MTH311-18 Hematology 1 Lecture Module 1 PDF

MTH311-18 HEMATOLOGY 1 LECTURE MODULE 1: INTRODUCTION TO HEMATOLOGY 1st SEMESTER I A.Y. 2024-2025 LECTURER: Ms. MOIRA SOLIMAN TRANSCRIBED BY: P.A.G. ALLAS LESSON 1 - HISTORICAL c...

MTH311-18 HEMATOLOGY 1 LECTURE MODULE 1: INTRODUCTION TO HEMATOLOGY 1st SEMESTER I A.Y. 2024-2025 LECTURER: Ms. MOIRA SOLIMAN TRANSCRIBED BY: P.A.G. ALLAS LESSON 1 - HISTORICAL composition during various systemic DEVELOPMENTS diseases. The major breakthrough in the George Hayem (1841 -1933) was study of blood occurred in 1942 when credited being the first to count platelets Anton van Leeuwenhoek, a Dutch in the blood and also wrote seminal microscopist, built a microscope and papers on hemolytic anemias and identified blood cells and compared their hematopoiesis. size with that of a grain of sand. German hematologists have In the 18th century, English made the case that Paul Ehrlich (1854 - physiologist, William Hewson, the 1915) whose aniline dye staining "Father of Hematology", introduced the techniques first distinguished clotting features of blood and shared his granulocyte subtypes and established knowledge of leukocytes or white blood the concepts of humoral immunity - cells. deserves a Vater designation. Bone marrow was recognized as Robert Virchow (1821 - 1902) co- the site of blood-cell formation along with described leukemia in 1845. Canadian- the first clinical descriptions of pernicious American William Osler (1849 -1919) anemia, leukemia and a number of other published numerous observations on disorders of the blood. platelets and vascular disorders. In 1963, Boston hematologist Bostonian George Minot (1885 - William Dameshek wrote an essay in 1950) and Wisconsinite William Murphy the journal he'd founded 17 years (1892 -1987) developed the first specific earlier, Blood, describing 18th century treatment for a hematologic malady when English anatomist William Hewson's they cured pernicious anemia with raw detailed studies of the thymus. liver in the 1920's as well as Austrian Canadian-American Maxwell Wintrobe Gabriel Andal (1797-1876) and (1901 - 1906) invented the hematocrit, Alfred Francoise Donne (1001-1878) trained many hematology department described changes in blood cell - chairs and published the most influential 3. He made a groundbreaking hematology textbook of the 20th century. discovery about chromosomal rearrangements in leukemia in the Russian-American Dameshek 1970s and beyond. made a key contribution in 1951, when A. J. Rowley he proposed a unified concept of B. R. Virchow "myeloproliferative disorders" and C. M. Wintrobe therefore is often called the father of D. P. Ehrlich these neoplasms. Janet Rowley (1925 - 2013) 4. He invented the hematocrit and made a groundbreaking discovery about published the most influential chromosomal rearrangements in hematology textbook of the 20th leukemia in the 1970's and beyond. century A. G. Hayem New machines are being B. P. Ehrlich developed at present and automation C. M. Wintrobe has considerably improved the precision D. R. Virchow and accuracy of testing. Assessment: 5. He wrote seminal papers on hemolytic anemias and Direction: Choose the BEST answer for hematopoiesis. each question. A. R. Virchow B. L. Pasteur 1. Who is known as the "Father of C. R. Hewson Hematology"? D. G. Hayem A. Donne B. Hewson References: C. Van Leeuwenhoek 1. https://www.ashclinicalnews.org D. Blundell 2. https://study.com.academy.lesson 2. A Russian-American scientist who LESSON 2 - BLOOD proposed a unified concept of Blood is the vital, life-sustaining "myeloproliferative disorders"? fluid circulating in a closed system of A. Van Leeuwenhoek blood vessel and the heart. B. Dameshek C. Murphy The systemic circulation provides D. Osler the functional blood supply to all body tissues. It carries oxygen and nutrients to the cell and picks up carbon dioxide and the blood and plasma proteins. This waste products. Systemic circulation also contributes to normal blood carries oxygenated blood from the left pressure. ventricle through the arteries to the capillaries in the tissues of the body. 3. pH of the blood: The normal pH range of blood is 7.35 - 7.45 (average is 7.4) which is slightly alkaline. The venous blood has a lower pH than the arterial blood because of the presence of more carbon dioxide. Blood pH is controlled by the buffer system of the blood. 4. Temperature: Temperature of blood is 38 degrees Celsius (100 degrees Fahrenheit). General Characteristics: 5. Osmolality: It is a measure of how 1. Color: The color of the blood is due much one substance has dissolved to the pigment hemoglobin within in another substance. The greater the red cells. The color of the blood the concentration of the substance varies with its oxygen content. dissolved, the higher the osmolality. Arterial blood is bright red color due Very salty water has higher to its high level of oxygen. Venous osmolality than water with a just a blood has given much of its oxygen hint of salt. When your body is and thus has a darker dull red functioning properly, it makes color. specific adjustments to maintain an appropriate osmolality. For example, 2. Viscosity: Viscosity means you may need to urinate frequently if thickness or resistance to flow blood. your blood osmolality is too low. This Whole blood is about 4.5 to 5.5 times helps your body get rid of excess as viscous as water, indicating that it water, raising the osmolality of your is more resistant to flow than water. blood. Blood osmolality is measured This viscosity is vital to the function in milliosmoles per kilogram. A of blood because of blood flows or normal result is typically 275 to 295 with too much resistance, it can milliosmoles per kilogram for adults strain the heart and lead to severe and older adults. cardiovascular problems. Viscosity is increased by the presence of cells of 6. Specific Gravity: This is the ratio of anemia), (c) loss of plasma (burns) and the weight or density of blood to the (d) loss of body fluids (diarrhea, loose density of an equal volume of water bowel movement, excessive sweating). at a specified temperature (25 Blood volume can be calculated degrees Celsius). It represents the given the hematocrit (Hct, the fraction of amount of dissolved substances and blood that is red blood cells) and plasma solid in the blood. The specific gravity volume (with the hematocrit being of blood is 1.048 - 1.066. If the liquid regulated via the blood oxygen content you are comparing has a specific regulation). Measurement may be used gravity lower than one (1) gram per in people with congestive heart failure, mL, it will float in water. If it has a chronic hypertension, kidney failure and specific gravity higher than one (1) critical care. gram per mL, it will sink. 7. Volume: The volume of blood (Red blood cells and plasma) in the circulatory system of any individual is regulated by the kidney. Blood constitutes about 20% of the extracellular fluid amounting to 8% of the total body mass. The blood volume is 5 liters to 6 liters (1.5 gal) in an average sized adult male and 4 liters to 5 liters (1.2 gal) in an average sized adult female. Newborn's blood COMPONENTS OF BLOOD volume is 250 to 350 mL of the total blood volume. Blood is composed of different kinds of cells (occasionally called Normovolemia refers to normal corpuscles), namely erythrocytes, blood volume. leukocytes and platelets. These formed Hypervolemia refers to increased elements of the blood constitute volume of blood during a) excessive fluid about 45% of whole blood. The intake, (b) blood transfusion, and (c) other 55% is blood plasma. intravenous injection of body fluids. Hypovolemia refers to decreased volume of blood seen in the following: (a) loss of blood (bleeding or hemorrhage), (b) loss of erythrocyte (hemolytic  B. Formed Elements The formed elements of the blood are so named because they are enclosed in a plasma membrane and have a definite structure and shape. All formed elements are cells, broadly classified as red blood cells (erythrocytes), white When a blood specimen is blood cells (leukocytes) except for centrifuged, leukocytes and platelets platelets (thrombocytes), which are tiny make up the buffy coat (small white layer fragments of bone marrow cells. Their of cells) lying between the packed red numbers remain remarkably constant for blood cells (erythrocyte layer) and the each individual in health. plasma. 1. Red Blood Cells (RBCs) A. Blood Plasma They are most numerous cells in When the formed elements are the blood. In adults, they are formed in removed from blood, a straw-colored the marrow of the bones that form the liquid called plasma is left. Plasma is axial skeleton. Mature red cells are non- about 91.5% water and 8.5% solutes, nucleated (anucleate) and are shaped most of which by weight (7%) are like flattened, bilaterally indented proteins. Some of the proteins in plasma spheres, a shaped often referred to are also found elsewhere in the body, but as biconcave disc with a diameter 7.0- those confined to blood are called plasma 8.0 µm and thickness of 1.7 - 2.4 µm. In proteins. These proteins play a role in stained smears, only the flattened maintaining proper blood osmotic surfaces are observed; hence the pressure which is important in total body appearance is circular with an area of fluid balance. Most plasma proteins are central pallor (or one third of their synthesized by the liver, including the center) corresponding to the indented albumins (54% of plasma proteins), region. globulins (38%) and fibrinogen (7%). Other solutes in plasma include waste products, such as urea, uric acid, creatinine, ammonia, and bilirubin; nutrients; vitamins; regulatory substances such as enzymes and hormones, gases and electrolytes.  They are primarily involved in nearly colorless in an unstained cell tissue respiration. The red cells contain suspension. the pigment hemoglobin which has the Leukopenia – decreased WBC ability to combine reversibly with oxygen. count (fewer than 4500/µL and increased In the lungs, the hemoglobin in the red WBC count (leukocytosis (more than cell combines with oxygen and releases 11,500/µL). Their production is in the it to the tissues of the body (where bone marrow and lymphoid tissues oxygen tension is low) during the (lymph nodes, lymph nodules and circulation. Carbon dioxide, a waste spleen). product of metabolism is then absorbed from the tissues by the red cells and is transported to the lungs to be exhaled. The red cell normally survives in the bloodstream for approximately 120 days after which time it is removed by the phagocytic cells of the reticuloendothelial system (RES), broken down and some of its constituents re-utilized for the formation of new cells. There are five distinct cell types RBCs counted in measured each with a characteristic morphologic volumes can detect anemia or appearance and specific physiologic role. polycythemia. Anemia means loss of These are: oxygen-carrying capacity and is often a. Polymorphonuclear reflected in a reduced RBC count or leukocytes/granulocytes decreased RBC hemoglobin concentration. Polycythemia means an They have, a single nucleus with a increased RBC count reflecting number of lobes. They contain small increased circulating RBC mass, a granules in their cytoplasm, and hence condition that leads to hyperviscosity. the name granulocytes. There are three types according to their staining 2. White Blood Cells (WBCs) reactions. WBCs protect their host from (a) Neutrophils infection and injury.They are transported in the blood from their source, usually Their size ranges from 10-12 um bone marrow or body cavity destination. in diameter. They are capable of They are so named because they are amoeboid movement. There are 2 - 5 lobes to their nucleus that stain purple  violet. The cytoplasm stains light pink 1. Small lymphocytes: Their size with pinkish dust like granules. range from 7 - 10 µm in diameter. Normal range is 2.0-7.5 x 103/µL. They have round, deep purple Their number increases in acute staining nucleus which occupies basement infections. most of the cell. There is only a rim of pale blue staining cytoplasm. (b) Eosinophils They are the predominant form found in the blood. They have the same size as neutrophils or may be a bit larger (12 2. Large lymphocytes: Their size -14 µm). There are two lobes to their ranges from 12 - 14 µm in nucleus in a "spectacle" arrangement. diameter. Large lymphocytes have Their nucleus stains a little paler than a little paler nucleus than small that of netrophils, Eosinophils lymphocytes that is usually cytoplasm contains many, large, eccentrically placed in the cell. round/oval orange pink granules. They have more plentiful They are involved in allergic reactions cytoplasm that stains pale blue and and in combating helminthic may contain a few reddish infections. Normal range is 40- granules. The average number of 400 µL. Increase in their number lymphocytes in the peripheral (eosinophilia) is associated with blood is 2500 µL. Lymphocytes are allergic reactions and helminthiasis. seen in viral infections especially in (c) Basophils children. Their size ranges from 10 - 12 µm (b) Monocytes in diameter. basophils have a kidney- shaped nucleus frequently observed These are the largest white cells by a mass of large deep purple/blue measuring 14 - 18 µm in diameter. staining granules. their cytoplasmic They have a centrally placed, large granules contain heparin and and "horseshoe" shaped nucleus that histamine that are released at the site stains pale violet. Their cytoplasm of inflammation. Normal range is 20 - stains pale grayish blue and contains 200 µL. Basophilia is rare except in reddish blue dust-like granules and a cases of chronic myeloid leukemia. few clear vacuoles. They are capable of ingesting bacteria and particulate b. Mononuclear Leukocytes matter and act as "scavenger cells" at the site of infection. Normal range is (a) Lymphocytes 700 - 1500 µL. Monocytosis is seen in There are two varieties:  bacterial infections, (e.g. tuberculosis) and protozoan infections. 3. Platelets (thrombocytes) These are small, non-nucleated, round/oval cells/ cell fragments that stain pale blue and contain many pink granules. Their size ranges 1 - 4 µm in diameter. They are produced in the bone marrow by fragmentation of cells called megakaryocytes which are large and multinucleated cells. Their primary function is preventing blood loss from hemorrhage. When blood vessels are injured, platelets rapidly adhere to the damaged vessels and with one another to form a platelet plug. During this process, the soluble blood coagulation factors are activated to produce a mesh of insoluble fibrin around the clumped platelets. This assists and strengthens the platelet plug and produces a blood clot which prevents further blood loss. Normal range: 150 - 400 x 103/µL. FUNCTIONS OF BLOOD conditions. These conditions should include the following: 1. Transportation Osmotic concentration: the Blood transport oxygen from the body/cellular water concentration, lungs to the cells of the body and carbon composed of 0.85% sodium chloride. dioxide from the cells to the lungs. It also This normal osmotic concentration is carries nutrients from the gastrointestinal termed isotonic. tract to the cells, heat and waste products away from cells and hormones Hypotonic solution (greater from endocrine glands to other body amount of water in relationship to lesser cells. amount of solutes) – water enters the cell; the cell swells and may lyse. 2. Regulation Hypertonic solution (lesser Blood regulates pH through amount of water in relationship to greater buffers. It also adjusts body temperature amount of solutes) – water leaves the through the heat absorbing and coolant cell; the cell may crenate. properties of its water content and its variable rate of flow through the skin, where excess heat can be lost to the environment. Blood osmotic pressure also influences the water content of cells, principally through dissolved ions and proteins. 3. Protection The clotting mechanism protects against blood loss and certain phagocytic BASIC HEMATOLOGY TERMINOLOGY white blood cells or specialized plasma proteins such as antibodies, interferon, 1. a- without and complement protect against foreign 2. – blast youngest microbes and toxins. 3. – chronic colored 4. – cyte cell Homeostasis: 5. dys abnormal The body’s tendency to move 6. – ermia in the blood toward physiological stability. In vitro 7. Ferro - iron testing of blood and other body fluids 8. Hyper - increased must replicate exact environmental body 9. Hypo - decreased 10. Iso - equal A. Blood consists of plasma and 11. Macro large formed elements 12. Mega - very large/huge B. Plasma is a straw-colored clear 13. Micro - small liquid containing cellular elements 14. Myelo - marrow and solutes 15. Noro - normal C. Plasma is approximately 92% 16. – oid like water 17. – osis increased D. All of the above statements are 18. Pan - all also true of serum 19. – penia decreased 20. – plasia formation 4. The percentage of formed elements 21. – poiesis cell production in the blood is: 22. Poly - many A. 45% 23. Pro - before B. 50% 24. Thrombo clot C. 55% D. 65% Assessment: Direction: Choose the BEST answer. 5. What are the three major functions of blood? 1. All of the following statements about _____________________________ platelets are correct except: _____________________________ A. Disk-shaped cell particles _____________________________ B. Also called thrombocytes C. Numerous: 140-440 x 103/µL of References: blood D. Able to clump together to begin 1. Elaine M. Keohane, Larry J. Smith and the coagulation process Jeanine M. Walenga. RODAK'S Hematology: Clinical Principles and 2. What is the name of the iron- Applications. 6th ed. Saunders containing protein that gives red 2. Hoffbrand, A. Victor. Color Atlas of blood cells their color? Clinical hematology. 4th ed. Philadelphia: A. Hemocyanin Mosby/ Elsevier, c2012. R616.15 h69C B. Pyrite 2010. C. Hemoglobin D. Myoglobin 3. Turgeon, Mary L., Clinical Hematology Theory and Procedure. 4th 3. All of the following statements are ed. (2006). Lippincott Williams & Willis true except: 4. Turgeon, Mary L. Clinical Laboratory Science, The Basics and Routine Techniques. 5th ed. 2007. Mosby, Elsevier 5. McPherson, Richard A. and Pincus Matthew R. HENRY'S Clinical Diagnosis and Management by Laboratory methods. 22nd ed. Elsevier Saunders  MTH311-18 HEMATOLOGY 1 LECTURE MODULE 2: HEMATOPOIESIS 1st SEMESTER I A.Y. 2024-2025 LECTURER: Ms. MOIRA SOLIMAN TRANSCRIBED BY: P.A.G. ALLAS gestation. These nests are referred to as LESSON 3 - HEMATOPOIETIC "blood islands". Some of these cells from DEVELOPMENT primitive erythroblasts in the central cavity of the yolk sac, where the other Hematopoiesis or hemopoiesis is (angioblasts) surround the cavity of the a continuous regulated process of blood yolk sac and eventually form blood cell production that includes cell renewal, vessels. These primitive but transient proliferation, differentiation and yolk sac erythroblast are important in maturation. These processes result in the early embryogenesis to produce formation, development and hemoglobin (Gower-1, Gower-2 and specialization of all the functional blood Portland) needed for delivery of oxygen cells that are released from the bone to rapidly developing embryonic tissues. marrow to the circulation. Yolk sac hematopoiesis that occurs later In healthy adults, hematopoiesis is in the fetus and the adult in that it occurs restricted primarily to the bone marrow. intravascularly, or within developing During fetal development, the restricted blood vessels. sequential distribution of cells initiates in the yolk sac and then progresses in the HEPATIC PHASE aorta-gonad mesonephros (AGM) region (6th week - 6 months) (mesoblastic phase), then to the fetal This phase begins at 5 to 7 liver (hepatic phase) and finally resides in gestational weeks and is characterized the bone marrow (medullary phase). by recognizable clusters of developing erythroblasts, granulocytes and MESOBLASTIC PHASE monocytes colonizing the fetal liver, (14th day - 1st month) thymus, spleen, placenta and ultimately the bone marrow space in the final Early in embryonic development, medullary phase. During this phase, cells from the mesoderm migrate to the hematopoiesis occurs extravascularly yolk sac, where small nests of blood cell with the liver remaining the major site of production can be visualized and begins hematopoiesis during the second between the 10th and 14th days of trimester of fetal life. Hematopoiesis in the fetal liver reaches its peak by the third month of fetal development, then gradually declines after the 6th month, retaining minimal activity until 1 to 2 weeks after birth. The developing spleen, kidney, thymus and lymph node s contribute to the hematopoietic process during this phase. The spleen gradually decreases granulocytic production and involves itself solely in lymphopoiesis. During the hepatic phase, fetal hemoglobin (HbF) is the predominant hemoglobin, but detectable levels of adult MEDULLARY (MYELOID) PHASE Prior to the 5th month of fetal development, hematopoiesis begins in the bone marrow cavity. This transition is called medullary hematopoiesis because it occurs in the medulla or inner part of the bone. Hematopoietic activity, especially myeloid activity, is apparent HEMATOPOIETIC TISSUES during this stage of development, and the myeloid-to-erythroid ratio gradually approaches 3:1 (adult levels). By the end of 24 weeks" gestation, the bone marrow becomes the primary site of hematopoiesis. Measurable levels of erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony- stimulating factor (GM-CSF), and hemoglobins F and A can be detected. BONE MARROW: Normal bone marrow contains two major components red marrow hematopoietically active marrow LIVER: consisting of the developing blood cells and their progenitors and yellow marrow, The liver serves as the major site hematopoietically inactive marrow of blood cell production during the composed primarily of adipocytes (fat second trimester of fetal development. In cells), with undifferentiated adults, the hepatocytes of the liver have mesenchymal cells and macophages. many functions including protein During infancy and early childhood, all synthesis and degradation, coagulation the bones in the body containprimarily factor synthesis, carbohydrate and lipid red (active) marrow. Between 5 and 7 metabolism, drug and toxin clearance, years of age, adipocytes become more iron recycling and storage and abundant and begin to occupy the hemoglobin degradation in which spaces in the long bones dominated by bilirubin is conjugated and transported to active marrow. the small intestine for eventual excretion. The process of replacing the Kupffer cells are macrophages active marrow by adipocytes (yellow that remove senescent cells and foreign marrow) during development is called debris from the blood that circulates regression and eventually results in through the liver, they also secrete restriction of the active marrow in the mediators that regulate protein synthesis adult to the sternum, vertebrae, in the hepatocytes. scapulae, pelvis, ribs, skull and proximal In porphyria, hereditary or portion of the long bones. Inactive yellow acquired defects in the enzyme involved marrow is scattered throughout the red in heme biosynthesis result in the marrow so that in adults, there is accumulation of the various intermediary approximately equal amount of red and porphyrins that damage hepatocytes , yellow marrow in these areas. Yellow erythrocyte precursors and other tissues. marrow is capable of reverting back to In severe hemolytic anemias, the liver active marrow in cases of increased increases the conjugation of bilirubin and demand on the bone marrow such as the storage of iron. The liver sequesters excessive loss or hemolysis. The membrane-damaged RBCs and remove hematopoietic inductive them from the circulation. It can maintain microenvironment in the bone marrow is hematopoietic stem and progenitor cells essential for regulating hematopoietic to produce various blood cells (called stem cell maintenance, self-renewal and extramedullary erythropoiesis) as a differentiation. response to infectious agents or in pathologic myelofibrosis. It is directly affected by storage diseases of the monocyte/macrophage (Kupffer) cells as of adjacent endothelial cells. The a result of enzyme deficiencies that combination of the slow passage and the cause hepatomegaly with ultimate continued RBC metabolism creates an dysfunction of the liver (Gaucher environment that is acidic, hypoglycemic disease, Niemann-Pick disease, Tay- and hypoxia. The increased Sach's disease). environmental stress on the RBCs circulating through the spleen leads to SPLEEN: possible hemolysis. In the rapid transit pathway, blood cells enter the splenic The spleen is the largest lymphoid artery and pass directly to the sinuses in organ in the body. It is vital but not the red pulp and continue to the venous essential for life and functions as an system to exit the spleen. indiscriminate filter of the circulating blood. As the RBCs pass through the When splenomegaly occurs, the cords of Billroth, there is a decrease in spleen becomes enlarged and is the flow of blood, which leads to palpable. This occurs as a result of many stagnation and depletion of the RBCs conditions such as chronic leukemias, glucose supply. These cells are subject inherited membrane or enzyme defects to increased damage and stress that may in RBCs, hemoglobinopathy, lead to their removal from the spleen. The thalassemia, malaria and the spleen uses two methods for removing myeloproliferative disorders. senescent or abnormal RBCs from the Splenectomy may be beneficial in cases circulation: culling in which the cells are of excessive destruction of RBCs such phagocytized with subsequent as autoimmune hemolytic anemia when degradation of cell organelles, and treatment with corticosteroids does not pitting, in which splenic macrophages effectively suppress hemolysis or in remove inclusions or damaged surface severe hereditary spherocytosis. membrane from the circulating RBCs. Splenectomy also may be indicated in The spleen also serves as a storage site some refractory immune for platelets. In a healthy individual, thrombocytopenic purpura or in storage approximately 30% of the total platelet disease/disorders with portal count is sequestered in the spleen. hypertension and splenomegaly resulting in peripheral cytopenias. After As blood enters the spleen, it may splenectomy, platelet and leukocyte follow one of two routes. The first is a count increase transiently. In sickle-cell slow-transit pathway through the red pulp anemia, repeated splenic infarcts caused in which the RBCs have a more difficult by sickled RBCs trapped in the small- time passing through the tiny openings vessel circulation of the spleen cause created by the interendothelial junctions tissue damage and necrosis, which often broken loose from malignant tumors. results in auto splenectomy. These malignant cells may grow and metastasize to other lymph nodes in the Hypersplenism is an enlargement same group. of the spleen resulting in some degree of pancytopenia despite the presence of a THYMUS: hyper active bone marrow. The most common cause is congestive In human beings, the thymus is splenomegaly secondary to cirrhosis of not an organ that is generally visible or the liver and portal hypertension. Often detectable from the outside. Depending causes incl, other vascular deformities on the age, chances are that you do have use thrombosis, vascular stenosis such at least the remnants of a thymus. but in as aneurysm of the splenic artery and most cases, adults don't really have an cysts. active thymus. After puberty, the thymus starts to slowly shrink, or atrophy and it LYMPH NODES: becomes replaced by fat. Not to worry, however, since it is generally accepted The organs of the lymphatic that thymus produces all the T cells you system located along the lymphatic will ever need prior to this point. Although capillaries that parallel, but are not part of activity of the thymus seems to grind to a the circulatory system. Lymph nodes halt in adulthood with rare exceptions, T have three main functions: they are a site lymphocytes continue to be generated in of lymphocyte proliferation from the the body and are replenished throughout germinal centers, they are involved in the the lifetime. The thymus facilitates the initiation of the specific immune maturation of cells, an important part of responses to foreign antigens and they the immune system providing cell filter particulate matter, debris and mediated immunity. bacteria entering the lymph node via the lymph. Nondevelopment of the thymus during gestation results in the lack of Lymph nodes by their nature, are formation of T lymphocytes. Related vulnerable to the same organisms that manifestations seen in patients with this circulate through the tissue. Sometimes condition are failure to thrive, increased numbers of microorganisms uncontrollable infections and death in enter the nodes, overwhelming infancy. Adults with thymic disturbance macrophages and causing adenitis are not affected because they have (infection of the lymph nodes). More developed and maintained a pool of T serious is the frequent entry into the lymphocytes for life. lymph nodes of malignant cells that have  accepted theory. The polyphyletic theory suggests that each of the blood cell lineage is derived from its own unique stem cell. Marrow hematopoiesis is divided into three major compartments. These are: 1. Stem cells are known as pluripotent or multipotential cells. They retain the Medullary hematopoiesis: Blood ability to differentiate into any cell cell production is within the bone marrow line. These cells are referred to and begins in the 5th month of gestation as colony-forming unit - spleen and continues throughout life, (CFU-S). CFU-S differentiate in while extramedullary hematopoiesis, either of two pathways: blood cell production is outside the bone the lymphoid stem cells, which give marrow and occurs when the bone rise to the primitive T or B marrow cannot meet body requirements lymphocytes. The other pathway is and mainly in the liver, spleen, with the myeloid stem cells, which give hepatomegaly and splenomegaly. rise to erythrocytes, monocytes, neutrophils, basophils and STEM CELL THEORY megakaryocytes. Morphologically unrecognizable 2. Progenitor (committed) cells are hematopoietic progenitor cells can be known as unipotential stem cells, divided into two major differentiating into one cell line. types: noncommitted or undifferentiat Committed stem cells include BFU- ed hematopoietic stem cells, E, CFU-E, CFU-MEG, CFU-GM and and committed progenitor cells. these CFU-L. They are characterized by two groups give rise to all of the mature their ability to form colonies in vitro in blood cells. response to a soluble factor. 3. Precursor cells comprise the third Originally there were two theories marrow compartment. Each type of describing the origin of hematopoietic unipotential stem cell matures into a progenitor cells. The monophyletic blast form: myeloblast, theory suggests that all blood cells are normoblast, pronormoblast, derived from a single progenitor stem cell megakaryoblast and lymphoblast. called a pluripotent hematopoietic stem cell. This theory is the most widely  basophilic granulocytes and those cells with affinity to both acidic and basic dyes are neutrophilic granulocytes. (c) Appearance of hemoglobin: This is a special feature of the maturation of erythrocytes. Immature cells contain no hemoglobin. Gradually the hemoglobin starts to appear as the cell becomes mature. Synchronistic maturation: 2. Changes in the nucleus Blood cells mature (a) Structure: The immature nucleus synchronistically when its nucleus and is round and oval and the nuclear cytoplasm mature simultaneously. If ever chromatin is very delicate, fine and one lags behind the other, asynchronistic linear and is called euchromatin. maturation is taken place. As the cell matures, chromatin strands become increasingly 1. Changes in the cytoplasm coarse and clumped and are called heterochromatin. The non-staining (a) Loss of basophilia: The areas in the nucleus of old cells are cytoplasm of an immature cell is called parachromatin. usually blue or basophilic due to its ribonucleic acid (RNA) content. The (b) Shape: As the cell matures, the more mature the cell, the less shape of the nucleus changes too. basophilic. This is especially true with granulocytes in which the nucleus (b) Cytoplasmic granules: In myeloid divides into segments or lobes into cells, the cytoplasm contain maturation. The older the cell, the granules. These granules contain m ore segments or lobes the some enzymes which distinguish nucleus possess. the myeloid stem cells from other cells. Those cells with an affinity to (c) Nuleolus: The chromatin is the red (acidic) dye are called considered as the best basis of the acidophilic or eosinophilic maturity of the cell, next is the granulocytes. Those with affinity to the blue (basic) dye are called  nucleolus. The more nucleoli in its series, the megaloblasts are larger nucleus, the younger the cell. than normal mature erythrocytes. Likewise, abnormally small cells may 3. Changes in the size also be seen. Generally, all cell lines increase in Cytokines and Growth Factors number but the individual cell's size 1. Erythropoietin (EPO) decreases because they undergo mitosis. With the exception of the a. Stimulates proliferation, growth megakaryocytic cells, all mature and differentiation of erythroid blood cells are smaller than the precursors and may have immature stages. minor effects on megakaryocytes. Asynchronistic Maturation b. Target cells are pronormoblast and CFU-Erythroid cells 1. Abnormal cytoplasmic differentiation c. Source: Kidney d. Recombinant EPO is used This is characterized clinically for the treatment of persistent cytoplasmic basophilia anemia, particularly those and late hemoglobinization in associated with renal failure. erythrocytes. Abnormal cytoplasmic inclusion bodies may be found in the 2. Interleukins are protein molecules cytoplasm of both erythrocytes and that work in conjunction with leukocytes, especially in the hematopoietic growth factors to granulocytes. stimulate proliferation and differentiation of specific cell lines. 2. Abnormal nuclear maturation Lineage-Specific Hematopoiesis The nucleus may be 1. Erythropoiesis hyposegmented or hypersegmented. It occurs in the bone marrow The megalocytes' nucleus takes a and is a complex, regulated process longer time to mature than its for maintaining adequate numbers cytoplasm. of erythrocytes in the peripheral blood. The CFU-GEMM gives rise 3. Abnormal size to the earliest identifiable colony of RBCs, called the burst-forming unit- Abnormally large cells are erythroid (BFU-E). The BFU-E frequently seen in benign or produces a large multiclustered malignant proliferation. In erythrocyte  colony that resembles a cluster of the proliferation and differentiation grapes containing a brightly colored of neutrophil and macrophage hemoglobin. BFU-Es contain only a colonies from the colony-forming few receptors for erythropoietin unit-granulocyte-monocyte. G-CSF (EPO), and their cycle activity is not and M-CSF stimulate neutrophil influenced significantly by the differentiation and monocyte presence of exogenous EPO. BFU- differentiation from the colony- Es under the influence of IL-3, GM- forming unit-monocyte. CSF, TPO, and KIT ligand develop into colony-forming unit-erythroid IL-3 stimulates growth of (CFU-E) colonies. granulocytes, monocytes, megakaryocytes and erythroid A small amount of EPO is cells. Eosinophils require GM-CSF, produced by the liver. Oxygen IL-5, and IL-3 for differentiation. The availability in the kidney is the requirements for basophil stimulus that activates production differentiation seem to depend on and secretion of EPO. EPO exerts it the presence of IL-3 and KIT ligand. effects by binding to Growth factors promoting lymphoid transmembrane receptors differentiation include IL-2, IL-7, IL- expressed by erythroid progenitors 12 and IL-15 and to some extent IL- and precursors. EPO serves to 4, IL-10, IL-13, IL-14 and IL-16. recruit CFU-E from the more primitive BFU-E compartment 3. Megakaryopoiesis prevents apoptosis of erythroid Earlier influences on progenitors and induces megakaryopoiesis include GM- hemoglobin synthesis. CSF; IL-3, IL-6, IL11, KIT ligand and thrombopoietin (TPO). The 2. Leukopoiesis stimulating hormonal factor (also Leukopoiesis can be divided known as MPL ligand), along with into two major categories: IL-11, controls the production and myelopoiesis and lymphopoiesis. release of platelets. The main site of Factors that promote differentiation production of TPO is the liver. of the CFU-GEMM into neutrophils, monocytes, eosinophils and Assessment: basophils include GM-CSF; G-CSF; 1. What is hemopoiesis and how macrophage colony-stimulating is the process regulated? factor (M-CSF), IL-3, IL-5, IL-11, and KIT ligand. GM-CSF stimulates ________________________________ B. The proportion of nucleus ________________________________ increases, the cytoplasmic ________________________________ proportion decreases ________________________________ C. Nucleoli becomes more prominent 2. What are the hematopoietic D. Cytoplasmic color changes from tissues during fetal life, in infancy, pink to gray to blue in childhood and in adulthood? ________________________________ References: ________________________________ ________________________________ 1. Keohane, E. A., Otto, C., & Walenga, ________________________________ J. M., (2019) RODAK'S HEMATOLOGY: Clinical Principles and Applications. Choose the best answer: 2. Turgeon, M. L., (2016). Clinical 3. Hematopoiesis that takes place Hematology Theory and Procedures. 6th within the bone marrow ed. Lippincott Williams & Willis A. Medullary hematopoiesis B. Extramedullary hematopoiesis C. Hematic hematopoiesis D. Mesoblastic hematopoiesis 4. As the erythrocyte mature, the nucleo-cytoplasmic ratio A. Decreases B. Increases C. Cannot be determined D. Stays the same 5. Which of these is true regarding maturation of RBC precursors? A. The nuclear chromatin becomes coarser, clumped, and condensed