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44 Cards in this Set
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Describe anaemia |
Anaemia is defined as decreased erythrocyte mass |
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Describe haemoglobinemia |
Free haemoglobin in the plasma (so when you spin down the blood, you may notice a red tint to the plasma) |
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What is erythropoietin? |
EPO is the principle growth factor promoting viability, proliferation, and differentiation |
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What are the sources of EPO? |
Adults-from the kidney and to a lesser degree the liver Foetus- from the liver |
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What stimulates the production of EPO? |
hormones and other growth factors, low blood volume |
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What are the inhibitors of EPO release? |
TNF-alpha, IL-1, IFN, TGF-beta These are all inflammatory mediators, they inhibit EPO release and its activity on RBC, hence why animals with inflammation will often become anaemic |
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What is the maturation of a RBC? |
Start with a pluripotent stem cell-->myeloid stem cel (committed cell) --> erythroid CFU --> primitive/mature --> rubriblast--> prorubricyte--> rubricyte--> metarubricyte-->chromatophil-->erythrocyte All of this occurs within the marrow. |
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What is the production of the platelets? |
Pluripotent stem cell--> myeloid stem cell (committed cell)--> megakaryoblast-->megakaryocyte--> platelets |
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What is a rubriblast? |
undifferentiated mother cell for all the RBCs. Rubriblasts, prorubricyte, and rubricytes can all continue to divide to make more cells, particularly under the influence of EPO. When the Hb reaches a desirable threshold, it signals to the rubricyte to stop dividing and mature. |
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Once the rubricytes stop dividing, how does the RBC mature? |
Metarubricytes, polychromatophils, and mature erythrocytes can no longer divide. The nucleus shrinks down and the Hb builds up in the cell. The cytoplasm turns from blue to pink. Finally, when the nucleus is shrunk down, the macrophages take out the nucleus and donates an iron to make the Hb. This process takes 3-5D |
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How does anaemia present itself in labwork? |
Decreased haematocrict/PCV Decreased RBC/L Decreased Hb level if any of the following are low, then the pt is said to be anaemic, resulting in decreased O2 carrying capacity |
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What are the two causes of anaemia? |
RBC loss (haemorrhage, haemolysis) or decreased RBC production |
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What is regenerative anaemia |
There's a marrow response Evidence: reticulocytosis, polychromasia, hypochromic macrocytic |
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Non-regenerative anaemia |
No marrow response Pre-regenerative (marrow has not had sufficient time to respond) or non-regenerative-> no reticulocytosis, minimal polychromasia Normocytic normochromic or hypochromic microcyctic |
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How do we assess for regeneration? |
Blood smear: look for polychromasia Reticulocytosis: done with a analyzer, most accurate means of assessment, lets us known the levels of immature RBCs in blood. We'll also see evidence of macrocytosis and hypochromasia Bone marrow evaluation: Erythroid hyperplasia |
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What is special about horses and regenerative anaemia? |
In horses, we will only see macrocytosis, no chromatophils. They prefer to hold onto their RBCs until they're more mature.
So we'll perform serial monitoring of PCV/CBC to assess improvement |
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What are the morphological changes that we will see on a blood smear with regenerative anaemia? |
Polychromasia (large blue cells) Macrocytosis anisocytosis Hypochromasia Increased howell-jolly bodies Increased nucleated RBCs Increased levels of basophilic stippling |
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How are reticulocyte counts performed? |
Manually using a new methylene blue stain--> equal parts blood and stain are mixed and then incubated 10-15 minutes before smear is made. Count the number of reticulocytes per 1000 RBCs Analyzer |
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What are the two forms of reticulocytes in cats? |
Aggregate and punctate (more mature reticulocytes). In all other species besides cats, the maturation is fast and won't tell us anything. |
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What are aggregate reticulocytes? |
Polychromatophils released in low numbers in dogs (1%) and cats (.4%). However, in active regenerative anaemia you will see these numbers increase. Aggregates tell us what the marrow did recently. |
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What are punctate reticulocytes? |
More mature form of reticulocyte. Reticulocytes take up to 2 weeks to mature in cats, so up to 10% punctate reticulocytes are seen in health (not very useful diagnostically) |
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How do we assess the degree of regeneration? |
Corrected reticulocyte % Absolute count |
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What is the absolute count? |
# of reticulocytes/L bloodNormal counts vary with species. 0-120 x10^9/L. If accounts are above reference level, indicative of regenerative anaemia
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What is the corrected reticulocyte %? |
Reticulocyte % x RBC If we determine the % of reticulocytes then we need to determine if this is normal. Perform corrected reticulocyte % Retic % x (pt hct/ avg species Hct) Average species Hct in dog: .45, cat:.37 CRP 0-1% in health We want higher counts with more severe anaemia otherwise considered non-regenerative healthy birds will have 4-5% |
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What is MCV |
Mean Corpuscular Volume (how much space do the cells take up) It's the average you can take, you can have quiet a few immature cells in circulation and it still won't take the average size above normal. So sometimes animals with regenerative anaemia will have normal average cell volume; they may not show up as macrocyte. |
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What is MCHC? |
Mean corpuscular Hb concentration Amount of Hb per average cell. Increase is not possible, hyperchromic indicates either free Hb or lipaemia. |
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What is RDW? |
Red cell distribution width Measures the variation in cell size An increase in RDW indicates anistocytosis |
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What are the responses to acute haemorrhage? |
Per-acute Acute stage I Acute stage II |
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What is per-acute haemorrhage |
No change in the Hct or the TP (just started to Haemorrhage, so we lose a lot of plasma, so we won't notice the change in the density of the blood). |
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What is Acute haemorrhaging? |
Stage I within hours, decrease Hct and TP as the fluid shifts from extravascular to the intervascular space, activation of RAAS. Pre-regenerative anaemia |
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What is the acute stage II of haemorrhaging? |
Within 3-5d. EPO is produced (stimulated by hypoxia). Evidence of regeneration in blood (polychromesia, macrocytes, reticulocytes) Increase in Hct and protein IF haemorrhage is controlled. If we lose bood we lose plasma. So after an animal has haemorrhaged, the first thing we check is the protein level. If this has dropped, then we need to be concerned about haemhorrage. If not, then look for alternatives to RBC loss. |
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What are the two forms of haemolysis? |
Intravascular (rupture of RBC in circulation) and extravascular (phagocytosis of RBC by macrophages in spleen marrow and liver) |
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What is the first stage of acute haemolysis? |
Within hours, decreased Hct with normal protein, no evidence of regeneration (pre-regenerative), +/- haemoglobinuria and haemoglobinuria (if filtered by the kidneys). |
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What is the second stage of acute haemolysis? |
within 3-5D, EPO is produced, evidence of regeneration in the blood. If under control, Hct increases. If ongoing, bone marrow may not meet destruction, same can occur with haemhorrage. |
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What is the evidence of haemolysis? |
+/- haemoglobinemia, haemoglobinuria (intravascular)
Often see hyperbilirubinaemia/jaundice (as the RBC is broken down, bilirubin production increases bc increased Hb recycling) Spherocytosis (extravascular) Schistocytes (irregular shapes) Keratocytes (tags hanging off) if microvascular fragmentation. Normal protein levels. |
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What are the causes behind intravascular haemolysis? |
IMHA, neonatal isoerythrolysis, transfusion reaction (disease) Oxidative injury Severe hypophosphatemia (phosphorous is essential in RBC metabolism, decreased levels may make RBC easy target for macrophages) Genetic disorders |
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What are some of the causes of extravascular haemolysis? |
Within the bone marrow, spleen, or induced via macrophages. Immune mediated disease (primary or secondary , e.g. drugs) Infections Oxidative damage neoplasia Fragmentation (e.g. DIC, haemangiosarcoma, heart worm) Genetic disease |
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What is IMHA? |
Primary is idiopathic autoimmune, common in dogs. Secondary is induced by drugs and vaccinations, infections, neoplasia; more common in cats. |
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Alloimmune? |
Antibody against foreign RBC, antigen of same species (neonatal isoerythrolysis-more common in horses), blood transfusions. |
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What are the mechanisms of haemolysis? |
Antibody or drug or parasite can bind to the RBC. Macrophages will identify and either destroy the cell (more common) or take a small chunk out, RBC becomes spherocyte. Clue of extravascular anaemia. |
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How is IMHA diagnosed? |
presence of spherocytosis or ghost cells |
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Which of the following is incorrect? |
D. |
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Why do we often see hyperbilirubinaemia with haemolytic disorders? |
Unconjugated bilirubin is a byproduct of erythrocyte breakdown. |
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What is the most reliable indicator of regenerative response in cats and dogs? |
D. Reticulocytosis |