Acute myelogenous leukemia - Patho, Anatomy, and Diagnostic test
-
Upload
charles-kevin-l-bataga -
Category
Documents
-
view
550 -
download
1
Transcript of Acute myelogenous leukemia - Patho, Anatomy, and Diagnostic test
ANATOMY AND PHYSIOLOGY
THE BLOOD
Humans can't live without blood. Without blood,
the body's organs couldn't get the oxygen and nutrients
they need to survive; we couldn't keep warm or cool off,
fight infections, or get rid of our own waste products.
Blood has always fascinated humans, and historically
there has been much speculation about its function.
Blood was considered the “essence of life” because the
uncontrolled loss of it can result in death.
Blood performs many functions essential to life and can reveal much about our
health. It is a fluid that circulates throughout the body, via arteries and veins, providing a
vehicle by which an immense variety of different substances are transported between
the various organs and tissue. It can carry nourishment and oxygen to and bringing
away waste products from all parts of the body. It also regulates pH through the use of
buffers, adjusts body temperature through the heat-absorbing and coolant properties of
the water in blood plasma. In addition, its white blood cells protect against disease by
carrying on phagocytosis.
FUNCTIONS OF BLOOD
Blood is pumped by the heart through blood vessels, which extend throughout
the body. Blood helps to maintain homeostasis in several ways:
1. Transport of gases, nutrients, and waste products.
- Oxygen enters blood in the lungs and is carried to cells while carbon
dioxide is carried in the blood to the lungs from which is expelled. The
ingested nutrients and water will transport from the digestive tract to cells
while waste products of the cells will be transported to kidneys for
elimination.
2. Transport of processed molecules.
- Many substances are produced in one part of the body and transported in
the blood in another part, where there are modified.
3. Transport of regulatory molecules.
- Many of the hormones and enzymes that regulate body processes are
carried from one part of the body to another within the blood.
4. Regulation of pH and osmosis.
- Buffers which help keep the blood’s pH within its normal limits of 7.35-
7.45, are found in the blood and the osmotic composition of blood is also
critical for maintaining normal fluid and ion balance.
5. Maintainence of body temperature.
- Blood is involved with body temperature regulationbecause warm blood is
transported from the interior to the surface of the body, where heat is
release from the blood.
6. Protection against foreign substances.
- Cells and chemicals of the blood constitute an important part of the
immune system, protecting against foreign substances such as
microorganism and toxins.
7. Clot formation.
- Blood clotting provides protection against excessive blood loss when
blood vessels are damaged.
-
COMPOSITION OF BLOOD
Blood is a type of connective tissue that consists of cells and cell fragments
surrounded by a liquid matrix. The cells and cell fragments are formed elements (blood
cells and platelets), and the liquid is the plasma. The total blood volume in the average
adult is about 4-5 liters in females and 5-6 liters in males. Blood makes up about 8% of
total body weight. About 55% of the blood volume consists of plasma, while 45% is
made up of blood cells and platelets.
Blood Plasma
Plasma is a pale yellow fluid that consist of about 91% water; 7% proteins; and
2% other substances, such as ions, nutrients, gases, and waste products. Plasma
proteins include albumin, globulins, and fibrinogen.
Albumin makes up 58% of the plasma proteins. Although the osmotic pressure of
blood results primarily from sodium chloride, albumin makes an important contribution.
Osmotic pressure determines the water balance between the blood and body cells.
Globulins account for 38% of the plasma proteins. It has three types: alpha, beta,
and gamma. The alpha and beta globulins carry lipids and fat-soluble vitamins in the
blood, while gamma globulins are produced in lymphoid tissues and consist of
antibodies that are involved in immunity.
Fibrinogens consititute 4% of plasma proteins and is responsible for the
formation of blood clots.
Plasma
Components
Functions
Water Acts as a solvent and suspending medium for blood
components.
Proteins Maintain osmotic pressure, destroy foreign substances,
transport molecules, and form clots.
Ions Involved in osmotic pressure, membrane potentials, and
acid-base balance.
Nutrients Source of energy and “building blocks” of more complex
molecules.
Gases Involved in aerobic respiration.
Waste products Breakdown products of protein metabolism, erythrocytes,
and anaerobic respiration.
Regulatory
substances
Catalyze chemical reactions and stimulate or inhibit many
body functions.
Formed Elements
About 95% of the volume of the formed elements consists of red blood cells, or
erythrocytes. The remaining 5% of the volume of the formed elements consists of white
blood cells, or leukocytes, and cell fragments called platelets, or thrombocytes.
Red blood cells or erythrocytes, are disk-shaped cells with edges that are
thicker than the center of the cell. The biconcave shape increases the surface area of
the red blood cell compared with a flat disk of the same size. The greater surface area
makes it easier for gases to move into and out of the red blood cell. In addition, the red
blood cell can bend or fold around its thin center, decreasing its size and enabling it to
pass more easily through small blood vessels. The main component of a red blood cell
is the pigmented protein hemoglobin, which accounts for about a third or the cell’s
volume and is responsible for its red color. The primary function of red blood cells is to
transport oxygen from the lungs to the various tissues of the body and to assist in the
transport of carbon dioxide from the tissues to the lungs. The percentage of total blood
volume occupied by RBC’s is called hematocrit. Normal hematocrit is adult males (40-
50%) is higher than in adult females (38-46%); the hormone testosterone, present much
higher in males, stimulates synthesis of erythropoietin, the hormone that in turn
stimulates production of RBCs.
White blood cells or leukocytes, are spherical cells that are whitish in color
because they lack hemoglobin. They are larger than red blood cells, and each has a
nucleus. Although white blood are the components of the blood, the blood serves
primarily as a means to transport these cells to other tissues of the body.
There are two functions of white blood cells which are:
1) To protect the body against
invading microorganism and;
2) to remove dead cells and debris
from the tissues by phagocytosis.
White blood cells are named according
to their appearance in stained preparations.
Those containing large cytoplasmic granules
are granulocytes and those with very small
granules that cannot be easily seen with the light microscope are agranulocytes. There
are three kinds of granulocytes: neutrophils, basophils, and eosinophils. Neutrophils, the
most common type of white blood cell, have small cytoplasmic granules that stain with
both acidic and basic dyes. Their nuclei are commonly lobed, with the number of lobes
varying from two to four. Neutrophils usually remains in the blood for a short time (10-12
hours), move into other tissues, and phagocytize microorganism and other foreign
substances. Basophils, the least common of all white blood cells, contain large
cytoplasmic granules that stain blue or purple with basic dyes. Basophils release
histamine and other chemicals that promote inflammation and also release heparin
which prevents the formation of clots. Eosinophils, contain cytoplasmic granules that
stain bright red with eosin, an acidic stain. It is a two-lobed nucleus which release
chemicals that reduce inflammation. There are two kinds of agranulocytes:
lymphocytes and monocytes. Lymphocyte, are the smallest of the white blood cells.
They are several types of lymphocytes, and they play an important role in the body’s
immune system response. It has two types, T Lymphocytes, directly attack and destroy
pathogens (bacteria and viruses), and B Lymphocytes, produce antibodies that attack
bacteria and bacterial toxins (poisons). Monocytes, are the largest of the white blood
cells. After they enter leave the blood and enter tissues, monocytes enlarge and
become macrophages, to which phagocytize bacteria, dead cells, cell fragments, and
any other debris within the tissues.
Platelets or thrombocytes, are minute fragments of cells, each consisting of a
small amount of cytoplasm surrounded by a cell membrane. It helps to stop blood loss
from damaged blood vessels by forming a platelet plug. Their granules contain also
chemicals that once released, promote blood clotting.
Preventing Blood Loss (Hemostasis)
When a blood vessel is damaged, blood can leak into other tissues and interfere
with normal tissue function, or
blood can be lost from the
body. A small amount of blood
loss from the body can be
tolerated, and new blood is
produced to replace it. If a
large amount of blood is lost,
death can occur. Fortunately,
when a blood vessel is
damaged, vascular spasm,
platelet plug formation, and
blood clotting minimize the loss
of blood.
Vascular spasm is an immediate but temporary constriction of a blood vessel
resulting from contraction of smooth muscle within the wall of the vessel. This
constriction can close small vessels completely and stop the flow of the blood through
them which lasts for several minutes and will allow time for formation of platelet plug
and clotting. As platelets accumulate at the site of the damage, they secrete serotonin,
a chemical that continues the contraction of the smooth muscles in the damaged
vessels.
Platelet plug is an accumulation of platelets that can seal up a small break in a
blood vessel. Platelet plug formation is very important in maintaining the integrity of
the circulatory system because small tears occur in the smaller vessels and capillaries
many times each day, and platelet plug formation quickly closes them. Platelet adhesion
results in platelets sticking to collagen exposed by blood vessel damage. Most platelet
adhesion is mediated through von Wilebrand’s factor, which is a protein produced and
secreted by blood vessel endothelial cells. Von Wilebrand’s factor forms a bridge
between collagen and platelets by binding to platelet surface receptors and collagen. In
the platelet release reaction, platelets release chemicals, such as ADP and
thromboxane, which activate other platelets. As platelets become activated they
express surface receptors called fibrinogen receptors, which can bind to fibrinogen, a
plasma protein. In platelet aggregation, fibrinogen forms bridges between the fibrinogen
receptors of numerous platelets, resulting in the formation of a platelet plug.
Blood vessel constriction and platelet plugs alone are not sufficient to close large
tears or cuts in blood vessels. When a blood vessel is severely damaged, blood
clotting, or coagulation, results in the formation of a clot. A clot is a network of
threadlike protein fibers, called fibrin, which traps blood cells, platelets, and fluid. The
formation of a blood clot depends on a number of proteins found within plasma called
clotting factors. This is a complex process involving many chemical reactions, but it can
be summarized in three main stages, which are:
1) The chemical reactions can be started in two ways:
a) The contact of inactive clotting factors with exposed connective
tissue can result in their activation;
b) chemicals, such as thromboplastin, released from injured tissues
can cause activation of clotting factors.
2) Prothrombinase acts on an inactive clotting factor called prothrombin to
convert it to its active form called thrombin.
3) Thrombin converts the inactive clotting factor fibrinogen into its active
form, fibrin.
Disorders of clotting
The most common causes of abnormal bleeding are platelet deficiency
(thrombocytopenia) and deficits of some of the clotting factors, such as might result
from impaired liver function or certain genetic conditions.
Thrombocytopenia results from an insufficient number of circulation platelets.
Even normal movements cause spontaneous bleeding from small blood vessels. This is
evidenced by many small purplish blotches, called petechiae, on the skin.
Thrombosis is the condition resulting from the formation of a blood clot in an
unbroken blood vessel. Such clots tend to form where the lining of a blood vessel is
roughed or damaged. They can cause serious effects if they plug an artery and deprive
vital tissue of blood. Blood clots form more frequently in veins than arteries, causing a
condition known as thrombophlebitis.
Sometimes, a clot formed in a vein breaks free and is carried by the blood only to
lodge in an artery, often a branch of pulmonary artery. Such a moving clot is called an
embolus, and when it blocks a blood vessel, the resulting condition is known as
embolism. An embolism can produce very serious and sometimes fatal results if it
lodges in a vital organ and blocks the flow of the blood.
Hemophilia applies to several different hereditary bleeding disorders that result
from a lack of any of the factors needed for clotting. Commonly called “bleeder’s
disease,” the hemophilias have similar signs and symptoms that begin early in life. Even
minor tissue trauma results in prolonged bleeding and can be life-threatening. There is
no cure for hemophilia, but it is treated by transfusion of the missing clotting factors.
HEMATOPOIESIS
The term hematopoiesis refers to the formation and
development of the cells of the blood. In humans, this
process begins in the yolk sac in the first weeks of embryonic
development. By the third month of gestation, stem cells
migrate to the fetal liver and then to the spleen (between 3-7
months gestation these two organs play a major hempatopoietic role).
Next, the bone marrow becomes the major hematopoietic organ and hematopoiesis
ceases in the liver and spleen.
Every functional specialized mature blood cell is derived from a common stem cell.
These stem cells are therefore, PLURIPOTENT.
It has been estimated that there is approximately 1 stem cell per 104 bone marrow cells.
These stem cells represent a self-renewing population of cells. These cells also must
have the potential to differentiate and to become committed to a particular blood cell
lineage.
Due to the low frequency of these cells and the inability to culture these cells in vitro,
stem cells have been very difficult to study.
Initial differentiation of pluripotent stem cells will be along one of two major pathways
(lymphoid or myeloid). Stem cells then become progenitor cells for each type of mature
blood cell. These cells have lost the capacity for self-renewal and are committed to a
given cell lineage. T&B progenitors, and progenitor cells for erythrocytes, neutrophils,
eosinophils, basophils, monocytes, mast cells, and platelets.
Pluripotent Stem Cell gives rise to:
Myeloid Stem Cell progenitor cells for each cell type neutrophil
monocyte macrophage
eosinophil
erythrocyte
megakaryocytes
mast cells
basophils
Or, Pluripotent Stem Cell gives rise to:
Lymphoid Stem Cell progenitor B precursor Bmature B
lymphocytePlasma Cell
Memory B Cell
or
progenitor T precursor Tc mature Tc CTL
memory Tc
or
precursor Th mature Th Th1
Th2
B cell development to the stage of the mature B lymphocyte is completed within the
bone marrow. Further differentiation into Plasma Cells or memory B cells does not
occur until the mature (but naïve) B lymphocyte encounters specific antigen. T cell
development to the stage of the precursor T lymphocyte occurs within the bone marrow.
The precursor T lymphocytes (otherwise known as pre-Ts) then must go to the thymus
to complete maturation. When mature T lymphocytes leave the thymus, they leave as
mature (but naïve ) Tc (T cytotoxic lymphocytes) or Th (T helper lymphocytes). Further
differentiation does not occur until the mature T cells encounter antigen (presented to
the T cell in association with MHC proteins).
Progenitor commitment depends upon the acquisition of responsiveness to certain
growth factors. The particular microenvironment within which the progenitor cell resides
controls differentiation. The hematopoietic cells grow and mature on a meshwork of
stromal cells, which are nonhematopoietic cells that support the growth and
differentiation of the hematopoietic cells. Include: fat cells, endothelial cells, fibroblasts,
and macrophages.
These cells provide a HEMATOPOIETIC -INDUCING MICROENVIRONMENT
This microenvironment consists of the actual cellular matrix and either membrane-
bound or diffusable growth factors.
Hematopoietic Growth Factors
Colony Stimulating Factors
multilineage colony-stimulating factor (multi-CSF or IL-3)
granulocyte-macrophage colony stimulating factor (GM-CSF)
macrophage colony stimulating factor (M-CSF)
granulocyte colony-stimulating factor (G-CSF)
Erythropoietin - Induces terminal erythrocyte development and regulates RBC
production.
These growth factors are present at extremely low concentrations and biological activity
at concentrations as low as 10-12 M.
Now all of the genes have been cloned and recombinant products have definable
activity in culture.
CSFs- act in a stepwise manner inducing proper maturation. IL-3 [multi-CSF] acts early,
possibly even at the level of the pluripotent stem cell, to induce formation of the
nonlymphoid cells (erythrocytes, monocytes, granulocytes[neutrophils, eosinophils,
basophils], and megakaryocytes).
GM-CSF acts at a slightly later stage, but it also induces formation of all the
nonlymphoid blood cells. M-CSF and G-CSF act still later to promote the formation of
monocytes and granulocytic cells, respectively.
IL-4 - stimulates B progenitors, mast progenitors, and basophil progenitors
IL-5 - stimulates eosinophil progenitor
IL-6 - stimulates the myeloid stem cell
*IL-7 - induces the differentiation of lymphoid progenitor into B progenitor and T
progenitor
IL-8 - stimulates the neutrophil progenitor
IL-9 - stimulates mast cell growth
Commitment of a progenitor cell is associated with the expression on the cell membrane
of membrane receptors that are specific for particular cytokines.
Hematopoiesis is a continuous process throughout adulthood. Production of mature
blood cells equals their loss. Estimated that the average human must produce 3.7X1011
blood cells per day. This process is regulated by complex mechanisms.
Cell division and differentiation during hematopoiesis are balanced by apoptosis - there
must by maintenance of a steady state.
During apoptosis you see:
a decrease in cell volume
modification of the cytoskeleton with pronounced membrane blebbing
condensation of chromatin
degradation of DNA into oligonulceosomal fragments
shedding of apoptotic bodies
quick phagocytosis to prevent inflammation
If apoptosis fails, a leukemic state can occur.
LYMPHATIC AND IMMUNE SYSTEM
The lymphatic system includes lymph, lymphocytes, lymphatic
vessels, lymph nodes, tonsils, the spleen, and the thymus gland.
Functions of the Lymphatic System:
The lymphatic system is part of the body’s defense system
against microorganisms and other harmful substances. In addition, it
helps to maintain fluid balance in tissues and to absorb fats from the
digestive tract.
1. Fluid balance – About 30 liters (L) of fluid pass from the blood capillaries into
the interstitial spaces each day, whereas only 27 L pass from the interstitial
spaces back into the blood capillaries. If the extra 3 L of interstitial fluid
remained in the interstitial spaces, edema would result, causing tissue
damage and eventually death. The 3 L of fluid enters the lymphatic
capillaries, where the fluid is called lymph (limf, meaning clear spring water),
and it passes through the lymphatic vessels to return to the blood. In addition
to water, lymph contains solutes derived from two sources: (a) substances in
plasma, such as ions, nutrients, gases, and some proteins, pass from blood
capillaries into the interstitial spaces and become part of the lymph; and (b)
substances, such as hormones, enzymes, and waste products, derived from
cells within the tissues are also part of the lymph.
2. Fat absorption – The lymphatic system absorbs fats and other substances
from the digestive tract. Special lymphatic vessels called lacteals (relating to
milk) are located in the lining of the small intestine. Fats enter the lacteals and
pass through the lymphatic vessels to the venous circulation. The lymph
passing through these lymphatic vessels has a milky appearance because of
its fat content, and it is called chyle (juice).
3. Defense – Microorganisms and other foreign substances are filtered from
lymph by lymph nodes and from blood from the spleen. In addition,
lymphocytes and other cells are capable of destroying microorganisms and
foreign substances.
Lymphatic capillaries and vessels
The lymphatic system, unlike the circulatory system, does not circulate fluid to
and from tissues. Instead, the lymphatic system carries fluid in one direction, from
tissues to the circulatory system. Fluid moves from blood capillaries into tissue spaces.
Most of the fluid returns to the blood, but some of the fluid moves from the tissue
spaces into lymphatic capillaries to become lymph. The lymphatic capillaries are tiny,
closed-ended vessels consisting of simple squamous epithelium. The lymphatic
capillaries are more permeable than blood capillaries because they lack a basement
membrane, and fluid moves easily into the lymphatic capillaries. The overlapping
squamous cells act as valves that prevent the back-flow of fluid.
Lymphatic capillaries are in almost all tissues of the body except the central
nervous system, bone marrow, and tissues without blood vessels such as the epidermis
and cartilage. A superficial group of lymphatic capillaries drains the dermis and
hypodermis, and a deep group drains muscle, viscera, and other deep structures.
The lymphatic
capillaries join to form larger lymphatic vessels, which resemble small veins. Small
lymphatic vessels have a beaded appearance because of one-way valves that are
similar to the valves of veins. When a lymphatic vessel is compressed, backward
movement of lymph is prevented by valves. Consequently, compression of lymphatic
vessels causes lymph to move forward through them. Three factors cause compression
of the lymphatic vessels: (1) contraction of surrounding skeletal muscle during activity,
(2) periodic contraction of smooth muscle in the lymphatic vessel wall, and (3) pressure
changes in the thorax during respiration.
The lymphatic vessels converge and eventually empty into the blood at two
locations in the body. Lymphatic vessels from the upper right limb and the right half of
the head, neck, and chest from the right lymphatic duct, which empties into the right
subclavian vein. Lymphatic vessels from the rest of the body enter the thoracic duct,
which empties into the left subclavian vein.
Lymphatic organs
Lymphatic organs include the tonsils, lymph nodes, the spleen, and the thymus
gland. Lymphatic tissue, which consists of many lymphocytes and other cells, is found
within lymphatic organs. The lymphocytes originate from red bone marrow and are
carried by the blood to lymphatic organs. When the body is exposed to microorganisms
or foreign substances, the lymphocytes divide and increase in number. The increased
number of lymphocytes is part of the immune response that causes the destruction of
microorganisms and foreign substances. In addition to cells, lymphatic tissue has very
fine reticular fibers. These fibers form an interlaced network that holds the lymphocytes
and other cells in place. When lymph or blood filters through lymphatic organs, the fiber
network also traps microorganisms and other items in the fluid.
Tonsils
There are three groups of tonsils. The palatine (palate) tonsils usually are
referred to as “the tonsils,” and they are located on each side of the posterior opening of
the oral cavity. The pharyngeal tonsil, or adenoid (glandlike), is located near the internal
opening of the nasal cavity. If enlarged, a pharyngeal tonsil can interfere with normal
breathing. The lingual (tongue) tonsil is on the posterior surface of the tongue.
The tonsils form a protective ring of lymphatic tissue around the openings
between the nasal and oral cavities and the pharynx. They provide protection against
pathogens and other potentially harmful material entering form the nose and mouth.
Sometimes the palatine or pharyngeal tonsils become chronically infected less often
than the other tonsils and is more difficult to remove. In adults the tonsils decrease in
size and may eventually disappear.
Lymph nodes
Lymph nodes are rounded structures, varying in size from that of small seeds to
that of shelled almonds. Lymph nodes are distributed along the various lymphatic
vessels, and most lymph passes through at least one lymph node before entering the
blood. Although lymph nodes are found throughout the body, there are three superficial
aggregations of lymph nodes on each side of the body: inguinal nodes in the groin,
axillary nodes in the axilla, and cervical nodes in the neck.
A dense connective tissue capsule surrounds each lymph node. Extensions of
the capsule, called trabeculae, subdivide lymph nodes into compartments containing
lymphatic tissue and lymphatic sinuses. The lymphatic tissue consists of lymphocytes
and other cells that can from dense aggregations of tissue lymph nodules. Lymphatic
sinuses are spaces between lymphatic tissues which contain macrophages on a
network of fibers. Lymph enters the lymph node through afferent vessels, passes
through the lymphatic tissue and sinuses, and exits through efferent vessels.
As lymph moves through the lymph nodes, two functions are performed. One
function is activation of the immune system. Microorganisms or other foreign
substances in the lymph can stimulate lymphocytes in the lymphatic tissue to start
dividing. The lymph nodules containing the rapidly dividing lymphocytes are called
germinal centers. The newly produced lymphocytes are released into the lymph and
eventually reach the blood, where they circulate and enter other lymphatic tissues.
Another function of the lymph nodes is the removal of microorganisms and foreign
substances from the lymph by macrophages.
Spleen
The spleen is roughly the size of a clenched fist, and it is located in the left,
superior corner of the abdominal cavity. The spleen has an outer capsule of dense
connective tissue and a small amount of smooth muscle. Trabeculae from the capsule
divide the spleen into small, interconnected compartments containing two specialized
types of lymphatic tissue. White pulp is lymphatic tissue surrounding the arteries within
the spleen. Red pulp is associated with the veins. It consists of a fibrous network, filled
with macrophages and red blood cells, and enlarged capillaries that connect to the
veins.
The spleen filters blood instead of lymph. Cells within the spleen detect and
respond to foreign substances in the blood and destroy worn-out red blood cells.
Lymphocytes in the white pulp can be stimulated in the same manner as in lymph
nodes. Before blood leaves the spleen through veins, it passes through the red pulp.
Macrophages in the red pulp remove foreign substances and worn-out red blood cells
through phagocytosis.
The spleen also functions as a blood reservoir, holding a small volume of blood.
In emergency situations such as hemorrhage, smooth muscle in splenic blood vessels
and in the splenic capsule can contract. The result is the movement of a small amount
of blood out of the spleen into the general circulation.
Thymus
The thymus is a bilobed gland roughly triangular in shape. It is located in the
superior mediastinum, the partition dividing the thoracic cavity into left and right parts. It
was once thought that the thymus increases in size until puberty after which it
dramatically decreases in size. It is now believed that the thymus increases in size until
the first year of life, after which it remains approximately the same size, even though,
the size of the individual increases. After 60 years of age, it decreases in size, and in
older adults, the thymus may be small that it is difficult to find during dissection.
Although the size of the thymus is fairly constant throughout much of life, by 40 years of
age much of the thymus has been replaced with adipose tissue.
Each lobe of the thymus is surrounded by a thin connective tissue capsule.
Trabeculae from the capsule divide each lobe into lobules. Near the capsule and
trabeculae, the lymphocytes are numerous and form dark-staining central portion of the
lobules, called the medulla, has fewer lymphocytes.
The thymus functions as a site for the production and maturation of lymphocytes.
Large numbers of lymphocytes are produced in the thymus, but for unknown reasons,
most degenerate. While in the thymus, lymphocytes do not respond to foreign
substances. After thymic lymphocytes have matured, however, they enter the blood and
travel to other lymphatic tissues, where they help to protect against microorganisms and
other foreign substances.
Immunity
Immunity is the ability to resist damage from foreign substances, such as
microorganisms, and harmful chemicals, such as toxins released by microorganisms.
Immunity is categorized as innate immunity (also called non specific resistance) or
adaptive immunity (also called specific immunity). In innate immunity, the body
recognizes and destroys certain foreign substances, but the response to them is the
same each time the body is exposed to them. In adaptive immunity, the body
recognizes and destroys foreign substances, but the response to them improves each
time the foreign substance is encountered.
Specificity and memory are characteristics of adaptive immunity but not innate
immunity. Specificity is the ability of adaptive immunity to recognize a particular
substance. For example, innate immunity can act against bacteria in general, whereas
adaptive immunity can distinguish among different kinds of bacteria. Memory is the
ability of adaptive immunity to “remember” previous encounters with a particular
substance. As a result, the response is faster, stronger, and lasts longer.
In innate immunity, each time the body is exposed to a substance, the response
is the same because specificity and memory of previous encounters are not present.
For example, each time a bacterial cell is introduced into the body, it is phagocytized
with the same speed and efficiency. In adaptive immunity, the response during the
second exposure is faster and stronger than the response to the first exposure because
the immune system exhibits memory for the bacteria from the first exposure. For
example, following the first exposure to the bacteria, the body can take many days to
destroy them. During this time the bacteria damage tissues, producing the symptoms of
disease. Following the second exposure to the same bacteria, the response is rapid and
effective. Bacteria are destroyed before any symptoms develop, and the person is said
to be immune.
Innate immunity
Innate immunity is accomplished by mechanical mechanisms, chemical
mediators, cells, and the inflammatory response.
Mechanical mechanisms
Mechanical mechanisms prevent the entry of microorganisms and chemicals into
the body in two ways: (1) the skin and mucous membranes from barriers that prevent
their entry, and (2) tears, saliva, and urine act to wash them from the surfaces of the
body. Microorganisms cannot cause a disease if they cannot get into the body.
Chemical mediators
Chemical mediators are molecules responsible for many aspects of innate
immunity. Some chemicals that are found on the surface of cells kill microorganisms or
prevent their entry into the cells. Lysozyme in tears and saliva kills certain bacteria, and
mucus on the mucous membranes prevents the entry of some microorganisms. Other
chemical mediators, such as histamine, complement, prostaglandins, and leukotrienes,
promote inflammation by causing vasodilation, increasing vascular permeability, and
stimulating phagocytosis. In addition, interferons protect cells against viral infections.
Complement
Complement is a group of approximately 20 proteins found in plasma. The
operation of complement proteins is similar to that of clotting proteins. Normally,
complement proteins circulate in the blood in an inactive form. Certain complement
proteins can be activated by combining with foreign substances, such as part of a
bacterial cell, or by combining with antibodies. Once activation begins, a series of
reaction results, in which each complement protein activates the next. Once activated,
certain complement proteins promote inflammation and phagocytosis and can directly
lyse (rupture) bacterial cells.
Interferons
Interferons are proteins that protect the body against viral infections. When a
virus infects a cell, the infected cell produces viral nucleic acids and proteins, which are
assembled into new viruses. The new viruses are then released to infect other cells.
Because infected cells usually stop their normal functions or die during viral replication,
viral infections are clearly harmful to the body. Fortunately, viruses often stimulate
infected cells to produce interferons. Interferons do not protect the cell that produces
them. Instead, interferons bind to the surface of neighboring cells where they stimulate
those cells to produce antiviral proteins. These antiviral proteins inhibit viral
reproduction by preventing the production of new viral nucleic acids and proteins.
Some inferons play a role in the activation of immune cells such as macrophages
and natural killer cells.
Cells
White blood cells and the cells derived from white blood cells are the most
important cellular components of immunity. White blood cells are produced in red bone
marrow and lymphatic tissue and are released into the blood. Chemicals released from
microorganisms or damaged tissues attract the white blood cells, and they leave the
blood and enter affected tissues. Important chemicals known to attract white blood cells
include complement, leukotrienes, kinins, and histamine. The movement of WBC’s
towards these chemicals is called chemotaxis.
Phagocytic cells
Phagocytosis is the ingestion and destruction of particles by cells called
phagocytes. The particles can be microorganisms or their parts, foreign substances, or
dead cells from the individual’s body. The most important phagocytes are neutrophils
and macrophages, although other WBC’s also have limited phagocytic ability.
Neutrophils are small phagocytic cells that are usually the first cells to enter
infected tissues from the blood in large numbers; however, neutrophils often die after
phagocytizing a single microorganism. Pus is an accumulation of fluid, dead neutrophils,
and other cells at a site of infection.
Macrophages are monocytes that leave the blood, enter tissues, and enlarge
about fivefold. Monocytes and macrophages from the mononuclear phagocytic system
because they are phagocytes with a single (mono), unlobed nucleus. Sometimes
macrophages are given specific names such as dust cells in the lungs. Kupffer cells in
the liver, and microglia in the CNS. Macrophages can ingest more and larger items than
can neutrophils. Macrophages usually appear in infected tissues after neutrophils and
are responsible for most of the phagocytic activity in the late stages of an infection,
including the cleanup of dead neutrophils and other cellular debris
In addition, to leaving the blood in response to an infection, macrophages are
also found in uninfected tissues. If microorganisms enter uninfected tissue, the
macrophages may phagocytize the microorganisms before they can replicate or cause
damage. For example, macrophages are located at potential points of entry for
microorganisms into the body, such as beneath the skin and mucous membranes, and
around blood and lymphatic vessels. They also protect lymph in lymph nodes and blood
in the spleen and liver.
Cells of inflammation
Basophils, which are derived from red bone marrow, are motile white blood cells
that can leave the blood and enter infected tissues. Mast cells, which are aso derived
from red bone marrow, are non-motile cells in connective tissue, especially near
capillaries. Like macrophages, mast cells are located at potential points of entry for
microorganisms into the body such as the skin, lungs, gastrointestinal tract, and
urogenital tract.
Basophils and mast cells can be activated through innate immunity or through
adaptive immunity or through adaptive immunity. When activated, they release
chemicals such as histamine and leukotrienes that produce an inflammatory response
or activate other mechanisms such as smooth muscle contraction in the lungs.
Eosinophils are produced in red bone marrow, enter the blood, and within a few
minutes enter the tissues. Enzymes released by eosinophils break down chemicals
released by basophils and mast cells. Thus at the same time that inflammation is
initiated, mechanisms are activated that contain and reduce the inflammatory response.
Inflammation is beneficial in the fight against microorganisms, but too much
inflammation can be harmful, resulting in the unnecessary destruction of healthy tissues
as well as the destruction of microorganisms.
Natural Killer Cells
NK cells are a type of lymphocyte produced in red bone marrow, and they
account for up to 15% of lymphocytes. NK cells recognize classes of cells, such as
tumor cells or virus-infected cells in general, rather than specific tumor cells or cells
infected by a specific virus. For this reason, and because NK cells do not exhibit a
memory response, NK cells are classified as part of innate immunity. NK cells use a
variety of methods to kill their target cells, including the release of chemicals that
damage cell membranes, causing the cells to lyse.
Inflammatory Response
The inflammatory response to injury involves many of the chemicals and cells
previously discussed. Most inflammatory responses are very similar, although some
details can vary depending on the intensity of the response and the type of injury. A
bacterial infection is used here to illustrate an inflammatory response. The bacteria, or
damage to tissues, cause the release or activation of chemical mediators, such as
histamine, prostaglandins, leukotrienes, complement, or kinins. The chemicals produce
several effects: (1) vasodialtion, which increases blood flow and brings phagocytes and
other WBCs to the area; (2) chemotactic attraction of phagocytes, which leaves the
blood and enter the tissue; and (3) increased vascular permeability, allowing fibrinogen
and complement to enter the tissue from the blood. Fibrinogen is converted into fibrin,
which isolates the infection by walling off the infected area. Complement further
enhances the inflammatory response and attract additional phagocytes. This process of
releasing chemical mediators and attracting phagocytes and other WBCs continues until
the bacteria are destroyed. Phagocytes remove microorganisms and dead tissue, and
the damaged tissues are repaired.
Inflammation can be localized or systemic. Local inflammation is an inflammatory
response confined in a specific area of the body. Symptoms of local inflammation
include redness, heat, swelling, pain, and loss of function. Redness, heat, and swelling
result from increased blood flow and increased vascular permeability. Pain is caused by
swelling and by chemical mediators acting on pain receptors. Loss of function results
from tissue destruction, swelling and pain.
Systemic inflammation is an inflammatory response that is generally distributed
throughout the body. In addition to the local symptoms at the sites of inflammation,
three additional features can be present:
1. Red bone marrow produces and releases large numbers f neutrophils, which
promote phagocytosis.
2. Pyrogens (fever producing), chemicals release by microorganisms,
neutrophils, and other cells, stimulate fever production. Pyrogens affect the
body temperature-regulating mechanism in the hypothalamus of the brain. As
a consequence, heat production and conservation increase, and body
temperature increases. Fever promotes the activities of the immune system,
such as phagocytosis, and inhibits the growth of some microorganisms.
3. In severe cases of systemic inflammation, vascular permeability can increase
so much that large amounts of fluid are lost from the blood into the tissues.
The decreased blood volume can cause shock and death.
Adaptive Immunity
Adaptive immunity exhibits specificity, the ability to recognize a particular
substance, and memory, the ability to respond with increasing effectiveness to
successive exposures to the antigen. Substances that stimulate adaptive immune
responses are called antigens. Antigens can be divided into two groups: foreign
antigens and self-antigens. Foreign antigens are introduced from outside the body.
Microorganisms, such as bacteria and viruses, cause diseases, and components of
microorganisms and chemicals released by microorganisms are examples of foreign
antigens. Pollens, animal hairs, food, and drugs can cause an allergic reaction because
they are foreign antigens that produce an overreaction of the immune system.
Transplanted tissues and organs contain foreign antigens can result in the rejection of
the transplant.
Self-antigens are molecules produced by the person’s body that stimulate an
immune system response. The response to self-antigens can be beneficial. For
example, the recognition of tumor antigens can result in destruction of the tumor. The
response to self-antigens can also be harmful. Autoimmune disease results when self-
antigens stimulate unwanted destruction of normal tissue.
The adaptive immune system response to antigens was historically divided into
two parts: humoral immunity and cell-mediated immunity. Early investigators of the
immune system found that when plasma from an immune animal was injected into the
blood of a non-immune animal, the non-immune animal became immune. Because this
process involved body fluids (humors), it was called humoral immunity. It was also
discovered that blood cells alone could be responsible for immunity, and this process
was called cell-mediated immunity.
It is now known that both types of immunity involve the activities of lymphocytes.
There are two types of lymphocytes: B cells and T cells. B cells give rise to cells that
produce proteins called antibodies, which are found in the plasma. The antibodies are
responsible for humoral immunity, which is now called antibody-mediated immunity. T
cells are responsible for cell-mediated immunity. Several subpopulations of T cells exist.
For example, cytotoxic T cells produce the effects of cell-mediated immunity and helper
T cells can promote or inhibit the activities of both antibody-mediated immunity and cell-
mediated immunity.
Stages in the process of antibody-mediated immunity are:
1. Antigen detection
2. Activation of helper T cells
3. Antibody production by B cells
4. Cell-mediated immunity
Each stage is directed by a specific cell type.
Macrophages / antigen detection
Macrophages are white blood cells that continually search for foreign (nonself)
antigenic molecules, viruses, or microbes. When found, the macrophages engulf and
destroy them. Small fragments of the antigen are displayed on the outer surface of the
macrophage plasma membrane.
Helper T cells / Activation of helper T cells
Helper T cells are macrophages that become activated when they encounter the
antigens now displayed on the macrophage surface. Activated T cells identify and
activate B cells.
B cells / antibody production
B cells divide, forming plasma cells and B memory cells. The production of
antibodies after the first exposure is different from that after a second or subsequent
exposure. The primary response results from the first exposure of a B cell to an antigen
for which it is specific. Before stimulation by an antigen, B cells are small lymphocytes.
After activation the B cells undergo a series of division to produce large lymphocytes.
Some of these enlarged cells become plasma cells that produce antibodies, and others
revert back to small lymphocytes and become memory B cells. The secondary or
memory response occurs when the immune system is exposed to an antigen against
which it has already produced a primary response. The secondary response results
from memory B cells, which rapidly divide to produce plasma cells and large amounts of
antibody when exposed to the antigen; it provides better protection than the primary
response for it requires lesser time to start producing antibodies and it produces much
larger amount of antibodies. Thus, the antigen is quickly destroyed, no disease
symptoms develop, and the person is immune.
Cell-mediated immunity
This is controlled by T cells. There are several subpopulations of T cells, each of
which is responsible for a particular aspect of cell-mediated immunity. Once activated, T
cells undergo a series of divisions and produce effects on T cells (such as cytotoxic T
cells) and memory T cells.
Cytotoxic T cells have two main effects: they lyse cells and produce cytokines.
Cytokines are proteins or peptides secreted by one cell as a regulator of neighboring
cells. Cytokines produced by lymphocytes are often called lymphokines. Cytotoxic T
cells can release chemical that causes the target cell to lyses. They bind to target cell
and releases chemical that causes the target cell to lyse. In addition to lysing cells,
cytotoxic T cells release cytokines that activate addition components of the immune
system. For example, one important function of cytokines is the recruitment of cells
such as macrophages, which are responsible for phagocytosis and inflammation.
Acquired Immunity
There are four ways to acquire adaptive immunity: active natural, active artificial,
passive natural and passive artificial. “Natural” and “artificial” refer to the method of
exposure. Natural exposure implies that contact with an antigen or antibody occurs as
part of everyday living and is not deliberate. Artificial exposure (immunization) is a
deliberate introduction of an antigen or antibody into the body. “Active” and “passive”
indicate whether or not an individual’s immune system is directly responding to the
antigen. When an individual is naturally or artificially exposed to an antigen, there can
be an adaptive immune system response that produces antibodies. This is called active
immunity because the individual’s own immune system is the cause of immunity.
Passive immunity occurs when another person or animal develops antibodies and the
antibodies are transferred to a non-immune individual.
Immunity can be long lasting if enough B and T memory cells are produced and
persist to respond to later antigen exposure. Passive immunity is not long lasting
because the individual does not produce his own memory cells.
Active Natural Immunity – natural exposure to an antigen such as disease-
causing microorganism can cause an individual’s immune system to mount an adaptive
immune system response against the antigen.
Active Artificial Immunity – an antigen is deliberately introduced into an individual
to stimulate his / her immune system. This process is called vaccination. The antigen
has been changed so that it stimulates the immune system but does not cause the
schemes. The first injection of the antigen stimulates a primary response, and the
booster shot causes a memory response, which produces high levels of antibody, many
memory cells, and long lasting protection.
Passive Natural Immunity – this results when antibodies are transferred from a
mother to her child. The mother has been exposed to many antigens, either naturally or
artificially, and she therefore has antibodies against many of these antigens. These
antibodies protect both the mother and the developing fetus against disease; the
antibody IgG can cross the placenta and enter the fetal circulation. After birth the
antibodies provide protection for the first few months of the infant’s life. Eventually the
antibodies are broken down, and the infant must rely on its own immune system.
Passive Artificial Immunity – This usually begins with vaccinating an animal such
as a horse. After the animal’s immune system responds to the antigen, antibodies
(sometimes T cells) are removed from the animal and injected to the individual requiring
immunity. In some cases a human who has developed immunity is used as a source.
This provides immediate protection for the individual; however, this technique provide
only temporary immunity because the antibodies are used or eliminated by the recipient.
PATHOPHYSIOLOGY
A. Etiology
Predisposing Factors Actual Justification
Age
√
All age groups are affected; 90% of cases occur in persons older than 60 years because developing mutations increases with age.
Gender
√
A slight male predominance is noted in all age groups of those with acute myelogenous leukemia.
Congenital causes Certain congenital disorders such as Bloom’s syndrome, Down syndrome, and Fanconi anemia have unstable genes and are more at risk of developing mutations.
Genetics Dysplastic abnormalities of hematopoietic stem cells has been associated with the loss of the long arm of chromosome 5 or the 5q – syndrome.
Precipitating Factor Actual JustificationChemical exposure Exposure to some environmental chemicals,
especially benzene and petroleum products, is associated with the development of AML.
Cigarette smoking Exposure to chemicals in tobaccos smoke may increase the risk of developing AML.
Cytotoxic chemotherapy People previously treated for cancer or other conditions with cytotoxic chemotherapy, are at an increased risk for developing what is called secondary or treatment-related AML.
Radiation Previous radiation therapy, or exposure to high levels of environmental irradiation, is associated with increased risk of AML.
Viral infections Some viral infections alter the genetic structure of cells causing mutations.
Drugs Certain drugs such as cytotoxic drugs, chloramphenicol, NSAIDs, and colchicine could decrease blood components.
B. Symptomatology
Signs/Symptoms Actual Justification
Weakness
√
A decrease in red blood cells impairs the distribution of oxygen and nutrients to tissues which are necessary for metabolic processes in the body.
Dyspnea There is a decrease in hemoglobin concentration in the blood which is important in the transportation of oxygen which results to the increase in effort during breathing process.
Pallor Anemia causes decline in circulating red blood cells and hemoglobin resulting to pale extremities.
Skin lesions
√
Skin lesions are due to decreased neutrophils causing increase in the risk for infection and decreased platelets slows down clotting process.
Splenomegaly It is cause by the increased activity of the spleen due to extramedullary hematopoiesis and destruction of ineffective red blood cells and platelets.
Petechiae Decrease in platelet count could cause microvascular bleeding due to impaired clotting process.
Bleeding Decrease in platelet count could cause microvascular bleeding due to impaired clotting process.
Fever
√
Fever is an inflammatory response due to the increased risk for infection brought about by neutropenia.
Chest pain Decrease in oxygen levels in the heart muscle due to anemia.
Pneumonia √ Decrease in neutrophil count predisposes the patient to bacterial infections.
Low serum reticulocyte Impaired hematopoiesis causes decrease in formation of new RBCs
Low blood components (RBCs, neutrophils, and
platelets) √
Impaired hematopoiesis causes decrease in formation of blood components.
Rapid heart rate
√
The heart compensates for low oxygen levels by increasing its pumping ability to pump more blood to the system.
Bone pain and tenderness √ Pain felt is due to the expansion of the bone marrow caused by increased proliferation of myeloid precursors.
Headache, nausea, vomiting, seizures, confusion, coma
√ Leukemic infiltration of the central nervous system.
Abdominal discomfort
√
Generalized lymphadenopathy, hepatomegaly, splenomegaly, due to leukemic cell infiltration.
Hyperuricemia Due to abnormal proliferation and metabolism of leukemic cells.
C. Schematic Diagram
PREDISPOSING FACTORS
Age, Gender, Genetics, Congenital
PRECIPITATING FACTORS
Drugs, Smoking, Chemical exposure, Cytotoxic chemotherapy, Radiation, Viral infections
Mutation in the multi-potent bone marrow stem cell forming neoplastic cells
Myeloblast affectation
Disruption in myeloid differentiation and maturation
Dysregulation in the formation of myeloid precursors
Clonal expansion of the undifferentiated myeloid precursor in the bone marrow
Dysfunction in the cell’s error detection and correction mechanisms
Transformation of Proto-oncogenes to Oncogenes
Mutation of tumor suppressor genes
Inactivation of tumor suppressor proteins
Uncontrolled cell cycle and cell division
Over expression of growth factor (IL-3, GM-CSF, M-CSF, G-CSF)
Alteration in DNA
Alteration in cellular transcription and translation pathways
Decreased in levels of apoptotic cell death of malignant cells
Treatment/ Management :
1. Blood transfusion
2. Dietary supplements
3. Diet4. Erythropoietin5. Bone marrow
transplant
Treatment / Management:1. Platelet Transfusion2. Prevent injury/trauma3. Corticosteroid
Treatment / Management:1. Antibiotics2. Infection control3. Hygiene
Dx: BMA: Presence of numerous blast cells
Dx: RBC: 32.27 10^12cells/L Hgb: 92g/L
Dx: leukocytes: 9.1 10^9/L Neutrophil: 0.02%
Dx: Platelets: 29 10^9/L
If Treated with:
Chemotherapy* Radiation therapy Allopurinol therapy Administration of
Tretinoin Bone marrow or stem
cell transplant
If Not Treated:
Metastasis
GOOD – FAIR PROGNOSIS
Continuous proliferation of leukemic cells in the bone marrow
Damage of surrounding blood vessels
Entry of malignant cells in the circulation
Invasion of surrounding tissues and organs
Lymph nodes
Lymphadenopathy
Spleen
Splenomegaly
Liver
Hepatomegaly
CNS
Leukemic cells pass the blood-
brain barrier
Increased leukemic blast
count in the CNS
Cerebral leukostasis
Accumulation of leukemic blast in the circulation
Increase in blood viscosity
Predisposition to leukoblastic emboli
Obstruction of small blood vessels
Occlusion of pulmonary vessels
Rupture of vessels and infiltration of lung tissue
Chemotherapy complications
Increased Leukemic cell death
Increased breakdown of purine nucleotides from DNA
Release of uric acid
Hyperuricemia
Uric acid crystallization in the urine
Renal complications
Respiratory failure
CNS depression
If Not Treated:
Complications
A
*
B
(CM) Abdominal discomfort(CM) headache, nausea, vomiting, seizures
(CM) headache, lethargy, confusion, coma
(CM) shortness of breath, dyspnea
Continuous decline in circulating RBC
Decreased haemoglobin levels
Decreased oxygen carrying capacity of the blood
Hypoxemia
Tissue hypoxia and cellular starvation
Decreased immune response to pathogens
Pathogenic invasion and propagation
Spread of pathogens through the circulation
Septicemia
Decreased platelet aggregation and clot formation
Increased bleeding tendencies
Internal and external hemorrhage
Hypovolemia
Shock
Narrative Pathophysiology
Formation of lactic acid
Metabolic acidosis
Anaerobic metabolism
Systemic failure
DEATH
Acute myeloid leukemia (AML) results from defect in the hematopoietic stem cell
that differentiates into all myeloid cells: monocytes, granulocytes (neutrophils,
basophils, eosinophils), erythrocytes, and platelets. AML is the most common non-
lymphocytic leukemia.
Certain risk factors influence the onset of the disease. Predisposing factors
would include age, gender, genetics, and congenital causes with higher incidence in
male patients aging more than 60 years old with genetic and congenital disorders that
causes mutations in the hematopoietic stem cells in the bone marrow. Other factors that
could precipitate the disease include chemical exposure, cigarette smoking, cytotoxic
chemotherapy, radiation, viral infections, and drugs which cause alterations in genetic
structure of stem cells.
The disease process starts with the alteration of the cell’s DNA structure caused
by the said factors. Proto-oncogenes, which are responsible for normal metabolic
processes in the body, are transformed to oncogenes - which are mutated genes which
serve no purpose in the body. There will be mutation of tumor suppressor genes which
are responsible for normal cell cycle and replication. This will lead to over expression of
growth factors that are necessary for cellular growth and proliferation. Normal cellular
functioning will be altered such as transcription and translation process. Due to
mutation, the cell’s error detection and correction mechanism is dysfunctional causing
production of more mutated cells. There will be uncontrolled cell cycle and cell division
due to the dysfunction in regulatory mechanisms. Since the bone marrow is the affected
site, there will be formation of neoplastic cells from mutated multi-potent stem cells. In
AML, the affected precursor cells are the myeloblast which differentiates to monocytes,
granulocytes (neutrophils, basophils, eosinophils), erythrocytes, and platelets. Due to
mutation, myeloblasts are in a state of “differentiation arrest” which renders them unable
to differentiate and mature. There will be clonal expansion of these myeloid precursors
since they still have the ability to proliferate but in an abnormal rate. These malignant
cells are insensitive to apoptotic cell death or programmed cell death. Accumulation of
neoplastic cells occurs in the bone marrow causing bone marrow expansion which can
lead to bone pain and tenderness. Normal bone marrow cells will be crowded by the
malignant cells causing destruction and bone marrow suppression. There will be
alteration in hematopoiesis, the process of formation of blood components. There will be
formation of dysfunctional blood components causing premature destruction and loss of
their function.
Anemia is a condition where there is a decline in erythrocyte concentration and
with an accompanying decrease in hemoglobin levels. Erythrocytes and hemoglobin are
important in the transportation of nutrients and oxygen to tissues and organs.
Decreased levels would result to weakness, pallor, splenomegaly, and chest pain due to
low oxygen levels needed for metabolic processes. Treatment for anemia would include
blood transfusion to replace dysfunctional RBCs, dietary supplements and proper diet
especially high in iron for RBC and hemoglobin production, erythropoietin to stimulate
the bone marrow to produce RBC, and bone marrow transplant to replace dysfunctional
ones.
Neutropenia results from decreased production of circulating neutrophils in the
blood and there is diminished ability to destroy bacteria through phagocytosis..
Neutrophils are responsible for immune response during infection and they are the first
ones to enter the site of infection. Decrease in neutrophil count could lead to increased
risk for infection and may cause fever, skin lesions, and pneumonia. Treatment would
include antibiotics to counteract infections, infection control and hygiene to prevent
occurrence and reoccurrence of infection.
Thrombocytopenia is a result of decreased platelet count in the blood. Platelets
may also exhibit diminished ability to aggregate during blood clotting and are less
adhesive. Platelets are responsible for blood clotting process in the presence of injury
to the skin and other membranes. Decreased platelet count could cause bleeding,
petechiae, and skin lesions due to prolonged blood clotting. Treatments would include
platelet transfusion and corticosteroid therapy to increase platelet count, and prevention
of injury/trauma to minimize risk for bleeding.
When these blood disorders are treated, accompanied by chemotherapy and
radiation therapy, allopurinol and Tretinoin administration, and bone marrow or stem cell
transplant, the patient may have a fair to good prognosis and will be able to have a
stable lifestyle. Chemotherapy and radiation therapy are used to destroy malignant cell
growth; this is usually accompanied by the administration of allopurinol since it could
increase uric acid levels and cause renal problems. Tretinoin is a vitamin A derivative
and is used as an adjunct treatment with chemotherapy to induce maturation of
immature cancer cells into mature granulocytes. Bone marrow or stem cell
transplantation is harvesting of bone marrow or stem cell from a HLA (human leukocyte
antigen) – matched donor.
If no treatment is done complications from blood dyscrasias may occur and
metastasis of leukemic cells is possible. There will be continuous proliferation of
malignant leukemic cells in the bone marrow. Damage to surrounding blood vessels
occurs due to overcrowding of malignant cells and there will be entry into the circulation.
These malignant cells could lodge to different organs and invade normal cells. They
could invade the lymph nodes, spleen, and liver, and will cause lymphadenopathy,
splenomegaly, and hepatomegaly which would cause abdominal discomfort. Leukemic
cells could pass through the blood-brain barrier and cause cerebral leukostasis or the
increased leukemic blast count in the CNS. The patient could experience episodes of
headache, nausea, omitting, seizures, lethargy, confusion, and may lead to coma.
Leukemic cells can accumulate in the blood and increase blood viscosity. Increased
blood viscosity predisposes the patient for emboli formation which could obstruct small
blood vessels such as in the lungs. This can cause rupture of pulmonary vessels and
infiltration of lung tissues and may lead to respiratory failure as manifested by shortness
of breath, and dyspnea. Complications of anemia are caused by continuous decline in
circulating RBC, the oxygen carrying component of the blood, and lead to a decrease in
haemoglobin levels. Low oxygen levels in the blood leads to hypoxemia causing tissue
hypoxia and cellular starvation. Low oxygen levels stimulates anaerobic metabolism,
which is energy production without oxygen consumption. Anaerobic metabolism
produces lactic acid as a waste product and can cause metabolic acidosis when it
accumulates in the blood. Neutropenia causes decreased immune response against
pathogens which increases pathogen invasion and propagation. Pathogens would
spread through the blood stream and lead to septicaemia. Thrombocytopenia causes
decreased platelet aggregation and formation of blood clot which predisposes the
patient for uncontrolled bleeding causing internal or external hemorrhage. This could
lead to hypovolemia and consequently cause shock. All of these complications would
lead to systemic failure of different organs and will later lead to death of the patient.
DIAGNOSTIC EXAMINATIONS
BASIC TEST
WITH NORMAL
VALUES
RATIONALE RESULT CLINICAL SIGNIFICANCE NURSING INTERVENTIONS
BEFORE AND AFTER EXAMS
COMPLETE BLOOD COUNT
Hemoglobin
Male: 140-180 g/L
The presence of a
large amount of
hemoglobin
enables the
erythrocyte to
perform its
principal function,
the transport of
oxygen between
the lungs and the
tissues. Low
hemoglobin and
hematocrit levels
have serious
consequences for
patients with
July 11:
55 g/dL
Low
July 14:
75 g/dL
Low
July 16:
68 g/dL
Low
July 19:
Decreased: It is decreased in cases
of fluid volume excess, hematologic
cancers, haemolytic disorders, blood
loss, anemia.
Increased: It is increased in cases
of dehydration, COPD, high
altitudes, polycythemia vera
Explain the purpose for the
laboratory and diagnostic
exams briefly to the family
and the client. A detailed
explanation during a crisis
might not be appropriate.
Check the results and return
and notify the physician of
the laboratory results.
Assess for excess bleeding
and apply pressure if
appropriate. Report changes
to the physician.
Determine if the test was
cardiovascular
disease, such as
more frequent
angina episodes
or acute
myocardial
infarction. Also
used in detecting
anemia and
polycythemia.
92 g/dL
Low
correctly performed.
Notify the laboratory if any
undesirable changes occur
after the test.
Erythrocytes
M: 4.5-5.0 10^12
cells/L
Erythrocytes or
red blood cells
function primarily
to ferry oxygen in
blood to all cells.
The red
Cell or
erythrocyte count
is a determination
of the number of
red cells found in
July 11:
1.92 10^12/L
LOW
July 14:
2.69 10^12/L
LOW
July 16:
2.44 10^12/L
Increased: intravascular or
extracellular fluid volume loss,
chronic hypoxia, iatrogenic
erythropoietin excess, polycythemia
vera
each rubic
millimeter of
whole blood.
Low
July 19:
32.27
10^12/L
HIGH
Mean
Corpuscular
Volume
85-96 fl
Volume of
hemoglobin in
each RBC
July 11:
91.6 fl
Normal
July 14:
85.8 fl
Normal
July 16:
82 fl
LOW
July 19:
MCV, MCH, MCHC values are
useful in the diagnosis of various
types of anemia.
86.7 fl
Normal
Mean
Corpuscular
Hemoglobin
27-33 pg/cell
Weight of the
hemoglobin in
each red blood
cell.
July 11:
28.4 pg/cell
Normal
July 14:
27.9 pg/cell
Normal
July 16:
28.1 pg/cell
Normal
July 19:
28.0 pg/cell
Normal
Mean
Corpuscular
Proportion of
haemoglobin
July 11:
Hemoglobin
Concentration
32-36 g/dl
contained in each
RBC
31.0 g/dl
Low
July 14:
32.5 g/dl
Normal
July 16:
34.3 g/dl
Normal
July 19:
32.3 g/dl
Normal
Leukocyte
5.0-10.0 10^9/L
The white blood
cell differential
assesses the
ability of the body
July 11:
69 10^9L
HIGH
July 14:
Increased:
Neutrophil: acute infection,
eclampsia, gout, myelocytic
leukemia, rheumatoid arthritis, acute
stress, thyroiditis, trauma
to respond to and
eliminate
infection. It also
detects the
severity of allergic
reactions,
parasitic infection
and other
infection and
identifies various
stages of
leukemia. Also
monitored in
patients that are
immunocompromi
sed and with
heart transplants.
Neutrophils
respond to tissue
damage and
infection.
11.3 10^9L
HIGH
July 16:
5.5 10^9L
Normal
July 19:
9.1 10^9L
Normal
Lymphocytes: infectious
mononucleosis, TB, Viral
pneumonia, infectious hepatitis,
cholera, rubella, lymphocytic
leukemia, malignant lymphoma
Monocyte: chronic anti-
inflammatory disease, parasitic
infection, TB, and viral infection
Eosinophil: allergic disorders,
parasitic infection, and Hodgkin’s
disease
Basophils: hypersensitivity
reactions, ulcerative colitis, chronic
hemolytic anemia, Hodgkin’s
disease, myxedema, chronic
myelogenous leukemia,
polycythemic vera.
Decreased:
Neutrophils: aplastic anemia,
influenza, chemotherapy,
Neutrophils
.55-.65%
July 11:
0.03%
LOW
July 14:
0.03%
LOW
July 16:
Eosinophils
contain toxic
substances that
kill foreign cells in
the blood.
Basophils are
involved in
modifying or
calming systemic
allergic reactions.
Lymphocytes
consists of the B
cells and T cells
that are
responsible for
the activities of
the immune
system.
Monocytes
remove debris or
foreign particles
from the
0.05%
LOW
July 19:
0.02%
LOW
overwhelming bacterial infection,
and secondary to medications
including:
Analgesics and anti-
inflammatory
Antibiotics
Anticonvulsants
Antimetabolites
Antineoplastics
Antithyroid drugs
Arsenicals
Barbiturates
Cardiovascular drugs
Diuretics
Lymphocytes: idiopathic
lymphopenia, acute viral infections,
drugs such as corticosteroids,
irradiation therapy and cancer
chemotherapy), neoplastic
carcinoma, lymphoma.
Monocytes: hairy cell leukemia,
Lymphocytes
0.25-0.40%
July 11:
0.90%
HIGH
July 14:
0.90%
HIGH
July 16:
0.93%
HIGH
July 19:
circulation. 0.87%
HIGH
bone marrow failure, aplastic
anemia.
Eosinophil: allergies, pyogenic
infection,,shock, postsurgical
response.
Basophils: hyperthyroidism,
pregnancy, stress, Cushing’s
syndrome.
Monocytes
0.02-0.06%
July 11:
0.07%
HIGH
July 14:
0.07%
HIGH
July 16:
0.02%
Normal
July 19:
0.10%
HIGH
Eosinophil July 11:
0.01-0.05% 0.00%
LOW
July 14:
0.00%
LOW
July 16:
0.00%
LOW
July 19:
0.00%
LOW
Basophil
0.000-0.005 %
July 11:
0.00%
HIGH
July 14:
0.00%
HIGH
July 16:
0.00%
HIGH
July 19:
0.01%
HIGH
Hematocrit
M: 0.40-0.48
Hematocrit is a
measurement of
the percentage of
red cells in the
total volume
blood. It is used
to detect massive
prolonged blood
loss, anemia,
leukemia and
excessive rapid
July 11:
0.18
LOW
July 14:
0.23
LOW
July 16:
Increased: in dehydration and
increased production of RBC’s
Decreased: in anemia, when RBC
production is impaired or there is
increased destruction of RBC’s, in
chronic disease, blood loss, and fluid
volume excess
intravenous fluid
administration.
Low hemoglobin
and hematocrit
levels have
serious
consequences for
patients with
cardiovascular
disease, such as
more frequent
angina episodes
or acute
myocardial
infarction.
0.20
LOW
July 19:
0.29
LOW
Thrombocyte
150.0-300.0
10^9 /L
The adhesive or
sticky quality of
platelets allows
them to clump
together or
aggregate and
adhere to injured
July 11:
73 10^9/L
LOW
July 14:
Increased: acute infections,
rheumatoid arthritis, burns, cirrhosis,
iron deficiency, myeloprofilerative
diseases, and hemorrhage.
Decreased: aplastic anemia,
megaloblastic or severe iron
surfaces. They
release a
substance that
begins a
coagulation
process. It is used
to detect
thrombocytopenia
, a decrease
number in
platelets and
thrombocytosis,
an elevation in
the number of
platelets.
51 10^9/L
LOW
July 16:
47 10^9/L
LOW
July 19:
29 10^9/L
LOW
deficiency anemia, DIC, following
massive hemorrhage, and side
effect of : alcohol, non-steroidal anti-
inflammatories, ranitidine
BLOOD TYPING
Blood Typing A blood type (also
called a blood
group) is a
classification
of blood based on
July 11:
“O” Rh (+)
positive
Blood typing is an essential
diagnostic tool in determining blood
compatibility during blood
transfusions.
Explain to the patient that
the test requires blood
sample and he may
experience slight
discomfort from the
the presence or
absence of
inherited
antigenic substan
ces on the
surface of red
blood
cells (RBCs).
tourniquet and needle
puncture.
Tell to the patient that this
test determines the blood
group and until he may
also be used to determine
the donor’s blood type.
Instruct the patient that
there is no restriction of
foods or fluids.
Inform the patient that it
would take less than 5
minutes.
Apply direct pressure to
the venipuncture site until
the bleeding stops.
BONE MARROW ASPIRATION
Bone Marrow
Aspiration
(BMA)
Bone marrow aspiration
removes a small amount of
bone marrow fluid and cells
through a needle put into a
July 14:
Smears are
hypercellular showing
Healthy adult bone
marrow contains
yellow fat cells,
connective tissue,
After the procedure is
complete, the patient is
typically asked to lie flat
for 5–10 minutes to
bone. The bone marrow
fluid and cells are checked
for problems with any of the
blood cells made in the
bone marrow. Cells can be
checked for chromosome
problems. Cultures can also
be done to look for infection.
numerous blast cells
(>60% of all nuclear
cells.)
The blast show large
nuclei with irregular
outline with nucleoli
from 3-5 and scant to
moderate amount of
cytoplasm
There is good
maturation pattern
exhibited by the
erythroid cells
Very few of the
myeloid cells (>5)
show maturation.
The megakayocites
are rarely seen
Impression:
and red marrow that
produces blood. The
bone marrow of a
healthy infant is
primarily red due to
active production of
red cells necessary
for growth.
provide pressure over
the procedure site.
After that, assuming no
bleeding is observed;
the patient can get up
and go about their
normal activities.
Paracetamol (acetamin
ophen) or other simple
analgesics can be used
to ease soreness, which
is common for 2–3 days
after the procedure.
Any worsening pain,
redness, fever, bleeding
or swelling may suggest
a complication.
Patients are also
advised to avoid
washing the procedure
site for at least 24 hours
after the procedure is
Consistent with acute
myeloid leukemia, M1
completed.
URINALYSIS
Appearance and
color
Clear; yellow
July 12:
Clear; Yellow
July 14:
Clear; Yellow
Concentrated urine is darker in
color. Dilute urine may appear
almost clear or very pale yellow.
RBC in the urine (hematuria) may be
evident as pink, bright red or rusty
brown urine. White blood cells,
bacteria, pus, or contaminants may
cause cloudy urine.
Explain to the client that a
urine specimen is
required, give the reason,
and explain the method to
be used to collect it.
Perform hand hygiene and
observe other appropriate
infection control
procedures.
Provide for client privacy.
Ask the patient to wash
and dry the genitals and
perineal area with soap
and water.
Cleanse the perineal area
from front to back for
female patients; in a
circular motion, clean the
Reaction (pH)
4.6-8.0
July 12:
6.5
Normal
July 14:
7.0
Normal
Freshly voided urine is normally
acidic. Alkaline urine may indicate a
state of alkalosis, urinary tract
infection, or a diet high in fruits and
vegetables. More acidic urine is
found in starvation, diarrhea, or with
a diet high in protein foods.
Specific Gravity Measures the July 12: Low: indicates the urine is dilute
1.005-1.030
concentration of
particles in the
urine and is he
indicator of the
kidney’s ability to
concentrate urine.
It also reflects
overall hydration
status.
1.015
Normal
July 14:
1.015
Normal
High: means the urine is
concentrated (volume depletion)
urinary meatus and the
distal portion of the penis
for male.
Place the specimen
container in the midstream
of urine and collect the
specimen, taking care not
to touch the container to
the perineum or penis.
Label the specimen and
transport it to the
laboratory.
Document pertinent data.
Protein
2-8 mg/dl
Protein and
Glucose are large
molecules which
are normally
reabsorbed by the
kidneys to be
used for
metabolic
processes.
July 12:
Negative
July 14:
Negative
Protein content in urine is indicative
of decreased renal function.
Glucose
Negative
July 12:
Negative
July 14:
Negative
Glucose in the urine indicated high
blood glucose (>180mg/dl) and may
be indicative of undiagnosed or
uncontrolled diabetes mellitus
RBC
0-11
July 12:
6
July 14:
36
High
RBC indicates damage to the renal
tubules.
WBC
0-11
July 12:
6
July 14:
4
White blood cells in the urine are an
indication of urinary tract infection.
Bacteria
0-111
In healthy
individuals, the
urinary tract is
sterile; there will
be
no microorganism
s seen in the
urine sediment
unless if there is
July 12:
2
July 14:
8
Presence of bacteria are indicative
of urinary tract infection
bacterial
infection.
Epithelial cells
0-11
Normally in men
and women, a
few epithelial cells
from the bladder
(transitional
epithelial cells) or
from the external
urethra
(squamous
epithelial cells)
can be found in
the urine
sediment. Cells
from the kidney
(kidney cells) are
less common.
July 12:
4
July 14:
4
Presence of more epithelial cells
suggests infection, inflammation,
and malignancies.
SERUM ELECTROLYTES
Sodium (Na) Sodium is critical
to body water
July 12: Increased: excessive dietary or IV
intake, Cushing’s syndrome,
Explain to the client that a
136-145 mmol/L distribution,
maintenance of
osmotic pressure,
neuromuscular
function, acid-
base balance,
and electrolyte
imbalance
136 mmol/L
Normal
July 14:
136.7 mmol/L
Normal
excessive sweating
Decreased: diarrhea, vomiting,
nasogastric suction, diuretics, and
congestive heart failure.
blood specimen is
required, give the reason,
and explain the method to
be used to collect it.
Perform hand hygiene and
observe other appropriate
infection control
procedures.
Before puncturing, the
patient's skin should be
cleaned. Povidone-iodine
(Betadine) can be used, or
alcohol.
After performing a
fingerstick or heelstick, a
gauze pad or cotton ball
should be applied for
about a minute, making
certain the bleeding has
stopped.
Potassium (K+)
3.5-5.1 mmol/L
Very narrow
normal range;
small changes in
potassium level
can have
profound effects
on body
functions.
Effects of
potassium include
transmission of
nerve impulses;
contraction of
July 12:
3.37 mmol/L
Low
July 14:
3.3 mmol/L
Low
Increased: excessive IV
administration, acute or chronic
renal failure, potassium-sparing
diuretics, infection, dehydration,
transfusion of hemolyzed blood
Decreased: Secondary to vomiting,
diarrhea, diuretic use, insulin
administration, burns, ascites
skeletal, smooth,
and cardiac
muscle; and
maintenance of
acid-base
balance and
osmolarity.
Calcium (Ca)
2.12-2.52 mmol/L
50% of calcium in
blood is bound to
albumin and is
inactive; the other
50%, called free
or ionized
calcium, is
metabolically
active.
July 12:
2.04 mmol/L
Low
July 14:
2.17 mmol/L
Normal
Assess for disease of the
parathyroid gland or kidneys;
metastatic cancer(bones, lungs,
breast, kidneys)
Magnesium (Mg)
.74-.94 mmol/L
Electrolyte critical
to many
metabolic
processes
including nerve
July 14:
1.2 mmol/L
HIGH
Decreased: may cause cardiac
irritability, weakness, arrhythmias,
seizures, and delirium
impulse
transmission,
muscle relaxation,
carbohydrate
metabolism, and
electrolyte
balance
LIVER FUNCTION TESTS
Alanine
Aminotransferase
(ALT)
Normal values:
30 – 65 u/L
The alanine
aminotransferase
(ALT) blood test is
typically used to
detect liver injury.
July 12:
49 u/L
Normal
Increase:
Severe hepatitis
Infectious mononucleosis
Shock
Reye’s syndrome
Congestive heart failure
Decrease:
Liver can no longer make enzymes
Explain the procedure to
the patient.
Avoid strenuous exercise
just before having this test
done.
Collect 5 to 10 ml. of
venous blood in a red- top
tube.
The nurse ensures that
the patient receives food
and medications that were
withheld.
BLOOD SMEAR for MALARIA PARASITE
Blood smear for
malaria parasite
(BSMP)
Microscopic examination
of thick and thin
peripheral blood smears
stained with
Romanovsky dye.
Proper therapy depends
upon identification of the
specific variety of
malaria parasite.
Release of trophozoites
and RBC debris result in
a febrile response.
Periodicity of fever
correlates with type of
malaria. Parasites are
most likely to be
detected just before
onset of fever which is
July 24:
Negative
Malaria
Peripheral
Smear
(NMPS)
Assess malarial blood infestation
of Plasmodium species:
P. vivax
P. falciparum
P. ovale
P. malariae
Explain to the patient that
the test requires blood
sample and he may
experience slight
discomfort from the
tourniquet and needle
puncture.
Tell to the patient that this
test determines the blood
group and until he may
also be used to determine
the donor’s blood type.
Instruct the patient that
there is no restriction of
foods or fluids.
Inform the patient that it
would take less than 5
minutes.
predictable in many
cases. Multiple sampling
at different times in the
fever cycle may prove
successful results.
Apply direct pressure to
the venipuncture site until
the bleeding stops.
RADIOLOGIC FINDINGS
Chest X-ray Assess lung
fields, cardiac
border, large
arteries, clavicle,
ribs, diaphragm,
and mediastinum.
Diagnose
pulmonary or
cardiac disorders
including heart
failure, COPD,
pneumonia, TB,
and neoplastic
disease.
July 11:
Lung fields clear;
The heart is magnified;
Aortic knob is calcified;
Diaphragm and costrophrenic sulci are intact;
The rest of the included structures are unremarkable
Impression: Normal chest findings
July 26:
As compared to previous study dated 7-11-11,
present study shows inhomogenous opacification in
the left hemithorax. Confluent density in right
perihilar area is noted. The rest of the right lung is
Determine if the patient is
pregnant or maybe
pregnant; if so, the
procedure is
contraindicated
Tell the patient that he or
she will have to stay very
still while films are being
taken.
Remove metal objects and
jewelleries.
Tell the patient that he or
she will have to take a
deep breath and hold it for
2 or 3 seconds while
clear. Diaphragm and costrophrenic sulci are intact.
Impression: Consider bilateral consolidative
pneumonia, more in the left. Atelectasis of the left
upper lobe is not ruled out.
pictures are taken
Tell the patient not to
expect discomfort during
the test
STOOL CULTURE
DATE RESULT
June 13, 2011 No growth up to 12 degree days of incubation
June 14, 2011 No growth up to 36 degree of incubation
June 15, 2011 No growth up to 60 degree of incubation
June 16, 2011 No growth after 94 degree of incubation
BLOOD COMPATABILITY TEST
June 12, 2011
Donor blood bag
serial no.
Anti A Anti B Anti D A cells B cells Result
NVBSP
20110041552
N N + + + O+
BLOOD COMPATABILITY TEST
June 15, 2011
Donor blood bag
serial no.
Anti A Anti B Anti D A cells B cells Result
NVBSP
20110041552
N N + + + O+
BLOOD COMPATABILITY TEST
June 17, 2011
Donor blood bag
serial no.
Anti A Anti B Anti D A cells B cells Result
NVBSP
20110041552
N N + + + O+
POSSIBLE DIAGNOSTIC TESTS
A. Spinal Tap
Spinal Tap is an important test to tell whether the fluid bathing the brain
and spinal cord ("cerebral spinal fluid or CSF ") is invaded by leukemic cells. If
so, then aggressive treatment will be mandatory to clear this area of disease.
The spinal fluid, the brain linings it bathes ("meninges") and the testicles in males
are considered "sanctuary sites" meaning that leukemic cells can hide there to
escape regular treatment. Thus, it must be ascertained if these areas are
involved, with spinal tap and testicular biopsy, to see if they will need extra
therapy to eradicate disease there. Since these areas are often the first site of
relapse after treatment, continued monitoring of them after treatment is essential
to detect any relapse early.
All leukemia comes from blood cells, which normally function to provide
the body's cells with oxygen (red blood cells), protect them from invading germs
(white blood cells), and promote blood clotting after an injury (platelets). This
system usually functions beautifully, and it's proper workings are crucial to
human life. The division of these blood cells is normally under tight control. When
a cell starts dividing out of control, it becomes "cancerous."
B. Peripheral smear - A microscopic examination of a stained, peripheral blood smear
may be useful in evaluating blood disorders.
Normal Values of the Peripheral Smear
Size Normocytic (7-8 µm)
Color Normochromic
Shape Normocyte
Structure No nucleated cells
Anisocytosis
These are abnormal in size
Hypochromic
The normally pale center of the RBC is even paler, suggesting reduced
concentrations of hemoglobin within the cell.
Nucleated RBCs
In an adult, RBCs are not normally nucleated.
The presence of NRBCs indicates the body is aggressively producing red cells
and releasing them into the circulation prior to full maturity.
This is commonly seen in cases of significant anemia