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# TITLE
t = doc.add_heading("White Blood Cells (Leukocytes) - Study Notes", level=0)
sub = doc.add_paragraph()
sub.add_run("Based strictly on the provided slide (Guyton & Hall, Textbook of Medical Physiology, Chapter 34, pp. 449-458)").italic = True

# 1. INTRODUCTION
h1("1. Introduction - Body's Defense System")
bullet("The body is continually exposed to bacteria, viruses, fungi, and parasites through the skin, mouth, respiratory passages, intestinal tract, eyes, and urinary tract.")
bullet("The body has a special defense system made of blood leukocytes (WBCs) and tissue cells derived from leukocytes.")
note("These cells work together in two ways to prevent disease:")
bullet("By actually destroying invading bacteria or viruses through phagocytosis.")
bullet("By forming antibodies and sensitized lymphocytes that destroy or inactivate the invader (immune system - covered separately).")

# 2. GENERAL CHARACTERISTICS OF LEUKOCYTES
h1("2. General Characteristics of Leukocytes")
note("Leukocytes (white blood cells) are the mobile units of the body's protective system.")
bullet("Formed partially in the bone marrow: granulocytes and monocytes (and a few lymphocytes).")
bullet("Formed partially in lymph tissue: lymphocytes and plasma cells.")
bullet("After formation, WBCs are transported in blood to the parts of the body where they are needed.")
bullet("Their real value lies in being transported specifically to areas of serious infection/inflammation, providing a rapid, potent defense. Granulocytes and monocytes can \"seek out and destroy\" a foreign invader.")

h2("Types of White Blood Cells (6 types normally present)")
bullet("Neutrophils (polymorphonuclear)")
bullet("Eosinophils (polymorphonuclear)")
bullet("Basophils (polymorphonuclear)")
bullet("Monocytes")
bullet("Lymphocytes")
bullet("Plasma cells (occasionally)")
note("The first three (neutrophils, eosinophils, basophils) have a granular appearance and are called granulocytes.")
note("Platelets are fragments of another bone marrow cell, the megakaryocyte, also present in blood.")
bullet("Granulocytes and monocytes protect the body by ingesting invading organisms (phagocytosis) or releasing antimicrobial/inflammatory substances.")
bullet("Lymphocytes and plasma cells function mainly with the immune system (antibodies and sensitized lymphocytes).")
bullet("Platelets specifically activate the blood-clotting mechanism.")

h2("Normal Blood Concentrations")
bullet("Total WBCs: about 7000 per microliter of blood (compared with 5 million RBCs per microliter).")
note("Normal percentage distribution of WBC types:")
bullet("Neutrophils - 62.0%")
bullet("Eosinophils - 2.3%")
bullet("Basophils - 0.4%")
bullet("Monocytes - 5.3%")
bullet("Lymphocytes - 30.0%")
bullet("Platelets: 150,000-450,000 per microliter, averaging about 300,000.")

img("image6.png", "Chapter 34 title page - Leukocytes, Granulocytes, the Monocyte-Macrophage System, and Inflammation (Guyton & Hall)")
source_note("449")

# 3. GENESIS OF WHITE BLOOD CELLS
h1("3. Genesis of White Blood Cells")
note("Two major lineages of WBCs are formed from the multipotential hematopoietic stem cell:")
bullet("Myelocytic lineage - begins with the myeloblast; gives rise to granulocytes and monocytes.")
bullet("Lymphocytic lineage - begins with the lymphoblast; gives rise to lymphocytes and plasma cells.")
note("Genesis of Myelocytes (numbered cells in Figure 34-1): 1, myeloblast; 2, promyelocyte; 3, megakaryocyte; 4, neutrophil myelocyte; 5, young neutrophil metamyelocyte; 6, band neutrophil metamyelocyte; 7, neutrophil; 8, eosinophil myelocyte; 9, eosinophil metamyelocyte; 10, eosinophil; 11, basophil myelocyte; 12, basophil; 13-16, stages of monocyte formation.")
bullet("Granulocytes and monocytes are formed only in the bone marrow.")
bullet("Lymphocytes and plasma cells are produced mainly in lymphogenous tissues - lymph glands, spleen, thymus, tonsils, and pockets of lymphoid tissue in the gut wall (e.g., Peyer's patches).")
bullet("WBCs formed in the bone marrow are stored there until needed, then released into the blood as required (release governed by specific factors).")
bullet("Normally, about three times as many WBCs are stored in the marrow as circulate in the entire blood - representing about a 6-day supply.")
bullet("Lymphocytes are mostly stored in lymphoid tissues, except for a small number temporarily in the blood.")
bullet("Megakaryocytes (cell 3) are also formed in the bone marrow; they fragment into platelets (thrombocytes) which pass into the blood - important in initiating blood clotting.")

img("image1.png", "Figure 34-1: Genesis of Myelocytes and Genesis of Lymphocytes; Figure 34-2: Movement of neutrophils by diapedesis and chemotaxis toward inflamed tissue")
source_note("450-451")

# 4. LIFE SPAN OF WHITE BLOOD CELLS
h1("4. Life Span of White Blood Cells")
bullet("Granulocytes: normally circulate in blood for 4 to 8 hours, then remain in tissues for another 4 to 5 days. In serious tissue infection, this life span is often shortened to only a few hours because granulocytes proceed rapidly to the infected area, perform their function, and are themselves destroyed.")
bullet("Monocytes: have a short transit time (10-20 hours) in blood before wandering through capillary membranes into tissues. There they swell to become tissue macrophages and can live for months, continually defending against infection (tissue macrophage system).")
bullet("Lymphocytes: enter the circulatory system continually along with lymph drainage, circulate for a few hours, then pass back into tissue, re-enter the lymph, and return to blood again - continual recirculation through the body. Life span of weeks to months.")
bullet("Platelets: replaced about once every 10 days; about 30,000 platelets formed each day per microliter of blood.")

# 5. NEUTROPHILS AND MACROPHAGES DEFEND AGAINST INFECTIONS
h1("5. Neutrophils and Macrophages Defend Against Infections")
note("It is mainly neutrophils and tissue macrophages that attack and destroy invading bacteria, viruses, and other harmful agents.")
bullet("Neutrophils are mature cells that can attack and destroy bacteria even in circulating blood.")
bullet("Tissue macrophages begin life as blood monocytes, which are immature with little phagocytic ability while in the blood; once in tissues, they swell (sometimes to 60-80 micrometers) and become full macrophages, extremely capable of combating disease.")

h2("White Blood Cells Enter Tissue Spaces by Diapedesis")
bullet("Neutrophils and monocytes squeeze through gaps between endothelial cells of blood capillaries and postcapillary venules by diapedesis, even though the gaps are much smaller than the cell - a small portion of the cell slides through at a time.")

h2("White Blood Cells Move by Ameboid Motion")
bullet("Both neutrophils and macrophages move through tissues by ameboid motion, at velocities as great as 40 micrometers/min - moving a distance as great as their own length each minute.")

h2("Chemotaxis")
bullet("Many chemical substances in tissues cause both neutrophils and macrophages to move toward the source of the chemical - a phenomenon called chemotaxis (Figure 34-2).")
note("Substances that can cause chemotaxis include:")
bullet("Bacterial or viral toxins")
bullet("Degenerative products of inflamed tissue")
bullet("Reaction products of the complement complex")
bullet("Reaction products caused by plasma clotting in the inflamed area")
bullet("Chemotaxis depends on the concentration gradient of the chemotactic substance - concentration is highest near the source, directing unidirectional WBC movement.")
bullet("Chemotaxis is effective up to about 100 micrometers away from an inflamed tissue; since almost no tissue area is more than 50 micrometers from a capillary, the signal can easily mobilize WBCs from capillaries into inflamed tissue.")

# 6. PHAGOCYTOSIS
h1("6. Phagocytosis")
note("A major function of neutrophils and macrophages is phagocytosis - cellular ingestion of the offending agent.")
bullet("Phagocytes must be selective, or normal cells and structures would be ingested too. Whether phagocytosis occurs depends on three selective procedures (Figure 34-3):")
bullet("Smooth surfaces resist phagocytosis; rough surfaces increase the likelihood of phagocytosis.")
bullet("Most natural body substances have protective coats that repel phagocytosis; dead/degenerated tissues and foreign particles usually lack these protective coats.")
bullet("The immune system develops antibodies against infectious agents such as bacteria. Antibodies adhere to bacterial membranes, making bacteria susceptible to phagocytosis. Antibodies also combine with C3 of the complement cascade, which binds to receptors on the phagocyte membrane, initiating phagocytosis - this process is called opsonization.")

h2("Phagocytosis by Neutrophils")
bullet("Neutrophils entering tissues are already mature and immediately begin phagocytosis.")
bullet("On approaching a particle, the neutrophil first attaches to it, projects pseudopodia in all directions around the particle, and the pseudopodia meet on the opposite side, fusing to enclose the particle within a phagocytic vesicle (phagosome).")
bullet("A single neutrophil can usually phagocytize 3 to 20 bacteria before it becomes inactivated and dies.")

h2("Phagocytosis by Macrophages")
bullet("Macrophages are the end-stage product of monocytes that enter tissues from the blood; once activated by the immune system, they are much more powerful phagocytes than neutrophils - capable of engulfing as many as 100 bacteria.")
bullet("Macrophages can engulf much larger particles, even whole RBCs or malarial parasites, which neutrophils cannot phagocytize.")
bullet("After digesting particles, macrophages can extrude residual products and survive/function for many more months.")

h2("Digestion of the Phagocytized Particle")
bullet("Once a particle is phagocytized, lysosomes and other cytoplasmic granules immediately contact and fuse with the phagocytic vesicle, dumping digestive enzymes and bactericidal agents into it - the vesicle becomes a digestive vesicle, and digestion begins immediately.")
bullet("Neutrophils and macrophages contain abundant lysosomes filled with proteolytic enzymes for digesting bacteria and other proteins. Macrophage lysosomes also contain large amounts of lipases, which digest the thick lipid membranes of some bacteria (e.g., tuberculosis bacillus).")

h2("Killing of Bacteria")
bullet("Phagocytes also contain bactericidal agents that kill most bacteria even when lysosomal enzymes fail to digest them - important because some bacteria have protective coats or other factors that resist digestion.")
bullet("Some of the killing effect comes from powerful oxidizing agents formed by enzymes in the membrane of the phagosome or by a special organelle called the peroxisome: superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl ions (OH-), which are lethal to most bacteria.")
bullet("One lysosomal enzyme, myeloperoxidase, catalyzes the reaction between H2O2 and chloride ions to form hypochlorite, which is exceedingly bactericidal.")
bullet("Some bacteria (e.g., the tuberculosis bacillus) have coats resistant to lysosomal digestion and partly resist killing, which is why they cause many chronic diseases.")

img("image2.png", "Figure 34-3: Phagocytosis of a pathogen by a phagocytic cell (pseudopod, phagosome, lysosome, phagolysosome, exocytosis); Figure 34-4: Functional diagram of a lymph node; Figure 34-5: Kupffer cells lining liver sinusoids")
source_note("452-453")

# 7. MONOCYTE-MACROPHAGE (RETICULOENDOTHELIAL) SYSTEM
h1("7. Monocyte-Macrophage Cell System (Reticuloendothelial System)")
note("Monocytes entering tissues enlarge to become tissue macrophages that may remain fixed in tissue for months or years until called upon to perform specific local protective functions.")
bullet("The combination of monocytes, mobile macrophages, fixed tissue macrophages, and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes is called the reticuloendothelial system.")
bullet("Because the reticuloendothelial system is almost synonymous with the monocyte-macrophage system, it is better known in current literature as the monocyte-macrophage system - a generalized phagocytic system located in all tissues, especially where large quantities of particles, toxins, and other unwanted substances need to be destroyed.")

h2("Macrophages in Lymph Nodes")
bullet("Particulate matter entering tissue is either absorbed directly through capillary membranes into blood, or enters the lymph and flows to lymph nodes located intermittently along lymphatic vessels, where it is trapped in a meshwork of tissue macrophages (Figure 34-4).")
bullet("Lymph enters through afferent lymphatics into the nodal medullary sinuses, and foreign particles are trapped there before lymph passes out through the hilus via efferent lymphatics into the venous circulation.")

h2("Alveolar Macrophages in the Lungs")
bullet("Inhaled particles that reach the alveoli are phagocytized by alveolar macrophages, which are integral components of the alveolar wall.")
bullet("Digestible particles are digested and released into the lymph; indigestible particles are often walled off in a capsule until eventually dissolved (or never), e.g. capsules around tuberculosis bacilli, silica dust particles, and carbon particles.")

h2("Macrophages (Kupffer Cells) in Liver Sinusoids")
bullet("Bacteria absorbed from the gastrointestinal tract pass through the portal blood to the liver, where they are removed by Kupffer cells lining the liver sinusoids (Figure 34-5), before the portal blood reaches the general circulation.")
bullet("Kupffer cells can phagocytize a single bacterium from the blood in less than 0.01 second.")

h2("Macrophages of the Spleen and Bone Marrow")
bullet("If an invading organism enters the general circulation, further lines of defense are the tissue macrophages of the spleen and bone marrow.")
bullet("In both organs, macrophages become entrapped in the reticular meshwork of the tissue; when foreign particles come in contact with these macrophages, they are phagocytized.")
bullet("The spleen is similar to lymph nodes, except that blood (instead of lymph) flows through the tissue spaces (Figure 34-6). Blood squeezes through the trabecular meshwork of the red pulp cords and returns to the circulation through the walls of the venous sinuses; the red pulp is lined with vast numbers of macrophages that phagocytize unwanted debris in the blood, including old and abnormal RBCs.")

img("image3.png", "Figure 34-6: Functional structures of the spleen; Figure 34-7: Migration of neutrophils from blood into inflamed tissue (rolling adhesion, tight binding, diapedesis, migration)")
source_note("454-455")

# 8. INFLAMMATION
h1("8. Inflammation: Role of Neutrophils and Macrophages")
note("When tissue injury occurs (from bacteria, trauma, chemicals, heat, or other phenomena), multiple substances are released by the injured tissues and cause dramatic secondary changes in surrounding uninjured tissue - this complex of tissue changes is called inflammation.")
note("Inflammation is characterized by five features:")
bullet("Vasodilation of local blood vessels, with consequent increased local blood flow (hyperemia).")
bullet("Increased permeability of the capillaries, allowing leakage of large quantities of fluid into the interstitial spaces.")
bullet("Clotting of fluid in the interstitial spaces because of increased amounts of fibrinogen and other proteins leaking from the capillaries.")
bullet("Migration of large numbers of granulocytes and monocytes into the tissue.")
bullet("Swelling of tissue cells.")
note("Some of the tissue products that cause these reactions are histamine, bradykinin, serotonin, prostaglandins, and several reaction products of the complement system, the blood clotting system, and lymphokines released by sensitized T cells (part of the immune system).")
bullet("Several of these substances strongly activate the macrophage system, and within a few hours macrophages begin devouring destroyed tissues; at times, however, macrophages also further injure still-living tissue cells.")

h2("Walling-Off Effect of Inflammation")
bullet("One of the first results of inflammation is to wall off the area of injury from the remaining tissues. The tissue spaces and lymphatics in the inflamed area are blocked by fibrinogen clots so that fluid barely flows through the spaces, delaying the spread of bacteria or toxic products.")
bullet("The intensity of the inflammatory process is proportional to the degree of tissue injury.")
bullet("Staphylococci: release lethal cellular toxins - inflammation develops rapidly, walling off the infection quickly, so staphylococcal infection is characteristically localized (though it can multiply and spread rapidly if not walled off).")
bullet("Streptococci: do not cause intense local tissue destruction; the walling-off process develops slowly, so streptococci tend to spread through the body causing far greater destructiveness than staphylococci, despite staphylococci often causing greater local tissue death.")

h2("Macrophage and Neutrophil Responses During Inflammation - Sequence of Events")
bullet("First line of defense - Tissue Macrophages: within minutes of tissue injury, macrophages already present (histiocytes in subcutaneous tissue, alveolar macrophages in lungs, microglia in the brain, etc.) begin phagocytic actions, activated by products of infection and inflammation. This response is rapid but not great in numbers, and these early mobilized macrophages are not long-lived.")
bullet("Second line of defense - Neutrophil Invasion: within the first hour after inflammation begins, large numbers of neutrophils invade the inflamed area from the blood, caused by inflammatory cytokines (e.g., tumor necrosis factor and interleukin-1) released by inflamed tissues, which initiate the following reactions:")
bullet("Increased expression of adhesion molecules such as selectins and intercellular adhesion molecule-1 (ICAM-1) on capillary/venule endothelial cells; complementary integrin adhesion molecules on neutrophils cause them to stick to the inflamed vessel wall (margination) (Figure 34-7).")
bullet("Loosened intercellular attachments between endothelial cells allow gaps large enough for neutrophils to crawl through by diapedesis.")
bullet("Chemotaxis then attracts neutrophils toward the injured tissue - the entire process (adhesion, diapedesis, chemotaxis) is often interchangeably termed extravasation.")
bullet("Neutrophilia - Acute Increase in Blood Neutrophils: within a few hours of acute severe inflammation, the number of neutrophils in blood can increase fourfold to fivefold, from a normal 4000-5000 to 15,000-25,000 neutrophils/microliter, due to inflammatory products mobilizing stored marrow neutrophils into the circulation.")
bullet("Third line of defense - Second Macrophage Invasion: monocytes from blood also enter the inflamed tissue and enlarge into macrophages, but this invasion is much slower than neutrophils since blood monocyte storage pools are low; full macrophage phagocytic capacity develops only after several days as they enlarge and develop lysosomal enzymes. Eventually, macrophages dominate the phagocytic cells of an inflamed area because of greatly increased bone marrow production of new monocytes.")
bullet("Macrophages can phagocytize far more bacteria (about five times as many) and much larger particles, including neutrophils themselves and necrotic tissue, than neutrophils. Macrophages also play a role in initiating antibody development.")

h2("Formation of Pus")
bullet("When large numbers of bacteria and necrotic tissue are engulfed, most neutrophils and many macrophages eventually die. After several days, a cavity forms in the inflamed tissue containing varying portions of necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid - this mixture is commonly called pus.")
bullet("After infection is suppressed, dead cells and necrotic tissue in pus gradually autolyze over days, and end products are eventually absorbed into surrounding tissue and lymph until most evidence of tissue damage is gone.")

# 9. FEEDBACK CONTROL OF BONE MARROW PRODUCTION
h1("9. Increased Production of Granulocytes and Monocytes by Bone Marrow (Fourth Line of Defense)")
bullet("Stimulation of the granulocyte and monocyte progenitor cells of the marrow greatly increases production of these cells - this is the fourth line of defense against infection.")
bullet("It takes 3 to 4 days before newly formed granulocytes and monocytes reach the stage of leaving the bone marrow. If the inflammatory stimulus continues, the marrow can continue producing these cells for months or years at a rate 20 to 50 times normal.")

h2("Feedback Control of Macrophage and Neutrophil Responses")
note("Five factors are believed to play dominant roles in feedback control (shown in Figure 34-8):")
bullet("Tumor necrosis factor (TNF)")
bullet("Interleukin-1 (IL-1)")
bullet("Granulocyte-monocyte colony-stimulating factor (GM-CSF)")
bullet("Granulocyte colony-stimulating factor (G-CSF)")
bullet("Monocyte colony-stimulating factor (M-CSF)")
note("These factors are formed by activated macrophage cells in inflamed tissues and, in smaller quantities, by other inflamed tissue cells.")
bullet("GM-CSF stimulates both granulocyte and monocyte production; G-CSF stimulates granulocyte production; M-CSF stimulates monocyte production specifically.")
bullet("This combination of TNF, IL-1, and colony-stimulating factors provides a powerful feedback mechanism that begins with tissue inflammation and proceeds to formation of large numbers of defensive WBCs that help remove the cause of the inflammation.")

img("image4.png", "Figure 34-8: Control of bone marrow production of granulocytes and monocyte-macrophages by multiple growth factors released from activated macrophages in an inflamed area (TNF, IL-1, GM-CSF, G-CSF, M-CSF)")
source_note("456-457")

# 10. EOSINOPHILS
h1("10. Eosinophils")
bullet("Eosinophils normally constitute about 2% of blood leukocytes.")
bullet("Eosinophils are weak phagocytes and exhibit chemotaxis, but compared with neutrophils, it is doubtful that eosinophils are significant in protecting against the usual types of infection.")
bullet("Eosinophils are often produced in large numbers in people with parasitic infections, and they migrate into tissues diseased by parasites. Although most parasites are too large to be phagocytized by eosinophils, eosinophils attach themselves to the parasite via special surface molecules and release substances that kill many parasites:")
bullet("Schistosomiasis - a parasitic infection found in as many as one-third of people in some developing countries of Africa, Asia, and South America (an estimated 85-90% of the world's cases are in Africa).")
bullet("The schistosome parasitic worms invade any part of the body; eosinophils attach to the juvenile forms of the parasite and kill many of them by (1) releasing hydrolytic enzymes from their granules (modified lysosomes); (2) releasing highly reactive forms of oxygen especially lethal to parasites; and (3) releasing from the granules a highly larvicidal polypeptide called major basic protein.")
bullet("Trichinosis (infestation by Trichinella, the pork worm, from eating undercooked infested pork) - eosinophilia is another parasitic disease that stimulates marked eosinophil production.")
bullet("Eosinophils also have a special propensity to collect in tissues where allergic reactions occur, such as the peribronchial tissues of the lungs in people with asthma and in the skin after an allergic skin reaction. This is caused partly by the fact that many mast cells and basophils participate in allergic reactions, and eosinophils migrate toward allergic tissue where mast cells and basophils release an eosinophil chemotactic factor.")
bullet("Eosinophils are believed to detoxify some inflammation-inducing substances released by mast cells and basophils, and probably also phagocytize and destroy allergen-antibody complexes, thus preventing excess spread of the local allergic process.")

# 11. BASOPHILS
h1("11. Basophils")
bullet("Basophils in circulating blood are similar to the large tissue mast cells located immediately outside many blood capillaries.")
bullet("Both mast cells and basophils liberate heparin into the blood - a substance that can prevent blood coagulation.")
bullet("Mast cells and basophils also release histamine, as well as smaller quantities of bradykinin and serotonin.")
bullet("Mast cells are mainly responsible for many allergic reactions because the type of antibody that causes allergic reactions, immunoglobulin E (IgE), has a special propensity to become attached to mast cells and basophils.")
bullet("When the specific antigen for a specific IgE antibody subsequently reacts with the antibody, the resulting attachment of antigen to antibody causes the mast cell or basophil to release increased quantities of histamine, bradykinin, serotonin, heparin, slow-reacting substance of anaphylaxis (a mixture of three leukotrienes), and several lysosomal enzymes.")
bullet("These substances cause local vascular and tissue reactions that mediate most of the allergic manifestations (discussed further in the immunology chapter).")

# 12. LEUKOPENIA
h1("12. Leukopenia")
bullet("Leukopenia is a clinical condition in which the bone marrow produces very few WBCs, leaving the body unprotected against many bacteria and other invading agents.")
bullet("Normally, the human body lives in symbiosis with many bacteria because it is constantly exposed to bacteria in the mouth (spirochetal, pneumococcal, and streptococcal organisms) and to a lesser extent throughout the entire respiratory tract, and the distal gastrointestinal tract is especially loaded with colon bacilli.")
bullet("These bacteria can invade tissues immediately adjacent to the body's surfaces, and normally the WBCs provide a first line of defense that prevents this. When the bone marrow stops producing white blood cells, ulcers may appear in the mouth and colon within 2 days, or severe respiratory infection may develop. Bacteria invade tissues and blood without treatment, and death usually occurs within a week after acute total leukopenia begins.")
bullet("Irradiation of the bone marrow by x-rays or gamma rays, or exposure to drugs and chemicals containing benzene or anthracene nuclei, is likely to cause aplasia of the bone marrow. Some common drugs, such as chloramphenicol (an antibiotic), thiouracil (used to treat thyrotoxicosis), and even various barbiturate hypnotics, can on rare occasions cause leukopenia, thus setting off the entire infectious sequence of this disorder.")
bullet("After moderate irradiation injury to the bone marrow, some stem cells, myeloblasts, and hemocytoblasts may remain unimpaired in the marrow and are capable of regenerating the bone marrow, provided sufficient time is available. A patient properly treated with transfusions, antibiotics, and other drugs to ward off infection usually develops enough new bone marrow within weeks to months for blood cell concentrations to return to normal.")

# 13. LEUKEMIAS
h1("13. Leukemias")
bullet("Uncontrolled production of WBCs can be caused by cancerous mutation of a myelogenous or lymphogenous cell; this process causes leukemia, which is usually characterized by greatly increased numbers of abnormal WBCs circulating in the blood.")
note("There are two general types of leukemia:")
bullet("Lymphocytic leukemia - caused by cancerous production of lymphoid cells, usually beginning in a lymph node or other lymphocytic tissue and spreading to other areas of the body.")
bullet("Myelogenous leukemia - begins by cancerous production of young myelogenous cells in the bone marrow and then spreads throughout the body, so that WBCs are produced in extramedullary tissues, especially the lymph nodes, spleen, and liver.")
bullet("In myelogenous leukemia, the cancerous process occasionally produces partially differentiated cells, resulting in what might be called neutrophilic leukemia, eosinophilic leukemia, basophilic leukemia, or monocytic leukemia; more frequently, however, the leukemia cells are bizarre and undifferentiated, and not identical to any of the normal WBCs.")
bullet("Usually, the more undifferentiated the cell, the more acute the leukemia, often leading to death within a few months if untreated. With some of the more differentiated cells, the process can be chronic, sometimes developing slowly over 10 to 20 years. Leukemic cells, especially the very undifferentiated cells, are usually nonfunctional for providing normal protection against infection.")

# 14. EFFECTS OF LEUKEMIA ON THE BODY
h1("14. Effects of Leukemia on the Body")
bullet("The first effect of leukemia is metastatic growth of leukemic cells in abnormal areas of the body. Leukemic cells from the bone marrow may reproduce so much that they invade the surrounding bone, causing pain and, eventually, a tendency for bones to fracture easily.")
bullet("Almost all leukemias eventually spread to the spleen, lymph nodes, liver, and other vascular regions, regardless of whether the leukemia originated in the bone marrow or lymph nodes.")
bullet("Common effects of leukemia include: development of infection, severe anemia, and a bleeding tendency caused by thrombocytopenia (lack of platelets). These effects result mainly from displacement of the normal bone marrow and lymphoid cells by the nonfunctional leukemic cells.")
bullet("An important effect of leukemia on the body is excessive use of metabolic substrates by the rapidly growing cancerous tissues. The leukemic tissues reproduce new cells so rapidly that tremendous demands are made on the body's reserves for foodstuffs, specific amino acids, and vitamins.")
bullet("Consequently, the patient's energy is greatly depleted, and excessive utilization of amino acids by leukemic cells causes especially rapid deterioration of the body's normal protein tissues. As other tissues become debilitated while leukemic tissue continues to grow, this metabolic starvation factor alone can eventually be sufficient to cause death.")

img("image5.png", "Guyton & Hall, Ch. 34 - closing page: Effects of Leukemia on the Body, and chapter Bibliography")
source_note("458")

doc.save("/tmp/workspace/wbc_notes/output/WBC_Study_Notes.docx")
print("saved")