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