Chapter III DISCUSSION OF THE DISEASE

A. Definition and Description of the Disease

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. This type of cancer
usually gets worse quickly if it is not treated. It is the most common type of acute leukemia in
adults. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute
granulocytic leukemia, and acute nonlymphocytic leukemia.

Leukemia may affect red blood cells, white blood cells, and platelets.

Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood
cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. A
lymphoid stem cell becomes a white blood cell.

A myeloid stem cell becomes one of three types of mature blood cells:

Red blood cells that carry oxygen and other substances to all tissues of the body.

White blood cells that fight infection and disease.

Platelets that form blood clots to stop bleeding.

In AML, the myeloid stem cells usually become a type of immature white blood cell called
myeloblasts (or myeloid blasts). The myeloblasts in AML are abnormal and do not become
healthy white blood cells. Sometimes in AML, too many stem cells become abnormal red blood
cells or platelets. These abnormal white blood cells, red blood cells, or platelets are also called
leukemia cells or blasts. Leukemia cells can build up in the bone marrow and blood so there is
less room for healthy white blood cells, red blood cells, and platelets. When this happens,
infection, anemia, or easy bleeding may occur. The leukemia cells can spread outside the blood
to other parts of the body, including the central nervous system (brain and spinal cord), skin, and
gums.

There are different subtypes of AML.

Most AML subtypes are based on how mature (developed) the cancer cells are at the time of
diagnosis and how different they are from normal cells.

Acute promyelocytic leukemia (APL) is a subtype of AML that occurs when parts of two genes
stick together. APL usually occurs in middle-aged adults. Signs of APL may include both
bleeding and forming blood clots.

Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk
of AML.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor
does not mean that you will get cancer; not having risk factors doesnt mean that you will not get
cancer. Talk with your doctor if you think you may be at risk. Possible risk factors for AML
include the following:

-Being male.
-Smoking, especially after age 60.
-Having had treatment with chemotherapy or radiation therapy in the past.
-Having had treatment for childhood acute lymphoblastic leukemia (ALL) in the past.
-Being exposed to radiation from an atomic bomb or to the chemical benzene.
-Having a history of a blood disorder such as myelodysplastic syndrome.

Signs and symptoms of adult AML include fever, feeling tired, and easy bruising or
bleeding.

The early signs and symptoms of AML may be like those caused by the flu or other common
diseases. Check with your doctor if you have any of the following:

-Fever.
-Shortness of breath.
-Easy bruising or bleeding.
-Petechiae (flat, pinpoint spots under the skin caused by bleeding).
-Weakness or feeling tired.
-Weight loss or loss of appetite.

B. Anatomy and Physiology/ Pathophysiology

Bone Marrow

Bone marrow is the soft, spongy, gelatinous tissue

found in the hollow spaces in the interior of bones. The
average weight of this tissue is about 4% of the total
body weight, or 2.6 kg in an adult weighing 65 kg.
Progenitor cell (stem cell) lines in the bone marrow
produce new blood cells and stromal cells. Bone
marrow is also an important part of the lymphatic
system.

Function of Bone Marrow

Mesenchymal stem cells

The bone marrow stroma contains mesenchymal stem cells (MSCs), also known as marrow
stromal cells. These are multipotent stem cells that can differentiate into a variety of cell types.
MSCs have been shown to differentiate, in vitro or in vivo, into osteoblasts, chondrocytes,
myocytes, adipocytes and beta-pancreatic islets cells.

Bone marrow barrier

The blood vessels of the bone marrow constitute a barrier, inhibiting immature blood cells from
leaving the marrow. Only mature blood cells contain the membrane proteins, such as aquaporin
and glycophorin, that are required to attach to and pass the blood vessel endothelium.
Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be harvested
from blood.

Lymphatic role

The red bone marrow is a key element of the lymphatic system, being one of the primary
lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells. The
bone marrow and thymus constitute the primary lymphoid tissues involved in the production and
early selection of lymphocytes. Furthermore, bone marrow performs a valve-like function to
prevent the backflow of lymphatic fluid in the lymphatic system.

Compartmentalization

Biological compartmentalization is evident within the bone marrow, in that certain cell types
tend to aggregate in specific areas. For instance, erythrocytes, macrophages, and their precursors
tend to gather around blood vessels, while granulocytes gather at the borders of the bone marrow.

Types of Bone Marrow

Bone marrow can be 1 of 2 types, red or yellow, depending on whether it consists of mainly
hematopoietic (and therefore, red-colored) tissue or fatty (and therefore a yellow-colored) tissue.
Both types of bone marrow are highly vascular, being enriched with numerous blood vessels and
capillaries.

Bone marrow first appears in the clavicle near the end of fetal life and becomes active about 3
weeks later. Bone marrow supersedes the liver as the major hematopoietic organ at 32-36 weeks'
gestation. At birth, all bone marrow is red. With age, more and more of it is converted to the
yellow type. In an adult, roughly half of the bone marrow is still red.

Red marrow is found mainly in the flat bones, such as the hip bone, sternum (breast) bone,
skull, ribs, vertebrae, and shoulder blades, as well as in the metaphyseal and epiphyseal ends of
the long bones, such as the femur, tibia, and humerus, where the bone is cancellous or spongy.

Yellow marrow is found in the hollow interior of the diaphyseal portion or the shaft of long
bones. By the time a person reaches old age, nearly all of the red marrow is replaced by yellow
marrow. However, the yellow marrow can revert to red if there is increased demand for red blood
cells, such as in instances of blood loss.

Blood Cell Formation

All types of blood cells are derived from 1 common stem cell. Stem cells
exist throughout the life of an individual. The common stem cell
produces 2 other stem cells, the myeloid stem cell and the
lymphoid stem cell. These stem cells divide to
eventually give rise to red blood cells, platelets,
and most white blood cells in the red marrow.
(See the image below.) Bone marrow thus contains
blood cells at varying stages of development.

Erythrocytes, granulocytes, monocytes, thrombocytes,

and lymphocytes are all formed in the bone marrow. T lymphocytes
originate via lymphoid stem cells that migrate to the thymus and differentiate under the influence
of the thymic hormones thymopoietin and thymosin.

The rate of blood cell production is controlled by the body's needs. Normal blood cells last for a
limited time. White blood cells last anywhere from a few hours to a few days, platelets for about
10 days, and red blood cells for about 120 days. These cells must be replaced constantly. Certain
conditions may trigger additional production of blood cells.

When the oxygen content of body tissues is low, if there is loss of blood or anemia, or if the
number of red blood cells decreases, the kidneys produce and release erythropoietin, a hormone
that stimulates the bone marrow to produce more red blood cells. Similarly, the bone marrow
produces and releases more white blood cells in response to infections, and it produces and
releases more platelets in response to bleeding. If a person experiences serious blood loss, yellow
bone marrow can be activated and transformed into red bone marrow. As age progresses, more of
the red bone marrow turns into yellow bone marrow and the production of new blood cells
becomes more difficult.

The Blood

Blood is a constantly circulating fluid providing the body with nutrition, oxygen, and waste
removal. Blood is mostly liquid, with numerous cells and proteins suspended in it, making blood
"thicker" than pure water. The average person has about 5 liters (more than a gallon) of blood.

A liquid called plasma makes up about half of the content of blood. Plasma contains proteins that
help blood to clot, transport substances through the blood, and perform other functions. Blood
plasma also contains glucose and other dissolved nutrients.

About half of blood volume is composed of blood cells:

Red blood cells, which carry oxygen to the tissues

White blood cells, which fight infections
Platelets, smaller cells that help blood to clot

Blood is conducted through blood vessels (arteries and veins). Blood is prevented from clotting
in the blood vessels by their smoothness, and the finely tuned balance of clotting factors.

FUNCTIONS OF BLOOD

Blood is pumped by the heart through blood vessels, which extend throughoutthe 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 inthe 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 bloods 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. Maintenance of body temperature.

Blood is involved with body temperature regulation because 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.

Lymphoid cell line

Lymphoid stem cells develop into lymphoblasts which develop into lymphocytes. Lymphocytes
are a type of white blood cell. They are also called leukocytes. Lymphocytes help fight infection
and destroy abnormal cells.

Myeloid cell line

Myeloid stem cells develop into red blood cells, platelets and some types of white blood cells.
Red blood cells carry oxygen to all tissues of the body. Platelets form clots in damaged blood
vessels to stop bleeding.

Myeloid stem cells develop into 2 different types of white blood cells, called granulocytes and
monocytes. These white blood cells destroy bacteria and other foreign invaders and help to fight
infection.

Lymphatic system
The lymphatic system is a system of thin tubes and lymph nodes that run throughout the body.
These tubes are called lymph vessels or lymphatic vessels. The lymph system is an important part
of our immune system. It plays a role in fighting bacteria and other infections and destroying old or
abnormal cells, such as cancer cells.
The lymphatic system is similar to the blood circulation. The lymph vessels branch through all parts
of the body like the arteries and veins that carry blood. But the lymphatic system tubes are much
finer and carry a colourless liquid called lymph. Lymph contains a high number of a type of white
blood cells called lymphocytes that fight infection and destroy damaged or abnormal cells.

As the blood circulates around the body, fluid leaks out from the blood vessels into the body tissues.
This fluid carries food to the cells and bathes the body tissues to form tissue fluid. The fluid then
collects waste products, bacteria, and damaged cells. It also collects any cancer cells if these are
present. This fluid then drains into the lymph vessels.

The lymph then flows through the lymph vessels into the lymph glands, which filter out any bacteria
and damaged cells.

From the lymph glands, the lymph moves into larger lymphatic vessels that join up. These eventually
reach a very large lymph vessel at the base of the neck called the thoracic duct. The thoracic duct
then empties the lymph back into the blood circulation.
Lymph nodes (lymph glands)
The lymph glands are small bean shaped structures, also called lymph nodes.

There are lymph nodes in many parts of the body including

Under your arms, in your armpits

In each groin (at the top of your legs)

In your neck

You may be able to feel some of them.

There are also lymph nodes that you cannot feel in

Your tummy (abdomen)

Your pelvis

Your chest

The lymph nodes filter the lymph fluid as it passes through them. White blood cells attack any
bacteria or viruses they find in the lymph. If cancer cells break away from a tumour, they
may become stuck in one or more of the nearest lymph nodes. So doctors check the lymph nodes
first when they are working out how far a cancer has grown or spread.

Other lymphatic system organs

The lymphatic system includes other body organs. These include the spleen, the thymus, the tonsils
and the adenoids.

The spleen

The spleen is under your ribs on the left side of your body. It has two main different types of tissue,
red pulp and white pulp.

The red pulp filters worn out and damaged red blood cells from the blood and recycles them.

The white pulp contains many B lymphocytes and T lymphocytes. These are white blood cells that
are very important for fighting infection. As blood passes through the spleen, these blood cells pick
up on any sign of infection or illness and begin to fight it.

The thymus

The thymus is a small gland under your breast bone. It helps to produce white blood cells to fight
infection. It is usually most active in teenagers and shrinks in adulthood.

The tonsils and adenoids

The tonsils are two glands in the back of your throat.

The adenoids are glands at the back of your nose, where it meets the back of your throat. The
adenoids are also called the nasopharyngeal tonsils.

The tonsils and adenoids help to protect the entrance to the digestive system and the lungs from
bacteria and viruses.

C. Drug Study

D. Medical/ Surgical Management