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179 Cards in this Set
- Front
- Back
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Where does hematopoiesis primarily occur in the fetus in the first 2-8 weeks of life?
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Yolk sac
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Where does hematopoiesis primarily occur in the fetus in the 2nd to 5th months of life?
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Liver and spleen
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Where does hematopoiesis primarily occur in the fetus in after the 5th month of life?
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bone marrow
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What is extramedullary hematopoiesis?
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hematopoiesis outside the bone marrow (i.e. in spleen, liver, lymph nodes)
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Where does hematopoiesis occur in children?
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the marrow of the long bones
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Where does hematopoiesis occur in adults?
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Ribs, sternum, pelvis, vertebrae and skull (flat bones)
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What stimulates erythropoietin production? What is the outcome of increased EPO?
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Cellular hypoxia in the kidney stimulates erythropoietin production. EPO stimulates stem cells (CFU-E) in the bone marrow to mature into erythrocytes.
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What cells are derived from a common a common multipotential stem cell in the bone marrow?
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erythrocytes, granulocytes, monocytes, thrombocytes
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What is the precursor of the platelet?
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Megakaryocyte. Platelets are fragments of megakaryocyte cytoplasm.
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Where are lymphocytes produced?
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Bone marrow, thymus (primary)
Spleen, lymph nodes, intestine-associated lymphoid tissue, tonsils (secondary) |
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What is the normal life span of an erythrocyte?
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120 days
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What removes aged RBCs from circulation?
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Phagocytic cells of the reticuloendothlial system (i.e. spleen)
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Heme is degraded to what product before excretion from the body?
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bilirubin
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(T/F) Iron and globin chains from aged/senescent RBCs are recycled
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True
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What happens to the N:C ratio as most cells mature?
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N:C ratio decreases as cells mature
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What is the best indicator of the age of a cell?
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Amount of chromatin clumping in the nucleus
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What is the color of the cytoplasm in blasts?
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Royal blue (basophilic) due to the presence of RNA
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What are nucleoli? When are they typically seen?
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Nucleoli are sites of ribosomal RNA synthesis. They are seen in the nuclei of immature cells and reactive lymphocytes.
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Name the first stage of erythrocyte development
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Rubriblast/pronormoblast
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Name the second stage of erythrocyte development
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Prorubricyte/basophilic normoblast
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Name the third stage of erythrocyte development
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Rubricyte/polychromatic normoblast
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Name the fourth stage of erythrocyte development
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Metarubricyte/orthochromic normoblast
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Name the fifth stage of erythrocyte development
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Diffusely basophilic erythrocyte/polychromatophilic erythrocyte/reticulocyte
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Name the sixth stage of erythrocyte development
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Mature erythrocyte
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What is the last nucleated stage in development of the erythrocyte?
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Metarubricyte
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What is asynchronous erythropoiesis? Give some examples of when this occurs.
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The nucleus and cytoplasm mature at different rates.
IDA (cytoplasm lags behind nucleus due to insufficient iron for hemoglobin synthesis) megaloblastic anemia (nucleus lags behind cytoplasm due to lack of B12 or folic acid) |
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What is the best way to judge the size of an erythrocyte on a Wright stained smear?
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A normocytic RBC is approximately the same size, or slightly smaller, than the nucleus of a mature lymphocyte
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What is the first sign of accelerated erythropoiesis?
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Increased reticulocyte count
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Define anisocytosis
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Variation in the size of RBCs (should see increased RDW)
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Define poikilocytosis
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Variation in the shape of RBCs
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What are schistocytes? When are they seen?
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RBC fragments
DIC, hemolysis, burns, MAHA, artificial heart valves |
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What is a drepanocyte?
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Sickle cell
Usually seen in sickle cell anemia but not sickle cell trait |
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What is the significance of hemoglobin C crystals? What do they look like?
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Hexagonal, dark staining crystals with blunt ends (Washington monuments)
Seen in patients with hemoglobin C disease and hemoglobin SC disease Not seen in patients with hemoglobin C trait |
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What are dacrocytes? When are they seen?
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Tear-drop cells, myelofibrosis and some anemias
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How can crenated RBCs be differentiated from burr cells?
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Burr cells may have more pointed projections than crenated cells. If in all cells in the thin part of the smear, probably crenation. Burr cells will be seen in variable numbers throughout the smear.
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What is the clinical significance of burr cells?
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Liver disease, uremia, hemolytic anemia, TTP, DIC, carcinoma of the stomach, pyruvate kinase deficiency
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What is hypochromia?
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Condition in which central pallor is greater than 1/3 the diameter of the RBC (also low MCHC)
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What is a codocyte? When will you see these?
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Target cells
Nonspecific but occur in hemoglobinopathies and many anemias |
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What is a leptocyte? When do these occur?
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A variation of a target cell in which the central portion is not completely detached from the outer membrane.
Associated with hepatic disorders, iron deficiency anemia, thalassemia. |
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What are spherocytes? Why do they form? When are they seen?
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Spherical RBCs that form due to damage to the RBC membrane. They have a shortened life span.
Seen in hereditary spherocytosis, hemolytic anemia, ABO HDN, burns, transfusion of stored blood. |
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How are the MCV and MCHC affected in hereditary spherocytosis?
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MCV may be normal to low, MCHC slightly increased
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What are stomatocytes? When are they formed?
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RBCs with slit-like central pallor. They may be found in liver disease, alcoholism, electrolyte imbalance and hereditary stomatocytosis.
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What is the clinical significance of marked polychromasia?
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Sign of accelerated erythropoiesis
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What is basophilic stippling? What disorders are associated with this?
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Multiple irregularly-shaped purple inclusions throughout the cytoplasm of the RBC. Due to aggregates of RNA.
Fine stippling - abnormal heme synthesis Coarse stippling - lead poisoning |
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What are Heinz bodies?
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Round inclusions attached to RBC membrane (appear peripherally in the cell). They are precipitated denatured hemoglobin.
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When are Heinz bodies seen?
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G6PD deficiency and drug-induced hemolytic anemia
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(T/F) Heinz bodies may be seen in a Wright stain
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False, Heinz bodies are only visible with supravital staining
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What are siderotic granules?
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Small, irregular, dark-staining iron granules near the periphery of the RBC.
Visible in a Prussian Blue stain; called Pappenheimer bodies when viewed in a Wright stain. |
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Which globin chains are found in Hemoglobin A?
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α2 ß2
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Which globin chains are found in hemoglobin A2?
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α2 δ2
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Which globin chains are found in hemoglobin F?
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α2 γ2
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Name several conditions in which hemoglobin F is increased.
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hemoglobinopathies, thalassemia, hereditary persistence of fetal hemoglobin
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How are abnormal hemoglobins identified?
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Hemoglobin electrophoresis
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Describe the migration of the most common hemoglobins on cellulose acetate at pH 8.6
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slowest to fastest: C/A2, S, F, A
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What controls are required from hemoglobin electrophoresis?
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At least A, F, and S
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Why is citrate agar used at acid pH when abnormal hemoglobins are identified on cellulose acetate at pH 8.6?
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It separates hemoglobins that migrate together on cellulose acetate.
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What is the order of migration of hemoglobins on citrate agar at acid pH?
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slowest to fastest: F, A2/A, S, C
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What is the substitution that results in hemoglobin S?
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Valine for glutamic acid in the 6th position of the beta chain
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What is the substitution that results in hemoglobin C?
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Lysine for glutamic acid in the 6th position of the beta chain
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Which hemoglobin is resistant to alkali denaturation and acid elution?
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Hemoglobin F. The Kleihauer-Betke acid elution stain uses this property.
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How does the fetus benefit from a high concentration of hemoglobin F?
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increased oxygen affinity so fetus can extract oxygen from maternal blood supply
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What makes up the buffy coat?
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Leukocytes and platelets
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What is MCV? How is it calculated?
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Indicator of the average/mean volume of erythrocytes
MCV (fL) = (Hct x 10)/RBC count |
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When is MCV increased?
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Megaloblastic anemia, hemolytic anemia with reticulocytosis, liver disease, newborns
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When is MCV decreased?
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Iron deficiency anemia, thalassemia, sideroblastic anemia, lead poisoning
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What is MCH? How is it calculated?
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Mean corpuscular hemoglobin, indicator of average weight of hemoglobin in individual RBCs
MCH (pg) = (Hemoglobin x 10)/RBC count |
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When is MCH increased?
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Macrocytic anemia
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When is MCH decreased?
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microcytic, hypochromic anemia
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What is MCHC? How it is calculated?
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Mean corpuscular hemoglobin concentration, indicator of average concentration of hemoglobin
MCHC (g/dL) = (Hemoglobin/Hct) X 100 |
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Low MCHC indicates what?
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hypochromic RBCs (iron deficiency, thalassemia)
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High MCHC indicates what?
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Spherocytes or error in RBC or hemoglobin measurement
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What is RDW?
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Red cell distribution width, measure of anisocytosis
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When is RDW increased?
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Anisocytosis
Post-transfusion, post-treatment for megaloblastic or microcytic anemia, sideroblastic anemia, etc. |
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What is hematocrit? How is it calculated (if not directly measured)?
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Percentage of RBCs in a given volume of whole blood
HCT = (MCV x RBC count)/10 |
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Wright's stain
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Methylene blue and eosin
Methylene blue stains acidic components blue and eosin stains basic components red-orange |
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Why is the Prussian blue stain used?
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used to visualize iron granules
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What is the purpose of supravital staining? Give two examples of supravital stains.
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Used to stain specific cellular components, no fixatives are used.
Two examples: New methylene blue for RNA, Neutral red with brilliant cresyl green for Heinz bodies |
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Blood cell production, maturation and death occur in organs of the ________ system.
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reticuloendothelial system (bone marrow, spleen, liver, thymus, lymph nodes)
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Describe normocellular bone marrow
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30-70% hematopoietic cells
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Describe hypercellular/hyperplastic bone marrow
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>70% hematopoietic cells
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Describe hypocellular/hypoplastic bone marrow
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<30% hematopoietic cells
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What is the normal range for the M:E ratio?
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3:1 to 4:1
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What is the M:E ratio?
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Myeloid precursor to erythroid precursor ratio in the bone marrow
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Name the primary lymphoid tissues. What occurs here?
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Bone marrow, thymus
Antigen-independent lymphopoiesis occurs here |
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Name the secondary lymphoid tissues. What occurs here?
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Lymph nodes, spleen, MALT
Antigen-dependent lymphopoiesis |
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_______ differentiate into macrophages
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Monocytes
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T lymphocytes provide what kind of immunity? When activated, they produce what?
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cellular, cytokines/interleukins
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Name the granulocytes
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neutrophils, eosinophiles, basophils
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B lymphocytes/plasma cells provide what type of immunity? They produce what?
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humoral immunity, antibodies
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NK cells do what?
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destroy tumor cells and cells infected with viruses
also known as large granular lymphocytes |
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Eosinophils do what?
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Modulate allergic response cased by basophil degranulation, involved in parasitic response
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Basophils do what?
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mediate immediate hypersensitivity reactions
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CD4 is expressed on what type of cell?
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Helper/inducer T cells
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CD8 is expressed on what type of cell?
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Suppressor/cytotoxic T cells
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CD16 and CD56 are expressed on what cells?
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NK
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CD14 is expressed on what cells?
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Monocytes
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CD19 and CD20 are expressed on what cells?
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B cells
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CD2 and CD3 are expressed on what cells?
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T cells
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CD33 is expressed on what cells?
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myelogenous cells
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CD13 is expressed on what cells?
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myelogenous
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CD34 is expressed on what cells?
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stem cells (myeloid and lymphoid precursors)
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Primary granules are visible in what precursor granulocytes?
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promyelocytes, myelocytes
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Secondary granules are visible in what precursor granulocytes?
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metamyelocyte, bands
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What is contained in the secondary granules of basophils?
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heparin, histamine
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50% of mature granulocytes are circulating, while the other 50% are located where?
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Marginating along vessel walls
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What is diapedesis?
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Neutrophils move from blood vessel marginating pool into tissues in response to antigenic stimulation
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What are chemotactic factors?
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Factors that attract neutrophils to the site of inflammation, include complement, bacterial products, injured tissue and hemostatic components
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What is the respiratory burst?
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Release of lytic enzymes in neutrophilic degranulation in order to kill organism after phagocytosis
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What is the difference between necrosis and apoptosis?
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Necrosis is induced by extracellular forces (killed), apoptosis is programmed cell death induced by intracellular processes (suicide)
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What are Dohle bodies?
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Small oval inclusions of RNA located in the cytoplasm that stain light blue. This is a toxic change.
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What is toxic granulation?
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A toxic change due to the persistent staining of primary granules in mature granulocytes
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What is toxic vacuolation?
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Colorless areas in the cytoplasm that indicate phagocytosis and degranulation have occured
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What is a shift to the left? What does this indicate?
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Increased number of myelocytes, metamyelocytes and/or bands in the peripheral blood. Associated with infection.
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Eosinophils express receptors for what immunoglobulin?
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IgE
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Basophils express membrane receptors for what immunoglobulin?
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IgE
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Pseudoneutrophilia
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Short term increase in WBC count due to redistribution of neutrophils from marginating pool to circulating pool. Caused by exercise, stress, pain and pregnancy. No shift to the left (bone marrow not involved)
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What is a leukoerythroblastic reaction? When would you see this?
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Presence of immature leukocytes and immature erythrocytes in blood. Seen in myelofibrosis.
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Causes of neutropenia
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severe infection exceeds neutrophil reserves, hypersplenism causes neutrophils to be removed from circulation, bone marrow injury/infiltration/suppression, B12/folate deficiency, viral infections
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Causes of eosinophilia
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parasitic infection, allergic reaction, chronic inflammation
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Causes of eosinopenia
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acute inflammation
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Causes of basophilia
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Type I hypersensitivity reactions, CML, polycythemia vera, hematopoietic growth factor administration
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What is chronic granulomatous disease? Who is normally affected?
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Morphologically normal but functionally abnormal neutrophils, normally affects males, fatal early in life
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What is Chediak-Higashi syndrome?
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Morphologically and functionally abnormal leukocytes, large gray-green granules in cytoplasm, photophobia, skin hypopigmentation, fatal early in life
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Hypersegmentation of neutrophils is associated with _______.
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Megaloblastic anemia
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Pseudo Pelger-Huet is associated with what disorders?
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Myeloproliferative disorders, myelodysplastic syndromes
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(T/F) Neutrophils in Pelger-Huet anomaly are functionally normal
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True, they are morphologically abnormal (pince-nez) but functionally normal
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Describe May-Hegglin anomaly
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Dohle-like inclusions, giant platelets, thrombocytopenia, clinical bleeding
Neutrophils are morphologically abnormal but functionally normal |
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Describe Alder-Reilly anomaly
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Large azurophilic granules, functionally normal cells, must differentiate from toxic granulation
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List the maturation stages of monocytes in order from youngest to oldest cell
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monoblast, promonocyte, monocyte, macrophage
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What is the purpose of monocytes/macrophages?
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Act as phagocytic cells that ingest foreign material, process antigenic information (antigen presenting cells), remove damaged RBCs (spleen) and secrete cytokines and TNF
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Causes of monocytosis
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tuberculosis, syphilis, autoimmune disorders, recovery stage from acute bacterial infection or marrow suppression
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Cause of monocytopenia
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aplastic anemia
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Name the maturation stages of lymphocytes from youngest to oldest cell
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lymphoblast, prolymphocyte, lymphocyte
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T cells make up what percentage of peripheral blood lymphocytes?
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80%
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What is the purpose of T helper cells?
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T4 cells promote activation of B cells by antigens
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What is the purpose of T suppressor cells? What CD marker do they have?
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T suppressor cells suppress activation of B cells by antigens, CD8
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What is the purpose of T cytotoxic cells? What CD marker do they have?
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Function in viral infections and organ rejections, have CD8 marker
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What is the normal ratio of T4/T8 cells? Why is this ratio used?
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Normal ratio is 2:1, this ratio is used to monitor HIV patients.
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When and where do T and B cells become immunocompetent?
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Both T and B cells become immunocompetent upon stimulation by an antigen in the secondary lymphoid tissue.
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Describe the appearance of plasma cells
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Abundant blue cytoplasm with prominent perinuclear (golgi) zone of clearing, eccentric nucleus with clumped chromatin pattern
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The Epstein-Barr virus infections what type of lymphocytes?
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B lymphocytes
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(T/F) Lymphocytosis occurs during infection with the Epstein-Barr virus
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True, lymphocytes are usually >50% of WBCs, with 20% being reactive T lymphocytes attacking affected B cells
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(T/F) A positive heterophile antibody test is associated with infection with the Epstein-Barr virus
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True
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(T/F) A positive heterophile antibody test is associated with infection with CMV
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False. CMV has symptoms similar to Epstein-Barr but is negative for the heterophile antibody test
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Explain the difference between leukemia and lymphoma
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Leukemia originates in the bone marrow and is initially systemic.
Lymphoma originates in the lymphoid tissue and is initially localized. |
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What is routinely assessed on bone marrow aspiration?
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cellularity, M:E ratio, megakaryocytes, iron stores and differential
may also include flow cytometry, cytogenetics and molecular testing |
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Lab findings of acute leukemia compared to chronic leukemia
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Acute: anemia, thrombocytopenia, neutropenia (fever/infection), variable leukocyte count, marrow cellularity >70%, marrow blasts >30%
Chronic: mild anemia, normal platelet count, high WBC count, marrow cellularity >70% |
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Myeloperoxidase stains what cell line(s)? What is this stain used for?
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Myeloperoxidase stains granulocytes and monocytes. It is used to differentiate AML (positive) from ALL (negative)
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Sudan Black B stains what component? What cells are stained? Is it used for what?
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Lipids, granulocytic cells, differentiates AML (positive) from ALL (negative)
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Monocytic cells are _____ for the specific esterase stain (naphthol AS-D chloroacetate esterase)
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negative
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Monocytic cells are _____ for the nonspecific esterase stain (alpha naphthyl acetate/butyrate).
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positive
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PAS stains intracellular _______. It stains what cells positive?
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glycogen; immature lymphoid cells, malignant erythroblasts, megakaryocytic cells
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The LAP score is high in _______ and low/normal in _______.
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High: leukemoid reaction, polycythemia vera, late pregnancy
Normal/low: CML, PNH |
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TRAP stain is positive in this leukemia
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Hair cell leukemia
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What are ringed sideroblasts? When are they seen? What stain is necessary to visualize them?
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Ringed sideroblasts are nucleated RBCs that contain iron that encircles the nucleus. They are abnormal and are seen in myelodysplastic syndrome and sideroblastic anemias. Prussian blue stain is used to visualize the iron in these cells.
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FAB L1
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Childhood leukemia, small lymphoblasts with homogenous appearance, good prognosis, most T cell ALLs are L1
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FAB L2
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adults, large lymphoblasts with heterogenous appearance
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FAB L3
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Leukemic phase of Burkitt lymphoma, both adults and children, blasts are large and uniform with prominent nucleoli, cytoplasm is basophilic and may show vacuoles, poor prognosis, B cell lineage
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Burkitt lymphoma is a _____ lymphoma associated with _____ virus
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non-Hodgkin, Epstein-Barr virus
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CD10 (CALLA) is positive is is which maturation phases of the B cell?
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Progenitor, early-pre-B, and pre-B (NOT early B cells)
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(T/F) Tdt will be positive in myelogenous cells
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False, it is positive only in precursor lymphoid cells
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What is the only marker expressed in all stages of B cells?
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CD19
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CD5 and CD7 are present in what type of cell?
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T cells
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(T/F) Mature T cells can have both CD4 and CD8
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False, only immature T cells can have both markers
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T cell ALL is most common is what gender? What is a very common physical finding?
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Males; mediastinal mass
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Chronic lymphotic leukemia is characterized by this type of cell which is caused by increased cellular fragility.
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Smudge cell
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What is the lymphoma phase of CLL?
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Small lymphocyte lymphoma
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A common complication of CLL is anemia due to what?
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Warm autoimmune hemolysis
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CLL lymphocytes appear
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homogenous, small, hyperclumped
(also smudge cells) |
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Multiple myeloma is a ____ cell malignancy that results in excessive production of _______.
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B/plasma, immunoglobulins (typically IgG, IgA)
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What are the characteristic findings in multiple myeloma?
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lytic bone lesions, increased blood calcium, M-spike, Rouleaux, increased blood viscosity, kidney damage, Bence-Jones proteins, increased ESR
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What are Bence-Jones proteins?
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free light chains found in urine, cause kidney damage
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What is Waldenstom Macroglobulinemia? What are the typical findings?
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Excess production of IgM by B cells, increased blood viscosity, lymphadenopathy, hepatosplenomegaly, M-spike, increased ESR, Rouleaux
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What is a lymphoma?
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Proliferation of malignant cells in solid lymphatic tissue
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Hodgkin lymphoma is characterized by what type of cell in lymph node biopsy? What is the morphology of this cell?
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Reed-Sternberg cells, large, multinucleated cells with prominent, large nucleoli
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Hodgkin lymphoma may be associated with what virus?
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Epstein-Barr
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Laboratory findings in Hodgkin lymphoma
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mild anemia, eosinophilia, monocytosis, increased LAP score, increased ESR
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Mycosis fungoides (cutaneous T cell lymphoma) causes what?
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Cutaneous lymphoma (ulcerative tumors) or Sezary syndrome (disseminated disease with widespread skin involvement and circulating lymphoma cells)
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Typical age of patients diagnosed with Non-Hodgkin lymphoma
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Over 55 years old
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