RBC Exam Questions With 100% Correct Answers 2023, Exams of Banking and Finance

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RBC Exam Questions With 100% Correct

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What is the first type of cell produced by the developing embryo? A. Erythrocyte B. Granulocyte C. Lymphocyte D. Thrombocyte - Correct Answer-A. Erythrocyte 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 beginw ehn 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 percentage of tissue located in the bone marrow cavities of adults is fat? A. 10% B. 25% C. 50% D. 75% - Correct Answer-C. 50% 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. 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 D. Are morphologically unrecognizable - Correct Answer-C. Express the stem cell marker CD 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. CD13 is a marker expressed by myeloid precursors. As an adult, what are the two best areas for obtaining active bone marrow by aspiration? A. Vertebra, tibia B. Sternum, vertebra C. Anteroir iliac crest, tibia D. Posterior iliac crest, sternum - Correct Answer-D. Posterior iliac crest, sternum Unlike the infant, in which all BM 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 may be used because of easy accessibility or if the aspirate is a dry tap in the iliac crest. To obtain both a BM 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. What is the normal ratio of myeloid to erythroid precursors in bone marrow (M:E ratio)? A. 1: B. 1: C. 4: D. 8:1 - Correct Answer-C. 4: The ratio between all granulocytes and their precursors and all nucleated red cell precursors represent the myeloid-to-erythroid ratio. Myeloid precursors outnumber erythroid precursors by about 3 or 4 to 1 in the normal BM. Although there are many more RBCs in the peripheral blood than granulocytes, RBCs 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. Alteration in the M:E ratio such as 1:1 or 8: may indicate erythroid hyperplasia or granulocytic hyperplasia, respectively. 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 - Correct Answer-B. Action of majority is lineage restricted A diverse group of growth factors (cytokines) regulate and maintain hematopoiesis in a steady state. Most are not lineage restricted but can act on more than on cell type and

have multiple functions. 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 physiological need. 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 - Correct Answer-A. Liver The liver of the fetus assumes responsibility for hematopoiesis about the second month of gestation. From 3-6 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 BM 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. 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 - Correct Answer-B. Kidney 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 (EPO levels rise in anemia and fall when tissue oxygen levels return to normal). 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 - Correct Answer-D. Thymus and bone marrow The marrow-derived common lymphoid progenitor cell ultimately gives rise to lymphocytes of T, B, or NK (presumably) cell lineages. Antigen-independent 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 GI tract) and begins with antigenic stimulation of immunocompetent cells. Programmed cell death is called A. Necrosis B. Apoptosis C. Cellular senescence D. Terminal differentiation - Correct Answer-B. Apoptosis 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. In what area of the bone marrow does hematopoiesis take place? A. Cords B. Endosteum C. Endothelium D. Sinuses - Correct Answer-A. Cords The BM 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 BM 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. BM 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 - Correct Answer-B. Hematopoietic tissue to adipose tissue BM cellularity in the normal adult is approximately 50% hematopoietic tissue and 50% adipose tissue with a range of 30-70% cellularity being normocellular. Marrow cellularity is usually estimated from the core biopsy. An intact BM 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, BM failure may result in

hypocellularity or aplasia with increased fat and a reduced number of hematopoietic cells. 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 - Correct Answer-C. Monocytes and T lymphocytes 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 BM 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 carrier to the BM, where it stimulates red cell production. What is the approximate total blood volume in an adult? A. 1L B. 2L C. 6L D. 12L - Correct Answer-C. 6 L In a normal adult, the total blood volume is approximately 12 pints or 6 L. Cells account for about 45% (44% 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. 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, granlocytic, monocytic, or lymphocytic lineages D. Erythocytic, granulocytic, lymphocytic, or megakaryocytic lineages - Correct Answer- A. Granulocytic, erythrocytic, monocytic, or megakaryocytic lineages The pluripotential 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 CFU (colony forming unit)-GEMM based on the cell colonies formed. The largest hematopoietic cells in normal bone marrow are A. Osteoblasts B. Osteoclasts

C. Megakaryocytes D. Plasma cells - Correct Answer-C. Megakaryocytes The mature megakaryocyte is the largest hematopoietic cell in normal BM, has a multilobed nucleus and abundant granular cytoplasm. Plasma cells are characterized by a round, eccentric nucleus and intensely blue cytoplasm. Osteoblasts/clasts are non- hematopoietic cells that may be present in normal BM. Osteoblasts are 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. When evaluating a BM 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 - Correct Answer-D. The presence of 10% myeloblasts on the cell differential count The normal BM has about 50% fat, 40% myeloid, and 10% erythroid cells. The M:E ratio is determined by performing a diff of marrow precursor cells. The presence of 10% myeloblasts is an abnormal finding (ref range 0-2%) and a hematological 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 is normal to see in macrophages as well as iron granules in the cytoplasm of developing red cell precursors. 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 - Correct Answer-B. Nucleus to cytoplasm ratio (N:C) decreases 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. Exception include megakaryocytes (because of endomitosis they grow larger as cytoplasm accumulates) and plasma cells (increased RNA and protein synthesis produces a deep basophilia). 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 - Correct Answer- C. Hormone produced by the liver that stimulates megakaryopoiesis

Thrombopoietin (TPO) is the major regulator of platelet production in the BM by its action on committed progenitor and precursor cells of the megakarocytic 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. 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 - Correct Answer-B. Myeloid metaplasia or extramedullary Hematopoiesis within the medulla or inner part of the BM is termed medullary or myeloid. Hematopoiesis that occurs in the liver and spleen is called extramedullary or myeloid metaplasia. Cell production outside of the marrow space takes place when the BM is unable to meet its production demands. This may occur in severe hemolytic anemias when the maximal capacity of the BM to increase activity is exceeded. Myeloid metaplasia may also be an extension of a disease process such as myelofibrosis. Myelopthisis 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. What is the average life span of a normal RBC? A. 1 day B. 10 days C. 60 days D. 120 days - Correct Answer-D. 120 days Normal RBCs survive about 4 months or 120 days. The entire life span of the red cell is spent inside the vascular tree, making it easier to determine the rate of production/destruction. Red cell survival depends upon an intact RBC membrane, sufficient cellular energy, and normal hemoglobin function. As red cells circulate for 120 days, enzymes are depleted and the ability to deform decreases. Under normal conditions, red cell loss due to aging (~1%) is equal to daily replacement. Most destruction of aged red cells occurs extravascularly by macrophages of the reticuloendothelial system (spleen, liver). The Na+-K+ cation pump is an important mechanism in keeping the red cell intact. Its function is to maintain a high level of A. Intracellular Na+ B. Intracellular K+ C. Plasma Na+ D. Plasma K+ - Correct Answer-B. Intracellular K+

The erythrocyte has a semipermeable membrane that allows water and some anions such as chloride and bicarbonate to enter the cell rapidly. Sodium ions enter the cell and potassium ions leave the cell slowly but continuously. In order to maintain a high intracellular K+ concentration and remove excess Na+, ATP-dependent cationic pumps expel Na+ cations and take in K+. This regulation of intracellular cations allows the red cell to control its volume and water content. Which of the following depicts the struction of the hemoglobin molecule? A. Two heme groups, two globin chains B. Four heme groups, two globin chains C. Two heme groups, four globin chains D. Four heme groups, four globin chains - Correct Answer-D. Four heme groups, four globin chains A molecule of hemoglobin is composed of four globular, protein subunits, and each subunit contains a heme group bound within a convoluted globin chain. Heme groups are identical and consist of protoporphyrin IX with a central iron atom, made largely in the mitochondria. Amino acids are sequenced on ribosomes to produce four types of globin chains (alpha, beta, delta, gamma) that combine in identical pairs. A normal hemoglobin molecule consists of two alpha-globin chains and two non-alpha globin chains, each of which binds to a heme group. The different globin chains determine the hemoglobin type (A, A2, F). Which of the following describes the process known as culling? A. Release of red cells from the bone marrow B. Binding of free hemoglobin by transport proteins C. Incorporation of iron into protoporphyrin IX D. Removal of abnormal red cells by the spleen - Correct Answer-D. Removal of abnormal red cells by the spleen Culling is the process of removing aged or abnormal RBCs from the circulation by the spleen. Red cells (7 um) enter the spleen through the splenic artery and must squeeze back into active circulation through 2-4 um clefts in the venous sinusoids. Aged or abnormally shaped red cells with impaired membrane flexibility are trapped in the splenic microcirculation and ingested by macrophages. The spleen is the largest filter of blood in the body and has an essential role in the quality control of red cells. Hemoglobin forms that are incapable of oxygen transport include A. Deoxyhemoglobin and oxyhemoglobin B. Oxyhemoglobin and carboxyhemoglobin C. Carboxyhemoglobin and methemoglobin D. Methemoglobin and deoxyhemoglobin - Correct Answer-C. Carboxyhemoglobin and methemoglobin Each hemoglobin molecule has four heme groups located at its surface and oxygen binds to the central ferrous iron in heme. Deoxyhemoglobin and oxyhemoglobin are normal physiologic forms of hemoglobin with iron in the ferrous state. Hemoglobin in which the ferrous iron has been oxidized to the ferric state is known as methemoglobin and is unable to carry oxygen. Carboxyhemoglobin is hemoglobin with carbon monoxide

attached to form ferrous iron rather than oxygen. Both methemoglobin and carboxyhemoglobin are reversible. The majority of iron found in an adult is a constituent of A. Ferritin B. Myoglobin C. Hemoglobin D. Peroxidase - Correct Answer-C. Hemoglobin Of the total body iron present in a normal adult, approximately 70% is contained in hemoglobin, 25% is found in storage sites such as ferritin or hemosiderin. A much smaller amount is contained in muscle myoglobin (4%) and respiratory enzymes such as peroxidase (1%). The structures of hemoglobin and myoglobin are similar but myoglobin functions as an oxygen trap in the tissues. A senscent RBC is one that has A. Been hemolyzed B. Lived its life span C. Become deformed D. Lost its mitochondria - Correct Answer-B. Lived its life span A senescent RBC is one that has lived its life span. Repeated passes through the spleen deplete the cells of glucose and decrease their surface area as membrane lipids are lost. The red cells are removed from the circulation by splenic macrophages that recognize subtle abnormalities in these cells, sequester them, and destroy them. What red cell morphologic abnormality is described by the term "poikilocytosis" A. Variations in size B. Deviations from normal shape C. Presence of inclusions D. Alterations in hemoglobin concentration - Correct Answer-B. Deviations from normal shape Poikilocytosis is a general term that refers to deviations from the normal red cell shape. Anisocytosis is the term used when differences in the sizes of the red cells are described. Color in red cells is designated as normochromic or hypochromic. Abnormally shaped red cells and red cell inclusions are associated with rigid red cells that have reduced deformability and shortened survival. Howell-Jolly bodies are composed of A. DNA B. Iron C. Reticulum D. RNA - Correct Answer-A. DNA H-J bodies are nuclear (DNA) remnants that remain in the red cell after the nucleus has been extruded and may represent nuclear instability. These inclusions are associated with the defective nuclear maturation found in megaloblastic anemias and the rapid cell division that occurs in severe hemolytic anemias. Under normal circumstances, the spleen effectively pits these bodies from the cell. Pitting is a process that removes

inclusions while leaving the rest of the red cell intact. It may be that the pitting mechanism is overwhelmed and cannot keep pace with inclusion formation in hemolytic anemias. H-J bodies can also be seen in individuals after splenectomy who lack the normal pitting function. When spherocytes are reported, what is observed on the peripheral blood smear? A. Red cells without a central pallor B. Red cells with blunt projections C. Red cells with sharp projections D. Red cells with intracellular rod-shaped crystals - Correct Answer-A. Red cells without a central pallor Spherocytes appear smaller and more densely staining than normal red cells and lack a central pallor area. Because they are the result of membrane loss, their surface area to volume ratio is decreased. Spherocytes should be distinguished from acanthocytes, which also lack a pallor area but have sharp, irregular projections. Echinocytes have a central pallor area and blunt, short projections. Red cells with intracellular rod/bar- shaped crystals contain hemoglobin C crystals. The red cells found in lead poisoning characteristically exhibit coarse granules composed of _____ that are reported as _____. A. Precipitated hemoglobin; Pappenheimer bodies B. Aggregated ribosomes; basophilic stippling C. Nuclear fragments; Pappenheimer bodies D. Excess iron deposits; basophilic stippling - Correct Answer-B. Aggregated ribosomes; basophilic stippling The presence of lead causes an inhibition of several of the enzymes important in heme synthesis. Among these is pyrimidine 5'-nucleotidase, which is normally responsible for degradation of RNA. The lack of this enzymes apparently allows aggregates of incompletely degraded RNA to remain in the cell cytoplasm. It is this ribosomal material that appears on Wright's stain as punctate basophilic stippling. Precipitated hemoglobin forms Heinz bodies, nuclear fragments are called Howell-Jolly bodies, and iron deposits are Pappenheimer bodies. Rouleaux of RBCs when seen in the monolayer of a blood smear is characteristic of A. Hypersplenism B. Hypogammaglobulinemia C. Cold hemagglutinin disease D. Multiple myeloma - Correct Answer-D. Multiple myeloma The presence of red cell rouleaux is a characteristic finding in multiple myeloma because of the increased concentration of immunoglobulins in the blood plasma. The excessive immunoglobulins are produced by malignant plasma cells. Cold hemagglutinin disease is characterized by red cell agglutination of clumping in a nonspecific pattern. Hypersplenism refers to an enlarged, overactive spleen that destroys both normal and abnormal cells, possibly causing pancytopenia.

Howell-Jolly bodies are most frequently associated with what condition? A. Iron overload state B. Post-transfusion C. Post-splenectomy D. Iron-deficient state - Correct Answer-C. Post-splenectomy During passage through the microvessels of the spleen, the red cell is examined for intracellular inclusions or membrane-bound antibodies, which, if present, are removed. Abnormal red cells circulate longer, and inclusions such as H-J bodies or Pappenheimer bodies will be seen post-splenectomy. The phagocytic removal of abnormal red cells is assumed by the liver, but the liver is not as efficient as the spleen. H-J bodies are not associated with iron deficient or iron overload states. Which of the following statements about iron reabsorption is true? A. Absorption occurs in the ileum B. The mucosal cell always absorbs the correct amount of iron to meet needs C. Absorption increased when erythropoietic activity increases D. Alkaline pH favors absorption - Correct Answer-C. Absorption increases when erythropoietic activity increases One of the reasons for increased intestinal absorption of iron is an accelerated rate of erythropoiesis. Although the mucosal cell does act as a barrier in normal circumstances, this function is not absolute and controls break down in the presence of large amounts of iron, causing an excess to be absorbed. An acid pH is required for iron absorption, and sites of maximal absorption are the duodenum and upper jejunum. The body has no effective means for iron excretion. What term describes a mature red blood cell that contains iron granules or deposits? A. Siderosome B. Sideroblast C. Ringed sideroblast D. Siderocyte - Correct Answer-D. Siderocyte The presence of iron granules or deposits can be detected with Perl's Prussian blue iron stain. Siderocytes are mature RBCs that contain stainable iron granules (abnormal). Sideroblasts are BM nucleated red cells (normoblasts) that contain small amounts of iron in the cytoplasm (normal). Ringed sideroblasts are marrow normoblasts that contain iron in the mitochondria that forms a ring around the nucleus (abnormal). Siderocytes and ringed sideroblasts are associated with iron overload problems, particularly sideroblastic anemia. Reticulocytes may contain small amounts of unused iron that is normally removed by the spleen. Which of the following is associated with a shift to the left in the oxygen dissociation curve of hemoglobin? A. Decreased pH and elevated temperature B. Decreased oxygen affinity C. Decreased oxygen release D. Presence of 2,3-BPG - Correct Answer-C. Decreased oxygen release

A shift to the left means that a higher percentage of hemoglobin will retain more of its oxygen at a given pressure. Thus affinity will be greater and oxygen delivery will be reduced. A higher/more alkaline pH and a lower temperature are associated with decreased oxygen dissociation. With conditions in the lungs (increased pH, decreased 2,3-BPG, decreased temperature), hemoglobin affinity for oxygen is increased, which favors oxygen uptake. With conditions in the tissues (decreased pH, increased 2,3- BPG, increased temperature), hemoglobin affinity for oxygen is decreased, which favors release of oxygen to the tissues. Which of the following statements does not characterize erythropoietin (EPO)? A. Transforms the CFU-E into the earliest recognizable RBC precursor B. Increases the rate of red blood cell production by the bone marrow C. Shortens the maturation time of developing erythroid precursors D. Decreases stimulation of erythropoiesis when cellular hypoxia increases - Correct Answer-D. Decreases stimulation of erythropoiesis when cellular hypoxia increases EPO is a hormone produced by the kidney that increases erythropoiesis in the BM in response to tissue hypoxia. The CFU-E is a committed erythroid progenitor cell with many receptors for EPO. EPO stimulation of the CFU-E produces the recognizable pronormoblast and promotes differentiation of RBC precursors. The maturation time of erythrocyte precursors (5-7 days) can be reduced in times of increased need for red cells by EPO. Which of the following factors will result in an immediate increase in oxygen delivery to the tissues? A. Increased pH B. High altitudes C. Increased hemoglobin binding of 2,3-BPG D. Increased renal release of EPO - Correct Answer-C. Increased hemoglobin binding of 2,3-BPG Increased binding of 2,3-BPG decreases the affinity of hemoglobin for oxygen, which promotes oxygen release to the tissues, a compensatory mechanism in anemic patients. Increased pH enhances oxygen affinity and thus inhibits delivery to the tissues. Less oxygen is available at higher altitudes and this affects blood saturation and delivery to tissues. An increase in EPO release will affect red cell production but does not have an immediate or direct impact on oxygen delivery. Periods of intense EPO activity cause premature release of marrow reticulocytes into the blood. Which of the following is not true of these early reticulocytes? A. Loss of residual RNA occurs immediately upon marrow release B. Circulate longer than usual before reaching maturity C. May be termed shift or stress reticulocytes D. Show diffuse basophilia with Wright's stain - Correct Answer-A. Loss of residual RNA occurs immediately upon marrow release

After the nucleus is extruded, reticulocytes spend about 2 days in the BM before release into the blood, where maturation continues for another day. Intense EPO stimulus can cause early release of BM reticulocytes. These reticulocytes are larger and contain more filamentous reticulum than a more mature reticulocyte. These shift or stress reticulocytes exhibit diffuse basophilia on the Wright's stained smear and will need more than the usual 1 day in circulation to mature (to lose RNA). A very high number of reticulocytes in the blood circulation can increase the MCV. The level of reticulocyte maturity is best assessed by the immature reticulocyte fraction (IRF), an index reported by automated cell counters that is based on RNA content. Which of the following inclusions is only visible with supravital staining? A. Basophilic stippling B. Cabot rings C. Heinz bodies D. Pappenheimer bodies - Correct Answer-C. Heinz bodies Heinz bodies do not stain with Wright's stain and appear as normal hemoglobin even though their presence causes cell rigidity and membrane damage. They can be visualized on wet preps with phase microscopy or by using a supravital stain such as crystal violet or brilliant green. Heinz bodies consist of intracellular globin or hemoglobin precipitate that results from hemoglobin denaturation (G6PD deficiency, unstable hemoglobin variants) or excess globin chains (thalassemia). Basophilic stippling, Cabot rings, and Pappenheimer bodies are visible with both Wright's and supravital stains. The presence of schistocytes on the peripheral blood smear is commonly associated with A. Increased iron mobilization B. Increased red cell destruction C. Decreased EPO activity D. Decreased red cell proliferation - Correct Answer-B. Increased red cell destruction The presence of schistocytes on the smear indicates that red cells have been subjected to some form of physical trauma that causes damage. Red cell fragmentation can be the result of impact with fibrin stands, mechanical trauma by artificial surfaces, injury by heat, partial phagocytosis, or damage by toxins and drugs. Schistocytes are characteristic of the increased RBC destruction that occurs in severe hemolytic anemias but are not associated with anemias that result from defective bone marrow delivery of red cells to the blood. Which of the following may be a sign of accelerated bone marrow erythropoiesis? A. Hypercellular marrow with a decreased number of RBC precursors B. Bone marrow M:E ratio of 6:! C. Nucleated red cells in the peripheral circulation D. Low erythrocyte, hemoglobin and hematocrit levels - Correct Answer-C. Nucleated red cells in the peripheral circulation

Tissue hypoxia associated with low erythrocyte and hemoglbin levels causes increased renal release of EPO to stimulate BM erythropoiesis. Depending on severity, the BM responds by increasing its activity 6-8 times normal and becomes hypercellular because of an increase in RBC precursors (erythroid hyperplasia); and the M:E ratio falls. Nucleated red cells may be released into the blood along with the outpouring of reticulocytes. The number of nucleated red cells tends to correlate with anemia severity. Microcytic, hypochromic red cells are most often associated with impaired A. DNA synthesis B. RNA metabolism C. Hemoglobin synthesis D. Enzyme metabolism - Correct Answer-C. Hemoglobin synthesis Millions of hemoglobin molecules are produced in the red cell cytoplasm during maturation. When developing erythroid cells are deprived of essential hemoglobin components the result is the production of microcytic, hypochromic red cells. It is thought that during maturation, extra cell divisions occur until a certain hemoglobin concentration is reached. Impaired hemoglobin synthesis may be the result of heme defects (involving iron or protoporphyrin) or may be caused by globin defects. Impaired DNA synthesis is associated with macrocytic red cells, and normocytic red cells are characteristic of enzyme defects. What is the production time of erythropoiesis? - Correct Answer-5 days What is the production time of granulopoiesis? - Correct Answer-5-7 days The red cell membrane consists of? - Correct Answer-Membrane is trilaminar. Outer layer - glycolipids, glycoproteins, proteins, carbohydrates Central layer - protein, cholesterol, phosphoplipids Inner - proteins How does the red cell generate ATP? - Correct Answer-Conversion of glucose to lactic acid (glycolysis) because the mature red cell lacks mitochondria. What is the Embden-Meyerhof pathway? - Correct Answer-major anaerobic pathway, red cell produces ATP by breaking down glucose to lactic acid. Regulates cationic pumps. PK deficiency is the most common problem. PK deficiency is a deficiency in what pathway? - Correct Answer-Embden-Meyerhof

What is the Hexose monophosphate shunt? - Correct Answer-Produces NADPH and reduced glutathione. Aerobic pathway in which G6P is catabolized to 6PG by G6PD. Provides defense against oxidative injury. If deficient, Heinz bodies (excess precipitates of oxidized hemoglobin) appear. G6PD deficiency is the most common problem. G6PD deficiency is a deficiency in which pathway? - Correct Answer-Hexose monophosphate shunt What is the function of the methemoglobin reductase pathway? - Correct Answer- Maintains heme iron in reduced state (Fe2+). Deficiency in this enzyme results in accumulation of Fe3+ which is nonfunctional. What is the function of the Leubering-Rapoport pathway? - Correct Answer-Produces no energy but is necessary for the ATP generation in the E-M pathway and accumulation of RBC 2,3-BPG for hemoglobin oxygen affinity function. Where does hemoglobin synthesis occur? - Correct Answer-In immature red cells Where does heme formation occur in the RBC? - Correct Answer-In the mitochondria What is the function of 2,3-BPG in the RBC? - Correct Answer-Influences the oxygen affinity and gives the dissociation curve its sigmoid shape. What is a shift to the right on the oxygen dissociation curve? - Correct Answer- Decreased affinity of hemoglobin for oxygen, results in more oxygen delivery to tissues. (anemic hypoxia and acidic states) What is a shift to the left on the oxygen dissociation curve? - Correct Answer-Increased affinity of hemoglobin for oxygen, results in less oxygen delivery to tissues. (methemoglobin and hyperventilation) What is the most important cause of iron deficiency anemia? - Correct Answer-blood loss GI bleeding (most common), also excessive menstrual flow and parasites (hookworm) What are the treatments for IDA? - Correct Answer-Correct cause, oral iron therapy (ferrous sulfate, Feosl), pareneral iron (dextran), transfusion What causes ACD or AOI? - Correct Answer-Increased acute phase proteins and secretion of cytokines that block iron release from macrophages and diminish erythropoiesis.

Hepcidin is increased which blocks the iron in gut cells and traps them in macrophages and liver cells. What is sideroblastic anemia? - Correct Answer-Defective heme synthesis (deficiency of delta ALA synthase and uroporphyrinogen decarboxylase). Characterized by presence of excessive iron deposition within the mitochondria of normoblasts in the BM (ringed sideroblasts). Siderocytes/Pappenheimer bodies in the peripheral smear. What is the effect of lead poisoning? - Correct Answer-Impaired heme synthesis by inhibiting the activity of delta ALA synthetase and heme synthetase. Causes photosensitivity, neurologic abnormalities. Sideroblastic changes in BM, increased dALA and coproporphyrin in urine. What are porphyrias? - Correct Answer-Rare disorders of porphyrin metabolism (enzyme deficiencies) in which there is tissue accumulation or increased excretion of porphyrins or its precursors. What is pernicious anemia? - Correct Answer-Development of gastric atrophy from antibodies to parietal cells and intrinsic factor. Causes a deficiency in vitamin B12 which leads to megaloblastic anemia. Can cause neurological damage (tingling in hands/feet, sensory loss and motor weakness). Glossitis, mild jaundice. Clinical findings include oval macrocytes and hypersegmented neutrophils. What is congenital dyserythropoietic anemia? - Correct Answer-Group of hereditary anemias characterized by ineffective erythropoiesis and profound blood and BM abnormalities. N/C asynchrony and maturation, erythroid multinuclearity, budding, fragmentation. Vacolization, basophilic stippling, iron overloading. Type II - HEMPAS - increased i antigen on RBCs. What is aplastic anemia? - Correct Answer-Pancytopenia associated with hypocellular BM. CD34+ stem cell deficiency. Usually idiopathic but can be caused by drugs/chemicals (chloramphenicol, benzene, arsenic), infections (viral hepatitis), ionizing radiation.

Can also be caused by stem cell defect/damage (PNH), autoimmune diseases (SLE), pregnancy What is Fanconi anemia? - Correct Answer-Autosomal recessive chromosomal instability disorder characterized by BM failure (inherited aplastic anemia). Associated with skin pigmentation, renal/splenic hypoplasia, hypoplastic thumbs/radii, mental retardation. Can develop into malignancy. Hb F markedly elevated, alpha-fetoprotein elevated, anti-i present. What is pure red cell aplasia? - Correct Answer-Selective decrease in erythroid precursor cells in the BM and anemia. TEC & Diamond-Blackfan anemia are two types. Which chromsomes contain the hemoglobin genes? - Correct Answer-c11 - epsilon, beta, delta, gamma c16 - zeta, alpha What globins compose each hemoglobin (A, A2, F, Gower I, Gower II, Hb Portland)? - Correct Answer-Hb A- alpha,beta Hb A2- alpha, delta Hb F - alpha, gamma Gower I- zeta, epsilon Gower II-alpha, epsilon Hb Portland- zeta, gamma What is the pH of the hemoglobin electrophoresis assays for the cellulose acetate and citrate acid? - Correct Answer-cellulose acetate - 8.4-8. citrate acid - 6.0-6. What is the mutation in Hb S? - Correct Answer-valine for glutamate at 6th position on the beta chain. What is the function of hydroxyurea in sickle cell patients? - Correct Answer-Increases the concentration of Hb F to decrease the amount of Hb S being produced. What is the mutation in Hb C? - Correct Answer-Lysine for glutamate at 6th position on beta chain. What do Hb C crystal look like? - Correct Answer-intracellular rods

What do Hb S/C crystals look like? - Correct Answer-Fingerlike projections What is the mutation in Hb C Harlem/Georgetown? - Correct Answer-double substitution on beta chain valine for glutamate at 6th position and aspartic acid for asparagine at 73rd position. Gives positive sickle solubility test. Use electrophoresis to differentiate. What is the mutation in Hb E? - Correct Answer-lysine for glutamate in 26th position. Can be confused with IDA (micro/hypo/target cells). How to quantitate Hb F? - Correct Answer-Acid or alkaline denaturation or Kleihauer- Betke stain What are the types of thalassemias associated with deletions of alpha alleles? - Correct Answer-1 deletion - silent carrier 2 deletions - alpha-thal minor 3 deletions - Hb H disease 4 deletions - Hb Bart Hydrops Fetalis What hemoglobin is formed in Barts hydrops fetalis? - Correct Answer-tetramers of gamma chains.