SCIE2020 Harmening Chapter 1 PDF

RECAP: SCIE1440 (Intro to Immunology & Hematology) 1  “hema” – blood “ology” – study of Hematology The study of blood & blood- forming organs, centering on the blood cells & coagulation...

RECAP: SCIE1440 (Intro to Immunology & Hematology) 1  “hema” – blood “ology” – study of Hematology The study of blood & blood- forming organs, centering on the blood cells & coagulation factors 2 Blood Volume Average blood volume in an adult is 4-6L Average male has 5-6L Average female has 4-5L Blood is composed of ~55% plasma (liquid portion) ~45% cells (WBCs, RBCs, & PLTs) 3 Plasma portion of blood: Mainly Water (90-92%) Proteins and other solutes Proteins (~7%) – Albumin, globulin, fibrinogen Organic constituents – urea, creatinine, glucose Inorganic constituents – Na, K, Ca, Cl Respiratory gases Internal secretions – enzymes, hormones, antibodies (immunoglobulins) 4  Blood Cells Red Blood Cells White Blood Cells Platelets 5  Blood Cells Erythrocytes Leukocytes Thrombocytes 100 50 0 1s Qtr t 4t Qt h r E W N a e o st s rt t h Granulocyt Lymphocyt Monocytes es es Basophils Eosinophils Neutrophils 6  Hematopoietic Cell Function Cell Function Granulocytes Fight infection / trigger immune response Neutrophils = ______________________________ Neutrophils Monocytes = _______________________________ Eosinophils Eosinophils = _______________________________ Basophils Basophils = _________________________________ Lymphocytes Cellular & humoral immunity (antibody production) Monocytes Lymphocytes = __________ Erythrocytes Phagocytosis & secrete cytokines Platelets Respiratory gas exchange (O2 and CO2) Hemostasis 7 In healthy individuals, there is a constant balance between the rates of formation and aging/destruction/removal of these cells Disturbance of this critical balance may result in changes in:  Rates of formation  Disordered formation  Increased utilization and/or destruction The above changes can be responsible for a subsequent pathological condition(s) 8 Ready? … Let’s begin!  9 Hematology I (SCIE2020) Harmening Chapter 1 Hematopoiesis Battlement Pattern for Slide Morphology & Differentials Used for assessment of morphology (WBCs, RBCs and PLTs) Used for performing a WBC Differential L A B E L Source: Harmening Fig 5-1, p. 96 Three Zones of Wedge Preparation L A B E L Head Region Body Region Tail Region Harmening Chapter 1  Reading Assignment: Chapter 1  Morphology of Human Blood and Marrow Cells: Hematopoiesis OBJECTIVES 2.1 Define the term hematopoiesis 2.2 Name organs responsible for hematopoiesis in the fetus 2.3 Define the term erythropoiesis 2.4 List the proper cell maturation sequence of the erythroid series 2.5 Recognize each cell in the erythrocytic series 2.7 Describe the process of hematopoiesis 2.9 Name the most common skeletal sites for hematologic studies  Harmening p. 8 Hematopoiesis Define  The dynamic processes of blood cell hematopoiesis production and development of the various cells of the blood  Harmening p. 8 Hematopoiesis  Current evidence indicates that all blood cells are derived from a hematopoietic stem cell.  Hematopoiesis is characterized by a constant Hematopoiesis turnover of cells.  The normal hematopoietic system continuously maintains a cell population of erythrocytes, leukocytes, and platelets through a complex network of tissues, organs, stem cells, and regulatory factors.  Harmening p. 8  This network of organs is responsible for the maturation and division of hematopoietic stem cells into various cell lines, that are committed to carry out various functions  Examples:  Transport oxygen and excrete carbon dioxide (RBCs) Hematopoiesis  Fight infection (granulocytes)  Perform immune functions (lymphocytes)  Maintain hemostasis, a process in which blood clots and bleeding is halted (platelets)  Source: Harmening p. 9 There are descriptions of these cells at the beginning of Chapter 1, p. 1-8 19  Harmening p. 8  Hematopoietic stem cells duplicate themselves during division  The hematopoietic stem cell has the capacity for continuous self-replication and proliferation, together with the ability to differentiate into committed progenitor cells of lymphoid and myeloid lineages  Under the influence of growth factors (cytokines), such as colony- stimulating factors (CSFs) and interleukins (ILs), progenitor cells divide and differentiate to form the mature cellular elements of the peripheral blood  (see diagram Fig 1-15 next slide) Source: Harmening Fig 1-15, p. 9 Harmening p. 9  Harmening p. 36 Note: Hematopoetic stem cell Colony- stimulatin g factors (CSFs) Interleukin s (ILs) Source: Harmening Figure 1-62  Harmening p. 8 The Hematopoietic System  The hematopoietic system is orchestrated by the following:  (a) Organs  (b) Pluripotent stem cells  (c) Regulatory factors (aka. Growth factors)  These features enable the hematopoietic system to respond to stimuli such as infection, bleeding or hypoxia, by increasing hematopoiesis with emphasis on the particular cell type needed.  Harmening p. 8 The Hematopoietic System  The hematopoietic system consists of the following (a) organs, which are are involved in the production, maturation, and destruction of blood cells:  Bone marrow  Liver  Spleen  Lymph nodes  Thymus.  The entire process of hematopoiesis evolves from the (b) stem cells that support hematopoiesis, the progenitor cells that are committed to particular cell lines, and the (c) regulatory factors (growth factors) to which the hematopoietic system responds.  These features enable the hematopoietic system to respond to stimuli such as infection, bleeding or hypoxia, by increasing hematopoiesis with emphasis on the particular cell type needed. Summary HEMATOPOIESIS IN PREGNANCY Origin of Hematopoiesis: Also, see illustration next slide Period Age Site(s) Comments Mesoblastic Embryo (3rd- Blood islands Primitive erythroblasts produce 12th) week of of Yolk Sac embryonic hemoglobin (Gower I, gestation Gower II, Portland) Hepatic Fetus Liver, spleen, The liver is the primary site of RBC (Beginning fifth thymus, lymph production until the sixth month and week of nodes may continue to produce blood gestation) cells to a lesser degree until 1-2 weeks after birth. In the adult, the liver and spleen may be reactivated for RBC production if the bone marrow fails to keep up with demand (extra-medullary hematopoiesis). The spleen, thymus, and lymph nodes produce lymphocytes through-out life. Myeloid Approximately Bone Marrow By 3 weeks of age, the bone 7th month of marrow is the only normal site of gestation and RBC production. In the child, all continuing marrow is active. In the adult, fat throughout fills the shafts of the long bones, adulthood and the only active hematopoietic sites are the pelvis, vertebrae, ribs, sternum, skull, and proximal extremities of the long bones. Fatty marrow may be reactivated to compensate for anemia. 25  Hematopoiesis (Source: Harmening p. 10, fig. 1-16) (Summarized in a table, previous slide) a. Tissues and organs At birth, BONE MARROW (BM) is major site of blood cell development Hematopoiesis begins At 18-20 years, hematopoietic marrow is found Location of active marrow growth in the fetus & adult: 2-3 exclusively in the sternum, ribs, pelvis, months vertebra & skull Birth Source: Harmening p. 10, fig. 1-16 Active marrow in all bones Moves to At 4years, fat cells begin to appear in long bones 26  Red Marrow- active Yellow Marrow - inactive By adulthood, BM is Source: Harmening p. 10, fig. 1-16 50% fat & 50% cells As the growth rate slows, there is less At birth, 90% of BM shows red demand for active marrow; fat infiltration marrow indicating very active blood begins ~ 4 yrs cell development 27 Hematopoiesis involves the production of stem cells, progenitor cells and precursor cells. b. Stem cells All blood cells are derived from a pod of multi potential stem cells or pluri potential stem cells ↓ Unipotential (committed) myeloid and lymphoid ↓ Colony forming units (CFU’S) 28  Hematopoiesis Harmening Fig. 1-17 p.10 Shows different cell pools according to their activity: 2 pools: storage & functional Pluripotential CFU’s Stored for Along stem cell later vessel PPSC’s release wall into blood Origin of all blood cells Source: Harmening Fig 1-17, p. 10 spleen BM 100% functional BM PB 29 c. Controlling Factors/Growth Factors Colony Stimulating Factors (CSFs)  human hematopoietic growth factors Interleukins (IL’s)  proteins/glycoproteins; they regulate and differentiate of precursor cells; they act on cell surface receptors & either stimulate or inhibit proliferation and differentiation e.g. Interleukin 1 (IL-1), Interleukin 2 (IL-2) Controlling Factors:  regulate blood cell development by mediating proliferation, differentiation and maturation of progenitor cells  regulate survival and function of mature blood cells  are produced by macrophages, activated T-lymphocytes, fibroblasts and endothelial cells and have factors to regulate their production and growth 30 Erythropoietin (EPO) - a growth factor that stimulates the erythroid precursors  Hormone produced primarily by kidney  Critical in RBC growth and differentiation  EPO test can be ordered; low EPO (anemia or kidney disease/dysfunction); high EPO (secondary polycythemia)  EPO stimulating drugs (such as Epoetin, Procrit, etc.) can be given as therapy See Harmening p. 34, Table 1-16 (Progenitor cells) 31  Harmening p. 36 Note: stem cell EPO = erythropoietin a growth factor that stimulates the erythroid precursors Source: Harmening Figure 1-62 Regulation of hematopoiesis by cytokines. BFU-E = burst-forming unit-erythroid; CFU-Bas = colony- forming unit-basophil; CFU-E = colony-forming unit-erythroid; CFU-Eo = colony-forming unit-eosinophil; CFU-G = colony-forming unit-granulocyte; CFU-GEMM = colony-forming unit-granulocyte, erythroid, monocyte macrophage, megakaryocyte; CFU-M = colony-forming unit-monocyte; CFU-Meg = colony-forming unit-megakaryocyte; EPO = erythropoietin; G-CSF = granulocyte colony- stimulating factor; M-CSF = monocyte-colony-stimulating factor.  Harmening p. 34 Hematopoietic Progenitor Cells - stem cells These cells develop into morphologically recognizable cell lines with distinctive features Committed cells that develop into a single cell line 33  Harmening p. 43 Hematopoietic Tissue Cells have their own “territory” in the bone marrow Intramedullary hematopoiesis – Production within the bone marrow Developing cell lines in hemopoietic cords of the BM cross over the walls of the sinuses (vascular spaces) & enter the blood via sinusoids A layer of endothelium lines these sinusoids Cells moves across theses walls & enter Source: Harmening, fig. 2-1, p. 43 blood via sinusoids Granulocytes begin here and then move closer to sinusoid Platelets directly released into sinusoidal blood 34 Internal Structure of Bone Marrow RBC’s in clusters, often around iron laden macrophages 35 General Cellular Characteristics to Consider as Cells Mature (Summary Slide, ahead): Overall Cell Size  WBCs + RBCs + PLTs all decrease ( ) in size as the cells mature  The EXCEPTION are megakaryocytes (aka. Immature platelet precursor)  Megakaryocytes get bigger and bigger until they burst open with platelets! Nuclear : Cytoplasmic Ratio  Definition: The amount of space occupied by the nucleus of a cell in relationship to the space occupied by the cytoplasm of that cell  The size of the nucleus generally decreases as the cell matures ( )  The nucleus gets smaller and smaller, while the cytoplasm becomes larger and larger as cells mature 36 37 General Cellular Characteristics to Consider as Cells Mature (see Summary Slide ahead): Nuclear Characteristics  Chromatin patterns - in general, the overall pattern progresses from a loose-looking arrangement to a more clumped pattern as the cell matures. Some terms used to describe various patterns include: smooth or homogeneous, fine, delicate, lacy or thready, smudged, clumped, or pyknotic (dense or compact). Usually, the chromatin is dense and clumped with distinct lighter areas of parachromatin.  nuclear shape - round or oval usually in young cells; as they mature, nuclear shapes become very distinctive for particular cell types  presence of nucleoli - present in earliest cell stages (blast). As cell matures, nucleoli are usually not visible. These changes in the appearance of nucleoli are related to the rate of synthesis of ribosomal RNA. The number of nucleoli varies depending on cell type. The part of the nucleus that contains nucleoli is called euchromatin. 38 The chromatin is dense and clumped with distinct lighter areas of parachromatin. Nucleoli With hematologic stains, nucleoli may appear as pale spots in a darker nuclear background 40 Chromatin Early stage chromatin – The content of the nucleus is fine, delicate As blood cells mature, chromatin becomes clumped, resulting in a distinctive dark pattern see solid black arrows of this basophilic erythroblast 41 Pyknosis Definition: Extreme condensation of nucleus 42 Cytoplasmic Characteristics, as Cells Mature  Staining color and intensity decreases (e.g. basophilia decreases)  Granulation - if present it varies in size (fine to coarse), in color, in amount per cell. Blasts do not have granules. Those cells that develop them go from no granules to non-specific granulation to specific granulation  Cytoplasmic shape (or outline)  Quantity of cytoplasm - may increase with age  Vacuolization - may normally be found in monocytes; abnormally - serious infection, old cells, as artifacts in stored blood  Inclusion bodies - may aid in cell identification, can indicate specific diseases, some require special staining techniques 43 Summary General Changes During Cell Maturation*- Summary Size Becomes smaller N:C ratio Becomes smaller Cytoplasm Less basophilic due to loss of RNA. Granulocytes produce granules. Erythrocytes produce hemoglobin (pink color) Nucleus Becomes smaller. Nuclear chromatin condenses. Nucleoli disappear. In granulocytic series, nucleus indents, then segments. In erythrocytic series, nucleus is extruded. * Note: exceptions Plasma cells - increased RNA and protein synthesis produces a deep basophilia Megakaryocytes - they grow larger as cytoplasm accumulates (will study this line next semester) 44  Blood Cells Site of Cell Production Primary Function Life Span Bone Erythrocytes Oxygen transport 120 days marrow Granulocytes Bone Defense against Variable; marrow bacterial infection 9-10days B-Lymphs Lymphocytes Lymphoid Cellular and humoral 1-5 days tissue immunity T-Lymphs 60-530 days Bone Platelets marrow Coagulation/hemostasis 7-10 days 45 Erythropoiesi s  The term erythropoiesis identifies the Erythropoiesi entire process by which erythrocytes are produced in the bone marrow s  Harmening p. 11 Erythropoiesis (cont’d)  In response to erythropoietin (EPO), a growth factor that stimulates the erythroid precursors, erythropoiesis occurs in the central sinus beds of medullary marrow over a period of about 5 days through at least three successive reduction-divisions from pronormoblast to basophilic normoblast to polychromatophilic normoblast, and finally to orthochromatic normoblast.  Harmening p. 11 Erythropoiesis (cont’d)  With successive developmental stages the following changes occur: reduction in cell volume, condensation of chromatin, decrease in N:C ratio, loss of nucleoli, decrease in ribonucleic acid (RNA) in the cytoplasm, decrease in mitochondria, and gradual increase in synthesis of hemoglobin (see p 11).  You will need to memorize the following developmental stages from immature to mature erythrocyte:  pronormoblast (rubriblast) to basophilic normoblast (prorubricyte) to polychromatophilic normoblast (rubricyte) to orthochromatic normoblast (metarubricyte)  The nucleus of the orthochromatic normoblast is eventually extruded, leaving a non-nucleated polychromatophilic (diffusely basophilic) erythrocyte (reticulocyte), which is released into the circulating blood to mature in 1 to 2 days  Progressive cellular divisions of one pronormoblast results in production of 14 to 16 erythrocytes Dietary Requirements for RBC Maturation  protein (source of amino acids)  iron  Vitamin B12  Folic acid  Vitamins B6, B12  trace metals (e.g. cobalt, copper, zinc) NOTE: The more common abnormalities of erythropoiesis arise due to a lack of any one or more of these factors. 51  Harmening p.  List the proper cell 11 maturation sequence of the erythroid series  Know names/terminology Source: Harmening Fig 1-18 p. 11  Harmening p. 15 Source: Harmening p. 15  Harmening p. 11 Pronormoblast (Rubriblast, Proerythroblast)  Pronormoblast:  Earliest recognizable cell of the erythrocytic series  Has a round, primitive nucleus with visible nucleoli and chromatin strands that are distinct and dispersed. There is no evidence of clumped chromatin  The nucleus stains reddish-blue with Wright's stain.  The cytoplasm stains a deep blue (royal blue) owing to the presence of RNA  The nuclear-to-cytoplasmic (N:C) ratio in a pronormoblast is 8:1 to 6:1  Note these cells in the slides ahead     Harmening p. 11 Pronormoblast (Rubriblast, Proerythroblast)  Pronormoblasts  Range in size between 14 and 24 µm  Usually slightly larger than a myeloblast and has more cytoplasm, which stains a deeper blue  Constitute ~1.5% or less of the cells observed in normal bone marrow  Pronormoblasts usually divide within 12 hours to make “daughter cells” (aka. basophilic normoblasts)  Harmening p. 12 Recognize the two prononoblasts below: Source: Harmening Fig. 1-19a p. 12 Harmening Figure 1-19 A. Two pronormoblasts (note the perinuclear halo) B. Two polychromatophilic normoblasts C. Neutrophilic band D. Segmented neutrophil E. Smudge cell  Harmening p. 12 Recognize the pronormoblast below: Harmening Figure 1-20 A. Pronormoblast – may have a round to slightly oval shaped nucleus B. Orthochromatic normoblast C. Two polychromatophilic normoblasts  Harmening p. 12 Harmening Figure 1-22 center: pronormoblast lower center: lymphocyte  Harmening p. 13 Source: Harmening Fig. 1-23 p. 13 Harmening Figure 1-23 A. Pronormoblasts B. Neutrophilic myelocyte C. Neutrophilic metamyelocyte D. Segmented neutrophil  Flash Card Pronormoblast Side 1 Rubriblast List some characteristics ________________________ ________________________ ________________________ ________________________ ________________________  Flash Card Pronormoblast Side 2 Rubriblast Earliest morphologically recognizable RBC precursor. 14-24 microns. 8:1-6:1 N:C ratio. Small-to-moderate amount of deep blue cytoplasm; pale area next to nucleus may be seen (referred to as perinuclear halo). 1-3 nucleoli possibly; reddish purple nucleus: homogeneous lacy chromatin. 0-1.5% in BM  Harmening p. 11- 12 Basophilic Normoblast (Prorubricyte, Basophilic Erythroblast)  Basophilic normoblasts, the daughter cells of pronormoblasts,  Require about 20 hours to develop  In normal bone marrow, there are about four times (4x) as many basophilic normoblasts as pronormoblasts  The basophilic normoblast is differentiated from the pronormoblast by the coarsening of the chromatin pattern and the nucleoli, which are ill defined or not visible under light microscopy.  Harmening p. 11- 12 Basophilic Normoblast (Prorubricyte, Basophilic Erythroblast)  As the basophilic normoblast matures, it accumulates more RNA and hemoglobin  The predominant color of the cytoplasm is blue due to the staining of RNA, but there may be a pinkish tinge reflecting the presence of varying amounts of hemoglobin.  The N:C ratio in the basophilic normoblast is 6:1 to 4:1.  A basophilic normoblast is somewhat smaller than a pronormoblast with a size of 12 to 17 µm.  Normal bone marrow contains 1% to 5% basophilic normoblasts.  The division of the basophilic normoblasts forms polychromatophilic normoblasts, which are smaller than basophilic normoblasts but have twice the amount of hemoglobin.  Harmening p. 13 Recognize the basophilic normoblasts below: Source: Harmening Fig. 1-24 p. 13 Harmening Figure 1-24 Basophilic normoblasts.  Harmening p. 14 Source: Harmening Fig. 1-26 p. 14 Harmening Figure 1-26 Left: Basophilic normoblast; center: plasmacyte.  Flash Card Basophilic Normoblast Side 1 Prorubricyte List some characteristics ________________________ ________________________ ________________________ ________________________ ________________________  Flash Card Basophilic Normoblast Side 2 Prorubricyte 2nd stage; 12-17 microns. 6:1-4:1 N:C ratio. Deep blue-purple cytoplasm with occasional small patches of pink. Irregular cell boarders and perinuclear halo may be present. Nucleus has indistinct nucleoli with coarsening chromatin that is deep purplish-blue.  Harmening p. 12 Polychromatophilic Normoblast (Rubricyte, Polychromatophilic Erythroblast)  Polychromatophilic normoblasts are smaller than basophilic normoblasts (10 to 15 µm), having relatively more cytoplasm and a smaller nucleus than basophilic normoblasts.  Nuclear chromatin is thicken and irregularly condensed, light- staining parachromatin areas are visible among the dark blue- staining irregular pyknotic masses. Nucleoli are no longer visible.  The cytoplasm contains a varying mixture of pink due to hemoglobin and blue due to RNA; in the late polychromatophilic normoblast, the pinkish color is usually predominant.  Maturation time in the bone marrow is about 30 hours  Not normally present in the peripheral blood of adults (but may appear in small numbers in the PB of normal newborns)  Harmening p. 14 Recognize the polychromatic normoblasts below: Source: Harmening Fig. 1-28 p. 14 Harmening Figure 1-28 Polychromatophilic normoblasts: early and late stages.  Harmening p. 14 Source: Harmening Fig. 1-29 p. 14 Harmening Figure 1-29 A. Polychromatophilic normoblasts. B. Lymphocyte. C. Segmented neutrophil.  Flash Card Polychromatophilic Normoblast Side 1 Rubricyte List some characteristics ________________________ ________________________ ________________________ ________________________ ________________________  Flash Card Polychromatophilic Normoblast Side 2 Rubricyte Nucleus: low N:C ratio due to condensation of nuclear chromatin (increased clumped chromatin) Cytoplasm: less basophilic than earlier stages; described as blue-pink (or light purple)  Harmening p. 13 Orthochromatic Normoblast (Metarubricyte, Orthochromatic Erythroblast)  Orthochromatic normoblasts are formed from polychromatophilic normoblasts and are recognized by the solid, blue-black, degenerated (pyknotic) nucleus with a nonlinear clumped chromatin pattern  The cytoplasm is predominantly pink (or reddish) because of increasing hemoglobin synthesis, but there may remain minimal amounts of blue cytoplasm due to the presence of RNA.  Harmening p. 13 Orthochromatic Normoblast (Metarubricyte, Orthochromatic Erythroblast)  The nucleus is called pyknotic because there is no parachromatin (white areas) present. The orthochromatic normoblast nucleus is incapable of further DNA synthesis, and therefore, cannot divide.  The degenerated nucleus of the orthochromatic normoblast is destined to be extruded and will be phagocytized.  The N:C ratio in an orthochromatic normoblast is 1:1 to 1:2.  Harmening p. 13 Orthochromatic Normoblast (Metarubricyte, Orthochromatic Erythroblast)  The maturation time for the orthochromatic normoblast is 48 hours.  The number of orthochromatic normoblasts in normal bone marrow varies between 5% and 10%  Orthochromatic normoblasts are not observed in the normal peripheral blood of adults, but they can be found in the blood of normal newborn infants.  The orthochromatic normoblast is the smallest of the nucleated erythrocyte precursors (8 to 12 µm).  Harmening p. 14 Source: Harmening Fig. 1-27 p. 14 Harmening Figure 1-27 Center: Basophilic normoblast; right: Orthochromatic normoblast.  Flash Card Orthochromic Normoblast Side 1 Metarubricyte List some characteristics ________________________________ ________________________________ ________________________________ ________________________________ ________________________________  Flash Card Orthochromic Normoblast Side 2 Metarubricyte 4th stage Size: 10-15um. Nucleus: pyknotic, eccentric Cytoplasm: full complement of Hb N:C: 1:1-1:2 ratio  Reticulocyte (Diffusely Basophilic Erythrocyte, Polychromatophilic Erythrocyte)  The condensed, pyknotic nucleus of an orthochromatic normoblast is extruded, leaving a diffusely basophilic or polychromatophilic cell. The membrane of the erythrocyte seals itself.  Some of the bluish-staining color remains because of the presence of RNA. The erythrocyte contains approximately two-thirds of its total hemoglobin content by the time the nucleus is lost. The RNA content soon begins to decrease.  Referred to as “retic” or “reticulocyte”  Flash Card Reticulocyte Side 2 Young/immature RBC Normally 1-2% of circulating blood No nucleus -Maturation into RBC in ~1 day Absolute Count: per cell field, Corrected: takes into account whether anemic or not The polychromatophilic stage of erythrocyte that still contains ribosomal material which can be identified by new methylene blue stain which forms an artifact of network or reticulum within the cytoplasm.  Flash Card Reticulocyte Side 1 List some characteristics _______________________________ ______________________________ ______________________________ ______________________________ ______________________________ Erythrocyte (Red Blood Cell)  A mature erythrocyte is not able to synthesize hemoglobin, because it is without a nucleus, mitochondria, or ribosomes, but it has a unique, yet limited, metabolism to sustain itself while traversing the microvasculature.  The erythrocyte carries oxygen from the lungs to the tissues where it is exchanged for carbon dioxide.  Erythrocytes are pliable or flexible and deformable, making them capable of unusual changes in shape that are necessary for the passage through the microcirculation to transport oxygen.  Harmening p. 16 Recall: Reticulocyte (Diffusely Basophilic Erythrocyte, Polychromatophilic Erythrocyte) and supravital stain Source: Harmening Fig. 1-30 p. 16 Harmening Figure 1-30 Reticulocytes. New methylene blue stain of peripheral blood. Note reticulocytes with varying amounts of stained reticulum (RNA). Reticulocytosis is associated with increased erythropoietic activity reflected by polychromasia on the Wright's stain of the peripheral blood.  Harmening p. 15  Begin to recognize each cell in the erythrocytic series  Name the characteristics of each red cell in the erythrocytic series  At this point, know the characteristics/morphology of the following MATURE white blood cells:  (Segmented) Neutrophil The following objectives relate  (Band) Neutrophil to white blood cells – We will  Eosinophil cover this next semester!   Basophil  Lymphocyte  Monocyte.  2.6 : List the proper cell sequence for myelopoiesis (granulocytopoiesis) We’ll look at these during our next lecture as well as in-lab. SOME SUMMARY POINTS ▪ Blood is composed of 55% plasma, the liquid portion, and 45% cells, the formed elements (RBCs, WBCs, and platelets). ▪ The average blood volume in an adult is 4 to 6 L. ▪ Plasma contains mainly water (91.5%), proteins (7%), other solutes (1.5%). ▪ The plasma proteins are albumin, globulin, and fibrinogen. ▪ Erythrocyte morphology is evaluated in the “body” area of every stained smear where red blood cells are evenly distributed, do not overlap, yet are close together. ▪ Blood smears should be well made and well stained in order to properly differentiate leukocytes, platelets, and erythrocytes SOME SUMMARY POINTS ▪ Hematopoiesis is defined as the dynamic processes of production and development of the various blood and marrow cells. ▪ Hematopoiesis begins in the yolk sac and, after 2 months, migrates to the liver and spleen, where it remains until the seventh month, before finally shifting to the bone marrow, which becomes the major site of blood cell development in the fetus and after birth. ▪ Erythropoiesis identifies the entire process by which erythrocytes are produced in the marrow and develop from pronormoblasts (rubriblasts) to diffusely basophilic cells and finally into a mature erythrocyte. ▪ A pronormoblast (rubriblast) differs little from a myeloblast: both have a round primitive nucleus, visible nucleoli, and chromatin strands that are distinct and dispersed; however, the pronormoblasts (rubriblast) is slightly larger than a myeloblast and has more cytoplasm, which stains a deeper blue. ▪ An orthrochromic normoblast (metarubricyte) is recognized by the solid, blue-black, degenerated nucleus with nonlinear clumped chromatin and cytoplasm that is predominately pinkish because of increasing hemoglobin synthesis; however, there may remain a minimal amount of bluish cytoplasm due to RNA.  SOME SUMMARY POINTS ▪ Normal neutrophil segmented cells contain from two to five lobes (usually three) connected by a threadlike filament(s); Segmented neutrophils constitute 50% to 70% of total leukocytes in an adult. ▪ Normal neutrophil band cells have a horseshoe-shaped nucleus without evidence of a filament; Band neutrophils make up only 2% to 6% of the leukocytes in an adult. ▪ Normal eosinophil granules are large, round, and stain orange to reddish-orange; Eosinophils are found in 0 to 4% of leukocytes in an adult. * Normal basophil granules are large, round, and stain dark blue to purple; Basophils are found in 0 to 2% of the leukocytes in an adult. ▪ The majority of lymphocytes on an adult blood smear are small, have a relatively round nucleus with clumped chromatin and a small amount of pale blue cytoplasm; Lymphocytes comprise 20% to 44% the leukocytes in an adult. ▪ A monocyte is larger than the mature neutrophil; has abundant gray blue cytoplasm with fine, reddish or purplish, evenly distributed granules; and has a nucleus with folds or brain-like convolutions, and lacy, often delicate, chromatin. Monocytes comprise 2% to 9% of the leukocytes in an adult. LAB THIS WEEK:  Safety in the Clinical Laboratory  “The Great Chocolate Pudding Self-Assessment”  My Additional Notes Harmening Chapter 1 My Additional Notes Harmening Chapter 1