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 bloods pH within its normal limits of 7.357.45, 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 Water

Functions

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 cells 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 RBCs is called hematocrit. Normal hematocrit is adult males (4050%) 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 bodys 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 Wilebrands factor, which is a protein produced and secreted by blood vessel endothelial cells. Von Wilebrands 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 bleeders 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 eosinophil erythrocyte megakaryocytes mast cells macrophage

basophils

Or, Pluripotent Stem Cell gives rise to: mature B lymphocyte

Lymphoid Stem Cell

progenitor B

precursor B

Plasma Cell

Memory B Cell or precursor Tc

progenitor T

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 nave) 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 nave ) 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 membranebound 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:
y y y y y y

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 bodys 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 WBCs 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 individuals body. The most important phagocytes are neutrophils and macrophages, although other WBCs 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 persons 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 selfantigens 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 cellmediated 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 individuals 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 individuals 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 diseasecausing microorganism can cause an individuals 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 infants 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 animals 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 Age Actual Justification All age groups are affected; 90% of cases occur in persons older than 60 years because developing mutations increases with age. Gender Congenital causes A slight male predominance is noted in all age groups of those with acute myelogenous leukemia. Certain congenital disorders such as Blooms syndrome, Down syndrome, and Fanconi anemia have unstable genes and are more at risk of developing mutations. Dysplastic abnormalities of hematopoietic stem cells has been associated with the loss of the long arm of chromosome 5 or the 5q syndrome.

Genetics

Precipitating Factor Chemical exposure

Actual

Cigarette smoking Cytotoxic chemotherapy

Radiation

Viral infections

Justification Exposure to some environmental chemicals, especially benzene and petroleum products, is associated with the development of AML. Exposure to chemicals in tobaccos smoke may increase the risk of developing AML. 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. Previous radiation therapy, or exposure to high levels of environmental irradiation, is associated with increased risk of AML. 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 Weakness Actual Justification A decrease in red blood cells impairs the distribution of oxygen and nutrients to tissues which are necessary for metabolic processes in the body. 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. Anemia causes decline in circulating red blood cells and hemoglobin resulting to pale extremities. Skin lesions are due to decreased neutrophils causing increase in the risk for infection and decreased platelets slows down clotting process. It is cause by the increased activity of the spleen due to extramedullary hematopoiesis and destruction of ineffective red blood cells and platelets. Decrease in platelet count could cause microvascular bleeding due to impaired clotting process. Decrease in platelet count could cause microvascular bleeding due to impaired clotting process.

Dyspnea

Pallor

Skin lesions

Splenomegaly

Petechiae

Bleeding

Fever Chest pain Pneumonia Low serum reticulocyte

Fever is an inflammatory response due to the increased risk for infection brought about by neutropenia. Decrease in oxygen levels in the heart muscle due to anemia. Decrease in neutrophil count predisposes the patient to bacterial infections. Impaired hematopoiesis causes decrease in formation of new RBCs Impaired hematopoiesis causes decrease in formation of blood components. The heart compensates for low oxygen levels by increasing its pumping ability to pump more blood to the system. Pain felt is due to the expansion of the bone marrow caused by increased proliferation of myeloid precursors. Leukemic infiltration of the central nervous system. Generalized lymphadenopathy, hepatomegaly, splenomegaly, due to leukemic cell infiltration. Due to abnormal proliferation and metabolism of leukemic cells.

Low blood components (RBCs, neutrophils, and platelets) Rapid heart rate

Bone pain and tenderness

Headache, nausea, vomiting, seizures, confusion, coma Abdominal discomfort

Hyperuricemia

C. Schematic Diagram
PREDISPOSING FACTORS Age, Gender, Genetics, Congenital PRECIPITATING FACTORS Drugs, Smoking, Chemical exposure, Cytotoxic chemotherapy, Radiation, Viral infections

Alteration in DNA Transformation of Proto-oncogenes to Oncogenes Mutation of tumor suppressor genes

Inactivation of tumor suppressor proteins Over expression of growth factor (IL-3, GM-CSF, M-CSF, G-CSF) Alteration in cellular transcription and translation pathways

Dysfunction in the cells error detection and correction mechanisms Uncontrolled cell cycle and cell division

Mutation in the multi-potent bone marrow stem cell forming neoplastic cells Myeloblast affectation Dysregulation in the formation of myeloid precursors

Disruption in myeloid differentiation and maturation Clonal expansion of the undifferentiated myeloid precursor in the bone marrow

Decreased in levels of apoptotic cell death of malignant cells

Dx: BMA: Presence of numerous blast cells

Accumulation of neoplastic cells in the bone marrow Destruction of normal functioning precursor cells in the bone marrow Bone marrow activity suppression Alteration in hematopoiesis Formation of dysfunctional blood components causing premature destruction and loss of functioning Bone marrow Expansion (CM) Bone pain and tenderness

Dx: RBC: 32.27 10^12cells/L Hgb: 92g/L

Anemia

Dx: leukocytes: 9.1 10^9/L Neutrophil: 0.02%

Neutropenia

Dx: Platelets: 29 10^9/L

Thrombocytopenia

Insufficient number of erythrocytes and insufficient hemoglobin count per cell

Diminished ability to destroy bacteria by phagocytosis

Less able to aggregate and are less adhesive

(CM) Weakness,
Treatment/ Management: 1. Blood transfusion 2. Dietary supplements 3. Diet 4. Erythropoietin 5. Bone marrow transplant Dyspnea, Pallor, Splenomegaly, Chest pain

(CM) Fever,
Treatment/ Management: 1. Antibiotics 2. Infection control 3. Hygiene Skin lesions, Pneumonia Treatment/ Management: 1. Platelet Transfusion 2. Prevent injury/trauma 3. Corticosteroids

(CM) Bleeding,
Petechiae, Skin lesions

If Treated with: y y y y y Chemotherapy* Radiation therapy Allopurinol therapy Administration of Tretinoin Bone marrow or stem cell transplant

If Not Treated: Metastasis

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

GOOD FAIR PROGNOSIS

Lymph nodes Lymphadenopathy

Spleen Splenomegaly

Liver Hepatomegaly

CNS Leukemic cells pass the bloodbrain barrier

Accumulation of leukemic blast in the circulation Increase in blood viscosity

(CM) Abdominal discomfort

(CM) headache, nausea,

vomiting, seizures

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 leukemic blast count in the CNS Cerebral leukostasis

Increased breakdown of purine nucleotides from DNA Release of uric acid Hyperuricemia Uric acid crystallization in the urine Renal complications

(CM) headache, lethargy,

confusion, coma CNS depression

(CM) shortness of breath,

dyspnea Respiratory failure

If Not Treated: Complications

Continuous decline in circulating RBC Decreased oxygen carrying capacity of the blood Decreased haemoglobin levels Hypoxemia Tissue hypoxia and cellular starvation Anaerobic metabolism Formation of lactic acid Metabolic acidosis

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

Systemic failure

DEATH

Narrative Pathophysiology 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 nonlymphocytic 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 cells 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 cells 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 COMPLETE BLOOD COUNT Hemoglobin The presence of a July 11: large amount of hemoglobin Male: 140-180 g/L enables erythrocyte perform the to its 55 g/dL Low July 14: 75 g/dL Low 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 y altitudes, polycythemia vera y 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. y Assess for excess bleeding and apply pressure if appropriate. Report changes July 19: to the physician. RATIONALE RESULT CLINICAL SIGNIFICANCE NURSING INTERVENTIONS BEFORE AND AFTER EXAMS

principal function, the transport of oxygen tissues. hemoglobin have between Low and

the lungs and the July 16: 68 g/dL Low

hematocrit levels serious consequences for

patients

with

92 g/dL Low

Determine if the test was correctly performed. Notify the laboratory if any undesirable changes occur after the test.

cardiovascular disease, such as more angina or myocardial infarction. anemia polycythemia. Erythrocytes Erythrocytes red blood Also and used in detecting frequent episodes acute

or July 11: cells 1.92 10^12/L LOW July 14: 2.69 10^12/L LOW July 16:

Increased: extracellular chronic vera

intravascular fluid hypoxia, volume

or loss,

function primarily M: 4.5-5.0 10^12 to ferry oxygen in cells/L blood to all cells. The red Cell or

iatrogenic

erythropoietin excess, polycythemia

erythrocyte count is a determination of the number of

red cells found in each millimeter whole blood. rubic of

2.44 10^12/L Low July 19: 32.27 10^12/L HIGH

Mean Corpuscular Volume 85-96 fl

Volume hemoglobin each RBC

of July 11: in 91.6 fl Normal July 14: 85.8 fl Normal July 16: 82 fl LOW MCV, MCH, MCHC values are

useful in the diagnosis of various types of anemia.

July 19: 86.7 fl Normal Mean Corpuscular Hemoglobin 27-33 pg/cell Weight each cell. of red the July 11: in blood 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

hemoglobin

Mean Corpuscular Hemoglobin Concentration 32-36 g/dl

Proportion haemoglobin

of July 11: 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

contained in each RBC

Leukocyte The white blood 5.0-10.0 10^9/L cell differential

July 11: 69 10^9L HIGH

Increased: Neutrophil: eclampsia, acute gout, infection, myelocytic

assesses

the July 14: 11.3 10^9L HIGH the July 16: 5.5 10^9L Normal

leukemia, rheumatoid arthritis, acute stress, thyroiditis, trauma Lymphocytes: mononucleosis, pneumonia, cholera, rubella, TB, infectious infectious Viral hepatitis, lymphocytic

ability of the body to respond to and eliminate infection. It also detects reactions, parasitic infection and infection stages Neutrophils .55-.65% leukemia. monitored and of Also in severity of allergic

leukemia, malignant lymphoma Monocyte: inflammatory chronic disease, antiparasitic

other July 19: 9.1 10^9L Normal July 11: 0.03% LOW July 14: 0.03% LOW

infection, TB, and viral infection Eosinophil: disease Basophils: hemolytic disease, myelogenous polycythemic vera. hypersensitivity anemia, myxedema, Hodgkins chronic leukemia, allergic disorders,

identifies various

parasitic infection, and Hodgkins

patients that are immunocompromi sed and with heart transplants. Neutrophils respond to tissue

reactions, ulcerative colitis, chronic

damage infection. Eosinophils contain substances the blood. Basophils Lymphocytes involved modifying 0.25-0.40%

and July 16: 0.05% toxic LOW

Decreased: Neutrophils: influenza, overwhelming and including: y Analgesics inflammatory y y y Antibiotics Anticonvulsants Antimetabolites Antineoplastics Antithyroid drugs Arsenicals Barbiturates Cardiovascular drugs Diuretics idiopathic as corticosteroids, and antisecondary to aplastic bacterial anemia, infection,

chemotherapy, medications

that July 19: 0.02% LOW

kill foreign cells in

are or

in July 11: 0.90% HIGH July 14: 0.90% HIGH

calming systemic allergic reactions. Lymphocytes consists of the B cells and T cells that responsible the the system. Monocytes activities are for

y y y y y y

of July 16: 0.93% HIGH

immune

Lymphocytes: drugs such

lymphopenia, acute viral infections,

remove debris or July 19: foreign from circulation. Monocytes particles the 0.87% HIGH July 11: 0.07% 0.02-0.06% HIGH July 14: 0.07% HIGH July 16: 0.02% Normal July 19: 0.10% HIGH

irradiation

therapy

and

cancer

chemotherapy), carcinoma, lymphoma.

neoplastic

Monocytes: hairy cell leukemia, bone anemia. Eosinophil: response. Basophils: pregnancy, syndrome. hyperthyroidism, stress, Cushings allergies, pyogenic postsurgical marrow failure, aplastic

infection,,shock,

Eosinophil 0.01-0.05%

July 11: 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 Hematocrit is measurement M: 0.40-0.48 a July 11: of 0.18 LOW July 14: 0.23 LOW Decreased: in anemia, when RBC production is impaired or there is increased destruction of RBCs, in chronic disease, blood loss, and fluid Increased: in dehydration and

increased production of RBCs

the percentage of red cells in the total volume blood. It is used to detect massive prolonged loss, blood anemia,

leukemia excessive intravenous Low and levels serious

and July 16: rapid fluid 0.20 LOW July 19: 0.29 LOW

volume excess

administration. hemoglobin hematocrit have

consequences for patients with cardiovascular disease, such as more angina or myocardial infarction. Thrombocyte frequent episodes acute

The adhesive or July 11: sticky quality of platelets allows clump or 73 10^9/L LOW

Increased: iron

acute

infections,

rheumatoid arthritis, burns, cirrhosis, deficiency, myeloprofilerative diseases, and hemorrhage.

150.0-300.0 10^9 them

to

together

/L

aggregate surfaces. release substance begins coagulation

and July 14: They a that a 51 10^9/L LOW July 16: 47 10^9/L detect LOW July 19: 29 10^9/L LOW

Decreased: megaloblastic massive

aplastic or

anemia, iron side

adhere to injured

severe and

deficiency anemia, DIC, following hemorrhage, effect of : alcohol, non-steroidal antiinflammatories, ranitidine

process. It is used to , a thrombocytopenia decrease in and in of number platelets an the elevation number thrombocytosis,

platelets. BLOOD TYPING Blood Typing A blood type (also July 11: called group) a blood is a O Rh (+) Blood typing is an essential blood y Explain to the patient that the test requires blood sample and he may

diagnostic tool in determining blood compatibility during

classification of blood based on the presence or absence inherited antigenic substan ces surface blood cells (RBCs). on the of red of

positive

transfusions.

experience slight discomfort from the tourniquet and needle puncture. y Tell to the patient that this test determines the blood group and until he may also be used to determine the donors blood type. y Instruct the patient that there is no restriction of foods or fluids. y Inform the patient that it would take less than 5 minutes. y Apply direct pressure to the venipuncture site until the bleeding stops.

BONE MARROW ASPIRATION Bone Marrow Bone marrow aspiration July 14: Healthy adult bone y After the procedure is

Aspiration (BMA)

removes a small amount of Smears

are marrow fat

contains cells, tissue,

complete, the patient is typically asked to lie flat for 510 minutes to provide pressure over the procedure site. y After that, assuming no bleeding is observed; the patient can get up and go about their normal activities. y Paracetamol (acetamin ophen) or other simple analgesics can be used to ease soreness, which is common for 23 days after the procedure. Any worsening pain, redness, fever, bleeding or swelling may suggest a complication. Patients are also advised to avoid

bone marrow fluid and cells hypercellular showing yellow

through a needle put into a numerous blast cells connective fluid and cells are checked cells.) 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. The blast show large nuclei outline with with irregular nucleoli

bone. The bone marrow (>60% of all nuclear 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.

from 3-5 and scant to moderate amount of cytoplasm There maturation exhibited by erythroid cells Very myeloid few of the (>5) is good pattern the

cells

show maturation. The megakayocites y

are rarely seen

Impression: Consistent with acute myeloid leukemia, M1 URINALYSIS Appearance color Clear; yellow and July 12: Clear; Yellow July 14: Clear; Yellow Concentrated urine is darker in color. Dilute urine may appear y 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. Reaction (pH) 4.6-8.0 July 12: 6.5 Normal July 14: 7.0 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. y y y y

washing the procedure site for at least 24 hours after the procedure is completed.

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 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 control

Normal Specific Gravity 1.005-1.030 Measures concentration particles indicator in of the July 12: of the the 1.015 Normal July 14: 1.015 Normal Low: indicates the urine is dilute High: means the urine is

from front to back for female patients; in a circular motion, clean the urinary meatus and the distal portion of the penis for male. y 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. Protein content in urine is indicative of decreased renal function. Label the specimen and transport laboratory. y Document pertinent data. it to the

urine and is he kidneys ability to concentrate urine. It also reflects hydration overall status. Protein 2-8 mg/dl Protein molecules are kidneys Glucose Negative used metabolic processes.

concentrated (volume depletion)

and July 12: which Negative

Glucose are large

normally July 14: to be Negative Glucose in the urine indicated high blood glucose (>180mg/dl) and may be indicative of undiagnosed or uncontrolled diabetes mellitus

reabsorbed by the

for July 12: Negative July 14:

Negative RBC 0-11 July 12: 6 July 14: 36 High WBC 0-11 July 12: 6 July 14: 4 Bacteria 0-111 In urinary be no microorganism s seen in the healthy July 12: the is tract 2 Presence of bacteria are indicative of urinary tract infection White blood cells in the urine are an indication of urinary tract infection. RBC indicates damage to the renal tubules.

individuals,

sterile; there will July 14: 8

urine bacterial infection. Epithelial cells 0-11

sediment

unless if there is

Normally in men July 12: and women, a few epithelial cells (transitional epithelial cells) or from the external urethra (squamous epithelial the sediment. cells) urine Cells can be found in 4

Presence of more epithelial cells suggests infection, inflammation, and malignancies.

from the bladder July 14: 4

from the kidney (kidney cells) are less common. SERUM ELECTROLYTES

Sodium (Na) 136-145 mmol/L

Sodium is critical July 12: to body water of distribution, maintenance neuromuscular function, base and balance, electrolyte osmotic pressure, 136 mmol/L Normal July 14:

Increased: excessive dietary or IV intake, Cushings syndrome, excessive sweating Decreased: diarrhea, vomiting,

Explain to the client that a 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 procedures. Before control puncturing, the

nasogastric suction, diuretics, and congestive heart failure. y

acid- 136.7 mmol/L Normal

imbalance Potassium (K+) 3.5-5.1 mmol/L Very normal potassium can profound on functions. Effects transmission of of narrow July 12: range; level effects body 3.37 mmol/L Low Increased: administration, renal failure, diuretics, excessive acute or IV chronic

patient's skin should be cleaned. Povidone-iodine (Betadine) can be used, or alcohol. y 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.

small changes in

potassium-sparing dehydration,

infection,

have July 14: 3.3 mmol/L Low

transfusion of hemolyzed blood Decreased: Secondary to vomiting, diarrhea, diuretic use, insulin administration, burns, ascites

potassium include

nerve

impulses; of

contraction and muscle; maintenance acid-base balance osmolarity. Calcium (Ca) 2.12-2.52 mmol/L

skeletal, smooth, cardiac and of and

50% of calcium in July 12: blood is bound to albumin and is inactive; the other or calcium, metabolically active. ionized is 2.04 mmol/L Low

Assess for disease of the parathyroid gland or kidneys; metastatic cancer(bones, lungs, breast, kidneys)

50%, called free July 14: 2.17 mmol/L Normal

Magnesium (Mg) .74-.94 mmol/L

Electrolyte critical July 14: to metabolic many 1.2 mmol/L

Decreased:

may

cause

cardiac

irritability, weakness, arrhythmias, seizures, and delirium

processes including impulse transmission, muscle relaxation, carbohydrate metabolism, electrolyte balance and nerve

HIGH

LIVER FUNCTION TESTS Alanine Aminotransferase (ALT) Normal values: 30 65 u/L The alanine July 12: 49 u/L Normal Increase:  Severe hepatitis  Infectious mononucleosis  Shock  Reyes syndrome  Congestive heart failure y y Collect 5 to 10 ml. of venous blood in a red- top tube. The nurse ensures that y y Explain the procedure to the patient. Avoid strenuous exercise just before having this test done.

aminotransferase (ALT) blood test is typically used to detect liver injury.

Decrease:

 Liver can no longer make enzymes

the patient receives food and medications that were withheld.

BLOOD SMEAR for MALARIA PARASITE Blood smear for Microscopic examination July 24: malaria parasite of (BSMP) thick and thin with dye. peripheral blood smears stained Romanovsky Negative Malaria Peripheral Smear (NMPS) y y y y Assess malarial blood infestation of Plasmodium species: P. vivax P. falciparum P. ovale P. malariae y y 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 donors blood type. y Instruct the patient that there is no restriction of foods or fluids.

Proper therapy depends upon identification of the specific malaria variety of parasite.

Release of trophozoites and RBC debris result in a febrile response. of fever are be Periodicity malaria. most

correlates with type of Parasites likely to

detected predictable

just in

before many

Inform the patient that it would take less than 5 minutes. Apply direct pressure to the venipuncture site until the bleeding stops.

onset of fever which is cases. Multiple sampling at different times in the fever cycle may prove successful results. RADIOLOGIC FINDINGS Chest X-ray Assess fields, border, ribs, lung July 11: cardiac large Lung fields clear; y

Determine if the patient is pregnant pregnant; procedure contraindicated or if maybe so, the is

arteries, clavicle, The heart is magnified; diaphragm, Aortic knob is calcified; Diaphragm and costrophrenic sulci are intact; The rest of the included structures are unremarkable y and mediastinum. Diagnose pulmonary

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

or Impression: Normal chest findings cardiac disorders including heart July 26: failure, and COPD, As compared to previous study dated 7-11-11, pneumonia, TB, present study shows inhomogenous opacification in neoplastic

disease.

the left hemithorax. Confluent density in right perihilar area is noted. The rest of the right lung is clear. Diaphragm and costrophrenic sulci are intact. Impression: Consider bilateral consolidative y

deep breath and hold it for 2 or 3 seconds while pictures are taken Tell the patient not to expect discomfort during the test

pneumonia, more in the left. Atelectasis of the left upper lobe is not ruled out.

STOOL CULTURE

DATE June 13, 2011 June 14, 2011 June 15, 2011 June 16, 2011

RESULT No growth up to 12 degree days of incubation No growth up to 36 degree of incubation No growth up to 60 degree of incubation No growth after 94 degree of incubation

BLOOD COMPATABILITY TEST June 12, 2011 Donor blood bag serial no. NVBSP 20110041552 BLOOD COMPATABILITY TEST June 15, 2011 Donor blood bag serial no. NVBSP 20110041552 BLOOD COMPATABILITY TEST June 17, 2011 Donor blood bag serial no. NVBSP 20110041552 N N + + + O+ Anti A Anti B Anti D A cells B cells Result N N + + + O+ Anti A Anti B Anti D A cells B cells Result N N + + + O+ Anti A Anti B Anti D A cells B cells Result

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 Color Shape Normocytic (7-8 m) Normochromic Normocyte

Structure

No nucleated cells

Anisocytosis
y

These are abnormal in size

Hypochromic
y

The normally pale center of the RBC is even paler, suggesting reduced concentrations of hemoglobin within the cell.

Nucleated RBCs
y y

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