SUCCESS! In Clinical Laboratory Science: Hematology- Hematopoiesis

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A.Liver A. The liver of the fetus assumes responsibility for hematopoiesis about the second month of gestation. From 3 to 6 months of fetal development, the spleen, thymus, and lymph nodes are also involved, but the principal site of hematopoiesis remains the liver. By the seventh gestational month, the bone marrow becomes the primary hematopoietic site. Around birth, the liver and spleen have ceased hematopoiesis (except for splenic lymphopoiesis) but maintain the potential for reactivation of hematopoiesis.

In the third month of gestation, what is the primary site of hematopoiesis? A.Liver B. Marrow of long bones C. Spleen D. Yolk sac

C. Megakaryocytes C. The mature megakaryocyte, the largest hematopoietic cell in normal bone marrow, has a multilobed nucleus and abundant, granular cytoplasm. Plasma cells are characterized by a round, eccentric nucleus and intensely blue cytoplasm. Osteoblasts and osteoclasts are nonhematopoietic cells that may be present in normal bone marrow. Osteoblasts are cells involved in bone formation that resemble plasma cells but are larger and often found in groups. Osteoclasts reabsorb bone and are similar to megakaryocytes in size but are multinucleated.

The largest hematopoietic cells in normal bone marrow are A. Osteoblasts B. Osteoclasts C. Megakaryocytes D. Plasma cells

D. Thymus and bone marrow D. The marrow-derived common lymphoid progenitor cell ultimately gives rise to lymphocytes of T, B, or NK (presumably) cell lineages. Antigenindependent lymphopoiesis occurs in primary lymphoid tissue located in the thymus and bone marrow. The formation of immunocompetent T and B cells from precursor cells is influenced by environment (thymus, bone marrow) and several interleukins. Antigen dependent lymphopoiesis occurs in secondary lymphoid tissue (spleen, lymph nodes, Peyer's patches of the gastrointestinal tract) and begins with antigenic stimulation of immunocompetent cells

Antigen-independent lymphopoiesis occurs in primary lymphoid tissue located in the A. Liver and kidney B. Spleen and lymph nodes C. Peyer's patches and spleen D. Thymus and bone marrow

B. Nucleus to cytoplasm ratio (N:C) decreases B. The nucleus-to-cytoplasm ratio decreases as blood cell lines mature. With maturation, cells generally become smaller, the nuclear chromatin becomes clumpy and condensed, nucleoli disappear, and the cytoplasm loses its deep blue basophilia when stained with Wright's stain. Exceptions include megakaryocytes (because of endomitosis they grow larger as cytoplasm accumulates) and plasma cells (increased RNA and protein synthesis produces a deep basophilia).

As most blood cell lines mature, which of the following is characteristic? A. Cell diameter increases B. Nucleus to cytoplasm ratio (N:C) decreases C. Nuclear chromatin becomes less condensed D. Basophilia of the cytoplasm increases

B. Hematopoietic tissue to adipose tissue B. Bone marrow cellularity in the normal adult is approximately 50% hematopoietic tissue and 50% adipose tissue (fat), with a range of 30- 70% cellularity being normocellular. Marrow cellularity is usually estimated from the core biopsy. An intact bone marrow can respond to demand by increasing its activity several times the normal rate if sufficient supplies and growth factors are available. The marrow becomes hypercellular when inactive fatty tissue is replaced by active hematopoietic marrow. In contrast, bone marrow failure may result in hypocellularity or aplasia with increased fat and a reduced number of hematopoietic cells.

Bone marrow cellularity refers to the ratio of A. Red cell precursors to white cell precursors B. Hematopoietic tissue to adipose tissue C. Granulocytic cells to erythrocytic cells D. Extravascular tissue to intravascular tissue

B. Apoptosis B. Apoptosis is physiological cell death that can be induced by deprivation of growth factors or prevented by growth-promoting cytokines. Apoptosis plays an important role in the regulation of cell number and is deregulated in certain malignancies. Necrosis is accidental cell death by phagocytic cells and is associated with lethal physical damage. Cellular senescence describes cells that have lived their life span and will die of old age. Terminal differentiation refers to mature end-stage cells that are no longer capable of replication

Programmed cell death is called A. Necrosis B. Apoptosis C. Cellular senescence D. Terminal differentiation

A. Cords A. Bone marrow consists of vessels, nerves, hematopoietic cells at various levels of maturation, and stromal cells encased in a membrane lining called the endosteum. The vascular system empties into a system of sinuses (venous sinusoids). A layer of endothelium lines these sinusoids. Blood cell formation occurs in hematopoietic cords located outside of the sinusoids and between the trabeculae of spongy bone. The bone marrow stroma (macrophages, adipocytes, fibroblasts, endothelial cells) forms an optimal microenvironment for developing cells by providing support and secreting cytokines. Mature differentiated cells can deform to penetrate the vessel wall and enter the sinuses and blood circulation.

In what area of the bone marrow does hematopoiesis take place? A. Cords B. Endosteum C. Endothelium D. Sinuses

C. Monocytes and T lymphocytes C. Interleukins and colony stimulating factors are cytokines produced by a variety of cells, including monocytes/macrophages, T lymphocytes, fibroblasts, and endothelial cells. It is essential that cytokines are continuously supplied by cells present in the bone marrow microenvironment during hematopoietic cell development, or cells will die. Erythropoietin functions as a true hormone because it is produced by the kidney, released into the blood, and carried to the bone marrow, where it stimulates red cell production.

Interleukins and colony stimulating factors are cytokines produced by A. B lymphocytes and erythrocytes B. Erythrocytes and thrombocytes C. Monocytes and T lymphocytes D. Neutrophils and monocytes

B. Kidney B. Erythropoietin (EPO) is a hormone that stimulates red cell production in the bone marrow by its action on the committed RBC progenitor cells. To maintain optimal erythrocyte mass for tissue oxygenation, the body's mechanism for sensing tissue oxygen levels is located in the kidney. Erythropoietin production increases when hypoxia is detected by renal oxygen sensors, with 90% being synthesized in the kidney and 10% in the liver. EPO levels in the blood vary according to the oxygen carrying capacity of the blood (e.g., EPO levels rise in anemia and fall when tissue oxygen levels return to normal).

The mechanism that relays information about tissue oxygen levels to erythropoietin-producing sites is located in the A. Brain B. Kidney C. Liver D. Spleen

A. Granulocytic, erythrocytic, monocytic, or megakaryocytic lineages A. The pluripotent hematopoietic stem cell gives rise to lymphoid and myeloid progenitor cells. The lymphoid progenitor produces cells destined to become lymphocytic cells, whereas the myeloid progenitor cell produces progenitors committed to differentiation into granulocytic, erythrocytic, monocytic, or megakaryocytic lineages with appropriate stimulus. The cells produced by progenitor cells can be demonstrated using in vitro culture techniques; thus, the myeloid progenitor cell is termed CPU (colony forming unit)-GEMM based on the cell colonies formed.

The myeloid progenitor cell can produce cells committed to A. Granulocytic, erythrocytic, monocytic, or megakaryocytic lineages B. Granulocytic, monocytic, lymphocytic, or megakaryocytic lineages C. Erythrocytic, granulocytic, monocytic, or lymphocytic lineages D. Erythrocytic, granulocytic, lymphocytic, or megakaryocytic lineages

C. 6L C. In a normal adult, the total blood volume is approximately 12 pints or 6 liters. Cells account for about 45% (44% is red cell mass) and plasma accounts for 55%. Alterations in red cell mass or plasma volume are reflected in the RBC count and in measurements of hemoglobin and hematocrit. True anemia or polycythemia is due to a decrease or increase in total RBC mass, respectively. A reduction in plasma volume with a normal RBC mass may cause relative (pseudo) polycythemia. Conversely, an increase in plasma volume with normal RBC mass may cause relative (pseudo) anemia.

What is the approximate total blood volume in an adult? A. 1L B. 2L C. 6L D. 12L

A. Erythrocyte A. The need for oxygen delivery to developing tissues results in the production of erythrocytes before other blood cells. Erythropoiesis commences in the yolk sac as early as the fourteenth day of embryonic development. These primitive red cells produce embryonic hemoglobins that temporarily serve oxygen needs of the fetus. Myelopoietic and lymphopoietic activities begin when the liver and spleen become sites of production at 6-9 weeks of gestation; however, erythropoiesis still predominates. At this time, the red cells produce hemoglobin F, which is the chief oxygen carrier during fetal life.

What is the first type of cell produced by the developing embryo? A. Erythrocyte B. Granulocyte C. Lymphocyte D. Thrombocyte

C. 4:1 C. The ratio between all granulocytes and their precursors and all nucleated red cell precursors represents the myeloid-to erythroid ratio. Myeloid precursors outnumber erythroid precursors by about 3 or 4 to 1 in the normal bone marrow. Although there are many more red blood cells in the peripheral blood than granulocytes, red blood cells have a much longer life span in circulation (120 days) as compared to granulocytes (about 8 hours). Granulocytes, therefore, require a more continual production than erythrocytes and are the most numerous marrow precursors. Alterations in the M:E ratio, such as 1:1 or 8:1, may indicate erythroid hyperplasia or granulocytic hyperplasia, respectively.

What is the normal ratio of myeloid to erythroid precursors in bone marrow (M:E ratio)? A. 1:1 B. 1:3 C. 4:1 D. 8:1

C. 50% C. In the infant, there is an increased demand for blood formation because of the rate of growth. At birth, all bone marrow cavities are filled with hematopoietic tissue (active red marrow). As the growth rate slows, there is less need for active marrow. Fatty infiltration of the marrow becomes noticeable at about 4 years of age as cell production diminishes within the shafts of the long bones and is filled with yellow inactive tissue. Fat comprises 50% of the total marrow space in the adult. Except for lymphopoiesis, hematopoiesis is confined to the flat bones and pelvic area by the age of 25 years.

What percentage of tissue located in the bone marrow cavities of adults is fat? A. 10% B. 25% C. 50% D. 75%

D. Posterior iliac crest, sternum D. Unlike the infant, in which all bone marrow is capable of forming blood cells, the active marrow in an adult is confined to the flat bones of the skeleton such as the sternum and posterior iliac crest. Although the spinous processes of the vertebrae contain active marrow, these sites are rarely used for aspiration in adults because of the danger of damage to the spinal cord. Sternal puncture also presents a possibility of serious damage to underlying structures, but this site may be used because of easy accessibility or if the aspirate is a "dry tap" in the iliac crest. To obtain both a bone marrow aspirate and core biopsy, most marrow specimens are taken from the posterior iliac crest. The anterior iliac crest may occasionally be used in adults and sometimes the tibia in children less than 2 years of age

4. In an adult, what are the two best areas for obtaining active bone marrow by aspiration? A. Vertebra, tibia B. Sternum, vertebra C. Anterior iliac crest, tibia D. Posterior iliac crest, sternum

D. The presence of 10% myeloblasts on the cell differential count D. In normal adult marrow, about 50% is fat, 40% is myeloid (granulocytic) cells, and 10% is erythroid cells. The M:E ratio is determined by performing a differential count of marrow precursor cells. The presence of 10% myeloblasts is an abnormal finding (reference range 0-2%), and a hematologic disease is likely. Megakaryocytes should be seen when scanning and are usually reported as normal, increased, or decreased in number. Marrow iron is assessed with Perl's Prussian blue stain, and it is normal to see stainable iron in macrophages, as well as iron granules in the cytoplasm of developing red cell precursors

When evaluating a bone marrow aspirate smear, which finding is considered abnormal? A. A predominance of granulocyte precursors as compared to nucleated red cells B. Detection of stainable iron in macrophages and erythroid precursors with Prussian blue C. An average of three megakaryocytes seen per low power (10X) field D. The presence of 10% myeloblasts on the cell differential count

B. Myeloid metaplasia or extramedullary B. Hematopoiesis within the medulla or inner part of the bone marrow is termed medullary or myeloid. Hematopoiesis that occurs in the liver and spleen (reactivation of fetal life) is called extramedullary or myeloid metaplasia (organs may enlarge). Cell production outside of the marrow space takes place when the bone marrow is unable to meet its production demands. This may occur in severe hemolytic anemias when the maximal capacity of the bone marrow to increase activity is exceeded. Myeloid metaplasia may also be an extension of a disease process such as myelofibrosis. Myelophthisis refers to the replacement of normal marrow hematopoietic tissue by fibrotic tissue or cancer cells, whereas myelodysplasia describes abnormal maturation of erythrocytic, granulocytic, and/or megakaryocytic cell lines. The period of intrauterine life when cell production occurs in the yolk sac may be termed mesoblastic.

When the hepatic phase of fetal life is reactivated in an adult, hematopoiesis can be termed A. Myeloid or medullary B. Myeloid metaplasia or extramedullary C. Myelophthisis or myelodysplasia D. Mesoblastic or mesenchymal

C. Hormone produced by the liver that stimulates megakaryopoiesis C. Thrombopoietin (TPO) is the major regulator of platelet production in the bone marrow by its action on committed progenitor and precursor cells of the megakaryocytic line. It is primarily produced by hepatocytes and possibly by the kidney. After marrow release, about 70% of platelets are in the blood circulation and 30% are sequestered in the spleen. Unlike erythropoietin, which is manufactured for routine therapeutic use, recombinant TPO is still being evaluated.

Which of the following describes thrombopoietin (TPO)? A. Renal hormone that regulates marrow red cell production B. Marrow hormone secreted by developing megakaryoblasts C. Hormone produced by the liver that stimulates megakaryopoiesis D. Pituitary hormone that controls platelet sequestration by the spleen

B. Action of majority is lineage restricted B. A diverse group of growth factors (cytokines) regulate and maintain hematopoiesis in a steady state. Most hematopoietic growth factors are not lineage restricted but can act on more than one cell type and have multiple functions. For example, interleukins (IL-3) and colony stimulating factors (GM-CSF) affect multiple cell lines; whereas erythropoietin action is limited to erythroid cells. Cytokines are glycoproteins that usually express activity by binding to specific receptors on target cells. The action of growth factors on hematopoietic progenitor and precursor cells can stimulate or inhibit cell proliferation and differentiation as well as promote or suppress cell death. Growth factors may act alone or together to exert a positive or negative influence on hematopoiesis as well as on the function of mature cells. A determining factor for controlling the rate of cell production is cytokine stimulation in response to physiologic need.

Which of the following does not accurately describe hematopoietic growth factors? A. Bind to target cell receptors to express activity B. Action of majority is lineage restricted C. May promote or suppress cell death D. Can stimulate or inhibit cell proliferation

C. Express the stem cell marker CD 13 C. Hematopoietic stem cells can make copies of themselves to maintain the stem cell pool and possess the ability to generate cells of all lineages (pluripotential). These stem cells give rise to multipotential myeloid and lymphoid progenitor cells, which ultimately produce progenitor cells that are restricted to a specific cell lineage. With appropriate cytokine stimulus, the committed progenitor cells undergo proliferation to recognizable precursors that produce an amplified number of mature end-stage cells. Stem cells and progenitor cells cannot be morphologically distinguished (look similar to small lymphocytes) but can be identified phenotypically by markers such as the stem cell marker CD34. CD34 expression is lost as antigens for a specific cell lineage are expressed. CD 13 is a marker expressed by myeloid precursors.

Which of the following is not characteristic of pluripotent hematopoietic stem cells? A. Possess self-renewal ability B. Produce progenitor cells committed to a single cell lineage C. Express the stem cell marker CD 13 D. Are morphologically unrecognizable


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