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240 Cards in this Set
- Front
- Back
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What sites are used for venipuncture in the cow?
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jugular, tail vein
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What sites are used for venipunture in the pig?
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anterior vena cava, jugular, ear veins
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What is the difference between plasma and serum?
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plasma is the fluid when anticoagulated blood is spun in a tube- fluid in which rbcs, platelets, and proteins are suspended
serum is the part of the blood that is left after coagulation- lacks proteins used during clot formation |
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What anticoagulant is in the lavendar top tube and how does it prevent coagulation?
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ethylenediaminetetraactic acid (EDTA) which chelates Ca2+ ions that are required by enzymes in the clotting cascade- suitable for platelet counts, blood films
need appropriate ratio of blood: EDTA |
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What anticoagulant is in the green top tube and how does it prevent coagulation?
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Heparin which complexes and potentiates the ability of antithrombin III to neutralizes the action of thrombin and coagulation factos
used for samples from submammalian species and small species not ideal for CBC |
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What anticoagulant is in the blue top tube and how does it work?
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sodium citrate which complexes Ca2+ ions and can be used in coagulation function studies because adding more Ca2+ can reverse the action
sometimes used for platelet counts |
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When is the coverslip method of making a blood film appropriate?
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it may be used with submammalian blood due to the small volume
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What are the components of Wright's stain?
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methylene blue: stains RNA of ribosomes an dnucleoli blue
Azure dye: stains DNA purple, mucopolysaccharides Eosin: stains proteins red-orange |
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What is the application of New methylene blue stain in hematology?
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it is used to detect the presence of reticulocytes and Heinz bodies
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What can cause errors in total protein measurement?
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lipemia, hemolysis, due to errors in refractometric properties
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what is the difference between the packed cell volume and hematocrit?
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packed cell volume is the volume of packed erythrocytes expressed as a percentage of the total column of blood
hematocrit is a calculated number by multiplying the number of red cells by the mean cell volume |
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What components are contained in the buffy coat?
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the leukocytes and the platelets
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What are the units for hemoglobin measurement?
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grams per deciliter
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How is hemoglobin measured?
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cyanmethemoglobin method
Fe2+ of hemoglobin is converted to Fe3+ and complexed to cyanide to form cyanmethemoglobin which is measured spectrophotometrically |
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What conditions falsely elevate hemoglobin?
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Hemolysis, lipemia, heinz bodies
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What are the units for the red blood cell count?
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expressed as N x 10^12 RBCs/L
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What is MCV and what information can you derive from it?
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mean corpuscular volume: expression of the average volume of individual red cells- PCV/RBC x10 expressed in femtoliters
can tell you about regeneration and type of anemia |
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What is a normal MCV for an elephant?
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120 fl
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What is MCHC and what information can you derive from it?
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mean corpuscular hemoglobin concentration
expressed as grams/dL measures the ratio of the weight of hemoglobin to the volume of red blood cells Hgb/PCV x 100 |
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What can cause false elevations in MCHC?
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Inherent error in Hgb or RBC count
excess anticoagulant lipemia hemolysis RBC agglutination Heinz bodies |
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What is RDW?
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it is the red cell distribution width- a numerical expression of variation in RBC size and can be increased in cases of either microcytosis or macrocytosis and may increase before MCV becomes abnormal
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What is the difference between TNCC and WBC count?
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TNCC expresses the total numer of nucleated cells per unit volume- includes nucleated RBCs as well as leukocytes, total leukocyte includes only leukocytes
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What are the methods of determination of WBC count?
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manual count using hemocytomenter
automated analyzers are used by most labs as it is faster and more accurate |
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What are the four sections of the blood smear?
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drop, body, counting area, feathered edge
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What observations should be made macroscopically on the blood smear?
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at 10x look for platelet clumbs and abnormally large cells
find the counting area- estimate total leukocyte count |
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What is a normal leukocyte count per 10x objective field on a blood smear?
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20-50 leukocytes per 10x objective field in the counting area
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How many platelets per oil immersion field are considered a normal platelet count?
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10-15 platelets per field
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What can macroplatelets and abnormal platelet shape tell you about the blood?
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it can indicate increased platelet turnover
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What is rouleaux formation?
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it is the stacking of red cells in linear chains- reversible adhesion between RBCs due to bridging by proteins and is normal in the horse and cat
least likely to form in cow, sheep, and goat |
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What does rouleaux formation indicate in the dog?
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inflammation possibly
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What is autoaggutination?
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it is the spontaneous, irregular clumping of RBCs on a smear due to antibody coating of the RBCs
useful in diagnosing IMHA |
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What is the test to distinguish rouleaux from autoagglutination?
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the saline dispersion test- 1 drop of blood from the purple top tube
several drops of saline mix on a microscope slide observe wet mount under microscope saline will disperse rouleaux but not autoagglutination |
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What is polychromasia?
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it is the proportion of polychromatophilic RBCs on the blood film that stain blue-gray due to increased amt of RNA and are large because they are younger
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What is a normal amount of polychromasia?
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0-2 per oil immersion field in the dog and cat
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What is the different nomenclature for rubrocytes?
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wright's or dif-quik: polychromatophilic RBCs
new methylene blue: reticulocytes |
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What is hypochromasia?
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it is the subjective assessment of an increase in the zone of central pallor- these cells have a decreased MCHC/ decreased hemoglobin
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What is anisocytosis?
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variation in size from cell to cell
-subjective RDW is the numerical term |
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What is a poikilocyte?
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it is an RBC with an abnormal shape- generic term
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What is a spherocyte and what do they indicate?
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it is an erythrocyte that appears smaller and stains uniformly dark red with no central zone of pallor;
increased surface area to volume ratio; increased numbers suggest membrane damage, frequently associated with IMHA difficult to detect in cats, horse, and some ruminants |
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What are leptocytes?
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folded erythrocytes with increased surface to volume area- Target cells/ stomatocytes
small numbers normal often nonspecific |
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What diseases can cause increased leptocytes?
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liver disease, hypothyroidism, iron deficiency, or chronic disease
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What are torocytes and what causes them?
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punched-out or bowl cells that have a large area of central pallor but are not hypochromic; hemoglobin is distributed to the outer margins of the cells- sharp demarcation between central non-hemoglobinized area and peripheral hemoglobinized area
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What are echinocytes and what causes it?
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artifact
short, blunt to sharp surface projections that are uniform in spacing and size in vitro artifact caused by slow drying patchy distribution- not on feathered edge |
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What causes pathogenic echinocytes?
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uniform distribution throughout the smear
associated with uremia in humans lymphoma, glomerulonephritis, rattle snake bites and doxorubicin toxicosis in dogs and exercising horses |
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What are acanthocytes?
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roughly spherical red cells with irregular thorny projections that are unevenly distributed- excess cholesterol in RBC membrane compared to phospholipids
liver disease, or RBC fragmentation diseases |
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What are schistocytes?
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irregular RBC fragments caused by mechanical trauma to the RBCs- associated with DIC, vascular neoplasms, vasculitis or altered vascular flow, or cells that are more rigid
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What are keratocytes?
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blister/helmet c ells: spiculated RBC with 1 or 2 projections
formed when there is a vacuole near the surface of RBC which may rupture- physical or chemical injury DIC, liver disease, iron deficiency (in dogs) |
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What is a dacryocyte?
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it is a teardrop shaped RBC
associated with myeloproliferative disorder in dogs and cats may be seen with anemia in llamas |
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What is an eccentrocyte?
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it is an RBC with condensed hemoglobin at one end of the cell and results from oxidative injury to the cell membrane
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What do nucleated red blood cells with reticulocytosis indicate?
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regenerative response
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What do nucleated red blood cells without reticulocytosis indicate?
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splenic dysfunction
hemangiosarcoma lead poisoning (mild reticulocyte increase) extramedullary hematopoiesis cushing's disease erythroleukemia in cat |
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What are howell-jolly bodies and what do they indicate?
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they are retained nuclear fragments resulting in a round basophilic body within the red blood cells that signify possible regenerative responses
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What are heinz bodies?
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denatured or precipitated hemoglobin that protrudes from the surface of the red blood cell
induced by oxidative injury to RBCs- from drugs and toxins seen more easily with vital stains |
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What is basophilic stippling?
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it describes RBCs with multiple punctate uniformly placed basophilic granules that consist of aggregates of ribosomes an dpolyribosomes
lead toxicity regenerative anemia in ruminants |
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What is a reticulocyte?
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it is an immature, anucleate RBC that retains ribosomes, polyribosomes, and mitochondria that will stain with new methylene blue
mature in 24-48 hours in dogs |
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What is unique about feline reticulocytes?
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they appear in 2 morphologies:
- aggregated contain large clumps of stain and is the immature form that matures within half a day - punctate form: only contain a few pinpoints of ER that has a long maturation and therefore accumulates in the blood- not counted here at OSU |
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What is the technique for new methylene blue stain (NMB)?
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mix equal volumes (5 drops) blood and NMB stain in a small tube
incubate for 10 minutes count 1000 erythrocytes, keeping track of the number of coarse (aggregate) reticulocytes express as a percentage |
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How are reticulocyte values reported?
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absolute values (% reticulocytes x RBCs),
corrected (patient PCV/ mean normal PCV x % retics) RPI- dogs only- (corrected retic % / reticulocyte maturation time for teh degree of anemia) |
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What are normal reticulocyte values?
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dog and cat: up to 60,000
Ruminants: 0/ low numbers Horses: do not release reticulocytes in response to anemia |
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How do you obtain the absolute number of each type of leukocyte?
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multiply the total count by the percentage of each leukocyte present
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How do avian erythrocytes differ from mammalian species?
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they are oval shaped and contain nuclei
the nucleas is oval to round and cytoplasm is pink/orange they are larger than mammalian RBCs to provide high O2 carrying capacity |
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What are avian neutrophils and how are they different?
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heterophils- most common WBC
round cells with lobed shaped nucleus, clear cytoplasm and eosinophilic rod-shaped granules |
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What is the most common white blood cell in waterfowl and amazon parrots?
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lymphocytes
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What physiological conditions can increase monocytes?
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chronic inflammation, fungal infections, chlamydial infections and chronic bacterial disease
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What are thrombocytes?
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they are avian platelets that are nucleated
small, round cells with a round nucleus containing dark clumped chromatin |
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What parameters are used to evaluate red cell mass?
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PCV, RBC count, and HGB
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What CBC parameters are used to evaluate anemia?
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PCV: anemia or polycytemia
Reticulocyte count: nonregenerative or regenerative MCV/MCHC: normocytic, microcytic, macrocytic |
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What is a left shift?
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it is an increased number of band neutrophils
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What is a stress leukogram?
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neutrophilia, monocytosis, lymphopenia
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What type of cells do blood cells derive from?
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hematopoietic stem cells
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What do hematopoietic stem cells differentiate into?
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common myeloid or common lymphoid progenitors
these can be inferred from cytokine-driven differentiation in culture |
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What do hematopoietic stem cells differentiate into?
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common myeloid or common lymphoid progenitors
these can be inferred from cytokine-driven differentiation in culture |
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What drives hematopoeisis?
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lineage- restricted transcription factors induced by multiple hematopoietic cytokines and direct contact with the bone marrow microenvironment
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What drives hematopoeisis?
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lineage- restricted transcription factors induced by multiple hematopoietic cytokines and direct contact with the bone marrow microenvironment
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Where does hematopoeisis occur in adult mammals?
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primarily in the bone marrow, especially in the axial skeleton and ends of long bones- expansion into the central areas of long bones occurs with increased demand
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Where does hematopoeisis occur in adult mammals?
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primarily in the bone marrow, especially in the axial skeleton and ends of long bones- expansion into the central areas of long bones occurs with increased demand
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What do hematopoietic stem cells differentiate into?
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common myeloid or common lymphoid progenitors
these can be inferred from cytokine-driven differentiation in culture |
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What do hematopoietic stem cells differentiate into?
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common myeloid or common lymphoid progenitors
these can be inferred from cytokine-driven differentiation in culture |
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What do hematopoietic stem cells differentiate into?
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common myeloid or common lymphoid progenitors
these can be inferred from cytokine-driven differentiation in culture |
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What drives hematopoeisis?
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lineage- restricted transcription factors induced by multiple hematopoietic cytokines and direct contact with the bone marrow microenvironment
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Where can extramedullary hematopoiesis occur in times of demand?
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spleen, liver, and lymph nodes
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Where can extramedullary hematopoiesis occur in times of demand?
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spleen, liver, and lymph nodes
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Where does hematopoeisis occur in adult mammals?
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primarily in the bone marrow, especially in the axial skeleton and ends of long bones- expansion into the central areas of long bones occurs with increased demand
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What drives hematopoeisis?
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lineage- restricted transcription factors induced by multiple hematopoietic cytokines and direct contact with the bone marrow microenvironment
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What are the components of the bone marrow microenvironment are important in hematopoiesis?
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macrophages, adipocytes, endothelial cells, nerves, osteoblasts, osteoclasts, endothelial cells and the extracellular matrix
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What drives hematopoeisis?
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lineage- restricted transcription factors induced by multiple hematopoietic cytokines and direct contact with the bone marrow microenvironment
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Where does hematopoeisis occur in adult mammals?
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primarily in the bone marrow, especially in the axial skeleton and ends of long bones- expansion into the central areas of long bones occurs with increased demand
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Where does hematopoeisis occur in adult mammals?
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primarily in the bone marrow, especially in the axial skeleton and ends of long bones- expansion into the central areas of long bones occurs with increased demand
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Where can extramedullary hematopoiesis occur in times of demand?
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spleen, liver, and lymph nodes
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What are the components of the bone marrow microenvironment are important in hematopoiesis?
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macrophages, adipocytes, endothelial cells, nerves, osteoblasts, osteoclasts, endothelial cells and the extracellular matrix
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What are the components of the bone marrow microenvironment are important in hematopoiesis?
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macrophages, adipocytes, endothelial cells, nerves, osteoblasts, osteoclasts, endothelial cells and the extracellular matrix
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Where can extramedullary hematopoiesis occur in times of demand?
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spleen, liver, and lymph nodes
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What are the components of the bone marrow microenvironment are important in hematopoiesis?
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macrophages, adipocytes, endothelial cells, nerves, osteoblasts, osteoclasts, endothelial cells and the extracellular matrix
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Where can extramedullary hematopoiesis occur in times of demand?
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spleen, liver, and lymph nodes
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What are the components of the bone marrow microenvironment are important in hematopoiesis?
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macrophages, adipocytes, endothelial cells, nerves, osteoblasts, osteoclasts, endothelial cells and the extracellular matrix
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What are the hematopoietic cytokines?
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IL-1 through IL-2
stem cell factor erythropoietin granulocyte-macrophage colony stimulating factor granulocyte colony stimulating factor thrombopoietin |
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What are the actions of the hematopoietic cytokines?
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survival, proliferation, differentiation commitment, maturation, functional activation
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Where does erythropoiesis occur specifically?
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in erythroblastic islands in which a central macrophage is surrounded by 10-30 erythroid cells in various stages of development
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What are BFU-E?
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burst forming unit- erythroid
originate from pluripotential stem cells in response to SCF and IL-3 they then differentiate into colony-forming units- erythroid |
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What are CFU-E?
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Colony forming unit- erythroid
arise from BFU-E in response to erythropoietin and other factors differentiate into rubriblasts in response to erythropoietin |
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How is maturation of erythroid precursors characterized?
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decreasing cell size
nucleus becomes smaller, chromatin becomes more condensed and nucleus eventually is extruded decreasing cytoplasmic basophilia increasing deformability of the cells loss of adhesion molecules to facilitate release into circulation |
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What is a rubriblast?
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the first identifiable cell of erythroid lineage
largest erythroid precursor loose, dark staining chromatin and a nucleolus deeply basophilic cytoplasm |
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What is a prorubricyte?
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it is smaller than a rubroblast
slightly clumped chromatin but no nucleolus basophilic cytoplasm hemoglobin synthesis begins |
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What is a rubricyte?
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smaller
more condensed chromatin cytoplasm is less basophilic DNA and RNA synthesis stops Hemoglobin synthesis continues last erythroid precursor capable of cell division |
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What is a metarubricyte?
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pyknotic nucleus appears homogeneously dense
cytoplasm is polychromatophilic due to hemoglobin do not circulate in healthy animals may circulate in severe regenerative anemia |
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What is a polychromatophilic erythrocyte?
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-the nucleus has been extruded
-hemoglobin synthesis continues -cytoplasm is still polychromatophilic -low numbers in circulation in health -increased in circulation with regenerative anemia -reticulocyte when stained with NMB |
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What do mature RBCs look like?
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red cytoplasm
biconcave disc complex cytoskeleton volume maintained by ion pumps mutations change shape- hemolytic anemia |
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How do mature RBCs differ among species?
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-Dogs/humans- central zone of pallor
-cats/horses- no central zone of pallor -camels- eliptical cells -goats- poikilocytosis -angora goats/deer- spindle-shaped RBCs |
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How long does it take a rubriblast to mature into a circulating RBC?
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dog: 7d
cow: 4-5 d bird: 36 hrs |
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What controls release and maturation of erythrocytes?
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via diapedeisis through sinusoidal endothelial cells in mammals
release controlled by EPO concentration, cellular deformability, loss of adhesion molecules, surface charge |
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How do RBCs respond to a hypoxic stimulus?
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it stimulates increased RBC production
immediate release of reticulocytes from maturation compartment of BM and from splenic contraction but does not result in detectable reticulocytosis -increased count in 2-3 days, peaks in 4-7 days |
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What is erythropoetin and where is it produced?
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it is a glycoprotein produced by the peritubular interstitial fibroblasts in the renal cortex in response to tissue hypoxia
it is produced by some cells in the liver and in some CNS tissue and reproductive organs |
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What are the actions of EPO on erythroid progenitors?
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-stimulates commitment of stem cells to erythroid lineage and BFU-E proliferation
-required for differentiation of CFU-E, rubriblasts and rubricytes -Prevents apoptosis of erythroid precursors -Reduces marrow transit time by shortening G1 phase of cell cycle -increases hemoglobin synthesis -induces release of reticulocytes into circulation -decreased EPO production results in a non-regenerative anemia |
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What is one of the most frequently prescribed products of recombinant DNA technology in human medicine?
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EPO
erythropoietin |
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What is the effect of testosterone and anabolic steroids on erythropoiesis?
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increase erythropoietin release
direct stimulation of precursors accounts for higher PCV in males |
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Why do males have a higher PCV?
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testosterone increases the release of erythropoietin
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What affect does estrogen have on erythropoiesis?
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it decreases the response to erythropoietin
may decrease erythropoietin production high levels suppress erythropoiesis (sertoli cell tumors) |
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What affect does thyroxine have on erythropoiesis?
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it causes increased tissue O2 demand
secondary increase in erythropoietin |
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What affect do corticosteroids have on erythropoiesis?
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they increase erythropoietin production
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What affect do prostaglandins have on erythropoiesis?
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increase erythropoietin prodution
activate EPO-responsive cells |
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What is the structure of the RBC membrane?
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phospholipid bilayer
membrane carbohydrates- blood group antigens glycolipids with specificty determined by CHO moiety |
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Why do RBCs repel each other?
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they penetrate the lipid bilayer and contribute a negative charge to the cell surface
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What are electrolyte concentrations in RBCs?
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dog and cat: low K,high Na
horses: high K, low Na |
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What are the cytoskeletal proteins in RBCs?
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spectrin, actin, ankyrin, band 3
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By how much does hemoglobin increase O2 carrying capacity?
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it increase it by 70x
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What is hemoglobin?
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a tetramere of 4 heme units, each of which is associated with a polypeptide globin portion
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Where does heme synthesis take place?
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it occurs in erythroid precurosors through the reticulocyte stage and involves steps that take place in the mitochondria and cytoplasm
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What is free heme and what is its fate?
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it is a potent oxidant that can damage cells, so in plasma it is bound to hemopexin to go to the liver for degradation
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What is the structure of heme?
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a protoporphrin ring with a central iron atom that is added to protoporphyrin in the final step in the mitochodnria after which it is transferred to the cytoplasm to be combined with globin
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How much oxygen can one Fe2+ carry?
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one molecule of O2 but only if iron is in the ferrous state
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How does lead toxicity affect heme synthesis?
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inhibits ALA dehydrase and inhibits enzymes that break down ribosomal RNA so ribosomes persist in mature RBCs- results in blue inclusions- basophilic stippling
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What affect does congenital erythropoietic porphyria in cattle, pigs, cats and humans have on heme synthesis?
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-porphyrins are produced in the intermediate steps of heme synthesis
-mutations that lead to excess porphyrins =>porphyrias -autosomal recessive deficiency in UPG II cosynthetase -affected animals accumulate abnormal porphyris in teeth, bone, gums, and skin (photosensitivity in non-pigmented) -porphyrins are excreted in urine causing brown to wine color RARE |
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What affect does copper deficiency have on heme synthesis?
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-Cu is part of ceruloplasmin which regluates Fe reelease from macrophages and Cu is a cofactor for ALA dehydrase which is necessary for heme synthesis
-Cu deficiency causes microcytic, hypochromic anemia but is less common than iron deficiency -excess molybdenum inhibits copper which could cause copper deficiency |
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What type of anemia would be caused by B6 deficiency?
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microcytic, hypochromic anemia
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What is the process of globin synthesis?
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polypeptides are synthesized on polyribosomes in teh cytoplasm, hemoglobin type depends on the globin chain
2 alpha and 1 non-alpha or beta chains occur in adult hemoglobin abnormalities= hemoglobinopathies (sickle cell anemia) |
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What are the 4 disorders of heme synthesis?
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lead toxicity
congenital erythropoietic porphyria in cattle, pigs, cats, humans copper deficiency pyridoxine (B6) deficiency |
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How much O2 can one hemoglobin molecule carry?
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4 O2 molecules
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Why is the oxyhemoglobin dissociation curve s-shaped?
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the binding of the 1st molecule of O2 causes a conformational change that allows easier binding of subsequent O2 molecules
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How do changes in the partial pressure of oxygen change the % saturation of Hb?
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as partial pressure of oxygen increases, the percent saturation of oxyhemoglobin increases
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what is the range of tissues where small decreases in O2 cause rapid release of O2 from Hb?
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around 50 down to 10 mmHg
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What conditions in the tissues cause a right shift in the oxyhemoglobin dissociation curve?
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low pH, high 2,3 DPG, high temperature and high CO2
--> decreased binding affinity of Hb for O2 so O2 is more readily released |
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What conditions in the lungs cause a left shift in the oxyhemoglobin dissociation curve?
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high pH; low 2,3 DPG; low temperature; low CO2
-->increased binding affinity of hemoglobin for O2 so O2 is less readily given up at the tissue level |
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What enzyme in RBCs is involved with Hb affinity for O2 in tissues?
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Carbonic anhydrase
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What is the effect of 2,3 DPG on Hb affinity for O2?
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it is produced in anaerobic glycolysis
When it combines with Hb, it allows increased unloading of O2 in the tissues |
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How do 2,3-DPG levels change in hypoxemic states and why?
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they increase so more oxygen can be available to the tissues from hemoglobin
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How does fetal hemoglobin differ from adult hemoglobin?
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amino acid composition of globin chains determines Hb type
fetal Hb has a higher affinity for O2 and decreased ability to bind 2,3-DPG than adult Hb facilitates O2 transport from mother to fetus |
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How does methemoglobin differ from normal hemoglobin?
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it has Fe3+ instead of Fe2+
-cannot carry oxygen -colors blood dark brown |
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What can cause methemoglobin?
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oxidant drugs, nitrites or a deficiency of NADH or methemoglobin reductase
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How does carboxyhemoglobin differ from normal hemoglobin?
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carbon monoxide combines with hemoglobin instead of O2
it cannot bind oxygen bright cherry red blood |
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How much iron is found in the hemoglobin?
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60-65%
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How much iron is found in ferritin and hemosiderin?
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30%
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Where does most of the iron for RBC production come from?
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recycling old RBCs
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Where is dietary Fe absorbed?
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from the duodenum and upper jejunum
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What compounds in the diet may decrease availability of dietary iron?
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phytates, oxylates, phosphates
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What can increase absorption of dietary iron?
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reducing agents (ascorbic acid)
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What can decrease absorption of dietary iron?
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prolonged anti-acids
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How is iron absorption related to Fe stores?
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inversely proportional
abundant stored Fe--> decreased absorption of iron |
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How is iron absorption related to erythropoiesis?
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they are proportional:
increased erythropoiesis-->increased Fe absorption |
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What is required for intestinal absorption of iron?
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appropriate changes in pH in the GI tract, functional divalent metal transporter 1 (DMT1) on the mucosal surface of intestinal epthelial cells, functional ferroportin to transport Fe out of mucosal epthelial cells
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How often are mucosal cells sloughed, taking residual iron with them?
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1-2 days
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What body conditions can increase demand for iron?
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growth, pregnancy, blood loss
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What is the usual cause for iron deficiency in veterinary medicine?
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chronic blood loss almost always
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How is iron transported from mucosal cells to tissues?
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transferrin binds two Fe3+ atoms for transport to tissues, RBC precurosors have transferrin receptors, once Fe is removed from transferrin it is recycled
Ceruloplasmin is required for mobilization of Fe from tissues |
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Where is transferrin synthesized?
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in the liver and is regulated by hepatic iron stores
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What is the only method of excretion of iron?
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sloughing of intestinal epithelial cells
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Where does excess iron accumulate?
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macrophages (usually)
bone marrow liver pancreas cardiac muscle tissue damage when in excess |
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How is iron stored in the liver, spleen and marrow?
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Ferritin- water soluble iron-protein complex that is not visible for light microscopy
Hemosiderin- relatively insoluble complex in RE cells - gold brown on light microscopy |
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Where is hepcidin synthesized and what is its role in iron?
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it is synthesized in the liver and is a major systemic regulator of iron distribution
it inhibits dietary iron absorption and icnreases iron uptake by and iron retention in macrophages |
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What can effect the synthesis of hepcidin?
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down regulated: anemia, hypoxia
upregulated: inflammation-->anemia of chronic disease |
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How is iron status assessed in the laboratory?
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measure serum iron, the capacity of transferrin to bind iron and ferritin
measured in patients with anemia due to iron deficiency |
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Why do RBCs need ATP?
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to maintain volume, shape, deformability and protect against oxidizing environment
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Why do mature RBCs rely on anaerobic glycolysis?
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they need it to generate ATP because they do not have mitochondria
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What are the two pathways for glucose metabolism in RBCs?
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anaerobic glycolysis- "energy" pathway
pentose phospate pathway- "antioxidant" pathway |
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What is the most common pathway of glucose metabolism?
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Emden-Meyerhof pathway- generates ATP
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What kinases are important in the Embden-Meyerhof Pathway?
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hexokinase, phosphofructokinase, pyruvate kinase
-rate limiting |
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What affects do abnormalities of anaerobic glycolysis have on RBCs and what is an example?
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they result in a shortened RBC lifespan w/o Heinz body formation
PFK deficiency in English Springer Spaniels and Whippets PK deficiency in basenjis, beagles, and Westies |
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Where in the anaerobic glycolysis pathway is 2,3-DPG produced?
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from the Rappaport-Luebering shunt of EMP
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What percentage of glucose metabolism is accomplished via the pentose phosphate pathway or hexose monophosphate shunt?
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5%
"antioxidant pathway" |
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What are the products of the pentose phosphate pathway?
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NADPH, glutathione which protect RBCs from oxidative damage
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What RBC changes will be seen with abnormalities in the pentose phosphate pathway?
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hemolytic anemia with Heinz body formation
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What percent of glutathione is reduced (GSH) in healthy cells?
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90%
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What generates GSH?
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glutathione reductase and NADPH
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What can decrease GSH production?
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oxidative damage--> heinz body formation and hemolytic anemia
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What can cause reduced GR activity in horses and what are the results?
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deficiency of flavin adenine dinucleotide
results in eccentrocyte and Heinz body formation and hemolytic anemia |
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What are examples of endogenously generated oxidants in blood?
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superoxide, H2O2, hydroxyl radical (OH-)
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What affect do oxidants have on RBCs?
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damages the iron moiety of hemoglobin (methemoglobin), the SH groups on the globin portion of the hemoglobin molecule and/or the RBC membrane
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How is normal methemoglobin processed in the body?
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it is reduced to functional hemoglobin by methemoglobin reductase which requires NADH generated by anaerobic glycolysis
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What are the clinical signs of methemoglobin reductase deficiency?
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exercise intolerance, intermittent lethargy, increased risk associated with anesthesia, darker blood than normal
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What causes Heinz bodies?
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cross linking of -SH groups in the globin portion of the hemoglobin molecule results in precipitation and formation of large aggregates of hemoglobin that bind to the RBC membrane causing visible protrusions from the RBC suface
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What causes eccentrocytes?
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oxidative damage to the RBC membrane causes oxidation of membrane SH groups and lipid peroxidation that results in adhesion of opposing areas fo the cytoplasmic face of the RBC membrane and formation of eccentrocytes
they have decreased deformability and are susceptible to subsequent splenic trapping |
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What is the RBC life span in a dog?
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120 days
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What changes are associated with senescence of RBCs?
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decreases in cell surface area, deformability, activity of membrane ion pumps, activity of enzyme systems, increases in oxidative damage and bidning of autologous immunoglobulin and complement
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How are senescent RBCs broken down and removed?
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phagocytized and degraded by macrophages in spleen and liver
~1% removed each day Hemoglobin from senescent RBCs is metabolized, amino acids are reutilized to synthesize proteins, Fe is stored or exported to tissues, Heme portion is metabolized to bilirubin |
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What is conjugated bilirubin and how is it made?
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"post-hepatic or direct"
conjugated by hepatocytes soluble in H2O and excreted in bile small portion passes back into blood-->excreted by kidney if unbound to protein bound to protein-->delta bilirubin in intestine it's converted to urobilinogen by bacterial reduction and excreted as stercobilinogen in feces 10% reabsorbed and enters blood removed from blood by hepatocytes and re-excreted or circulates to kidneys--> out in urine |
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What is unconjugated bilirubin and how is it made?
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it results from the metabolism of heme by macrophages
unconjugated bilirubin is insoluble in water so it binds to albumin in plasma and is metabolized in the liver -->not lost in urine |
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What can cause hyperbilirubinemia?
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hemolysis (prehepatic)
liver disease (hepatic) obstruction of bile flow (post-hepatic) |
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What are the clinical signs of hyperbilirubinemia?
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yellow discoloration of plasma and tissues (icterus)
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What will be on the labwork of an animal with prehepatic hyperbilirubinemia?
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moderate to severe hemolysis
-unconjugated bilirubin -anemia -spherocytes, heinz bodies, and hemotropic parasites on blood film -unconjugated bilirubin rapidly cleared |
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What causes hepatic hyperbilirubinemia?
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conjugated or unconjugated
-impaired ability of hepatocytes to uptake, conjugate, or secrete bilirubin -due to lipidosis, cirrhosis, inflammation, neoplasia, or genetic defects -->increased liver enzymes |
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What causes post-hepatic hyperbilirubinemia?
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conjugated
-obstruction of bile from intrahepatic or extrahepatic cholestasis most often due to pancreatitis, cholangitis or neoplasia |
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What is the most common form of hyperbilirubinemia?
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mixed- occurs from hemolysis with secondary hepatocellular injury due to hypoxia
-or hepatocellular damage and inflammation that causes post-hepatic obstruction |
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What test can be used to quantify unconjugated and conjugated bilirubin in the plasma?
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the Van der Bergh test
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What is the rule of thumb for small animals and hyperbilirubinemia?
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if >50% unconjugated- Hemolysis
if >50% conjugated- cholestasis or hepatocellular disease |
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How do horses differ from other species in terms of bilirubin?
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normally have higher serum bilirubin
fasting and fever cause unconjugated bilirubin anorexia should be differential for bilirubinemia >50% unconjugated- hemolysis and cholestasis |
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What is the definition of anemia?
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a decrease in RBC mass
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Why might the PCV be normal in acute, severe blood loss?
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initially, RBCs and plasma are both lost
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What can duration tell you about cause of anemia?
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abrupt= acute hemorrhage or hemolysis
gradual=chronic blood loss, chronic renal failure, anemia of chronic disease, bone marrow suppression |
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What can periodic episodes of weakness tell you about the cause of anemia?
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intra-abdominal vascular tumors that periodically bleed into the abdomen
tumor ruptures then seals, blood is rebsorbed |
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What do polyuria and polydipsia indicate with anemia?
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it is likely due to chronic renal disease
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What does a history of weight loss, fever, general malaise indicate with anemia?
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anemia of chronic disease or inflammation
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What are the clinical signs of anemia?
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weakness, lethargy, exercise intolerance
hyperpnea, exertional dyspnea pale mucous membranes tachycardia or functional murmur due to low blood viscosity fever with hemolysis pica |
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How are clinical signs related to severity and rapidity of the development of the anemia?
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if onset is acute, animal may show signs of distress at PCV of 15-20%
if onset is gradual, animals can adapt and may tolerate a PCV of 6-10% |
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How can you differentiate between hematuria and hemoglobinuria?
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if you centrifuge the sample- hematuria will clear b/c the RBCs will sink to the bottom
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What are the physiologic mechanisms of adaptation to anemia?
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-decreased activity
-increase RR and CO -Splenic contraction and mobilization of RBC reserves -selective vasoconstriction -increased thirst -increased production of 2,3-DPG -BM stimulation in response to erhythropoietin-->regenerative -few clinical signs at rest, but stress or exercise precipitate clinical signs or collapse |
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What is the most commonly used scheme to classify anemia?
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regenerative or non-regenerative based on the reticulocyte count
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What are the most common causes of regenerative anemia?
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hemorrhage or hemolysis
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How do you evaluate regeneration in horses?
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serial MCV because they do not release reticulocytes
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What causes non-regenerative anemia?
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chronic disease, chronic renal failure, or primary bone marrow disease
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What are reticulocytes?
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non-nucleated, immature RBCs that are larger than mature RBCs. Ribosomes make them blue-gray staining
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What is evidence of regeneration in terms of corrected reticulocyte index?
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>1% in dogs
>0.5% in cats |
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How do you obtain an absolute reticulocyte count?
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multiply the percentage of reticulocytes by the RBC count
>60,000 in dogs >50,000 in cats indicates regenerative response |
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Why are only aggregate reticulocytes counted in cats?
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they represent active regeneration whereas punctate reticulocytes represent cummulative regeneration
-important if anemia is initiall regenerative then becomes non-regenerative |
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Why are reticulocyte counts not usually used in cows?
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the bone marrow releases them unpredictably so lack of reticulocytosis does not indictate non-regeneration
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What blood values are used to determine regeneration in horses?
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MCV and RDW
>2fl in MCV or increased RDW is evidence of regeneration |
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When does the initial reticulocyte response occur in the body?
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in 2-3 days
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What is MCV and how is it useful in classifying anemia?
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mean corpuscular volume- measures RBC size-
anemia is classified as normocytic, macrocytic, or microcytic |
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What is MCHC and how is it useful in classifying anemia?
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measures hemoglobin concentration
-normochromic or hypochromic |
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Increased MCV and decreased MCHC is what type of anemia?
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macrocytic, hypochromic usually regenerative anemia due to hemorrhage or hemolysis
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Normocytic normochromic RBCs indicate what type of anemia?
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nonregenerative anemia due to chronic disease, chronic renal failure or primary bone marrow disease
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If MCV and MCHC are both low, what type of anemia is it?
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microcytic, hypochromic anemia
usually due to iron deficiency (could be copper or pyridoxine deficiency) |
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What does microcytic, normochromic RBCs indicate?
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portosystemic shunts, Japanese Akitas, Sharpeis, and Shiba Inus
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What can cause macrocytic, normochromic RBCs?
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horses with regenerative anemia
FeLV infection Greyhounds/poodles/miniature/toy poodles cobalt deficiency in ruminants B12/folic acid defciency-->megaloblastic anemia |
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What are the classifications of anemia based on pathogenesis?
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blood loss (acute or chronic hemorrhage)
increased destruction (intravascular or extravascular hemolysis) decreased proliferation of hematopoietic precursors |
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What do nRBCs on blood film examination indicate?
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splenic dysfunction
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RBC fragments on blood films are indicative of what?
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microangiopathic disease
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What does microcytic, normochromic RBCs indicate?
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portosystemic shunts, Japanese Akitas, Sharpeis, and Shiba Inus
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What can cause macrocytic, normochromic RBCs?
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horses with regenerative anemia
FeLV infection Greyhounds/poodles/miniature/toy poodles cobalt deficiency in ruminants B12/folic acid defciency-->megaloblastic anemia |
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What are the classifications of anemia based on pathogenesis?
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blood loss (acute or chronic hemorrhage)
increased destruction (intravascular or extravascular hemolysis) decreased proliferation of hematopoietic precursors |
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What do nRBCs on blood film examination indicate?
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splenic dysfunction
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RBC fragments on blood films are indicative of what?
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microangiopathic disease
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