in the bloodstream than
monocytes/Macrophages. Consider neutrophils to be
the most numerous white blood cell.
However, there are more macrophages in the tissues of
the body. They are everywhere!
Neutrophils live only a few days. Monocytes/Macrophages
live a few months. Lymphocytes live for years.
Monocytes/Macrophages are larger and slower than
neutrophils, but they can phagocytize larger organisms
and more of them.
Neutrophils usually just phagocytize bacteria until they
die. Macrophages phagocytize and then take pieces of the
dead bacteria and present them to lymphocytes so a
69
larger immune response can occur.
Differences in Function


There are two types of phagocytes: Neutrophils and
macrophages.
– Neutrophils and macrophages both mainly function by
phagocytizing bacteria (not viruses).
Lymphocytes are mostly needed to kill off body cells
infected by viruses.
70
Differences in Function
Neutrophils just phagocytize bacteria and secrete
chemicals to recruit more white blood cells to the
site.
 Unlike neutrophils, macrophages have surface
receptors; these "recognize" the surface of the
pathogen’s cell membrane.
 Macrophages phagocytize the bacteria, pop their
lysosomes onto it, and dissolve it, except for
some pieces of the bacteria’s cell membrane.
 The macrophage places these pieces of bacteria
on its own cell membrane, and finds a
lymphocyte to present it to.
71

Differences in Function
Macrophages present these pieces to T cell
lymphocytes and to B cells lymphocytes.
 The lymphocyte feels the shape of the bacteria
pieces on top of the macrophage, (this is called
“antigen presentation”) and the lymphocyte can
then launch an attack on the rest of the bacteria
still alive in the body.
 In this way, the macrophage recruits even more
lymphocytes to join the war.
 So, what is a lymphocyte?

72
Lymphocytes

20–45% of WBCs
– The most important cells of the
immune system
– There are two types of
lymphocytes; one type is
effective in fighting infectious
organisms like body cells
infected with viruses
– Both types of lymphocytes act
against a specific foreign
molecule (antigen)
73
Lymphocytes
Two main classes of lymphocyte

–
–
B cells – Originate in the bone marrow,
mature into plasma cells. A mature
plasma cell fights infection by
producing antibodies
T cells – Originate in the thymus gland.
They attack foreign cells directly (including
organ transplants!). They can also kill
viruses.
74
Lymphocytes
B cells – mature into plasma cells
Plasma cells secrete antibodies; the
plasma cell’s antibodies are what
kills the attacking cell.
Antibodies attack in two ways:



–
–
They attach to bacteria and pop the cell
membrane
They attach to encapsulated bacteria to
help neutrophils and macrophages to
phagocytize them.
75
Disorder of B-cell Lymphocytes
Mononucleosis: Epstein Barr virus
attacks B lymphocytes. It is
characterized by inflammation of lymph
vessels (lymphangitis).

–
Lymphangitis: lymph vessel inflammation;
usually from infection.
Infected lymphocytes have a
characteristic scalloped
edge where they touch
RBC’s
76
Function of a B Lymphocyte
Figure 17.6b
77
T-cell Lymphocytes





T cells – coordinate the immune response by
recruiting other white blood cells.
They can directly destroy bacteria by popping their cell
membrane.
T cells can also directly destroy foreign cells by
popping the cell membrane.
They do not need to phagocytize the invading cell.
They do not need the assistance of antibodies.
T-cells can therefore kill a body cell that has become
infected with viruses.
78
T-Cell
79
T-cell Lymphocytes

T cells are the cells that attack
organ transplants!



Immunosuppression drugs are designed to
inhibit the action of T cells.
T cells are attacked by the HIV (AIDS)
virus.
The thymus gland secrets certain
hormones which can cause T cells to
become immunocompetent (makes the
cells mature and start to work)
80
T Cells
There are several types of T cells. The main types are
 Cytotoxic (Killer) T cells
– Go out and directly kill bacteria or infected host cells
 Helper T cells
– Release chemicals called “cytokines” to call in more white blood
cells of all types to join in the war. They also present the
macrophage’s antigen to a B cell, which causes it to produce
antibodies against that particular bacteria. The B cell is now
called a plasma cell
 Suppressor T cells
– Stop the immune process when it is over, and also "tell" some
plasma cells to "remember" how to destroy that specific
pathogen. Those plasma B-cells are then called Memory B-Cells.
They can react to the same pathogen faster, the next time it
invades because Memory B-cells already have the proper
antibodies stored up for that pathogen.
81
Killer TCell
82
Virus-Infected Cell
83
Function of a T- Lymphocyte
Figure 17.6a
84
Summary




A pathogen somehow gets past the body's physical and
chemical barriers and the inflammation response.
The pathogen is engulfed by a macrophage (or
neutrophil).
The macrophage releases the contents of its lysosomes
onto the bacterium and dissolves most of it. There are
still some pieces of the bacterium’s cell membrane left.
The macrophage then forces the surface proteins of the
bacterium (antigens) to it's own cell surface.
Helper T-Cells touch these surface antigens, make a
copy of their shape, and present them to B-cells to make
antibodies against them.
85
Summary






These Helper T-Cells begin to multiply and have two main roles.
The first is to activate B-Cells and "tell" them how to neutralize the
pathogen by presenting the pieces of the bacterium cell membrane
so the B-cells can turn into plasma cells which make the antibodies.
– The B-Cells (now called Plasma cells because they have been
activated) begin to multiply and produce the antibodies to
neutralize this specific pathogen.
The second role of Helper T-Cells is to activate the Killer T-Cells by
secreting cytokines.
Killer T-Cells can either destroy the pathogen itself (bacteria), or
destroy the entire body cell which is infected (viruses).
When the immune response is over, Suppressor T-Cells stop the
process and also "tell" some B-Cells (plasma cells) to "remember"
how to destroy that specific pathogen.
Those B-cells (plasma cells) now become Memory B-Cells.
86
Capsule
Pops
the cell
Virus
Opsonization
Bacteria
Bacteria
Antibodies
Plasma
Cell
Pops the cell
Cytokines
Phagocytosis
STOP
Presentation
Neutrophil
Macrophage
(Monocyte
in bloodstream)
B-Cell
Helper
T-Cell
Killer
T-Cell
Lymphocytes
Suppressor
T-Cell
87
LEUKEMIA
Cancer of the blood is called leukemia. It
actually only involves the white blood cells.
 Something goes wrong in one stem cell, and it
starts making huge amounts of clones of itself
which don’t work right and not enough normal
white blood cells are made. Therefore, the body
cannot fight infection. So, the immature white
cells are sent into the bloodstream. It’s better to
send a young cell with no weapons to the war
than to send nothing at all!
 Think of Leukemia as too few mature
white blood cells.
 Even though the WBC count is high, they are all
immature forms.

88
Disorders of WBCs

Disorders of leukocytes
– Leukemia – too few mature WBC’s (may see
increase in immature forms); a form of cancer
– Classified as lymphoblastic (too many
immature lymphocytes) or myeloblastic (too
many immature neutrophils)
89
Bone Marrow Transplant
People with severe leukemia may need a bone
marrow transplant.
 First, all of their WBC’s have to be killed off with
a medicine because they are mostly
malfunctioning anyway.
 A donor has a small cylinder of bone removed
from their hip. This is ground up and given by
i.v. to the recipient.
 The new WBC’s may kill the patient or it may
save their life. It is done as a last resort.

90
WBC Count

White blood cell (WBC) count is a count of the actual
number of white blood cells per volume of blood. Both
increases and decreases can be significant.

White blood cell differential looks at the types of
white blood cells present. There are five different types
of white blood cells, each with its own function in
protecting us from infection. The differential classifies a
person's white blood cells into each type: neutrophils
(also known as segs, PMNs, granulocytes, grans),
lymphocytes, monocytes, eosinophils, and basophils.
91
Terms
Excess neutrophils: neutrophilia
 Few neutrophils: neutropenia

Excess platelets: thrombocytophilia
 Few platelets: thrombocytopenia

92
Antibodies
Antibodies (also known as immunoglobulins,
abbreviated Ig) are proteins made by plasma
cells.
 They are used to identify and neutralize foreign
objects, such as bacteria and viruses.
 They are typically made of basic structural
units—each with two large heavy chains and two
small light chains—to form a unit shaped like the
letter “Y”

93
A Typical
Antibody
The tips of the “Y”
have receptors that
are specific for a
particular antigen.
The stem of the “Y”
can be grasped by a
phagocyte.
94
Antibodies
The small region at the tip of the protein is
extremely variable, allowing millions of
antibodies with slightly different tip structures,
or antigen binding sites, to exist.
 This region is known as the hypervariable
region. Each of these variants can bind to a
different target, known as an antigen.
 This huge diversity of antibodies allows the
immune system to recognize an equally wide
diversity of antigens.

95
Antibodies




Some of these “Y” shaped units
exist by themselves (monomers)
Some are in pairs (dimers)
Some are in a cluster of five
(pentamers)
There are five different antibody
types , which perform different
roles, and help direct the
appropriate immune response for
each different type of foreign
object they encounter.
96
#1
#2
#3
Precipitation/agglutination
97
Types of
Antibodies
IgD – initiation of immune response
IgE – stimulates allergic reactions, good for
worm infections
IgG – highest concentration in blood, highest
amounts in most secondary responses,
crosses the placenta
IgA – secretory Ig, found in secretions,
highest concentration in body
IgM – produced first, best at C’ activation
98
IMMUNITY

Most people are sick more often as
children than as adults in their 20s
through 30s because we build up many
varieties of memory lymphocytes during
childhood, providing immunity from more
and more antigens during adulthood.
99
Myasthenia gravis
Myasthenia gravis (MG): autoimmune
disease where antibodies destroy or block
receptors for acetylcholine, a
neurotransmitter.
 Causes muscle paralysis.
 First attacks small muscles especially
those that keep eyes open; will spread to
diaphragm  death.
 To stave off effects, do thymectomy.

100
PLATELETS
(thrombocytes)
Very small compared to all other blood cells.
These are pieces of another cell found in the red
marrow called a MEGAKARYOCYTE.
 Pieces break off of a megakaryocte and are
known as platelets.
 When a platelet encounters a broken blood
vessel it uses clotting factors (made in the liver
and circulating in the blood) to form a web to
clots blood.
 Platelets are responsible for clot formation.

101
Platelets
Platelets need certain proteins in the
plasma called CLOTTING FACTORS in
order for them to become activated and
form a clot.
 Two main clotting factors are called
FIBRIN and FIBRINOGEN.
 Thrombocytopenia is too few platelets.

102
Platelets

Cell fragments
– Break off from
megakaryocytes

Function in clotting of
blood
Platelets
Megakaryocyte
103
Blood
Clot
104
Vitamin K
Found in green, leafy vegetables.
 Needed for blood clotting factors.
 Some types of rat poisons work by
eliminating the blood clotting ability.
 In case of accidental ingestion of rat
poison, a child needs an I.V. of vitamin K.
 It works for accidental poisoning in dogs,
too!

105
Aspirin
One baby aspirin a day can help prevent blood
clots.
 It blocks the ability of an enzyme called COX
(cyclo-oxidase) to cleave arachidonic acid into a
molecule called a prostaglandin.
 Prostaglandins are needed for inflammatory
reactions and for making clotting factors.
 COX inhibitors, such as aspirin, block pain from
inflammation, but they also INCREASE blood
clotting time.

106
Disorders of Platelets
– Thrombocytopenia
 Abnormally low
concentration of platelets
 Blood does not clot
properly
107
HEMOPHILIA
A hereditary disease of males, where they are
unable to clot properly because they are missing
some clotting factors.
 When they get even a slight bump or bruise
they have to have an intravenous infusion of
clotting factors or they will bleed to death.
 This is probably the disease that was in the
genes of Henry VIII, which caused all of his
male children to become weak and die in
infancy.

108
Blood Clots

Thrombus
– A clot in a vessel

Embolism
– a thrombus that broke away and
travels in the blood stream.
– It usually lodges in a smaller blood
vessel and blocks circulation distal
to that point.
109
Blood Clots
Thrombus
 Embolism

110
Thrombus
111
Thrombus
112
Platelet Count and MPV



The platelet count is the number of platelets in a
given volume of blood.
Both increases (thrombocytophilia) and decreases
(thrombocytopenia) can point to abnormal conditions of
excess bleeding or clotting.
Mean platelet volume (MPV) is a machine-calculated
measurement of the average size of your platelets. New
platelets are larger, and an increased MPV occurs when
increased numbers of platelets are being produced.
113
Prothrombin Time (PT) and
Partial Thromboplastin Time (PTT)

The PTT test is used to investigate unexplained bleeding or clotting.
It may be ordered along with a PT (Prothrombin Time) test to
evaluate hemostasis (the process of clot formation). The PTT
evaluates the coagulation factors XII, XI, IX, VIII, X, V, II
(prothrombin), and I (fibrinogen). A PT test evaluates the
coagulation factors VII, X, V, II, and I (fibrinogen). By evaluating
the results of the two tests together, a doctor can gain clues as to
what bleeding or clotting disorder may be present.

These tests are used to monitor heparin anticoagulant therapy.
Heparin is a drug that is given intravenously (IV) or by injection to
prevent and to treat blood clots. IV’s are also flushed with heparin
to prevent clot formation. When it is administered for therapeutic
purposes, it must be closely monitored. If too much is given, the
treated person may bleed excessively; with too little, the treated
person may continue to clot.
114
Complete Blood Count (CBC)











The complete blood count or CBC test is used as a broad screening test to
check for such disorders as anemia, infection, and many other diseases. It
is actually a panel of tests that examines different parts of the blood and
includes the following:
White blood cell (WBC) count
White blood cell differential
Red blood cell (RBC) count
Hemoglobin
Hematocrit
platelet count , PT, PTT
Mean corpuscular volume (MCV)
Mean corpuscular hemoglobin (MCH)
Mean corpuscular hemoglobin concentration (MCHC)
Red cell distribution width (RDW)
115
116
Summary of Formed Elements
Table 17.1117
(1)
Summary of Formed Elements
Table 17.1118
(2)
Life span, from longest-lived
to shortest-lived:
Lymphocytes
 Erythrocytes
 Platelets
 Neutrophils

119
Septicemia
Septicemia (aka bacteremia) is the condition when bacteria invade the body
and circulate in the blood.
 Bacteria can enter the bloodstream as a severe complication of infections
(like pneumonia or meningitis), during surgery (especially when involving
mucous membranes such as the gastrointestinal tract), or due to catheters
and other foreign bodies entering the arteries or veins (including
intravenous drug abuse).
 Bacteremia can have several consequences. The immune response to the
bacteria can cause sepsis and septic shock, which has a relatively high
mortality rate (kills 1 person in 5). Bacteria can also use the blood to spread
to other parts of the body (which is called hematogenous spread), causing
infections away from the original site of infection. Examples include
endocarditis or osteomyelitis.
 Treatment is with antibiotics, and prevention with antibiotic prophylaxis can
be given in situations where problems are to be expected.

120
121
STEM CELLS IN THE RED MARROW
STEM CELL: A cell that has not matured and
differentiated yet.
 An embryo has lots of stem cells which have not
decided to become a nerve cell, muscle cell, liver
cell, etc. Stem cells become the type of cell the
body needs. The placenta of a newborn infant
has many of these stem cells, too, but not as
many as an embryo. That’s why people want to
research stem cells on embryos; there are more
stem cells there.

122
Stem Cells
The first step for a stem cell is to
DIFFERENTIATE, which is to decide what
system of cells it will belong to. A stem cell that
matures in the bone marrow will become a
blood cell.
 Adults don’t have too many stem cells that are
so immature that they have not yet decided
what system of cells to belong to.
 Most of our stem cells have matured to the next
step, which is that they have decided what
system to evolve into.
 An adult has stem cells that will ONLY become
blood, nerve tissue, organs, etc.

123
Blood Cell Formation
Hematopoiesis – process by which blood
cells are formed
 100 billion new blood cells formed each
day
 The plasma proteins are made in the liver.
 The blood cells are made in the red
marrow.

124
Bone Marrow as the Site of
Hematopoiesis

Bone marrow – located within all bones
– Red marrow – actively generates new blood
cells
 Contains immature erythrocytes
 Remains in epiphyses, girdles, and axial skeleton
125
Bone Marrow as the Site of
Hematopoiesis
Yellow marrow – dormant
 Contains many fat cells
 Located in the long bones of adults
126
RED BONE MARROW
Most blood cells mature in the red bone
marrow.
 When they are almost completely mature,
they are released into the bloodstream.
 When they are old, they are destroyed in
the spleen and liver.

127
128
Cell Lines in Blood Cell
Formation
All blood cells originate in bone marrow
 All originate from one cell type – blood
stem cell

– Erythroblasts – give rise to red blood cells
– Lymphoblasts – give rise to lymphocytes
– Myeloblasts – give rise to all other white blood
cells
129
Stages of
Differentiation of
Red Blood Cells
130
RBC Development



ERYTHROBLASTS mature until they
are ready to enter the circulation. The
nucleus gets pinched off as it enters the
blood vessel.
When a RBC loses its nucleus, it gains
room for more hemoglobin.
Some bits of its nucleus are still there for
about 2 days, so during this time, they
are called RETICULOCYTES.
131
ERYTHROBLASTS

These mature into
RETICULOCYTES, a
RBC with bits of
nucleus material,
which later dissolves
to make room for
more Hgb. It is now
called an
ERYTHROCYTE.
132
LYMPHOBLASTS
Give rise to lymphocytes
133
MYELOBLASTS
These are the stem cells that mature into
the other leukocytes:
Neutrophil, macrophage, eosinophil,
basophil, platelets.
134
Leukemia
Leukemia is cancer of the stem cells.
See all these different types of stem cells?
That’s about how many types of leukemia
there are.
135
Stages of
Differentiation
of White Blood
Cells
Figure 136
17.9
Fig. 9-1
Hematopoiesis
137
IMMUNE SYSTEM
INFLAMMATORY REACTION: When you get
stuck by a thorn or have an infected cut, the
body goes through a series of events called an
inflammatory reaction.
 Four outward signs:

–
–
–
–
Redness (erythema or rubor)
Heat (calor)
Swelling (edema)
Pain (dolor)
138
INFLAMMATORY REACTION




Redness is caused from the blood vessels dilating to
allow more blood flow to the area. Within the blood are
platelets to clot the blood, proteins to repair the
damage, and macrophages, which are white blood cells
that eat up the foreign body, bacteria, or the dead cells.
Heat is caused because of the extra amount of warm
blood flow to the area.
Swelling is caused from the plasma that leaks out of
the swollen blood vessels.
Pain is caused from the pressure of the extra fluid
pressing on nerves in the area.
139
ADAPTIVE IMMUNITY

Two types of Adaptive Immunity
– ACTIVE immunity
 Naturally Acquired
 Artificially Acquired
– PASSIVE immunity
 Naturally Acquired
 Artificially Acquired
You can also think
of it this way
140
Active Immunity
ACTIVE means the person’s own body
makes the antibodies.
 Naturally Acquired

– The body is naturally exposed to an infectious
agent and launches an immune reaction

Artificially Acquired
– The person is injected with a weakened
(attenuated) or killed organism, as found in a
vaccination
141
Naturally Acquired
Active Immunity
This is when the body is exposed to an
infectious agent and the body has to work to
produce antibodies which specifically attack that
infectious agent.
 The white blood cells secrete these antibodies
which will continue to circulate sometimes for
years, ready to attack that type of bacteria and
cause them to pop like a balloon before the
body can become sick.

142
Naturally Acquired
Active Immunity
– You catch a cold and eventually get better. You can
never get the same cold virus twice because you will
have become immune to it. Your next cold is from a
different virus. There are hundreds of thousands of
cold viruses; that’s why there is no cure for the
common cold.
– Another example is when an unvaccinated child is
exposed to the measles at school and gets the
disease, but never gets the disease again.
143
However, there are some diseases that you
don’t want to get, even once, such as polio,
diphtheria, tetanus, and influenza, because the
first exposure could kill or disable you.
 For these diseases, we have vaccines which are
made of those organisms which have been
altered (attenuated) so that the body recognizes
them as foreign, but they can’t cause disease.
 That way, if the person is exposed to the real
organism later, the antibodies are already there
to kill it off without the body getting sick.

144
Artificially Acquired
Active Immunity

An example is when a child is vaccinated against
measles as a baby, so when he gets to school
and is exposed to the disease, he doesn’t get
sick.
145
Passive Immunity
PASSIVE means the person’s body does
not have to make the antibodies.
 Naturally Acquired

– Example is the passing of antibodies from
mother to infant in breast milk

Artificially Acquired
– Example is when a person receives an
infusion of antibodies from someone else.
146
Active vs. Passive Immunity
Active immunity is long-lived, and may last
for years or even a life time.
 Passive immunity is short lived, and may
last only for a few months.

NOTE: A vaccination is not the same as
receiving an anti-toxin or anti-venom
injection. More on that in Micro class.
147
ALLERGIES

From a hypersensitivity to substances such
as pollen or animal hair that would not
ordinarily cause a reaction. There are two
types of allergic responses:
Immediate
Delayed
148
Immediate allergic response
Occurs within seconds of contact with the thing
causing the allergy.
This is the case with anaphylactic allergies, where
someone who is allergic to seafood or peanuts
can actually die within minutes because the
allergic reaction is so severe the throat swells
shut and they can’t breathe.
They need an injection immediately of epinephrine
that will stop the reaction.
149
150
Delayed allergic response
Delayed allergic response is when the body’s
first exposure to the substance will not
cause a reaction, but all exposures
afterward will trigger the response.
An example is poison ivy.
You won’t itch the first time you touch it.
151
Common
allergens
152
Chemical mediators of allergies

Preformed
– histamine - ↑
vascular permeability; smooth muscle
contraction
– proteases
– mucous secretion, generation of complement split
products

Newly formed (30-60seconds)
– leukotrienes - ↑
vascular permeability;
contraction of pulmonary smooth muscles
– platelet activating factor –
platelet aggregation;
contraction of pulmonary smooth muscles
– prostaglanin D2 – vasodilation; contraction of smooth muscles
– cytokines – chemotactic and inflammatory
153
Symptoms of allergy
dependent upon site of allergen exposure
 wheal-and-flare reaction

– Pruritis (itching), erythema
– skin
bronchoconstriction
 mucous secretion
 vasodilation (shock)

154
155
Localized anaphylaxis
(atopy)
reaction limited to the site of allergen
exposure
 pruritis (itchy) and urticaria (hives)

allergic rhinitis (hay fever)
 asthma (atopic asthma)
 atopic dermatitis (eczema)
 food allergies

156
Allergic asthma

stimulation of ‘allergy attack’
– airborne allergens – pollen, dust, insect parts
– blood borne allergens – viral antigens
– degranulation of mast cells due to IgE cross-linking
 lower respiratory tract

symptoms
–
–
–
–
airway edema
mucous secretion
inflammation
= airway obstruction and damage
asthmatics are hypersensitive to allergens
~5% of U.S. population


symptoms can range from somewhat mild to lifethreatening (<5% severe asthma)
157
AUTOIMMUNE DISEASE

A hereditary problem where the body
thinks its own tissues are foreign bodies,
and it constantly tries to kill off its own
tissues.
Cats worse than dogs for allergies, http://fxn.ws/O5jueJ
158
159