Term
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Definition
| The process by which erythrocytes (i.e. RBCs) are formed from precursors within the bone marrow. |
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Term
| These cells arise from the same pluripotent stem cell. |
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Definition
-erythroid cells
-granulocytes
-lymphocytes
-megakaryocytes |
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Term
| Production of RBCs is regulated by____________that are released from cells either within the bone marrow or in other body tissues |
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Definition
| -cytokines (termed poietins, colony stimulating factors, or interleukins) |
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Term
| True or false: in healthy animals, production and destruction of RBCs are carefully regulated to maintain a constant hematocrit (HCT) in the blood. |
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Definition
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Term
| A pluripotent stem cell gives rise to lymphoid and myeloid cells. What do lymphoid and myeloid cells give rise to? |
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Definition
-Lymphoid: B, T lymphocytes, and NK cells
-Myeloid: Megakaryocytes-> platelets, erythrocytes, neutrophils, monocytes, eosinophils, basophils, and mast cells. |
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Term
| What makes up hematopoeitic cells? |
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Definition
-pluripotent stem cell pool (cells that can produce all or most cell lines)
-progenitor cell pool (committed to producing one or a few cell lines)
-a proliferative pool (rapid proliferation but committed to one cell line)
-maturation pool (cells no longer have capacity to divide) |
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Term
| What primarily controls erythropoesis? Describe this. |
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Definition
-largely controlled and stimulated by the glycoprotein hormone erythropoeitin (Epo)
-Epo is produced by cells in the renal cortex that have the ability to sense blood oxygenation |
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Term
| What stimulated an increase in amounts of Epo? |
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Definition
| When cells in the renal cortex sense renal hypoxia. |
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Term
| Describe the sequence of erythrocyte differentiation. |
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Definition
| Rubriblast->prorubricyte-> rubricyte (early)-> rubricyte (middle)-> rubricyte (late)-> metarubricyte-> reticulocyte-> erythrocyte |
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Term
| What happens as erythroid cells develop? |
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Definition
-they become smaller and more hemoglobinated
-as hemoglobin is produced by the developing cell, a critical hemoglobin concentration is reached within the cell which triggers these cells to stop dividing |
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Term
| How long does it take for rubriblasts to become reticulocytes? |
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Definition
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Term
| During times of increased stimulus (i.e. increased Epo), erythrocytes can be released early from the bone marrow, showing up in circulation in approximately how many days? |
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Definition
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Term
| What is the main function of erythrocyte? |
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Definition
| To transport hemoglobin (Hgb). |
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Term
| Describe the characteristics of Hemoglobin. |
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Definition
-produced in developing erythrocytes
-tetramer composed of four globin chains and four iron-containing heme groups |
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Term
| What are the main functions of hemoglobin? |
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Definition
1. transport O2 from lungs to the tissues
2. transport CO2 from tissues to lungs
3. buffer H+ |
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Term
| Iron in the hemoglobin molecule must be in the reduced (i.e. ferrous) form to bind oxygen (i.e. oxyhemoglobin). When the iron moiety in Hgb is oxidized (i.e. ferric state) it can no longer bind oxygen and is called what? |
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Definition
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Term
| What may produce cyanosis and cause blood to appear brown in color? |
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Definition
| -erythrocytes have metabolic pathways that protect the iron in Hgb from oxidation, however, these pathways can become overwhelmed with exposure to large amounts of oxidants. If methemoglobin exceeds 10% of total hemoglobin, mucus membranes may appear cyanotic and blood may appear brown in color |
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Term
| Where is iron absorbed? What is the amount absorbed dependent on? |
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Definition
-intestine
-amount is dependent on age, health status, and iron status of the animal and the amount of iron ingested |
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Term
| What causes iron absorption to be increased? |
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Definition
| -when total body iron content is low, when erythropoeisis is increased, and when hypoxia is present |
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Term
| How is iron transported? Stored? |
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Definition
-transported: in plasma bound to protein transferrin
-stored: in body tissues as hemosiderin or in plasma and body tissues bound to the protein ferritin |
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Term
| How does hemosiderin appear in bone marrow aspirates or other tissues? |
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Definition
| -brown-black clumps of material |
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Term
| How is iron content of the body evaluated? |
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Definition
| -by measuring serum iron, serum total iron-binding capacity (TIBC), serum ferritin, or by evaluating bone marow hemosiderin content |
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Term
| Serum iron is (high or low) in iron deficiency? |
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Definition
| low but can also be low in conditions where tissue iron is normal or increased |
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Term
| What is the best serum indicator of total body iron content? |
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Definition
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Term
| What is TIBC a measure of? |
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Definition
| Transferrin in the blood. |
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Term
| What are the erythrocyte life spans for dogs, cats, cows, and horses? |
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Definition
-dogs-120 days
-cats-70 days
-cows-130 days
-horses-145 days |
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Term
| What are the lifespans of the main cellular components of peripheral blood (i.e. neutrophils, platelets, and RBCs)? |
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Definition
-Neutrophils: 6 hours
-Platelets: 6 days
-RBCs: 60-120 days
(NPR) |
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Term
| Erythrocytes circulate for a finite period of time and then are removed by the mononuclear phagocyte system (i.e. macrophages). How does this process occur? |
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Definition
-as erythrocytes age, changes occur in the cell membranes that provide sites for macrophages to bind and then phagocytose these cells
-within macrophages, erythrocytes are lysed and hemoglobin is degraded |
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Term
| As erythrocytes are lysed and hemoglobin is degraded what products are they degraded in to (i.e. what is the sequence of events in this degradation pathway)? |
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Definition
-erythrocytes are lysed and hemoglobin is degraded to heme and globin
-globin is further degraded to amino acids (which are used by the macrophage and returned to circulation)
-heme is degraded to iron and bilirubin
-Iron is stored as ferritin or hemosiderin or can be transported by to the bone marrow bound to transferrin (to be used for future RBC production)
-bilirubin is released from the macrophage into circulation where it is conjugated and excreted in the bile |
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Term
| What can cause a yellow to orange discoloration to the serum/plasma (i.e. icteric serum/plasma)? |
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Definition
| -bilirubin in circulation (from degradation of erythrocytes) |
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Term
| How is erythrocyte size reported and how is it measured? |
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Definition
-average erythrocyte size is reported on CBC as the mean cell volume (MCV)
-MCV is a measured value
-MCV can be within the RI(normocytic), below the RI (microcytic), or above the RI (macrocytic) |
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Term
| Normocytic (normal sized RBCs) varies between species. Lis the average size for dogs, pigs, horses, cats, cows, and goats. |
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Definition
-dog: 60-77 fl
-hores: 34-58 fl
-cow: 40-60 fl
-pig: 52-62 fl
-cat: 39-55 fl
-goat: 16-25 fl |
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Term
| List causes of microcytic RBCs (increased numbers of small RBCs) |
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Definition
1. IRON DEFICIENCY ANEMIA-> in iron deficient states, Hgb production is inhibited, and thus cells go through extra divisions (getting smaller) in an attempt to reach critical Hgb concentration)** Recall that as erythroid precursors mature in the bone marrow, it is a critical concentration of Hgb that triggers cells to stop division.
2. Hepatic failure/portosystemic shunts (may relate to iron kinetics)
3. Akita and Shiba inu dogs have smaller RBCs than other dog breeds |
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Term
| What triggers erythroid precursor to stop cell division? |
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Definition
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Term
| List causes of macrocytic RBCs (increased numbers of large RBCs). |
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Definition
1. seen when increased numbers of young RBCs (i.e. reticulocytes) are present in circulation
2. macrocytosis without polychromasia can be seen in feline patients with feline leukemia virus infection (may or may not be anemic).
3. a few other relatively rare causes of macrocytosis are: a. poodle macrocytosis (mini and toy; hereditary/rare), b. hereditary stomatocytosis (not like microcytosis in Akitas and Shibas which is consistent within the breed) |
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Term
| Define and describe anisocytosis. |
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Definition
-term used to describe variation in RBC size
-this could be due to increased numbers of small RBCs, large RBCs, or both |
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Term
| How is anisocytosis measured? |
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Definition
-Red cell distribution width
-generated by automated hematology analyzers |
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Term
| Define and describe how erythrocyte color is measured? |
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Definition
-MCHC
-erythrocyte color is dependent on the hemoglobin concentration within the cell
-this is quantified on a CBC as the mean cell hemocglobin concentration (MCHC)
-MCHC is a calculated value based on a measured hemoglobin concentration value and the HCT
-the MCHC is a similar measure, but we will MCHC
-MCHC=(Hgb/HCT) X 100
-MCHC can be within the reference range (normochromic), below the reference range (hypochromic), or above the reference range (hyperchromic) |
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Term
| What causes hypochromasia (low MCHC)? |
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Definition
1. Iron deficiency: Hgb synthesis is impaired with iron deficiency resulting in RBCs with a decreased intracellular Hgb concentration. These cells appear as small RBCs with an increased area of central pallor
2. Associated with increased numbers of young RBCs (ie.e reticulocytes) in circuation. Compared to mature RBCs, reticulocytes are relatively larger and have a lower intracellular Hgb concentration. |
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Term
| What causes hyperchromic (high MCHC) RBCs? |
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Definition
-increased MCHC is almost always an artifact (animals do not produce RBCs with too much Hgb)
-artifactual hyperchromasia can result from causes such as hemoglobinemia (free Hgb in plasma), in vitro hemolysis, or the presence of interfering substances or structures (e.g. lipemia, icterus, Heinz bodies) |
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Term
| Describe how RBC shape varies between species. |
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Definition
-dog: RBCs are biconcave discs meaning that they are discoid but are pinched in the center. This can be seen on the blood smear as a central clear area termed central pallor
-cat, horse, cow, sheep: discoid shape, little to no central pallor
-llama, camel, bird, and reptile: elliptical shape (birds and reptiles also have nucleated RBCs) |
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Term
| Define poikilocytes. What can cause their formation? |
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Definition
-general term for an abnormally shaped RBC
-can represent artifact or pathologic changes. Poikocytes may be present in healthy goats, pigs, and young cattle. Poikocytosis is frequently seen in dogs and ruminants with iron deficiency. Generic term (include a description of specific shape abnormalities when possible) |
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Term
| Describe the appearance of spherocytes. |
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Definition
-RBC characterized by decreased diameter, decreased central pallor, and increased staining intensity
-while spherocytes have a decreased diameter adn appear "small," they typically have relatively normal volumes. |
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Term
| Spherocytes are generally recognized in which species? |
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Definition
| The dog, since central pallor is often absent in RBCs or other species |
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Term
| The presence of spherocytes suggests which diseases/pathologic processes? |
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Definition
-IMMUNE-MEDIATED DAMAGE TO RBCs-> in cases if IMHA, large numbers of spherocytes can be seen in circulation. Spherocytes form from partial phagocytosis of RBC membranes by macrophages
-have also been associated with blood transfusion, bee sting, and zinc toxicity
-small numbers of spherocytes are also occasionally seen with fragmentation processes, however, in the case other RBC shape changes such as schistocytes are also usually present |
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Term
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Definition
| -irregularly-shaped RBC fragments that occur when RBCs are foced through altered vasculat channel, vessels containing fibrin strands, or exposed to turbulent blood flow (i.e. physical damage to RBCs) |
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Term
| What are schistocytes associated with? |
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Definition
-DIC
-HEMANGIOSARCOMA
-VASCULITIS
-IRON-DEFICIENCY |
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Term
| Describe keratocytes and what they are caused by. |
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Definition
-RBC with a blister or two "horn-like" projections
-formed by intravascular trauma (similar to processes causing schistocyte formation)
-also seen in cases of iron deficiency |
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Term
| Describe eccentrocytes and what they are caused by. |
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Definition
-RBC with the hemoglobin shifted to one side and a clear, membrane-bound area on the opposite side
-eccentrocytes form from oxidative damage to RBC membranes and may be seen with Heinz bodies
-seen with similar causes as Heinz body formation |
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Term
| Describe ghost cells and what they are caused by. |
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Definition
-formed from lysis of RBCs
-ghost cells appear as very pale staining cells consisting of an empty RBC membrane
-can be artifactual (i.e. sample preparation) or pathologic as with intravascular hemolysis (e.g. Heinz body hemolysis, IMHA) |
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Term
| Describe acanthocytes and what they are caused by. |
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Definition
-RBC with irregularly spaced surface projections of variable length and diameter
-acanthocyte formation is thought to be the result of altered lipid/cholesterol content of cellular membranes
-can be associated with splenic hemangiosarcoma, liver disease (esp. hepatic lipidosis in cats), and renal disease |
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Term
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Definition
| -RBC with many short evenly spaced uniform surface projections |
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Term
| What can cause the formation of echinocytes? |
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Definition
-artifact: echinocyte formation can be an artifactual change (e.g. crenation) associated with blood film preparation and slow drying
-pathologic: echinocyte formation can be associated with pathologic processes such as electrolyte depletion, renal disease, neoplasia, rattlesnake envenomation, and chemotherapy |
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Term
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Definition
-RBC that has excess membrane, also called a "target cell"
-characterized by a central area of hemoglobin surrounded by a clear ring and an outer rim of hemoglobin |
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Term
| What can cause the formation of codocytes? |
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Definition
-may be seen in some dogs with regenerative anemias
-also associated with hepatic and renal disease
-usually of limited diagnostic significance |
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Term
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Definition
| -clumps of denatured Hgb that result from oxidation of sulfhydrl groups within the Hgb molecule |
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Term
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Definition
Clumps of denatured Hgb that result from oxidation of sulfhydryl groups withing the Hgb molecule
-RBCs have metabolic pathways that attempt to keep these sulfhydryl grops in a reduced state |
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Term
| When do heinz bodies form? |
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Definition
| When exposed to a an overwhelming dose of oxidants |
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Term
| How do heinz bodies appear on a Wright's stained blood smear? |
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Definition
| -Heinz bodies appear as a small eccentric pale structures that often protrude from the cell margin |
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Term
| How do Heinz bodies appear when stained with new methylene blue stain? |
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Definition
| -dense blue structures and are easily recognized |
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Term
| Heinz bodies make RBCs more susceptible to which kind of hemolysis? |
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Definition
| -intravascular and extravascular |
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Term
| Which species tends to form Heinz bodies more easily than other species and why? |
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Definition
-cats
-because Feline Hbg has twice the numbers of sulfhydryl groups
-Note: most healthy cats can have up to 10% Heinz bodies (i.e. 10% of RBCs have Heinz bodies) |
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Term
| What is basophilic stippling? |
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Definition
| -aggregates of ribosomes that are visualized as small basophilic granules within a RBC |
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Term
| Where is basophilic stippling most often seen? |
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Definition
-immature erythrocytes of ruminants
-can also be seen in immature erythrocytes of dogs and cats with highly regenerative anemias |
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Term
| Basophilic stippling not associated with anemia can also be seen with which type of poisoning? |
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Definition
-lead poisoning
-lead inhibits the enzyme that normally breaks down the ribosomes |
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Term
| What are Howell-Jolly bodies and how do they appear? |
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Definition
-Nuclear fragments within an RBC
-appear as small round dark blue inclusions |
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Term
| Which diseases commonly present with Howell-Jolly bodies? |
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Definition
-regenerative anemia
-splenectomy
-suppressed splenic function |
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Term
| What are siderotic granules (Pappenheimer bodies)? |
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Definition
-iron granules within mitochondria and lysosomes
-relatively uncommon in animals
-may be seen with impaired Heme synthesis, myelodysplasia and ineffective erythropoeiseis |
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Term
| What are nuclear erythrocytes? |
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Definition
-erythrocytes in which the nucleus still remains
-most often theses are metarubricytes, however, rubricytes adn sometimes earlier precursors are rarely seen in the peripheral blood
-nuclear RBCs are never really "normal" to see in circulation |
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Term
| What are nucleated erythrocytes (metarubicytes) associated with? |
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Definition
-may be present due to toxic, hypoxic, or physical damage to bone marrow endothelium allowing early release of these cells into circulation
-often associated with REGENERATIVE ANEMIA
-increased numbers in circulation may also be due to: lead poisoning, chemotherapeutic use, neoplasia or inflammation within the marrow space, and splenic contraction or dysfunction |
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Term
| Why are nucleated erythrocytes associated withe anemia? Can they be used as an indicator of regeneration? Why or why not? |
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Definition
-likely present due to a combination of hypoxic damage to marrow endothelium and increased erythropoeisis
-NUCLEATED RBCS SHOULD NOT BE SUED AS AN INDICATOR OF RBC REGENERATION (USE RETICULOCYTE COUNT AND/OR DEGREE OF POLYCHROMASIA) |
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Term
| What term describes the presence of nucleated RBCs in circulation? |
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Definition
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Term
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Definition
| -spontaneous association of RBCs in linear stacks ("stacks of coins") |
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Term
| In which species is rouleaux normal? |
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Definition
Horses
(slight amount may be seen in dogs and cats) |
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Term
| Why is rouleaux enhanced in certain states? |
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Definition
-enhanced with increased plasma proteins (hyperglobulinemia and hyperfibrinogenemia)
-RBCs normally have negative charges on their surface that tend to repel other RBCs
-when plasma proteins are increased, they mask these negative charges and allow RBCs to get closer together, forming linear stacks |
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Term
| What is agglutination? What is it caused by? |
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Definition
-irregular, spherical clumps of RBCs ("grape-like clusters")
-caused by antibody bridging between RBCs |
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Term
| In which diseases is agglutination sometimes seen? |
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Definition
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Term
| How is agglutination differentiated from rouleaux? |
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Definition
-small amount of blood and saline are mixed together
-with rouleaux, the RBCs will disperse
-with true agglutination, they will not |
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