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The Lower Urinary Tract & Male Reproductive System

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The Lower Urinary Tract & Male Reproductive System Chapter 21 Hematopathology Nam Deuk Kim, Ph.D. Pusan National University 1 Contents I. Red blood cells II. Hemostasis III. White blood cells IV. Disorders of the lymphopoietic system V. Spleen VI. Thymus 2 THE HEMATOPOIETIC SYSTEM Composition of Human Blood Blood • Transports oxygen, nutrients, hormones, leukocytes (white cells), red cells, platelets and antibodies to tissues in the body and carbon dioxide and other waste products of cell metabolism to the excretory organs of the body • Volume of blood: Represents about 8% of total body weight • approximately 5 quarts, but it varies according to size of individual (5 liters in women; 5.5 liters in men) • Almost half of the blood consists of cellular elements suspended in plasma (viscous fluid) 3 4 Hemopoiesis Cellular differentiation and maturation of the lymphoid and myeloid components of the hematopoietic system. Only the precursor cells (blasts and maturing cells) are identifiable by light microscopic evaluation of the bone marrow. BFU = burst-forming unit; CFU = colony-forming unit (Ba = basophils; E = erythroid; Eo = eosinophils; G = polymorphonuclear leukocytes; GM = granulocyte-monocyte; M = monocyte/macrophages; Meg = megakaryocytic); EPO = erythropoietin; Gm-CSF = granulocyte-macrophage colony-stimulating factor; IL = interleukin; NK = natural killer; SCF = stem cell factor; TPO = thrombopoietin. 5 Composition of Human Blood • All blood cells arise from precursor cells within the bone marrow, called stem cells • These undergo further differentiation to form red cells, white cells, and platelets The cellular elements are: • Red cells • Leukocytes . Neutrophils . Monocytes . Eosinophils . Lymphocytes . Basophils • Platelets 6 Composition of Human Blood • Red cells • Are primarily concerned with transport of oxygen • Most numerous cells • Survival 4 months (120 days) • Erythroblast is precursor cell in bone marrow • Hemoglobin is the oxygen-carrying protein that is formed by the developing red cell • ~5 million cells/microliter • Leukocytes • Less numerous • Different types • Survival from several hours to several days, except for lymphocytes 7 Normal Leukocyte Cell Counts Mean Number Normal Per Microliter Range WBC (leukocytes) 7,400 4,500-11,000 Neutrophils 4,400 1,800-7,700 Eosinophils 200 0-450 Basophils 40 0-200 Lymphocytes 2,500 1,000-4,800 Monocytes 300 0-800 8 Composition of Human Blood • Lymphocytes may last for 2. Monocytes several years • Actively phagocytic • Lymphocytes are also • Increased in certain types of produced in the bone marrow chronic infection but are mainly produced in the lymph nodes and spleen 3. Eosinophils Types of Leukocytes • Increase in allergic reactions 1. Neutrophils • Increase in the presence of • Most numerous in adults animal-parasite infections • Comprise about 70% of total 4. Lymphocytes circulating white cells • Next most common in adults • Actively phagocytic • Predominant leukocyte in • Predominant in inflammatory children reactions 9 Composition of Human Platelets Blood: Lymphocytes • Are essential for blood • Mostly located in the lymph coagulation nodes, the spleen, and other • Are much smaller than lymphoid tissues leukocytes • Take part in both the cell- mediated and humoral defense • They represent bits of the reactions cytoplasm of megakarocytes, which are the largest precursor cell in the bone marrow • Have a relatively short survival, about 10 days • ~250,000 cells/microliter 10 NORMAL HEMATOPOIESIS Factors that may cause white Hematopoiesis: the formation cell production and development of blood • Products of cell necrosis cells • Hormone secretion by the • The bone marrow replenishes adrenals and other endocrine the blood cells glands • Substances necessary for hematopoiesis Red cells – Protein • Red cells develop from erythroblasts, which are large – Vitamin B12 – Folic acid (one of the vitamin precursor cells in the bone B group) marrow – Iron • Hemoglobin, formed by • Red cell production is developing red cells, is a regulated by the oxygen tetramer composed of four content of the arterial blood different subunits, each one • White cell production is not consisting of heme and globin well understood 11 Normal Hematopoiesis • Heme is a porphyrin ring that contains an iron atom • Globin forms the largest part of the hemoglobin, that forms different chains designated by Greek letters such as alpha, beta, gamma, delta, and epsilon • The heme and the globin are synthesized separately in different locations within the Heme b group erythoblast • The porphyrin ring is produced by the mitochondria; then the iron is inserted to form heme • The globin chains are produced by the ribosomes, and are joined to heme to form a hemoglobin unit Biliverdin 12 Normal Hematopoiesis • Finally, the four subunits aggregate to form the complete hemoglobin tetramer • The developing red cell accumulates increasing amounts of hemoglobin as it matures • The nucleus is extruded when 80% of its total hemoglobin has been synthesized • The cell is discharged from the bone marrow into the circulation, where it completes its maturation process within the next 24 hours • A newly formed red cell that lacks a nucleus but retains some of its organelles can be identified by special strains and is called a reticulocyte • After about 24 hours, it becomes a mature red cell where it survives in the circulation for about four months. 13 Normal Hematopoiesis Regulation of Hematopoiesis • The worn out red cells are • The red cell production is removed in the spleen regulated by the oxygen • The hemoglobin is content of the arterial blood degraded • A decreased oxygen supply stimulates erythropoiesis • The globin chains are • The low oxygen tension does broken down and their not act directly on the bone products used to make marrow other proteins • It is mediated by the kidneys • The iron is extracted and which produce erythropoietin, saved to make new which is a hormone-like hemoglobin erythrocyte-stimulating • The porphyrin ring cannot material be salvaged and is excreted by the liver as bile pigment 14 Bilirubin metabolism and elimination. 1. Normal bilirubin production from heme (0.2 to 0.3 gm/day) is derived primarily from the breakdown of senescent circulating erythrocytes, with a minor contribution from degradation of tissue heme-containing proteins. 2. Extrahepatic bilirubin is bound to serum albumin and delivered to the liver. 3. Hepatocellular uptake and (4) glucuronidation in the endoplasmic reticulum generate bilirubin monoglucuronides and diglucuronides, which are water soluble and readily excreted into bile. 5. Gut bacteria deconjugate the bilirubin and degrade it to colorless urobilinogens. The urobilinogens and the residue of intact pigments are excreted in the feces, with some reabsorption and excretion into urine. 15 1. Anemia A decrease in red blood cells or a subnormal level of hemoglobin • Anemia: “without blood” • Two different methods of classification are used 1. Etiologic classification: the factor responsible for anemia (Table 20-1) a. Acute blood loss b. Decreased production c. Ineffective hematopoiesis d. Increased destruction 2. Morphologic classification: shape and appearance of red cell 16 17 Etiologic Classification of Anemia 1. Inadequate production of red 2. Excessive loss of red cells cells • External blood loss • Insufficiency of raw materials: (hemorrhage) iron deficiency, Vitamin B12 • Shortened survival of red cells deficiency, folic acid in circulation, with defective deficiency red cells as in hereditary hemolytic anemia • Inability to deliver adequate • Accelerated destruction of red cells into circulation cells as caused by anti-red because of marrow damage antibodies, or by mechanical or destruction (as in aplastic trauma to circulating red cells anemia), or by the replacement of marrow by foreign or abnormal cells (as in bone marrow replacement anemia) 18 Morphologic Classification of Anemia • Normocytic anemia (정상혈구빈혈): appearance and size of cells is normal • Macrocytic anemia (대적혈구빈혈): cells larger than normal • Microcytic anemia (소적혈구빈혈): cells are smaller than normal • Hypochromic anemia (저색소성빈혈): reduced hemoglobin content • Hypochromic microcytic anemia (저색소성, 소적혈구빈혈): smaller than normal and reduced hemoglobin content • Classification of anemia based on red cell appearance is useful since it suggests the etiology of the anemia. 19 Morphologic Classification of Anemia • Iron deficiency anemia = hypochromic microcytic • Vitamin B12 or folic acid deficiency anemia = macrocytic anemia • Most other types of anemia = normocytic Macrocytic- normochromic Anemia 20 Major examples of anemias with morphological changes • Macrocytic-normochromic anemias : pernicious and folate-deficiency • Microcytic-hypochromic anemias : iron-deficiency, sideroblastic, thalassemia • Normocytic-normochromic anemias : aplastic, post- hemorrhagic, hemolytic, chronic disease, sickle cell 21 A. Megaloblastic anemia (disturbance in DNA synthesis) B. Iron deficiency (disturbance in hemoglobin synthesis; lack of iron): Hypochromic, microcytic erythrocytes C. Hereditary spherocytosis (membrane defect): Spherocytes D. Hereditary elliptocytosis (membrane defect): Elliptocytes E. Hemoglobin C disease (abnormal globin chain): Target cells, rhomboid crystals F. Acanthocytosis (membrane lipid defect, e.g., abetalipoproteinemia): Irregular spiculation G. Disseminated intravascular coagulation (DIC), thrombocytic thrombocytopenic purpura (TTP), heart valve prosthesis sequela (mechanical damage to erythrocytes): Schistocytes H. Sickle cell disease
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