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140 Cards in this Set

  • Front
  • Back
Match the process to its function:
Erythropoiesis Host Defense
Leukopoiesis Primary Hemostasis
Thrombopoiesis Oxygen Delivery
Erythropoiesis --> Oxygen Delivery
Leukopoiesis --> Host Defense
Thrombopoiesis --> Primary Hemostasis
TRUE/FALSE: Hematopoiesis is under the control of cytokines, among other hormonal and chemical interactions.
TRUE!
How are unipotential and multipotential stem cells and their development different from each other?
Multipotential cells are present in very low numbers and are scattered throughout the marrow. The are able to give rise to any type of cell in any type of cell line.
Unipotential stem cells give rise to only one line of blood cells, with 1 daughter cell producing the blast cell of the corresponding cell line and the other cell replenishing the unipotential cell.
Erythroid hyperplasia would be expected to be seen under what conditions?
Following trauma
Following blood loss
Following erythrocyte destruction
How can a Myeloid:Erythroid ratio be the same in cases of Myeloid hypoplasia and erythroigd hyperplasia?
Because the ratio is relative to the amount of cells present in each cell line, reduced to a factor of one. Therefore a decrease in one cell line will produce the same ratio as an increase in the other cell line.
Where are sites of extramedullary hematopoiesis?
Liver
Spleen
What are 3 methods of measring erythrocyte mass?
Packed cell volume (PCV)
Red blood cell count (RBC)
Hemoglobin concentration (HGB)
What is the process (in general terms) of erythrocyte destruction within normal physiology?
Degenerative RBCs are phagocytized by macrophages within the spleen (and other organs). The hemoglobin is broken down and reutilized as is the iron in the hemoglobin. Portions of the pyrolle molecule are transported to the liver as free bilirubin where it's conjugated & excreted through the bile duct into the intestine.
List the different RBC progenitor cells in order from least differentiated to most. Where are 2 areas of critical development?
Rubriblast
Prorubricyte
Early rubricyte --> Start of hemoglobin production
Middle rubricyte
Late rubricyte --> Critical concentration of hemoglobin halts RBC division. (Without enough iron, cells will divide once more, producing abnormal RBCs)
Metarubricyte
Reticulocyte
Erythrocyte
How long does it take to go from a rubriblast to a reticulocyte?
5 days
How does the kidney affect erythropoiesis?
The kidney produces erythropoietin. This process is dependent on the presence of enough function tissue to produce erythropoietin, which is why a patient may be anemic with kidney disease.
At what rate, normally, are RBC's replaced?
1% RBCs replaced daily
What morphologic changes can be seen throughout erythrocyte maturation?
Cells become smaller
Chromatin aggregates, matures & the nucleus is eventually extruded.
Cytoplasm changes from blue to orange.
What is another name for a nucleated RBC?
Metarubricyte
What is the best staining technique to visualize Reticulocytes?
Incubate a mixture of 1 PART Blood : 1 PART New Methylene Blue for 15 MINUTES
An increased number of reticulocytes in the systemic circulation is an indication of what?
Regenerative anemia
In what species will you NEVER see a regenerative anemia?
REMEMBER THIS QUESTION!!!!!
HORSES!
What is the range in lifespan for mature erythrocytes?
70-160 days
Is the Hematocrit (HCT) a measured or calculated value? How is it quantified?
Calculated
HCT = ( MCV x [RBC]) / 10
Identify whether each erythrogram value is either MEASURED or CALCULATED:

MCV
HCT
MCHC
MCV = MEASURED
HCT = Calculated
MCHC = CALCULATED
What are some sources of error in the determination of RBC indices? What effect would they have on the measurements?
Inadequate mixing of blood with EDTA tubes
Too little blood added to too much EDTA & subsequent shrinking of RBCs from osmotic pressure gradient
Small clots
Lysed RBCs from poor handling --> Falsely lowers
Inadequate centrifigation --> Falsely elevates
Agglutination --> Falsely decreases
Poor recognition by automated analyzer --> Falsely decreases
What are the 3 processes that result in anemia?
Increased RBC destruction
Decreased RBC production
Increase RBC loss
Under normal circumstances, what physiologic processes occur to accommodate/fix anemia?
Lowered oxygen tension from anemia leads to hypoxia (in renal tissue)
Renal cortices detect lowered oxygen tension
Cortical cells respond via increased production & release of EPO
EPO travels bone marrow where it stimulates RBC production & early release of reticulocytes
After how many days from the start of anemia (assuming RBC production is normal) would you expect an increase in the number of circulating reticulocytes?
2-3 days
What are some clinical signs associated with anemia?
NON-SPECIFIC (so don't get too hung up on the details...)
Weakness, exercise intolerance, pale mucus membranes, tachypnea, heart murmur, tachycardia, syncope, malaise, depression, lethargy, etc.
What lab values are key in determining anemia?
RBC count
HGB
HCT
PCV
TRUE/FALSE: Anemia can be classified as a disease/diagnosis.
FALSE!
What schemes are used to classify anemia?
Red cell indices
Number of reticulocytes
Pathophysiologic characteristics/mechanisms
How is the MCV calculated?
(HCT x 10) / RBC
What are some differentials for Microcytosis?
Iron deficiency!!!!
Portosystemic shunt
Japanese breed dog
Foals
+/- Copper toxicity
What are some differentials for Macrocytosis?
Reticulocytosis (regenerative anemia)
Poodles
Agglutination of RBCs (ARTIFACT)
FeLV
Folate/cobalamine deficiency
Why can microcytic anemia be a sequale of iron deficiency?
Without enough iron, the transition from a late rubricyte to a metarubricyte is delayed, forcing the cell to undergo an additional division. Undergoing another division maintains the relative concentration of Hb in the cell by reducing its cytoplasm concentration/size. Thus, microcytosis.
Why is microcytosis thought to occur with a portosystemic shunt?
Secondary iron deficiency from blood not traveling through the liver, decreasing the rate of recycling Hb and its iron.
Why is the MCV sometimes elevated with regenerative anemia?
Regenerative anemia is characterized by an increase in circulating reticulocytes. Reticulocytes are typically larger than mature RBCs, leading to a macrocytosis.
What does the MCHC correlate with? How is it calculated?
average concentration of hemoglobin within circulating RBCs.
MCHC = (HGB x 10) / HCT
What are some differentials for hypochromasia?
Iron deficiency
Reticulocytosis
What are some differentials for hyperchromasia?
Artifact from hemolysis (in vitro OR in vivo)
Heinz bodies (a LOT)
Why are hypochromic RBCs associated with iron deficiency or RBC regeneration?
Iron deficiency --> because the RBCs don't have enough iron to aptly concentrate the Hb in the cell.
RBC regeneration --> because Reticulocytes are typically larger than mature RBC's with the same concentration of Hb in the cell, so the hypochromasia is relative.
Why does hemolysis often result in an increased MCHC?
Because MCHC is a CALCULATED value and is dependent on the measured HGB concentration in the blood. During cases of intravascular hemolysis, the HGB is "falsely" elevated due to an increased release of it from lysed RBCs. This then increases the MCHC.
Reticulocytes typically appear blue - blue gray because of higher concentrations of what in the cell?
RNA!
How is the Absolute Reticulocyte number calculated?
KNOW THIS QUESTION!
Absolute Retics = Reticulocyte % x RBC count.
Reported in thousands/uL
If you wanted to determine what a patient's reticulocyte count would be were the patient NOT currently anemic, how would you calculate that? What is this called?
Corrected Reticulocyte Percentage

CRP = % retics x (patient's HCT/normal HCT)
What are normal HCT levels for a dog? Cat? Cow?
Dog = 45
Cat = 35
Cow = 35
Match the absolute Retic count to its description:

0 - 10,000 Regenerative, mild to moderate
10,000 - 60,000 Non-regenerative
60,000 - 200,000 Maximal regeneration
200,000 - 500,000 Non to poorly regenerative.
0 - 10,000 = Non-regenerative
10,000 - 60,000 = Non to poorly regenerative
60,000 - 200,000 = Regenerative, mild to moderate
200,000 - 500,000 = Maximal regeneration
How long does it take for a reticulocyte to mature into a full RBC?
1-2 days
What are the 2 forms of reticulocytes in the cat? What is their significance?
Aggregate retics = Lifespan of 1-2 days. Indicate an active RBC regeneration
Punctate retics = Lifespan of 1-3 weeks. NOT a measure of recent RBC regeneration
Red cell distribution width (RDW) gives a quantitative measure of what morphologic characteristic?
Anisocytosis
In What types of anemias might you expect an increased RDW?
Microcytosis
Macrocytosis
Reticulocytosis
How can you differentiate between appropriate and inappropriate metarubricytosis?
Appropriate means there are greater numbers of later stages of erythrocytes than metarubricytes.
Inappropriate means there are greater numbers of metarubricytes than later stages of erythrocytes.
What is the primary cause for an INappropriate metarubricytosis?
Loss of finely controlled release of nRBCs from the bone marrow and/or other erythropoeitic sites, including:
Severe/extreme peracute anemia
Toxic damage to membranes separating marrow sinuses from hematopoeitic sites.
Fracture/surgery
Splenic contraction/injury
Leukemia
What is Rouleaux? What condition does it typically correlate with?
Rouleaux = stacking of RBCs (observable in monolayer)
Typically indicates an increase in plasma proteins.
Common in horse and cat
What is agglutination? What does it typically indicate? How can you differentiate it from Rouleaux?
Agglutination is the aggregation/clumping of RBCs into GRAPE-LIKE clusters (vs. STACKS as in Rouleaux). Typically indicates EITHER auto-agglutination due to an auto-antibody/immune-mediate disease OR heparin (especially for in vitro blood of horses).
What are Ghost Cells? Why are they significant?
Extremely pale staining RBCs that contain mostly cell membrane with minimal residual cytoplasmic HGB.
Usually indicates intravascular hemolysis.
What abnormal cell types/inclusions would you expect to see from intravascular hemolysis?
Ghost cells
Spherocytes
Heinz bodies
Mycoplasma inclusions
What is a poikilocyte?
A hypochromic RBC.
What is a polychromatophilic RBC?
Basically, a reticulocyte.
What is anisocytosis?
Variation in the volumes of erythrocyte cells.
Presence of Acanthocytes (or spur/burr cells) in high numbers indicate what pathologic process/disease?
Splenic & hepatic disease.
Especially splenic hemangiosarcoma or infiltrative splenic disorders.
An elevation of acanthocytes, keratocytes and schistocytes is evidence of what?
Intravascular trauma/shearing of RBCs.
An elevation of acanthocytes, keratocytes, schistocytes, microcytes and hypochromasia is evidence of what?
Iron deficiency from decreased RBC membrane strength.
What are the defining characteristics of eccentrocytes?
Bonding of RBC membranes leading to a collapsed peripheral, crescent-shaped region where the Hb is displaced eccentrically caused by oxidative damage. Seen more in dogs and horses than cats.
Echinocytes are seen with what pathologic conditions?
Dehydration
Metabolic derangement
Envenomation
Keratocytes can be found from what pathologic condition? What do they look like?
Iron deficiency
DIC/microangiopathic shearing
Liver disease

Look like "helmet" or "blister" cells
Schistocytes can be found in what pathologic conditions? How are they recognized?
Seen in DIC
Vasculitis
Iron deficiency
Hemangiosarcoma
Caval syndrome of dirofilariosis
Endocarditis
Recognized as fragments of RBCs
How can you identify a target cell?
Polychromatophilic RBC that have multiple "layers" of pigmentation due to an excess of cell membrane.
How are spherocytes formed? What pathologic conditions are they found in?
Formed by partial phagocytosis from macrophages attempting to consume cell & antibodies bound to cell surface.
Found in IMHA
Precipitation of ribosomes in RBCs is called what? What does it indicate?
Basophilic stippling
Common in regenerative anemias of CATTLE & strongly regenerative anemias of dogs, cats.
Also seen in lead poisoning (lead inhibits multiple enzymes in heme synthesis)
Aggregates of denatured Hb due to oxidative damage are called what?
Heinz bodies!
What stain is used to highlight heinz bodies?
New Methylene blue!
What are Howell-Jolly bodies? What conditions are they seen with?
Nuclear remnants that appear as small, dark purple round structures in RBCs.
Seen with regenerative anemia
Spleen dysfunction
Steroid use
After stimulation of the bone marrow by EPO, in how many days can you expect a reticulocytosis? Peak production of RBCs?
Reticulocytosis in 3-4 days
Peak production in 7-10 days
Blood loss anemia due to hemorrhage is typically caused by what events/conditions?
Blood vessels damaged through trauma, ulceration, neoplasia, etc.
Acquired or congenital coagulalopathy (factor deficiency, von Wilebrands disease)
Thrombocytopenia of <25,000 platelets/uL
What are some internal parasites that can cause blood loss anemia?
Dogs = hookworms (ancylostoma) & whipworms (trichuris)
Ruminants = Haemonchus & ostertagia
Coccidiosis
How are the PCV and plasma proteins characterized in a patient suffering from acute blood loss?
PCV and plasma protein are relatively equal to each other initially due to their concurrent loss.
What are the physiologic effects associated with acute blood loss (and the body's attempt to correct for it)?
A sudden anemia leads to hypoxia, which stimulates EPO production & release.
Splenic contraction releases concentrated RBCs & platelets.
After fluid therapy or plasma fluid redistribution, a clinical anemia will be apparent, followed by a reticulocytosis (3 days from initial loss).
What do you look for when diagnosing acute blood loss anemia?
History of bleeding/clinical evidence.
Hypoproteinemia
Regenerative anemia
What is chronic blood loss typical caused by?
External blood loss, usually from the GI (think parasites!) or urinary tract that occurs over a span of weeks to months.
How does a patient with chronic anemia adapt to the anemic conditions?
Patient's RBCs adapt via increased 2,3-DPG -->
shifts oxygen-Hb association curve to the RIGHT to LOWER Hb's AFFINITY for OXYGEN.
Consequentially, the patient's PCV may be markedly lower before clinical signs are apparent.
Later stages of chronic blood loss are due to what cause?
Iron deficiency
When diagnosing Chronic Blood Loss Anemia, what should you look for?
Clinical signs associated with external blood loss (melena, parasites, etc.)
Poorly regenerative - non-regenerative anemia
Microcytosis
Hypochromasia
Variable bone marrow appearance
Hypoproteinemia
Keratocytes, schistocytes (ass'd with iron deficiency)
Thrombocytosis (reactive)
Decreased serum ferritin
Younger animal
Increased BUN WITHOUT an increased Creatinine.
What is the process of RBC degeneration/lysis (whether it's normal or abnormal)?
Macrophages engulf RBC --> Red cell lysed & hemoglobin is digested into --> Globin protein to amino acids --> Heme into iron and bilirubin
What is the fate of bilirubin?
Bilirubin, from a lysed RBC enters the blood and is bound to albumin (unconjugated).
Bilirubin goes to the liver where it is conjugated and excreted in the bile.
What are typical areas of extravascular hemolysis?
Spleen
Liver
Bone marrow
What is the primary difference between intravascular and extravascular hemolysis that can be detected with clinical pathology?
Extravascular hemolysis shows NO Hemoglobinemia OR Hemoglobinuria. Intravascular hemolysis does.
What is formed from partial phagocytosis of an RBC?
Spherocyte!
What lab results can you expect from increased extravascular hemolysis?
Hyperbilirubinemia
Bilirubinuria
Anemia, typically regenerative
Moderate - marked reticulocytosis
How can you determine if intravascular hemolysis is present with just HGB and HCT?
Normally, the HCT should be 3 times higher than HGB. If this ratio is lower (HCT < HGBx3), then there is likely an increase in circulating hemoglobin from intravascular hemolysis.
Why does the body have scavenging systems for freely circulating Hb?
Recovery of iron
Prevention of kidney damage (acute tubular necrosis/nephrosis)
What protein, made by the liver, is primarily responsible for the collection of freely circulating Hb?
Haptoglobin.
Binds free Hb and carries it to the liver to be broken down & processed.
What are some causes of Immune hemolytic disease?
Idiopathic (primary)
Secondary: drugs, infectious agents, neoplasia, neonatal isoerythrolysis, incompatible transfusion.
What test can you run to detect patient autoantibodies to RBCs?
Direct antiglobulin test (Coombs' test).
How/Why does Rouleaux occur?
RBC membranes contain negatively charged groups
Change in plasma proteins from inflammation or infection increase binding to RBCs
Increased binding masks the negative charges and allows RBCs to stack on top of each other
What proteins are typically involved in Rouleaux?
Mostly fibrinogen
Others possible
In what species is some level of Rouleaux normal?
Horses & their relatives --> fewer negative charges on RBCs naturally
What are some materials that can cause oxidative damage to RBCs?
Onions
Garlic
Zinc
Red Maple
Skunk spray
Smoke
What are some infectious causes of intravascular hemolysis?
Hemotropic Mycoplasma
Anaplasma marginale/ovis
Leptospirosis
Some clostridial diseases
Equine Infectious Anemia virus
Babesia
FeLV
Therileria buffeli
Trypanosoma
What is the most common cause of non-regenerative anemia?
Anemia of Inflammatory Disease
How long would an anemia from decreased production (aka non-regenerative) take to display clinically?
Weeks to months.
RBC lifespan is 2-5 months, so clinical signs wouldn't develop until a significant number of RBCs had been destroyed.
What will the MCV and MCHC indicate as to the type of anemia for non-regenerative anemia?
Normocytic
Normochromic
What other CBC characteristics would be consistent with anemia of chronic/inflammatory disease?
Inflammatory leukogram
Hyperglobulinemia
How does the marrow look in cases of non-regenerative anemia?
Normal to mild decrease in marrow erythroid population
Abundant marrow hemosiderin (DOG) --> NOT IRON DEFICIENT!
What is the pathogenesis associated with AID/ACD?
Shortened RBC survival (due to some complicated process)...
Impaired iron mobilization/utilization
IL-6 induces hepcidin release from liver
Hepcidin inhibits iron absorption from the gut & inhibits iron release from the liver & spleen
Cytokines blunt EPO response
Non-regenerative anemia due to marrow hypoplasia will also manifest as what?
Multiple "-penias" of other cell lines:
Neutropenia
Thrombocytopenia
etc.
How might hypothyroidism cause a non-regenerative anemia?
Decreased metabolic rate decreases the need for Oxygen in the tissues, which selectively decreases the marrow population of erythrocytes.
What are the 2 main differentials for a relative erythrocytosis/polycythemia?
Hemoconcentration --> Dehydration
Redistribution --> Excitement/Splenic contraction
What is polycythemia vera?
A primary absolute erythrocytosis characterized by uncontrolled production of mature RBCs. It's a chronic, neoplastic myeloproliferative disorder.
What are some examples of cases of appropriate secondary erythrocytosis?
Increased EPO due to chronic hypoxia.
Chronic hypoxia from high altitude conditions, chronic pulmonary disease, right to left cardiac shunts
What are some examples of cases of inappropriate secondary erythrocytosis?
Renal cystic disease
EPO-secreting tumors
What are some differentials for Hyperferremia (increased serum iron)?
Iatrogenic excess (iron injection)
Hepatocyte damage
Increased glucocorticoids --> DOG, HORSE
What are some differentials for Hypoferremia (decreased serum iron?)
Loss causing iron deficiency
Young animals (think baby pigs)
Portosystemic shunt
TRUE/FALSE: Both the relative and the absolute leukocyte counts are used to interpret lab data.
FALSE! The relative counts should NOT be used to interpret lab data because, well, they're relative to the situation. It's kind of like analyzing a diet based on as fed vs. dry matter.
Describe the morphology of a segmented neutrophil.
Nucleus looks like a rope with various pinches - the segments.
The cytoplasm contains many granules which stain poorly and appear a very dusty/pale pink (neutral staining).
Describe the morphology of an eosinophil.
Red to dark pink-staining cytoplasmic granules with an affinity for Eosin dye.
Describe the morpholoy of a basophil.
Purple-staining granules in cytoplasm which have an affinity for Basic dyes.
In what species can basophils be increased in number normally?
Turtles
Rabbits
Describe the morphology of monocytes.
Larger than neutrophils
Various nuclear shapes
Light blue-grey cytoplasm
May have a few, punctate clear vacuoles in their cytoplasm.
The total number of neutrophils in the BLOOD is divided into 2 pools. Where are these pools?
Marginal neutrophil pool is found along vessel walls, temporarily adhered to microvasculature endothelium.
Circulating neutrophil poolis traveling in the blood & are the primary cells observed in a blood sample.
What are the 3 basic differentials for a neutrophilia?
Excitement/epinephrine response
Stress
Inflammation
Why does an epinephrine response lead to a neutrophilia?
Epinephrine increases the heart rate, leading to an increase in blood pressure and muscular activity. This, in turn, washing the marginated neutrophils into the circulating pool to be included in those cells drawn in the blood sample.
What other leukogram values, besides neutrophilia, can you expect to see in the case of an Excitement leukogram?
Lymphocytosis
Normal monocytes, eosinophils, and basophils.
How long does an excitement neutrophilia last?
NOT LONG! It should be relatively transient and only last as long as the epinephrine response.
What does a stress leukogram typically consist of?
Neutrophilia with NO left shift
Lymphocytopenia
Monocytosis
Eosinopenia
How does stress & an increase in corticosteroids cause a neutrophilia?
Decrease the "stickiness" (cell adhesion molecules) of the vascular endothelial cells, transitioning marginated neutrophils to circulating neutrophils.
Increase rate of neutrophil release from bone marrow.
What types of cells are found in the Proliferation pool in the bone marrow?
Mitotically active precursor cells including stem cells, myeloblasts, progranulocytes, myelocytes.
What types of cells are found in the Storage (Maturation) pool in the bone marrow?
Contains cells that can no longer divide, such as neutrohpils, metamyelocytes, bands, and segmented cell forms.
How long does it take to develop a stress neutrophilia?
Hours to days.
How can steroids decrease the body's ability to fight infection?
Neutrophils that have lost their adhesive properties take longer to marginate into tissues (where the infection is taking place). Thus, it takes longer for neutrophils to exhibit their microbicidal function.
Hypersegmented neutrophils are an indication of what?
Neutrophils that have been in circulation for longer than they perhaps should be. Typically seen with stress neutrophilia.
Corticosteroids release neutrophils from what bone marrow pool to which vascular pool?
From mature/storage pool to peripheral circulating pool.
Why do neutrophils increase in number in the marginal pool during inflammation?
Chemotactic factors, such as interleukins, complement molecules, leukotrienes, chemically stimulate to increase neutrophil margination.
What toxic changes may be observed in neutrophils that have not had adequate time for maturation?
Doehle bodies
Diffuse cytoplasmic basophilia
Toxic vacuolization
Toxic granulation
"Donut-shaped" nucleus
"Giant" neutrophil.
What is the pathogenesis (and effects on the proliferation/storage/peripheral pools) of neutrophils in acute inflammation?
During an acute inflammatory phase, the marrow STORAGE pool is depleted. This depletion stimulates T cells to produce GM-CSF to stimulate the mitotic activity of the PROLIFERATION pool. If an acute inflammation remains established, neutrophils continue to travel into tissues, maintaining the demand in the PROLIFERATION pool while the STORAGE pool may still be depleted.
What are the characteristics of a chronic neutrophilia?
Bone marrow production has caught up with peripheral demand for neutrophils. Both the storage and proliferation pools in marrow are hyperplastic and rate of neutrophil release from marrow remains increased.
Leukogram may reveal a neutrophilia with NO to a minimal Left shift.
When is a left shift degenerate/inappropritate?
When immature neutrophils exceed the number of mature neutrophils.
What is a leukemoid response?
An extreme inflammatory leukocytosis that approach numbers seen with leukemia, but without really being leukemic.
What diseases are associated with a leukemoid response?
Canine pyometra
Pyothorax
Peritonitis
Pneumonia
IMHA
How many neutrophils recorded in a leukogram reflect a leukemoid response?
> 50,000 neutrophils/uL
what are the 3 primary causes of neutropenia?
Excessive tissue demand
Sequestration
Decreased production
How long does neutrophil sequestration typically last?
Transiently!
What are some causes for decreased neutrophil production?
Marrow insult from:
Viruses
Rickettsial agents
Toxins
Drugs
Estrogen
Necrosis/myelophthisis.